Abnormal striatal resting-state functional connectivity in adolescents with obsessive–compulsive disorder
Open accessAbstract
Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed.
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Frontostriatal functional connectivity stemming from the dlPFC and altered striatal connectivity to the insula are linked to OCD severity.
“Frontostriatal functional connectivity stemming from the dlPFC (Vaghi et al., 2016), and altered striatal connectivity to the insula (Bernstein et al., 2016) has been linked to OCD severity.”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Bernstein et al., 2016
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Variants of uncertainty in decision-making and their neural correlates
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ResultCorticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder
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“Consistent with functional connectivity study in OCD patients (Stern et al., 2012; Jhung et al., 2014; Bernstein et al., 2016), we found a small region of the insula that showed increased EC from the putamen in OCD patients only.”
BackgroundCyr, M., Pagliaccio, D., Yanes-Lukin, P. K., Fontaine, M., Rynn, M. A., & Marsh, R. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0613-3 · Cited by 41 · see citing works
“Previous findings from a small sample of youth with OCD (N= 15, 80% medicated) suggested reduced connectivity between left putamen and a cluster of regions in the salience/cingulo-opercular network, including a portion of the anterior insula [8].”
BackgroundCan Neuroimaging Provide Reliable Biomarkers for Obsessive-Compulsive Disorder? A Narrative Review
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Classification of obsessive-compulsive disorder from resting-state fMRI
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“More details of the preprocessing can be found in [6].”
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“, 2013) in OCD patients, two recent studies reported opposite results (Posner et al., 2014; Bernstein et al., 2016).”
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“For example, Obsessive-Compulsive Disorder has been linked to weak cortico-striatal connectivity (Bernstein et al., 2016), but also abnormally small striatum and hyperactivity of the cortico-striatal pathway during ObsessiveCompulsive Disorder symptomatic state (Rauch et al.”
BackgroundResting‐state connectivity and modulated somatomotor and default‐mode networks in Huntington disease
Sánchez‐Castañeda, C., de Pasquale, F., Caravasso, C. F., Marano, M., Maffi, S., Migliore, S., Sabatini, U., & Squitieri, F. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12701 · Cited by 21 · see citing works
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“Note that the ranking can be validated for OCD by considering the regions from CSTC circuitry [23].”
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Transcranial sonography in psychiatry as a potential tool in diagnosis and research
Drepper, C., Geissler, J. M., Pastura, G. M. C., Yılmaz, R., Berg, D., Romanos, M., & Gerlach, M. (2017) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2017.1386325 · Cited by 12 · see citing works
“It is generally assumed that the functional connectivity of the cortico-striatothalamocortical circuitry is affected in OCD (Bernstein et al. 2016; Chen et al. 2016; Tang et al. 2016), especially the decreased left CN-thalamus connectivity (Chen et al. 2016).”
BackgroundInfluentialHall, M. D., Gipson, K. S., Gipson, S. Y.-M. T., Colvin, M. K., Nguyen, S. T. T., & Greenberg, E. (2025) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000429 · Cited by 13 · see citing works
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Functional neuroimaging in Tourette syndrome: recent perspectives
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“83 In patients with ADHD, dysfunctions in the cortico-striatal-thalamo-cortical circuits, 84 changes in cortical thickness and gyrification, 85 changes in the serotonin transporter binding potential, 86 changes in callosal thickness, 87 and reduced gray matter volumes in various regions of the…”
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“The aforementioned GM alterations in the PFC combined with our findings support theories of prefrontal–striatal circuit abnormalities in pediatric OCD (66).”
ResultSuñol, M., Alemany, S., Bustamante, M., Diez, I. P., Contreras‐Rodríguez, O., Laudo, B., Macià, D., Martínez‐Vilavella, G., Martínez‐Zalacaín, I., Menchón, J. M., et al. (2021) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2021.11.009 · Cited by 5 · see citing works
“Youths and adults with OCD show reduced FC within this loop (11,65), and in adults, compulsivity has been associated with diminished resting-state activity within this area (66).”
BackgroundConnectome-wide Functional Connectivity Abnormalities in Youth With Obsessive-Compulsive Symptoms
Alexander‐Bloch, A. F., Sood, R., Shinohara, R. T., Moore, T. M., Calkins, M. E., Chertavian, C., Wolf, D. H., Gur, R. C., Satterthwaite, T. D., Gur, R. E., et al. (2021) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2021.07.014 · Cited by 5 · see citing works
Obsessive‐Compulsive and Related Disorders
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Neural correlates of doubt in decision-making
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Acute effects of deep brain stimulation on brain function in obsessive–compulsive disorder
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“…OCD have reported altered activation in frontal, cingulate, insula, and striatal regions during inhibitory control, error monitoring, and executive processing [8–11], whereas resting-state studies have further suggested abnor - mal connectivity among these regions and related networks [12–14 ].”
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“Numerous fMRI studies revealed abnormal FC between OCD and controls in regions like the frontal cortex, thalamus and cerebellum 16,17 , meta-analysis results indicated hypoconnectivity within corticostriato-thalamo-cortical circuit, frontoparietal and salience network, and between salience,…”
BackgroundStatic and Dynamic Connectivity Analysis of Human Brain via Functional Magnetic Resonance ImagingPreprint
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The Obsessive-Compulsive Dimension
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Research Overview of the application of fMRI in Psychiatric Disorders in Children and Adolescents
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“K = number of voxels; FDR = False Discovery Rate. considered to be heavily involved in the creation of habits (Graybiel 2008; Graybiel and Grafton, 2015; Bernstein et al., 2016; Xu et al., 2021; Sjoerds et al., 2013).”
- Authors
- Bernstein, G. A., Mueller, B. A., Schreiner, M. W., Campbell, S. M., Regan, E. K., Nelson, P. M., Houri, A. K., Lee, S. S., Zagoloff, A. D., Lim, K. O., Yacoub, E. S., & Cullen, K. R.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Bernstein, Gail A.
- ORCID
- Venue
- Psychiatry Research: Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 247
- Pages
- 49-56
- ISSN
- 0925-4927 (ISSN-L)
- PMC
- PMC4716880
- OpenAlex
- W2176956094
- Cited by
- 49
- References
- 60
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 4
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychiatry Research Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Minnesota Academic Health Center Seed Grant
- National Institutes of Health (R21MH101395)
- Human Connectome Project (1U54MH091657, 1P30NS076408, P41EB015894)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- pediatric obsessive-compulsive disorder, putamen, caudate nucleus, nucleus accumbens, salience network, insula, operculum, orbitofrontal cortex, adolescents, resting-state functional connectivity
- MeSH terms
- Adolescent, Brain, Brain Mapping, Cerebral Cortex, Child, Corpus Striatum, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Nucleus Accumbens, Obsessive-Compulsive Disorder, Putamen, Signal Processing, Computer-Assisted, Thalamus, Case-Control Studies, Prefrontal Cortex, Young Adult
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