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van Stee A. Apples and oranges: Conceptual review as task analysis method. Eur J Neurosci 2025; 61:e16623. [PMID: 39803873 PMCID: PMC11726614 DOI: 10.1111/ejn.16623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 09/30/2024] [Accepted: 11/18/2024] [Indexed: 01/16/2025]
Abstract
Conceptual review is a method to address issues of task comparability and task validity in cognitive neuroscience. Meta-analyses within cognitive neuroscience (CNS) as well as integration of neuroscientific findings with findings from adjacent disciplines both involve gathering studies that have purportedly investigated the same mental concept. After all, it is no use comparing apples and oranges. Tasks, and in particular the experimental contrasts implemented through tasks, determine whether studies are in fact comparable. Yet studies tend to be grouped together or kept apart based on the mental label researchers have applied and unfortunately, labels are an unreliable proxy for experimental contrasts. Different contrasts may receive the same label: 'working memory' studies rely on a variety of contrasts, derived from a variety of tasks. Vice versa, the same contrast may receive different labels: 'task switching' and 'working memory' studies can be exactly the same in terms of their experimental contrast. Label use thus obscures comparability problems. What is more, even when experimental contrasts are comparable, they may be invalid operationalizations of the mental label attached to them. In this paper, I introduce conceptual review as a method for task analysis. It can stand on its own or be combined with a cognitive ontology. Conceptual review applies philosophical strategies for analysing concepts to methodological choices in CNS studies, to uncover their conceptual implications. Conceptual review thus sheds light on the precise concept that was studied and thereby, on the comparability of CNS studies and the validity of tasks.
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Jimenez AM, Green MF. Disturbance at the self-other boundary in schizophrenia: Linking phenomenology to clinical neuroscience. Schizophr Res 2024; 272:51-60. [PMID: 39190982 DOI: 10.1016/j.schres.2024.07.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 07/21/2024] [Accepted: 07/24/2024] [Indexed: 08/29/2024]
Abstract
In this selective review, we describe the current neuroscientific literature on disturbances of the self-other boundary in schizophrenia as they relate to structural and experiential aspects of the self. Within these two broad categories, the structural self includes body ownership and agency, and the experiential self includes self-reflection, source monitoring, and self-referential and autobiographical memory. Further, we consider how disturbances in these domains link to the phenomenology of schizophrenia. We identify faulty internal predictive coding as a potential mechanism of disturbance in body ownership and agency, which results in susceptibility to bias (over- or under-attributing outcomes to one's own actions or intentions). This is reflected in reduced activity in the temporoparietal junction (TPJ), a heteromodal association area implicated in several aspects of self-other processing, as well as reduced fronto-parietal functional connectivity. Deficits of the experiential self in schizophrenia may stem from a lack of salience of self-related information, whereby the mental representation of self is not as rich as in healthy controls and therefore does not result in the same level of privileged processing. As a result, memory for self-referential material and autobiographical memory processes is impaired, which hinders creation of a cohesive life narrative. Impairments of the experiential self implicate abnormal activation patterns along the cortical midline, including medial prefrontal cortex and posterior cingulate/precuneus, as well as TPJ. In fact, TPJ appears to be involved in all the reviewed aspects of the self-other disturbance. We conclude with suggestions for future work, including implications for interventions with critical timing considerations.
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Affiliation(s)
- Amy M Jimenez
- Department of Veterans Affairs, Desert Pacific Mental Illness Research, Education, and Clinical Center, USA; VA Rehabilitation R&D Center on Enhancing Community Integration for Homeless Veterans, USA; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, UCLA, USA.
| | - Michael F Green
- Department of Veterans Affairs, Desert Pacific Mental Illness Research, Education, and Clinical Center, USA; VA Rehabilitation R&D Center on Enhancing Community Integration for Homeless Veterans, USA; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, UCLA, USA
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Morfini F, Bauer CCC, Zhang J, Whitfield-Gabrieli S, Shinn AK, Niznikiewicz MA. Targeting the superior temporal gyrus with real-time fMRI neurofeedback: A pilot study of the indirect effects on self-referential processes in schizophrenia. Schizophr Res 2024; 270:358-365. [PMID: 38968807 PMCID: PMC11531859 DOI: 10.1016/j.schres.2024.06.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 06/20/2024] [Accepted: 06/22/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs. METHODS In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group). During NFB, participants were instructed to upregulate their STG activity by attending to pre-recorded sentences spoken in their own voice and downregulate it by ignoring unfamiliar voices. Before and after NFB, participants completed a self-reference task where they evaluated if trait adjectives referred to themselves (self condition), Abraham Lincoln (other condition), or whether adjectives had a positive valence (semantic condition). FMRI activation analyses of self-reference task data tested between-group changes after NFB (self>semantic, post>pre-NFB, experimental>control). Analyses were pre-masked within a self-reference network. RESULTS Activation analyses revealed significantly (p < 0.001) greater activation increase in the experimental, compared to the control group, after NFB within anterior regions of the self-reference network (mPFC, ACC, superior frontal cortex). CONCLUSIONS STG-NFB was associated with activity increase in the mPFC, ACC, and superior frontal cortex during self-reference. Modulating the STG is associated with activation changes in other, not-directly targeted, regions subserving higher-level cognitive processes associated with self-referential processes and AHs psychopathology in SZ. CLINICALTRIALS GOV: Rt-fMRI Neurofeedback and AH in Schizophrenia; https://clinicaltrials.gov/study/NCT03504579.
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Affiliation(s)
- Francesca Morfini
- Northeastern University, Department of Psychology, Boston, MA 02115, USA.
| | - Clemens C C Bauer
- Northeastern University, Department of Psychology, Boston, MA 02115, USA; Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge, MA 02139, USA
| | - Jiahe Zhang
- Northeastern University, Department of Psychology, Boston, MA 02115, USA
| | - Susan Whitfield-Gabrieli
- Northeastern University, Department of Psychology, Boston, MA 02115, USA; Harvard Medical School, Department of Psychiatry, Boston, MA 02115, USA; Massachusetts General Hospital, Department of Psychiatry, Boston, MA, USA; Massachusetts Institute of Technology, McGovern Institute for Brain Research, Cambridge, MA 02139, USA
| | - Ann K Shinn
- Harvard Medical School, Department of Psychiatry, Boston, MA 02115, USA; McLean Hospital, Psychotic Disorders Division, Belmont, MA 02478, USA
| | - Margaret A Niznikiewicz
- Harvard Medical School, Department of Psychiatry, Boston, MA 02115, USA; Veterans Affairs Boston Healthcare System, Department of Psychiatry, Brockton, MA 02301, USA; Boston VA Research Institute, Boston, MA 02130, USA
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He H, Long J, Song X, Li Q, Niu L, Peng L, Wei X, Zhang R. A connectome-wide association study of altered functional connectivity in schizophrenia based on resting-state fMRI. Schizophr Res 2024; 270:202-211. [PMID: 38924938 DOI: 10.1016/j.schres.2024.06.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 05/09/2024] [Accepted: 06/19/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Aberrant resting-state functional connectivity is a neuropathological feature of schizophrenia (SCZ). Prior investigations into functional connectivity abnormalities have primarily employed seed-based connectivity analysis, necessitating predefined seed locations. To address this limitation, a data-driven multivariate method known as connectome-wide association study (CWAS) has been proposed for exploring whole-brain functional connectivity. METHODS We conducted a CWAS analysis involving 46 patients with SCZ and 40 age- and sex-matched healthy controls. Multivariate distance matrix regression (MDMR) was utilized to identify key nodes in the brain. Subsequently, we conducted a follow-up seed-based connectivity analysis to elucidate specific connectivity patterns between regions of interest (ROIs). Additionally, we explored the spatial correlation between changes in functional connectivity and underlying molecular architectures by examining correlations between neurotransmitter/transporter distribution densities and functional connectivity. RESULTS MDMR revealed the right medial frontal gyrus and the left calcarine sulcus as two key nodes. Follow-up analysis unveiled hypoconnectivity between the right medial frontal superior gyrus and the right fusiform gyrus, as well as hypoconnectivity between the left calcarine sulcus and the right lingual gyrus in SCZ. Notably, a significant association between functional connectivity strength and positive symptom severity was identified. Furthermore, altered functional connectivity patterns suggested potential dysfunctions in the dopamine, serotonin, and gamma-aminobutyric acid systems. CONCLUSIONS This study elucidated reduced functional connectivity both within and between the medial frontal regions and the occipital cortex in patients with SCZ. Moreover, it indicated potential alterations in molecular architecture, thereby expanding current knowledge regarding neurobiological changes associated with SCZ.
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Affiliation(s)
- Huawei He
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jixin Long
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xiaoqi Song
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Qian Li
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Lijing Niu
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Lanxin Peng
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xinhua Wei
- Department of Radiology, Guangzhou First Affiliated Hospital, Guangzhou, China.
| | - Ruibin Zhang
- Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China; Department of Psychiatry, Zhujiang Hospital, Southern Medical University, Guangzhou, PRC, China; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for PsychiatricDisorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, PR China.
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Sabbah SG, Northoff G. Global neural self-disturbance in schizophrenia: A systematic fMRI review. Schizophr Res 2024; 269:163-173. [PMID: 38820980 DOI: 10.1016/j.schres.2024.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 04/04/2024] [Accepted: 05/23/2024] [Indexed: 06/02/2024]
Abstract
There is a general consensus that schizophrenia (SZ) is characterized by major changes in the sense of self. Phenomenological studies suggest that these changes in the sense of self stem from a basic disturbance, hence the term 'basic self-disturbance'. While imaging studies demonstrate changes in various regions during self-focused tasks, the exact neural correlates of such basic self-disturbances remain unclear. If the self-disturbance is indeed basic and thereby underlies all other symptoms, one would expect it to be related to more global rather than local changes in the brain. Testing this hypothesis, we conducted a systematic review of fMRI studies on self in SZ. Our main findings are 1. Abnormal activity related to the self can be observed in a variety of different regions ranging from higher-order transmodal to lower-order unimodal regions, 2. These findings hold true across different tasks including self-reflection, self-referentiality, and self-agency, and 3. The global neural abnormalities related to the self in SZ correspond to all layers of the self, predominantly the mental and exteroceptive self. Such global neural disturbance of self converges well with the basic self-disturbance as described in phenomenology.
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Affiliation(s)
- Sami George Sabbah
- Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; The Royal's Institute of Mental Health Research & University of Ottawa, Brain and Mind Research Institute, Centre for Neural Dynamics, Faculty of Medicine, University of Ottawa, 145 Carling Avenue, Rm. 6435, Ottawa, ON, K1Z 7K4, Canada
| | - Georg Northoff
- The Royal's Institute of Mental Health Research & University of Ottawa, Brain and Mind Research Institute, Centre for Neural Dynamics, Faculty of Medicine, University of Ottawa, 145 Carling Avenue, Rm. 6435, Ottawa, ON, K1Z 7K4, Canada
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Crown LM, Agyeman KA, Choi W, Zepeda N, Iseri E, Pahlavan P, Siegel SJ, Liu C, Christopoulos V, Lee DJ. Theta-frequency medial septal nucleus deep brain stimulation increases neurovascular activity in MK-801-treated mice. Front Neurosci 2024; 18:1372315. [PMID: 38560047 PMCID: PMC10978728 DOI: 10.3389/fnins.2024.1372315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 02/29/2024] [Indexed: 04/04/2024] Open
Abstract
Introduction Deep brain stimulation (DBS) has shown remarkable success treating neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. DBS is now being explored to improve cognitive and functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-D-aspartate (NMDA) function (i.e., schizophrenia). While DBS for movement disorders generally involves high-frequency (>100 Hz) stimulation, there is evidence that low-frequency stimulation may have beneficial and persisting effects when applied to cognitive brain networks. Methods In this study, we utilize a novel technology, functional ultrasound imaging (fUSI), to characterize the cerebrovascular impact of medial septal nucleus (MSN) DBS under conditions of NMDA antagonism (pharmacologically using Dizocilpine [MK-801]) in anesthetized male mice. Results Imaging from a sagittal plane across a variety of brain regions within and outside of the septohippocampal circuit, we find that MSN theta-frequency (7.7 Hz) DBS increases hippocampal cerebral blood volume (CBV) during and after stimulation. This effect was not present using standard high-frequency stimulation parameters [i.e., gamma (100 Hz)]. Discussion These results indicate the MSN DBS increases circuit-specific hippocampal neurovascular activity in a frequency-dependent manner and does so in a way that continues beyond the period of electrical stimulation.
