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Bayat M, Hernandez M, Curzon M, Garic D, Graziano P, Dick AS. Reduced recruitment of inhibitory control regions in very young children with ADHD during a modified Kiddie Continuous Performance Task: A fMRI study. Cortex 2025; 185:153-169. [PMID: 40058332 PMCID: PMC12013342 DOI: 10.1016/j.cortex.2024.11.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 08/23/2024] [Accepted: 11/22/2024] [Indexed: 03/19/2025]
Abstract
Attention-Deficit/Hyperactivity Disorder (ADHD) symptom profiles are known to undergo changes throughout development, rendering the neurobiological assessment of ADHD challenging across different developmental stages. Particularly in young children (ages 4- to 7-years), measuring inhibitory control network activity in the brain has been a formidable task due to the lack of child-friendly functional Magnetic Resonance Imaging (fMRI) paradigms. This study aims to address these difficulties by focusing on measuring inhibitory control in very young children within the MRI environment. A total of 56 children diagnosed with ADHD and 78 typically developing (TD) 4-7-year-old children were successfully examined using a modified version of the Kiddie-Continuous Performance Test (K-CPT) during BOLD fMRI to assess inhibitory control. We also evaluated their performance on the standardized K-CPT outside the MRI scanner. Our findings suggest that the modified K-CPT effectively elicited robust and expected brain activity related to inhibitory control in both groups who were successfully scanned. Comparisons between the two groups revealed differences in brain activity, primarily observed in inferior frontal gyrus, anterior insula, dorsal striatum, medial pre-supplementary motor area (pre-SMA), and cingulate cortex (p < .005, corrected). Notably, for both groups increased activity in the right anterior insula was associated with improved response time (RT) and reduced RT variability on the K-CPT administered outside the MRI environment, although this did not survive statistical correction for multiple comparisons. The study also revealed continuing challenges for scanning this population-an additional 51 TD children and 78 children with ADHD were scanned, but failed to provide useable data due to movement. In summary, for a subsample of children, we successfully overcame some of the challenges of measuring inhibitory control in very young children within the MRI environment by using a modified K-CPT during BOLD fMRI, but further challenges remain for scanning in this population. The findings shed light on the neurobiological correlates of inhibitory control in ADHD and TD children, provide valuable insights for understanding ADHD across development, and potentially inform ADHD diagnosis and intervention strategies. The research also highlights remaining challenges with task fMRI in very young clinical samples.
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Affiliation(s)
- Mohammadreza Bayat
- Department of Psychology and the Center for Children and Families, Florida International University, Miami, FL, USA
| | - Melissa Hernandez
- Department of Psychology and the Center for Children and Families, Florida International University, Miami, FL, USA
| | - Madeline Curzon
- Department of Psychology and the Center for Children and Families, Florida International University, Miami, FL, USA
| | - Dea Garic
- Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Paulo Graziano
- Department of Psychology and the Center for Children and Families, Florida International University, Miami, FL, USA
| | - Anthony Steven Dick
- Department of Psychology and the Center for Children and Families, Florida International University, Miami, FL, USA.
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Ramos L, Harr AE, Zakas FL, Essig SR, Kempskie GJ, Fadil NA, Schmid MG, Pompy MD, Curley MC, Gabel LA, Hallock HL. Overexpression of the Apoe gene in the frontal cortex of mice causes sex-dependent changes in learning, attention, and anxiety-like behavior. Learn Mem 2025; 32:a054064. [PMID: 40054882 PMCID: PMC11924598 DOI: 10.1101/lm.054064.124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/17/2024] [Indexed: 03/12/2025]
Abstract
Apolipoprotein E (ApoE) is a protein that is important for lipid storage, transport, and metabolism. APOE gene variants are associated with Alzheimer's disease, as well as attentional function in healthy humans. Previous research has shown that Apoe transcription is increased following stimulation of the pathway between the locus coeruleus (LC) and frontal cortex (FC) in mice. This result suggests that Apoe may affect attentional function by virtue of its expression in circuits that control attention. Does Apoe causally regulate attention, or is its expression simply a byproduct of neuronal activity in the LC and FC? To answer this question, we synthetically induced Apoe transcription in the FC of male and female mice, and subsequently tested their ability to learn a touchscreen-based rodent version of the continuous performance test of sustained attention (the rCPT). We found that increased Apoe transcription impaired performance when attentional demand was increased in male mice, while in female mice, increased Apoe transcription significantly accelerated rCPT learning. We further found that this increase in Apoe transcription affected one metric of the open field test, as well as cellular activity in the FC in a sex-dependent manner. The results of this study provide insight into how Apoe causally regulates translationally relevant behaviors in rodent models.
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Affiliation(s)
- Lizbeth Ramos
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Abigail E Harr
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Finian L Zakas
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Samuel R Essig
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Griffen J Kempskie
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Nelly A Fadil
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Makayla G Schmid
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Madison D Pompy
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Michael C Curley
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Lisa A Gabel
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
| | - Henry L Hallock
- Neuroscience Program, Lafayette College, Easton, Pennsylvania 18042, USA
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Mark CA, Poltavski DV. Functional near-infrared spectroscopy is a sensitive marker of neurophysiological deficits on executive function tasks in young adults with a history of child abuse. APPLIED NEUROPSYCHOLOGY. ADULT 2025; 32:471-484. [PMID: 36803059 DOI: 10.1080/23279095.2023.2179399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Previous research has shown the utility of imaging measures of neural activity in identifying deficits in cognitive functioning in individuals with a history of child abuse. The purpose of the present study was to measure differences that may exist between individuals who reported physical, emotional, or sexual abuse as children (n = 37) vs. those who did not (n = 47) using Functional Near Infrared Spectroscopy (fNIRS) during the completion of cognitive tasks of executive function. The results showed a significantly higher rate and number of errors of commission on the Conners CPT test in the child abuse group compared to the control group. The analyses also showed a statistically significant decrease in oxyhemoglobin (oxy-Hb) concentration in the left rostral prefrontal cortex in the child abuse group compared to the no-abuse group during the Wisconsin Card Sorting Test (WCST). A similar, albeit non-significant, trend toward decreased oxy-Hb concentration was observed in the child abuse group in the right dorsolateral prefrontal cortex (dlPFC) on the OSPAN and Connors CPT. The results suggest that the latter group may show subtle neurological deficits that persist into adulthood that may not manifest on traditional measures of cognitive function. These findings have implications for the development of remediation and treatment strategies in this population.
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Affiliation(s)
- Christopher A Mark
- Department of Psychology, University of North Dakota, Grand Forks, ND, USA
| | - Dmitri V Poltavski
- Department of Psychology, University of North Dakota, Grand Forks, ND, USA
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Wehrli JM, Xia Y, Meister L, Tursunova S, Kleim B, Bach DR, Quednow BB. Forget me not: The effect of doxycycline on human declarative memory. Eur Neuropsychopharmacol 2024; 89:1-9. [PMID: 39217739 DOI: 10.1016/j.euroneuro.2024.08.006] [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: 05/08/2024] [Revised: 08/08/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024]
Abstract
Investigations into neuroprotective drugs are in high demand for the treatment of neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, but also psychiatric disorders, such as depression, trauma, and substance use. One potential drug class being investigated are tetracyclines impacting on a variety of neuroprotective mechanisms. At the same time, tetracyclines like doxycycline have been suggested to affect human fear and spatial memory as well as reducing declarative memory retention. Based on the assumed necessity for synaptic consolidation in hippocampus-dependent learning, we hypothesised declarative memory may be similarly impaired by doxycycline as fear and spatial memory. Therefore, in this study we investigate the potential diminishing effects of doxycycline on consolidation of declarative memory in healthy humans. Additionally, to test for effect specificity we assessed motor memory, sustained attention, and processing speed. We administered a neuropsychological test battery in three independent randomized placebo-controlled double-blind trials (RCTs), in which healthy young volunteers (total N = 252) either received a single oral dose doxycycline (200 mg, n = 126) or placebo (n = 126) in a between-subject design. We found no evidence for a detrimental effect of doxycycline on declarative memory; instead, doxycycline improved declarative learning (p-value=0.022, Cohen's d=0.15) and memory consolidation (p=0.040, d=0.26). Contrarily, doxycycline slightly reduced motor learning (p=0.001, d=0.10) but subtly strengthened long-term motor memory (p=0.001, d=0.10). These results suggest that doxycycline can improve declarative learning and memory without having long term negative effects on other cognitive domains in healthy humans. Our results give hope to further investigate doxycycline in neuroprotective treatment applications.
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Affiliation(s)
- Jelena M Wehrli
- Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland.
| | - Yanfang Xia
- Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland
| | - Laura Meister
- Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland
| | - Sarrina Tursunova
- Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland
| | - Birgit Kleim
- Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland
| | - Dominik R Bach
- Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Lenggstrasse 31, Zurich 8032, Switzerland; University of Bonn, Transdisciplinary Research Area "Life and Health", Hertz Chair for Artificial Intelligence and Neuroscience, Bonn, Germany
| | - Boris B Quednow
- Experimental Pharmacopsychology and Psychological Addiction Research, Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, Joint Center of University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland
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Ramos L, Harr AE, Zakas FL, Essig SR, Kempskie GJ, Fadil NA, Schmid MG, Pompy MD, Curley MC, Gabel LA, Hallock HL. Overexpression of the Apoe gene in the frontal cortex of mice causes sex-dependent changes in learning, attention, and anxiety-like behavior. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.08.607225. [PMID: 39149404 PMCID: PMC11326296 DOI: 10.1101/2024.08.08.607225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
Apolipoprotein E (ApoE) is a protein that is important for lipid storage, transport, and metabolism. APOE gene variants are associated with Alzheimer's disease (AD), as well as attentional function in healthy humans. Previous research has shown that Apoe transcription is increased following stimulation of the pathway between the locus coeruleus (LC) and frontal cortex (FC) in mice. This result suggests that Apoe may affect attentional function by virtue of its expression in circuits that control attention. Does Apoe causally regulate attention, or is its expression simply a byproduct of neuronal activity in the LC and FC? To answer this question, we synthetically induced Apoe transcription in the FC of male and female mice, and subsequently tested their ability to learn a touchscreen-based rodent version of the continuous performance test of sustained attention (the rCPT). We found that increased Apoe transcription impaired performance when attentional demand was increased in male mice, while in female mice, increased Apoe transcription significantly accelerated rCPT learning. We further found that this increase in Apoe transcription affected subsequent anxiety-like behavior and cellular activity in the FC in a sex-dependent manner. The results of this study provide insight into how Apoe causally regulates translationally relevant behaviors in rodent models.
