Functional disruption of cerebello-thalamo-cortical networks in obsessive-compulsive disorder
Open accessAbstract
Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. Neuroimaging studies have implicated altered connectivity among the functional networks of the cerebral cortex in the pathophysiology of OCD. However, there has been no comprehensive investigation of the cross-talk between the cerebellum and functional networks in the cerebral cortex.Methods This functional neuroimaging study was completed by 44 adult participants with OCD and 43 healthy control participants. We performed large-scale data-driven brain network analysis to identify functional connectivity patterns using resting-state functional magnetic resonance imaging data.Results Participants with OCD showed lower functional connectivity within the somatomotor network and greater functional connectivity among the somatomotor network, cerebellum, and subcortical network (e.g., thalamus and pallidum; all p < .005). Network-based statistics analyses demonstrated one component comprising connectivity within the somatomotor network that showed lower connectivity and a second component comprising connectivity among the somatomotor network, and motor regions in particular, and the cerebellum that showed greater connectivity in participants with OCD relative to healthy control participants. In participants with OCD, abnormal connectivity across both network-based statistics-derived components positively correlated with OCD symptom severity (p = .006).Conclusions To our knowledge, this study is the first comprehensive investigation of large-scale network alteration across the cerebral cortex, subcortical regions, and cerebellum in OCD. Our findings highlight a critical role of the cerebellum in the pathophysiology of OCD.
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- Findingown data
OCD participants showed greater connectivity between the SMN and the subcortical network compared with healthy participants.
“greater connectivity between the SMN and SCN(T=2.81,P=0.003)”
Quote in the paperSubstantial claim - Findingown data
OCD participants showed lower connectivity in the somatomotor network compared with healthy participants.
“We observed lower connectivity in the SMN(T=−2.82,P=0.003)”
Quote in the paperSubstantial claim - Findingown data
In OCD participants, the SMN showed greater connectivity with the thalamus compared with healthy participants.
“The SMN showed greater connectivity with the thalamus(T=2.54,P=0.005)”
Quote in the paperSubstantial claim - Findingown data
In OCD participants, the SMN showed greater connectivity with the pallidum compared with healthy participants.
“and pallidum(T=2.69,P=0.005) in the SCN”
Quote in the paperSubstantial claim - Findingown data
Only one connectivity PLS component (PLS1) explained more than 20% of the variance in Y-BOCS scores (44.2%).
“Only one connectivity PLS component(the first,PLS1) explained more than 20% of the variance in Y-BOCS scores(PLS1: 44.2%).”
Quote in the paperSubstantial claim
- Findingown data
OCD participants showed greater connectivity between the SMN and the cerebellum compared with healthy participants.
“between the SMN and cerebellum(T=3.26,P=0.001) in OCD”
Quote in the paperSubstantial claim - Findingown data
In OCD participants, the SMN showed greater connectivity with the limbic, frontoparietal, and default-mode nodes of the cerebellum compared with healthy participants.
“with the limbic(T=2.65,P=0.005), frontoparietal(T=3.45,P<0.001) and default-mode nodes(T=2.92,P=0.002) in the cerebellum”
Quote in the paperSubstantial claim - Findingown data
OCD participants showed greater connectivity in the cerebellum compared with healthy participants.
“greater connectivity in the cerebellum(T=2.87,P=0.003,Fig.1A,Table2) in OCD versus HC”
Quote in the paperSubstantial claim - Findingown data
Across both groups, there was a negative correlation between Component 1 and Component 2 connectivity (R=-0.73, P<0.001).
“There was a negative correlation between Components 1 and 2 across both groups(R=−0.73,P<0.001;Fig.2C).”
Quote in the paperNot a substantial claim - Findingown data
OCD participants showed lower within-network connectivity in the SMN compared with healthy participants.
“We observed lower within-network SMN connectivity(T=−3.10,P=0.001)”
Quote in the paperSubstantial claim - Findingown data
The study found greater SMN-SCN connectivity in OCD.
“We identified lower connectivity within the SMN and greater SMN-SCN and SMN-cerebellar connectivity in OCD.”
