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García-Fernández L, Romero-Ferreiro V, Padilla S, Wynn R, Pérez-Gálvez B, Álvarez-Mon MÁ, Sánchez-Cabezudo Á, Rodriguez-Jimenez R. Transcranial direct current stimulation (tDCS) enhances cognitive function in schizophrenia: A randomized double-blind sham-controlled trial. Psychiatry Res 2025; 344:116308. [PMID: 39647260 DOI: 10.1016/j.psychres.2024.116308] [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: 07/12/2024] [Revised: 11/26/2024] [Accepted: 11/30/2024] [Indexed: 12/10/2024]
Abstract
This study aimed to examine the cognitive effects of tDCS and the subjective cognitive improvement perceived by patients with schizophrenia. A total of 173 outpatients diagnosed with schizophrenia were recruited for this double-blind, randomized, placebo-controlled trial. Two different stimulation modes were applied: 2 mA 20 minutes active tDCS and sham tDCS. Ten daily sessions over 10 consecutive weekdays were applied, using a bifrontal montage (F3/F4). The Positive and Negative Syndrome Scale for Schizophrenia and the MATRICS Consensus Cognitive Battery (MCCB) were administered at baseline. The MCCB and a scale designed for measuring subjective cognitive improvement were administered to evaluate the outcomes. Post hoc comparisons revealed significant effects between the two types of interventions in Working Memory (EMM difference = 2.716, p < .001) and Neurocognition (EMM difference = 1.289, p = .007. Chi-squared tests demonstrated a significant association between subjective improvement and the treatment group, χ² (2) = 10.413, p = .005, Cramer's V = 0.295. A higher proportion of patients in active tDCS (68.6%) reported cognitive improvement compared to sham tDCS (31.4%). We concluded that tDCS can enhance cognition and generate a satisfactory perception of cognitive improvement in patients with schizophrenia.
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Affiliation(s)
- Lorena García-Fernández
- Clinical Medicine Department, Universidad Miguel Hernández, Investigador. Cibersam isciii, Crta. Nacional 332 s/n, Alicante 03550, Spain; Psychiatry Department, Hospital Universitario de San Juan, Alicante, Spain; CIBERSAM-ISCIII (Biomedical Research Networking Centre for Mental Health), Spain.
| | - Verónica Romero-Ferreiro
- CIBERSAM-ISCIII (Biomedical Research Networking Centre for Mental Health), Spain; European University of Madrid, Madrid, Spain; Health Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Sergio Padilla
- Clinical Medicine Department, Universidad Miguel Hernández, Investigador. Cibersam isciii, Crta. Nacional 332 s/n, Alicante 03550, Spain; Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Rolf Wynn
- Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Education, ICT and Learning, Østfold University College, Halden, Norway
| | - Bartolomé Pérez-Gálvez
- Clinical Medicine Department, Universidad Miguel Hernández, Investigador. Cibersam isciii, Crta. Nacional 332 s/n, Alicante 03550, Spain; Psychiatry Department, Hospital Universitario de San Juan, Alicante, Spain
| | - Miguel Ángel Álvarez-Mon
- Department of Medicine and Medical Specialities. University of Alcala, Alcala de Henares, Spain; Department of Psychiatry and Mental Health. Hospital Universitario Infanta Leonor, Madrid, Spain; Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid 28034, Spain
| | | | - Roberto Rodriguez-Jimenez
- CIBERSAM-ISCIII (Biomedical Research Networking Centre for Mental Health), Spain; Health Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain; Complutense University of Madrid (UCM), Madrid, Spain
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Gee A, Dazzan P, Grace AA, Modinos G. Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review. Transl Psychiatry 2025; 15:21. [PMID: 39856031 PMCID: PMC11760974 DOI: 10.1038/s41398-024-03221-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 12/06/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
Schizophrenia spectrum disorders (SSD) involve disturbances in the integration of perception, emotion and cognition. The corticolimbic system is an interacting set of cortical and subcortical brain regions critically involved in this process. Understanding how neural circuitry and molecular mechanisms within this corticolimbic system may contribute to the development of not only positive symptoms but also negative and cognitive deficits in SSD has been a recent focus of intense research, as the latter are not adequately treated by current antipsychotic medications and are more strongly associated with poorer functioning and long-term outcomes. This review synthesises recent developments examining corticolimbic dysfunction in the pathophysiology of SSD, with a focus on neuroimaging advances and related novel methodologies that enable the integration of data across different scales. We then integrate how these findings may inform the identification of novel therapeutic and preventive targets for SSD symptomatology. A range of pharmacological interventions have shown initial promise in correcting corticolimbic dysfunction and improving negative, cognitive and treatment-resistant symptoms. We discuss current challenges and opportunities for improving the still limited translation of these research findings into clinical practice. We argue how our knowledge of the role of corticolimbic dysfunction can be improved by combining multiple research modalities to examine hypotheses across different spatial and temporal scales, combining neuroimaging with experimental interventions and utilising large-scale consortia to advance biomarker identification. Translation of these findings into clinical practice will be aided by consideration of optimal intervention timings, biomarker-led patient stratification, and the development of more selective medications.
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Affiliation(s)
- Abigail Gee
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Paola Dazzan
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Anthony A Grace
- Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Gemma Modinos
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
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3
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Deng Q, Wu C, Parker E, Zhu J, Liu TCY, Duan R, Yang L. Mystery of gamma wave stimulation in brain disorders. Mol Neurodegener 2024; 19:96. [PMID: 39695746 PMCID: PMC11657232 DOI: 10.1186/s13024-024-00785-x] [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: 04/11/2024] [Accepted: 12/03/2024] [Indexed: 12/20/2024] Open
Abstract
Neuronal oscillations refer to rhythmic and periodic fluctuations of electrical activity in the central nervous system that arise from the cellular properties of diverse neuronal populations and their interactions. Specifically, gamma oscillations play a crucial role in governing the connectivity between distinct brain regions, which are essential in perception, motor control, memory, and emotions. In this context, we recapitulate various current stimulation methods to induce gamma entrainment. These methods include sensory stimulation, optogenetic modulation, photobiomodulation, and transcranial electrical or magnetic stimulation. Simultaneously, we explore the association between abnormal gamma oscillations and central nervous system disorders such as Alzheimer's disease, Parkinson's disease, stroke, schizophrenia, and autism spectrum disorders. Evidence suggests that gamma entrainment-inducing stimulation methods offer notable neuroprotection, although somewhat controversial. This review comprehensively discusses the functional role of gamma oscillations in higher-order brain activities from both physiological and pathological perspectives, emphasizing gamma entrainment as a potential therapeutic approach for neuropsychiatric disorders. Additionally, we discuss future opportunities and challenges in implementing such strategies.
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Affiliation(s)
- Qianting Deng
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China
| | - Chongyun Wu
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China
| | - Emily Parker
- Augusta University, 1120 15th Street, Augusta, GA, 30912, USA
| | - Jing Zhu
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China
| | - Timon Cheng-Yi Liu
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China
| | - Rui Duan
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China.
| | - Luodan Yang
- School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China.
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Negrón-Oyarzo I, Dib T, Chacana-Véliz L, López-Quilodrán N, Urrutia-Piñones J. Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models. Front Neural Circuits 2024; 18:1286111. [PMID: 38638163 PMCID: PMC11024307 DOI: 10.3389/fncir.2024.1286111] [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: 08/30/2023] [Accepted: 03/11/2024] [Indexed: 04/20/2024] Open
Abstract
Cognitive control of behavior is crucial for well-being, as allows subject to adapt to changing environments in a goal-directed way. Changes in cognitive control of behavior is observed during cognitive decline in elderly and in pathological mental conditions. Therefore, the recovery of cognitive control may provide a reliable preventive and therapeutic strategy. However, its neural basis is not completely understood. Cognitive control is supported by the prefrontal cortex, structure that integrates relevant information for the appropriate organization of behavior. At neurophysiological level, it is suggested that cognitive control is supported by local and large-scale synchronization of oscillatory activity patterns and neural spiking activity between the prefrontal cortex and distributed neural networks. In this review, we focus mainly on rodent models approaching the neuronal origin of these prefrontal patterns, and the cognitive and behavioral relevance of its coordination with distributed brain systems. We also examine the relationship between cognitive control and neural activity patterns in the prefrontal cortex, and its role in normal cognitive decline and pathological mental conditions. Finally, based on these body of evidence, we propose a common mechanism that may underlie the impaired cognitive control of behavior.
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Affiliation(s)
- Ignacio Negrón-Oyarzo
- Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Tatiana Dib
- Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Lorena Chacana-Véliz
- Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Programa de Doctorado en Ciencias Mención en Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Nélida López-Quilodrán
- Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Programa de Doctorado en Ciencias Mención en Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Jocelyn Urrutia-Piñones
- Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Programa de Doctorado en Ciencias Mención en Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
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Bonassi G, Semprini M, Mandich P, Trevisan L, Marchese R, Lagravinese G, Barban F, Pelosin E, Chiappalone M, Mantini D, Avanzino L. Neural oscillations modulation during working memory in pre-manifest and early Huntington's disease. Brain Res 2023; 1820:148540. [PMID: 37598900 DOI: 10.1016/j.brainres.2023.148540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 07/21/2023] [Accepted: 08/17/2023] [Indexed: 08/22/2023]
Abstract
INTRODUCTION We recently demonstrated specific spectral signatures associated with updating of memory information, working memory (WM) maintenance and readout, with relatively high spatial resolution by means of high-density electroencephalography (hdEEG). WM is impaired already in early symptomatic HD (early-HD) and in pre-manifest HD (pre-HD). The aim of this study was to test whether hdEEG coupled to source localization allows for the identification of neuronal oscillations in specific frequency bands in 16 pre-HD and early-HD during different phases of a WM task. METHODS We examined modulation of neural oscillations by event-related synchronization and desynchronization (ERS/ERD) of θ, β, gamma low, γLOW and γHIGH EEG bands in a-priori selected large fronto-parietal network, including the insula and the cerebellum. RESULTS We found: (i) Reduced θ oscillations in HD with respect to controls in almost all the areas of the WM network during the update and readout phases; (ii) Modulation of β oscillations, which increased during the maintenance phase of the WM task in both groups; (iii) correlation of γHIGH oscillations during WM task with disease burden score in HD patients. CONCLUSIONS Our data show reduced phase-specific modulation of oscillations in pre-HD and early-HD, even in the presence of preserved dynamic of modulation. Particularly, reduced synchronization in the θ band in the areas of the WM network, consistent with abnormal long-range coordination of neuronal activity within this network, was found in update and readout phases in HD groups.
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Affiliation(s)
- Gaia Bonassi
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy
| | - Marianna Semprini
- Rehab Technologies, Istituto Italiano di Tecnologia, 16163 Genoa, Italy
| | - Paola Mandich
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy; IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Lucia Trevisan
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | | | - Giovanna Lagravinese
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy; IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Federico Barban
- Rehab Technologies, Istituto Italiano di Tecnologia, 16163 Genoa, Italy; Dept. of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genoa, 16145 Genoa, Italy
| | - Elisa Pelosin
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy; IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Michela Chiappalone
- Rehab Technologies, Istituto Italiano di Tecnologia, 16163 Genoa, Italy; Dept. of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genoa, 16145 Genoa, Italy
| | - Dante Mantini
- Research Center for Motor Control and Neuroplasticity, KU Leuven, 3001 Leuven, Belgium; Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, 30126 Venice, Italy
| | - Laura Avanzino
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; Department of Experimental Medicine, Section of Human Physiology, University of Genoa, 16132 Genoa, Italy.
