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Identification of Common Neural Circuit Disruptions in Cognitive Control Across Psychiatric Disorders
Open accessAbstract
OBJECTIVE: Cognitive deficits are a common feature of psychiatric disorders. The authors investigated the nature of disruptions in neural circuitry underlying cognitive control capacities across psychiatric disorders through a transdiagnostic neuroimaging meta-analysis. METHOD: A PubMed search was conducted for whole-brain functional neuroimaging articles published through June 2015 that compared activation in patients with axis I disorders and matched healthy control participants during cognitive control tasks. Tasks that probed performance or conflict monitoring, response inhibition or selection, set shifting, verbal fluency, and recognition or working memory were included. Activation likelihood estimation meta-analyses were conducted on peak voxel coordinates. RESULTS: The 283 experiments submitted to meta-analysis included 5,728 control participants and 5,493 patients with various disorders (schizophrenia, bipolar or unipolar depression, anxiety disorders, and substance use disorders). Transdiagnostically abnormal activation was evident in the left prefrontal cortex as well as the anterior insula, the right ventrolateral prefrontal cortex, the right intraparietal sulcus, and the midcingulate/presupplementary motor area. Disruption was also observed in a more anterior cluster in the dorsal cingulate cortex, which overlapped with a network of structural perturbation that the authors previously reported in a transdiagnostic meta-analysis of gray matter volume. CONCLUSIONS: These findings demonstrate a common pattern of disruption across major psychiatric disorders that parallels the "multiple-demand network" observed in intact cognition. This network interfaces with the anterior-cingulo-insular or "salience network" demonstrated to be transdiagnostically vulnerable to gray matter reduction. Thus, networks intrinsic to adaptive, flexible cognition are vulnerable to broad-spectrum psychopathology. Dysfunction in these networks may reflect an intermediate transdiagnostic phenotype, which could be leveraged to advance therapeutics.
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“many of these findings are unlikely to be specific to PTSD, and may instead represent common neural abnormalities across psychiatric disorders [9,10].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [10]
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“Further, meta-analyses across psychiatric disorders have found evidence of more similarities in functional and structural neuroimaging abnormalities across disorders than differences, despite variance in symptoms (Goodkind et al., 2015; McTeague et al., 2017).”
From Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety (2018) · cites this paper as McTeague et al., 2017
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The p Factor: One General Psychopathology Factor in the Structure of Psychiatric Disorders?
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Lorenzo, G. D., Jannini, T. B., Longo, L., Rossi, R., Siracusano, A., & Dell’Osso, B. M. (2020) · Springer eBooks · doi:10.1007/978-3-030-43356-7_13
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Fei, H. N., Tng, J. X. J., Tan, J. S., & Sim, K. (2021) · Springer eBooks · doi:10.1007/978-3-030-59797-9_18
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Frangou, S. (2021) · Springer eBooks · doi:10.1007/978-3-030-59797-9_22
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van Wingen, G. A. (2020) · doi:10.31234/osf.io/whns9
Xiao, X.-Z., Hammond, C., Salmeron, B., Wang, D.-N., Gu, H., Zhai, T., Nguyen, H., Lu, H., Ross, T., & Yang, Y. (2021) · bioRxiv · doi:10.1101/2021.10.14.464403 · Cited by 15
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Venta, A. C., Sharp, C., & Fonagy, P. (2021) · Wiley eBooks · doi:10.1002/9781118686089.ch16
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(2021) · Cambridge University Press eBooks · doi:10.1017/9781108635462.013
Taquet, M., Smith, S. M., Prohl, A. K., Peters, J. M., Warfield, S. K., Scherrer, B., & Harrison, P. J. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.09.231
Miceli, R., Satz, S., Swartz, H. A., & Manelis, A. (2022) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2022.100014
“This finding suggests that disrupted levels of myelin might be an early biological risk marker specific to MDD or common across various mental illnesses (McTeague et al., 2017).”
BackgroundPetrican, R., & Fornito, A. (2022) · medRxiv · doi:10.1101/2022.07.19.22277815
Wu, Y., Kong, L., Yang, A., Xin, K., Lu, Y., Yan, X., Liu, W., Zhu, Y., Jiang, X., Zhou, Y., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4189465
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“…are considered to be one of the foundations of brain function, it is unsurprising that virtually all psychiatric disorders display at least some circuit aberrations, where differences range from hypo- to hyperconnectivity and generally associate with symptom severity (McTeague et al., 2017, 2020).”