Quote in the paperSubstantial claim - Findingown data
The connectivity patterns were linked to OCD symptoms.
“These connectivity patterns were also associated with OCD symptoms.”
Quote in the paperSubstantial claim - Findingown data
The study found greater SMN-cerebellar connectivity in OCD.
“We identified lower connectivity within the SMN and greater SMN-SCN and SMN-cerebellar connectivity in OCD.”
Quote in the paperSubstantial claim - Findingown data
The correlation between abnormal SMN-cerebellar connectivity and symptom severity was localized to the motor cortex and to ventral attention, frontoparietal, and default-mode nodes of the posterior cerebellum (Lobules VI-VIII and Crus I and II).
“These findings were localized to the motor cortex, as well as the ventral attention, frontoparietal and default-mode nodes of the posterior cerebellum(Lobules VI-VIII and Crus I and II).”
Quote in the paperSubstantial claim - Findingown data
The study found lower connectivity within the SMN in OCD.
“We identified lower connectivity within the SMN and greater SMN-SCN and SMN-cerebellar connectivity in OCD.”
Quote in the paperSubstantial claim - Findingown data
Using NBS components that showed between-group differences in network connectivity, a positive correlation was found between abnormal SMN-cerebellar connectivity and OCD symptom severity, as measured by the Y-BOCS, in OCD participants.
“Using NBS components showing between-group differences in network connectivity, we observed a positive correlation between abnormal SMN-cerebellar connectivity and OCD symptom severity, as measured by the Y-BOCS, in OCD participants.”
Quote in the paperSubstantial claim - Premisecitation
The cerebellum is involved in developing habits.
“The cerebellum is also involved in developing habits(28).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Watson, 2018, Conflicted between goal-directed and habitual control, an fMRI investigation, eNeuro source
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- Premisecitation
There is evidence for cerebellar dysfunction in OCD.
“There is evidence for cerebellar dysfunction in OCD(31), however.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Zhang, 2019, Altered functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical circuit in obsessive-compulsive disorder, Frontiers in Psychiatry source
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- Premisecitation
Disrupted functional connectivity within and among cortical networks is present in OCD.
“These studies indicate disrupted functional connectivity within and among cortical networks in OCD”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [9] Shin, 2014, The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder, Biol Psychiatry source
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- cites [24] Reggente, 2018, Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder, Proc Natl Acad Sci U S A source
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- Interpretationcitation
The somatomotor cortex is a potential treatment target in OCD.
“These findings suggest that the somatomotor cortex is a potential treatment target in OCD.”
Quote in the paperSubstantial claim - Interpretationcitation
Our findings are consistent with an emerging model for OCD that suggests heightened internal focus mediated by increased between-network rsFC.
“Overall, our findings are consistent with an emerging model for OCD that suggests heightened internal focus mediated by increased between-network rsFC(63).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [63] Rossi, 2005, Hypofunctioning of sensory gating mechanisms in patients with obsessive-compulsive disorder, Biol Psychiatry source
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- Interpretationown data
These findings implicate cortical and subcortical networks and the cerebellum in the pathophysiology of OCD.
“These findings implicate cortical and subcortical networks and the cerebellum in the pathophysiology of OCD.”
Quote in the paperSubstantial claim - Study design and conductown data
The overall pattern of findings persisted when replacing the functional parcellation with 228 nodes and 428 nodes, excluding effects of head motion, medicated participants, and TRIO scanner.
“We repeated network strength, and within- and between-network connectivity, analyses replacing the functional parcellation with 228 nodes(TableS1) and 428 nodes(TableS2), excluding effects of head motion(TableS3), and medicated participants(TableS4) and TRIO scanner(TableS5). The overall pattern of findings persisted.”
Quote in the paperSubstantial claim - Premisecitation
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).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [34] Anticevic, 2014, Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder, Biol Psychiatry source
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- cites [35] Tian, 2016, Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study, Prog Neuropsychopharmacol Biol Psychiatry source
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- Premisecitation
Sensorimotor gating is impaired in OCD.
