• This record comes from PubMed

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

. 2024 Mar ; 29 (3) : 611-623. [epub] 20240110

Language English Country England, Great Britain Media print-electronic

Document type Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't

Grant support
I01 RX002171 RRD VA - United States
R21MH106998 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01 RX002170 RRD VA - United States
27040 Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)
R01 MH129832 NIMH NIH HHS - United States
R01MH105535 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01 RX002172 RRD VA - United States
P41 EB015922 NIBIB NIH HHS - United States
P50 U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)
I01 RX002174 RRD VA - United States
W81XWH-10-1-0925 U.S. Department of Defense (United States Department of Defense)
R56 MH071537 NIMH NIH HHS - United States
20ZDA079 National Natural Science Foundation of China (National Science Foundation of China)
P30 HD003352 NICHD NIH HHS - United States
R01AG059874 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
R01MH107382 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
R61NS120249 U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
K01 MH122774 NIMH NIH HHS - United States
I01 RX003444 RRD VA - United States
IK2 RX002922 RRD VA - United States
R01AG022381 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
31971020 National Natural Science Foundation of China (National Science Foundation of China)
R21 MH098212 NIMH NIH HHS - United States
R01 MH113574 NIMH NIH HHS - United States
K12 HD085850 NICHD NIH HHS - United States
1IK2CX001680 U.S. Department of Veterans Affairs (Department of Veterans Affairs)
R01 MH071537 NIMH NIH HHS - United States
HD085850 U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
R21 MH106998 NIMH NIH HHS - United States
I01 RX003442 RRD VA - United States
IK2 CX001680 CSRD VA - United States
14848 Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)
R01 AG064955 NIA NIH HHS - United States
R01MH110483 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01 CX001135 CSRD VA - United States
1IK2RX000709 U.S. Department of Veterans Affairs (Department of Veterans Affairs)
R21 MH112956 NIMH NIH HHS - United States
W81XWH-08-2-0038 United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)
R01 MH105355 NIMH NIH HHS - United States
K23MH090366 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
K01 MH118428 NIMH NIH HHS - United States
R01 MH105535 NIMH NIH HHS - United States
MH101380 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
WA 1539/8-2 Deutsche Forschungsgemeinschaft (German Research Foundation)
M01RR00039 U.S. Department of Health & Human Services | National Institutes of Health (NIH)
M01 RR000039 NCRR NIH HHS - United States
I01 RX003443 RRD VA - United States
R01 MH111671 NIMH NIH HHS - United States
R01 MH106574 NIMH NIH HHS - United States
R01 MH116147 NIMH NIH HHS - United States
R01MH111671 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
R01MH117601 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
1K2RX002922 U.S. Department of Veterans Affairs (Department of Veterans Affairs)
I01 RX001880 RRD VA - United States
R21MH102634 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
MH071537 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01 RX000622 RRD VA - United States
R01MH096987 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
K01MH122774 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01 HX003155 HSRD VA - United States
R01MH106574 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
U54 EB020403 NIBIB NIH HHS - United States
R01 MH117601 NIMH NIH HHS - United States
I01 RX001774 RRD VA - United States
I01 CX002097 CSRD VA - United States
UL1TR000454 U.S. Department of Health & Human Services | National Institutes of Health (NIH)
I01 RX002076 RRD VA - United States
R01 MH119227 NIMH NIH HHS - United States
K01MH118467 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
SFB/TRR 58: C06, C07 Deutsche Forschungsgemeinschaft (German Research Foundation)
U21A20364 National Natural Science Foundation of China (National Science Foundation of China)
BK20221554 Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)
UL1 TR000454 NCATS NIH HHS - United States
R01 MH107382 NIMH NIH HHS - United States
R01MH119227 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01 CX001246 CSRD VA - United States
MH098212 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
R56 AG058854 NIA NIH HHS - United States
40-00812-98-10041 ZonMw (Netherlands Organisation for Health Research and Development)
T32 MH018931 NIMH NIH HHS - United States
R01 AG076838 NIA NIH HHS - United States
K23 MH101380 NIMH NIH HHS - United States
R01 MH043454 NIMH NIH HHS - United States
R21 MH102634 NIMH NIH HHS - United States
K01MH118428 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
HD071982 U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
R01 HD071982 NICHD NIH HHS - United States
K23 MH090366 NIMH NIH HHS - United States
I01 RX002173 RRD VA - United States
R01MH105355 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
I01RX000622 U.S. Department of Veterans Affairs (Department of Veterans Affairs)
W81XWH-12-2-0012 U.S. Department of Defense (United States Department of Defense)
R61 NS120249 NINDS NIH HHS - United States
R21MH098198 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
K01 MH118467 NIMH NIH HHS - United States
I01 CX002096 CSRD VA - United States
I01 CX001820 CSRD VA - United States
R21MH112956 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
IK2 RX000709 RRD VA - United States
I01 RX001135 RRD VA - United States
DA 1222/4-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
R01 MH096987 NIMH NIH HHS - United States
1184403 Department of Health | National Health and Medical Research Council (NHMRC)
R01 AG022381 NIA NIH HHS - United States
R01 AG050595 NIA NIH HHS - United States
M01RR00039 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
R01AG050595 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
R01 AG059874 NIA NIH HHS - United States