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Murphy OW, Hoy KE, Wong D, Bailey NW, Fitzgerald PB, Segrave RA. Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder. Brain Cogn 2023; 173:106105. [PMID: 37963422 DOI: 10.1016/j.bandc.2023.106105] [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: 06/19/2023] [Revised: 09/25/2023] [Accepted: 10/31/2023] [Indexed: 11/16/2023]
Abstract
OBJECTIVE To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.
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Affiliation(s)
- O W Murphy
- Central Clinical School, Monash University, Clayton, VIC, Australia; Bionics Institute, East Melbourne, VIC, Australia.
| | - K E Hoy
- Central Clinical School, Monash University, Clayton, VIC, Australia; Bionics Institute, East Melbourne, VIC, Australia
| | - D Wong
- School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia
| | - N W Bailey
- Central Clinical School, Monash University, Clayton, VIC, Australia; Monarch Research Institute Monarch Mental Health Group, Sydney, NSW, Australia; School of Medicine and Psychology, Australian National University, Canberra, ACT, Australia
| | - P B Fitzgerald
- Monarch Research Institute Monarch Mental Health Group, Sydney, NSW, Australia; School of Medicine and Psychology, Australian National University, Canberra, ACT, Australia
| | - R A Segrave
- BrainPark, Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, Australia
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Nikolin S, Martin D, Loo CK, Boonstra TW. Transcranial Direct Current Stimulation Modulates Working Memory Maintenance Processes in Healthy Individuals. J Cogn Neurosci 2023; 35:468-484. [PMID: 36603051 DOI: 10.1162/jocn_a_01957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The effects of transcranial direct current stimulation (tDCS) at the pFC are often investigated using cognitive paradigms, particularly working memory tasks. However, the neural basis for the neuromodulatory cognitive effects of tDCS, including which subprocesses are affected by stimulation, is not completely understood. We investigated the effects of tDCS on working memory task-related spectral activity during and after tDCS to gain better insights into the neurophysiological changes associated with stimulation. We reanalyzed data from 100 healthy participants grouped by allocation to receive either sham (0 mA, 0.016 mA, and 0.034 mA) or active (1 mA or 2 mA) stimulation during a 3-back task. EEG data were used to analyze event-related spectral power in frequency bands associated with working memory performance. Frontal theta event-related synchronization (ERS) was significantly reduced post-tDCS in the active group. Participants receiving active tDCS had slower RTs following tDCS compared with sham, suggesting interference with practice effects associated with task repetition. Theta ERS was not significantly correlated with RTs or accuracy. tDCS reduced frontal theta ERS poststimulation, suggesting a selective disruption to working memory cognitive control and maintenance processes. These findings suggest that tDCS selectively affects specific subprocesses during working memory, which may explain heterogenous behavioral effects.
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Affiliation(s)
- Stevan Nikolin
- University of New South Wales, Sydney, Australia
- Black Dog Institute, Sydney, New South Wales, Australia
| | - Donel Martin
- University of New South Wales, Sydney, Australia
- Black Dog Institute, Sydney, New South Wales, Australia
| | - Colleen K Loo
- University of New South Wales, Sydney, Australia
- Black Dog Institute, Sydney, New South Wales, Australia
| | - Tjeerd W Boonstra
- University of New South Wales, Sydney, Australia
- Maastricht University, The Netherlands
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Rahimi V, Mohammadkhani G, Alaghband Rad J, Mousavi SZ, Khalili ME. Modulation of auditory temporal processing, speech in noise perception, auditory-verbal memory, and reading efficiency by anodal tDCS in children with dyslexia. Neuropsychologia 2022; 177:108427. [PMID: 36410540 DOI: 10.1016/j.neuropsychologia.2022.108427] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 10/30/2022] [Accepted: 11/17/2022] [Indexed: 11/23/2022]
Abstract
Dyslexia is a neurodevelopmental disorder that is prevalent in children. It is estimated that 30-50% of individuals diagnosed with dyslexia also manifest an auditory perceptual deficit characteristic of auditory processing disorder (APD). Some studies suggest that defects in basic auditory processing can lead to phonological defects as the most prominent cause of dyslexia. Thus, in some cases, there may be interrelationships between dyslexia and some of the aspects of central auditory processing. In recent years, transcranial direct current stimulation (tDCS) has been used as a safe method for the modulation of central auditory processing aspects in healthy adults and reading skills in children with dyslexia. Therefore, the objectives of our study were to investigate the effect of tDCS on the modulation of different aspects of central auditory processing, aspects of reading, and the relationship between these two domains in dyslexic children with APD. A within-subjects design was employed to investigate the effect of two electrode arrays (the anode on the left STG (AC)/cathode on the right shoulder and anode on the left STG/cathode on the right STG) on auditory temporal processing; speech-in-noise perception, short-term auditory memory; and high-frequency word, low-frequency word, pseudoword, and text reading. The results of this clinical trial showed the modulation of the studied variables in central auditory processing and the accuracy and speed of reading variables compared to the control and sham statuses in both electrode arrays. Our results also showed that the improvement of the accuracy and speed of text reading, as well as the accuracy of pseudoword reading were related to the improvement of speech in noise perception and temporal processing. The results of this research can be effective in clarifying the basis of the neurobiology of dyslexia and, in particular, the hypothesis of the role of basic auditory processing and subsequently the role of the auditory cortex in dyslexia. These results might provide a framework to facilitate behavioral rehabilitation in dyslexic children with APD.
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Affiliation(s)
- Vida Rahimi
- Department of Audiology, School of Rehabilitation, Tehran University of Medical Science, Tehran, Iran
| | - Ghassem Mohammadkhani
- Department of Audiology, School of Rehabilitation, Tehran University of Medical Science, Tehran, Iran.
| | - Javad Alaghband Rad
- Department of Psychiatry, Tehran University of Medical Sciences, Roozbeh Hospital, Tehran, Iran
| | - Seyyedeh Zohre Mousavi
- Department of Speech Therapy, School of Rehabilitation, Iran University of Medical Science, Tehran, Iran
| | - Mohammad Ehsan Khalili
- Department of Audiology, School of Rehabilitation, Tehran University of Medical Science, Tehran, Iran
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Arvin S, Yonehara K, Glud AN. Therapeutic Neuromodulation toward a Critical State May Serve as a General Treatment Strategy. Biomedicines 2022; 10:biomedicines10092317. [PMID: 36140418 PMCID: PMC9496064 DOI: 10.3390/biomedicines10092317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/11/2022] [Accepted: 09/14/2022] [Indexed: 11/18/2022] Open
Abstract
Brain disease has become one of this century’s biggest health challenges, urging the development of novel, more effective treatments. To this end, neuromodulation represents an excellent method to modulate the activity of distinct neuronal regions to alleviate disease. Recently, the medical indications for neuromodulation therapy have expanded through the adoption of the idea that neurological disorders emerge from deficits in systems-level structures, such as brain waves and neural topology. Connections between neuronal regions are thought to fluidly form and dissolve again based on the patterns by which neuronal populations synchronize. Akin to a fire that may spread or die out, the brain’s activity may similarly hyper-synchronize and ignite, such as seizures, or dwindle out and go stale, as in a state of coma. Remarkably, however, the healthy brain remains hedged in between these extremes in a critical state around which neuronal activity maneuvers local and global operational modes. While it has been suggested that perturbations of this criticality could underlie neuropathologies, such as vegetative states, epilepsy, and schizophrenia, a major translational impact is yet to be made. In this hypothesis article, we dissect recent computational findings demonstrating that a neural network’s short- and long-range connections have distinct and tractable roles in sustaining the critical regime. While short-range connections shape the dynamics of neuronal activity, long-range connections determine the scope of the neuronal processes. Thus, to facilitate translational progress, we introduce topological and dynamical system concepts within the framework of criticality and discuss the implications and possibilities for therapeutic neuromodulation guided by topological decompositions.
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Affiliation(s)
- Simon Arvin
- Center for Experimental Neuroscience—CENSE, Department of Neurosurgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200 Aarhus N, Denmark
- Danish Research Institute of Translational Neuroscience—DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, Ole Worms Allé 8, 8000 Aarhus C, Denmark
- Department of Neurosurgery, Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 11 Building A, 8200 Aarhus N, Denmark
- Correspondence: ; Tel.: +45 6083-1275
| | - Keisuke Yonehara
- Danish Research Institute of Translational Neuroscience—DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, Ole Worms Allé 8, 8000 Aarhus C, Denmark
- Multiscale Sensory Structure Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
- Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan
| | - Andreas Nørgaard Glud
- Center for Experimental Neuroscience—CENSE, Department of Neurosurgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200 Aarhus N, Denmark
- Department of Neurosurgery, Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 11 Building A, 8200 Aarhus N, Denmark
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10
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Pross B, Strube W, Papazova I, Güler D, Häckert J, Keeser D, Padberg F, Siamouli M, Falkai P, Hasan A. Anodal transcranial direct current stimulation sustainably increases EEG alpha activity in patients with schizophrenia. Neuropsychopharmacol Rep 2022; 42:323-332. [PMID: 35716122 PMCID: PMC9515721 DOI: 10.1002/npr2.12274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 05/11/2022] [Accepted: 05/14/2022] [Indexed: 11/20/2022] Open
Abstract
AIMS Transcranial direct current stimulation (tDCS) applied to the prefrontal cortex has been frequently used to elicit behavioral changes in patients with schizophrenia. However, the interaction between prefrontal tDCS and electrophysiological changes remains largely uncharted. The present study aimed to investigate cortical electrophysiological changes induced by tDCS in frontal areas by means of repeated electroencephalography (EEG) in patients with schizophrenia. METHODS In total, 20 patients with schizophrenia received 13 minutes of anodal tDCS (1 mA) applied to the left dorsolateral prefrontal cortex (DLPFC). Repeated resting EEG was recorded before (once) and following (at five follow-up time-bins) tDCS to trace post-tDCS effects. We used sLORETA for source reconstruction to preserve the localization of brain signals with a low variance and to analyze frequency changes. RESULTS We observed significant changes after the stimulation in areas highly connected with the stimulated DLPFC areas. The alpha 1 (8.5-10.0 Hz) activity showed a highly significant, long-lasting, increase for up to 1 hour after the stimulation in the postcentral gyrus (Brodmann area 2, 3, and 40). Significant yet unstable changes were also seen in the alpha-2 frequency band precentral at 10 minutes, in the beta-1 frequency band occipital at 20 minutes, and in the beta-3 frequency band temporal at 40 minutes. CONCLUSION We were able to show that anodal tDCS can induce stable EEG changes in patients with schizophrenia. The results underline the potential of tDCS to induce long-lasting neurophysiological changes in patients with schizophrenia showing the possibility to induce brain excitability changes in this population.
