Hyper-influence of the orbitofrontal cortex over the ventral striatum in obsessive-compulsive disorder
Open accessAbstract
Dysfunction of the fronto-striato-thalamic circuit routing through the orbitofrontal cortex (OFC) is thought to play the main role in the pathophysiology of obsessive-compulsive disorder (OCD). Repetitious stimulation of the OFC-ventral striatum (VS) projections in mice has been shown to increase the firing of the postsynaptic VS cells and the frequency of OCD-like symptoms. Moreover, increased functional connectivity (FC) between the OFC and the VS has been reported in patients with OCD. While FC is a synchronous, non-directed correlation, the directed influence between these brain regions remains unclear in patients with OCD. We obtained resting state functional magnetic resonance imaging scans from 37 non-medicated patients with OCD and 38 matched healthy volunteers, and calculated bivariative voxel-wise Granger Causality (GC) to and from three striatal regions of interest (ROI) using a blind deconvolution procedure. Additionally, we conducted multivariative GC analysis to determine if the effect revealed by the bivariative voxel-wise GCA is mediated by another seed ROI. We found a significant hyper-influence of the OFC over the VS of subjects with OCD (p<.05, corrected). Multivariative GC analysis confirmed this effect (p<.05, corrected) and that it was not mediated by another brain area within the striatum. This is the first study investigating the directed influence of the fronto-striato-thalamic loop in non-medicated patients with OCD. We confirmed the hyperactive connection from the OFC to the VS that is consistent with previous animal studies. These findings provide evidence for the more detailed pathophysiology of OCD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hyperactivity in the OFC-striatum pathway plays a pivotal role in the pathology of compulsivity.
“Accumulating evidence from animal and clinical research has shown that hyperactivity in the OFC-striatum pathway plays a pivotal role in the pathology of compulsivity64–66.”
From Dissociable roles of prefrontal plasticity in decision-making strategy and execution of habitual behavior (2026) · cites this paper as [65]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Investigating causal relations by econometric models and cross-spectral methods
Granger, C. W. J. (1969) · Econometrica · doi:10.2307/1912791 · Cited by 22,989 · see citing works
The assessment of anxiety states by rating
HAMILTON, M. (1959) · British Journal of Medical Psychology · doi:10.1111/j.2044-8341.1959.tb00467.x · Cited by 11,455 · see citing works
Development of a Rating Scale for Primary Depressive Illness
Hamilton, M. (1967) · British Journal of Social and Clinical Psychology · doi:10.1111/j.2044-8260.1967.tb00530.x · Cited by 8,410 · see citing works
Investigating Causal Relations by Econometric Models and Cross-Spectral Methods
Granger, C. W. J. (2010) · Essays in Econometrics · doi:10.1017/cbo9780511753978.002 · Cited by 4,762 · see citing works
Friston, K. J., Harrison, L., & Penny, W. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00202-7 · Cited by 4,583 · see citing works
The reward circuit: linking primate anatomy and human imaging
Haber, S. N., & Knutson, B. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.129 · Cited by 3,718 · see citing works
DPARSF: a MATLAB toolbox for “pipeline” data analysis of resting-state fMRI
Yan (2010) · Frontiers in System Neuroscience · doi:10.3389/fnsys.2010.00013 · Cited by 3,475 · see citing works
Functional and Effective Connectivity: A Review
Friston, K. J. (2011) · Brain Connectivity · doi:10.1089/brain.2011.0008 · Cited by 3,415 · see citing works
Circular analysis in systems neuroscience: the dangers of double dipping
Kriegeskorte, N., Simmons, W. K., Bellgowan, P. S. F., & Baker, C. I. (2009) · Nature Neuroscience · doi:10.1038/nn.2303 · Cited by 2,696 · see citing works
Network modelling methods for FMRI
Smith, S. M., Miller, K. L., Salimi-Khorshidi, G., Webster, M., Beckmann, C. F., Nichols, T. E., Ramsey, J. D., & Woolrich, M. W. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.08.063 · Cited by 1,878 · see citing works
Menzies, L., Chamberlain, S. R., Laird, A. R., Thelen, S. M., Sahakian, B. J., & Bullmore, E. T. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.09.005 · Cited by 1,190 · see citing works
Functional connectivity of human striatum: a resting state FMRI study
Di Martino, A., Scheres, A., Margulies, D. S., Kelly, A. M. C., Uddin, L. Q., Shehzad, Z., Biswal, B., Walters, J. R., Castellanos, F. X., & Milham, M. P. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn041 · Cited by 1,090 · see citing works
Obsessive-compulsive disorder: An integrative genetic and neurobiological perspective
Pauls, D. L., Abramovitch, A., Rauch, S. L., & Geller, D. A. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3746 · Cited by 793 · see citing works
Weissenbacher, A., Kasess, C., Gerstl, F., Lanzenberger, R., Moser, E., & Windischberger, C. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.005 · Cited by 776 · see citing works
Altered corticostriatal functional connectivity in obsessive-compulsive disorder
Harrison, B. J., Soriano-Mas, C., Pujol, J., Ortiz, H., López-Solà, M., Hernández-Ribas, R., Deus, J., Alonso, P., Yücel, M., Pantelis, C., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.152 · Cited by 571 · see citing works
Repeated cortico-striatal stimulation generates persistent OCD-like behavior
Ahmari, S. E., Spellman, T., Douglass, N. L., Kheirbek, M. A., Simpson, H. B., Deisseroth, K., Gordon, J. A., & Hen, R. (2013) · Science · doi:10.1126/science.1234733 · Cited by 502 · cited 2× · see citing works
“Additionally, Ahmari et al. (2013) reported that repeated stimulation of the OFC–ventromedial striatum (VMS) projections in mice using optogenetics increased the firing of postsynaptic VMS cells and the frequency of overgrooming behavior, which represents OCD symptoms in mice.”
Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder
Figee, M., Luigjes, J., Smolders, R., Valencia-Alfonso, C.-E., van Wingen, G., de Kwaasteniet, B., Mantione, M., Ooms, P., de Koning, P., Vulink, N., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3344 · Cited by 466 · see citing works
Pittenger, C., Bloch, M. H., & Williams, K. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.09.006 · Cited by 426 · see citing works
Hamilton, J. P., Chen, G., Thomason, M. E., Schwartz, M., & Gotlib, I. H. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.46 · Cited by 329 · see citing works
Neural Primacy of the Salience Processing System in Schizophrenia
Palaniyappan, L. K., Simmonite, M., White, T. P., Liddle, E. B., & Liddle, P. F. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.027 · Cited by 297 · see citing works
Wu, G., Liao, W., Stramaglia, S., Ding, J.-R., Chen, H., & Marinazzo, D. (2013) · Medical Image Analysis · doi:10.1016/j.media.2013.01.003 · Cited by 279 · see citing works
de Koning, P. P., Figee, M., van den Munckhof, P., Schuurman, P. R., & Denys, D. (2011) · Current Psychiatry Reports · doi:10.1007/s11920-011-0200-8 · Cited by 202 · see citing works
Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder
Sakai, Y., Narumoto, J., Nishida, S., Nakamae, T., Yamada, K., Nishimura, T., & Fukui, K. (2011) · European Psychiatry · doi:10.1016/j.eurpsy.2010.09.005 · Cited by 173 · see citing works
Self-citationLiao, W., Ding, J., Marinazzo, D., Xu, Q., Wang, Z., Yuan, C., Zhang, Z., Lu, G., & Chen, H. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.11.007 · Cited by 171 · see citing works
Zang, Z., Yan, C., Dong, Z.-Y., Huang, J., & Zang, Y. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2011.10.006 · Cited by 170 · see citing works
Deshpande, G., Santhanam, P., & Hu, X. P. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.024 · Cited by 163 · see citing works
Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry
Kopell, B. H., & Greenberg, B. D. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.07.004 · Cited by 156 · see citing works
Deshpande, G., & Hu, X. P. (2012) · Brain Connectivity · doi:10.1089/brain.2012.0091 · Cited by 142 · see citing works
Schippers, M. B., Renken, R. J., & Keysers, C. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.02.008 · Cited by 104 · see citing works
Zhuang, J., LaConte, S. M., Peltier, S., Zhang, K., & Hu, X. P. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2004.11.007 · Cited by 97 · see citing works
Reliability and validity of the Japanese version of the Yale‐Brown Obsessive‐Compulsive Scale
NAKAJIMA, T., NAKAMURA, M., TAGA, C., YAMAGAMI, S., KIRIIKE, N., NAGATA, T., SAITOH, M., KINOSHITA, T., OKAJIMA, Y., HANADA, M., et al. (1995) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.1995.tb01875.x · Cited by 87 · see citing works
Miao, X., Wu, X., Li, R., Chen, K., & Li, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025546 · Cited by 75 · see citing works
BOLD Granger Causality Reflects Vascular Anatomy
Webb, J., Ferguson, M. A., Nielsen, J. A., & Anderson, J. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084279 · Cited by 57 · see citing works
Neurosurgical targets for compulsivity: What can we learn from acquired brain lesions?