Links

PubMed 38195980
PubMed Central PMC11153161
DOI 10.1038/s41380-023-02352-0
PII: 10.1038/s41380-023-02352-0
Knihovny.cz E-resources

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

1st Department of Neurology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Amsterdam UMC University of Amsterdam Psychiatry Amsterdam Neuroscience Amsterdam The Netherlands

Amsterdam UMC Vrije Universiteit Psychiatry Amsterdam Neuroscience Amsterdam The Netherlands

ARQ National Psychotrauma Centre Diemen The Netherlands

Brain Health Research Centre Department of Anatomy University of Otago Dunedin New Zealand

Brain Imaging and Analysis Center Duke University Durham NC USA

CEITEC Central European Institute of Technology Multimodal and Functional Neuroimaging Research Group Masaryk University Brno Czech Republic

Center for Behavior Genetics of Aging University of California San Diego La Jolla CA USA

Center for Brain and Behavior Research University of South Dakota Vermillion SD USA

Center for Depression Anxiety and Stress Research McLean Hospital Harvard University Belmont MA USA

Center for Global Health Equity New York University Shanghai Shanghai China

Center for Healthy Minds University of Wisconsin Madison Madison WI USA

Center for Vital Longevity School of Behavioral and Brain Sciences University of Texas at Dallas Dallas TX USA

CIC1415 CHRU de Tours Inserm Tours France

Civil Aerospace Medical Institute US Federal Aviation Administration Oklahoma City OK USA

Comprehensive Injury Center Medical College of Wisconsin Milwaukee WI USA

Department of Clinical Psychology University of Groningen Groningen The Netherlands

Department of Experimental Clinical and Health Psychology Ghent University Ghent Belgium

Department of Medical Imaging Jinling Hospital Medical School of Nanjing University Nanjing Jiangsu China

Department of Neurology University of Utah School of Medicine Salt Lake City UT USA

Department of Neuroscience Central Clinical School Monash University Melbourne Vic Australia

Department of Neuroscience University of Rochester Medical Center Rochester NY USA

Department of Neurosciences University of Toledo Toledo OH USA

Department of Pediatrics University of Minnesota Minneapolis MN USA

Department of Physical Medicine and Rehabilitation Virginia Commonwealth University Richmond VA USA

Department of Psychiatry and Behavioral Health Institute for Behavioral Medicine Research The Ohio State University Columbus OH USA

Department of Psychiatry and Behavioral Neuroscience Wayne State University School of Medicine Detroit MI USA

Department of Psychiatry and Behavioral Science Texas A and M University Health Science Center Bryan TX USA

Department of Psychiatry and Behavioral Sciences Duke School of Medicine Durham NC USA

Department of Psychiatry and Behavioral Sciences Emory University School of Medicine Atlanta GA USA

Department of Psychiatry and Behavioral Sciences Stanford University Stanford CA USA

Department of Psychiatry and Behavioral Sciences University of Minnesota Minneapolis MN USA

Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center Nashville TN USA

Department of Psychiatry Baylor College of Medicine Houston TX USA

Department of Psychiatry Columbia University Medical Center New York NY USA

Department of Psychiatry Erasmus University Medical Center Rotterdam the Netherlands

Department of Psychiatry Harvard Medical School Boston MA USA

Department of Psychiatry Stellenbosch University Cape Town South Africa

Department of Psychiatry Texas A and M University Bryan Texas USA

Department of Psychiatry University of California San Diego La Jolla CA USA

Department of Psychiatry University of Michigan Ann Arbor MI USA

Department of Psychiatry University of Texas at Austin Austin TX USA

Department of Psychiatry University of Toledo Toledo OH USA

Department of Psychiatry University of Wisconsin Madison Madison WI USA

Department of Psychiatry Yale University School of Medicine New Haven CT USA

Department of Psychological Sciences Center for Trauma Recovery University of Missouri St Louis St Louis MO USA