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Affiliation(s)
- Benjamin Pross
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical FacultyUniversity of Augsburg, BKH AugsburgAugsburgGermany
- Department of Psychiatry and PsychotherapyLMU University HospitalMunichGermany
| | - Wolfgang Strube
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical FacultyUniversity of Augsburg, BKH AugsburgAugsburgGermany
| | - Irina Papazova
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical FacultyUniversity of Augsburg, BKH AugsburgAugsburgGermany
| | - Duygu Güler
- Department of Psychiatry and PsychotherapyLMU University HospitalMunichGermany
| | - Jan Häckert
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical FacultyUniversity of Augsburg, BKH AugsburgAugsburgGermany
| | - Daniel Keeser
- Department of Psychiatry and PsychotherapyLMU University HospitalMunichGermany
| | - Frank Padberg
- Department of Psychiatry and PsychotherapyLMU University HospitalMunichGermany
| | - Melina Siamouli
- 3rd Department of Psychiatry, School of MedicineAristotle University of ThessalonikiThessalonikiGreece
| | - Peter Falkai
- Department of Psychiatry and PsychotherapyLMU University HospitalMunichGermany
| | - Alkomiet Hasan
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical FacultyUniversity of Augsburg, BKH AugsburgAugsburgGermany
- Department of Psychiatry and PsychotherapyLMU University HospitalMunichGermany
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11
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Shu IW, Granholm EL, Singh F. Targeting Frontal Gamma Activity with Neurofeedback to Improve Working Memory in Schizophrenia. Curr Top Behav Neurosci 2022; 63:153-172. [PMID: 35989397 DOI: 10.1007/7854_2022_377] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Optimal working memory (WM), the mental ability to internally maintain and manipulate task-relevant information, requires coordinated activity of dorsal-lateral prefrontal cortical (DLPFC) neurons. More specifically, during delay periods of tasks with WM features, DLPFC microcircuits generate persistent, stimulus-specific higher-frequency (e.g., gamma) activity. This activity largely depends on recurrent connections between parvalbumin positive inhibitory interneurons and pyramidal neurons in more superficial DLPFC layers. Due to the size and organization of pyramidal neurons (especially apical dendrites), local field potentials generated by DLPFC microcircuits are strong enough to pass outside the skull and can be detected using electroencephalography (EEG). Since patients with schizophrenia (SCZ) exhibit both DLPFC and WM abnormalities, EEG markers of DLPFC microcircuit activity during WM may serve as effective biomarkers or treatment targets. In this review, we summarize converging evidence from primate and human studies for a critical role of DLPFC microcircuit activity during WM and in the pathophysiology of SCZ. We also present a meta-analysis of studies available in PubMed specifically comparing frontal gamma activity between participants with SCZ and healthy controls, to determine whether frontal gamma activity may be a valid biomarker or treatment target for patients with SCZ. We summarize the complex cognitive and neurophysiologic processes contributing to neural oscillations during tasks with WM features, and how such complexity has stalled the development of neurophysiologic biomarkers and treatment targets. Finally, we summarize promising results from early reports using neuromodulation to target DLPFC neural activity and improve cognitive function in participants with SCZ, including a study from our team demonstrating that gamma-EEG neurofeedback increases frontal gamma power and WM performance in participants with SCZ. From the evidence discussed in this review, we believe the emerging field of neuromodulation, which includes extrinsic (electrical or magnetic stimulation) and intrinsic (EEG neurofeedback) modalities, will, in the coming decade, provide promising treatment options targeting specific neurophysiologic properties of specific brain areas to improve cognitive and behavioral health for patients with SCZ.
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Affiliation(s)
- I-Wei Shu
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Eric L Granholm
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Fiza Singh
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
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12
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Caulfield KA, Indahlastari A, Nissim NR, Lopez JW, Fleischmann HH, Woods AJ, George MS. Electric Field Strength From Prefrontal Transcranial Direct Current Stimulation Determines Degree of Working Memory Response: A Potential Application of Reverse-Calculation Modeling? Neuromodulation 2022; 25:578-587. [PMID: 35670064 DOI: 10.1111/ner.13342] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/24/2020] [Accepted: 11/30/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Transcranial direct current stimulation (tDCS) for working memory is an enticing treatment, but there is mixed evidence to date. OBJECTIVES We tested the effects of electric field strength from uniform 2 mA dosing on working memory change from prestimulation to poststimulation. Second, we statistically evaluated a reverse-calculation method of individualizing tDCS dose and its effect on normalizing electric field at the cortex. MATERIALS AND METHODS We performed electric field modeling on a data set of 28 healthy older adults (15 women, mean age = 73.7, SD = 7.3) who received ten sessions of active 2 mA tDCS (N = 14) or sham tDCS (N = 14) applied over bilateral dorsolateral prefrontal cortices (DLPFC) in a triple-blind design. We evaluated the relationship between electric field strength and working memory change on an N-back task in conditions of above-median, high electric field from active 2 mA (N = 7), below-median, low electric field from active 2 mA (N = 7), and sham (N = 14) at regions of interest (ROI) at the left and right DLPFC. We then determined the individualized reverse-calculation dose to produce the group average electric field and measured the electric field variance between uniform 2 mA doses vs individualized reverse-calculation doses at the same ROIs. RESULTS Working memory improvements from pre- to post-tDCS were significant for the above-median electric field from active 2 mA condition at the left DLPFC (mixed ANOVA, p = 0.013). Furthermore, reverse-calculation modeling significantly reduced electric field variance at both ROIs (Levene's test; p < 0.001). CONCLUSIONS Higher electric fields at the left DLPFC from uniform 2 mA doses appear to drive working memory improvements from tDCS. Individualized doses from reverse-calculation modeling significantly reduce electric field variance at the cortex. Taken together, using reverse-calculation modeling to produce the same, high electric fields at the cortex across participants may produce more effective future tDCS treatments for working memory.
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Affiliation(s)
- Kevin A Caulfield
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA.
| | - Aprinda Indahlastari
- Center for Cognitive Aging and Memory Clinical Translational Research, McKnight Brain Institute, Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA
| | - Nicole R Nissim
- Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
| | - James W Lopez
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA
| | - Holly H Fleischmann
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA
| | - Adam J Woods
- Center for Cognitive Aging and Memory Clinical Translational Research, McKnight Brain Institute, Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA
| | - Mark S George
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA
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13
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Mathematical Model Insights into EEG Origin under Transcranial Direct Current Stimulation (tDCS) in the Context of Psychosis. J Clin Med 2022; 11:jcm11071845. [PMID: 35407453 PMCID: PMC8999473 DOI: 10.3390/jcm11071845] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/12/2022] [Accepted: 03/22/2022] [Indexed: 02/04/2023] Open
Abstract
Schizophrenia is a psychotic disease that develops progressively over years with a transition from prodromal to psychotic state associated with a disruption in brain activity. Transcranial Direct Current Stimulation (tDCS), known to alleviate pharmaco-resistant symptoms in patients suffering from schizophrenia, promises to prevent such a psychotic transition. To understand better how tDCS affects brain activity, we propose a neural cortico-thalamo-cortical (CTC) circuit model involving the Ascending Reticular Arousal System (ARAS) that permits to describe major impact features of tDCS, such as excitability for short-duration stimulation and electroencephalography (EEG) power modulation for long-duration stimulation. To this end, the mathematical model relates stimulus duration and Long-Term Plasticity (LTP) effect, in addition to describing the temporal LTP decay after stimulus offset. This new relation promises to optimize future stimulation protocols. Moreover, we reproduce successfully EEG-power modulation under tDCS in a ketamine-induced psychosis model and confirm the N-methyl-d-aspartate (NMDA) receptor hypofunction hypothesis in the etiopathophysiology of schizophrenia. The model description points to an important role of the ARAS and the δ-rhythm synchronicity in CTC circuit in early-stage psychosis.
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14
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No effects of transcranial direct current stimulation on visual evoked potential and peak gamma frequency. Cogn Process 2022; 23:235-254. [PMID: 35099659 DOI: 10.1007/s10339-022-01076-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 01/12/2022] [Indexed: 11/03/2022]
Abstract
Evidence suggests that the visual evoked potential (VEP) and gamma oscillations elicited by visual stimuli reflect the balance of excitatory and inhibitory (E-I) cortical processes. As tDCS has been shown to modulate E-I balance, the current study investigated whether amplitudes of VEP components (N1 and P2) and peak gamma frequency are modulated by transcranial direct current stimulation (tDCS). Healthy adults underwent two electroencephalography (EEG) recordings while viewing stimuli designed to elicit a robust visual response. Between the two recordings, participants were randomly assigned to three tDCS conditions (anodal-, cathodal-, and sham-tDCS) or received no-tDCS. tDCS electrodes were placed over the occipital cortex (Oz) and the left cheek with an intensity of 2 mA for 10 min. Data of 39 participants were analysed for VEP amplitudes and peak gamma frequency using mixed-model ANOVAs. The results showed no main effects of tDCS in any metric. Possible explanations for the absence of tDCS effects are discussed.
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15
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Rossi S, Santarnecchi E, Feurra M. Noninvasive brain stimulation and brain oscillations. HANDBOOK OF CLINICAL NEUROLOGY 2022; 184:239-247. [PMID: 35034738 DOI: 10.1016/b978-0-12-819410-2.00013-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Recent technological advances in the field of noninvasive brain stimulation (NIBS) have allowed to interact with endogenous brain oscillatory activity, the main neural communication code of our brain, opening new scenarios for transient modifications of cognitive and behavioral performances: such a possibility can be capitalized both for research purposes in healthy subjects, as well as in the context of therapeutic and rehabilitative settings. Among NiBS methodologies, transcranial magnetic stimulation (TMS) has been the first used to this purpose, and also thanks to the technical development of TMS-EEG co-registering systems, the mechanistic knowledge regarding the role of brain oscillations has been improved. Another approach to brain oscillations considers electric stimulation methods, such as transcranial direct current stimulation (tDCS), and especially transcranial alternating current stimulation (tACS), for which -however- some technical and conceptual caveats have emerged. In this chapter, we briefly review the uses of NiBS in this field up to now, by providing an update on the current status of research applications as well as of its attempts of exploitation in translational clinical applications, especially regarding motor disorders and for understanding and reducing some psychiatric symptoms.
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Affiliation(s)
- Simone Rossi
- Unit of Neurology and Clinical Neurophysiology, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
| | - Emiliano Santarnecchi
- Unit of Neurology and Clinical Neurophysiology, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy; Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Matteo Feurra
- Centre for Cognition and Decision Making, Institute for Cognitive Neuroscience, National Research University Higher School of Economics, Moscow, Russian Federation
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16
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Fathi Azar E, Hosseinzadeh S, Nosrat Abadi M, Sayad Nasiri M, Haghgoo HA. Impact of Psychosocial Occupational Therapy Combined with Anodal Transcranial Direct Current Stimulation to the Left Dorsolateral Prefrontal Cortex on the Cognitive Performance of Patients with Schizophrenia: A Randomized Controlled Trial. Hong Kong J Occup Ther 2022; 34:121-131. [PMID: 34987350 PMCID: PMC8721578 DOI: 10.1177/15691861211065155] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 11/21/2021] [Indexed: 11/15/2022] Open
Abstract
Background The most common cognitive dysfunctions in patients with schizophrenia are information processing, memory, and learning. Based on the hypothesis of rehabilitation and brain stimulation in memory and learning, adding a form of neuromodulation to conventional rehabilitation might increase the effectiveness of treatments. Aims To explore the effects of psychosocial occupational therapy combined with anodal Transcranial Direct Current Stimulation (tDCS) on cognitive performance in patients with Schizophrenia. Methods Twenty-four patients diagnosed with schizophrenia were randomized into the experimental and control groups. We used The Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Loewenstein Occupational Therapy Cognitive Assessment battery (LOTCA) to assess spatial recognition, attention, visual memory, learning abilities, and high-level cognitive functions like problem-solving. All participants received customized psychosocial occupational therapy activities. Furthermore, the experimental group received 12 sessions of active anodal tDCS for 20 minutes with 2 mA intensity on the left dorsolateral prefrontal cortex (DLPFC) while the patients in the sham group received sham tDCS. Results Combining tDCS to conventional psychosocial occupational therapy resulted in a significant increase in spatial memory, visual learning, and attention. Conclusions Anodal tDCS on the left DLPFC improved visual memory, attention, and learning abilities. Contrary to our expectations, we could not find any changes in complex and more demanding cognitive functions.
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Affiliation(s)
- Elahe Fathi Azar
- MSc in Occupational Therapy, The University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Samaneh Hosseinzadeh
- Biostatics Department, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Masoud Nosrat Abadi
- Clinical Psychology Department, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Mohamad Sayad Nasiri
- Assistant Professor of Neurology, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Hojjat Allah Haghgoo
- Occupational Therapy Department, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
- Hojjat Allah Haghgoo, Occupational Therapy Department, The University of Social Welfare and Rehabilitation Sciences, Kodakyar st.,Velenjak, Tehran, 1985713871, Iran.