BackgroundBayesian methods for optimizing deep brain stimulation to enhance cognitive controlPreprint
Nagrale, S. S., Yousefi, A., Netoff, T. I., & Widge, A. S. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.14.520473
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Antoniades, M., Haas, S. S., Moukaled, S., New, F., Pescatore, S. D., & Frangou, S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-89832-4.00008-1
Wagels, L., Habel, U., & Nickl‐Jockschat, T. (2023) · Springer eBooks · doi:10.1007/978-3-030-42825-9_31-1
Neuroanatomy of Obsessive-Compulsive and Related Disorders
Thorsen, A. L., & van den Heuvel, O. A. (2023) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190068752.013.7
Objective Measure of a Subjective Experience: A Real-Time Biomarker of Mood Status?
Árgyelán, M., & Fenoy, A. J. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.06.011
Ivanov, I., Krone, B., Schulz, K. P., Shaik, R., Parvaz, M. A., & Newcorn, J. H. (2024) · Journal of Attention Disorders · doi:10.1177/10870547231219762
“…the future development of substance use, the relationship between nondrug reward-elicited brain activation and later SUD development is complex and context specific (Mahmood et al., 2013; McTeague et al., 2017; Norman et al., 2011; Smith et al., 2006; Spechler at al., 2018; Wetherill et al., 2013).”
BackgroundA common neural signature between genetic and environmental riskPreprint
Vedechkina, M., Holmes, J., Warrier, V., & Astle, D. E. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.13.598859
MAJOR DEPRESSIVE DISORDER: COGNITIVE, EMOTIVE AND MOTIVATIONAL CONSEQUENCES IN ADOLESCENTS.
Uwajeh, K., Egbuchulem, K. I., & Afolabi, O. A. (2024) · PubMed Central
Chapter 62. Treatment of Women Excluding Pregnancy and Postpartum
Duffy, K. A., Nagle-Yang, S. M., & Epperson, C. N. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as62
Desfossés, C. Y., & Blier, P. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as16
Chapter 59. Treatment of Chronic Pain
Key, R. G., & Kroenke, K. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as59
Chapter 15. Trazodone and Nefazodone
Golden, R., Dawkins, K., & Nicholas, L. M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as15
Chapter 58. Treatment of Insomnia
Krystal, A. D. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as58
Chapter 64. Treatment of Attention-Deficit/Hyperactivity Disorder in Adults
Deckler, E., & Coffey, B. J. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as64
Chapter 13. Sertraline and Paroxetine
Howlett, J. R., & Schatzberg, A. F. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as13
Chapter 61. Treatment During Late Life
Brewster, K., Rutherford, B. R., & Roose, S. P. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as61
Chapter 12. Fluoxetine and Fluvoxamine
Aboujaoude, E. N., Rosenbaum, J. F., Ionescu, D. F., & Koran, L. M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as12
Chapter 56. Treatment of Personality Disorders
Hollander, E., Vats, T., & Desilva, N. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as56
Chapter 19. Venlafaxine and Desvenlafaxine
Thase, M. E. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as19 · Cited by 1
Chapter 10. Monoamine Oxidase Inhibitors
Krishnan, K. R. R. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as10 · Cited by 1
Chapter 54. Treatment of Substance Use Disorders
Sherman, B. J., Hartwell, K. J., McRae‐Clark, A. L., Herron, A., & Brady, K. T. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as54
Stevenson, K. A., Hamilton, D. V., & Clayton, A. H. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as18
Ballon, J. S., Nunes, J. C., & Salaheldin, K. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as27
Chapter 30. Aripiprazole and Brexpiprazole
Birze, N., Yuan, C., & Garcia-Pittman, E. C. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as30
Buckley, P. F., & Foster, A. E. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as28
Chapter 65. Treatment of Individuals With Intellectual Developmental Disorder
Stratigos, K. A., Katz, J., & Hong, D. S. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as65
Chapter 66. Treatment of Autism Spectrum Disorder
Hegarty, J. P., & Hardan, A. Y. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as66
Chapter 53. Treatment of Schizophrenia
Brunette, M. F., Ballon, J. S., Gnanasegaram, S. A., Kalinowski, A., Keller, W. R., Reed, J. D., & Noordsy, D. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as53
Chapter 40. Gabapentin and Pregabalin
Frye, M. A., Moore, K. M., & Schatzberg, A. F. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as40
Chapter 21. Ketamine and Esketamine
Mathai, D. S., & Mathew, S. J. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as21