Department of Psychology and Neuroscience Baylor University Waco TX USA

Department of Psychology Marquette University Milwaukee WI USA

Department of Psychology The Education University of Hong Kong Ting Kok Hong Kong

Department of Psychology University of Chinese Academy of Sciences Beijing China

Department of Psychology University of Minnesota Minneapolis MN USA

Department of Psychology University of South Dakota Vermillion SD USA

Department of Psychology University of Wisconsin Madison Madison WI USA

Department of Psychology University of Wisconsin Milwaukee Milwaukee WI USA

Department of Psychology Vanderbilt University Nashville TN USA

Department of Psychosomatic Medicine and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim Heidelberg University Heidelberg Germany

Department of Radiology Washington University School of Medicine St Louis MO USA

Department of Veteran Affairs Mid Atlantic Mental Illness Research Education and Clinical Center Durham NC USA

Departments of Comparative Medicine Neuroscience and Psychology Wu Tsai Institute Yale University New Haven CT USA

Departments of Psychiatry and of Psychology Wu Tsai Institute Yale University New Haven CT USA

Departments of Radiology Psychiatry and Biomedical Engineering University of Iowa Iowa City IA USA

Dept of Psychological and Brain Sciences Boston University Boston MA USA

Disaster Mental Health Institute Vermillion SD USA

Division of Basic Biomedical Sciences Sanford School of Medicine University of South Dakota Vermillion SD USA

Division of Clinical Neuroscience National Center for PTSD West Haven CT USA

Division of Depression and Anxiety Disorders McLean Hospital Belmont MA USA

Division of Epidemiology and Social Sciences Institute of Health and Equity Medical College of Wisconsin Milwaukee Milwaukee WI USA

Division of Trauma and Acute Care Surgery Department of Surgery Medical College of Wisconsin Milwaukee WI USA

Division of Women's Mental Health McLean Hospital Belmont MA USA

Donders Institute for Brain Cognition and Behavior Centre for Cognitive Neuroimaging Radboud University Nijmegen Nijmegen The Netherlands

George E Wahlen Veterans Affairs Medical Center Salt Lake City UT USA

H Ben Taub Department of Physical Medicine and Rehabilitation Baylor College of Medicine Houston TX USA

Imaging Genetics Center Stevens Neuroimaging and Informatics Institute Keck School of Medicine of USC Marina del Rey CA USA

Institute for Technology in Psychiatry McLean Hospital Belmont MA USA

Institute of Medical Psychology and Systems Neuroscience University of Münster Münster Germany

Laboratory for Traumatic Stress Studies Chinese Academy of Sciences Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences Beijing China

Masonic Institute for the Developing Brain Minneapolis MN USA

Minneapolis VA Health Care System Minneapolis MN USA

Monash Biomedical Imaging Monash University Melbourne Vic Australia

Munroe Meyer Institute University of Nebraska Medical Center Omaha NE USA

Neuroscience Research Australia Randwick NSW Australia

New York State Psychiatric Institute New York NY USA

Northwestern Neighborhood and Network Initiative Northwestern University Institute for Policy Research Evanston IL USA

SA MRC Unit on Risk and Resilience in Mental Disorders Department of Psychiatry and Neuroscience Institute University of Cape Town Cape Town South Africa

School of Medicine and Public Health University of Wisconsin Madison Madison WI USA

School of Psychology University of New South Wales Sydney Sydney NSW Australia

Sioux Falls VA Health Care System Sioux Falls SD USA

South African Medical Research Council Unit on the Genomics of Brain Disorders Department of Psychiatry Stellenbosch University Stellenbosch South Africa

Tel Aviv University Tel Aviv Yafo Israel

UMR1253 Université de Tours Inserm Tours France

University Medical Centre Charité Berlin Germany

University of Haifa Haifa Israel

VA Palo Alto Health Care System Palo Alto CA USA

Veterans Affairs Richmond Health Care Richmond VA USA

Veterans Integrated Service Network 17 Center of Excellence for Research on Returning War Veterans Waco TX USA

See more in PubMed

Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013;26:537–47. PubMed PMC

Association AP. Diagnostic and statistical manual of mental disorders(5th ed), 2013.