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17
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Mendes AJ, Pacheco-Barrios K, Lema A, Gonçalves ÓF, Fregni F, Leite J, Carvalho S. Modulation of the cognitive event-related potential P3 by transcranial direct current stimulation: Systematic review and meta-analysis. Neurosci Biobehav Rev 2021; 132:894-907. [PMID: 34742723 DOI: 10.1016/j.neubiorev.2021.11.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 07/16/2021] [Accepted: 11/01/2021] [Indexed: 10/19/2022]
Abstract
Transcranial direct current stimulation (tDCS) has been widely used to modulate cognition and behavior. However, only a few studies have been probing the brain mechanism underlying the effects of tDCS on cognitive processing, especially throughout electrophysiological markers, such as the P3. This meta-analysis assessed the effects of tDCS in P3 amplitude and latency during an oddball, n-back, and Go/No-Go tasks, as well as during emotional processing. A total of 36 studies were identified, but only 23 were included in the quantitative analysis. The results show that the parietal P3 amplitude increased during oddball and n-back tasks, mostly after anodal stimulation over the left dorsolateral prefrontal cortex (p = 0.018, SMD = 0.4) and right inferior frontal gyrus (p < 0.001, SMD = 0.669) respectively. These findings suggest the potential usefulness of the parietal P3 ERP as a marker of tDCS-induced effects during task performance. Nonetheless, this study had a low number of studies and the presence of considerable risk of bias, highlighting issues to be addressed in the future.
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Affiliation(s)
- Augusto J Mendes
- Psychological Neuroscience Laboratory, CIPsi, School of Psychology, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal
| | - Kevin Pacheco-Barrios
- Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, USA; Universidad San Ignacio de Loyola, Vicerrectorado de Investigación, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru
| | - Alberto Lema
- Psychological Neuroscience Laboratory, CIPsi, School of Psychology, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal
| | - Óscar F Gonçalves
- Proaction Laboratory - CINEICC, Faculty of Psychology and Educational Sciences, University of Coimbra, Portugal
| | - Felipe Fregni
- Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, USA
| | - Jorge Leite
- INPP, Portucalense University, Porto, Portugal
| | - Sandra Carvalho
- Psychological Neuroscience Laboratory, CIPsi, School of Psychology, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal; Department of Education and Psychology, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
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18
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Investigating neurophysiological markers of impaired cognition in schizophrenia. Schizophr Res 2021; 233:34-43. [PMID: 34225025 DOI: 10.1016/j.schres.2021.06.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 04/21/2021] [Accepted: 06/21/2021] [Indexed: 01/22/2023]
Abstract
Cognitive impairment is highly prevalent in schizophrenia and treatment options are severely limited. A greater understanding of the pathophysiology of impaired cognition would have broad implications, including for the development of effective treatments. In the current study we used a multimodal approach to identify neurophysiological markers of cognitive impairment in schizophrenia. Fifty-seven participants (30 schizophrenia, 27 controls) underwent neurobiological assessment (electroencephalography [EEG] and Transcranial Magnetic Stimulation combined with EEG [TMS-EEG]) and assessment of cognitive functioning using an n-back task and the MATRICS Consensus Cognitive Battery. Neurobiological outcome measures included oscillatory power during a 2-back task, TMS-related oscillations and TMS-evoked potentials (TEPs). Cognitive outcome measures were d prime and accurate reaction time on the 2-back and MATRICS domain scores. Compared to healthy controls, participants with schizophrenia showed significantly reduced theta oscillations in response to TMS, and trend level decreases in task-related theta and cortical reactivity (i.e. reduced N100 and N40 TEPs). Participants with schizophrenia also showed significantly impaired cognitive performance across all measures. Correlational analysis identified significant associations between cortical reactivity and TMS-related oscillations in both groups; and trend level associations between task-related oscillations and impaired cognition in schizophrenia. The current study provides experimental support for possible neurophysiological markers of cognitive impairment in schizophrenia. The potential implications of these findings, including for treatment development, are discussed.
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19
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Lahogue C, Pinault D. Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies. Transl Neurosci 2021; 12:282-296. [PMID: 34239718 PMCID: PMC8240415 DOI: 10.1515/tnsci-2020-0157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 05/05/2021] [Accepted: 05/14/2021] [Indexed: 12/26/2022] Open
Abstract
During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies) during the wake-sleep cycle. Neural oscillations are electrobiomarkers of the connectivity state within systems. A single-systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological model may help the research and development of innovative treatments against psychotic transition. Transcranial electrical stimulation is recognized as an appropriate non-invasive therapeutic modality since it can increase cognitive performance and modulate neural oscillations with little or no side effects. Therefore, our objective was to set up, in the sedated adult rat, a stimulation method that is able to normalize ketamine-induced increase in gamma-frequency (30-80 Hz) oscillations and decrease in sigma-frequency (10-17 Hz) oscillations. Unilateral and bipolar frontoparietal (FP), transcranial anodal stimulation by direct current (<+1 mA) was applied in ketamine-treated rats. A concomitant bilateral electroencephalographic recording of the parietal cortex measured the stimulation effects on its spontaneously occurring oscillations. A 5 min FP anodal tDCS immediately and quickly reduced, significantly with an intensity-effect relationship, the ketamine-induced gamma hyperactivity, and sigma hypoactivity at least in the bilateral parietal cortex. A duration effect was also recorded. The tDCS also tended to diminish the ketamine-induced delta hypoactivity. These preliminary neurophysiological findings are promising for developing a therapeutic proof-of-concept against neuropsychiatric disorders.
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Affiliation(s)
- Caroline Lahogue
- Université de Strasbourg, Strasbourg, France
- INSERM U1114, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Strasbourg, France
- Fédération de Médecine Translationnelle de Strasbourg (FMTS), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Faculté de médecine, Strasbourg, France
| | - Didier Pinault
- Université de Strasbourg, Strasbourg, France
- INSERM U1114, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Strasbourg, France
- Fédération de Médecine Translationnelle de Strasbourg (FMTS), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Faculté de médecine, Strasbourg, France
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20
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Aryutova K, Paunova R, Kandilarova S, Todeva-Radneva A, Stoyanov D. Implications from translational cross-validation of clinical assessment tools for diagnosis and treatment in psychiatry. World J Psychiatry 2021; 11:169-180. [PMID: 34046313 PMCID: PMC8134869 DOI: 10.5498/wjp.v11.i5.169] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/17/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Traditional therapeutic methods in psychiatry, such as psychopharmacology and psychotherapy help many people suffering from mental disorders, but in the long-term prove to be effective in a relatively small proportion of those affected. Therapeutically, resistant forms of mental disorders such as schizophrenia, major depressive disorder, and bipolar disorder lead to persistent distress and dysfunction in personal, social, and professional aspects. In an effort to address these problems, the translational approach in neuroscience has initiated the inclusion of novel or modified unconventional diagnostic and therapeutic techniques with promising results. For instance, neuroimaging data sets from multiple modalities provide insight into the nature of pathophysiological mechanisms such as disruptions of connectivity, integration, and segregation of neural networks, focusing on the treatment of mental disorders through instrumental biomedical methods such as electro-convulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). These methodologies have yielded promising results that have yet to be understood and improved to enhance the prognosis of the severe and persistent psychotic and affective disorders. The current review is focused on the translational approach in the management of schizophrenia and mood disorders, as well as the adaptation of new transdisciplinary diagnostic tools such as neuroimaging with concurrently administered psychopathological questionnaires and integration of the results into the therapeutic framework using various advanced instrumental biomedical tools such as ECT, TMS, tDCS and DBS.
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Affiliation(s)
- Katrin Aryutova
- Department of Psychiatry and Medical Psychology, Scientific Research Institute, Medical University of Plovdiv, Plovdiv 4002, Bulgaria
| | - Rositsa Paunova
- Department of Psychiatry and Medical Psychology, Scientific Research Institute, Medical University of Plovdiv, Plovdiv 4002, Bulgaria
| | - Sevdalina Kandilarova
- Department of Psychiatry and Medical Psychology, Scientific Research Institute, Medical University of Plovdiv, Plovdiv 4002, Bulgaria
| | - Anna Todeva-Radneva
- Department of Psychiatry and Medical Psychology, Scientific Research Institute, Medical University of Plovdiv, Plovdiv 4002, Bulgaria
| | - Drozdstoy Stoyanov
- Department of Psychiatry and Medical Psychology, Scientific Research Institute, Medical University of Plovdiv, Plovdiv 4002, Bulgaria
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21
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Yang D, Shin YI, Hong KS. Systemic Review on Transcranial Electrical Stimulation Parameters and EEG/fNIRS Features for Brain Diseases. Front Neurosci 2021; 15:629323. [PMID: 33841079 PMCID: PMC8032955 DOI: 10.3389/fnins.2021.629323] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 02/25/2021] [Indexed: 01/09/2023] Open
Abstract
Background Brain disorders are gradually becoming the leading cause of death worldwide. However, the lack of knowledge of brain disease’s underlying mechanisms and ineffective neuropharmacological therapy have led to further exploration of optimal treatments and brain monitoring techniques. Objective This study aims to review the current state of brain disorders, which utilize transcranial electrical stimulation (tES) and daily usable noninvasive neuroimaging techniques. Furthermore, the second goal of this study is to highlight available gaps and provide a comprehensive guideline for further investigation. Method A systematic search was conducted of the PubMed and Web of Science databases from January 2000 to October 2020 using relevant keywords. Electroencephalography (EEG) and functional near-infrared spectroscopy were selected as noninvasive neuroimaging modalities. Nine brain disorders were investigated in this study, including Alzheimer’s disease, depression, autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, Parkinson’s disease, stroke, schizophrenia, and traumatic brain injury. Results Sixty-seven studies (1,385 participants) were included for quantitative analysis. Most of the articles (82.6%) employed transcranial direct current stimulation as an intervention method with modulation parameters of 1 mA intensity (47.2%) for 16–20 min (69.0%) duration of stimulation in a single session (36.8%). The frontal cortex (46.4%) and the cerebral cortex (47.8%) were used as a neuroimaging modality, with the power spectrum (45.7%) commonly extracted as a quantitative EEG feature. Conclusion An appropriate stimulation protocol applying tES as a therapy could be an effective treatment for cognitive and neurological brain disorders. However, the optimal tES criteria have not been defined; they vary across persons and disease types. Therefore, future work needs to investigate a closed-loop tES with monitoring by neuroimaging techniques to achieve personalized therapy for brain disorders.
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Affiliation(s)
- Dalin Yang
- School of Mechanical Engineering, Pusan National University, Busan, South Korea
| | - Yong-Il Shin
- Department of Rehabilitation Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan-si, South Korea
| | - Keum-Shik Hong
- Department of Rehabilitation Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan-si, South Korea
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22
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Boudewyn MA, Scangos K, Ranganath C, Carter CS. Using prefrontal transcranial direct current stimulation (tDCS) to enhance proactive cognitive control in schizophrenia. Neuropsychopharmacology 2020; 45:1877-1883. [PMID: 32604401 PMCID: PMC7608454 DOI: 10.1038/s41386-020-0750-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/16/2020] [Accepted: 06/19/2020] [Indexed: 11/09/2022]
Abstract
The goal of this study was to use transcranial direct current stimulation (tDCS) to examine the role of the prefrontal cortex (PFC) in neural oscillatory activity associated with proactive cognitive control in schizophrenia. To do so, we tested the impact of PFC-targeted tDCS on behavioral and electrophysiological markers of proactive cognitive control engagement in individuals with schizophrenia. Using a within-participants, double-blinded, sham-controlled crossover design, we recorded EEG while participants with schizophrenia completed a proactive cognitive control task (the Dot Pattern Expectancy (DPX) Task), after receiving 20 min of active prefrontal stimulation at 2 mA or sham stimulation. We hypothesized that active stimulation would enhance proactive cognitive control, leading to changes in behavioral performance on the DPX task and in activity in the gamma frequency band during key periods of the task designed to tax proactive cognitive control. The results showed significant changes in the pattern of error rates and increases in EEG gamma power as a function of tDCS condition (active or sham), that were indicative of enhanced proactive cognitive control. These findings, considered alongside our previous work in healthy adults, provides novel support for the role gamma oscillations in proactive cognitive control and they suggest that frontal tDCS may be a promising approach to enhance proactive cognitive control in schizophrenia.