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Affiliation(s)
- Lizbeth Ramos
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
| | - Abigail E. Harr
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
| | - Finian L. Zakas
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
| | - Samuel R. Essig
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
| | | | - Nelly A. Fadil
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
| | | | | | | | - Lisa A. Gabel
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
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de Sampaio Barros MF, Stefano Filho CA, de Menezes LT, Araújo-Moreira FM, Trevelin LC, Pimentel Maia R, Radel R, Castellano G. Psycho-physio-neurological correlates of qualitative attention, emotion and flow experiences in a close-to-real-life extreme sports situation: low- and high-altitude slackline walking. PeerJ 2024; 12:e17743. [PMID: 39076780 PMCID: PMC11285370 DOI: 10.7717/peerj.17743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 06/24/2024] [Indexed: 07/31/2024] Open
Abstract
It has been indicated that extreme sport activities result in a highly rewarding experience, despite also providing fear, stress and anxiety. Studies have related this experience to the concept of flow, a positive feeling that individuals undergo when they are completely immersed in an activity. However, little is known about the exact nature of these experiences, and, there are still no empirical results to characterize the brain dynamics during extreme sport practice. This work aimed at investigating changes in psychological responses while recording physiological (heart rate-HR, and breathing rate-BR) and neural (electroencephalographic-EEG) data of eight volunteers, during outdoors slackline walking in a mountainous environment at two different altitude conditions (1 m-low-walk- and 45 m-high-walk-from the ground). Low-walk showed a higher score on flow scale, while high-walk displayed a higher score in the negative affect aspects, which together point to some level of flow restriction during high-walk. The order of task performance was shown to be relevant for the physiological and neural variables. The brain behavior during flow, mainly considering attention networks, displayed the stimulus-driven ventral attention network-VAN, regionally prevailing (mainly at the frontal lobe), over the goal-directed dorsal attention network-DAN. Therefore, we suggest an interpretation of flow experiences as an opened attention to more changing details in the surroundings, i.e., configured as a 'task-constantly-opened-to-subtle-information experience', rather than a 'task-focused experience'.
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Affiliation(s)
- Marcelo Felipe de Sampaio Barros
- Programa de Pós-graduação em Biotecnologia, Universidade Federal de São Carlos (UFSCar), São Carlos, São Paulo, Brazil
- Laboratoire LAMHESS, Université de Nice Sophia Antipolis, Nice, Côte d’Azur, France
| | - Carlos Alberto Stefano Filho
- Neurophysics Group, Gleb Wataghin Institute of Physics, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
- Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil
| | - Lucas Toffoli de Menezes
- Neurophysics Group, Gleb Wataghin Institute of Physics, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
- Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil
| | - Fernando Manuel Araújo-Moreira
- Programa de Pós-graduação em Biotecnologia, Universidade Federal de São Carlos (UFSCar), São Carlos, São Paulo, Brazil
- Programa de pós-graduação em Engenharia Nuclear, Instituto Militar de Engenharia/IME, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luis Carlos Trevelin
- Programa de Pós-graduação em Biotecnologia, Universidade Federal de São Carlos (UFSCar), São Carlos, São Paulo, Brazil
- Departamento de Computação, Universidade Federal de São Carlos (UFSCar), São Carlos, São Paulo, Brazil
| | - Rafael Pimentel Maia
- Department of Statistics, Institute of Mathematics, Statistics and Scientific Computing, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
| | - Rémi Radel
- Laboratoire LAMHESS, Université de Nice Sophia Antipolis, Nice, Côte d’Azur, France
| | - Gabriela Castellano
- Neurophysics Group, Gleb Wataghin Institute of Physics, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
- Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil
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Schmidt J, da Silva Senges G, Gonçalves Fernandes Campos R, Lucieri Alonso Costa G, Eliza Moreira Boechat Y, da Cunha Barbosa Leite J, Santos Portela A, Lewandrowski KU, de Corrêa BorgesLacerda G, Schmidt G, Schmidt S. Sustained attention can be measured using a brief computerized attention task. Sci Rep 2024; 14:17001. [PMID: 39043835 PMCID: PMC11266567 DOI: 10.1038/s41598-024-68093-4] [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: 03/05/2024] [Accepted: 07/19/2024] [Indexed: 07/25/2024] Open
Abstract
The Continuous Visual Attention Test (CVAT) is a test that detects visuomotor reaction time (RT, alertness), variability of reaction time (VRT, sustained attention), omission errors (OE, focused attention), and commission errors (CE, response inhibition). The standard test takes 15 min, while the ultrafast version only 90 s. Besides overall task length, the two versions differ by target probability (20% and 80% in the 15-min vs. only 80% in the 90-s test) and stimulus-onset asynchrony (SOA) (1, 2, and 4 s in the 15-min vs. only 1 s in the 90-s test. We aimed to analyze the effect of target probability, SOA, and time length on the CVAT variables across the 15-min task and to verify correlations and agreements between the 15-min and the 90-s CVATs. 205 healthy participants performed the two CVATs on the same day. Considering the 15-min task, RT and CE were strongly affected by target probability. Conversely, VRT was not affected. When the 15-min task was compared to the 90-s task, we found no significant difference in the VRT variable. Additionally, a significant agreement between the two tasks was found for the VRT variable. We concluded that sustained attention can be measured with the 90-s CVAT.
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Affiliation(s)
- Juliana Schmidt
- Post-Graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gabriel da Silva Senges
- Post-Graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | | | - Alessandra Santos Portela
- Department of Internal Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Kai-Uwe Lewandrowski
- Post-Graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Center for Advanced Spine Care of Southern Arizona, Tucson, USA
| | | | - Guilherme Schmidt
- Post-Graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
- Department of Internal Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sergio Schmidt
- Post-Graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
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Bayat M, Hernandez M, Curzon M, Garic D, Graziano P, Dick AS. Reduced recruitment of inhibitory control regions in very young children with ADHD during a modified Kiddie Continuous Performance Task: a fMRI study. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.17.576033. [PMID: 38293209 PMCID: PMC10827162 DOI: 10.1101/2024.01.17.576033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2024]
Abstract
Attention-Deficit/Hyperactivity Disorder (ADHD) symptom profiles are known to undergo changes throughout development, rendering the neurobiological assessment of ADHD challenging across different developmental stages. Particularly in young children (ages 4 to 7 years), measuring inhibitory control network activity in the brain has been a formidable task due to the lack of child-friendly functional Magnetic Resonance Imaging (fMRI) paradigms. This study aims to address these difficulties by focusing on measuring inhibitory control in very young children within the MRI environment. A total of 56 children diagnosed with ADHD and 78 typically developing (TD) 4-7-year-old children were examined using a modified version of the Kiddie-Continuous Performance Test (K-CPT) during BOLD fMRI to assess inhibitory control. We concurrently evaluated their performance on the established and standardized K-CPT outside the MRI scanner. Our findings suggest that the modified K-CPT effectively elicited robust and expected brain activity related to inhibitory control in both groups. Comparisons between the two groups revealed subtle differences in brain activity, primarily observed in regions associated with inhibitory control, such as the inferior frontal gyrus, anterior insula, dorsal striatum, medial pre-supplementary motor area (pre-SMA), and cingulate cortex. Notably, increased activity in the right anterior insula was associated with improved response time (RT) and reduced RT variability on the K-CPT administered outside the MRI environment, although this did not survive statistical correction for multiple comparisons. In conclusion, our study successfully overcame the challenges of measuring inhibitory control in very young children within the MRI environment by utilizing a modified K-CPT during BOLD fMRI. These findings shed light on the neurobiological correlates of inhibitory control in ADHD and TD children, provide valuable insights for understanding ADHD across development, and potentially inform ADHD diagnosis and intervention strategies. The research also highlights remaining challenges with task fMRI in very young clinical samples.
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Pamplona GSP, Heldner J, Langner R, Koush Y, Michels L, Ionta S, Salmon CEG, Scharnowski F. Preliminary findings on long-term effects of fMRI neurofeedback training on functional networks involved in sustained attention. Brain Behav 2023; 13:e3217. [PMID: 37594145 PMCID: PMC10570501 DOI: 10.1002/brb3.3217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 07/25/2023] [Accepted: 07/29/2023] [Indexed: 08/19/2023] Open
Abstract
INTRODUCTION Neurofeedback based on functional magnetic resonance imaging allows for learning voluntary control over one's own brain activity, aiming to enhance cognition and clinical symptoms. We previously reported improved sustained attention temporarily by training healthy participants to up-regulate the differential activity of the sustained attention network minus the default mode network (DMN). However, the long-term brain and behavioral effects of this training have not yet been studied. In general, despite their relevance, long-term learning effects of neurofeedback training remain under-explored. METHODS Here, we complement our previously reported results by evaluating the neurofeedback training effects on functional networks involved in sustained attention and by assessing behavioral and brain measures before, after, and 2 months after training. The behavioral measures include task as well as questionnaire scores, and the brain measures include activity and connectivity during self-regulation runs without feedback (i.e., transfer runs) and during resting-state runs from 15 healthy individuals. RESULTS Neurally, we found that participants maintained their ability to control the differential activity during follow-up sessions. Further, exploratory analyses showed that the training increased the functional connectivity between the DMN and the occipital gyrus, which was maintained during follow-up transfer runs but not during follow-up resting-state runs. Behaviorally, we found that enhanced sustained attention right after training returned to baseline level during follow-up. CONCLUSION The discrepancy between lasting regulation-related brain changes but transient behavioral and resting-state effects raises the question of how neural changes induced by neurofeedback training translate to potential behavioral improvements. Since neurofeedback directly targets brain measures to indirectly improve behavior in the long term, a better understanding of the brain-behavior associations during and after neurofeedback training is needed to develop its full potential as a promising scientific and clinical tool.
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Affiliation(s)
- Gustavo Santo Pedro Pamplona
- Sensory‐Motor Laboratory (SeMoLa), Jules‐Gonin Eye Hospital/Fondation Asile des AveuglesDepartment of Ophthalmology/University of LausanneLausanneSwitzerland
- InBrain Lab, Department of PhysicsUniversity of Sao PauloRibeirao PretoBrazil
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric HospitalUniversity of ZurichZurichSwitzerland
- Rehabilitation Engineering Laboratory (RELab), Department of Health Sciences and TechnologyETH ZurichZurichSwitzerland
| | - Jennifer Heldner
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric HospitalUniversity of ZurichZurichSwitzerland
| | - Robert Langner
- Institute of Systems NeuroscienceHeinrich Heine University DusseldorfDusseldorfGermany
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM‐7)Research Centre JulichJulichGermany
| | - Yury Koush
- Department of Radiology and Biomedical Imaging, Yale School of MedicineYale UniversityNew HavenConnecticutUSA
| | - Lars Michels
- Department of NeuroradiologyUniversity Hospital ZurichZurichSwitzerland
- Neuroscience Center ZurichUniversity of Zurich and Swiss Federal Institute of TechnologyZurichSwitzerland
| | - Silvio Ionta
- Sensory‐Motor Laboratory (SeMoLa), Jules‐Gonin Eye Hospital/Fondation Asile des AveuglesDepartment of Ophthalmology/University of LausanneLausanneSwitzerland
| | | | - Frank Scharnowski
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric HospitalUniversity of ZurichZurichSwitzerland
- Neuroscience Center ZurichUniversity of Zurich and Swiss Federal Institute of TechnologyZurichSwitzerland
- Department of Cognition, Emotion, and Methods in Psychology, Faculty of PsychologyUniversity of ViennaViennaAustria
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Kondo HM, Terashima H, Kihara K, Kochiyama T, Shimada Y, Kawahara JI. Prefrontal GABA and glutamate-glutamine levels affect sustained attention. Cereb Cortex 2023; 33:10441-10452. [PMID: 37562851 PMCID: PMC10545440 DOI: 10.1093/cercor/bhad294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/22/2023] [Accepted: 07/23/2023] [Indexed: 08/12/2023] Open
Abstract
Attention levels fluctuate during the course of daily activities. However, factors underlying sustained attention are still unknown. We investigated mechanisms of sustained attention using psychological, neuroimaging, and neurochemical approaches. Participants were scanned with functional magnetic resonance imaging (fMRI) while performing gradual-onset, continuous performance tasks (gradCPTs). In gradCPTs, narrations or visual scenes gradually changed from one to the next. Participants pressed a button for frequent Go trials as quickly as possible and withheld responses to infrequent No-go trials. Performance was better for the visual gradCPT than for the auditory gradCPT, but the 2 were correlated. The dorsal attention network was activated during intermittent responses, regardless of sensory modality. Reaction-time variability of gradCPTs was correlated with signal changes (SCs) in the left fronto-parietal regions. We also used magnetic resonance spectroscopy (MRS) to measure levels of glutamate-glutamine (Glx) and γ-aminobutyric acid (GABA) in the left prefrontal cortex (PFC). Glx levels were associated with performance under undemanding situations, whereas GABA levels were related to performance under demanding situations. Combined fMRI-MRS results demonstrated that SCs of the left PFC were positively correlated with neurometabolite levels. These findings suggest that a neural balance between excitation and inhibition is involved in attentional fluctuations and brain dynamics.