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Affiliation(s)
- Lindsey M Crown
- Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Kofi A Agyeman
- Department of Bioengineering, University of California Riverside, Riverside, CA, United States
| | - Wooseong Choi
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Nancy Zepeda
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Ege Iseri
- Department of Bioengineering, University of California Riverside, Riverside, CA, United States
| | - Pooyan Pahlavan
- Department of Bioengineering, University of California Riverside, Riverside, CA, United States
| | - Steven J Siegel
- Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Charles Liu
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United States
- Rancho Los Amigos National Rehabilitation Center, Downey, CA, United States
| | - Vasileios Christopoulos
- Department of Bioengineering, University of California Riverside, Riverside, CA, United States
- Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Neuroscience Graduate Program, University of California Riverside, Riverside, CA, United States
| | - Darrin J Lee
- Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Bioengineering, University of California Riverside, Riverside, CA, United States
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United States
- Rancho Los Amigos National Rehabilitation Center, Downey, CA, United States
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Vallath AL, Sivasubramanian BP, Ravikumar DB, Lalendran A, Krishnan S, Samanta S, Banerjee S, Das T, Kundu R, Richharia V, More R, Khithani M, Nazimudeen S, Gunturu S, Dasgupta I. The importance of rapid assessment tools in evaluating mental health in emergency departments among patients with chronic diseases. Front Public Health 2024; 12:1258749. [PMID: 38496389 PMCID: PMC10940474 DOI: 10.3389/fpubh.2024.1258749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 01/30/2024] [Indexed: 03/19/2024] Open
Abstract
Background Rapid screening tools such as the WHO well-being Index (WWBI), Six-item screener (SIS), and the CLOX-1 test can be used to assess overall mental health and cognition, respectively. We sought to evaluate mental health with cognition in individuals with chronic diseases and stable vital signs presenting to the Emergency Department (ED). Methods An observational study in the ED with 279 participants was conducted. Results Chronic diseases were more prevalent among 51-70 years (43.4%) and diabetes was most common (58.8%). Fever (22.6%) and GI bleeding (32.6%) presentation were high. Participants with low WWBI had low SIS compared to the ones with higher scores (83.3% vs. 17.7%, p < 0.001) and also had low CLOX-1 compared to ones with high CLOX-1 (67.3% vs. 5%, <0.001). A positive correlation between WWBI with SIS (correlation coefficient = 0.305, p < 0.001) and CLOX-1 (0.441, <0.001). Regression analysis indicates a positive association between WWBI and the SIS (standardized regression coefficient = 0.187, 95%CI = 0.236-1.426, and p = 0.006) and CLOX 1 (0.338, 0.2-0.463, <0.001). Conclusion In the ED, the evaluation of mental health even among cognitive impaired is feasible and crucial.
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Affiliation(s)
- Aditya Lal Vallath
- Department of Emergency Medicine, Peerless Hospital and BK Roy Research Center, Kolkata, India
| | | | | | - Akshita Lalendran
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | | | - Sudeshna Samanta
- BBA Hospital Management, George Group of Colleges, Kolkata, India
| | - Snigda Banerjee
- Clinical Pharmacology and Research, Peerless Hospital and BK Roy Research Center, Kolkata, India
| | - Tania Das
- Department of Orthopedics and Trauma, Peerless Hospital and BK Roy Research Center, Kolkata, India
| | - Ritwick Kundu
- Department of Emergency Medicine, Peerless Hospital and BK Roy Research Center, Kolkata, India
| | - Vyom Richharia
- Department of Public Health, Bharati Vidyapeeth Deemed University Medical College, Pune, India
| | - Ravisha More
- National AIDS Research Center, University of Aberdeen, Aberdeen, Scotland, United Kingdom
| | | | - Sahana Nazimudeen
- Department of Emergency Medicine, Peerless Hospital and BK Roy Research Center, Kolkata, India
| | - Sasidhar Gunturu
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Indraneel Dasgupta
- Department of Emergency Medicine, Peerless Hospital and BK Roy Research Center, Kolkata, India
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Giordano GM, Pezzella P, Giuliani L, Fazio L, Mucci A, Perrottelli A, Blasi G, Amore M, Rocca P, Rossi A, Bertolino A, Galderisi S, Italian Network for Research on Psychoses. Resting-State Brain Activity Dysfunctions in Schizophrenia and Their Associations with Negative Symptom Domains: An fMRI Study. Brain Sci 2023; 13:brainsci13010083. [PMID: 36672064 PMCID: PMC9856573 DOI: 10.3390/brainsci13010083] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/07/2022] [Accepted: 12/22/2022] [Indexed: 01/03/2023] Open
Abstract
The aim of the present study was to examine the neurobiological correlates of the two negative symptom domains of schizophrenia, the Motivational Deficit domain (including avolition, anhedonia, and asociality) and the Expressive Deficit domain (including blunted affect and alogia), focusing on brain areas that are most commonly found to be associated with negative symptoms in previous literature. Resting-state (rs) fMRI data were analyzed in 62 subjects affected by schizophrenia (SZs) and 46 healthy controls (HCs). The SZs, compared to the HCs, showed higher rs brain activity in the right inferior parietal lobule and the right temporoparietal junction, and lower rs brain activity in the right dorsolateral prefrontal cortex, the bilateral anterior dorsal cingulate cortex, and the ventral and dorsal caudate. Furthermore, in the SZs, the rs brain activity in the left orbitofrontal cortex correlated with negative symptoms (r = -0.436, p = 0.006), in particular with the Motivational Deficit domain (r = -0.424, p = 0.002), even after controlling for confounding factors. The left ventral caudate correlated with negative symptoms (r = -0.407, p = 0.003), especially with the Expressive Deficit domain (r = -0.401, p = 0.003); however, these results seemed to be affected by confounding factors. In line with the literature, our results demonstrated that the two negative symptom domains might be underpinned by different neurobiological mechanisms.
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Affiliation(s)
- Giulia Maria Giordano
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Pasquale Pezzella
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Luigi Giuliani
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- Correspondence: ; Tel.: +39-0815666512
| | - Leonardo Fazio
- Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, 70124 Bari, Italy
- Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy
| | - Armida Mucci
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Andrea Perrottelli
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Giuseppe Blasi
- Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, 70124 Bari, Italy
| | - Mario Amore
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, 16132 Genoa, Italy
| | - Paola Rocca
- Department of Neuroscience, Section of Psychiatry, University of Turin, 10126 Turin, Italy
| | - Alessandro Rossi
- Department of Biotechnological and Applied Clinical Sciences, Section of Psychiatry, University of L’Aquila, 67100 L’Aquila, Italy
| | - Alessandro Bertolino
- Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, 70124 Bari, Italy
| | - Silvana Galderisi
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
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Assaf R, Ouellet J, Bourque J, Stip E, Leyton M, Conrod P, Potvin S. A functional neuroimaging study of self-other processing alterations in atypical developmental trajectories of psychotic-like experiences. Sci Rep 2022; 12:16324. [PMID: 36175570 PMCID: PMC9522794 DOI: 10.1038/s41598-022-20129-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/08/2022] [Indexed: 11/09/2022] Open
Abstract
Self-disturbances constitute a hallmark of psychosis, but it remains unclear whether these alterations are present in at-risk populations, and therefore their role in the development of psychosis has yet to be confirmed. The present study addressed this question by measuring neural correlates of self-other processing in youth belonging to three developmental trajectories of psychotic experiences. Eighty-six youths were recruited from a longitudinal cohort of over 3800 adolescents based on their trajectories of Psychotic-Like Experiences from 12 to 16 years of age. Participants underwent neuroimaging at 17 years of age (mean). A functional neuroimaging task evaluating self- and other-related trait judgments was used to measure whole-brain activation and connectivity. Youth who showed an increasing trajectory displayed hypoactivation of the dorsomedial prefrontal cortex and hypoconnectivity with the cerebellum. By contrast, youth who showed a decreasing trajectory displayed decreased activation of the superior temporal gyrus, the inferior frontal gyrus, and the middle occipital gyrus. These findings suggest that the increasing trajectory is associated with alterations that might erode distinctions between self and other, influencing the emergence of symptoms such as hallucinations. The decreasing trajectory, in comparison, was associated with hypoactivations in areas influencing attention and basic information processing more generally. These alterations might affect the trajectories’ susceptibilities to positive vs. negative symptoms, respectively.
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Affiliation(s)
- Roxane Assaf
- Centre de Recherche, Institut Universitaire en Santé Mentale de Montréal, 7331 Hochelaga, Montreal, H1N 3V2, Canada.,Department of Psychiatry and Addiction, Faculty of Medicine, University of Montreal, Montreal, Canada
| | - Julien Ouellet
- Department of Psychiatry and Addiction, Faculty of Medicine, University of Montreal, Montreal, Canada.,Centre de Recherche du Centre Hospitalier, Universitaire Sainte-Justine, Montreal, Canada
| | - Josiane Bourque
- Department of Psychiatry, Perelman Faculty of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Emmanuel Stip
- Department of Psychiatry and Addiction, Faculty of Medicine, University of Montreal, Montreal, Canada
| | - Marco Leyton
- Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada
| | - Patricia Conrod
- Department of Psychiatry and Addiction, Faculty of Medicine, University of Montreal, Montreal, Canada.,Centre de Recherche du Centre Hospitalier, Universitaire Sainte-Justine, Montreal, Canada
| | - Stéphane Potvin
- Centre de Recherche, Institut Universitaire en Santé Mentale de Montréal, 7331 Hochelaga, Montreal, H1N 3V2, Canada. .,Department of Psychiatry and Addiction, Faculty of Medicine, University of Montreal, Montreal, Canada.
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10
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Weng Y, Lin J, Ahorsu DK, Tsang HWH. Neuropathways of theory of mind in schizophrenia: A systematic review and meta-analysis. Neurosci Biobehav Rev 2022; 137:104625. [PMID: 35339482 DOI: 10.1016/j.neubiorev.2022.104625] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 03/11/2022] [Accepted: 03/14/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Social cognition is significantly associated with daily functioning in patients with schizophrenia. Its neural basis remains unknown. METHODS A systematic literature search was performed. Studies using imaging to measure theory of mind (ToM) in schizophrenia were identified. Imaging data were synthesized using the seed-based d mapping approach. Potential neuropathways were hypothesized based on the identified brain regions activated during ToM tasks. RESULTS A total of 25 studies were included in the present study. Compared with healthy people, patients with schizophrenia showed hyperactivations in superior longitudinal fasciculus II and hypoactivations in superior frontal gyrus, precuneus and cuneus, and precentral gyrus during ToM tasks. The primary brain regions involved in the potential neuropathways in schizophrenia were the middle temporal gyrus, superior and inferior frontal gyrus, and supplementary motor areas. CONCLUSION Deactivated brain regions in schizophrenia overlapped with the default mode and salience networks. Our findings shed light on how to develop a diagnostic tool for deficits in social cognition using neuroimaging techniques and effective therapeutic interventions to rectify dysfunction in schizophrenia.
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Affiliation(s)
- Yiting Weng
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, People's Republic of China
| | - Jingxia Lin
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, People's Republic of China; Mental Health Research Centre, The Hong Kong Polytechnic University, Hung Hom, Kowloon, People's Republic of China
| | - Daniel Kwasi Ahorsu
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, People's Republic of China
| | - Hector W H Tsang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, People's Republic of China; Mental Health Research Centre, The Hong Kong Polytechnic University, Hung Hom, Kowloon, People's Republic of China.
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11
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Salgado-Pineda P, Fuentes-Claramonte P, Spanlang B, Pomes A, Landin-Romero R, Portillo F, Bosque C, Franquelo JC, Teixido C, Sarró S, Salvador R, Pomarol-Clotet E. Neural correlates of disturbance in the sense of agency in schizophrenia: An fMRI study using the 'enfacement' paradigm. Schizophr Res 2022; 243:395-401. [PMID: 34218983 DOI: 10.1016/j.schres.2021.06.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 05/26/2021] [Accepted: 06/22/2021] [Indexed: 10/21/2022]
Abstract
An altered sense of self-awareness and agency has been proposed to underlie symptoms of schizophrenia. In this study, we used the enfacement illusion paradigm - in which perception of another person's face leads to changes in perception of one's own peri-personal space - to examine the brain correlates of the sense of agency and its potential disruption in schizophrenia. Thirty-three schizophrenic patients and 27 healthy controls underwent fMRI scanning during performance of a task designed to elicit the enfacement illusion. Activations were examined using whole-brain analysis and also in an a priori identified region of interest (ROI) in the temporoparietal junction (TPJ), a region that has been described as involved in self/other differentiation and sense of agency. Both groups showed a pattern of cortical activation involving the pre and postcentral cortex, Rolandic operculum, insula, parietal, temporal and occipital cortex bilaterally as well as TPJ (but only right-side in patients). Examination of the TPJ ROI revealed significantly reduced activation on the left in the patients that was associated with poorer insight. The findings suggest brain functional abnormality in schizophrenia related to the formation or maintenance of processes related to self and/or agency. Decreased function in the TPJ may have a role in the impaired insight seen in patients with the disorder.