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Affiliation(s)
- Megan A. Boudewyn
- grid.205975.c0000 0001 0740 6917University of California, Santa Cruz, CA USA
| | - Katherine Scangos
- grid.266102.10000 0001 2297 6811University of California, San Francisco, CA USA
| | - Charan Ranganath
- grid.27860.3b0000 0004 1936 9684University of California, Davis, CA USA
| | - Cameron S. Carter
- grid.27860.3b0000 0004 1936 9684University of California, Davis, CA USA
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23
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Dissanayaka T, Zoghi M, Hill AT, Farrell M, Egan G, Jaberzadeh S. The Effect of Transcranial Pulsed Current Stimulation at 4 and 75 Hz on Electroencephalography Theta and High Gamma Band Power: A Pilot Study. Brain Connect 2020; 10:520-531. [PMID: 32962422 DOI: 10.1089/brain.2020.0756] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Introduction: Transcranial pulsed current stimulation (tPCS) is an emerging noninvasive brain stimulation technique that has shown significant effects on cortical excitability. To date, electrophysiological measures of the efficiency of monophasic tPCS have not been reported. Objective: We aimed to explore the effects of monophasic anodal and cathodal-tPCS (a-tPCS/c-tPCS) at theta (4 Hz) and gamma (75 Hz) frequencies on theta and high gamma electroencephalography (EEG) oscillatory power. Methods: In a single-blind, randomized, sham-controlled crossover design, 15 healthy participants were randomly assigned into 5 experimental sessions in which they received a-PCS/c-tPCS at 4 and 75 Hz or sham stimulation over the left primary motor cortex (M1) for 15 min at an intensity of 1.5 mA. Changes in theta and high gamma oscillatory power were recorded at baseline, immediately after, and 30 min after stimulation using EEG at rest with eyes open. Results: a-tPCS at 4 Hz showed a significant increase in theta power compared with sham, whereas c-tPCS at 4 Hz had no significant effect on theta power. a-tPCS at 75 Hz produced no changes in high gamma power compared with sham. Importantly, c-tPCS at 75 Hz led to a significant reduction in high gamma power compared with baseline, as well as compared with c-tPCS at 4 Hz and sham stimulation. Conclusion: The results demonstrate the modulation of oscillatory brain activity by monophasic tPCS, and highlight the need for future studies on a larger scale to confirm these initial findings. Impact statement Transcranial pulsed current stimulation (tPCS) is a novel brain stimulation technique. Recently, tPCS has been introduced to directly modulate brain oscillations by applying pulsatile current over the target brain area. Using both anodal and cathodal monophasic tPCS at theta and gamma frequencies, we demonstrate the ability of the stimulation to modulate brain activity. The present findings are the first direct electroencephalography evidence of an interaction between tPCS and ongoing oscillatory activity in the human motor cortex. Our work recommends tPCS as a tool for investigating human brain oscillations and open more studies in this area.
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Affiliation(s)
- Thusharika Dissanayaka
- Non-invasive Brain Stimulation & Neuroplasticity Laboratory, Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Maryam Zoghi
- Department of Rehabilitation, Nutrition and Sport, School of Allied Health, La Trobe University, Melbourne, Australia
| | - Aron T Hill
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada
| | - Michael Farrell
- Monash Biomedical Imaging, Monash University, Melbourne, Australia.,Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, Australia
| | - Gary Egan
- Monash Biomedical Imaging, Monash University, Melbourne, Australia
| | - Shapour Jaberzadeh
- Non-invasive Brain Stimulation & Neuroplasticity Laboratory, Department of Physiotherapy, School of Primary and Allied Health Care, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
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24
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Non-Invasive Brain Stimulation Does Not Improve Working Memory in Schizophrenia: A Meta-Analysis of Randomised Controlled Trials. Neuropsychol Rev 2020; 31:115-138. [PMID: 32918254 DOI: 10.1007/s11065-020-09454-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 08/26/2020] [Indexed: 10/23/2022]
Abstract
Poor working memory functioning is commonly found in schizophrenia. A number of studies have now tested whether non-invasive brain stimulation can improve this aspect of cognitive functioning. This report used meta-analysis to synthesise the results of these studies to examine whether transcranial electrical stimulation (tES) or repetitive transcranial magnetic stimulation (rTMS) can improve working memory in schizophrenia. The studies included in this meta-analysis were sham-controlled, randomised controlled trials that utilised either tES or rTMS to treat working memory problems in schizophrenia. A total of 22 studies were included in the review. Nine studies administered rTMS and 13 administered tES. Meta-analysis revealed that compared to sham/placebo stimulation, neither TMS nor tES significantly improved working memory. This was found when working memory was measured with respect to the accuracy on working memory tasks (TMS studies: Hedges' g = 0.112, CI95: -0.082, 0.305, p = .257; tES studies Hedges' g = 0.080, CI95: -0.117, 0.277, p = .427) or the speed working memory tasks were completed (rTMS studies: Hedges' g = 0.233, CI95: -0.212, 0.678, p = .305; tES studies Hedges' g = -0.016, CI95: -0.204, 0.173, p = .871). For tES studies, meta-regression analysis found that studies with a larger number of stimulation sessions were associated with larger treatment effects. This association was not found for TMS studies. At present, rTMS and tES is not associated with a reliable improvement in working memory for individuals with schizophrenia.
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25
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Kayarian FB, Jannati A, Rotenberg A, Santarnecchi E. Targeting Gamma-Related Pathophysiology in Autism Spectrum Disorder Using Transcranial Electrical Stimulation: Opportunities and Challenges. Autism Res 2020; 13:1051-1071. [PMID: 32468731 PMCID: PMC7387209 DOI: 10.1002/aur.2312] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/15/2020] [Accepted: 04/22/2020] [Indexed: 12/12/2022]
Abstract
A range of scalp electroencephalogram (EEG) abnormalities correlates with the core symptoms of autism spectrum disorder (ASD). Among these are alterations of brain oscillations in the gamma-frequency EEG band in adults and children with ASD, whose origin has been linked to dysfunctions of inhibitory interneuron signaling. While therapeutic interventions aimed to modulate gamma oscillations are being tested for neuropsychiatric disorders such as schizophrenia, Alzheimer's disease, and frontotemporal dementia, the prospects for therapeutic gamma modulation in ASD have not been extensively studied. Accordingly, we discuss gamma-related alterations in the setting of ASD pathophysiology, as well as potential interventions that can enhance gamma oscillations in patients with ASD. Ultimately, we argue that transcranial electrical stimulation modalities capable of entraining gamma oscillations, and thereby potentially modulating inhibitory interneuron circuitry, are promising methods to study and mitigate gamma alterations in ASD. Autism Res 2020, 13: 1051-1071. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Brain functions are mediated by various oscillatory waves of neuronal activity, ranging in amplitude and frequency. In certain neuropsychiatric disorders, such as schizophrenia and Alzheimer's disease, reduced high-frequency oscillations in the "gamma" band have been observed, and therapeutic interventions to enhance such activity are being explored. Here, we review and comment on evidence of reduced gamma activity in ASD, arguing that modalities used in other disorders may benefit individuals with ASD as well.
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Affiliation(s)
- Fae B. Kayarian
- Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ali Jannati
- Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Neuromodulation Program and Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Alexander Rotenberg
- Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Neuromodulation Program and Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
- F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Emiliano Santarnecchi
- Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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26
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Papazova I, Strube W, Wienert A, Henning B, Schwippel T, Fallgatter AJ, Padberg F, Falkai P, Plewnia C, Hasan A. Effects of 1 mA and 2 mA transcranial direct current stimulation on working memory performance in healthy participants. Conscious Cogn 2020; 83:102959. [PMID: 32502908 DOI: 10.1016/j.concog.2020.102959] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 05/18/2020] [Accepted: 05/22/2020] [Indexed: 12/25/2022]
Abstract
Anodal transcranial current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) has been shown to enhance working memory (WM) in neuropsychiatric patients. In healthy populations, however, tDCS obtains inconclusive results, mostly due to heterogeneous study and stimulation protocols. Here, we approached these issues by investigating effects of tDCS intensity on simultaneous WM performance with three cognitive loads by directly comparing findings of two double-blind, cross-over, sham-controlled experiments. TDCS was administrated to the left DLPFC at intensity of 1 mA (Experiment 1) or 2 mA (Experiment 2), while participants completed a verbal n-back paradigm (1-, 2-, 3-back). Analysis showed no overall effects of tDCS on WM, but a significant interaction with cognitive load. The present study suggests that cognitive load rather than tDCS intensity could be a decisive factor for effects on WM. Moreover, it emphasizes the need of thorough investigation on study parameters to develop more efficient stimulation protocols.
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Affiliation(s)
- Irina Papazova
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany.
| | - Wolfgang Strube
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany
| | - Aida Wienert
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany
| | - Bettina Henning
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany
| | - Tobias Schwippel
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Germany
| | - Andreas J Fallgatter
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Germany
| | - Frank Padberg
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany
| | - Peter Falkai
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany
| | - Christian Plewnia
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Germany
| | - Alkomiet Hasan
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilians University, München, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, BKH Augsburg, Medical Faculty, University of Augsburg, Germany
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27
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Kostova R, Cecere R, Thut G, Uhlhaas PJ. Targeting cognition in schizophrenia through transcranial direct current stimulation: A systematic review and perspective. Schizophr Res 2020; 220:300-310. [PMID: 32204971 DOI: 10.1016/j.schres.2020.03.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 02/28/2020] [Accepted: 03/02/2020] [Indexed: 01/03/2023]
Abstract
Cognitive deficits are a fundamental feature of schizophrenia for which currently no effective treatments exist. This paper examines the possibility to use transcranial direct current stimulation (tDCS) to target cognitive deficits in schizophrenia as evidence from studies in healthy participants suggests that tDCS may improve cognitive functions and associated neural processes. We carried out a systematic review with the following search terms: 'tDCS', 'electric brain stimulation', 'schizophrenia', 'cognitive', 'cognition' until March 2019. 659 records were identified initially, 612 of which were excluded after abstract screening. The remaining 47 articles were assessed for eligibility based on our criteria and 26 studies were excluded. In addition, we compared several variables, such as online vs. offline-stimulation protocols, stimulation type and intensity on mediating positive vs. negative study outcomes. The majority of studies (n = 21) identified significant behavioural and neural effects on a range of cognitive functions (versus n = 11 with null results), including working memory, attention and social cognition. However, we could not identify tDCS parameters (electrode montage, stimulation protocol, type and intensity) that clearly mediated effects on cognitive deficits. There is preliminary evidence for the possibility that tDCS may improve cognitive deficits in schizophrenia. We discuss the rationale and strength of evidence for using tDCS for targeting cognitive deficits in schizophrenia as well as methodological issues and potential mechanisms of action.
