Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder
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Cortico‐striato‐thalamo‐cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive‐Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional‐connectivity MRI (rs‐fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs‐fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs‐fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity. Hum Brain Mapp 35:2852–2860, 2014. © 2013 Wiley Periodicals, Inc.
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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 [61]
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 [61]
A recent study found a significant negative correlation between ventral striatum and mOFC connectivity and YBOCS score.
“a recent study found a significant negative correlation between VS and mOFC connectivity and YBOCS score (Posner et al., 2014)”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Posner et al., 2014
Some groups have reported decreased connectivity between ventral striatum and frontal cortex regions in OCD.
“some groups have reported decreased connectivity between VS and frontal cortex regions (Admon et al., 2012; Posner et al., 2014)”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Posner et al., 2014
These studies employed seed-based analyses.
“these studies employed seed-based analyses(38–41).”
From Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder (2020) · cites this paper as [41]
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- Authors
- Posner, J., Marsh, R., Maia, T. V., Peterson, B. S., Gruber, A., & Simpson, H. B.
- Affiliations
- University of Lisbon (PT)
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2013-09-30
- Volume
- 35
- Issue
- 6
- Pages
- 2852-2860
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC4142493
- OpenAlex
- W1914669721
- Cited by
- 197
- References
- 46
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 25 · 2023: 16 · 2022: 13 · 2021: 17 · 2020: 22 · 2019: 13 · 2018: 16 · 2017: 10 · 2016: 23 · 2015: 18 · 2014: 6
- FWCI
- 17.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02mh074677-05)
- National Institute of Mental Health (K02 MH-74677, K24MH091555, R21MH093889, K23MH091249, K02-MH-074677)
- 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, cortico-striato-thalamo-cortical loop, resting-state functional connectivity, hypoconnectivity, unmedicated patients, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, globus pallidus, symptom severity
- MeSH terms
- Adult, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Rest, Young Adult
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