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Affiliation(s)
- Pilar Salgado-Pineda
- FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
| | - P Fuentes-Claramonte
- FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
| | - Bernhard Spanlang
- Event Lab, Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain; Institute of Neuroscience of the University of Barcelona, Barcelona, Spain; Virtual Bodyworks S.L., Barcelona, Spain
| | - Ausias Pomes
- Event Lab, Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain; Accenture, Barcelona, Spain
| | - Ramón Landin-Romero
- FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney,NSW, Australia
| | | | - Clara Bosque
- Benito Menni Complex Assistencial en Salut Mental, Barcelona, Spain
| | | | - Cristina Teixido
- Hospital Mare de Dèu de la Mercé, Unitat Polivalent Barcelona Nord, Barcelona, Spain
| | - Salvador Sarró
- FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
| | - Raymond Salvador
- FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
| | - Edith Pomarol-Clotet
- FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
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12
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Mäntylä T, Kieseppä T, Suvisaari J, Raij TT. Delineating insight-processing-related functional activations in the precuneus in first-episode psychosis patients. Psychiatry Res Neuroimaging 2021; 317:111347. [PMID: 34403968 DOI: 10.1016/j.pscychresns.2021.111347] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 03/19/2021] [Accepted: 04/18/2021] [Indexed: 11/24/2022]
Abstract
Poor insight is a central characteristic of psychotic disorders, and it has been suggested to result from a general dysfunction in self-reflection. However, brain processing of clinical insight and more general self-reflection has not been directly compared. We compared tasks on (1) self-reflection on psychosis-related mental functioning (clinical insight, in patients only), (2) self-reflection on mental functioning unrelated to psychosis (general metacognition), and (3) semantic control during blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging with 19 first-episode psychosis patients and 24 control participants. Arterial-spin-labeling (ASL) images were collected at rest. Clinical insight was evaluated with the Schedule for the Assessment of Insight. In patients, posterosuperior precuneus showed stronger activation during the insight task than during the semantic control task, while anteroinferior precuneus and posterior cingulate cortex (PCC) showed stronger activation during the insight task than during the general metacognition task. No significant group differences in brain activation emerged during the general metacognition task. Although the BOLD measures did not correlate with clinical insight measures, ASL-measured cerebral blood flow (CBF) values did correlate when extracted from the task-selective precuneus/PCC areas: higher CBF correlated with higher clinical insight scores. These results suggest that regions in the posteromedial cortex are selective for clinical insight.
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Affiliation(s)
- Teemu Mäntylä
- Mental Health Team, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland; Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland; P.O. Box 13000, FI-00076 Aalto, Finland; Department of Psychology and Logopedics, University of Helsinki, P.O. Box 21, FIN-00014 Helsinki, Finland.
| | - Tuula Kieseppä
- Mental Health Team, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland; Department of Psychiatry, Helsinki University and Helsinki University Hospital, P.O. Box 590, FIN-00029, Helsinki, Finland.
| | - Jaana Suvisaari
- Mental Health Team, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland.
| | - Tuukka T Raij
- Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland; P.O. Box 13000, FI-00076 Aalto, Finland; Department of Psychiatry, Helsinki University and Helsinki University Hospital, P.O. Box 590, FIN-00029, Helsinki, Finland.
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13
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Increased Global-Brain Functional Connectivity Is Associated with Dyslipidemia and Cognitive Impairment in First-Episode, Drug-Naive Patients with Bipolar Disorder. Neural Plast 2021; 2021:5560453. [PMID: 34194487 PMCID: PMC8203345 DOI: 10.1155/2021/5560453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/10/2021] [Accepted: 05/22/2021] [Indexed: 01/01/2023] Open
Abstract
Objectives Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.
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14
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Shen J, Shen G, Kim WS, Tsogt U, Liu C, Sui J, Chung YC. Neuronal Signatures of Negative and Positive Schemas towards the Self and Others in Patients with Early Stage Schizophrenia. Psychiatry Investig 2021; 18:284-294. [PMID: 33849245 PMCID: PMC8103021 DOI: 10.30773/pi.2020.0335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/18/2020] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE The present study investigated the functional neuroanatomy underlying negative and positive schemas towards the self and others in patients with early stage schizophrenia spectrum disorders (SSDs) using a task-based fMRI procedure. METHODS This study included 50 patients with SSDs and 52 controls. The schema-evoking task consisted of four active conditions and neutral condition. Differences in brain activation were compared between the two groups. Correlation analysis was performed between task-related activation and psychopathology. RESULTS The SSD patients exhibited higher activity of the left middle and inferior frontal gyri under the negative-others minus neutral contrast as well as greater activation of the left superior and middle frontal gyri and right medial superior frontal gyrus under the positive- self minus neutral and positive-others minus neutral contrasts. Under the positive-others minus neutral contrast, negative correlation was observed between activity of the right inferior parietal gyrus and right angular and total score of the Positive and Negative Syndrome Scale (PANSS), whereas positive correlation between activity of the left middle cingulate gyrus and left/right precuneus and positive-others score of the Brief Core Schema Scales (BCSS). CONCLUSION The present findings suggest that the frontal brain regions of SSD patients are more sensitive to negative and positive schemas towards the self and/or others compared to those of controls.
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Affiliation(s)
- Jie Shen
- Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Guangfan Shen
- Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Woo-Sung Kim
- Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Uyanga Tsogt
- Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Congcong Liu
- Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Jing Sui
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing, China
| | - Young-Chul Chung
- Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea.,Department of Psychiatry, Jeonbuk National University Hospital, Jeonju, Republic of Korea.,Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
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15
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Collin G, Bauer CCC, Anteraper SA, Gabrieli JDE, Molokotos E, Mesholam-Gately R, Thermenos HW, Seidman LJ, Keshavan MS, Shenton ME, Whitfield-Gabrieli S. Hyperactivation of Posterior Default Mode Network During Self-Referential Processing in Children at Familial High-Risk for Psychosis. Front Psychiatry 2021; 12:613142. [PMID: 33633608 PMCID: PMC7900488 DOI: 10.3389/fpsyt.2021.613142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 01/04/2021] [Indexed: 11/28/2022] Open
Abstract
Patients with schizophrenia spectrum disorders show disturbances in self-referential processing and associated neural circuits including the default mode network (DMN). These disturbances may precede the onset of psychosis and may underlie early social and emotional problems. In this study, we examined self-referential processing in a group of children (7-12 years) at familial high risk (FHR) for psychosis (N = 17), compared to an age and sex-matched group of healthy control (HC) children (N = 20). The participants were presented with a list of adjectives and asked to indicate whether or not the adjectives described them (self-reference condition) and whether the adjectives described a good or bad trait (semantic condition). Three participants were excluded due to chance-level performance on the semantic task, leaving N = 15 FHR and N = 19 HC for final analysis. Functional MRI (fMRI) was used to measure brain activation during self-referential vs. semantic processing. Internalizing and externalizing problems were assessed with the Child Behavior Checklist (CBCL). Evaluating main effects of task (self > semantic) showed activation of medial prefrontal cortex in HC and precuneus/posterior cingulate cortex (PCC) in FHR. Group-comparison yielded significant results for the FHR > HC contrast, showing two clusters of hyperactivation in precuneus/ PCC (p = 0.004) and anterior cerebellum / temporo-occipital cortex (p = 0.009). Greater precuneus/PCC activation was found to correlate with greater CBCL internalizing (r = 0.60, p = 0.032) and total (r = 0.69, p = 0.009) problems. In all, this study shows hyperactivity of posterior DMN during self-referential processing in pre-adolescent FHR children. This finding posits DMN-related disturbances in self-processing as a developmental brain abnormality associated with familial risk factors that predates not just psychosis, but also the prodromal stage. Moreover, our results suggest that early disturbances in self-referential processing may be related to internalizing problems in at-risk children.
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Affiliation(s)
- Guusje Collin
- Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States.,Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.,Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht, Netherlands
| | - Clemens C C Bauer
- Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States.,Department of Psychology, Northeastern University, Boston, MA, United States
| | - Sheeba Arnold Anteraper
- Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States.,Department of Psychology, Northeastern University, Boston, MA, United States
| | - John D E Gabrieli
- Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Elena Molokotos
- Department of Psychology, Suffolk University, Boston, MA, United States
| | - Raquelle Mesholam-Gately
- Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Heidi W Thermenos
- Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Larry J Seidman
- Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Matcheri S Keshavan
- Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Martha E Shenton
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Susan Whitfield-Gabrieli
- Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States.,Department of Psychology, Northeastern University, Boston, MA, United States
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16
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Kim JH, Son YD, Kim HK, Kim JH. Association Between Lack of Insight and Prefrontal Serotonin Transporter Availability in Antipsychotic-Free Patients with Schizophrenia: A High-Resolution PET Study with [ 11C]DASB. Neuropsychiatr Dis Treat 2021; 17:3195-3203. [PMID: 34707358 PMCID: PMC8544267 DOI: 10.2147/ndt.s336126] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/08/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between serotonin transporter (SERT) availability in regions of the prefrontal cortex (dorsolateral, ventrolateral, ventromedial, and orbitofrontal cortices) and insight deficits in antipsychotic-free patients with schizophrenia using high-resolution positron emission tomography (PET) with [11C]DASB. METHODS Nineteen patients underwent [11C]DASB PET and 7-Tesla magnetic resonance imaging scans. To assess SERT availability, the binding potential with respect to non-displaceable compartment (BPND) was derived using the simplified reference tissue model. Patients' level of insight was assessed using the Insight and Treatment Attitude Questionnaire (ITAQ). The relationship between ITAQ scores and [11C]DASB BPND values was examined using the region-of-interest (ROI)- and voxel-based analyses with relevant variables as covariates. The prefrontal cortex and its four subregions were selected as a priori ROIs since the prefrontal cortex has been implicated as the critical neuroanatomical substrate of impaired insight in schizophrenia. RESULTS The ROI-based analysis revealed that the ITAQ illness insight dimension had significant negative correlations with the [11C]DASB BPND in the left dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ treatment insight dimension had significant negative correlations with the [11C]DASB BPND in the bilateral dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ total score showed significant negative correlations with the [11C]DASB BPND in the bilateral prefrontal cortex and three subregions (dorsolateral, ventrolateral, and orbitofrontal cortices). A supplementary voxel-based analysis corroborated a significant negative association between the ITAQ score and the [11C]DASB BPND in the prefrontal cortices. CONCLUSION Our study provides in vivo evidence of significant negative correlations between insight deficits and prefrontal SERT availability in patients with schizophrenia, suggesting significant involvement of prefrontal serotonergic signaling in impaired insight, one of the core symptoms of schizophrenia.