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Affiliation(s)
- Hirohito M Kondo
- Department of Psychology, School of Psychology, Chukyo University, Nagoya, Aichi 466-8666, Japan
| | - Hiroki Terashima
- Human Information Science Laboratory, NTT Communication Science Laboratories, NTT Corporation, Atsugi, Kanagawa 243-0198, Japan
| | - Ken Kihara
- Department of Information Technology and Human Factors, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan
| | - Takanori Kochiyama
- Brain Activity Imaging Center, ATR-Promotions, Seika-cho, Kyoto 619-0288, Japan
| | - Yasuhiro Shimada
- Brain Activity Imaging Center, ATR-Promotions, Seika-cho, Kyoto 619-0288, Japan
| | - Jun I Kawahara
- Department of Psychology, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan
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11
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Langner R, Scharnowski F, Ionta S, G. Salmon CE, Piper BJ, Pamplona GSP. Evaluation of the reliability and validity of computerized tests of attention. PLoS One 2023; 18:e0281196. [PMID: 36706136 PMCID: PMC9882756 DOI: 10.1371/journal.pone.0281196] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 01/17/2023] [Indexed: 01/28/2023] Open
Abstract
Different aspects of attention can be assessed through psychological tests to identify stable individual or group differences as well as alterations after interventions. Aiming for a wide applicability of attentional assessments, Psychology Experiment Building Language (PEBL) is an open-source software system for designing and running computerized tasks that tax various attentional functions. Here, we evaluated the reliability and validity of computerized attention tasks as provided with the PEBL package: Continuous Performance Task (CPT), Switcher task, Psychomotor Vigilance Task (PVT), Mental Rotation task, and Attentional Network Test. For all tasks, we evaluated test-retest reliability using the intraclass correlation coefficient (ICC), as well as internal consistency through within-test correlations and split-half ICC. Across tasks, response time scores showed adequate reliability, whereas scores of performance accuracy, variability, and deterioration over time did not. Stability across application sites was observed for the CPT and Switcher task, but practice effects were observed for all tasks except the PVT. We substantiate convergent and discriminant validity for several task scores using between-task correlations and provide further evidence for construct validity via associations of task scores with attentional and motivational assessments. Taken together, our results provide necessary information to help design and interpret studies involving attention assessments.
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Affiliation(s)
- Robert Langner
- Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany
| | - Frank Scharnowski
- Department of Cognition, Emotion, and Methods in Psychology, University of Vienna, Vienna, Austria
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland
- Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
| | - Silvio Ionta
- Sensory-Motor Laboratory (SeMoLa), Jules-Gonin Eye Hospital/Fondation Asile des Aveugles, Department of Ophthalmology/University of Lausanne, Lausanne, Switzerland
| | - Carlos E. G. Salmon
- InBrain Lab, Department of Physics, University of São Paulo, Ribeirão Preto, Brazil
| | - Brian J. Piper
- Department of Medical Education, Geisinger Commonwealth School of Medicine, Scranton, PA, United States of America
- Center for Pharmacy Innovation and Outcomes, Forty Fort, Pennsylvania, United States of America
| | - Gustavo S. P. Pamplona
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland
- Sensory-Motor Laboratory (SeMoLa), Jules-Gonin Eye Hospital/Fondation Asile des Aveugles, Department of Ophthalmology/University of Lausanne, Lausanne, Switzerland
- InBrain Lab, Department of Physics, University of São Paulo, Ribeirão Preto, Brazil
- Rehabilitation Engineering Laboratory (RELab), Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
- * E-mail:
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12
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Greenwood TA. Genetic Influences on Cognitive Dysfunction in Schizophrenia. Curr Top Behav Neurosci 2022; 63:291-314. [PMID: 36029459 DOI: 10.1007/7854_2022_388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Schizophrenia is a severe and debilitating psychotic disorder that is highly heritable and relatively common in the population. The clinical heterogeneity associated with schizophrenia is substantial, with patients exhibiting a broad range of deficits and symptom severity. Large-scale genomic studies employing a case-control design have begun to provide some biological insight. However, this strategy combines individuals with clinically diverse symptoms and ignores the genetic risk that is carried by many clinically unaffected individuals. Consequently, the majority of the genetic architecture underlying schizophrenia remains unexplained, and the pathways by which the implicated variants contribute to the clinically observable signs and symptoms are still largely unknown. Parsing the complex, clinical phenotype of schizophrenia into biologically relevant components may have utility in research aimed at understanding the genetic basis of liability. Cognitive dysfunction is a hallmark symptom of schizophrenia that is associated with impaired quality of life and poor functional outcome. Here, we examine the value of quantitative measures of cognitive dysfunction to objectively target the underlying neurobiological pathways and identify genetic variants and gene networks contributing to schizophrenia risk. For a complex disorder, quantitative measures are also more efficient than diagnosis, allowing for the identification of associated genetic variants with fewer subjects. Such a strategy supplements traditional analyses of schizophrenia diagnosis, providing the necessary biological insight to help translate genetic findings into actionable treatment targets. Understanding the genetic basis of cognitive dysfunction in schizophrenia may thus facilitate the development of novel pharmacological and procognitive interventions to improve real-world functioning.
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Affiliation(s)
- Tiffany A Greenwood
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
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13
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Liu W, Liu J, Bhavsar R, Mao T, Mamikonyan E, Raizen D, Detre JA, Weintraub D, Rao H. Perfusion Imaging of Fatigue and Time-on-Task Effects in Patients With Parkinson's Disease. Front Aging Neurosci 2022; 14:901203. [PMID: 35754969 PMCID: PMC9226473 DOI: 10.3389/fnagi.2022.901203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/17/2022] [Indexed: 11/13/2022] Open
Abstract
Fatigue is a highly prevalent and debilitating non-motor symptom in Parkinson's disease (PD), yet its' neural mechanisms remain poorly understood. Here we combined arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) with a sustained mental workload paradigm to examine the neural correlates of fatigue and time-on-task effects in PD patients. Twenty-one PD patients were scanned at rest and during continuous performance of a 20-min psychomotor vigilance test (PVT). Time-on-task effects were measured by the reaction time changes during the PVT and by self-reported fatigue ratings before and after the PVT. PD subjects demonstrated significant time-on-task effects, including progressively slower reaction time on the PVT and increased post-PVT fatigue ratings compared to pre-PVT. Higher levels of general fatigue were associated with larger increases in mental fatigue ratings after the PVT. ASL imaging data showed increased CBF in the right middle frontal gyrus (MFG), bilateral occipital cortex, and right cerebellum during the PVT compared to rest, and decreased CBF in the right MFG at post-task rest compared to pre-task rest. The magnitude of regional CBF changes in the right MFG and right inferior parietal lobe correlated with subjective fatigue rating increases after the PVT task. These results demonstrate the utility of continuous PVT paradigm for future studies of fatigue and cognitive fatigability in patients, and support the key role of the fronto-parietal attention network in mediating fatigue in PD.
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Affiliation(s)
- Wanting Liu
- School of Psychology, South China Normal University, Guangzhou, China,Center for Magnetic Resonance Imaging Research and Key Laboratory of Applied Brain and Cognitive Sciences, School of Business and Management, Shanghai International Studies University, Shanghai, China,Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States
| | - Jianghong Liu
- Department of Family and Community Health, University of Pennsylvania School of Nursing, Philadelphia, PA, United States
| | - Rupal Bhavsar
- Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States
| | - Tianxin Mao
- Center for Magnetic Resonance Imaging Research and Key Laboratory of Applied Brain and Cognitive Sciences, School of Business and Management, Shanghai International Studies University, Shanghai, China,Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States
| | - Eugenia Mamikonyan
- Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
| | - David Raizen
- Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States
| | - John A. Detre
- Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States
| | - Daniel Weintraub
- Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
| | - Hengyi Rao
- Center for Magnetic Resonance Imaging Research and Key Laboratory of Applied Brain and Cognitive Sciences, School of Business and Management, Shanghai International Studies University, Shanghai, China,Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States,*Correspondence: Hengyi Rao,
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14
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Piani MC, Maggioni E, Delvecchio G, Brambilla P. Sustained attention alterations in major depressive disorder: A review of fMRI studies employing Go/No-Go and CPT tasks. J Affect Disord 2022; 303:98-113. [PMID: 35139418 DOI: 10.1016/j.jad.2022.02.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 12/23/2021] [Accepted: 02/04/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND Major depressive disorder (MDD) is a severe psychiatric condition characterized by selective cognitive dysfunctions. In this regard, functional Magnetic Resonance Imaging (fMRI) studies showed, both at resting state and during tasks, alterations in the brain functional networks involved in cognitive processes in MDD patients compared to controls. Among those, it seems that the attention network may have a role in the disease pathophysiology. Therefore, in this review we aim at summarizing the current fMRI evidence investigating sustained attention in MDD patients. METHODS We conducted a search on PubMed on case-control studies on MDD employing fMRI acquisitions during Go/No-Go and continuous performance tasks. A total of 12 studies have been included in the review. RESULTS Overall, the majority of fMRI studies reported quantitative alterations in the response to attentive tasks in selective brain regions, including the prefrontal cortex, the cingulate cortex, the temporal and parietal lobes, the insula and the precuneus, which are key nodes of the attention, the executive, and the default mode networks. LIMITATIONS The heterogeneity in the study designs, fMRI acquisition techniques and processing methods have limited the generalizability of the results. CONCLUSIONS The results from the included studies showed the presence of alterations in the activation patterns of regions involved in sustained attention in MDD, which are in line with current evidence and seemed to explain some of the key symptoms of depression. However, given the paucity and heterogeneity of studies available, it may be worthwhile to continue investigating the attentional domain in MDD with ad-hoc study designs to retrieve more robust evidence.