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Affiliation(s)
- R Kostova
- Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK
| | - R Cecere
- Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK
| | - G Thut
- Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK
| | - Peter J Uhlhaas
- Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK; Department of Child and Adolescent Psychiatry, Charite Universitätsmedizin Berlin, Berlin, Germany.
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28
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Transcranial direct current stimulation: a roadmap for research, from mechanism of action to clinical implementation. Mol Psychiatry 2020; 25:397-407. [PMID: 31455860 PMCID: PMC6981019 DOI: 10.1038/s41380-019-0499-9] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 06/27/2019] [Accepted: 07/09/2019] [Indexed: 01/24/2023]
Abstract
Transcranial direct current stimulation (tDCS) is a promising method for altering the function of neural systems, cognition, and behavior. Evidence is emerging that it can also influence psychiatric symptomatology, including major depression and schizophrenia. However, there are many open questions regarding how the method might have such an effect, and uncertainties surrounding its influence on neural activity, and human cognition and functioning. In the present critical review, we identify key priorities for future research into major depression and schizophrenia, including studies of the mechanism(s) of action of tDCS at the neuronal and systems levels, the establishment of the cognitive impact of tDCS, as well as investigations of the potential clinical efficacy of tDCS. We highlight areas of progress in each of these domains, including data that appear to favor an effect of tDCS on neural oscillations rather than spiking, and findings that tDCS administration to the prefrontal cortex during task training may be an effective way to enhance behavioral performance. Finally, we provide suggestions for further empirical study that will elucidate the impact of tDCS on brain and behavior, and may pave the way for efficacious clinical treatments for psychiatric disorders.
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29
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Smith RC, Md WL, Wang Y, Jiang J, Wang J, Szabo V, Faull R, Jin H, Davis JM, Li C. Effects of transcranial direct current stimulation on cognition and symptoms in Chinese patients with schizophrenia ✰. Psychiatry Res 2020; 284:112617. [PMID: 31806403 DOI: 10.1016/j.psychres.2019.112617] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 10/13/2019] [Accepted: 10/13/2019] [Indexed: 01/10/2023]
Abstract
There is preliminary evidence that transcranial direct current stimulation(tDCS) may improve symptoms and cognitive function in schizophrenia, but the generalizability of these results needs further investigation. We present a study of the effects of active vs. sham tDCS on cognition and symptoms in a sample of 45 Chinese patients with schizophrenia who showed significant cognitive deficits and were treated for 10 sessions with active or sham tDCS. Psychiatric symptoms were assessed by PANSS scores, and cognitive symptoms assessed by MATRICS battery and other tests. There were no differences between cognitive or symptom scores between subjects treated with active vs. sham tDCS tested within 1-2 days after the end of the 10th session. However, two weeks later subjects treated with active tDCS showed significantly more improvements on MATRICS Speed of Processing domain. MATRICS Overall Composite and a CogState measure related to accuracy on a 1-back working memory task were improved at two weeks in statistical tests without multiple corrections. The improvement in cognitive test scores 2 weeks after the last tDCS session, suggests longer term effects may be related to changes in neuroplasticity induced by 10 sessions of tDCS. The lack of significant changes in cognition shortly after the completion of 10 tDCS sessions contrasts with our earlier positive findings in U.S. patients with schizophrenia.
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Affiliation(s)
- Robert C Smith
- Nathan Kline Institute for Psychiatric Research; Department of Psychiatry, NYU Medical School; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine.
| | - Wei Li Md
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
| | - Yiran Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
| | - Jiangling Jiang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
| | - JiJun Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
| | | | - Robert Faull
- Psychiatric institute, Department of Psychiatry, Univ. of Illinois College of Medicine, and John Hopkins School of Medicine
| | - Hua Jin
- University of California San Diego, Department of Psychiatry, San Diego, California, and VA San Diego Healthcare System, San Diego, CA, United States of America
| | - John M Davis
- Psychiatric institute, Department of Psychiatry, Univ. of Illinois College of Medicine, and John Hopkins School of Medicine
| | - Chunbo Li
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
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30
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Weickert TW, Salimuddin H, Lenroot RK, Bruggemann J, Loo C, Vercammen A, Kindler J, Weickert CS. Preliminary findings of four-week, task-based anodal prefrontal cortex transcranial direct current stimulation transferring to other cognitive improvements in schizophrenia. Psychiatry Res 2019; 280:112487. [PMID: 31376788 DOI: 10.1016/j.psychres.2019.112487] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 07/16/2019] [Accepted: 07/17/2019] [Indexed: 02/07/2023]
Abstract
Most transcranial Direct Current Stimulation (tDCS) trials of schizophrenia administer few sessions and do not assess transfer effects to other cognitive domains. In a randomized, double-blind, sham-controlled, parallel groups trial, we determined the extent to which 4-weeks of 2 mA tDCS at 20 min/day totalling 20 tDCS sessions administered during a spatial working memory test, with anodal right dorsolateral prefrontal cortex (DLPFC) and cathodal left tempo-parietal junction (TPJ) placement, as an adjunct to antipsychotics reduced auditory hallucinations and improved cognition in 12 outpatients with schizophrenia. Anodal tDCS significantly improved language-based working memory after 2 weeks and verbal fluency after 2 and 4 weeks. Thus, four weeks of tDCS appears to be safe and elicits transfer benefits to other prefrontal-dependent cognitive abilities in schizophrenia.
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Affiliation(s)
- T W Weickert
- School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia.
| | - H Salimuddin
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - R K Lenroot
- School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia; Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, USA
| | - J Bruggemann
- School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia
| | - C Loo
- School of Psychiatry, University of New South Wales, Sydney, Australia; Black Dog Institute, Sydney, Australia
| | - A Vercammen
- School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia; Faculty of Natural Sciences, Imperial College London, London, UK
| | - J Kindler
- School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
| | - C S Weickert
- School of Psychiatry, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia
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31
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Widge AS, Miller EK. Targeting Cognition and Networks Through Neural Oscillations: Next-Generation Clinical Brain Stimulation. JAMA Psychiatry 2019; 76:671-672. [PMID: 31116372 PMCID: PMC7067567 DOI: 10.1001/jamapsychiatry.2019.0740] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Alik S. Widge
- Department of Psychiatry, University of Minnesota, Minneapolis
| | - Earl K. Miller
- The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge
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32
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Ikeda T, Takahashi T, Hiraishi H, Saito DN, Kikuchi M. Anodal Transcranial Direct Current Stimulation Induces High Gamma-Band Activity in the Left Dorsolateral Prefrontal Cortex During a Working Memory Task: A Double-Blind, Randomized, Crossover Study. Front Hum Neurosci 2019; 13:136. [PMID: 31105540 PMCID: PMC6491895 DOI: 10.3389/fnhum.2019.00136] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 04/08/2019] [Indexed: 01/17/2023] Open
Abstract
Transcranial direct current stimulation (tDCS) has been shown to have mixed effects on working memory (WM) capacity in healthy individuals. Different stimulation paradigms may account for these discrepancies, with certain features being favored. To determine the effect in the context of anodal tDCS, we investigated whether anodal tDCS induced cortical oscillatory changes during a WM task. Specifically, we tested whether anodal offline tDCS over the left prefrontal cortex (PFC) enhances WM capacity by modulating the oscillatory activity in the left dorsolateral PFC (DLPFC) using magnetoencephalography (MEG). This study employed a double-blind, randomized, crossover design, in which 24 healthy right-handed participants conducted MEG recordings during a 3-back task after administration of 2 mA tDCS or sham stimulation as a placebo. Our results showed that the effect of tDCS did not appear in the behavioral indices—WM accuracy (d′) or reaction time (RT). From the results of the time-frequency analysis, significant event-related synchronization (ERS) in the high-gamma band (82–84 Hz) of the left DLPFC was found under the tDCS condition; however, ERS was not correlated with WM capacity. Furthermore, we calculated the modulation index (MI), which indicates the strength of phase-amplitude coupling (PAC). tDCS significantly decreased MI of the left DLPFC, representing the theta-gamma PAC during the n-back task using color names as verbal stimuli. Our results suggest that although tDCS increased the gamma-band oscillation indicating greater neural activity in the left DLPFC, it did not lead to an improvement of WM capacity; this may be due to the inability of gamma-band oscillation to couple with the task-induced theta wave. WM capacity might not increase unless theta-gamma PAC is not enhanced by tDCS.
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Affiliation(s)
- Takashi Ikeda
- Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan
| | - Tetsuya Takahashi
- Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.,Department of Neuropsychiatry, University of Fukui, Fukui, Japan
| | - Hirotoshi Hiraishi
- Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Daisuke N Saito
- Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan
| | - Mitsuru Kikuchi
- Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.,Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
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33
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Pellegrino G, Arcara G, Di Pino G, Turco C, Maran M, Weis L, Piccione F, Siebner HR. Transcranial direct current stimulation over the sensory-motor regions inhibits gamma synchrony. Hum Brain Mapp 2019; 40:2736-2746. [PMID: 30854728 DOI: 10.1002/hbm.24556] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 01/27/2019] [Accepted: 02/20/2019] [Indexed: 12/16/2022] Open
Abstract
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce plasticity phenomena. Although tDCS application has been spreading over a variety of neuroscience domains, the mechanisms by which the stimulation acts are largely unknown. We investigated tDCS effects on cortical gamma synchrony, which is a crucial player in cortical function. We performed a randomized, sham-controlled, double-blind study on healthy subjects, combining tDCS and magnetoencephalography. By driving brain activity via 40 Hz auditory stimulation during magnetoencephalography, we experimentally tuned cortical gamma synchrony and measured it before and after bilateral tDCS of the primary sensory-motor hand regions (anode left, cathode right). We demonstrated that the stimulation induces a remarkable decrease of gamma synchrony (13 out of 15 subjects), as measured by gamma phase at 40 Hz. tDCS has strong remote effects, as the cortical region mostly affected was located far away from the stimulation site and covered a large area of the right centro-temporal cortex. No significant differences between stimulations were found for baseline gamma synchrony, as well as early transient auditory responses. This suggests a specific tDCS effect on externally driven gamma synchronization. This study sheds new light on the effect of tDCS on cortical function showing that the net effect of the stimulation on cortical gamma synchronization is an inhibition.
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Affiliation(s)
- Giovanni Pellegrino
- Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, Venice, Italy
| | - Giorgio Arcara
- Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, Venice, Italy
| | - Giovanni Di Pino
- Department of Neurology, NeXT: Neurophysiology and Neuroengineering of Human-Technology Interaction Research Unit, Campus Bio-Medico University, Rome, Italy
| | - Cristina Turco
- Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, Venice, Italy
| | - Matteo Maran
- Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, Venice, Italy
| | - Luca Weis
- Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, Venice, Italy
| | - Francesco Piccione
- Brain Imaging and Neural Dynamics Research Group, IRCCS San Camillo Hospital, Venice, Italy
| | - Hartwig Roman Siebner
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.,Department of Neurology, Copenhagen University Hospital, Bispebjerg, Denmark
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34
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Schwippel T, Papazova I, Strube W, Fallgatter AJ, Hasan A, Plewnia C. Beneficial effects of anodal transcranial direct current stimulation (tDCS) on spatial working memory in patients with schizophrenia. Eur Neuropsychopharmacol 2018; 28:1339-1350. [PMID: 30292415 DOI: 10.1016/j.euroneuro.2018.09.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 03/23/2018] [Accepted: 09/21/2018] [Indexed: 12/19/2022]
Abstract
Schizophrenia is a severe and often detrimental psychiatric disorder. The individual patients' level of functioning is essentially determined by cognitive, particularly working memory (WM), deficits that are critically linked to dysfunctional activity of the dorsolateral prefrontal cortex (dlPFC). Transcranial direct current stimulation (tDCS) can transiently modulate activity of the dlPFC and remote areas and has been shown to improve WM functions. It may therefore provide a new, targeted treatment option. For this aim, the present study investigated the effect of anodal tDCS of different intensities on spatial WM in patients with schizophrenia. In two experiments, 32 patients performed a spatial n-back task with increasing WM load (1-, 2-, and 3-back) at baseline and in two sessions with anodal or sham tDCS (EXP I [n = 16]: 1 mA; EXP II [n = 16]: 2 mA) to the right dlPFC (cathode: left m. deltoideus). With 1 mA anodal tDCS, no effect on WM performance could be detected. However, 2 mA anodal tDCS increased accuracy (measured by d') of the task with the highest WM load (3-back). This effect was larger in patients with a lower level of general neurocognitive functioning. These results demonstrate a beneficial effect of 2 mA anodal tDCS on deficient WM accuracy in patients with schizophrenia particularly under challenging conditions and in subjects with higher cognitive impairments. This data will inform future clinical trials on tDCS-enhanced cognitive training to improve treatment of schizophrenia.