Harnett NG, Goodman AM, Knight DC. PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. Exp Neurol. 2020;330:113331. PubMed

Hayes JP, Hayes SM, Mikedis AM. Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol Mood Anxiety Disord. 2012;2:9. PubMed PMC

Karl A, Schaefer M, Malta LS, Dorfel D, Rohleder N, Werner A. A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev. 2006;30:1004–31. PubMed

Kitayama N, Vaccarino V, Kutner M, Weiss P, Bremner JD. Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis. J Affect Disord. 2005;88:79–86. PubMed

Logue MW, van Rooij SJH, Dennis EL, Davis SL, Hayes JP, Stevens JS, et al. Smaller Hippocampal volume in posttraumatic stress disorder: a multisite ENIGMA-PGC Study: Subcortical volumetry results from posttraumatic stress disorder consortia. Biol Psychiatry. 2018;83:244–53. PubMed PMC

Woon FL, Sood S, Hedges DW. Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1181–8. PubMed

O’Doherty DC, Chitty KM, Saddiqui S, Bennett MR, Lagopoulos J. A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res. 2015;232:1–33. PubMed

Morey RA, Haswell CC, Hooper SR, De Bellis MD. Amygdala, Hippocampus, and ventral medial prefrontal cortex volumes differ in maltreated youth with and without chronic posttraumatic stress disorder. Neuropsychopharmacology. 2016;41:791–801. PubMed PMC

Kuhn S, Gallinat J. Gray matter correlates of posttraumatic stress disorder: a quantitative meta-analysis. Biol Psychiatry. 2013;73:70–74. PubMed

Keding TJ, Herringa RJ. Abnormal structure of fear circuitry in pediatric post-traumatic stress disorder. Neuropsychopharmacology. 2015;40:537–45. PubMed PMC

Morey RA, Gold AL, LaBar KS, Beall SK, Brown VM, Haswell CC, et al. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatry. 2012;69:1169–78. PubMed PMC

Rogers MA, Yamasue H, Abe O, Yamada H, Ohtani T, Iwanami A, et al. Smaller amygdala volume and reduced anterior cingulate gray matter density associated with history of post-traumatic stress disorder. Psychiatry Res. 2009;174:210–6. PubMed

Veer IM, Oei NY, van Buchem MA, Spinhoven P, Elzinga BM, Rombouts SA. Evidence for smaller right amygdala volumes in posttraumatic stress disorder following childhood trauma. Psychiatry Res. 2015;233:436–42. PubMed

Herringa R, Phillips M, Almeida J, Insana S, Germain A. Post-traumatic stress symptoms correlate with smaller subgenual cingulate, caudate, and insula volumes in unmedicated combat veterans. Psychiatry Res. 2012;203:139–45. PubMed PMC

Chen S, Xia W, Li L, Liu J, He Z, Zhang Z, et al. Gray matter density reduction in the insula in fire survivors with posttraumatic stress disorder: a voxel-based morphometric study. Psychiatry Res. 2006;146:65–72. PubMed

Meng Y, Qiu C, Zhu H, Lama S, Lui S, Gong Q, et al. Anatomical deficits in adult posttraumatic stress disorder: a meta-analysis of voxel-based morphometry studies. Behav Brain Res. 2014;270:307–15. PubMed

Woodward SH, Kaloupek DG, Streeter CC, Martinez C, Schaer M, Eliez S. Decreased anterior cingulate volume in combat-related PTSD. Biol Psychiatry. 2006;59:582–7. PubMed

Kitayama N, Quinn S, Bremner JD. Smaller volume of anterior cingulate cortex in abuse-related posttraumatic stress disorder. J Affect Disord. 2006;90:171–4. PubMed PMC

Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35:169–91. PubMed PMC

Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research–past, present, and future. Biol Psychiatry. 2006;60:376–82. PubMed

Blithikioti C, Nuno L, Guell X, Pascual-Diaz S, Gual A, Balcells-Olivero M, et al. The cerebellum and psychological trauma: A systematic review of neuroimaging studies. Neurobiol Stress. 2022;17:100429. PubMed PMC

Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, et al. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex. 2010;46:845–57. PubMed

Adamaszek M, D’Agata F, Ferrucci R, Habas C, Keulen S, Kirkby KC, et al. Consensus paper: cerebellum and emotion. Cerebellum. 2017;16:552–76. PubMed