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Affiliation(s)
- Maria Chiara Piani
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy
| | - Eleonora Maggioni
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy
| | - Giuseppe Delvecchio
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy.
| | - Paolo Brambilla
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy
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15
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Kondo HM, Terashima H, Ezaki T, Kochiyama T, Kihara K, Kawahara JI. Dynamic Transitions Between Brain States Predict Auditory Attentional Fluctuations. Front Neurosci 2022; 16:816735. [PMID: 35368290 PMCID: PMC8972573 DOI: 10.3389/fnins.2022.816735] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/23/2022] [Indexed: 11/23/2022] Open
Abstract
Achievement of task performance is required to maintain a constant level of attention. Attentional level fluctuates over the course of daily activities. However, brain dynamics leading to attentional fluctuation are still unknown. We investigated the underlying mechanisms of sustained attention using functional magnetic resonance imaging (fMRI). Participants were scanned with fMRI while performing an auditory, gradual-onset, continuous performance task (gradCPT). In this task, narrations gradually changed from one to the next. Participants pressed a button for frequent Go trials (i.e., male voices) as quickly as possible and withheld responses to infrequent No-go trials (i.e., female voices). Event-related analysis revealed that frontal and temporal areas, including the auditory cortex, were activated during successful and unsuccessful inhibition of predominant responses. Reaction-time (RT) variability throughout the auditory gradCPT was positively correlated with signal changes in regions of the dorsal attention network: superior frontal gyrus and superior parietal lobule. Energy landscape analysis showed that task-related activations could be clustered into different attractors: regions of the dorsal attention network and default mode network. The number of alternations between RT-stable and erratic periods increased with an increase in transitions between attractors in the brain. Therefore, we conclude that dynamic transitions between brain states are closely linked to auditory attentional fluctuations.
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Affiliation(s)
- Hirohito M. Kondo
- School of Psychology, Chukyo University, Nagoya, Japan
- *Correspondence: Hirohito M. Kondo,
| | - Hiroki Terashima
- NTT Communication Science Laboratories, Nippon Telegraph and Telephone Corporation, Atsugi, Japan
| | - Takahiro Ezaki
- Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
| | | | - Ken Kihara
- Department of Information Technology and Human Factors, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
| | - Jun I. Kawahara
- Department of Psychology, Hokkaido University, Sapporo, Japan
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16
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Pamplona GS, Heldner J, Langner R, Koush Y, Michels L, Ionta S, Scharnowski F, Salmon CE. Network-based fMRI-neurofeedback training of sustained attention. Neuroimage 2020; 221:117194. [DOI: 10.1016/j.neuroimage.2020.117194] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 07/07/2020] [Accepted: 07/20/2020] [Indexed: 11/29/2022] Open
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17
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TbCAPs: A toolbox for co-activation pattern analysis. Neuroimage 2020; 211:116621. [DOI: 10.1016/j.neuroimage.2020.116621] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 01/16/2020] [Accepted: 02/06/2020] [Indexed: 01/03/2023] Open
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18
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Fellah S, Cheung YT, Scoggins MA, Zou P, Sabin ND, Pui CH, Robison LL, Hudson MM, Ogg RJ, Krull KR. Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia. J Natl Cancer Inst 2020; 111:201-209. [PMID: 29790971 DOI: 10.1093/jnci/djy089] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 03/22/2018] [Accepted: 04/17/2018] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. METHODS Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided. RESULTS Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate. CONCLUSIONS Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors.
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Affiliation(s)
- Slim Fellah
- Departments of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN
| | - Yin T Cheung
- Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN
| | - Matthew A Scoggins
- Departments of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN
| | - Ping Zou
- Departments of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN
| | - Noah D Sabin
- Departments of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN
| | - Ching-Hon Pui
- Oncology, St. Jude Children's Research Hospital, Memphis, TN
| | - Leslie L Robison
- Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN
| | - Melissa M Hudson
- Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN.,Oncology, St. Jude Children's Research Hospital, Memphis, TN
| | - Robert J Ogg
- Departments of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN
| | - Kevin R Krull
- Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN
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19
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Imaging cognitive fatigability in multiple sclerosis: objective quantification of cerebral blood flow during a task of sustained attention using ASL perfusion fMRI. Brain Imaging Behav 2019; 14:2417-2428. [PMID: 31468375 DOI: 10.1007/s11682-019-00192-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Cognitive fatigability (CF) can be defined as an inability to maintain performance throughout a sustained cognitive task. Individuals with multiple sclerosis (MS) are more susceptible to CF than healthy controls (HCs); however, the neural correlates underlying CF are still under investigation. Arterial spin labeling (ASL) perfusion imaging provides a non-invasive method of objectively quantifying cerebral blood flow (CBF) during sustained attention tasks. To date, no study has yet evaluated CF in MS using this methodology. 10 MS and 10 HCs completed a 20-min psychomotor vigilance task (PVT). CF was evaluated by dividing the PVT into quintiles and examining performance from the 1st to the last. Mean reaction times (RTs) and number of lapses were recorded. Global and regional CBF changes were evaluated throughout the PVT as well as during pre- and post-task rest. Increased susceptibility to CF was noted in the MS group. Distinct patterns of CBF activation were observed in areas comprising fronto-parietal, cortico-striatal, cerebellar, and basal ganglia regions; however, when and how these regions were engaged differed between the MS and HC groups. In particular, dysfunction in CBF to the middle frontal gyrus may underlie the CF effects observed. In addition, individuals with MS appear to struggle with "switching off" regions of the attentional network at rest following sustained cognitive effort. Findings support the use of ASL as an appropriate methodology for evaluating CF in MS with an overall pattern of attentional network dysfunction being observed. Objectively quantifying CF in this manner can help validate patients' subjective complaints.
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20
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Cognitive Performance, Aerobic Fitness, Motor Proficiency, and Brain Function Among Children Newly Diagnosed With Craniopharyngioma. J Int Neuropsychol Soc 2019; 25:413-425. [PMID: 31050329 PMCID: PMC6499492 DOI: 10.1017/s1355617718001170] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Craniopharyngioma survivors experience cognitive deficits that negatively impact quality of life. Aerobic fitness is associated with cognitive benefits in typically developing children and physical exercise promotes recovery following brain injury. Accordingly, we investigated cognitive and neural correlates of aerobic fitness in a sample of craniopharyngioma patients. METHODS Patients treated for craniopharyngioma [N=104, 10.0±4.6 years, 48% male] participated in fitness, cognitive and fMRI (n=51) assessments following surgery but before proton radiation therapy. RESULTS Patients demonstrated impaired aerobic fitness [peak oxygen uptake (PKVO2)=23.9±7.1, 41% impaired (i.e., 1.5 SD<normative mean)], motor proficiency [Bruininks-Oseretsky (BOT2)=38.6±9.0, 28% impaired], and executive functions (e.g., WISC-IV Working Memory Index (WMI)=96.0±15.3, 11% impaired). PKVO2 correlated with better executive functions (e.g., WISC-IV WMI r=.27, p=.02) and academic performance (WJ-III Calculation r=.24, p=.04). BOT2 correlated with better attention (e.g., CPT-II omissions r=.26, p=.04) and executive functions (e.g., WISC-IV WMI r=.32, p=.01). Areas of robust neural activation during an n-back task included superior parietal lobule, dorsolateral prefrontal cortex, and middle and superior frontal gyri (p<.05, corrected). Higher network activation was associated with better working memory task performance and better BOT2 (p<.001). CONCLUSIONS Before adjuvant therapy, children with craniopharyngioma demonstrate significantly reduced aerobic fitness, motor proficiency, and working memory. Better aerobic fitness and motor proficiency are associated with better attention and executive functions, as well as greater activation of a well-established working memory network. These findings may help explain differential risk/resiliency with respect to acute cognitive changes that may portend cognitive late effects. (JINS, 2019, 25, 413-425).
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21
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Increased Functional Connectivity Between Ventral Attention and Default Mode Networks in Adolescents With Bulimia Nervosa. J Am Acad Child Adolesc Psychiatry 2019; 58:232-241. [PMID: 30738550 PMCID: PMC6462410 DOI: 10.1016/j.jaac.2018.09.433] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 09/19/2018] [Accepted: 10/22/2018] [Indexed: 11/20/2022]
Abstract
OBJECTIVE Bulimia nervosa (BN) is characterized by excessive attention to self and specifically to body shape and weight, but the ventral attention (VAN) and default mode (DMN) networks that support attentional and self-referential processes are understudied in BN. This study assessed whether altered functional connectivity within and between these networks contributes to such excessive concerns in adolescents with BN early the course of the disorder. METHOD Resting-state functional magnetic resonance images were acquired from 33 adolescents with BN and 37 healthy control adolescents (12-21 years) group matched by age and body mass index. Region-of-interest analyses were performed to examine group differences in functional connectivity within and between the VAN and DMN. In addition associations of VAN-DMN connectivity with BN symptoms, body shape/weight concerns, and sustained attention were explored using the Continuous Performance Test (CPT). RESULTS Compared with control adolescents, those with BN showed significantly increased positive connectivity between the right ventral supramarginal gyrus and all DMN regions and between the right ventrolateral prefrontal cortex and the left lateral parietal cortex. Within-network connectivity did not differ between groups. VAN-DMN connectivity was associated with BN severity and body shape/weight concerns in the BN group. No significant group-by-CPT interactions on VAN-DMN connectivity were detected. CONCLUSION Increased positive VAN-DMN connectivity in adolescents with BN could reflect abnormal engagement of VAN-mediated attentional processes at rest, perhaps related to their excessive attention to self-referential thoughts about body shape/weight. Future studies should further investigate these circuits as targets for the development of early interventions aimed at decreasing excessive body shape/weight concerns.
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22
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Darcey VL, McQuaid GA, Fishbein DH, VanMeter JW. Dietary Long-Chain Omega-3 Fatty Acids Are Related to Impulse Control and Anterior Cingulate Function in Adolescents. Front Neurosci 2019; 12:1012. [PMID: 30686978 PMCID: PMC6333752 DOI: 10.3389/fnins.2018.01012] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 12/17/2018] [Indexed: 11/13/2022] Open
Abstract
Impulse control, an emergent function modulated by the prefrontal cortex (PFC), helps to dampen risky behaviors during adolescence. Influences on PFC maturation during this period may contribute to variations in impulse control. Availability of omega-3 fatty acids, an essential dietary nutrient integral to neuronal structure and function, may be one such influence. This study examined whether intake of energy-adjusted long-chain omega-3 fatty acids [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] was related to variation in impulse control and PFC activity during performance of an inhibitory task in adolescents (n = 87; 51.7% female, mean age 13.3 ± 1.1 years) enrolled in a longitudinal neuroimaging study. Intake of DHA + EPA was assessed using a food frequency questionnaire and adjusted for total energy intake. Inhibitory control was assessed using caregiver rating scale (BRIEF Inhibit subscale) and task performance (false alarm rate) on a Go/No-Go task performed during functional MRI. Reported intake of long-chain omega-3 was positively associated with caregiver ratings of adolescent ability to control impulses (p = 0.017) and there was a trend for an association between intake and task-based impulse control (p = 0.072). Furthermore, a regression of BOLD response within PFC during successful impulse control (Correct No-Go versus Incorrect No-Go) with energy-adjusted DHA + EPA intake revealed that adolescents reporting lower intakes display greater activation in the dorsal anterior cingulate, potentially suggestive of a possible lag in cortical development. The present results suggest that dietary omega-3 fatty acids are related to development of both impulse control and function of the dorsal anterior cingulate gyrus in normative adolescent development. Insufficiency of dietary omega-3 fatty acids during this developmental period may be a factor which hinders development of behavioral control.