“Sensorimotor gating is impaired in OCD(67).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [67] Ahmari, 2012, Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder, Neuropsychopharmacology source
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- Study design and conductown data
Network strength findings in the SMN and cerebellum were replicated over the threshold range of 0.10≤Sparsity≤0.20.
“Network strength findings in the SMN and cerebellum were replicated over the threshold range of 0.10≤Sparsity≤0.20(Fig. S1)”
Quote in the paperNot a substantial claim - Interpretationcitation
Greater connectivity between these regions and the cortex might be associated with intrusive thoughts and compulsive behaviors in OCD.
“Greater connectivity between these regions and the cortex might be associated with intrusive thoughts and compulsive behaviors in OCD(5,22,76).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [5] Graybiel, 2000, Toward a neurobiology of obsessive-compulsive disorder, Neuron source
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- cites [22] Hou, 2013, Morphologic and functional connectivity alterations of corticostriatal and default mode network in treatment-naive patients with obsessive-compulsive disorder, PLoS One source
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- cites [76] Vaghi, 2017, Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: Evidence from resting-state functional connectivity, Biol Psychiatry source
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- Premisecitation
A meta-analysis of task-based fMRI studies showed greater activity in anterior lobules I-VI of the cerebellum during task switching and response inhibition in OCD.
“A meta-analysis of task-based fMRI studies showed greater activity in anterior lobules I-VI of the cerebellum during task switching and response inhibition(33).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] Eng, 2015, Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: An integrative review, Neurosci Biobehav Rev source
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- Interpretationreasoning
Disrupted cerebellar-cortical connectivity is implicated in the pathophysiology of OCD.
“These findings suggest that disrupted cerebellar-cortical connectivity is implicated in the pathophysiology of OCD”
Quote in the paperSubstantial claim - Premisecitation
These studies employed seed-based analyses.
“these studies employed seed-based analyses(38–41).”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [38] Harrison, 2013, Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder, Biol Psychiatry source
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- cites [39] Harrison, 2009, Altered corticostriatal functional connectivity in obsessive-compulsive disorder, Arch Gen Psychiatry source
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- cites [40] Fitzgerald, 2011, Developmental alterations of frontal-striatal-thalamic connectivity in obsessive-compulsive disorder, J Am Acad Child Adolesc Psychiatry source
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- cites [41] Posner, 2014, Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder, Hum Brain Mapp source
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- Premisecitation
OCD symptoms are positively correlated with parietal cortex-cerebellar connectivity.
“OCD symptoms are also positively correlated with parietal cortex-cerebellar connectivity(36,37).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [36] King, 2019, Functional boundaries in the human cerebellum revealed by a multi-domain task battery, Nat Neurosci source
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- cites [37] Xu, 2019, Altered resting-state cerebellar-cerebral functional connectivity in obsessive-compulsive disorder, Psychol Med source
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- Interpretationown data
The study found disrupted functional connectivity among specific cortical, subcortical, and cerebellar regions in OCD.
“Using large-scale network analysis, we observed disrupted functional connectivity among specific cortical, subcortical and cerebellar regions in OCD.”
Quote in the paperSubstantial claim - Interpretationnone given
Functional abnormalities in the cerebellum likely disrupt the function of connected cortical regions.
“Functional abnormalities in the cerebellum likely disrupt the function of connected cortical regions.”
Quote in the paperNot a substantial claim - Interpretationown data
We report elevated between-network connectivity in OCD participants, in regions that comprise the cerebello-thalamo-motor circuit.
“We report elevated between-network connectivity in OCD participants, in regions that comprise the cerebello-thalamo-motor circuit.”
Quote in the paperSubstantial claim - Interpretationown data
Our findings highlight elevated connectivity within the cerebellothalamo-motor circuit in OCD.
“Our findings highlight elevated connectivity within the cerebellothalamo-motor circuit in OCD.”
Quote in the paperSubstantial claim - Interpretationcitation
Elevated posterior cerebellar connectivity may contribute to disrupted executive control and attention shifting that underlies obsessional thoughts and compulsive behaviors in OCD.
