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

Abstract

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.

Imbalance between the caudate and putamen connectivity in obsessive–compulsive disorder

“…Combined with the results mentioned above, the increased caudate connectivity may mainly originate from central CSTC structures (caudate) to the regions outside the CSTC loop. In accordance with recent evidence, increased connectivity between the caudate and regions outside the CSTC (e.g., the parieto-occipital cortex, the angular gyrus and dorsolateral prefrontal cortex) may counterbalance the disconnectivity of the traditional CSTC loops in OCD ( Fajnerova et al, 2020 ). Furthermore, the increased connectivity reported outside the CSTC (e.g., the frontal gyrus and temporal gyrus) could be related to visuo-spatial and sensory-motor processing, which may indirectly impact cognitive flexibility in OCD ( Wolff et al, 2017 ).…”

Executive Functioning in Chinese Patients With Obsessive Compulsive Disorder

“…Moreover, within the patient group, no significant performance differences were detected between patients who were classified as having either relatively mild or severe OCD symptoms. These results are unexpected and do not seem to support the view that impaired executive functioning is a core cognitive and pathophysiological feature of OCD (5)(6)(7)(8)(9). However, several factors partly related to limitations of the present study need to be considered before this conclusion can be well accepted.…”

“…Studies have shown that patients with OCD typically perform more poorly than matched healthy control participants (HCs) on neuropsychological tests involving high-level cognitive or 'executive' functions, including planning, working memory, cognitive flexibility, and inhibitory motor control (5)(6)(7). These results have led to the hypothesis that impaired executive functioning (EF), including hyper excitability of the orbital frontal cortex and its functional connections, is a core cognitive and pathophysiological feature of OCD (8,9). Indeed, the current dominant view on the neuropathology of OCD focuses on abnormalities in prefrontal-striatal circuits implicated in EF (10).…”

Four-Class Classification of Neuropsychiatric Disorders by Use of Functional Near-Infrared Spectroscopy Derived Biomarkers

“…For instance, hypoactivation in frontal lobe regions has been detected in patients with schizophrenia (SCZ) and major depressive disorder (MDD) during verbal fluency tasks when compared to their healthy counterparts [ 5 , 14 ]. Similarly, hyper- and hypo-connectivity between different brain regions during resting state have been identified in patients with schizophrenia (SCZ) [ 15 , 16 , 17 , 18 , 19 ] and major depressive disorder (MDD) [ 8 , 9 , 14 ], while decreased cerebral blood flow in bilateral symmetric regions of the inferior PFC has been detected in patients with obsessive compulsive disorder (OCD) when compared to their healthy counterparts [ 20 , 21 ]. PFC dysfunction in the form of hypo- or hyper-connectivity during resting state or hypoactivation during various cognitive tests (e.g., Stroop and verbal fluency test) has been extensively observed and reported in patient groups diagnosed with a variety of major neuropsychiatric disorders, which include SCZ, MDD, bipolar disorder (BD), post-traumatic stress disorder (PTSD), and attention deficiency and hyperactivity disorder (ADHD).…”