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Affiliation(s)
- Valerie L Darcey
- The Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, United States.,Center for Functional and Molecular Imaging, Georgetown University Medical Center, Washington, DC, United States
| | - Goldie A McQuaid
- Center for Functional and Molecular Imaging, Georgetown University Medical Center, Washington, DC, United States
| | - Diana H Fishbein
- Department of Human Development and Family Studies, Pennsylvania State University, University Park, PA, United States
| | - John W VanMeter
- Center for Functional and Molecular Imaging, Georgetown University Medical Center, Washington, DC, United States
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23
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Zaytseva Y, Fajnerová I, Dvořáček B, Bourama E, Stamou I, Šulcová K, Motýl J, Horáček J, Rodriguez M, Španiel F. Theoretical Modeling of Cognitive Dysfunction in Schizophrenia by Means of Errors and Corresponding Brain Networks. Front Psychol 2018; 9:1027. [PMID: 30026711 PMCID: PMC6042473 DOI: 10.3389/fpsyg.2018.01027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 05/31/2018] [Indexed: 01/22/2023] Open
Abstract
The current evidence of cognitive disturbances and brain alterations in schizophrenia does not provide the plausible explanation of the underlying mechanisms. Neuropsychological studies outlined the cognitive profile of patients with schizophrenia, that embodied the substantial disturbances in perceptual and motor processes, spatial functions, verbal and non-verbal memory, processing speed and executive functioning. Standardized scoring in the majority of the neurocognitive tests renders the index scores or the achievement indicating the severity of the cognitive impairment rather than the actual performance by means of errors. At the same time, the quantitative evaluation may lead to the situation when two patients with the same index score of the particular cognitive test, demonstrate qualitatively different performances. This may support the view why test paradigms that habitually incorporate different cognitive variables associate weakly, reflecting an ambiguity in the interpretation of noted cognitive constructs. With minor exceptions, cognitive functions are not attributed to the localized activity but eventuate from the coordinated activity in the generally dispersed brain networks. Functional neuroimaging has progressively explored the connectivity in the brain networks in the absence of the specific task and during the task processing. The spatio-temporal fluctuations of the activity of the brain areas detected in the resting state and being highly reproducible in numerous studies, resemble the activation and communication patterns during the task performance. Relatedly, the activation in the specific brain regions oftentimes is attributed to a number of cognitive processes. Given the complex organization of the cognitive functions, it becomes crucial to designate the roles of the brain networks in relation to the specific cognitive functions. One possible approach is to identify the commonalities of the deficits across the number of cognitive tests or, common errors in the various tests and identify their common "denominators" in the brain networks. The qualitative characterization of cognitive performance might be beneficial in addressing diffuse cognitive alterations presumably caused by the dysconnectivity of the distributed brain networks. Therefore, in the review, we use this approach in the description of standardized tests in the scope of potential errors in patients with schizophrenia with a subsequent reference to the brain networks.
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Affiliation(s)
- Yuliya Zaytseva
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | | | | | - Eva Bourama
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Ilektra Stamou
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Kateřina Šulcová
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Jiří Motýl
- National Institute of Mental Health, Klecany, Czechia
| | - Jiří Horáček
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | | | - Filip Španiel
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
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Flow experience and the mobilization of attentional resources. COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE 2018; 18:810-823. [DOI: 10.3758/s13415-018-0606-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Berner LA, Stefan M, Lee S, Wang Z, Terranova K, Attia E, Marsh R. Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa. J Psychiatry Neurosci 2018; 43:170070. [PMID: 29336774 PMCID: PMC5915236 DOI: 10.1503/jpn.170070] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 07/10/2017] [Accepted: 08/08/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. METHODS We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. RESULTS We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. LIMITATIONS These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. CONCLUSION Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.
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Affiliation(s)
- Laura A Berner
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
| | - Mihaela Stefan
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
| | - Seonjoo Lee
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
| | - Zhishun Wang
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
| | - Kate Terranova
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
| | - Evelyn Attia
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
| | - Rachel Marsh
- From the Eating Disorders Center for Treatment and Research, Department of Psychiatry, University of California, San Diego (Berner); the Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Stefan, Lee, Wang, Terranova, Marsh); and the Eating Disorders Research Unit, Division of Clinical Therapeutics, Department of Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute (Attia, Marsh)
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Simões EN, Padilla CS, Bezerra MS, Schmidt SL. Analysis of Attention Subdomains in Obstructive Sleep Apnea Patients. Front Psychiatry 2018; 9:435. [PMID: 30337887 PMCID: PMC6180239 DOI: 10.3389/fpsyt.2018.00435] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Accepted: 08/23/2018] [Indexed: 12/12/2022] Open
Abstract
Background: Obstructive sleep apnea (OSA) is characterized by apnea-hypopnea during sleep. Overnight polysomnography (PSG) is usually used to detect the frequency of apneic and hypopneic events. Attention and executive deficits are commonly reported in OSA patients. Previous investigations suggested that cognitive impairments were dependent on attention deficits. However, attention is not a unitary domain and consists of different subdomains such as alertness, sustained attention, focused attention, and executive attention (impulsivity/hyperactivity). Little is known about the attention subdomains affected in OSA. Attention is commonly assessed using continuous performance tests, such as the continuous visual attention test (CVAT). Distinct variables can be derived from the CVAT. Each CVAT variable is associated with a specific attention subdomain. Objective: This study aimed to examine the variables of the CVAT that are affected by OSA and to identify the most reliable CVAT variable that distinguishes OSA from controls via discriminant analysis. Method: Patients scheduled to perform a PSG were invited to participate in this study. Immediately before the PSG, they performed the CVAT. Based on the PSG results, 27 treatment-naïve OSA patients were sampled. The same number of healthy controls were selected to match the two groups by age and gender. Five CVAT variables were examined: commission errors, omission errors, reaction time (RT), variability of reaction time (VRT), and coefficient of variability (VRT/RT). Results: ANCOVAs indicated that RT and VRT were affected by OSA. No difference in accuracy (omission and commission errors) was observed between healthy controls and OSA patients. When the VRT measurements were corrected for their respective RT values (VRT/RT), the mean difference on this coefficient did not reach significance. The discriminant analysis indicated that the two groups could be best differentiated by the RT variable. Conclusions: Attention problems, commonly observed in OSA patients, may reflect a primary problem on the alertness subdomain. The CVAT was able to detect the primary (alertness-RT parameter) and the secondary deficits (sustained attention-VRT parameter) associated with OSA. As there is no learning effect in the condition of retests, the CVAT can be used to assess the cognitive recovery in OSA patients during treatment.
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Affiliation(s)
- Eunice N Simões
- Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Catarina S Padilla
- Department of Psychology, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Sergio L Schmidt
- Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
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McLoughlin G, Palmer J, Makeig S, Bigdely-Shamlo N, Banaschewski T, Laucht M, Brandeis D. EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes. Brain Topogr 2017; 31:392-406. [PMID: 29222686 PMCID: PMC5889775 DOI: 10.1007/s10548-017-0601-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 10/10/2017] [Indexed: 01/09/2023]
Abstract
Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.
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Affiliation(s)
- G McLoughlin
- MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO80, London, UK.
| | - J Palmer
- Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA
| | - S Makeig
- Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA
| | - N Bigdely-Shamlo
- Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA
| | - T Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
| | - M Laucht
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
- Department of Psychology, University of Potsdam, Potsdam, Germany
| | - D Brandeis
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology, University of Zürich, Zurich, Switzerland
- Neuroscience Center Zurich, University and ETH Zürich, Zurich, Switzerland
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Chung YS, Hyatt CJ, Stevens MC. Adolescent maturation of the relationship between cortical gyrification and cognitive ability. Neuroimage 2017; 158:319-331. [PMID: 28676299 DOI: 10.1016/j.neuroimage.2017.06.082] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 06/12/2017] [Accepted: 06/30/2017] [Indexed: 12/31/2022] Open
Abstract
There are changes to the degree of cortical folding from gestation through adolescence into young adulthood. Recent evidence suggests that degree of cortical folding is linked to individual differences in general cognitive ability in healthy adults. However, it is not yet known whether age-related cortical folding changes are related to maturation of specific cognitive abilities in adolescence. To address this, we examined the relationship between frontoparietal cortical folding as measured by a Freesurfer-derived local gyrification index (lGI) and performance on subtests from the Wechsler Abbreviated Scale of Intelligence and scores from Conner's Continuous Performance Test-II in 241 healthy adolescents (ages 12-25 years). We hypothesized that age-related lGI changes in the frontoparietal cortex would contribute to cognitive development. A secondary goal was to explore if any gyrification-cognition relationships were either test-specific or sex-specific. Consistent with previous studies, our results showed a reduction of frontoparietal local gyrification with age. Also, as predicted, all cognitive test scores (i.e., Vocabulary, Matrix Reasoning, the CPT-II Commission, Omission, Variabiltiy, d') showed age × cognitive ability interaction effects in frontoparietal and temporoparietal brain regions. Mediation analyses confirmed a causal role of age-related cortical folding changes only for CPT-II Commission errors. Taken together, the results support the functional significance of cortical folding, as well as provide the first evidence that cortical folding maturational changes play a role in cognitive development.
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Affiliation(s)
- Yu Sun Chung
- Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, 200 Retreat Avenue, Whitehall Building, Institute of Living, Hartford, CT 06106, USA
| | - Christopher J Hyatt
- Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, 200 Retreat Avenue, Whitehall Building, Institute of Living, Hartford, CT 06106, USA
| | - Michael C Stevens
- Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, 200 Retreat Avenue, Whitehall Building, Institute of Living, Hartford, CT 06106, USA; Department of Psychiatry, Yale University School of Medicine, 300 George St., Suite 901, New Haven, CT 06511, USA.
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de Joux NR, Wilson KM, Russell PN, Finkbeiner KM, Helton WS. A functional near-infrared spectroscopy study of the effects of configural properties on sustained attention. Neuropsychologia 2017; 94:106-117. [PMID: 27919661 DOI: 10.1016/j.neuropsychologia.2016.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 08/17/2016] [Accepted: 12/01/2016] [Indexed: 11/25/2022]
Abstract
Forty-five participants performed a vigilance task during which they were required to respond to a critical signal at a local feature level, while the global display was altered between groups (either a circle, a circle broken apart and reversed, or a reconnected figure). The shape in two of the groups formed a configurative whole (the circle and reconnected conditions), while the remaining shape had no complete global element (broken circle). Performance matched the results found in the previous experiments using this stimulus set, where a configural superiority effect was found to influence accuracy over time. Physiological data, measured using functional near-infrared spectroscopy, revealed elevated activation in the right pre-frontal cortex compared to the left pre-frontal cortex during the task. Additionally, bilateral activation was found in the conditions that formed configurative wholes, while hemispheric differences over time were found in the condition that did not. These findings suggest that configural aspects of stimuli may explain why non-typical laterality effects have been found in similar research.