“Elevated posterior cerebellar connectivity might be involved in disrupted executive control and attention shifting that reflects the obsessional thoughts and compulsive behaviors in OCD(94).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [94] Ravizza, 2001, Comparison of the basal ganglia and cerebellum in shifting attention, J Cogn Neurosci source
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- Interpretationcitation
Altered connectivity in these regions might underlie sensorimotor gating anomalies in OCD described in prepulse inhibition studies.
“Altered connectivity in these regions might underlie sensorimotor gating anomalies in OCD described in prepulse inhibition studies(88).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [88] Middleton, 2000, Basal ganglia and cerebellar loops: Motor and cognitive circuits, Brain Res Brain Res Rev source
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- Interpretationcitation
The observed correlation between within-SMN and SMN-cerebellar connectivity is consistent with theories of reciprocal network connectivity in psychiatric disorders, which propose that reduced localized information processing may accompany increased information transfer between regions.
“This is consistent with theories of reciprocal network connectivity(90,91) in psychiatric disorders, which posits that lower localized information processing might be associated with greater information transfer between regions.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [90] Mataix-Cols, 2004, Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder, Arch Gen Psychiatry source
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- cites [91] Zhou, 2010, Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease, Brain source
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- May combine two claims. 28
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 26
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Findingown dataNBS analysis identified a component (Component 1) with 30 nodes and 48 connections that showed lower connectivity in OCD participants, with all nodes restricted to the SMN (within-network).
“A component(Component 1) with 30 nodes and 48 connections showed significantly lower connectivity in OCD(Fig.2A). All these nodes were restricted to the SMN network, i.e., a within network component.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThere was a positive correlation between participant loadings on the PLS1 component and Y-BOCS scores (R=0.66, P<0.001), indicating that more abnormal connectivity was associated with greater symptom severity.
“There was a positive correlation between participant loadings on the PLS1 component and Y-BOCS scores(R=0.66,P<0.001;Fig.2D), indicating that more abnormal connectivity was associated with greater symptom severity.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn OCD participants, greater SMN-cerebellum connectivity was specific to the limbic, frontoparietal, and default-mode nodes (Crus I and II), but not the somatomotor nodes (Lobules I-V).
“OCD participants showed greater SMN-cerebellum connectivity, specifically, the limbic, frontoparietal and default-mode nodes(Crus I and II), but not the somatomotor nodes(Lobules I-V).”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataIn OCD participants, connectivity in NBS-derived components correlated with Y-BOCS scores (P=0.006), but not with anxiety (HAMA-14) or depressive symptom severity (HRSD-17) after correction.
“Connectivity correlated with Y-BOCS scores in OCD participants(P=0.006), but not with anxiety(HAMA-14,P=0.04) or depressive symptom severity(HRSD-17,P=0.03).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOCD participants had more severe depression, anxiety, and obsessive-compulsive symptoms than healthy participants.
“OCD participants had more severe depression(HRSD-17), anxiety(HAMA-14), and obsessive-compulsive symptoms(Y-BOCS,P<0.001;Table 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNBS analysis identified a component (Component 2) with 23 nodes and 28 connections that showed greater connectivity in OCD participants, linking regions in the motor cortex and cerebellum, including ventral attention, frontoparietal and default-mode nodes of the posterior cerebellum (Lobules VI-VIII and Crus I and II), i.e., a between-network component.
“There was one component with greater connectivity in OCD versus healthy participants(Component 2), which included 23 nodes and 28 connections linking regions in the motor cortex and cerebellum, including the ventral attention, frontoparietal and default-mode nodes of the posterior cerebellum(Lobules VI-VIII and Crus I and II), i.e., a between-network component(Fig.2B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataNetwork analysis showed greater connectivity in the thalamus and pallidum in OCD participants, and these connections were not disrupted in the NBS analysis.
“Our network analysis revealed greater connectivity in the thalamus and pallidum in OCD participants that were not disrupted in the NBS analysis.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPLS analysis showed associations between network connectivity and OCD symptom severity, but not anxiety or depressive symptom severity.
“PLS analysis revealed associations between network connectivity and OCD, but not anxiety and depressive, symptom severity.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn participants with OCD, within-SMN connectivity and SMN-cerebellar connectivity were significantly negatively correlated, with lower within-SMN connectivity associated with greater SMN-cerebellar connectivity.