Figee, M., Wielaard, I., Mazaheri, A., & Denys, D. A. J. P. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.01.005 · Cited by 53 · see citing works
Kujala, J., Sudre, G. P., Vartiainen, J., Liljeström, M., Mitchell, T. M., & Salmelin, R. H. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.01.057 · Cited by 24 · see citing works
From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder
Hendler, T., Gonen, T., Harel, E. V., & Sharon, H. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.017 · Cited by 7 · see citing works
Ooms, P., de Koning, P. P., & Denys, D. A. J. P. (2014) · doi:10.1002/9781118775349.ch66 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- MB, S.R., Gibbon, M., Williams, J.B.W., 1994. Structured Clinical Interview For Axis I DSM-IV Disorders-Patient Edition (CID-I/P). Biometrics Research Department, New York State Psychiatric Institute, New York.
- First MB, S.R., Gibbon, M., Williams, J.B.W., 2001. Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Non-patient Edition (SCID-I/NP). Biometrics Research Department, New York State Psychiatric Institute, New York.
Cited by
Sorted by citations
Fettes, P., Schulze, L., & Downar, J. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00025 · Cited by 299 · see citing works
Gonçalves, Ó. F., Carvalho, S., Leite, J., Fernandes-Gonçalves, A., Carracedo, A., & Sampaio, A. (2016) · Porto Biomedical Journal · doi:10.1016/j.pbj.2016.07.005 · Cited by 55 · see citing works
Functional neural mechanisms of sensory phenomena in obsessive-compulsive disorder
Brown, C., Shahab, R., Collins, K., Fleysher, L., Goodman, W. K., Burdick, K. E., & Stern, E. R. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.11.018 · Cited by 52 · see citing works
Dong, C., Yang, Q., Liang, J., Seger, C. A., Han, H., Ning, Y., Chen, Q., & Peng, Z. (2020) · Psychological Medicine · doi:10.1017/s0033291719001429 · Cited by 43 · see citing works
Perera, M. P. N., Gotsis, E. S., Bailey, N. W., Fitzgibbon, B. M., & Fitzgerald, P. B. (2024) · Cerebral Cortex · doi:10.1093/cercor/bhae327 · Cited by 34 · see citing works
Akkermans, S. E. A., Rheinheimer, N., Bruchhage, M. M. K., Durston, S., Brandeis, D., Banaschewski, T., Boecker-Schlier, R., Wolf, I., Williams, S. C. R., Buitelaar, J. K., et al. (2019) · Psychological Medicine · doi:10.1017/s0033291718003136 · Cited by 33 · see citing works
Haynes, W. I. A., Clair, A.-H., Fernandez-Vidal, S., Gholipour, B., Morgiève, M., & Mallet, L. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.01.005 · Cited by 29 · see citing works
Shan, P. W., Liu, W., Liu, C., Han, Y., Wang, L., Chen, Q., Tian, H., Sun, X., Luan, S., Lin, X., et al. (2019) · Journal of International Medical Research · doi:10.1177/0300060518807058 · Cited by 12 · see citing works
Shi, W., Tian, Y., Yang, H., Guo, H., Wen, B., Liu, Z., Zhang, Y., Han, S., & Cheng, J. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1529983 · Cited by 7 · see citing works
Nishat, E., Dockstader, C., Wheeler, A. L., Tan, T., Anderson, J. A. E., Mendlowitz, S., Mabbott, D. J., Arnold, P. D., & Ameis, S. H. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.632736 · Cited by 3 · see citing works
Asaoka, N., Pagano, D., & Hayashi, Y. (2026) · Nature Communications · doi:10.1038/s41467-026-75706-1
- Authors
- Abe, Y., Sakai, Y., Nishida, S., Nakamae, T., Yamada, K., Fukui, K., & Narumoto, J.
- Affiliations
- Kyoto Prefectural University of Medicine (JP)
- Corresponding author
- Abe, Yoshinari
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 25
- Issue
- 11
- Pages
- 1898-1905
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1462915242
- Cited by
- 56
- References
- 37
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2022: 3 · 2021: 12 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 3
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Neuropsychopharmacology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (26461753)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- obsessive-compulsive disorder, orbitofrontal cortex, ventral striatum, directed functional connectivity, Granger causality, resting-state fMRI, OCD pathophysiology
- MeSH terms
- Adult, Brain Mapping, Female, Humans, Interview, Psychological, Magnetic Resonance Imaging, Male, Neural Pathways, Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Psychotropic Drugs, Rest, Multivariate Analysis, Prefrontal Cortex, Ventral Striatum
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