Schmahmann JD. The cerebellum and cognition. Neurosci Lett. 2019;688:62–75. PubMed

Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain. 2006;129:290–2. PubMed

Balsters JH, Cussans E, Diedrichsen J, Phillips KA, Preuss TM, Rilling JK, et al. Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules. Neuroimage. 2010;49:2045–52. PubMed PMC

Barton RA, Venditti C. Rapid evolution of the cerebellum in humans and other great apes. Curr Biol. 2014;24:2440–4. PubMed

Sereno MI, Diedrichsen J, Tachrount M, Testa-Silva G, d’Arceuil H, De Zeeuw C. The human cerebellum has almost 80% of the surface area of the neocortex. Proc Natl Acad Sci USA. 2020;117:19538–43. PubMed PMC

Solov’ev SV. The weight and linear dimensions of the human cerebellum. Neurosci Behav Physiol. 2006;36:479–81. PubMed

Azevedo FA, Carvalho LR, Grinberg LT, Farfel JM, Ferretti RE, Leite RE, et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009;513:532–41. PubMed

Bernard JA, Seidler RD, Hassevoort KM, Benson BL, Welsh RC, Wiggins JL, et al. Resting state cortico-cerebellar functional connectivity networks: a comparison of anatomical and self-organizing map approaches. Front Neuroanat. 2012;6:31. PubMed PMC

Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:2322–45. PubMed PMC

Schmahmann JD. Emotional disorders and the cerebellum: Neurobiological substrates, neuropsychiatry, and therapeutic implications. Handb Clin Neurol. 2021;183:109–54. PubMed

Moreno-Rius J. The cerebellum under stress. Front Neuroendocrinol. 2019;54:100774. PubMed

Carletto S, Borsato T. Neurobiological correlates of post-traumatic stress disorder: a focus on cerebellum role. Eur J Trauma Dissoc. 2017;1:153–7.

Ernst TM, Brol AE, Gratz M, Ritter C, Bingel U, Schlamann M, et al. The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm. Elife 2019;8:e46831. PubMed PMC

Frontera JL, Baba Aissa H, Sala RW, Mailhes-Hamon C, Georgescu IA, Lena C, et al. Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey. Nat Commun. 2020;11:5207. PubMed PMC

Lange I, Kasanova Z, Goossens L, Leibold N, De Zeeuw CI, van Amelsvoort T, et al. The anatomy of fear learning in the cerebellum: A systematic meta-analysis. Neurosci Biobehav Rev. 2015;59:83–91. PubMed

Milad MR, Quirk GJ. Fear extinction as a model for translational neuroscience: ten years of progress. Annu Rev Psychol. 2012;63:129–51. PubMed PMC

Sevenster D, Visser RM, D’Hooge R. A translational perspective on neural circuits of fear extinction: Current promises and challenges. Neurobiol Learn Mem. 2018;155:113–26. PubMed PMC

Belleau EL, Ehret LE, Hanson JL, Brasel KJ, Larson CL, deRoon-Cassini TA. Amygdala functional connectivity in the acute aftermath of trauma prospectively predicts severity of posttraumatic stress symptoms. Neurobiol Stress. 2020;12:100217. PubMed PMC

Pannu Hayes J, Labar KS, Petty CM, McCarthy G, Morey RA. Alterations in the neural circuitry for emotion and attention associated with posttraumatic stress symptomatology. Psychiatry Res. 2009;172:7–15. PubMed PMC

Koch SB, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M. Aberrant resting-state brain activity in posttraumatic stress disorder: a meta-analysis and systematic review. Depress Anxiety. 2016;33:592–605. PubMed

Wang T, Liu J, Zhang J, Zhan W, Li L, Wu M, et al. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis. Sci Rep. 2016;6:27131. PubMed PMC

Baldacara L, Jackowski AP, Schoedl A, Pupo M, Andreoli SB, Mello MF, et al. Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample. J Psychiatr Res. 2011;45:1627–33. PubMed

Holmes SE, Scheinost D, DellaGioia N, Davis MT, Matuskey D, Pietrzak RH, et al. Cerebellar and prefrontal cortical alterations in PTSD: structural and functional evidence. Chronic Stress 2018;2:2470547018786390. PubMed PMC

De Bellis MD, Kuchibhatla M. Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry. 2006;60:697–703. PubMed