McElroy, S. L., Guerdjikova, A. I., & Romo‐Nava, F. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as42
Robinson, D. S., Rickels, K., & Farrington, J. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as23
Sheehan, D. V. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as22
Chapter 67. Treatment of Psychiatric Emergencies
McRoberts, R. L., & Garlow, S. J. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as67
Chapter 24. Brexanolone and Other Neurosteroids
Patterson, R., Krohn, H., & Meltzer-Brody, S. E. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as24
Hirschfeld, R. M. A., & Bowden, C. L. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as38
Almeida, J., Spelber, D., & Smith, T. L. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as37
Chapter 46. Electroconvulsive Therapy and Other Neuromodulation Therapies
McDonald, W. M., Meeks, T. W., McCall, W. V., & Zorumski, C. F. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as46
Citrome, L. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as34
Chapter 36. Management of Psychiatric Medication–Induced Movement Disorders
Marsh, L. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as36
Harvey, P. D. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as33
Cummings, J. L. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as35
Chapter 47. Psychedelic Drugs as Treatments in Psychiatry
Nutt, D., & Erritzøe, D. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as47
Chapter 5. Brain–Immune System Interactions
Dhabhar, F. S., Raison, C. L., & Miller, A. H. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as05
Chapter 1. Basic Principles of Molecular Biology and Genomics
Wahlestedt, C., Rasenick, M. M., Yu, J.-Z., & Zeier, Z. R. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as01
Chapter 48. Treatment of Depression
Collier, S. J., & Nemeroff, C. B. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as48
Chapter 2. Neurotransmitters, Receptors, and Transporters
Berg, K. A., Clarke, W. P., Daws, L. C., Frazer, A., Girotti, M., & Lodge, D. J. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as02
Chapter 52. Treatment of Obsessive-Compulsive Disorder
Kayser, R. R., & Simpson, H. B. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as52 · Cited by 1
Chapter 43. Agents for Neurocognitive Disorders
Ayers, G. M., & Brown, F. W. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as43
Chapter 44. Sedative-Hypnotics
Nishino, S., Ono, T., Nishino, N., Sakai, N., & Mignot, E. J.-M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as44
Chapter 7. Neuroimaging and Psychiatry
Paulus, M. P., & Guinjoan, S. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as07
Chapter 9. Machine Learning in Psychopharmacology
Galatzer‐Levy, I. R., & Abbas, A. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as09
Chapter 45. Psychostimulants and Wakefulness-Promoting Agents
DeBattista, C. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as45
Chapter 51. Treatment of Posttraumatic Stress Disorder
Nemeroff, C. B., Rosen, V., & Ortiz, N. F. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as51
Willentliche Handlungssteuerung und kognitive Kontrolle
Goschke, T. (2024) · Springer eBooks · doi:10.1007/978-3-662-68476-4_9
Deng, Q., Levitis, E., Adams, R. A., & Altmann, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.29.626043
Goena, J., Vidal-Adroher, C., Solis-Barquero, S., Jiménez-Mesa, C., Garcés, M. S., Fernandez, M. A. R., García-Eulate, R., Molero, P., Catalán, A., Alústiza, I., et al. (2025) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2025.01.042
Hoy, N., Waszczuk, M. A., Sunderland, M., Lynch, S. J., Sachdev, P. S., Brodaty, H., Reppermund, S., & Mewton, L. R. (2025) · Psychological Medicine · doi:10.1017/s0033291724003490
“…that abnormalities in both brain structure and function are largely shared across putatively distinct diagnostic categories (Goodkind et al., 2015; McTeague et al., 2017; Sha et al., 2019), consistent with the correlational structure of psychopathology identified through latent variable modeling.”
Biophysical mechanisms of default mode network function and dysfunctionPreprint
Nghiem, T.-A. E., & Menon, V. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.16.649208
Johnstone, N., & Kadosh, K. C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.07.652653
Stohr, G. M., Harrewijn, A., Morales, S., Zeytinoglu, S., Laky, Z. E., Khosravi, P., Cardinale, E. M., Lorenzo, N. E., Stoddard, J., Pine, D. S., et al. (2025) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-025-01293-1
“Aberrant cognitive control, specifically in the ability to inhibit prepotent responses and monitor errors, relates to concurrent anxiety (Dudeney et al., 2015; Fani et al., 2012; Hayes et al., 2012; MacLeod & Mathews, 1988; McTeague et al., 2017).”