“There was a significant correlation between the two NBS components comprising within-SMN connectivity and SMN-cerebellar connectivity in participants with OCD, such that participants with lower within-SMN connectivity had greater connectivity between the SMN and the cerebellum.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationOCD is associated with alterations in several large-scale cortical networks, including the frontoparietal, default-mode, salience, and limbic networks.
“Consistent with this range of symptoms, OCD is associated with alterations in several large-scale networks (e.g. the frontoparietal network(FPN), default-mode network(DMN), salience network(SN) and limbic network(LN,9,10).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [9] Shin, 2014, The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder, Biol Psychiatry source
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- cites [10] Zhang, 2011, Abnormal small-world architecture of top-down control networks in obsessive-compulsive disorder, J Psychiatry Neurosci source
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Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe cerebellum provides output to the cortex and tunes sensory input to facilitate behavioral adjustment in response to feedback.
“The cerebellum provides output to the cortex, and “tunes” sensory input to facilitate behavioral (particularly motor) adjustment in response to feedback(25–27).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [25] Stoodley, 2010, Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing, Cortex source
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- cites [26] Kelly, 2003, Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate, J Neurosci source
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- cites [27] Gao, 2018, A cortico-cerebellar loop for motor planning, Nature source
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InterpretationreasoningAlterations in cerebellar-cortical network connectivity might underlie habitual behavior dysfunction in OCD that occurs across multiple domains.
“Given these roles, and because the cerebellum provides output across the cortex(29), alterations in cerebellar-cortical network connectivity might underlie habitual behavior dysfunction in OCD that occurs across multiple domains(30).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [29] Buckner, 2013, The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging, Neuron source
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- cites [30] Gruner, 2016, Arbitration between action strategies in obsessive-compulsive disorder, Neuroscientist source
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA single photon emission computed tomography study revealed elevated regional cerebral blood flow in the cerebellum in OCD.
“A single photon emission computed tomography study revealed elevated regional cerebral blood flow in the cerebellum in OCD(32).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] Lacerda, 2003, Elevated thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder: a SPECT study, Psychiatry Res source
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Classified as probably not a substantial claim. May combine two claims.
Study design and conductown dataPLS analysis regressed out effects of sex, gender, and scanner, used 1,000 permutations, and Bonferroni correction for 3 parallel comparisons.
“Prior to PLS analysis, the effects of sex, gender and scanner were regressed out.”
- Also stated in: § Relationship between network connectivity and symptoms · plain
“The PLS components were considered significant at alpha=0.05 with 1,000 permutations, after permuting the clinical score labels assigned as each set of outcome variables.”
- Also stated in: § Relationship between network connectivity and symptoms · plain
“The statistical threshold for PLS analyses was set to P<0.05 for each PLS component, with Bonferroni correction for 3 parallel comparisons.”
Quote in the paperSubstantial claim- Also stated in: § Relationship between network connectivity and symptoms · plain
May combine two claims.
PremisecitationSMN changes have been associated with OCD treatment response, including greater somatomotor activity following cognitive behavior therapy.
“SMN changes have also been associated with OCD treatment response, including greater somatomotor activity following cognitive behavior therapy(68).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [68] Russo, 2014, Obsessive-compulsive disorder: A “sensory-motor” problem?, Int J Psychophysiol source
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Study design and conductown dataPermutation 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).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [9] Shin, 2014, The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder, Biol Psychiatry source
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- cites [14] Posner, 2017, Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder, Hum Brain Mapp source
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- cites [34] Anticevic, 2014, Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder, Biol Psychiatry source
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Study design and conductcitationWithin- and between-network connectivity analyses retained correlation coefficients of P<0.01 (FDR corrected) and selected only connections that remained for at least 50% of participants.
“We used the original weighted connectivity graph. Within these individual subject maps, we retained correlation coefficients of P<0.01, FDR corrected. All other correlations were set to zero. In order to ensure sufficient power, we selected only the connections that remained following FDR correction for at least 50% of the participants for statistical analysis(48).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [48] Schaefer, 2018, Local-global parcellation of the human cerebral cortex from intrinsic functional connectivity MRI, Cereb Cortex source
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Study design and conductown dataNBS used two-sample t-tests (P<0.001) controlling for age, gender, and scanner, with permutation tests (N=10,000) and family-wise error correction (PFWE<0.05).