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Affiliation(s)
- Jeong-Hee Kim
- Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea.,Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon, Republic of Korea
| | - Young-Don Son
- Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea.,Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon, Republic of Korea.,Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea
| | - Hang-Keun Kim
- Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea.,Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon, Republic of Korea.,Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea
| | - Jong-Hoon Kim
- Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea.,Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea.,Department of Psychiatry, Gachon University College of Medicine, Gil Medical Center, Incheon, Republic of Korea
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17
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Wang J, Yu W, Gao Q, Ju C, Wang K. Prefrontal inhibition of neuronal K v 7 channels enhances prepulse inhibition of acoustic startle reflex and resistance to hypofrontality. Br J Pharmacol 2020; 177:4720-4733. [PMID: 32839968 PMCID: PMC7520443 DOI: 10.1111/bph.15236] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 07/31/2020] [Accepted: 08/06/2020] [Indexed: 11/28/2022] Open
Abstract
Background and Purpose Dysfunction of the prefrontal cortex (PFC) is involved in the cognitive deficits in neuropsychiatric diseases, such as schizophrenia, characterized by deficient neurotransmission known as NMDA receptor hypofrontality. Thus, enhancing prefrontal activity may alleviate hypofrontality‐induced cognitive deficits. To test this hypothesis, we investigated the effect of forebrain‐specific suppression or pharmacological inhibition of native Kv7/KCNQ/M‐current on glutamatergic hypofrontality induced by the NMDA receptor antagonist MK‐801. Experimental Approach The forebrain‐specific inhibition of native M‐current was generated by transgenic expression, in mice, of a dominant‐negative pore mutant G279S of Kv7.2/KCNQ2 channels that suppresses channel function. A mouse model of cognitive impairment was established by single i.p. injection of 0.1 mg·kg−1 MK‐801. Mouse models of prepulse inhibition (PPI) of acoustic startle reflex and Y‐maze spontaneous alternation test were used for evaluation of cognitive behaviour. Hippocampal brain slice recordings of LTP were used to assess synaptic plasticity. Hippocampus and cortex were dissected for detecting protein expression using western blot analysis. Key Results Genetic suppression of Kv7 channel function in the forebrain or pharmacological inhibition of Kv7 channels by the specific blocker XE991 enhanced PPI and also alleviated MK‐801 induced cognitive decline. XE991 also attenuated MK‐801‐induced LTP deficits and increased basal synaptic transmissions. Western blot analysis revealed that inhibiting Kv7 channels resulted in elevation of pAkt1 and pGSK‐3β expressions in both hippocampus and cortex. Conclusions and Implications Both genetic and pharmacological inhibition of Kv7 channels alleviated PPI and cognitive deficits. Mechanistically, inhibition of Kv7 channels promotes synaptic transmission and activates Akt1/GSK‐3β signalling.
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Affiliation(s)
- Jing Wang
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
| | - Wenwen Yu
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China.,Institute of Innovative Drugs, Qingdao University, Qingdao, China
| | - Qin Gao
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
| | - Chuanxia Ju
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China
| | - KeWei Wang
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China.,Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, China.,Institute of Innovative Drugs, Qingdao University, Qingdao, China
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18
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Pijnenborg GHM, Larabi DI, Xu P, Hasson-Ohayon I, de Vos AE, Ćurčić-Blake B, Aleman A, Van der Meer L. Brain areas associated with clinical and cognitive insight in psychotic disorders: A systematic review and meta-analysis. Neurosci Biobehav Rev 2020; 116:301-336. [PMID: 32569706 DOI: 10.1016/j.neubiorev.2020.06.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 03/04/2020] [Accepted: 06/13/2020] [Indexed: 02/06/2023]
Abstract
In the past years, ample interest in brain abnormalities related to clinical and cognitive insight in psychosis has contributed several neuroimaging studies to the literature. In the current study, published findings on the neural substrates of clinical and cognitive insight in psychosis are integrated by performing a systematic review and meta-analysis. Coordinate-based meta-analyses were performed with the parametric coordinate-based meta-analysis approach, non-coordinate based meta-analyses were conducted with the metafor package in R. Papers that could not be included in the meta-analyses were systematically reviewed. Thirty-seven studies were retrieved, of which 21 studies were included in meta-analyses. Poorer clinical insight was related to smaller whole brain gray and white matter volume and gray matter volume of the frontal gyri. Cognitive insight was predominantly positively associated with structure and function of the hippocampus and ventrolateral prefrontal cortex. Impaired clinical insight is not associated with abnormalities of isolated brain regions, but with spatially diffuse global and frontal abnormalities suggesting it might rely on a range of cognitive and self-evaluative processes. Cognitive insight is associated with specific areas and appears to rely more on retrieving and integrating self-related information.
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Affiliation(s)
- G H M Pijnenborg
- Department of Psychotic Disorders, GGZ Drenthe, Dennenweg 9, 9404 LA, Assen, the Netherlands; Department of Clinical and Developmental Neuropsychology and Experimental Psychopathology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, the Netherlands.
| | - D I Larabi
- University of Groningen, University Medical Center Groningen, Department of Biomedical Sciences of Cells and Systems, Cognitive Neuroscience Center, A. Deusinglaan 2, 9713 AW, Groningen, the Netherlands; Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany; Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - P Xu
- Shenzhen Key Laboratory of Affective and Social Neuroscience, Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen 518060, China; Center for Neuroimaging, Shenzhen Institute of Neuroscience, Shenzhen 518054, China; Great Bay Neuroscience and Technology Research Institute (Hong Kong), Kwun Tong, Hong Kong
| | - I Hasson-Ohayon
- Department of Psychology, Bar-Ilan University, Ramat-Gan 5290002, Israel
| | - A E de Vos
- Department of Psychotic Disorders, GGZ Drenthe, Dennenweg 9, 9404 LA, Assen, the Netherlands
| | - B Ćurčić-Blake
- University of Groningen, University Medical Center Groningen, Department of Biomedical Sciences of Cells and Systems, Cognitive Neuroscience Center, A. Deusinglaan 2, 9713 AW, Groningen, the Netherlands
| | - A Aleman
- Department of Psychotic Disorders, GGZ Drenthe, Dennenweg 9, 9404 LA, Assen, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Biomedical Sciences of Cells and Systems, Cognitive Neuroscience Center, A. Deusinglaan 2, 9713 AW, Groningen, the Netherlands; Shenzhen Key Laboratory of Affective and Social Neuroscience, Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen 518060, China
| | - L Van der Meer
- Department of Rehabilitation, Lentis Mental Health Care, PO box 128, 9470 KA, Zuidlaren, the Netherlands; Department of Clinical and Developmental Neuropsychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, the Netherlands
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19
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Park HY, Park K, Seo E, Koo SJ, Bang M, Park JY, Kang JI, Lee E, Lee SK, An SK. Reduced activation of the ventromedial prefrontal cortex during self-referential processing in individuals at ultra-high risk for psychosis. Aust N Z J Psychiatry 2020; 54:528-538. [PMID: 31957464 DOI: 10.1177/0004867419898529] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Defects in self-referential processing and perspective-taking are core characteristics that may underlie psychotic symptoms and impaired social cognition in schizophrenia. Here, we investigated the neural correlates of self-referential processing regardless of the perspective taken and third-person perspective-taking regardless of the target person to judge relevance in individuals at ultra-high risk for psychosis. We also explored relationships between alterations in neural activity and neurocognitive function and basic self ('ipseity') disorder. METHODS Twenty-two ultra-high-risk individuals and 28 healthy controls completed a functional magnetic resonance imaging task. While being scanned, participants were asked to take a first-person perspective or to put themselves in their close relative's place thereby adopting a third-person perspective during judgments of the relevance of personality trait adjectives to one's self and a close relative. RESULTS For self-referential (vs other-referential) processing, ultra-high-risk individuals showed less neural activity in the left ventromedial prefrontal cortex/medial orbitofrontal cortex, which was correlated with poor working memory performance. When taking a third-person perspective (vs first-person perspective), ultra-high-risk individuals showed more activity in the middle occipital gyrus. CONCLUSION Taken together, our findings suggest that ultra-high-risk individuals already show aberrant neural activity during self-referential processing which may possibly be related to engagement of working memory resources.
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Affiliation(s)
- Hye Yoon Park
- Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.,Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyoungri Park
- College of Medicine, Chosun University, Gwangju, Republic of Korea
| | - Eunchong Seo
- Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.,Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Se Jun Koo
- Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Graduate Program in Cognitive Science, Yonsei University, Seoul, Republic of Korea
| | - Minji Bang
- Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Jin Young Park
- Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.,Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jee In Kang
- Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.,Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Lee
- Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.,Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung-Koo Lee
- Department of Radiology, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Suk Kyoon An
- Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.,Section of Self, Affect and Neuroscience, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Graduate Program in Cognitive Science, Yonsei University, Seoul, Republic of Korea
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20
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Thirioux B, Harika-Germaneau G, Langbour N, Jaafari N. The Relation Between Empathy and Insight in Psychiatric Disorders: Phenomenological, Etiological, and Neuro-Functional Mechanisms. Front Psychiatry 2020; 10:966. [PMID: 32116810 PMCID: PMC7020772 DOI: 10.3389/fpsyt.2019.00966] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 12/06/2019] [Indexed: 01/12/2023] Open
Abstract
Lack of insight, i.e., unawareness of one's mental illness, is frequently encountered in psychiatric conditions. Insight is the capacity to recognize (psychical insight) and accept one's mental illness (emotional insight). Insight growth necessitates developing an objective perspective on one's subjective pathological experiences. Therefore, insight has been posited to require undamaged self-reflexion and cognitive perspective-taking capacities. These enable patients to look objectively at themselves from the imagined perspective of someone else. Preserved theory-of-mind performances have been reported to positively impact insight in psychosis. However, some patients with schizophrenia or obsessive-compulsive disorders, although recognizing their mental disease, are still not convinced of this and do not accept it. Hence, perspective-taking explains psychical insight (recognition) but not emotional insight (acceptance). Here, we propose a new conceptual model. We hypothesize that insight growth relies upon the association of intact self-reflexion and empathic capacities. Empathy (feeling into someone else) integrates heterocentered visuo-spatial perspective (feeling into), embodiment, affective (feeling into) and cognitive processes, leading to internally experience the other's thought. We posit that this subjective experience enables to better understand the other's thought about oneself and to affectively adhere to this. We propose that the process of objectification, resulting from empathic heterocentered, embodiment, and cognitive processes, generates an objective viewpoint on oneself. It enables to recognize one's mental illness and positively impacts psychical insight. The process of subjectification, resulting from empathic affective processes, enables to accept one's illness and positively impacts emotional insight. That is, affectively experiencing the thought of another person about oneself reinforces the adhesion of the emotional system to the objective recognition of the disease. Applying our model to different psychiatric disorders, we predict that the negative effect of impaired self-reflexion and empathic capacities on insight is a transnosographic state and that endophenotypical differences modulate this common state, determining a psychiatric disease as specific.
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Affiliation(s)
- Bérangère Thirioux
- Unité de Recherche Clinique Intersectorielle en Psychiatrie à vocation régionale Pierre Deniker, Centre Hospitalier Henri Laborit, Poitiers, France
| | - Ghina Harika-Germaneau
- Unité de Recherche Clinique Intersectorielle en Psychiatrie à vocation régionale Pierre Deniker, Centre Hospitalier Henri Laborit, Poitiers, France
| | - Nicolas Langbour
- Unité de Recherche Clinique Intersectorielle en Psychiatrie à vocation régionale Pierre Deniker, Centre Hospitalier Henri Laborit, Poitiers, France
| | - Nematollah Jaafari
- Unité de Recherche Clinique Intersectorielle en Psychiatrie à vocation régionale Pierre Deniker, Centre Hospitalier Henri Laborit, Poitiers, France
- Université de Poitiers, CHU de Poitiers, INSERM U 1084, Experimental and Clinical Neuroscience Laboratory, Groupement de Recherche CNRS 3557, Poitiers, France
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21
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Fuentes-Claramonte P, Martin-Subero M, Salgado-Pineda P, Santo-Angles A, Argila-Plaza I, Salavert J, Arévalo A, Bosque C, Sarri C, Guerrero-Pedraza A, Capdevila A, Sarró S, McKenna PJ, Pomarol-Clotet E, Salvador R. Brain imaging correlates of self- and other-reflection in schizophrenia. NEUROIMAGE-CLINICAL 2019; 25:102134. [PMID: 31877452 PMCID: PMC6931228 DOI: 10.1016/j.nicl.2019.102134] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 11/29/2019] [Accepted: 12/13/2019] [Indexed: 01/06/2023]
Abstract
Self- and other-reflection in schizophrenia were studied with fMRI. Patients failed to activate the right temporo-parietal junction in other-reflection. They also hyperactivated lateral prefrontal cortex for self and other-reflection. These findings might be linked to altered self/other processing in schizophrenia. Background An alteration in self/other differentiation has been proposed as a basis for several symptoms in schizophrenia, including delusions of reference and social functioning deficits. Dysfunction of the right temporo-parietal junction (TPJ), a region linked with social cognition, has been proposed as the basis of this alteration. However, imaging studies of self- and other-processing in schizophrenia have shown, so far, inconsistent results. Methods Patients with schizophrenia and healthy controls underwent fMRI scanning while performing a task with three conditions: self-reflection, other-reflection and semantic processing. Results Both groups activated similar brain regions for self- and other-reflection compared to semantic processing, including the medial prefrontal cortex, the precuneus and the TPJ. Compared to healthy subjects, patients hyperactivated the left lateral frontal cortex during self- and other-reflection. In other-reflection, compared to self-reflection, patients failed to increase right TPJ activity. Conclusions Altered activity in the right TPJ supports a disturbance in self/other differentiation in schizophrenia, which could be linked with psychotic symptoms and affect social functioning in patients. Hyperactivity of the lateral frontal cortex for self- and other-reflection suggests the presence of greater cognitive demand to perform the task in the patient group.