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Affiliation(s)
- Neil R de Joux
- Department of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
| | - Kyle M Wilson
- Department of Psychology, University of Huddersfield, Huddersfield, United Kingdom
| | - Paul N Russell
- Department of Psychology, University of Canterbury, Christchurch, New Zealand
| | | | - William S Helton
- Department of Psychology, University of Canterbury, Christchurch, New Zealand
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30
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Goetz M, Schwabova JP, Hlavka Z, Ptacek R, Surman CB. Dynamic balance in children with attention-deficit hyperactivity disorder and its relationship with cognitive functions and cerebellum. Neuropsychiatr Dis Treat 2017; 13:873-880. [PMID: 28356743 PMCID: PMC5367596 DOI: 10.2147/ndt.s125169] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Attention-deficit hyperactivity disorder (ADHD) is linked to the presence of motor deficiencies, including balance deficits. The cerebellum serves as an integrative structure for balance control and is also involved in cognition, including timing and anticipatory regulation. Cerebellar development may be delayed in children and adolescents with ADHD, and inconsistent reaction time is commonly seen in ADHD. We hypothesized that dynamic balance deficits would be present in children with ADHD and they would correlate with attention and cerebellar functions. METHODS Sixty-two children with ADHD and no other neurological conditions and 62 typically developing (TD) children were examined with five trials of the Phyaction Balance Board, an electronic balancing platform. Cerebellar clinical symptoms were evaluated using an international ataxia rating scale. Conners' Continuous Performance Test was used to evaluate patterns of reaction. RESULTS Children with ADHD had poorer performance on balancing tasks, compared to TD children (P<0.001). They exhibited significantly greater sway amplitudes than TD children (P<0.001) in all of the five balancing trials. The effect size of the difference between the groups increased continuously from the first to the last trial. Balance score in both groups was related to the variation in the reaction time, including reaction time standard error (r =0.25; P=0.0409, respectively, r =0.31; P=0.0131) and Variability of Standard Error (r =0.28; P=0.0252, respectively, r =0.41; P<0.001). The burden of cerebellar symptoms was strongly related to balance performance in both groups (r =0.50, P<0.001; r =0.49, P=0.001). CONCLUSION This study showed that ADHD may be associated with poor dynamic balance control. Furthermore, we showed that maintaining balance correlates with neuropsychological measures of consistency of reaction time. Balance deficits and impaired cognitive functioning could reflect a common cerebellar dysfunction in ADHD children.
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Affiliation(s)
- Michal Goetz
- Department of Child Psychiatry, Second Faculty of Medicine, Motol University Hospital
| | | | | | - Radek Ptacek
- Department of Psychiatry, Charles University, Prague, Czech Republic
| | - Craig Bh Surman
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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31
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Schmidt SL, Carvaho ALN, Simoes EN. Effect of handedness on auditory attentional performance in ADHD students. Neuropsychiatr Dis Treat 2017; 13:2921-2924. [PMID: 29238197 PMCID: PMC5716334 DOI: 10.2147/ndt.s149454] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The relationship between handedness and attentional performance is poorly understood. Continuous performance tests (CPTs) using visual stimuli are commonly used to assess subjects suffering from attention deficit hyperactivity disorder (ADHD). However, auditory CPTs are considered more useful than visual ones to evaluate classroom attentional problems. A previous study reported that there was a significant effect of handedness on students' performance on a visual CPT. Here, we examined whether handedness would also affect CPT performance using only auditory stimuli. From an initial sample of 337 students, 11 matched pairs were selected. Repeated ANOVAs showed a significant effect of handedness on attentional performance that was exhibited even in the control group. Left-handers made more commission errors than right-handers. The results were interpreted considering that the association between ADHD and handedness reflects that consistent left-handers are less lateralized and have decreased interhemispheric connections. Auditory attentional data suggest that left-handers have problems in the impulsive/hyperactivity domain. In ADHD, clinical therapeutics and rehabilitation must take handedness into account because consistent sinistrals are more impulsive than dextrals.
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Affiliation(s)
- Sergio L Schmidt
- Department of Neurophysiology, State University of Rio de Janeiro, Rio de Janeiro.,Neurology Department, Federal University of the State of Rio de Janeiro, Rio de Janeiro
| | | | - Eunice N Simoes
- Neurology Department, Federal University of the State of Rio de Janeiro, Rio de Janeiro
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Zou P, Conklin HM, Scoggins MA, Li Y, Li X, Jones MM, Palmer SL, Gajjar A, Ogg RJ. Functional MRI in medulloblastoma survivors supports prophylactic reading intervention during tumor treatment. Brain Imaging Behav 2016; 10:258-71. [PMID: 25967954 DOI: 10.1007/s11682-015-9390-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Development of reading skills is vulnerable to disruption in children treated for brain tumors. Interventions, remedial and prophylactic, are needed to mitigate reading and other learning difficulties faced by survivors. A functional magnetic resonance imaging (fMRI) study was conducted to investigate long-term effects of a prophylactic reading intervention administered during radiation therapy in children treated for medulloblastoma. The fMRI study included 19 reading-intervention (age 11.7 ± 0.6 years) and 21 standard-of-care (age 12.1 ± 0.6 years) medulloblastoma survivors, and 21 typically developing children (age 12.3 ± 0.6 years). The survivors were 2.5 [1.2, 5.4] years after completion of tumor therapies and reading-intervention survivors were 2.9 [1.6, 5.9] years after intervention. Five fMRI tasks (Rapid Automatized Naming, Continuous Performance Test using faces and letters, orthographic and phonological processing of letter pairs, implicit word reading, and story reading) were used to probe reading-related neural activation. Woodcock-Johnson Reading Fluency, Word Attack, and Sound Awareness subtests were used to evaluate reading abilities. At the time of fMRI, Sound Awareness scores were significantly higher in the reading-intervention group than in the standard-of-care group (p = 0.046). Brain activation during the fMRI tasks was detected in left inferior frontal, temporal, ventral occipitotemporal, and subcortical regions, and differed among the groups (p < 0.05, FWE). The pattern of group activation differences, across brain areas and tasks, was a normative trend in the reading-intervention group. Standardized reading scores and patterns of brain activation provide evidence of long-term effects of prophylactic reading intervention in children treated for medulloblastoma.
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Affiliation(s)
- Ping Zou
- Department of Radiological Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA
| | - Heather M Conklin
- Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Matthew A Scoggins
- Department of Radiological Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA
| | - Yimei Li
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Xingyu Li
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Melissa M Jones
- Department of Radiological Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA
| | - Shawna L Palmer
- Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Amar Gajjar
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Robert J Ogg
- Department of Radiological Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
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Zane KL, Gfeller JD, Roskos PT, Bucholz RD. The Clinical Utility of the Conners' Continuous Performance Test-II in Traumatic Brain Injury. Arch Clin Neuropsychol 2016; 31:996-1005. [PMID: 27650713 DOI: 10.1093/arclin/acw078] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2016] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE The Conners' Continuous Performance Test Second Edition (CPT-II) is a measure commonly used in persons with suspected attentional deficits. Our study examined the utility of the CPT-II as a measure of attention in adults with traumatic brain injury (TBI) of varying severity. METHOD As part of a larger investigation, several measures of cognitive functioning, including the CPT-II, were administered to 30 healthy control participants (HCP), 30 mild TBI participants (M-TBI), and 30 moderate to severe TBI participants (MS-TBI). Multivariate and correlational analyses compared group performances and examined convergent and divergent relationships between the CPT-II and various measures, including other tests of attention and neuropsychological function. RESULTS Group differences were found for four of six CPT-II variables, with the MS-TBI group exhibiting greater impairment, relative to M-TBI and HCP. In addition, the CPT-II commission and detectability variables were found to correlate significantly with TBI severity. The CPT-II variables also demonstrated correlations of varying magnitude between commonly used neuropsychological measures. CONCLUSIONS These findings support the utility of the CPT-II for assessing attentional abilities in persons with TBI of varying severity, particularly those with moderate to severe status. Moreover, the current study also demonstrates relationships that are consistent with convergent validity but inconsistent findings with regard to divergent validity. As a result, the CPT-II measures components of attention that is unique to other commonly used neuropsychological measures of attentive functioning. Further research examining CPT-II performance in TBI populations is recommended.
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Affiliation(s)
- Katherine L Zane
- Department of Psychology, Saint Louis University, St. Louis, MO63108, United States
| | - Jeffrey D Gfeller
- Department of Psychology, Saint Louis University, St. Louis, MO63108, United States
| | - P Tyler Roskos
- Department of Physical Medicine and Rehabilitation Oakwood, Wayne State University School of Medicine, Dearborn, MI48201, United States
| | - Richard D Bucholz
- Department of Neurosurgery, Saint Louis University School of Medicine, St. Louis, MO63104, United States
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Jacola LM, Conklin HM, Scoggins MA, Ashford JM, Merchant TE, Mandrell BN, Ogg RJ, Curtis E, Wise MS, Indelicato DJ, Crabtree VM. Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma. J Pediatr Psychol 2016; 41:610-22. [PMID: 27189690 PMCID: PMC4913761 DOI: 10.1093/jpepsy/jsw026] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 01/25/2016] [Accepted: 01/25/2016] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVE Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. METHODS Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. RESULTS EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. CONCLUSION Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity.
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Affiliation(s)
| | | | | | | | | | | | | | - Elizabeth Curtis
- Indiana University School of Medicine, Indiana University-Purdue University
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Bhandari J, Daya R, Mishra RK. Improvements and important considerations for the 5-choice serial reaction time task-An effective measurement of visual attention in rats. J Neurosci Methods 2016; 270:17-29. [PMID: 27265297 DOI: 10.1016/j.jneumeth.2016.06.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 05/27/2016] [Accepted: 06/02/2016] [Indexed: 10/21/2022]
Abstract
BACKGROUND The 5-choice serial reaction time task (5-CSRTT) is an automated operant conditioning task that measures rodent attention. The task allows the measurement of several parameters such as response accuracy, speed of processing, motivation, and impulsivity. The task has been widely used to investigate attentional processes in rodents for attention deficit and hyperactivity disorder and has expanded to other illnesses such as Alzheimer's disease, depression, and schizophrenia. NEW METHOD The 5-CSRTT is accompanied with two significant caveats: a time intensive training period and largely varied individual rat capability to learn and perform the task. Here we provide a regimented acquisition protocol to enhance training for the 5-CSRTT and discuss important considerations for researchers using the 5-CSRTT. RESULTS We offer guidelines to ensure that inferences on performance in the 5-CSRTT are in fact a result of experimental manipulation rather than training differences, or individual animal capability. According to our findings only rats that have been trained successfully within a limited time frame should be used for the remainder of the study. COMPARISON WITH EXISTING METHOD(S) Currently the 5-CSRTT employs a training period of variable duration and procedure, and its inferences on attention must overcome heterogeneous innate animal differences. CONCLUSIONS The 5-CSRTT offers valuable and valid insights on various rodent attentional processes and their translation to the underpinnings of illnesses such as schizophrenia. The recommendations made here provide important criteria to ensure inferences made from this task are in fact relevant to the attentional processes being measured.