“We utilized NBS to localize edge-level group differences in both positive and negative connectivity using two sample t tests(P<0.001), controlling for age, gender, and scanner(58).”
- Also stated in: § Network analysis · hedged
“A family-wise error(FWE)-corrected p-value(PFWE<0.05) for the network component was estimated by the proportion of permutations for which a component of greater size was identified.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [58] Li, 2019, Global signal regression strengthens association between resting-state functional connectivity and behavior, Neuroimage source
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- Also stated in: § Network analysis · hedged
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOthers 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).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [17] Stern, 2012, Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder, PLoS One source
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- cites [77] Woolley, 2008, Brain activation in paediatric obsessive compulsive disorder during tasks of inhibitory control, Br J Psychiatry source
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- cites [34] Anticevic, 2014, Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder, Biol Psychiatry source
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PremisecitationRepetitive low frequency transcranial magnetic stimulation to the somatomotor cortex normalizes activity and improves symptoms in OCD.
“Repetitive low frequency transcranial magnetic stimulation to the somatomotor cortex also normalizes activity and improves symptoms(69).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [69] Nabeyama, 2008, Functional MRI study of brain activation alterations in patients with obsessive-compulsive disorder after symptom improvement, Psychiatry Res source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAn OCD resting-state analysis demonstrated elevated connectivity between cerebellar and basal ganglia nodes that was associated with less cognitive flexibility.
“Consistent with our results, an OCD resting-state analysis demonstrated elevated connectivity between cerebellar and basal ganglia nodes that was associated with less cognitive flexibility(75).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [75] Bernard, 2014, Cerebellar-motor dysfunction in schizophrenia and psychosis-risk: The importance of regional cerebellar analysis approaches, Front Psychiatry source
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PremisecitationThe pallidum is involved in habitual behavior and learning.
“The pallidum is involved in habitual behavior and learning(78,79).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [78] Stern, 2011, Hyperactive error responses and altered connectivity in ventromedial and frontoinsular cortices in obsessive-compulsive disorder, Biol Psychiatry source
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- cites [79] Piron, 2016, The globus pallidus pars interna in goal-oriented and routine behaviors: Resolving a long-standing paradox, Mov Disord source
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InterpretationreasoningLower connectivity in the SMN and enhanced thalamic-SMN connectivity could be related to sensorimotor gating anomalies in OCD.
“Lower connectivity in the SMN and enhanced thalamic-SMN connectivity could be related to sensorimotor gating anomalies in OCD.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThe literature suggests that OCD symptoms are explained by aberrant functional connectivity among large-scale brain networks, including the FPN, SN, DMN and LN.
“While the literature suggests that OCD symptoms are explained by aberrant functional connectivity among large-scale brain networks, including the FPN, SN, DMN and LN(9,10)”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [9] Shin, 2014, The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder, Biol Psychiatry source
Not checked in the free run.
- cites [10] Zhang, 2011, Abnormal small-world architecture of top-down control networks in obsessive-compulsive disorder, J Psychiatry Neurosci source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCerebral-cerebellum connectivity disruption has been reported in several psychiatric disorders, including psychotic disorders, depressive disorder, autism and attention-deficit/hyperactivity disorder.
“Cerebral-cerebellum connectivity disruption has been reported in several psychiatric disorders, including psychotic disorders(70), depressive disorder(71), autism(72) and attention-deficit/hyperactivity disorder(73).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [70] Mantovani, 2010, Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder, Int J Neuropsychopharmacol source
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- cites [71] Cao, 2018, Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization, Nat Commun source
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- cites [72] Ma, 2013, Altered cerebellar–cerebral resting-state functional connectivity reliably identifies major depressive disorder, Brain Res source
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Study design and conductown dataThere were no significant between-group differences in age, gender, or educational attainment.
“There were no significant between-group differences in age, gender or educational attainment(P>0.05).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenThis study is the first comprehensive investigation of cerebello-cerebral network connectivity in OCD.