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Affiliation(s)
- Paola Fuentes-Claramonte
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain
| | - Marta Martin-Subero
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Pilar Salgado-Pineda
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain
| | - Aniol Santo-Angles
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain
| | - Isabel Argila-Plaza
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain
| | - Josep Salavert
- Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Psychiatry Department, Hospital Sant Rafael, Barcelona, Spain
| | - Antoni Arévalo
- Psychiatry Department, Hospital Sagrat Cor Martorell Barcelona, Spain
| | - Clara Bosque
- Benito Menni Centre Assistencial en Salut Mental, Sant Boi de Llobregat, Barcelona, Spain
| | - Carmen Sarri
- Benito Menni Centre Assistencial en Salut Mental, Sant Boi de Llobregat, Barcelona, Spain
| | | | - Antoni Capdevila
- Radiology Unit, Hospital de la Santa Creu i Sant Pau (HSCSP), Barcelona, Spain; CIBER-BBN (Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina), Spain
| | - Salvador Sarró
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain
| | - Peter J McKenna
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain
| | - Edith Pomarol-Clotet
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain.
| | - Raymond Salvador
- FIDMAG Germanes Hospitalàries Research Foundation, Carrer Dr. Antoni Pujadas, 38, 08830 Sant Boi de Llobregat, Barcelona Spain; CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Spain
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22
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Taylor SF, Grove TB, Ellingrod VL, Tso IF. The Fragile Brain: Stress Vulnerability, Negative Affect and GABAergic Neurocircuits in Psychosis. Schizophr Bull 2019; 45:1170-1183. [PMID: 31150555 PMCID: PMC6811817 DOI: 10.1093/schbul/sbz046] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Persons with schizophrenia exhibit sensitivity to stress and negative affect (NA), both strongly correlated with poor functional outcome. This theoretical review suggests that NA reflects a "fragile brain," ie, vulnerable to stress, including events not experienced as stressful by healthy individuals. Based on postmortem evidence of altered gamma-aminobutyric acid (GABA) function in parvalbumin positive interneurons (PVI), animal models of PVI abnormalities and neuroimaging data with GABAergic challenge, it is suggested that GABAergic disruptions weaken cortical regions, which leads to stress vulnerability and excessive NA. Neurocircuits that respond to stressful and salient environmental stimuli, such as the hypothalamic-pituitary-adrenal axis and the amygdala, are highly dysregulated in schizophrenia, exhibiting hypo- and hyper-activity. PVI abnormalities in lateral prefrontal cortex and hippocampus have been hypothesized to affect cognitive function and positive symptoms, respectively; in the medial frontal cortex (dorsal anterior cingulate cortex and dorsal medial prefrontal cortex), these abnormalities may lead to vulnerability to stress, NA and dysregulation of stress responsive systems. Given that postmortem PVI disruptions have been identified in other conditions, such as bipolar disorder and autism, stress vulnerability may reflect a transdiagnostic dimension of psychopathology.
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Affiliation(s)
- Stephan F Taylor
- Department of Psychiatry, University of Michigan, Rachel Upjohn Building, Ann Arbor, MI,To whom correspondence should be addressed; tel: 734-936-4955, fax: 734-936-7868, e-mail:
| | - Tyler B Grove
- Department of Psychiatry, University of Michigan, Rachel Upjohn Building, Ann Arbor, MI
| | | | - Ivy F Tso
- Department of Psychiatry, University of Michigan, Rachel Upjohn Building, Ann Arbor, MI
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23
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Potvin S, Gamache L, Lungu O. A Functional Neuroimaging Meta-Analysis of Self-Related Processing in Schizophrenia. Front Neurol 2019; 10:990. [PMID: 31572296 PMCID: PMC6749044 DOI: 10.3389/fneur.2019.00990] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 08/30/2019] [Indexed: 01/27/2023] Open
Abstract
Background: Schizophrenia is characterized by self-disturbances, including impaired self-evaluation abilities and source monitoring. The cortical midline structures (e.g., medial prefrontal cortex, anterior and posterior cingulate cortex, and precuneus) and the temporoparietal junction are known to play a key role in self-related processing. In theory, self-disturbances in schizophrenia may arise from impaired activity in these regions. We performed a functional neuroimaging meta-analysis to verify this hypothesis. Methods: A literature search was performed with PubMed and Google Scholar to identify functional neuroimaging studies examining the neural correlates of self-processing in schizophrenia, using self-other or source monitoring paradigms. Fourteen studies were retrieved, involving 245 patients and 201 controls. Using peak coordinates to recreate an effect-size map of contrast results, a standard random-effects variance weighted meta-analysis for each voxel was performed with the Seed-based d Mapping software. Results: During self-processing, decreased activations were observed in schizophrenia patients relative to controls in the bilateral thalamus and the left dorsal anterior cingulate cortex (dACC) and dorso-medial prefrontal cortex. Importantly, results were homogeneous across studies, and no publication bias was observed. Sensitivity analyses revealed that results were replicable in 93-100% of studies. Conclusion: The current results partially support the hypothesized impaired activity of cortical midline brain regions in schizophrenia during self-processing. Decreased activations were observed in the dACC and dorsomedial prefrontal cortex, which are involved in cognitive control and/or salience attribution, as well as decision-making, respectively. These alterations may compromise patients' ability to direct their attention toward themselves and/or others and to make the decision whether a certain trait applies to one's self or to someone else. In addition, decreased activations were observed in the thalamus, which is not a core region of the default-mode network, and is involved in information integration. These thalamic alterations may compromise self-coherence in schizophrenia.
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Affiliation(s)
- Stéphane Potvin
- Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal, Montreal, QC, Canada.,Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, QC, Canada
| | - Lydia Gamache
- Department of Psychology, University of Montreal, Montreal, QC, Canada
| | - Ovidiu Lungu
- Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.,Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Montreal, QC, Canada
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24
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Damme KSF, Pelletier-Baldelli A, Cowan HR, Orr JM, Mittal VA. Distinct and opposite profiles of connectivity during self-reference task and rest in youth at clinical high risk for psychosis. Hum Brain Mapp 2019; 40:3254-3264. [PMID: 30941844 DOI: 10.1002/hbm.24595] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 03/24/2019] [Accepted: 03/26/2019] [Indexed: 11/10/2022] Open
Abstract
Self-reference is impaired in psychotic disorders such as schizophrenia, associated with disability, and closely related to characteristic patterns of aberrant brain connectivity. However, at present, it is unclear whether self-reference is impacted in pathogenesis of the disorder. Alterations in connectivity during a self-reference task or resting-state in the psychosis risk (i.e., prodromal) period may yield important clues for biomarker development, as well as for novel treatment targets. This study examined a task-based and resting-state functional magnetic resonance imaging in individuals at clinical high risk (CHR) for psychosis (n = 22) and healthy control unaffected peers (n = 20). The self-reference task comprised three task conditions where subjects were asked if an adjective was relevant to themselves (self), a designated other individual (other), or to evaluate the word's spelling (letter). Connectivity analyses examined medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), regions commonly found in conjunction analyses of self-reference, during both the self-reference task and rest. In task connectivity analyses, CHR individuals exhibited decreased mPFC-PCC connectivity when compared to controls. In resting-state analyses, CHR participants showed greater mPFC-PCC connectivity. Taken together, results suggest that psychosis-like alterations in mPFC-PCC connectivity is present prior to psychosis onset across both task and rest.
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Affiliation(s)
| | | | - Henry R Cowan
- Department of Psychology, Northwestern University, Evanston, Illinois
| | - Joseph M Orr
- Department of Psychological and Brain Sciences, Texas A&M University, College Station, Texas.,Texas A&M Institute for Neuroscience, Texas A&M University, College Station, Texas
| | - Vijay A Mittal
- Department of Psychology, Northwestern University, Evanston, Illinois.,Department of Psychiatry, Northwestern University, Chicago, Illinois.,Medical Social Sciences, Northwestern University, Chicago, Illinois.,Institute for Policy Research (IPR), Northwestern University, Chicago, Illinois.,Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston, Illinois
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25
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Shi L, Sun J, Wei D, Qiu J. Recover from the adversity: functional connectivity basis of psychological resilience. Neuropsychologia 2018; 122:20-27. [PMID: 30529246 DOI: 10.1016/j.neuropsychologia.2018.12.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 11/26/2018] [Accepted: 12/03/2018] [Indexed: 01/16/2023]
Abstract
Psychological resilience refers to the ability that individuals can positively adapt and respond to stress and adversity. It is important for mental health and well-being. However, there was few study examined the functional connectivity basis of psychological resilience. The present study used resting-state seed-based functional connectivity to explore the neural basis of psychological resilience and its association with positive affect in a big healthy sample. Results showed that resilience is associated with functional connectivity between regions involved in emotional flexibility, coping ability, and inhibitory control. Specifically, resilience is positively correlated with the strength of the left insula and the right parahippocampus connectivity which is involved in the self-evaluation process. It is also positively correlated with the strength of the left orbitofrontal gyrus (OFC) and the left inferior frontal gyrus (IFG) connectivity which is associated with the flexible use of emotional resources and flexible control in processing affective information. Additionally, resilience is negatively correlated with the strength of the left OFC and the right precuneus connectivity which is implicated in the rumination in negatively self-related thoughts. Crucially, the left OFC-IFG connectivity mediated the effect of positive affect on resilience, supporting the opinion that positive affect facilitates resilience by broadening one's attention and promoting flexible thinking and coping abilities. In summary, these findings extend previous studies by revealing the functional connectivity basis of psychological resilience and highlighting the left OFC-IFG connectivity as a neural substrate linking positive affect and psychological resilience.
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Affiliation(s)
- Liang Shi
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, China; School of Psychology, Southwest University (SWU), Chongqing, China
| | - Jiangzhou Sun
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, China; School of Psychology, Southwest University (SWU), Chongqing, China
| | - Dongtao Wei
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, China; School of Psychology, Southwest University (SWU), Chongqing, China
| | - Jiang Qiu
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, China; School of Psychology, Southwest University (SWU), Chongqing, China; Southwest University Branch, Collaborative Innovation Center of Assessment Toward Basic Education Quality, Beijing Normal University, Beijing 100875, China.
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26
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Affiliation(s)
- Anthony S David
- PO Box 68, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AF, UK.
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27
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Tordesillas-Gutierrez D, Ayesa-Arriola R, Delgado-Alvarado M, Robinson JL, Lopez-Morinigo J, Pujol J, Dominguez-Ballesteros ME, David AS, Crespo-Facorro B. The right occipital lobe and poor insight in first-episode psychosis. PLoS One 2018; 13:e0197715. [PMID: 29856773 PMCID: PMC5983855 DOI: 10.1371/journal.pone.0197715] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 05/02/2018] [Indexed: 12/12/2022] Open
Abstract
Lack of insight is a core feature of non-affective psychosis and has been associated with poorer outcomes. Brain abnormalities underlying lack of insight have been suggested, mostly in the frontal lobe, although previous research showed mixed results. We used a voxel-based morphometry (VBM) analysis in 108 first-episode non-affective psychosis patients to investigate the pattern of brain structural abnormalities related to lack of insight. In addition, 77 healthy volunteers were compared with the patients classified as having poor and good insight. The shortened version of the Scale to Assess Unawareness of Mental Disorder was used to evaluate insight. Patients with poor insight (n = 68) compared with patients with good insight (n = 40) showed a single significant cluster (kc = 5834; PcFWE = 0.001) of reduced grey matter volume (GMV) in the right occipital lobe extending to its lateral and medial surfaces, the cuneus, and the middle temporal gyrus. In addition, GMV at this cluster showed a negative correlation with the score of the SUMD (r = -0.305; p = 0.001). When comparing patients with poor insight with healthy subjects overall reductions of GMV were found, mainly in frontal and occipital lobes. Hence, poor insight in non-affective psychosis seems to be associated with specific brain abnormalities in the right occipital and temporal cortical regions. Dysfunction in any combination of these areas may contribute to lack of insight in non-affective psychosis. Specifically, the 'right' hemisphere dysfunction underlying impaired insight in our sample is consistent with previously reported similarities between lack of insight in psychosis and anosognosia in neurological disorders.
