Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder
Open accessAbstract
Background Obsessive-compulsive disorder (OCD) is associated with regional hyperactivity in cortico-striatal circuits. However, the large-scale patterns of abnormal neural connectivity remain uncharacterized. Resting-state functional connectivity studies have shown altered connectivity within the implicated circuitry, but they have used seed-driven approaches wherein a circuit of interest is defined a priori. This limits their ability to identify network abnormalities beyond the prevailing framework. This limitation is particularly problematic within the prefrontal cortex (PFC), which is large and heterogeneous and where a priori specification of seeds is therefore difficult. A hypothesis-neutral, data-driven approach to the analysis of connectivity is vital.Methods We analyzed resting-state functional connectivity data collected at 3T in 27 OCD patients and 66 matched control subjects with a recently developed data-driven global brain connectivity (GBC) method, both within the PFC and across the whole brain.Results We found clusters of decreased connectivity in the left lateral PFC in both whole-brain and PFC-restricted analyses. Increased GBC was found in the right putamen and left cerebellar cortex. Within regions of interest in the basal ganglia and thalamus, we identified increased GBC in dorsal striatum and anterior thalamus, which was reduced in patients on medication. The ventral striatum/nucleus accumbens exhibited decreased global connectivity but increased connectivity specifically with the ventral anterior cingulate cortex in subjects with OCD.Conclusions These findings identify previously uncharacterized PFC and basal ganglia dysconnectivity in OCD and reveal differentially altered GBC in dorsal and ventral striatum. Results highlight complex disturbances in PFC networks, which could contribute to disrupted cortical-striatal-cerebellar circuits in OCD.
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Resting state fMRI studies generally support a role for cortical-basal ganglia circuit dysfunction in OCD, demonstrating abnormal connectivity of OFC, ACC, ventral striatum, dorsal striatum, putamen, and anterior thalamus.
“recent fMRI studies of resting state connectivity have also generally supported a role for cortical-basal ganglia circuit dysfunction in OCD, demonstrating abnormal connectivity of orbitofrontal cortex 60–62, anterior cingulate 61,63, ventral striatum 61–63, dorsal striatum 62,63, putamen 60,63, and anterior thalamus 63.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [63]
Other regions including subthalamic nucleus, cerebellum, and temporal cortex have also been implicated in OCD, and directionality of findings varies across studies.
“other regions including subthalamic nucleus 60, cerebellum 63,64, and temporal cortex 64 have also been implicated, and directionality of findings varies across studies”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [63]
These studies did not assess specific thalamic connections, whereas we showed greater connectivity between the thalamus and SMN using whole-brain network analysis, thereby refining understanding of thalamic connectivity in OCD.
“These studies did not assess specific thalamic connections, whereas we showed greater connectivity between the thalamus and SMN using whole-brain network analysis, thereby refining our understanding of thalamic connectivity in OCD.”
From Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder (2020) · cites this paper as [34]
Permutation testing (N=10,000) was used to test differences in network strength between OCD and healthy participants, controlling for age, gender, and scanner, with Bonferroni correction for 9 comparisons.
“Finally, we used permutation testing(N=10,000) to test for differences in network strength between OCD and healthy participants(PBonferroni<0.05 for 9 comparisons), controlling for age, gender, and scanner(9,14,34).”
From Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder (2020) · cites this paper as [34]
Resting-state functional connectivity studies report greater global connectivity in the posterior cerebellum in OCD.
“Resting-state functional connectivity studies report greater global connectivity in the posterior cerebellum in OCD(34,35).”
From Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder (2020) · cites this paper as [34]
Others report elevated FPN-thalamic connectivity and thalamic global connectivity in OCD.
“Others report elevated FPN-thalamic connectivity(17,77) and thalamic global connectivity in OCD(34).”
From Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder (2020) · cites this paper as [34]
Reduced dorsal caudate-anterior thalamus functional connectivity on resting-state fMRI is associated with symptomatic improvement following fluoxetine in OCD.
“On resting-state fMRI, reduced dorsal caudate-anterior thalamus functional connectivity was associated with symptomatic improvement following fluoxetine (Anticevic et al., 2014).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Anticevic et al., 2014
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Ji, J. L., Diehl, C., Schleifer, C. H., Tamminga, C. A., Keshavan, M. S., Sweeney, J. A., Clementz, B. A., Hill, S. K., Pearlson, G. D., Yang, G., et al. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy306 · Cited by 42 · see citing works
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- Authors
- Anticevic, A., Hu, S., Zhang, S., Savic, A., Billingslea, E., Wasylink, S., Repovs, G., Cole, M. W., Bednarski, S., Krystal, J. H., Bloch, M. H., Li, C.-S. R., & Pittenger, C.
- Affiliations
- Yale University (US)
- Washington University in St. Louis (US)
- Corresponding author
- Pittenger, Christopher
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 75
- Issue
- 8
- Pages
- 595-605
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3969771
- OpenAlex
- W2009341243
- Cited by
- 268
- References
- 84
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 19 · 2023: 14 · 2022: 28 · 2021: 19 · 2020: 27 · 2019: 23 · 2018: 25 · 2017: 19 · 2016: 29 · 2015: 20 · 2014: 17 · 2013: 1
- FWCI
- 24.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- The Yale Center for Clinical Investigation (UL1RR024139)
- The Fullbright Foundation (K99MH0968010 (MWC), K08MH081190 (CP), R01MH095790 (CP))
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- obsessive-compulsive disorder, resting-state functional connectivity, global brain connectivity, basal ganglia, dorsal striatum, ventral striatum, nucleus accumbens, cerebellum, anterior thalamic nuclei, antipsychotic effects, ventral anterior cingulate cortex
- MeSH terms
- Adolescent, Adult, Aged, Brain, Brain Mapping, Cerebellum, Corpus Striatum, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Obsessive-Compulsive Disorder, Rest, Young Adult
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