“To our knowledge, this study is the first comprehensive investigation of cerebello-cerebral network connectivity in OCD.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThese 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.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [17] Stern, 2012, Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder, PLoS One source
Not checked in the free run.
- cites [77] Woolley, 2008, Brain activation in paediatric obsessive compulsive disorder during tasks of inhibitory control, Br J Psychiatry source
Not checked in the free run.
- cites [34] Anticevic, 2014, Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder, Biol Psychiatry source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataThe robustness of brain network results was evaluated by examining network sparsity and effects of functional atlas, medication, head motion, and scanner.
“To evaluate the robustness of the brain network results, we examined network sparsity and the effects of functional atlas, medication, head motion, and scanner.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningBecause the basal ganglia and thalamus have heterogeneous functional subdivisions, the study could not determine how cytoarchitectonically distinct subdivisions might contribute to circuit alterations in OCD.
“Finally, due to heterogeneous functional subdivisions in the basal ganglia and thalamus, we were unable to pinpoint how cytoarchitectonically distinct subdivisions might be involved in circuit alterations in OCD.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThis circuit underlies motor control and learning via the integration of interoceptive, sensory, and motor information.
“This circuit underlies motor control and learning via the integration of interoceptive, sensory, and motor information(86,87).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [86] Alexander, 1986, Parallel organization of functionally segregated circuits linking basal ganglia and cortex, Annu Rev Neurosci source
Not checked in the free run.
- cites [87] D’Angelo, 2012, Seeking a unified framework for cerebellar function and dysfunction: From circuit operations to cognition, Front Neural Circuits
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe posterior cerebellum is regarded as the 'cognitive cerebellum' because it connects multiple cerebral cortex regions involved in executive function and attention switching.
“The posterior cerebellum is considered the “cognitive cerebellum”, because it links multiple regions of the cerebral cortex involved in executive function and attention switching(74,92,93).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [74] Durston, 2011, Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder, Biol Psychiatry source
Not checked in the free run.
- cites [92] Seeley, 2007, Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: Reciprocal networks and neuronal evolution, Alzheimer Dis Assoc Disord source
Not checked in the free run.
- cites [93] Stoodley, 2009, Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies, Neuroimage source
Not checked in the free run.
Classified as probably not a substantial claim.
InterpretationreasoningThe difference between the network analysis and NBS findings can be accounted for by methodological distinctions between the two approaches.
“This discrepancy can be explained by distinctions between these two methodologies.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPallidal damage produces compulsive behavior.
“pallidal damage produces compulsive behavior(5,81).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThere are two subsystems in the cerebello-thalamo-motor circuit: the cerebellar motor loop and the basal ganglia motor loop.
“There are two subsystems in this circuit. The first, the cerebellar motor loop, sends output from the cerebellum to the motor cortex via the superior cerebellar peduncle and ventrolateral thalamus. The cerebellum also receives input from the motor cortex through the pons(25,26). The second, the basal ganglia motor loop, comprises reciprocal connections between motor cortex and basal ganglia(e.g. p”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [25] Stoodley, 2010, Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing, Cortex source
Not checked in the free run.
- cites [26] Kelly, 2003, Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate, J Neurosci source
Not checked in the free run.
- cites [84] Baioui, 2013, Neural response in obsessive-compulsive washers depends on individual fit of triggers, Front Hum Neurosci source
Not checked in the free run.
- cites [85] DeLong MR, Georgopoulos AP (1981): Motor functions of the basal ganglia. In: Handbook of Physiology, Sec. 1, The Nervous System, Vol. 2: Motor Control. Part 2. American Physiological Society, 1017–1061. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPallidal, thalamic, and motor cortex activity is also associated with checking symptoms in OCD.
“Pallidal, thalamic, and motor cortex activity is also associated with checking symptoms in OCD(89).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [89] Geyer, 2006, The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?, Neurotox Res source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisereasoningNBS identifies significant components, analogous to clusters, with nodal connections analogous to voxels, using principles from conventional permutation testing of cluster-thresholded brain maps.