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Affiliation(s)
- Diana Tordesillas-Gutierrez
- Neuroimaging Unit, Technological Facilities,Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, Spain
- CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain
- * E-mail:
| | - Rosa Ayesa-Arriola
- CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain
- Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain
| | - Manuel Delgado-Alvarado
- Neuroimaging Unit, Technological Facilities,Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, Spain
| | - Jennifer L. Robinson
- Department of Psychology, Auburn University, Auburn, Alabama, United States of America
- Department of Electrical and Computer Engineering, Auburn University, Auburn University Magnetic Resonance Imaging Research Center, Auburn, Alabama, United States of America
- Department of Kinesiology, Auburn University, Auburn, Alabama, United States of America
| | - Javier Lopez-Morinigo
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
| | - Jesus Pujol
- CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain
- MRI Research Unit, Hospital del Mar, Barcelona, Spain
| | | | - Anthony S. David
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
| | - Benedicto Crespo-Facorro
- CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain
- Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain
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28
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Genetic correlates of insight in schizophrenia. Schizophr Res 2018; 195:290-297. [PMID: 29054485 DOI: 10.1016/j.schres.2017.10.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 10/09/2017] [Accepted: 10/09/2017] [Indexed: 12/15/2022]
Abstract
UNLABELLED Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. METHOD Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. RESULTS We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R2=0.005, P=0.05, empirical P=0.054) and treatment insight (R2=0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). CONCLUSION To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed.
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29
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Jimenez AM, Lee J, Wynn JK, Green MF. The neural correlates of self-referential memory encoding and retrieval in schizophrenia. Neuropsychologia 2017; 109:19-27. [PMID: 29217224 DOI: 10.1016/j.neuropsychologia.2017.12.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 11/29/2017] [Accepted: 12/01/2017] [Indexed: 11/17/2022]
Abstract
BACKGROUND Enhanced memory for self-oriented information is known as the self-referential memory (SRM) effect. fMRI studies of the SRM effect have focused almost exclusively on encoding, revealing selective engagement of the medial prefrontal cortex (mPFC) during "self" relative to other processing conditions. Other critical areas for self-processing include ventrolateral prefrontal cortex (vlPFC), temporo-parietal junction (TPJ) and posterior cingulate/precuneus (PCC/PC). Previous behavioral studies show that individuals with schizophrenia fail to benefit from this memory boost. However, the neural correlates of this deficit, at either encoding or retrieval, are unknown. METHODS Twenty individuals with schizophrenia and 16 healthy controls completed an event-related fMRI SRM paradigm. During encoding, trait adjectives were judged in terms of structural features ("case" condition), social desirability ("other" condition), or as self-referential ("self" condition). Participants then completed an unexpected recognition test (retrieval phase). We examined BOLD activation during both encoding and retrieval within mPFC, vlPFC, TPJ, and PCC/PC regions-of-interest (ROIs). RESULTS During encoding, fMRI data indicated both groups had greater activation during the "self" relative to the "other" condition across ROIs. Controls showed this primarily in mPFC whereas patients showed this in PCC/PC. During retrieval, fMRI data indicated controls showed differentiation across ROIs between "self" and "other" conditions, but patients did not. CONCLUSIONS Results suggest regional differences in the neural processing of self-referential information in individuals with schizophrenia, perhaps because representation of the self is not as well established in patients relative to controls. The current study presents novel findings that add to the literature implicating impaired self-oriented processing in schizophrenia.
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Affiliation(s)
- Amy M Jimenez
- Desert Pacific MIRECC, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, 405 Hilgard Ave., Los Angeles, CA 90095, USA.
| | - Junghee Lee
- Department of Psychiatry and Biobehavioral Sciences, University of California, 405 Hilgard Ave., Los Angeles, CA 90095, USA; Desert Pacific MIRECC, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA
| | - Jonathan K Wynn
- Desert Pacific MIRECC, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, 405 Hilgard Ave., Los Angeles, CA 90095, USA
| | - Michael F Green
- Desert Pacific MIRECC, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, 405 Hilgard Ave., Los Angeles, CA 90095, USA
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Kronbichler L, Tschernegg M, Martin AI, Schurz M, Kronbichler M. Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis. Schizophr Bull 2017; 43:1240-1250. [PMID: 28575475 PMCID: PMC5737081 DOI: 10.1093/schbul/sbx073] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects.
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Affiliation(s)
- Lisa Kronbichler
- Neuroscience Institute, Paracelsus Medical University, Christian-Doppler Clinic, Salzburg, Austria,To whom correspondence should be addressed; Neuroscience Institute Paracelsus Medical University, 5020 Salzburg, Austria; tel: +43-57255-56795, fax: +43-662-4483-3089, e-mail:
| | - Melanie Tschernegg
- Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria,Department of Psychology, University of Salzburg, Salzburg, Austria
| | - Anna Isabel Martin
- Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria,Department of Psychology, University of Salzburg, Salzburg, Austria
| | - Matthias Schurz
- Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria,Department of Psychology, University of Salzburg, Salzburg, Austria
| | - Martin Kronbichler
- Neuroscience Institute, Paracelsus Medical University, Christian-Doppler Clinic, Salzburg, Austria,Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria,Department of Psychology, University of Salzburg, Salzburg, Austria
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Abstract
BACKGROUND Insight in schizophrenia is defined as awareness into illness, symptoms, and need for treatment and has long been associated with cognition, other psychopathological symptoms, and several adverse clinical and functional outcomes. However, the biological basis of insight is not clearly understood. OBJECTIVE The aim of this systematic review was to critically evaluate and summarize advances in the study of the biological basis of insight in schizophrenia and to identify gaps in this knowledge. METHODS A literature search of PubMed, CINAHL, PsycINFO, and EMBASE databases was conducted using search terms to identify articles relevant to the biology of insight in schizophrenia published in the last 6 years. Articles that focused on etiology of insight in schizophrenia and those that examined the neurobiology of insight in schizophrenia or psychoses were chosen for analysis. Articles on insight in conditions other than schizophrenia or psychoses and which did not investigate the neurobiological underpinnings of insight were excluded from the review. RESULTS Twenty-six articles met the inclusion criteria for this review. Of the 26 articles, 3 focused on cellular abnormalities and 23 were neuroimaging studies. Preliminary data identify the prefrontal cortex, cingulate cortex, and regions of the temporal and parietal lobe (precuneus, inferior parietal lobule) and hippocampus as the neural correlates of insight. DISCUSSION A growing body of literature attests to the neurobiological basis of insight in schizophrenia. Current evidence supports the neurobiological basis of insight in schizophrenia and identifies specific neural correlates for insight types and its dimensions. Further studies that examine the precise biological mechanisms of insight are needed to apply this knowledge to effective clinical intervention development.
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Chahine G, Richter A, Wolter S, Goya-Maldonado R, Gruber O. Disruptions in the left frontoparietal network underlie resting state endophenotypic markers in schizophrenia. Hum Brain Mapp 2016; 38:1741-1750. [PMID: 28009080 DOI: 10.1002/hbm.23477] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Revised: 11/12/2016] [Accepted: 11/15/2016] [Indexed: 11/10/2022] Open
Abstract
Advances in functional brain imaging have improved the search for potential endophenotypic markers in schizophrenia. Here, we employed independent component analysis (ICA) and dynamic causal modeling (DCM) in resting state fMRI on a sample of 35 schizophrenia patients, 20 first-degree relatives and 35 control subjects. Analysis on ICA-derived networks revealed increased functional connectivity between the left frontoparietal network (FPN) and left temporal and parietal regions in schizophrenia patients (P < 0.001). First-degree relatives shared this hyperconnectivity, in particular in the supramarginal gyrus (SMG; P = 0.008). DCM analysis was employed to further explore underlying effective connectivity. Results showed increased inhibitory connections to the left angular gyrus (AG) in schizophrenia patients from all other nodes of the left FPN (P < 0.001), and in particular from the left SMG (P = 0.001). Relatives also showed a pattern of increased inhibitory connections to the left AG (P = 0.008). Furthermore, the patient group showed increased excitatory connectivity between the left fusiform gyrus and the left SMG (P = 0.002). This connection was negatively correlated to inhibitory afferents to the left AG (P = 0.005) and to the negative symptom score on the PANSS scale (P = 0.001, r = -0.51). Left frontoparietotemporal dysfunction in schizophrenia has been previously associated with a range of abnormalities, including formal thought disorder, working memory dysfunction and sensory hallucinations. Our analysis uncovered new potential endophenotypic markers of schizophrenia and shed light on the organization of the left FPN in patients and their first-degree relatives. Hum Brain Mapp 38:1741-1750, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- George Chahine
- Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems, Neuroscience and Clinical Psychiatry, George August University, Göttingen, Germany.,Department of Psychiatry, Maimonides Medical Center, Brooklyn, New York
| | - Anja Richter
- Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany
| | - Sarah Wolter
- Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems, Neuroscience and Clinical Psychiatry, George August University, Göttingen, Germany
| | - Roberto Goya-Maldonado
- Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems, Neuroscience and Clinical Psychiatry, George August University, Göttingen, Germany
| | - Oliver Gruber
- Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany
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Mindful Disintegration and the Decomposition of Self in Healthy Populations: Conception and Preliminary Study. PSYCHOLOGICAL STUDIES 2016. [DOI: 10.1007/s12646-016-0374-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Rao N, Menon S. A heuristic model linking yoga philosophy and self-reflection to examine underlying mechanisms of add-on yoga treatment in schizophrenia. Int Rev Psychiatry 2016; 28:265-72. [PMID: 27310309 DOI: 10.1080/09540261.2016.1194259] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Preliminary evidence suggests efficacy of yoga as add-on treatment for schizophrenia, but the underlying mechanism by which yoga improves the symptoms of schizophrenia is not completely understood. Yoga improves self-reflection in healthy individuals, and self-reflection abnormalities are typically seen in schizophrenia. However, whether yoga treatment improves impairments in self-reflection typically seen in patients with schizophrenia is not examined. This paper discusses the potential mechanism of yoga in the treatment of schizophrenia and proposes a testable hypothesis for further empirical studies. It is proposed that self-reflection abnormalities in schizophrenia improve with yoga and the neurobiological changes associated with this can be examined using empirical behavioural measures and neuroimaging measures such as magnetic resonance imaging.
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Affiliation(s)
- Naren Rao
- a National Institute of Mental Health and Neurosciences , Bangalore , India
| | - Sangeetha Menon
- b National Institute of Advanced studies , Bangalore , India
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35
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Abstract
The concept of insight in psychosis has been an interesting area in clinical psychiatry for well over a century with a surge in research interest over the past 25 years. Moreover, the past 5 years have been particularly fruitful in deciphering its neurobiological underpinnings. This article presents the development of the concept of insight in psychosis and reviews the current neurobiological research findings in this area.
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Affiliation(s)
- Starlin Vijay Mythri
- Asha Bipolar Clinic, Asha Hospital, Road no.14, Banjara Hills, Hyderabad, Telangana, India
| | - Y Sanjay
- Professor, Department of Psychiatry, Katuri Medical College and Hospital, Eudulapalem, Guntur - 522019, Andhra Pradesh, India
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Abstract
In spite of the increasing number of studies on insight in psychiatry and also in neurology and psychology, its nature is still elusive. It encompasses at least three fundamental characteristics: the awareness of suffering from an illness, an understanding of the cause and source of this suffering, and an acknowledgment of the need for treatment. As such, insight is fundamental for patients' management, prognosis, and treatment. Not surprisingly, the majority of available data, which have been gathered on schizophrenia, show a relationship between low insight and poorer outcomes. For mood disorders, however, insight is associated with less positive results. For other psychiatric disorders, insight has rarely been investigated. In neurology, the impaired ability to recognize the presence of sensory, perceptual, motor, affective, or cognitive functioning-referred to as anosognosia-has been related to damage of specific brain regions. This article provides a comprehensive review of insight in different psychiatric and neurological disorders, with a special focus on brain areas and neurotransmitters that serve as the substrate for this complex phenomenon.