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Affiliation(s)
- Jayant Bhandari
- Department of Psychiatry & Behavioural Neurosciences, Health Sciences Centre 4N73, McMaster University, 1280 Main Street West, Hamilton, L8S4L8 Ontario, Canada.
| | - Ritesh Daya
- Department of Psychiatry & Behavioural Neurosciences, Health Sciences Centre 4N73, McMaster University, 1280 Main Street West, Hamilton, L8S4L8 Ontario, Canada.
| | - Ram K Mishra
- Department of Psychiatry & Behavioural Neurosciences, Health Sciences Centre 4N73, McMaster University, 1280 Main Street West, Hamilton, L8S4L8 Ontario, Canada.
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Almeida DM, Jandacek RJ, Weber WA, McNamara RK. Docosahexaenoic acid biostatus is associated with event-related functional connectivity in cortical attention networks of typically developing children. Nutr Neurosci 2016; 20:246-254. [PMID: 26463682 DOI: 10.1179/1476830515y.0000000046] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
OBJECTIVE Although extant preclinical evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is important for neurodevelopment, little is known about its role in human cortical structural and functional maturation. In the present cross-sectional study, we investigated the relationship between DHA biostatus and functional connectivity in cortical attention networks of typically developing children. METHODS Male children (aged 8-10 years, n = 36) were divided into 'low-DHA' (n = 18) and 'high-DHA' (n = 18) biostatus groups by a median split of erythrocyte DHA levels. Event-related functional connectivity during the performance of a sustained attention task (identical pairs continuous performance task (CPT-IP)) was conducted using functional magnetic resonance imaging. A voxelwise approach used the anterior cingulate cortex (ACC) as the seed-region. RESULTS Erythrocyte DHA composition in the low-DHA group (2.6 ± 0.9%) was significantly lower than the high-DHA group (4.1 ± 1.1%, P ≤ 0.0001). Fish intake frequency was greater in the high-DHA group (P = 0.003) and was positively correlated with DHA levels among all subjects. The low-DHA group exhibited reduced functional connectivity between the ACC and the ventrolateral prefrontal cortex, insula, precuneus, superior parietal lobule, middle occipital gyrus, inferior temporal gyrus, and lingual gyrus compared with the high-DHA group (P < 0.05; corrected). The low-DHA group did not exhibit greater ACC functional connectivity with any region compared with the high-DHA group. On the CPT-IP task, the low-DHA group had slower reaction time (P = 0.03) which was inversely correlated with erythrocyte DHA among all subjects. DISCUSSION These data suggest that low-DHA biostatus is associated with reduced event-related functional connectivity in cortical attention networks of typically developing children.
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Affiliation(s)
- Daniel M Almeida
- a Division of Child and Adolescent Psychiatry , Cincinnati Children's Hospital Medical Center , OH 45224 , USA
| | - Ronald J Jandacek
- b Department of Pathology and Laboratory Medicine , University of Cincinnati , OH 45237 , USA
| | - Wade A Weber
- c Department of Psychiatry and Behavioral Neuroscience , University of Cincinnati College of Medicine , OH 45267 , USA
| | - Robert K McNamara
- c Department of Psychiatry and Behavioral Neuroscience , University of Cincinnati College of Medicine , OH 45267 , USA
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Piper B, Mueller ST, Talebzadeh S, Ki MJ. Evaluation of the validity of the Psychology Experiment Building Language tests of vigilance, auditory memory, and decision making. PeerJ 2016; 4:e1772. [PMID: 27014512 PMCID: PMC4806597 DOI: 10.7717/peerj.1772] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Accepted: 02/16/2016] [Indexed: 11/20/2022] Open
Abstract
Background. The Psychology Experimental Building Language (PEBL) test battery (http://pebl.sourceforge.net/) is a popular application for neurobehavioral investigations. This study evaluated the correspondence between the PEBL and the non-PEBL versions of four executive function tests. Methods. In one cohort, young-adults (N = 44) completed both the Conner’s Continuous Performance Test (CCPT) and the PEBL CPT (PCPT) with the order counter-balanced. In a second cohort, participants (N = 47) completed a non-computerized (Wechsler) and a computerized (PEBL) Digit Span (WDS or PDS) both Forward and Backward. Participants also completed the Psychological Assessment Resources or the PEBL versions of the Iowa Gambling Task (PARIGT or PEBLIGT). Results. The between-test correlations were moderately high (reaction time r = 0.78, omission errors r = 0.65, commission errors r = 0.66) on the CPT. DS Forward was significantly greater than DS Backward on the WDS (p < .0005) and the PDS (p < .0005). The total WDS score was moderately correlated with the PDS (r = 0.56). The PARIGT and the PEBLIGTs showed a very similar pattern for response times across blocks, development of preference for Advantageous over Disadvantageous Decks, and Deck selections. However, the amount of money earned (score–loan) was significantly higher in the PEBLIGT during the last Block. Conclusions. These findings are broadly supportive of the criterion validity of the PEBL measures of sustained attention, short-term memory, and decision making. Select differences between workalike versions of the same test highlight how detailed aspects of implementation may have more important consequences for computerized testing than has been previously acknowledged.
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Affiliation(s)
- Brian Piper
- Neuroscience Program, Bowdoin College, Brunswick, ME, United States; Department of Psychology, Willamette University, Salem, OR, United States; School of Pharmacy, Husson University, Bangor, ME, United States
| | - Shane T Mueller
- Cognitive and Learning Sciences, Michigan Technological University , Houghton, MI , United States
| | - Sara Talebzadeh
- Department of Biology, Husson University , Bangor, ME , United States
| | - Min Jung Ki
- School of Pharmacy, Husson University , Bangor, ME , United States
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Hamilton KR, Littlefield AK, Anastasio NC, Cunningham KA, Fink LHL, Wing VC, Mathias CW, Lane SD, Schütz CG, Swann AC, Lejuez CW, Clark L, Moeller FG, Potenza MN. Rapid-response impulsivity: definitions, measurement issues, and clinical implications. Personal Disord 2016; 6:168-181. [PMID: 25867840 DOI: 10.1037/per0000100] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Impulsivity is a multifaceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity is limited by a lack of precision and consistency in its definition and assessment. Rapid-response impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI measures in terms of reliability, sensitivity, and validity, with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI measures. Their recommendations are described in this article. Commonly used clinical and preclinical RRI tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, "refraining from action initiation" (RAI) and "stopping an ongoing action" (SOA) are described. RAI and SOA tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that (a) selection of RRI measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; (b) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and (c) similar considerations be made for human and nonhuman studies in an effort to harmonize and integrate preclinical and clinical research.
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Affiliation(s)
- Kristen R Hamilton
- Department of Psychology, Maryland Neuroimaging Center, Center for Addictions, Personality, and Emotion Research, University of Maryland
| | | | - Noelle C Anastasio
- Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch
| | - Kathryn A Cunningham
- Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch
| | - Latham H L Fink
- Center for Addiction Research, University of Texas Medical Branch
| | - Victoria C Wing
- Schizophrenia Division, Complex Mental Illness, Centre for Addiction and Mental Health
| | - Charles W Mathias
- Department of Psychiatry, Division of Neurobehavioral Research, University of Texas Health Science Center at San Antonio
| | - Scott D Lane
- Department of Psychiatry and Behavioral Sciences, University of Texas at Houston Medical School
| | | | - Alan C Swann
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine
| | - C W Lejuez
- Department of Psychology, Maryland Neuroimaging Center, Center for Addictions, Personality, and Emotion Research, University of Maryland
| | - Luke Clark
- Centre for Gambling Research at UBC, Department of Psychology, University of British Columbia
| | - F Gerard Moeller
- Department of Psychiatry, Virginia Commonwealth University School of Medicine
| | - Marc N Potenza
- Department of Psychiatry, Yale University School of Medicine
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de Joux NR, Wilson K, Russell PN, Helton WS. The effects of a transition between local and global processing on vigilance performance. J Clin Exp Neuropsychol 2015; 37:888-98. [PMID: 26240987 DOI: 10.1080/13803395.2015.1068744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Sixty participants performed a sustained attention task in which they were required to perform either global or local feature discrimination. Two groups required just one type of discrimination, while the remaining two groups started on one type of discrimination before transitioning to the other type halfway through. A transition resulted in worse performance when compared to no transition. It was also found that the local discrimination group showed improved performance over time compared to the global discrimination group. Functional near-infrared spectroscopy (fNIRS) was used to measure blood oxygenation during the task and was used as an index of cerebral hemodynamic activity. Total oxygenation was found to increase more in global discrimination tasks. It was also found that the left prefrontal cortex showed little change in nontransition tasks while in transition tasks it followed the same trend as the right prefrontal cortex. Combined with performance data, it suggests that an increased utilization of bilateral resources may in some cases improve performance over time.
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Affiliation(s)
- Neil R de Joux
- a Department of Psychology , University of Canterbury , Christchurch , New Zealand
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Albrecht B, Uebel-von Sandersleben H, Wiedmann K, Rothenberger A. ADHD History of the Concept: the Case of the Continuous Performance Test. CURRENT DEVELOPMENTAL DISORDERS REPORTS 2015. [DOI: 10.1007/s40474-014-0035-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Wagshal D, Knowlton BJ, Suthana NA, Cohen JR, Poldrack RA, Bookheimer SY, Bilder RM, Asarnow RF. Evidence for corticostriatal dysfunction during cognitive skill learning in adolescent siblings of patients with childhood-onset schizophrenia. Schizophr Bull 2014; 40:1030-9. [PMID: 24162516 PMCID: PMC4133665 DOI: 10.1093/schbul/sbt147] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Patients with schizophrenia perform poorly on cognitive skill learning tasks. This study is the first to investigate the neural basis of impairment in cognitive skill learning in first-degree adolescent relatives of patients with schizophrenia. We used functional magnetic resonance imaging to compare activation in 16 adolescent siblings of patients with childhood-onset schizophrenia (COS) and 45 adolescent controls to determine whether impaired cognitive skill learning in individuals with genetic risk for schizophrenia was associated with specific patterns of neural activation. The siblings of patients with COS were severely impaired on the Weather Prediction Task (WPT) and showed a relative deactivation in frontal regions and in the striatum after extensive training on the WPT compared with controls. These differences were not accounted for by performance differences in the 2 groups. The results suggest that corticostriatal dysfunction may be part of the liability for schizophrenia.
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Affiliation(s)
- Dana Wagshal
- Department of Neurology, University of California San Francisco, San Francisco, CA;
| | | | | | | | - Russel Alan Poldrack
- Departments of Psychology and Neurobiology, Imaging Research Center, University of Texas at Austin, Austin, TX
| | - Susan Yost Bookheimer
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA
| | - Robert Martin Bilder
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA
| | - Robert Franklin Asarnow
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA
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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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Spatially distributed effects of mental exhaustion on resting-state FMRI networks. PLoS One 2014; 9:e94222. [PMID: 24705397 PMCID: PMC3976406 DOI: 10.1371/journal.pone.0094222] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Accepted: 03/13/2014] [Indexed: 12/29/2022] Open
Abstract
Brain activity during rest is spatially coherent over functional connectivity networks called resting-state networks. In resting-state functional magnetic resonance imaging, independent component analysis yields spatially distributed network representations reflecting distinct mental processes, such as intrinsic (default) or extrinsic (executive) attention, and sensory inhibition or excitation. These aspects can be related to different treatments or subjective experiences. Among these, exhaustion is a common psychological state induced by prolonged mental performance. Using repeated functional magnetic resonance imaging sessions and spatial independent component analysis, we explored the effect of several hours of sustained cognitive performances on the resting human brain. Resting-state functional magnetic resonance imaging was performed on the same healthy volunteers in two days, with and without, and before, during and after, an intensive psychological treatment (skill training and sustained practice with a flight simulator). After each scan, subjects rated their level of exhaustion and performed an N-back task to evaluate eventual decrease in cognitive performance. Spatial maps of selected resting-state network components were statistically evaluated across time points to detect possible changes induced by the sustained mental performance. The intensive treatment had a significant effect on exhaustion and effort ratings, but no effects on N-back performances. Significant changes in the most exhausted state were observed in the early visual processing and the anterior default mode networks (enhancement) and in the fronto-parietal executive networks (suppression), suggesting that mental exhaustion is associated with a more idling brain state and that internal attention processes are facilitated to the detriment of more extrinsic processes. The described application may inspire future indicators of the level of fatigue in the neural attention system.