“Based on the principles underpinning traditional cluster-based thresholding of brain maps with permutation tests, NBS identifies significant components(similar to “clusters”) with nodal connections(similar to “voxels”).”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningOur findings of elevated SMN-thalamic and SMN-pallidal connectivity might underlie aberrant sensory integration and habit learning, respectively, in OCD.
“Our findings of elevated SMN-thalamic and SMN-pallidal connectivity might underlie aberrant sensory integration and habit learning, respectively, in OCD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe study used appropriate statistical correction approaches.
“Although we employed appropriate statistical correction approaches, replication studies with larger samples are needed to make generalizations about the overall OCD population.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationChanges in SMN and pallidal activity are associated with motor automation.
“Changes in SMN and pallidal activity are associated with motor automation(80)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [80] Pezzulo, 2014, Internally generated sequences in learning and executing goal-directed behavior, Trends Cogn Sci source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe study was cross-sectional and was not designed to assess illness course or risk for developing OCD.
“This study employed a cross-sectional approach and was not designed to assess effects of illness course or risk for the development of OCD.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOthers have reported pallidal hyperactivity and structural deficits in OCD.
“Others have reported pallidal hyperactivity and structural deficits in OCD(82,83).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [82] Laplane, 1989, Obsessive-compulsive and other behavioural changes with bilateral basal ganglia lesions. A neuropsychological, magnetic resonance imaging and positron tomography study, Brain source
Not checked in the free run.
- cites [83] Zarei, 2011, Changes in gray matter volume and white matter microstructure in adolescents with obsessive-compulsive disorder, Biol Psychiatry source
Not checked in the free run.
The paper relies on this without support.
Few studies have examined cerebellar-cortical network contributions in OCD.
“Yet, few studies have examined cerebellar-cortical network contributions in OCD.”
The paper relies on this without support.
The sample of OCD participants is representative of the broader OCD population.
“Forty-four adult participants with OCD and 43 healthy participants completed this functional neuroimaging study.”
The paper relies on this without support.
No prior study has comprehensively examined cerebellar-cerebral connectivity in OCD.
“To our knowledge, this study is the first to comprehensively examine cerebellar-cerebral connectivity in OCD.”
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?
Increased coupling between thalamus and the postcentral gyrus mediates severity of clinical symptoms, documented by convergent findings in obsessions and Stroop interference.
“In line with a recent study (79), our data suggest the important role of increased coupling between thalamus and the postcentral gyrus in mediating severity of clinical symptoms, documented by convergent findings in obsessions and Stroop interference.”
From Functional connectivity changes in obsessive-compulsive disorder correspond to interference control and obsessions severity (2020) · cites this paper as [79]
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“Others have reported pallidal hyperactivity and structural deficits in OCD(82,83).”
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- Authors
- Sha, Z., Edmiston, E. K., Versace, A., Fournier, J. C., Graur, S., Greenberg, T., Lima Santos, J. P., Chase, H. W., Stiffler, R. S., Bonar, L., Hudak, R., Yendiki, A., Greenberg, B. D., Rasmussen, S., Liu, H., Quirk, G., Haber, S., & Phillips, M. L.
- Affiliations
- University of Pittsburgh (US)
- Harvard University (US)
- Brown University (US)
- University of Puerto Rico, Medical Sciences Campus (PR)
- University of Rochester Medicine (US)
- Corresponding author
- Sha, Zhiqiang
- ORCID
- Venue
- Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 5
- Issue
- 4
- Pages
- 438-447
- ISSN
- 2451-9022 (ISSN-L)
- PMC
- PMC7150632
- OpenAlex
- W2998688799
- Cited by
- 48
- References
- 100
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 9 · 2023: 12 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 1
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pittsburgh Foundation
- National Institute of Mental Health (P50MH106435)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- obsessive-compulsive disorder, cerebellum, functional connectivity, sensorimotor network, subcortical network, thalamus, globus pallidus, network-based statistics, symptom severity, resting-state functional connectivity
- MeSH terms
- Adult, Brain, Cerebellum, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Obsessive-Compulsive Disorder
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.
Statistics and arithmetic are recomputed, not judged.
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