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37
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Renes RA, Vink M, van der Weiden A, Prikken M, Koevoets MGJC, Kahn RS, Aarts H, van Haren NEM. Impaired frontal processing during agency inferences in schizophrenia. Psychiatry Res Neuroimaging 2016; 248:134-141. [PMID: 26776080 DOI: 10.1016/j.pscychresns.2015.12.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 11/24/2015] [Accepted: 12/22/2015] [Indexed: 11/30/2022]
Abstract
People generally experience themselves as the cause of outcomes following from their own actions. Such agency inferences occur fluently and are essential to social interaction. However, schizophrenia patients often experience difficulties in distinguishing their own actions from those of others. Building on recent research into the neural substrates underlying agency inferences in healthy individuals, the present study investigates how these inferences are represented on a neural level in patients with schizophrenia. Thirty-one schizophrenia patients and 31 healthy controls performed an agency inference task while functional magnetic resonance images were obtained. Participants were presented with a task wherein the relationship between their actions and the subsequent outcomes was ambiguous. They received instructions to cause specific outcomes to occur by pressing a key, but the task was designed to match or mismatch the color outcome with the participants' goal. Both groups experienced stronger agency when their goal matched (vs. mismatched) the outcome. However, region of interest analyses revealed that only controls showed the expected involvement of the medial prefrontal cortex and superior frontal gyrus, whereas in patients the agency experience was not related to brain activation. These findings are discussed in light of a hypofrontality model of schizophrenia.
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Affiliation(s)
- Robert A Renes
- Department of Psychology, Utrecht University, Utrecht, The Netherlands.
| | - Matthijs Vink
- Department of Psychiatry of the Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Anouk van der Weiden
- Department of Psychiatry of the Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Merel Prikken
- Department of Psychiatry of the Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Martijn G J C Koevoets
- Department of Psychiatry of the Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - René S Kahn
- Department of Psychiatry of the Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Henk Aarts
- Department of Psychology, Utrecht University, Utrecht, The Netherlands
| | - Neeltje E M van Haren
- Department of Psychiatry of the Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
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38
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de Vos AE, Pijnenborg GHM, Aleman A, van der Meer L. Implicit and explicit self-related processing in relation to insight in patients with schizophrenia. Cogn Neuropsychiatry 2016; 20:311-29. [PMID: 26017116 DOI: 10.1080/13546805.2015.1040151] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Self-related processing (SRP) has been associated with clinical and cognitive insight. We investigated the relationship between implicit SRP (ISRP) and explicit SRP (ESRP) and insight. We first hypothesised that impaired insight is associated with the extent to which implicit feedback is incorporated in the self-image and subsequently influences behaviour. Second, we hypothesised that impaired insight is related to the way patients handle explicit feedback and use it to guide subsequent behaviour, therefore we expected to find a positive relationship between level of insight and the explicit self-related processing task. METHODS Thirty-four schizophrenia patients and 23 healthy controls participated in the study. Patients were assessed with the Schedule for the Assessment of Insight-Expanded and the Beck Cognitive Insight Scale. ISRP was measured using a working memory two-back priming task. ESRP was measured with an adapted version of the Wisconsin Card Sorting Task where patients received explicit feedback on their performance. RESULTS Cognitive insight, but not clinical insight, was positively associated with ISRP after implicit positive cues. Both clinical and cognitive insight were positively associated with the ability to adjust performance upon receiving explicit feedback, though cognitive insight was more strongly associated with overall task performance. CONCLUSIONS Priming with positive cues improved performance on a working memory task in patients with good cognitive insight, but worsened performance in patients with impaired cognitive insight. Furthermore, our findings suggest that the ability to adequately use feedback may be a specific capacity that is related to insight.
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Affiliation(s)
- Annerieke E de Vos
- a Department of Psychotic Disorders , GGZ Drenthe , Assen , the Netherlands
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Pankow A, Katthagen T, Diner S, Deserno L, Boehme R, Kathmann N, Gleich T, Gaebler M, Walter H, Heinz A, Schlagenhauf F. Aberrant Salience Is Related to Dysfunctional Self-Referential Processing in Psychosis. Schizophr Bull 2016; 42. [PMID: 26194892 PMCID: PMC4681553 DOI: 10.1093/schbul/sbv098] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis. We investigated the neural correlates of self-referential processing, aberrant salience attribution, and the relationship between these 2 measures across the psychosis continuum. METHODS Twenty-nine schizophrenia patients, 24 healthy individuals with subclinical delusional ideation, and 50 healthy individuals participated in this study. Aberrant salience was assessed behaviorally in terms of reaction times to task irrelevant cues. Participants performed a self-reference task during fMRI in which they had to apply neutral trait words to them or to a public figure. The correlation between self-referential processing and aberrant salience attribution was tested. RESULTS Schizophrenia patients displayed increased aberrant salience attribution compared with healthy controls and individuals with subclinical delusional ideation, while the latter exhibited intermediate aberrant salience scores. In the self-reference task, schizophrenia patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC), but individuals with subclinical delusional ideation did not differ from healthy controls. In schizophrenia patients, vmPFC activation correlated negatively with implicit aberrant salience attribution. CONCLUSIONS Higher aberrant salience attribution in schizophrenia patients is related to reduced vmPFC activation during self-referential judgments suggesting that aberrant relevance coding is reflected in decreased neural self-referential processing as well as in aberrant salience attribution.
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Affiliation(s)
- Anne Pankow
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany;
| | - Teresa Katthagen
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Sarah Diner
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | | | - Rebecca Boehme
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Nobert Kathmann
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Tobias Gleich
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Gaebler
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Faculty of Medicine, Universität Leipzig, Leipzig, Germany
| | - Henrik Walter
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Heinz
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Florian Schlagenhauf
- Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany; Max Planck Fellow Group 'Cognitive and Affective Control of Behavioral Adaption', Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
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40
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Pang Y, Cui Q, Duan X, Chen H, Zeng L, Zhang Z, Lu G, Chen H. Extraversion modulates functional connectivity hubs of resting-state brain networks. J Neuropsychol 2015; 11:347-361. [PMID: 26566723 DOI: 10.1111/jnp.12090] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 08/25/2015] [Indexed: 12/31/2022]
Abstract
Personality dimension extraversion describes individual differences in social behaviour and socio-emotional functioning. The intrinsic functional connectivity patterns of the brain are reportedly associated with extraversion. However, whether or not extraversion is associated with functional hubs warrants clarification. Functional hubs are involved in the rapid integration of neural processing, and their dysfunction contributes to the development of neuropsychiatric disorders. In this study, we employed the functional connectivity density (FCD) method for the first time to distinguish the energy-efficient hubs associated with extraversion. The resting-state functional magnetic resonance imaging data of 71 healthy subjects were used in the analysis. Short-range FCD was positively correlated with extraversion in the left cuneus, revealing a link between the local functional activity of this region and extraversion in risk-taking. Long-range FCD was negatively correlated with extraversion in the right superior frontal gyrus and the inferior frontal gyrus. Seed-based resting-state functional connectivity (RSFC) analyses revealed that a decreased long-range FCD in individuals with high extraversion scores showed a low long-range functional connectivity pattern between the medial and dorsolateral prefrontal cortex, middle temporal gyrus, and anterior cingulate cortex. This result suggests that decreased RSFC patterns are responsible for self-esteem, self-evaluation, and inhibitory behaviour system that account for the modulation and shaping of extraversion. Overall, our results emphasize specific brain hubs, and reveal long-range functional connections in relation to extraversion, thereby providing a neurobiological basis of extraversion.
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Affiliation(s)
- Yajing Pang
- Center for Information in BioMedicine, Key laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
| | - Qian Cui
- School of Political Science and Public Administration, University of Electronic Science and Technology of China, Chengdu, China
| | - Xujun Duan
- Center for Information in BioMedicine, Key laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
| | - Heng Chen
- Center for Information in BioMedicine, Key laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
| | - Ling Zeng
- Center for Information in BioMedicine, Key laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhiqiang Zhang
- Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, China
| | - Guangming Lu
- Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, China
| | - Huafu Chen
- Center for Information in BioMedicine, Key laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
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Ćurčić-Blake B, van der Meer L, Pijnenborg GHM, David AS, Aleman A. Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia. Hum Brain Mapp 2015; 36:4859-68. [PMID: 26467308 DOI: 10.1002/hbm.22955] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/11/2015] [Accepted: 08/17/2015] [Indexed: 01/01/2023] Open
Abstract
Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self-reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty-five schizophrenia patients and 19 healthy subjects performed a self-reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small-scale significant changes in white matter integrity associated with clinical insight. Self-reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small-scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self-processing regions. Similarly, the observed hyper-connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study.
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Affiliation(s)
- Branislava Ćurčić-Blake
- Department of Neuroscience, University of Groningen, BCN Neuroimaging Center (NIC), University Medical Center, Groningen, The Netherlands
| | - Lisette van der Meer
- Department of Neuroscience, University of Groningen, BCN Neuroimaging Center (NIC), University Medical Center, Groningen, The Netherlands.,Department of Rehabilitation, Lentis, Zuidlaren, The Netherlands
| | - Gerdina H M Pijnenborg
- Department of Clinical Psychosis and Experimental Psychopathalogy, University of Groningen, Grote Kruisstraat, The Netherlands.,Department of Psychotic Disorders, GGZ Drenthe, Assen, The Netherlands
| | - Anthony S David
- Department of Psychosis Studies, Institute of Psychiatry, King's College London, Denmark, Hill, United Kingdom
| | - André Aleman
- Department of Neuroscience, University of Groningen, BCN Neuroimaging Center (NIC), University Medical Center, Groningen, The Netherlands
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Tan S, Zhao Y, Fan F, Zou Y, Jin Z, Zen Y, Zhu X, Yang F, Tan Y, Zhou D. Brain Correlates of Self-Evaluation Deficits in Schizophrenia: A Combined Functional and Structural MRI Study. PLoS One 2015; 10:e0138737. [PMID: 26406464 PMCID: PMC4583545 DOI: 10.1371/journal.pone.0138737] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 09/01/2015] [Indexed: 11/11/2022] Open
Abstract
Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC) and the anterior cingulate cortex (ACC) than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC) as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC) among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment.
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Affiliation(s)
- Shuping Tan
- Institute of Mental Health, Peking University, Beijing, 100191, China
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
| | - Yanli Zhao
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
| | - Fengmei Fan
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
| | - Yizhuang Zou
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
- * E-mail: (YZZ); (DFZ)
| | - Zhen Jin
- Magnetic Research Imaging Unit, The 306th Hospital of PLA, Beijing, 100101, China
| | - Yawei Zen
- Magnetic Research Imaging Unit, The 306th Hospital of PLA, Beijing, 100101, China
| | - Xiaolin Zhu
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
| | - Fude Yang
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
| | - Yunlong Tan
- Center of Psychiatry Research, Beijing Huilongguan Hospital, Beijing, 100096, China
| | - Dongfeng Zhou
- Institute of Mental Health, Peking University, Beijing, 100191, China
- * E-mail: (YZZ); (DFZ)
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Shad MU, Keshavan MS. Neurobiology of insight deficits in schizophrenia: An fMRI study. Schizophr Res 2015; 165:220-6. [PMID: 25957484 PMCID: PMC4457549 DOI: 10.1016/j.schres.2015.04.021] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 04/15/2015] [Accepted: 04/17/2015] [Indexed: 12/20/2022]
Abstract
Prior research has shown insight deficits in schizophrenia to be associated with specific neuroimaging changes (primarily structural) especially in the prefrontal sub-regions. However, little is known about the functional correlates of impaired insight. Seventeen patients with schizophrenia (mean age 40.0±10.3; M/F=14/3) underwent fMRI on a Philips 3.0 T Achieva system while performing on a self-awareness task containing self- vs. other-directed sentence stimuli. SPM5 was used to process the imaging data. Preprocessing consisted of realignment, coregistration, and normalization, and smoothing. A regression analysis was used to examine the relationship between brain activation in response to self-directed versus other-directed sentence stimuli and average scores on behavioral measures of awareness of symptoms and attribution of symptoms to the illness from Scale to Assess Unawareness of Mental Disorders. Family Wise Error correction was employed in the fMRI analysis. Average scores on awareness of symptoms (1=aware; 5=unaware) were associated with activation of multiple brain regions, including prefrontal, parietal and limbic areas as well as basal ganglia. However, average scores on correct attribution of symptoms (1=attribute; 5=misattribute) were associated with relatively more localized activation of prefrontal cortex and basal ganglia. These findings suggest that unawareness and misattribution of symptoms may have different neurobiological basis in schizophrenia. While symptom unawareness may be a function of a more complex brain network, symptom misattribution may be mediated by specific brain regions.