Carrion VG, Weems CF, Watson C, Eliez S, Menon V, Reiss AL. Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res. 2009;172:226–34. PubMed PMC

Fennema-Notestine C, Stein MB, Kennedy CM, Archibald SL, Jernigan TL. Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder. Biol Psychiatry. 2002;52:1089–101. PubMed

Levitt JJ, Chen QC, May FS, Gilbertson MW, Shenton ME, Pitman RK. Volume of cerebellar vermis in monozygotic twins discordant for combat exposure: lack of relationship to post-traumatic stress disorder. Psychiatry Res. 2006;148:143–9. PubMed PMC

Clouston SAP, Kritikos M, Huang C, Kuan PF, Vaska P, Pellecchia AC, et al. Reduced cerebellar cortical thickness in World Trade Center responders with cognitive impairment. Transl Psychiatry. 2022;12:107. PubMed PMC

Singh R. Cerebellum: its anatomy, functions and diseases, 2020.

Kerestes R, Han S, Balachander S, Hernandez-Castillo C, Prince JL, Diedrichsen J, et al. A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging. J Vis Exp. 2022 10.3791/63340. PubMed

Oscarsson O. Functional organization of the Spino- and Cuneocerebellar tracts. Physiol Rev. 1965;45:495–522. PubMed

Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2009;44:489–501. PubMed

Schmahmann JD, Pandya DN. Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function. Neurosci Lett. 1995;199:175–8. PubMed

Schmahmann JD, Pandya DN. The cerebrocerebellar system. Int Rev Neurobiol. 1997;41:31–60. PubMed

Marvel CL, Desmond JE. Functional topography of the cerebellum in verbal working memory. Neuropsychol Rev. 2010;20:271–9. PubMed PMC

Moulton EA, Elman I, Pendse G, Schmahmann J, Becerra L, Borsook D. Aversion-related circuitry in the cerebellum: responses to noxious heat and unpleasant images. J Neurosci. 2011;31:3795–804. PubMed PMC

Schutter DJ, van Honk J. The cerebellum on the rise in human emotion. Cerebellum. 2005;4:290–4. PubMed

Pierce JE, Thomasson M, Voruz P, Selosse G, Peron J. Explicit and implicit emotion processing in the cerebellum: a meta-analysis and systematic review. Cerebellum. 2023;22:852–64. PubMed PMC

Canu E, Calderaro D, Castelnovo V, Basaia S, Magno MA, Riva N, et al. Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration. Mol Psychiatry. 2022;27:4809–21. PubMed PMC

Schienle A, Scharmuller W. Cerebellar activity and connectivity during the experience of disgust and happiness. Neuroscience. 2013;246:375–81. PubMed

Rabellino D, Densmore M, Theberge J, McKinnon MC, Lanius RA. The cerebellum after trauma: Resting-state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype. Hum Brain Mapp. 2018;39:3354–74. PubMed PMC

Naegeli C, Zeffiro T, Piccirelli M, Jaillard A, Weilenmann A, Hassanpour K, et al. Locus Coeruleus activity mediates hyperresponsiveness in posttraumatic stress disorder. Biol Psychiatry. 2018;83:254–62. PubMed

Rabellino D, Densmore M, Frewen PA, Theberge J, Lanius RA. The innate alarm circuit in post-traumatic stress disorder: Conscious and subconscious processing of fear- and trauma-related cues. Psychiatry Res Neuroimaging. 2016;248:142–50. PubMed

Sui SG, Zhang Y, Wu MX, Xu JM, Duan L, Weng XC, et al. Abnormal cerebellum density in victims of rape with post-traumatic stress disorder: voxel-based analysis of magnetic resonance imaging investigation. Asia Pac Psychiatry. 2010;2:129–35.

Kerestes R, Cummins H, Georgiou-Karistianis N, Selvadurai LP, Corben LA, Delatycki MB, et al. Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia. J Neurol. 2023;270:2360–9. PubMed PMC

O’Neil ME, Agyemang A, Walker WC, Pogoda TK, Klyce DW, Perrin PB, et al. Demographic, military, and health comorbidity variables by mild TBI and PTSD status in the LIMBIC-CENC cohort. Brain Inj. 2022;36:598–606. PubMed

Han S, Carass A, He Y, Prince JL. Automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization. Neuroimage. 2020;218:116819. PubMed PMC

Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67:1–48.

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc, Ser B. 1995;57:289–300.

