Functional Disruption of Cerebello-thalamo-cortical Networks in Obsessive-Compulsive Disorder

Sha, Zhiqiang; Edmiston, E. Kale; Versace, Amelia; Fournier, Jay C.; Graur, Simona; Greenberg, Tsafrir; Santos, João Paulo Lima; Chase, Henry W.; Stiffler, Richelle; Bonar, Lisa; Hudak, Robert; Yendiki, Anastasia; Greenberg, Benjamin D.; Rasmussen, Steven A.; Liu, Hesheng; Quirk, Gregory J.; Haber, Suzanne N.; Phillips, Mary L.

doi:10.1016/j.bpsc.2019.12.002

Cited by 22 publications

(19 citation statements)

References 91 publications

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“…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. Our results suggest that a common neuronal mechanism may underlie both cognitive and clinical scores, in means of interference control (filtering or suppression of irrelevant or intrusive information).…”

Section: Discussionsupporting

confidence: 92%

Functional Connectivity Changes in Obsessive–Compulsive Disorder Correspond to Interference Control and Obsessions Severity

et al. 2020

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Introduction: Deficits in neurocognitive mechanisms such as inhibition control and cognitive flexibility have been suggested to mediate the symptoms in obsessive-compulsive disorder (OCD). These mechanisms are proposedly controlled by the "affective" and "executive" orbitofronto-striato-thalamo-cortical (CSTC) circuits with well-documented morphological and functional alterations in OCD that are associated with OCD symptoms. The precuneus region has been suggested in OCD as another key structure associated with the mechanism of "thought-action fusion." Our study aimed to elucidate the association of the altered functional coupling of the CSTC nodes (and precuneus), the OCD symptoms, and interference control/cognitive flexibility. Methods: In a group of 36 (17 medicated and 19 drug-free) OCD patients and matched healthy volunteers, we tested functional connectivity (FC) within the constituents of the dorsolateral prefrontal cortex "executive" CSTC, the orbitofrontal cortex/anterior cingulate "affective" CSTC, and precuneus. The functional connections showing the strongest effects were subsequently entered as explanatory variables to multiple regression analyses to identify possible associations between observed alterations of functional coupling and cognitive (Stroop test) and clinical measures (obsessions, compulsions, and anxiety level). Results: We observed increased FC (FWE p < 0.05 corr.) between CSTC seeds and regions of the parieto-occipital cortex, and between the precuneus and the angular gyrus and dorsolateral prefrontal cortex. Decreased FC was observed within the CSTC loop (caudate nucleus and thalamus) and between the anterior cingulate cortex and the limbic lobe. Linear regression identified a relationship between the altered functional coupling of thalamus with the right somatomotor parietal cortex and the Stroop color-word score. Similar association of thalamus FC has been identified also for obsessions severity. No association was observed for compulsions and anxiety. Conclusions: Our findings demonstrate altered FC in OCD patients with a prevailing increase in FC originating in CSTC regions toward other cortical areas, and a decrease in FC within the constituents of CSTC loops. Moreover, our results support the role of Fajnerova et al. Altered Rest-FC and Cognitive Interference in OCD precuneus in OCD. The association of the cognitive and clinical symptoms with the FC between the thalamus and somatomotor cortex indicates that cognitive flexibility and inhibitory control are strongly linked and both mechanisms might contribute to the symptomatology of OCD.

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Section: Discussionsupporting

confidence: 92%

Functional Connectivity Changes in Obsessive–Compulsive Disorder Correspond to Interference Control and Obsessions Severity

et al. 2020

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“…Indeed, recent literature has shown cerebellar involvement in psychiatric diseases and neurodevelopmental disorders, specifically in schizophrenia, autism and obsessive-compulsive disorder [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Furthermore, in recent years, some evidence has highlighted the potential role of the cerebellum in other psychiatric conditions characterized by mood swings, such as bipolar disorder [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Cerebellar Grey Matter Alterations in Bipolar and Cerebellar Patients: Evidence from Voxel-Based Analysis