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Affiliation(s)
- T Schwippel
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany
| | - I Papazova
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians University Munich, Nußbaumstraße 7, 80336 Munich, Germany
| | - W Strube
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians University Munich, Nußbaumstraße 7, 80336 Munich, Germany
| | - A J Fallgatter
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany
| | - A Hasan
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians University Munich, Nußbaumstraße 7, 80336 Munich, Germany
| | - C Plewnia
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Calwerstrasse 14, 72076 Tübingen, Germany.
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35
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Papazova I, Strube W, Becker B, Henning B, Schwippel T, Fallgatter AJ, Padberg F, Palm U, Falkai P, Plewnia C, Hasan A. Improving working memory in schizophrenia: Effects of 1 mA and 2 mA transcranial direct current stimulation to the left DLPFC. Schizophr Res 2018; 202:203-209. [PMID: 29954701 DOI: 10.1016/j.schres.2018.06.032] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Revised: 04/03/2018] [Accepted: 06/11/2018] [Indexed: 10/28/2022]
Abstract
Deficits in various cognitive processes, such as working memory, are characteristic for schizophrenia, lowering patients' functioning and quality of life. Recent research suggests that transcranial direct stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) may be a potential therapeutic intervention for cognitive deficits in schizophrenia. Here, we examined the effects of online tDCS to the DLPFC on working memory (WM) performance in 40 schizophrenia patients in two separate experiments with a double blind, sham-controlled, cross-over design. Patients underwent single sessions of active and sham tDCS in a randomized order. Stimulation parameters were anode F3, cathode right deltoid muscle, 21 min tDCS duration, 1 mA tDCS in Experiment 1 (N = 20) and 2 mA tDCS in Experiment 2 (N = 20). Primary outcome was the change in WM performance as measured by a verbal n-back paradigm (1- to 3-back). Irrespective of the stimulation intensity, data analysis showed a significant higher WM accuracy during active tDCS than during sham tDCS (p = 0.019), but no main effect of stimulation intensity (p = 0.392). Subsequent separate analyses revealed a significantly improved WM performance only during 1 mA (p = 0.048). TDCS facilitated WM functioning in schizophrenia, with an advantage of 1 mA over 2 mA. Our results support the notion that tDCS may be a potential treatment for cognitive deficits in schizophrenia and emphasize the need for future research on the specific stimulation parameters.
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Affiliation(s)
- Irina Papazova
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany.
| | - Wolfgang Strube
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
| | - Benedikt Becker
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
| | - Bettina Henning
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
| | - Tobias Schwippel
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen
| | - Andreas J Fallgatter
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen
| | - Frank Padberg
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
| | - Ulrich Palm
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
| | - Peter Falkai
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
| | - Christian Plewnia
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen
| | - Alkomiet Hasan
- Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
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36
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Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI. Brain Stimul 2018; 11:998-1007. [DOI: 10.1016/j.brs.2018.05.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 03/25/2018] [Accepted: 05/01/2018] [Indexed: 11/19/2022] Open
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Effects of single versus dual-site High-Definition transcranial direct current stimulation (HD-tDCS) on cortical reactivity and working memory performance in healthy subjects. Brain Stimul 2018; 11:1033-1043. [DOI: 10.1016/j.brs.2018.06.005] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 05/12/2018] [Accepted: 06/12/2018] [Indexed: 11/20/2022] Open
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Abstract
Direct current stimulation is a neuromodulatory noninvasive brain stimulation tool, which was first introduced in animal and human experiments in the 1950s, and added to the standard arsenal of methods to alter brain physiology as well as psychological, motor, and behavioral processes and clinical symptoms in neurological and psychiatric diseases about 20 years ago. In contrast to other noninvasive brain stimulation tools, such as transcranial magnetic stimulation, it does not directly induce cerebral activity, but rather alters spontaneous brain activity and excitability by subthreshold modulation of neuronal membranes. Beyond acute effects on brain functions, specific protocols are suited to induce long-lasting alterations of cortical excitability and activity, which share features with long-term potentiation and depression. These neuroplastic processes are important foundations for various cognitive functions such as learning and memory formation and are pathologically altered in numerous neurological and psychiatric diseases. This explains the increasing interest to investigate transcranial direct current stimulation (tDCS) as a therapeutic tool. However, for tDCS to be used effectively, it is crucial to be informed about physiological mechanisms of action. These have been increasingly elucidated during the last years. This review gives an overview of the current knowledge available regarding physiological mechanisms of tDCS, spanning from acute regional effects, over neuroplastic effects to its impact on cerebral networks. Although knowledge about the physiological effects of tDCS is still not complete, this might help to guide applications on a scientifically sound foundation.
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Affiliation(s)
| | - Andrea Antal
- Department of Clinical Neurophysiology, University Medical Center Göttingen, University of Göttingen, Göttingen
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Kim M, Kwak YB, Lee TY, Kwon JS. Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review. Psychiatry Investig 2018; 15:434-444. [PMID: 29695150 PMCID: PMC5976006 DOI: 10.30773/pi.2018.01.10] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 11/15/2017] [Accepted: 01/10/2018] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique increasingly used to relieve symptoms of psychiatric disorders. Electrophysiologic markers, such as electroencephalography (EEG) and event-related potentials (ERP), have high temporal resolution sensitive to detect plastic changes of the brain associated with symptomatic improvement following tDCS application. METHODS We performed systematic review to identify electrophysiological markers that reflect tDCS effects on plastic brain changes in psychiatric disorders. A total of 638 studies were identified by searching PubMed, Embase, psychINFPO. Of these, 21 full-text articles were assessed eligible and included in the review. RESULTS Although the reviewed studies were heterogeneous in their choices of tDCS protocols, targeted electrophysiological markers, and disease entities, their results strongly support EEG/ERPs to sensitively reflect plastic brain changes and the associated symptomatic improvement following tDCS. CONCLUSION EEG/ERPs may serve a potent tool in revealing the mechanisms underlying psychiatric symptoms, as well as in localizing the brain area targeted for stimulation. Future studies in each disease entities employing consistent tDCS protocols and electrophysiological markers would be necessary in order to substantiate and further elaborate the findings of studies included in the present systematic review.
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Affiliation(s)
- Minah Kim
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoo Bin Kwak
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, Republic of Korea
| | - Tae Young Lee
- Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jun Soo Kwon
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, Republic of Korea
- Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea
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40
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Bilateral Transcranial Direct Current Stimulation Reshapes Resting-State Brain Networks: A Magnetoencephalography Assessment. Neural Plast 2018; 2018:2782804. [PMID: 29593782 PMCID: PMC5821992 DOI: 10.1155/2018/2782804] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 09/11/2017] [Accepted: 10/02/2017] [Indexed: 12/30/2022] Open
Abstract
Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders.
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41
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Abstract
Schizophrenia is a complex disorder lacking an effective treatment option for the pervasive and debilitating cognitive impairments experienced by patients. Working memory is a core cognitive function impaired in schizophrenia that depends upon activation of distributed neural network, including the circuitry of the dorsolateral prefrontal cortex (DLPFC). Accordingly, individuals diagnosed with schizophrenia show reduced DLPFC activation while performing working-memory tasks. This lower DLPFC activation appears to be an integral part of the disease pathophysiology, and not simply a reflection of poor performance. Thus, the cellular and circuitry alterations that underlie lower DLPFC neuronal activity in schizophrenia must be determined in order to identify appropriate therapeutic targets. Studies using human postmortem brain tissue provide a robust way to investigate and characterize these cellular and circuitry alterations at multiple levels of resolution, and such studies provide essential information that cannot be obtained either through in vivo studies in humans or through experimental animal models. Studies examining neuronal morphology, protein expression and localization, and transcript levels indicate that a microcircuit composed of excitatory pyramidal cells and inhibitory interneurons containing the calcium-binding protein parvalbumin is altered in the DLPFC of subjects with schizophrenia and likely contributes to DLPFC dysfunction.
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Affiliation(s)
- Jill R Glausier
- Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
| | - David A Lewis
- Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States.
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42
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Habich A, Klöppel S, Abdulkadir A, Scheller E, Nissen C, Peter J. Anodal tDCS Enhances Verbal Episodic Memory in Initially Low Performers. Front Hum Neurosci 2017; 11:542. [PMID: 29163115 PMCID: PMC5681927 DOI: 10.3389/fnhum.2017.00542] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 10/24/2017] [Indexed: 12/20/2022] Open
Abstract
The left dorsolateral prefrontal cortex (DLPFC) is involved in encoding and retrieval of episodic memories, and thus, is frequently targeted in non-invasive brain stimulation paradigms, aiming for its functional modulation. Anodal transcranial direct current stimulation (tDCS), that boosts neuronal excitability in stimulated cortical areas, has been found to increase cognitive skills differentially, depending on the initial performance. We hypothesize that the benefit of tDCS on verbal episodic memory can be extrapolated from the participants’ baseline performance. In the present randomized, double-blind, parallel group study, healthy young adults (n = 43) received either real anodal or sham tDCS over their left DLPFC during the encoding phase of a verbal episodic memory task. Forty words were presented visually thrice with immediate vocal retrieval after each block and an additional delayed recall. We conducted a moderation analysis to test the modulating effect of initial episodic memory retrieval, adjusted for primacy and recency effects, on delayed recall under real or sham stimulation. Despite the absence of a significantly beneficial tDCS effect at the group level, we found that the number of remembered midlist words in the first retrieval significantly moderated the stimulation effect in such a way that initially low performers experienced the highest gain from real stimulation. These results suggest that anodal tDCS to the left DLPFC improves memory functions only so far. While only marginal stimulation-induced gains occur in cognitively unimpaired populations, greater stimulation benefits might be expected in individuals with clinically relevant deficiencies in the verbal episodic memory domain.
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Affiliation(s)
- Annegret Habich
- University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.,Faculty of Biology, University of Freiburg, Freiburg, Germany
| | - Stefan Klöppel
- University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.,Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Ahmed Abdulkadir
- University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.,Department of Computer Science, University of Freiburg, Freiburg, Germany
| | - Elisa Scheller
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Christoph Nissen
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.,Department of Neurology, Inselspital, University of Bern, Bern, Switzerland
| | - Jessica Peter
- University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.,Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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43
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Dinakaran D, Parlikar R, Sreeraj VS, Neikar A, Nagendrappa S, Shivakumar V, Venkatasubramanian G. Right-sided Transcranial Direct Current Stimulation and Attentional Salience of Auditory Hallucinations in Schizophrenia. Indian J Psychol Med 2017; 39:821-822. [PMID: 29284822 PMCID: PMC5733439 DOI: 10.4103/ijpsym.ijpsym_44_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Transcranial direct current stimulation (tDCS) is a safe, noninvasive technique demonstrated to reduce persistent auditory hallucinations in patients with schizophrenia. Here, we report the differential effect of tDCS on auditory hallucinations against other positive symptoms and also the use of right-sided tDCS in patients with increased attentional salience toward auditory hallucinations.