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Xu J, Rees G, Yin X, Song C, Han Y, Ge H, Pang Z, Xu W, Tang Y, Friston K, Liu S. Spontaneous neuronal activity predicts intersubject variations in executive control of attention. Neuroscience 2014; 263:181-192. [PMID: 24447598 DOI: 10.1016/j.neuroscience.2014.01.020] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 01/10/2014] [Accepted: 01/10/2014] [Indexed: 01/27/2023]
Abstract
Executive control of attention regulates our thoughts, emotion and behavior. Individual differences in executive control are associated with task-related differences in brain activity. But it is unknown whether attentional differences depend on endogenous (resting state) brain activity and to what extent regional fluctuations and functional connectivity contribute to individual variations in executive control processing. Here, we explored the potential contribution of intrinsic brain activity to executive control by using resting-state functional magnetic resonance imaging (fMRI). Using the amplitude of low-frequency fluctuations (ALFF) as an index of spontaneous brain activity, we found that ALFF in the right precuneus (PCUN) and the medial part of left superior frontal gyrus (msFC) was significantly correlated with the efficiency of executive control processing. Crucially, the strengths of functional connectivity between the right PCUN/left msFC and distributed brain regions, including the left fusiform gyrus, right inferior frontal gyrus, left superior frontal gyrus and right precentral gyrus, were correlated with individual differences in executive performance. Together, the ALFF and functional connectivity accounted for 67% of the variability in behavioral performance. Moreover, the strength of functional connectivity between specific regions could predict more individual variability in executive control performance than regionally specific fluctuations. In conclusion, our findings suggest that spontaneous brain activity may reflect or underpin executive control of attention. It will provide new insights into the origins of inter-individual variability in human executive control processing.
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Affiliation(s)
- J Xu
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China; UCL Institute of Cognitive Neuroscience, London, United Kingdom; Wellcome Trust Centre for Neuroimaging, University College London (UCL) Institute of Neurology, London, United Kingdom
| | - G Rees
- UCL Institute of Cognitive Neuroscience, London, United Kingdom; Wellcome Trust Centre for Neuroimaging, University College London (UCL) Institute of Neurology, London, United Kingdom
| | - X Yin
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China
| | - C Song
- UCL Institute of Cognitive Neuroscience, London, United Kingdom
| | - Y Han
- Department of Radiology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China
| | - H Ge
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China
| | - Z Pang
- Department of Epidemiology, Qingdao Municipal Central for Disease Control and Prevention, Qingdao, Shandong, China
| | - W Xu
- Department of Radiology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China
| | - Y Tang
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China
| | - K Friston
- Wellcome Trust Centre for Neuroimaging, University College London (UCL) Institute of Neurology, London, United Kingdom
| | - S Liu
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China.
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Sun Y, Lim J, Kwok K, Bezerianos A. Functional cortical connectivity analysis of mental fatigue unmasks hemispheric asymmetry and changes in small-world networks. Brain Cogn 2014; 85:220-30. [DOI: 10.1016/j.bandc.2013.12.011] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Revised: 12/23/2013] [Accepted: 12/26/2013] [Indexed: 10/25/2022]
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Olsen A, Brunner JF, Indredavik Evensen KA, Finnanger TG, Vik A, Skandsen T, Landrø NI, Håberg AK. Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function. Cereb Cortex 2014; 25:2170-80. [PMID: 24557637 PMCID: PMC4494028 DOI: 10.1093/cercor/bhu023] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations.
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Affiliation(s)
- Alexander Olsen
- MI-Lab and Department of Circulation and Medical Imaging
- Department of Physical Medicine and Rehabilitation
| | - Jan Ferenc Brunner
- Department of Neuroscience
- Department of Physical Medicine and Rehabilitation
| | - Kari Anne Indredavik Evensen
- Department of Public Health and General Practice
- Department of Laboratory Medicine, Children's and Women's Health and
- Department of Physiotherapy, Trondheim Municipality, Trondheim, Norway
| | - Torun Gangaune Finnanger
- The Regional Centre for Child and Youth Mental Health and Child Welfare (RKBU) – Central Norway, Norwegian University of Science and Technology, Trondheim, Norway
- Children's Clinic
| | - Anne Vik
- Department of Neuroscience
- Department of Neurosurgery
| | - Toril Skandsen
- Department of Neuroscience
- Department of Physical Medicine and Rehabilitation
| | - Nils Inge Landrø
- National Competence Centre for Complex Symptom Disorders and
- Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway
| | - Asta Kristine Håberg
- Department of Neuroscience
- Department of Radiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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Rodriguez Vega B, Melero-Llorente J, Bayon Perez C, Cebolla S, Mira J, Valverde C, Fernández-Liria A. Impact of mindfulness training on attentional control and anger regulation processes for psychotherapists in training. Psychother Res 2013; 24:202-13. [DOI: 10.1080/10503307.2013.838651] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Prisciandaro JJ, Myrick H, Henderson S, McRae-Clark AL, Brady KT. Prospective associations between brain activation to cocaine and no-go cues and cocaine relapse. Drug Alcohol Depend 2013; 131:44-9. [PMID: 23683790 PMCID: PMC3703628 DOI: 10.1016/j.drugalcdep.2013.04.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 04/03/2013] [Accepted: 04/06/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND The ability to predict potential for relapse to substance use following treatment could be very useful in targeting aftercare strategies. Recently, a number of investigators have focused on using neural activity measured by fMRI to predict relapse propensity. The purpose of the present study was to use fMRI to investigate prospective associations between brain reactivity to cocaine and response inhibition cues and relapse to cocaine use. METHODS Thirty cocaine-dependent participants with clean cocaine urine drug screens (UDS) completed a baseline fMRI scan, including a cocaine-cue reactivity task and a go no-go response inhibition task. After participating in a brief clinical trial of d-cycloserine for the facilitation of cocaine-cue extinction, they returned for a one-week follow-up UDS. Associations between baseline activation to cocaine and inhibition cues and relapse to cocaine use were explored. RESULTS Positive cocaine UDS was significantly associated with cocaine-cue activation in the right putamen and insula, as well as bilateral occipital regions. Associations between positive cocaine UDS and activation to no-go cues were concentrated in the postcentral gyri, a region involved in response execution. CONCLUSIONS Although preliminary, these results suggest that brain imaging may be a useful tool for predicting risk for relapse in cocaine-dependent individuals. Further, larger-scale naturalistic studies are needed to corroborate and extend these findings.
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Affiliation(s)
- James J Prisciandaro
- Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Clinical Neuroscience Division, 67 President Street, Charleston, SC 29425, USA.
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Shaw TH, Funke ME, Dillard M, Funke GJ, Warm JS, Parasuraman R. Event-related cerebral hemodynamics reveal target-specific resource allocation for both "go" and "no-go" response-based vigilance tasks. Brain Cogn 2013; 82:265-73. [PMID: 23727665 DOI: 10.1016/j.bandc.2013.05.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Revised: 04/20/2013] [Accepted: 05/05/2013] [Indexed: 01/08/2023]
Abstract
Transcranial Doppler sonography was used to measure cerebral blood flow velocity (CBFV) in the right and left cerebral hemispheres during the performance of a 50-min visual vigilance session. Observers monitored a simulated flight of unmanned aerial vehicles for cases in which one of the vehicles was flying in an inappropriate direction relative to its cohorts. Two types of vigilance tasks were employed: a traditional task in which observers made button press ("go") responses to critical signals, and a modification of the traditional task called the Sustained Attention to Response Task (SART) in which "go" responses acknowledged nonsignal events and response withholding ("no-go") signified signal detection. Signal detections and global CBFV scores declined over time. In addition, fine-grained event-related analyses revealed that the detection of signals was accompanied by an elevation of CBFV that was not present with missed signals. As was the case with the global scores, the magnitude of the transient CBFV increments associated with signal detection also declined over time, and these findings were independent of task type. The results support the view of CBFV as an index of the cognitive evaluation of stimulus significance, and a resource model of vigilance in which the need for continuous attention produces a depletion of information-processing assets that are not replenished as the task progresses. Further, temporal declines in the magnitude of event-related CBFV in response to critical signals only is evidence that the decrement function in vigilance is due to attentional processing and not specific task elements such as the required response format.
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Affiliation(s)
- Tyler H Shaw
- Center of Excellence in Neuroergonomics, Technology, and Cognition-CENTEC, George Mason University, Department of Psychology, 4400 University Drive, Fairfax, VA, USA.
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Krull KR, Bhojwani D, Conklin HM, Pei D, Cheng C, Reddick WE, Sandlund JT, Pui CH. Genetic mediators of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 2013; 31:2182-8. [PMID: 23650422 DOI: 10.1200/jco.2012.46.7944] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive problems, with significant interindividual variability in outcome. This study examined genetic polymorphisms associated with variability in neurocognitive outcome. PATIENTS AND METHODS Neurocognitive outcomes were evaluated at the end of therapy in 243 survivors treated on an institutional protocol featuring risk-adapted chemotherapy without prophylactic cranial irradiation. Polymorphisms in genes related to pharmacokinetics or pharmacodynamics of antileukemic agents, drug metabolism, oxidative stress, and attention problems in noncancer populations were examined as predictors of outcome, using multiple general linear models and controlling for age at diagnosis, sex, race, and treatment intensity. RESULTS Compared with national norms, the cohort demonstrated significantly higher rates of problems on direct assessment of sustained attention (P = .01) and on parent ratings of attention problems (P = .02). Children with the A2756G polymorphism in methionine synthase (MS) were more likely to demonstrate deficits in attentiveness (P = .03) and response speed (P = .02), whereas those with various polymorphisms in glutathione S-transferase demonstrated increased performance variability (P = .01) and reduced attentiveness (P = .003). Polymorphisms in monoamine oxidase (T1460CA) were associated with increased attention variability (P = .03). Parent-reported attention problems were more common in children with the Cys112Arg polymorphism in apoliopoprotein E4 (P = .01). CONCLUSION These results are consistent with our previous report of association between attention problems and MS in an independent cohort of long-term survivors of childhood ALL treated with chemotherapy only. The results also raise the possibility of an impact from genetic predispositions related to oxidative stress and CNS integrity.
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Affiliation(s)
- Kevin R Krull
- Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Place, MS 735, Memphis, TN 38105-3678, USA.
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