Cognitive interference elicits developmental sex differences in inhibitory control
Son, J. J., Killanin, A. D., Schantell, M. D., Arif, Y., Ward, T. W., Rempe, M. P., Ende, G. C., Okelberry, H. J., Rice, D. L., Coutant, A. T., et al. (2025) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2025.101590
“…observed in a wide range of mental health disorders, including attention-deficit hyperactivity disorder (ADHD), alcohol and substance use disorders, and mood disorders (Li et al., 2021; Lipszyc and Schachar, 2010; McTeague et al., 2016, 2017; Nigg, 2001, 2017; Verdejo-García et al., 2008).”
Watson, K. H., Ciriegio, A. E., Fraley, C. E., Roth, M. C., & Compas, B. E. (2025) · Neuropsychology Review · doi:10.1007/s11065-025-09669-3 · Cited by 1
“Specifically, research has shown that deficits in executive function confer risk for a range of psychiatric conditions (e.g., Catalan et al., 2021; McTeague et al., 2016, 2017).”
Wang, D., Hammond, C. J., Salmeron, B. J., Xiao, X., Murray, L., Gu, H., Zhai, T., Quam, A., Hill, J., Nguyen, H., et al. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.03.230
Liu, T., You, S., Chen, Y., Wu, Q., & Wu, T. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5375743
Sendi, M. S. E., Halko, M. A., Traynor, J. M., Brown, J. C., Copersino, M. L., Nickerson, L. D., Harnett, N. G., van Rooij, S. J. H., Pizzagalli, D. A., House, S. L., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7200801/v1
“Dysfunction in this network is linked to emotion regulation de�cits in psychiatric disorders 44 , including depression 45 and PTSD 46,47 , and increased impulsivity in PTSD and related conditions 48 , underscoring its importance in mental health.”
Prentice, A., Arns, M., Middleton, V. J., Bowman, J., Donachie, N., Kriske, J., Kriske, J., Sack, A. T., Downar, J. H., & van der Vinne, N. (2025) · Transcranial magnetic stimulation . · doi:10.1016/j.transm.2025.100190
Kognitive und neuronale Grundlagen von Motivation, Belohnung und Selbstkontrolle
Goschke, T. (2025) · Springer eBooks · doi:10.1007/978-3-662-69368-1_10
The Affective Neuroscience of Emotion Regulation
Kohn, N., & Morawetz, C. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009342919.029
Cognition–Emotion Interactions
Armony, J., & Vuilleumier, P. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009342919.024
Cesco, M., Garzitto, M., Pischiutta, L., Lombardelli, T., Moratti, E., Zamparutti, G., Balestrieri, M., Albert, U., & Colizzi, M. (2025) · American Journal on Addictions · doi:10.1111/ajad.70103
“34 The preliminary results of our research indicate that different ADHD dimensions exert distinct impacts, suggesting separate underlying neurobiological pathways.”
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Metadata
- Authors
- McTeague, L. M., Huemer, J., Carreon, D. M., Jiang, Y., Eickhoff, S. B., & Etkin, A.
- Affiliations
- Medical University of South Carolina (US)
- Venue
- American Journal of Psychiatry
- Published
- 2017-07-01
- Volume
- 174
- Issue
- 7
- Pages
- 676-685
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5543416
- OpenAlex
- W2602886720
- Cited by
- 635
- References
- 48
- Citations by year
- 2026: 55 · 2025: 61 · 2024: 127 · 2023: 60 · 2022: 74 · 2021: 86 · 2020: 66 · 2019: 50 · 2018: 40 · 2017: 16
- FWCI
- 26.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Österreichischen Akademie der Wissenschaften
- National Institute of Mental Health (R01MH074457, K23MH104849)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- cognitive control, mental illness, multiple-demand network, salience network, prefrontal cortex, anterior insula, intraparietal sulcus, schizophrenia, bipolar disorder, depression, anxiety disorders, substance use disorders, cognitive impairment, activation likelihood estimation
- MeSH terms
- Mental Disorders, Brain, Brain Mapping, Dominance, Cerebral, Humans, Nerve Net, Neuropsychological Tests, Psychometrics, Reference Values, Cognitive Dysfunction
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