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Zhang L, Opmeer EM, Ruhé HG, Aleman A, van der Meer L. Brain activation during self- and other-reflection in bipolar disorder with a history of psychosis: Comparison to schizophrenia. NEUROIMAGE-CLINICAL 2015; 8:202-9. [PMID: 26106544 PMCID: PMC4473805 DOI: 10.1016/j.nicl.2015.04.010] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 04/14/2015] [Accepted: 04/16/2015] [Indexed: 01/03/2023]
Abstract
Objectives Reflecting on the self and on others activates specific brain areas and contributes to metacognition and social cognition. The aim of the current study is to investigate brain activation during self- and other-reflection in patients with bipolar disorder (BD). In addition, we examined whether potential abnormal brain activation in BD patients could distinguish BD from patients with schizophrenia (SZ). Methods During functional magnetic resonance imaging (fMRI), 17 BD patients, 17 SZ patients and 21 healthy controls (HCs) performed a self-reflection task. The task consisted of sentences divided into three conditions: self-reflection, other-reflection and semantic control. Results BD patients showed less activation in the posterior cingulate cortex (PCC) extending to the precuneus during other-reflection compared to HCs (p = 0.028 FWE corrected on cluster-level within the regions of interest). In SZ patients, the level of activation in this area was in between BD patients and HCs, with no significant differences between patients with SZ and BD. There were no group differences in brain activation during self-reflection. Moreover, there was a positive correlation between the PCC/precuneus activation during other-reflection and cognitive insight in SZ patients, but not in BD patients. Conclusions BD patients showed less activation in the PCC/precuneus during other-reflection. This may support an account of impaired integration of emotion and memory (evaluation of past and current other-related information) in BD patients. Correlation differences of the PCC/precuneus activation with the cognitive insight in patients with BD and SZ might reflect an important difference between these disorders, which may help to further explore potentially distinguishing markers.
We investigated self-reflection and other-reflection in bipolar disorder. Bipolar had less PCC/precuneus activation during other-reflection than controls. PCC/precuneus activation was unrelated to cognitive insight in bipolar patients.
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Affiliation(s)
- Liwen Zhang
- Neuroimaging Center, Department of Neuroscience, University Medical Center, University of Groningen, Groningen, The Netherlands
| | - Esther M Opmeer
- Neuroimaging Center, Department of Neuroscience, University Medical Center, University of Groningen, Groningen, The Netherlands
| | - Henricus G Ruhé
- University Medical Center Groningen, Department of Psychiatry, University of Groningen, Program for Mood and Anxiety Disorders, Groningen, The Netherlands
| | - André Aleman
- Neuroimaging Center, Department of Neuroscience, University Medical Center, University of Groningen, Groningen, The Netherlands ; Department of Psychology, University of Groningen, Groningen, The Netherlands
| | - Lisette van der Meer
- Neuroimaging Center, Department of Neuroscience, University Medical Center, University of Groningen, Groningen, The Netherlands ; Department of Rehabilitation, Lentis Psychiatric Institute, Zuidlaren, The Netherlands
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Yan C, Yang T, Yu QJ, Jin Z, Cheung EFC, Liu X, Chan RCK. Rostral medial prefrontal dysfunctions and consummatory pleasure in schizophrenia: a meta-analysis of functional imaging studies. Psychiatry Res 2015; 231:187-96. [PMID: 25637357 DOI: 10.1016/j.pscychresns.2015.01.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 08/22/2014] [Accepted: 01/01/2015] [Indexed: 01/10/2023]
Abstract
A large number of imaging studies have examined the neural correlates of consummatory pleasure and anticipatory pleasure in schizophrenia, but the brain regions where schizophrenia patients consistently demonstrate dysfunctions remain unclear. We performed a series of meta-analyses on imaging studies to delineate the regions associated with consummatory and anticipatory pleasure dysfunctions in schizophrenia. Nineteen functional magnetic resonance imaging or positron emission tomography studies using whole brain analysis were identified through a literature search (PubMed and EBSCO; January 1990-February 2014). Activation likelihood estimation was performed using the GingerALE software. The clusters identified were obtained after controlling for the false discovery rate at p<0.05 and applying a minimum cluster size of 200 mm(3). It was found that schizophrenia patients exhibited decreased activation mainly in the rostral medial prefrontal cortex (rmPFC), the right parahippocampus/amygala, and other limbic regions (e.g., the subgenual anterior cingulate cortex, the putamen, and the medial globus pallidus) when consummating pleasure. Task instructions (feeling vs. stimuli) were differentially related to medial prefrontal dysfunction in schizophrenia. When patients anticipated pleasure, reduced activation in the left putamen was observed, despite the limited number of studies. Our findings suggest that the medial prefrontal cortex and limbic regions may play an important role in neural dysfunction underlying deficits in consummatory pleasure in schizophrenia.
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Affiliation(s)
- Chao Yan
- Shanghai Key Laboratory of Brain Functional Genomics (MOE & STCSM), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China; Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
| | - Tammy Yang
- Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Qi-Jing Yu
- Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Zhen Jin
- Beijing 306 Hospital, Beijing, China
| | - Eric F C Cheung
- Castle Peak Hospital, Hong Kong Special Administrative Region, China
| | - Xun Liu
- Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Magnetic Resonance Imaging Research Centre, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Raymond C K Chan
- Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Magnetic Resonance Imaging Research Centre, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
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Gerretsen P, Menon M, Mamo DC, Fervaha G, Remington G, Pollock BG, Graff-Guerrero A. Impaired insight into illness and cognitive insight in schizophrenia spectrum disorders: resting state functional connectivity. Schizophr Res 2014; 160:43-50. [PMID: 25458571 PMCID: PMC4429527 DOI: 10.1016/j.schres.2014.10.015] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Revised: 10/10/2014] [Accepted: 10/14/2014] [Indexed: 01/17/2023]
Abstract
BACKGROUND Impaired insight into illness (clinical insight) in schizophrenia has negative effects on treatment adherence and clinical outcomes. Schizophrenia is described as a disorder of disrupted brain connectivity. In line with this concept, resting state networks (RSNs) appear differentially affected in persons with schizophrenia. Therefore, impaired clinical, or the related construct of cognitive insight (which posits that impaired clinical insight is a function of metacognitive deficits), may reflect alterations in RSN functional connectivity (fc). Based on our previous research, which showed that impaired insight into illness was associated with increased left hemisphere volume relative to right, we hypothesized that impaired clinical insight would be associated with increased connectivity in the DMN with specific left hemisphere brain regions. METHODS Resting state MRI scans were acquired for participants with schizophrenia or schizoaffective disorder (n=20). Seed-to-voxel and ROI-to-ROI fc analyses were performed using the CONN-fMRI fc toolbox v13 for established RSNs. Clinical and cognitive insight were measured with the Schedule for the Assessment of Insight-Expanded Version and Beck Cognitive Insight Scale, respectively, and included as the regressors in fc analyses. RESULTS As hypothesized, impaired clinical insight was associated with increased connectivity in the default mode network (DMN) with the left angular gyrus, and also in the self-referential network (SRN) with the left insula. Cognitive insight was associated with increased connectivity in the dorsal attention network (DAN) with the right inferior frontal cortex (IFC) and left anterior cingulate cortex (ACC). CONCLUSION Increased connectivity in DMN and SRN with the left angular gyrus and insula, respectively, may represent neural correlates of impaired clinical insight in schizophrenia spectrum disorders, and is consistent with the literature attributing impaired insight to left hemisphere dominance. Increased connectivity in the DAN with the IFC and ACC in relation to cognitive insight may facilitate enhanced mental flexibility in this sample.
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Affiliation(s)
- Philip Gerretsen
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada,Geriatric Mental Health Program, Centre for Addiction & Mental Health, Canada,Department of Psychiatry, University of Toronto, Canada,Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Mahesh Menon
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada,Department of Psychiatry, University of British Columbia, Canada
| | - David C. Mamo
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada,Department of Psychiatry, University of Toronto, Canada,Department of Psychiatry, Faculties of Medicine and Health Science, University of Malta, Msida, Malta
| | - Gagan Fervaha
- Schizophrenia Program, Centre for Addiction & Mental Health, Canada,Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Gary Remington
- Schizophrenia Program, Centre for Addiction & Mental Health, Canada,Department of Psychiatry, University of Toronto, Canada,Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Canada,Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Bruce G. Pollock
- Geriatric Mental Health Program, Centre for Addiction & Mental Health, Canada,Department of Psychiatry, University of Toronto, Canada,Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Canada,Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Ariel Graff-Guerrero
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada; Geriatric Mental Health Program, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
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Ouzir M, Azorin JM. Neuroimagerie de l’insight dans la schizophrénie : revue de la littérature. ANNALES MEDICO-PSYCHOLOGIQUES 2014. [DOI: 10.1016/j.amp.2013.07.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Brent BK, Seidman LJ, Coombs G, Keshavan MS, Moran JM, Holt DJ. Neural responses during social reflection in relatives of schizophrenia patients: relationship to subclinical delusions. Schizophr Res 2014; 157:292-8. [PMID: 24951401 PMCID: PMC4109724 DOI: 10.1016/j.schres.2014.05.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Revised: 05/21/2014] [Accepted: 05/23/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND Deficits in the capacity to reflect about the self and others ("social reflection" [SR]) have been identified in schizophrenia, as well as in people with a genetic or clinical risk for the disorder. However, the neural underpinnings of these abnormalities are incompletely understood. METHODS Responses of a network of brain regions known to be involved in self and other processing (e.g., medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and superior temporal gyrus (STG)) were measured during SR in 16 first-degree, non-psychotic relatives (RELS) of schizophrenia patients and 16 healthy controls (CONS). Because of prior evidence linking dysfunction in this network and delusions, associations between SR-related responses of this network and subclinical delusions (measured using the Peters et al. Delusions Inventory) were also examined. RESULTS Compared with CONS, RELS showed significantly less SR-related activity of the right and left PCC and STG. Moreover, response magnitudes were negatively correlated with levels of delusional thinking across both groups. CONCLUSIONS These findings suggest that aberrant function of the neural circuitry underpinning SR is associated with the genetic liability to schizophrenia and confers vulnerability to delusional beliefs.
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Affiliation(s)
- Benjamin K. Brent
- The Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,The Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Larry J. Seidman
- The Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,The Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Garth Coombs
- The Department of Psychology, Harvard University, Cambridge, MA
| | - Matcheri S. Keshavan
- The Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Joseph M. Moran
- The Center for Brain Sciences, Harvard University, Cambridge, MA,U.S. Army Natick Soldier Research, Development, and Engineering Center
| | - Daphne J. Holt
- The HST-MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA,The Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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The neuropsychology of self-reflection in psychiatric illness. J Psychiatr Res 2014; 54:55-63. [PMID: 24685311 PMCID: PMC4022422 DOI: 10.1016/j.jpsychires.2014.03.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 02/10/2014] [Accepted: 03/07/2014] [Indexed: 01/02/2023]
Abstract
The development of robust neuropsychological measures of social and affective function-which link critical dimensions of mental health to their underlying neural circuitry-could be a key step in achieving a more pathophysiologically-based approach to psychiatric medicine. In this article, we summarize research indicating that self-reflection (the inward attention to personal thoughts, memories, feelings, and actions) may be a useful model for developing such a paradigm, as there is evidence that self-reflection is (1) measurable with self-report scales and performance-based tests, (2) linked to the activity of a specific neural circuit, and (3) dimensionally related to mental health and various forms of psychopathology.
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Sepede G, Spano MC, Lorusso M, Berardis DD, Salerno RM, Giannantonio MD, Gambi F. Sustained attention in psychosis: Neuroimaging findings. World J Radiol 2014; 6:261-273. [PMID: 24976929 PMCID: PMC4072813 DOI: 10.4329/wjr.v6.i6.261] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 02/07/2014] [Accepted: 05/16/2014] [Indexed: 02/06/2023] Open
Abstract
To provide a systematic review of scientific literature on functional magnetic resonance imaging (fMRI) studies on sustained attention in psychosis. We searched PubMed to identify fMRI studies pertaining sustained attention in both affective and non-affective psychosis. Only studies conducted on adult patients using a sustained attention task during fMRI scanning were included in the final review. The search was conducted on September 10th, 2013. 15 fMRI studies met our inclusion criteria: 12 studies were focused on Schizophrenia and 3 on Bipolar Disorder Type I (BDI). Only half of the Schizophrenia studies and two of the BDI studies reported behavioral abnormalities, but all of them evidenced significant functional differences in brain regions related to the sustained attention system. Altered functioning of the insula was found in both Schizophrenia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlighting differences and similarities between Schizophrenia and BDI.
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