Lupo

Olivito

Gragnani

et al. 2021

IJMS

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The aim of this study was to compare the patterns of cerebellar alterations associated with bipolar disease with those induced by the presence of cerebellar neurodegenerative pathologies to clarify the potential cerebellar contribution to bipolar affective disturbance. Twenty-nine patients affected by bipolar disorder, 32 subjects affected by cerebellar neurodegenerative pathologies, and 37 age-matched healthy subjects underwent a 3T MRI protocol. A voxel-based morphometry analysis was used to show similarities and differences in cerebellar grey matter (GM) loss between the groups. We found a pattern of GM cerebellar alterations in both bipolar and cerebellar groups that involved the anterior and posterior cerebellar regions (p = 0.05). The direct comparison between bipolar and cerebellar patients demonstrated a significant difference in GM loss in cerebellar neurodegenerative patients in the bilateral anterior and posterior motor cerebellar regions, such as lobules I−IV, V, VI, VIIIa, VIIIb, IX, VIIb and vermis VI, while a pattern of overlapping GM loss was evident in right lobule V, right crus I and bilateral crus II. Our findings showed, for the first time, common and different alteration patterns of specific cerebellar lobules in bipolar and neurodegenerative cerebellar patients, which allowed us to hypothesize a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder.

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“…We illustrate a case of OCD possibly secondary to a posterior cerebellar infarct, supporting the role of the cerebellum in the pathophysiology of OCD 3 . That OCD was perhaps secondary to the posterior cerebellar lesion is supported by several lines of evidence.…”

Section: Resultsmentioning

confidence: 54%

“…Cortico-striato-thalamocortical circuitry dysfunction is central to an integrated neuroscience formulation of obsessive-compulsive disorder (OCD) 1 , 2 . However, more recent large-scale brain connectivity analyses implicate the role of the cerebello-thalamocortical networks also 3 . Here, we report a case of OCD secondary to a cerebellar lesion.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Obsessive compulsive disorder in posterior cerebellar infarction - illustrating clinical and functional connectivity modulation using MRI-informed transcranial magnetic stimulation

et al. 2020

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Objectives: We describe atypical and resistant neuropsychiatric clinical manifestations in a young male with posterior cerebellar gliosis. We also attempt to test the mediating role of the cerebellum in the clinical presentation by manipulating the frontal-cerebellar network using MRI-informed transcranial magnetic stimulation (TMS). Methods: A case report of a young adult male describing obsessive-compulsive symptoms, probably secondary to an infarct in the cerebellar right crus II, combined with an examination of behavioral and functional connectivity changes following TMS treatment. Results: Obsessions, compulsions, and pathological slowing were observed in the background of a posterior cerebellar infarct, along with impairments in vigilance, working memory, verbal fluency, visuospatial ability, and executive functions, in the absence of any motor coordination difficulties. These symptoms did not respond to escitalopram. MRI-informed intermittent theta-burst stimulation delivered to the pre-supplementary motor area identified based on its connectivity with the cerebellar lesion in the crus II resulted in partial improvement of symptoms with enhanced within and between-network modularity of the cerebellar network connectivity. Conclusion: We illustrate a case of OCD possibly secondary to a posterior cerebellar infarct, supporting the role of the cerebellum in the pathophysiology of OCD. Functional connectivity informed non-invasive neuromodulation demonstrated partial treatment response. A seriation technique showed extended connectivity of the cerebellar lesion regions following the neuromodulatory treatment.

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Functional Disruption of Cerebello-thalamo-cortical Networks in Obsessive-Compulsive Disorder

Cited by 22 publications

References 91 publications

Functional Connectivity Changes in Obsessive–Compulsive Disorder Correspond to Interference Control and Obsessions Severity

Functional Connectivity Changes in Obsessive–Compulsive Disorder Correspond to Interference Control and Obsessions Severity

Comparison of Cerebellar Grey Matter Alterations in Bipolar and Cerebellar Patients: Evidence from Voxel-Based Analysis

Case Report: Obsessive compulsive disorder in posterior cerebellar infarction - illustrating clinical and functional connectivity modulation using MRI-informed transcranial magnetic stimulation

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