Lupo M, Siciliano L, Leggio M. From cerebellar alterations to mood disorders: A systematic review. Neurosci Biobehav Rev. 2019;103:21–28. PubMed

Peng J, Liu J, Nie B, Li Y, Shan B, Wang G, et al. Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study. Eur J Radiol. 2011;80:395–9. PubMed

Miquel M, Vazquez-Sanroman D, Carbo-Gas M, Gil-Miravet I, Sanchis-Segura C, Carulli D, et al. Have we been ignoring the elephant in the room? Seven arguments for considering the cerebellum as part of addiction circuitry. Neurosci Biobehav Rev. 2016;60:1–11. PubMed

Segobin SH, Chetelat G, Le Berre AP, Lannuzel C, Boudehent C, Vabret F, et al. Relationship between brain volumetric changes and interim drinking at six months in alcohol-dependent patients. Alcohol Clin Exp Res. 2014;38:739–48. PubMed

Clausen AN, Aupperle RL, Yeh HW, Waller D, Payne J, Kuplicki R, et al. Machine learning analysis of the relationships between gray matter volume and childhood trauma in a transdiagnostic community-based sample. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4:734–42. PubMed PMC

Teicher MH, Samson JA. Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect. J Child Psychol Psychiatry. 2016;57:241–66. PubMed PMC

Bernstein DP, Fink L. Childhood Trauma Questionnaire: a retrospective self-report manual. The Psychological Corporation: San Antonio, TX, 1998.

Phillips JR, Hewedi DH, Eissa AM, Moustafa AA. The cerebellum and psychiatric disorders. Front Public Health. 2015;3:66. PubMed PMC

Yin Y, Li L, Jin C, Hu X, Duan L, Eyler LT, et al. Abnormal baseline brain activity in posttraumatic stress disorder: a resting-state functional magnetic resonance imaging study. Neurosci Lett. 2011;498:185–9. PubMed

Quide Y, Clery H, Andersson F, Descriaud C, Saint-Martin P, Barantin L, et al. Neurocognitive, emotional and neuroendocrine correlates of exposure to sexual assault in women. J Psychiatry Neurosci. 2018;43:318–26. PubMed PMC

Abdallah CG, Averill CL, Ramage AE, Averill LA, Goktas S, Nemati S, et al. Salience network disruption in U.S. army soldiers with posttraumatic stress disorder. Chronic Stress 2019;3:2470547019850467. PubMed PMC

Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V, et al. Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci. 2009;29:8586–94. PubMed PMC

Guell X, Schmahmann JD, Gabrieli J, Ghosh SS. Functional gradients of the cerebellum. Elife 2018;7:e36652. PubMed PMC

Ke J, Zhang L, Qi R, Xu Q, Li W, Hou C, et al. Altered blood oxygen level-dependent signal variability in chronic post-traumatic stress disorder during symptom provocation. Neuropsychiatr Dis Treat. 2015;11:1805–15. PubMed PMC

Claassen J, Labrenz F, Ernst TM, Icenhour A, Langhorst J, Forsting M, et al. Altered cerebellar activity in visceral pain-related fear conditioning in irritable bowel syndrome. Cerebellum. 2017;16:508–17. PubMed

Frings M, Maschke M, Erichsen M, Jentzen W, Muller SP, Kolb FP, et al. Involvement of the human cerebellum in fear-conditioned potentiation of the acoustic startle response: a PET study. Neuroreport. 2002;13:1275–8. PubMed

Sacchetti B, Baldi E, Lorenzini CA, Bucherelli C. Cerebellar role in fear-conditioning consolidation. Proc Natl Acad Sci USA. 2002;99:8406–11. PubMed PMC

Batsikadze G, Diekmann N, Ernst TM, Klein M, Maderwald S, Deuschl C, et al. The cerebellum contributes to context-effects during fear extinction learning: A 7T fMRI study. Neuroimage. 2022;253:119080. PubMed

Fullana MA, Albajes-Eizagirre A, Soriano-Mas C, Vervliet B, Cardoner N, Benet O, et al. Fear extinction in the human brain: A meta-analysis of fMRI studies in healthy participants. Neurosci Biobehav Rev. 2018;88:16–25. PubMed

Utz A, Thurling M, Ernst TM, Hermann A, Stark R, Wolf OT, et al. Cerebellar vermis contributes to the extinction of conditioned fear. Neurosci Lett. 2015;604:173–7. PubMed