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Affiliation(s)
- Damodharan Dinakaran
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Rujuta Parlikar
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Vanteemar S Sreeraj
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Anuradha Neikar
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Sachin Nagendrappa
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Venkataram Shivakumar
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Ganesan Venkatasubramanian
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
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44
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Orlov ND, Tracy DK, Joyce D, Patel S, Rodzinka-Pasko J, Dolan H, Hodsoll J, Collier T, Rothwell J, Shergill SS. Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning. Brain Stimul 2017; 10:560-566. [DOI: 10.1016/j.brs.2016.12.013] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 10/07/2016] [Accepted: 12/23/2016] [Indexed: 12/20/2022] Open
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Mervis JE, Capizzi RJ, Boroda E, MacDonald AW. Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex in Schizophrenia: A Quantitative Review of Cognitive Outcomes. Front Hum Neurosci 2017; 11:44. [PMID: 28210217 PMCID: PMC5288642 DOI: 10.3389/fnhum.2017.00044] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 01/20/2017] [Indexed: 11/13/2022] Open
Abstract
Cognitive deficits are a core and disabling feature of psychotic disorders, specifically schizophrenia. Current treatments for impaired cognition in schizophrenia remain insufficient. Recent research suggests transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex can potentiate cognitive improvements in healthy individuals and those with psychiatric conditions, such as schizophrenia. However, this burgeoning literature has not been quantitatively evaluated. Through a literature search and quantitative review, we identified 194 papers on tDCS, psychosis, and cognition. Selection criteria included pre/post design and sham control to achieve specific sham-adjusted effect sizes. The 6 retained studies all address schizophrenia populations and include single and repeated stimulation, as well as within and between subject designs. Small positive effects were found for anodal stimulation on behavioral measures of attention and working memory, with tentative findings for cognitive ability and memory. Cathodal stimulation yielded a small positive effect on behaviorally measured cognitive ability. Neurophysiological measures of attention showed a small to medium down-modulation effect for anodal stimulation. Implications of these findings and guidelines for future research are discussed. As revealed by this report, due to the paucity of data available, much remains unknown regarding the clinical efficacy of tDCS in schizophrenia.
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Affiliation(s)
- Joshua E Mervis
- Department of Psychology, University of Minnesota Minneapolis, MN, USA
| | - Riley J Capizzi
- Department of Psychology, University of Minnesota Minneapolis, MN, USA
| | - Elias Boroda
- Department of Neuroscience, University of Minnesota Minneapolis, MN, USA
| | - Angus W MacDonald
- Department of Psychology, University of MinnesotaMinneapolis, MN, USA; Department of Psychiatry, University of Minnesota Medical SchoolMinneapolis, MN, USA
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46
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Narita Z, Inagawa T, Maruo K, Sueyoshi K, Sumiyoshi T. Effect of Transcranial Direct Current Stimulation on Functional Capacity in Schizophrenia: A Study Protocol for a Randomized Controlled Trial. Front Psychiatry 2017; 8:233. [PMID: 29180969 PMCID: PMC5694143 DOI: 10.3389/fpsyt.2017.00233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Accepted: 10/31/2017] [Indexed: 12/13/2022] Open
Abstract
UNLABELLED Schizophrenia patients elicit a wide range of psychopathology, including psychotic symptoms, mood symptoms, and cognitive impairment. Functional capacity is defined as the ability to perform everyday living skills, which is linked to cognition and real-world functional outcome. In a previous open trial, we demonstrated that transcranial direct current stimulation (tDCS), one of the neuromodulation methods, improved cognition and functional capacity in 28 patients with schizophrenia. However, since it was a pilot study, a controlled trial is needed. Therefore, we present a study protocol for a randomized controlled trial designed to evaluate the effect of tDCS on functional capacity in patients with schizophrenia. This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Patients meeting DSM-5 criteria for schizophrenia will be enrolled and randomized to receive either active or sham stimulation (with 10 sessions in five consecutive days). Functional capacity will be evaluated by the UCSD Performance-based Skills Assessment-Brief as primary outcome. Cognition, as measured by the Brief Assessment of Cognition in Schizophrenia, and psychotic symptoms, as measured by the Positive and Negative Syndrome Scale, will also be evaluated. Data will be collected at baseline, immediately after the last stimulation, and 1 and 2 months thereafter. If active stimulation elicits greater effects compared with those of sham stimulation, it may add to the efforts to improve functional outcomes by neuromodulation in patients with schizophrenia. TRIAL REGISTRATION UMIN000028224; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000032305.
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Affiliation(s)
- Zui Narita
- Department of Psychiatry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Takuma Inagawa
- Department of Psychiatry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Kazushi Maruo
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Kazuki Sueyoshi
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Tomiki Sumiyoshi
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
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47
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Narita Z, Inagawa T, Sueyoshi K, Lin C, Sumiyoshi T. Possible Facilitative Effects of Repeated Anodal Transcranial Direct Current Stimulation on Functional Outcome 1 Month Later in Schizophrenia: An Open Trial. Front Psychiatry 2017; 8:184. [PMID: 29033856 PMCID: PMC5626815 DOI: 10.3389/fpsyt.2017.00184] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 09/11/2017] [Indexed: 11/13/2022] Open
Abstract
UNLABELLED Recent research on neuromodulation techniques, such as transcranial direct current stimulation (tDCS), for the treatment of schizophrenia has mainly focused on psychotic symptoms. We aimed to determine whether repetitive tDCS is efficacious in improving determinants of outcome, such as cognitive function, daily living skills, and depressive mood in patients with schizophrenia. Twenty-eight patients underwent tDCS (2 mA × 20 min) two times per day for 5 consecutive days. The anodal electrode was placed over the left dorsolateral prefrontal cortex while the cathodal electrode was placed over the right supraorbital region. One month after the last stimulation, there was a significant improvement on cognitive function, measured by the brief assessment of cognition in schizophrenia (d = 0.49). Significant effects were also shown on daily living skills (functional capacity), measured by the UCSD performance-based skills assessment-brief (d = 0.70). Depressive symptoms, measured by the Calgary depression rating scale, as well as psychotic symptoms measured by on the positive and negative syndrome scale positive and general psychopathology subscales also responded to the treatment (d = 0.38, d = 0.48, and d = 0.50, respectively). This is the first study to suggest that tDCS with the anodal electrode on the left prefrontal cortex improves functional capacity and depressive symptoms in patients with schizophrenia. These results may add to the concept that tDCS provides a strategy to enhance functional outcomes in patients with schizophrenia. TRIAL REGISTRATION https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000018556, UMIN000015953.
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Affiliation(s)
- Zui Narita
- Department of Psychiatry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Takuma Inagawa
- Department of Psychiatry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Kazuki Sueyoshi
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Crystal Lin
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Tomiki Sumiyoshi
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
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48
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Thomas ML, Green MF, Hellemann G, Sugar CA, Tarasenko M, Calkins ME, Greenwood TA, Gur RE, Gur RC, Lazzeroni LC, Nuechterlein KH, Radant AD, Seidman LJ, Shiluk AL, Siever LJ, Silverman JM, Sprock J, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Braff DL, Light GA. Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia. JAMA Psychiatry 2017; 74:37-46. [PMID: 27926742 PMCID: PMC5453308 DOI: 10.1001/jamapsychiatry.2016.2980] [Citation(s) in RCA: 163] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
IMPORTANCE Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene. OBJECTIVES To characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment. MAIN OUTCOME AND MEASURES Mismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale. RESULTS Participants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (β = 0.37, P < .001), cognition had a direct effect on negative symptoms (β = -0.16, P < .001), and both cognition (β = 0.26, P < .001) and experiential negative symptoms (β = -0.75, P < .001) had direct effects on functional outcome. The indirect effect of EAP on functional outcome was significant as well (β = 0.14, P < .001). Overall, EAP had a fully mediated effect on functional outcome, engaging general rather than modality-specific cognition, with separate pathways that involved or bypassed negative symptoms. CONCLUSIONS AND RELEVANCE The data support a model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms. Results can be used to help guide mechanistically informed, personalized treatments and support the strategy of using EAP measures as surrogate end points in early-stage procognitive intervention studies.
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Affiliation(s)
- Michael L. Thomas
- Department of Psychiatry, University of California San Diego, La Jolla, CA,VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA
| | - Michael F. Green
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA,VA Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Gerhard Hellemann
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA,VA Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Catherine A. Sugar
- Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, CA
| | - Melissa Tarasenko
- Department of Psychiatry, University of California San Diego, La Jolla, CA,VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA
| | - Monica E. Calkins
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
| | | | - Raquel E. Gur
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
| | - Ruben C. Gur
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
| | - Laura C. Lazzeroni
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA
| | - Keith H. Nuechterlein
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA
| | - Allen D. Radant
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA,VA Puget Sound Health Care System, Seattle, WA
| | - Larry J. Seidman
- Department of Psychiatry, Harvard Medical School, Boston, MA,Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA
| | | | - Larry J. Siever
- Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY,James J. Peters VA Medical Center, New York, NY
| | - Jeremy M. Silverman
- Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY,James J. Peters VA Medical Center, New York, NY
| | - Joyce Sprock
- Department of Psychiatry, University of California San Diego, La Jolla, CA
| | - William S. Stone
- Department of Psychiatry, Harvard Medical School, Boston, MA,Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA
| | - Neal R. Swerdlow
- Department of Psychiatry, University of California San Diego, La Jolla, CA
| | - Debby W. Tsuang
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA,VA Puget Sound Health Care System, Seattle, WA
| | - Ming T. Tsuang
- Department of Psychiatry, University of California San Diego, La Jolla, CA,Center for Behavioral Genomics, and Institute for Genomic Medicine, University of California San Diego, La Jolla, CA,Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA
| | - Bruce I. Turetsky
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
| | - David L. Braff
- Department of Psychiatry, University of California San Diego, La Jolla, CA
| | - Gregory A. Light
- Department of Psychiatry, University of California San Diego, La Jolla, CA,VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA
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Abstract
PURPOSE OF REVIEW The review aims at highlighting the additional benefit that can be gained from combining noninvasive brain stimulation as well as repetitive sensory stimulation protocols with MRI techniques to account for the intersubject variability observed in those treatments. Potentially, this should help to identify predictive patterns in the individual receptiveness to the treatment. RECENT FINDINGS Knowledge about the underlying physiological principles of excitability changes as induced by noninvasive brain stimulation or repetitive sensory stimulation is accumulating, revealing strong associations with plasticity processes at the synaptic level. In this context, MRI techniques, such as magnetic resonance spectroscopy and functional MRI, emerged as valuable tools for the qualitative assessment of baseline states and induced changes. Those physiological readouts can help explain the interindividual heterogeneity found in behavioural and/or clinical responses to the specific stimulation protocols. This knowledge will eventually translate, first, into the preliminary classification of study participants into treatment groups according to their neurophysiological baseline state and expected responses to a particular stimulation. Subsequently, this should also aid the optimization of stimulation protocols according to the classification outcome, resulting in retuned protocols for particular groups of study participants. SUMMARY The consistent MRI-based monitoring of stimulation effects in the neural network promises a considerable gain for the customization of intervention protocols with improved therapeutic potential and rehabilitative predictions.
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Mancini M, Brignani D, Conforto S, Mauri P, Miniussi C, Pellicciari MC. Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis. Neuroimage 2016; 140:57-65. [DOI: 10.1016/j.neuroimage.2016.06.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 06/01/2016] [Accepted: 06/02/2016] [Indexed: 01/22/2023] Open
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