Habas C, Manto M. Probing the neuroanatomy of the cerebellum using tractography. Handb Clin Neurol. 2018;154:235–49. PubMed

Koutsikou S, Crook JJ, Earl EV, Leith JL, Watson TC, Lumb BM, et al. Neural substrates underlying fear-evoked freezing: the periaqueductal grey-cerebellar link. J Physiol. 2014;592:2197–213. PubMed PMC

Thome J, Densmore M, Frewen PA, McKinnon MC, Theberge J, Nicholson AA, et al. Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder. Hum Brain Mapp. 2017;38:27–40. PubMed PMC

Bushara KO, Wheat JM, Khan A, Mock BJ, Turski PA, Sorenson J, et al. Multiple tactile maps in the human cerebellum. Neuroreport. 2001;12:2483–6. PubMed

Grodd W, Hulsmann E, Lotze M, Wildgruber D, Erb M. Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization. Hum Brain Mapp. 2001;13:55–73. PubMed PMC

Twamley EW, Allard CB, Thorp SR, Norman SB, Hami Cissell S, Hughes Berardi K, et al. Cognitive impairment and functioning in PTSD related to intimate partner violence. J Int Neuropsychol Soc. 2009;15:879–87. PubMed

Aupperle RL, Melrose AJ, Stein MB, Paulus MP. Executive function and PTSD: disengaging from trauma. Neuropharmacology. 2012;62:686–94. PubMed PMC

Argyropoulos GPD, van Dun K, Adamaszek M, Leggio M, Manto M, Masciullo M, et al. The cerebellar cognitive affective/Schmahmann Syndrome: a task force paper. Cerebellum. 2020;19:102–25. PubMed PMC

Xu LY, Xu FC, Liu C, Ji YF, Wu JM, Wang Y, et al. Relationship between cerebellar structure and emotional memory in depression. Brain Behav. 2017;7:e00738. PubMed PMC

O’Donnell ML, Creamer M, Pattison P. Posttraumatic stress disorder and depression following trauma: understanding comorbidity. Am J Psychiatry. 2004;161:1390–6. PubMed

Brady KT, Killeen TK, Brewerton T, Lucerini S. Comorbidity of psychiatric disorders and posttraumatic stress disorder. J Clin Psychiatry. 2000;61:22–32. PubMed

Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14:365–76. PubMed

Cattaneo Z, Ferrari C, Ciricugno A, Heleven E, Schutter D, Manto M, et al. New horizons on non-invasive brain stimulation of the social and affective cerebellum. Cerebellum. 2022;21:482–96. PubMed

Tomlinson SP, Davis NJ, Bracewell RM. Brain stimulation studies of non-motor cerebellar function: a systematic review. Neurosci Biobehav Rev. 2013;37:766–89. PubMed

Depping MS, Nolte HM, Hirjak D, Palm E, Hofer S, Stieltjes B, et al. Cerebellar volume change in response to electroconvulsive therapy in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017;73:31–35. PubMed

Vuper TC, Philippi CL, Bruce SE. Altered resting-state functional connectivity of the default mode and central executive networks following cognitive processing therapy for PTSD. Behav Brain Res. 2021;409:113312. PubMed PMC

Harricharan S, Rabellino D, Frewen PA, Densmore M, Theberge J, McKinnon MC, et al. fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype. Brain Behav. 2016;6:e00579. PubMed PMC

Nicholson AA, Friston KJ, Zeidman P, Harricharan S, McKinnon MC, Densmore M, et al. Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry. Hum Brain Mapp. 2017;38:5551–61. PubMed PMC

Nicholson AA, Densmore M, Frewen PA, Theberge J, Neufeld RW, McKinnon MC, et al. The dissociative subtype of posttraumatic stress disorder: unique resting-state functional connectivity of basolateral and centromedial amygdala complexes. Neuropsychopharmacology. 2015;40:2317–26. PubMed PMC

Lebois LAM, Harnett NG, van Rooij SJH, Ely TD, Jovanovic T, Bruce SE, et al. Persistent dissociation and its neural correlates in predicting outcomes after trauma exposure. Am J Psychiatry. 2022;179:661–72. PubMed PMC

Terpou BA, Densmore M, Thome J, Frewen P, McKinnon MC, Lanius RA. The innate alarm system and subliminal threat presentation in posttraumatic stress disorder: neuroimaging of the midbrain and cerebellum. Chronic Stress. 2019;3:2470547018821496. PubMed PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...