Trans-diagnostic comparison of response inhibition in Tourette’s disorder and obsessive-compulsive disorder

<p><b>Objectives:</b> Impaired response inhibition is related to neurodevelopmental disorders, such as Tourette’s disorder (TD) and obsessive-compulsive disorder (OCD). Unlike OCD, in which neural correlates of response inhibition have been extensively studied, TD literature is limited. By using a Stop-Signal task, we investigated the neural mechanisms underlying response inhibition deficits in TD compared to OCD and healthy controls (HCs).</p> <p><b>Methods:</b> Twenty-three TD patients, 20 OCD patients and 22 HCs were scanned (3T MRI). Region-of-interest analyses were performed between TD, OCD and HCs.</p> <p><b>Results:</b> Performance was similar across all subject groups. During inhibition TD compared with HCs showed higher right inferior parietal cortex (IPC) activation. During error processing TD compared with HCs showed hyperactivity in the left cerebellum, right mesencephalon, and right insula. Three-group comparison showed an effect of group for error-related activation in the supplementary motor area (SMA). Post-hoc analyses showed higher error-related SMA activity in TD compared with OCD and HCs. Error-related left cerebellar activity correlated positively with tic severity.</p> <p><b>Conclusions:</b> Hyperactivation of IPC during inhibition and a widespread hyperactivated network during error processing in TD suggest compensatory inhibition- and error-related circuit recruitment to boost task performance. The lack of overlap with activation pattern in OCD suggests such compensatory mechanism is TD-specific.</p

Cognitive control networks in OCD: A resting-state connectivity study in unmedicated patients with obsessive-compulsive disorder and their unaffected relatives

<p><b>Objectives:</b> Executive network deficits are putative neurocognitive endophenotypes for obsessive-compulsive disorder (OCD). Yet, unlike alterations in fronto-striatal and limbic connectivity, connectivity in the fronto-parietal (FPN) and cingulo-opercular (CON) networks involved in cognitive control has received little attention.</p> <p><b>Methods:</b> The coherence of FPN, CON and fronto-limbic networks was investigated in 39 unmedicated OCD patients, 16 of their unaffected siblings and 36 healthy controls using resting-state functional-connectivity MRI and a seed-based analysis approach.</p> <p><b>Results:</b> FPN and CON connectivity was similar for patients and controls. Siblings showed higher connectivity than patients within the CON, and between the CON and FPN compared to patients and controls (trend level). In OCD patients, but not in siblings, fronto-limbic hyperconnectivity was present compared to controls. In contrast to our expectations, no group differences in resting-state connectivity of the cognitive control networks were observed between OCD patients and controls.</p> <p><b>Conclusions:</b> The increased within- and between-network connectivity in siblings, but not in patients, could indicate a mechanism of increased cognitive control that may act as a protective mechanism. None of the observed network alterations can be considered an endophenotype for OCD since differences were present in either patients or siblings, but not in both groups.</p

Partial correlations of (sub)cortical volume and surface area with neuropsychological task performance, corrected for age, sex, education, and tGM volume.

<p>Partial correlations of (sub)cortical volume and surface area with neuropsychological task performance, corrected for age, sex, education, and tGM volume.</p

(Sub)cortical volume + cortical pial surface area group analysis.

<p>(Sub)cortical volume + cortical pial surface area group analysis.</p

Demographic and clinical data for patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls.

<p># chi-square ‡ One-way ANOVA * Tukey and Scheffe post-hoc tests.</p

Vertex-wise cortical thickness group analysis.

<p>Vertex-wise cortical thickness group analysis.</p

Between-group differences in cortical thickness and thickness and correlation with task performance.

<p>HC had increased cortical thickness in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, when compared with PD patients (a-d). Within the PD sample, we found a negative correlation between the left lateral occipital and lingual gyrus and performance on the RAVLT (e-f). Clusters were significant after multiple comparison correction with Monte Carlo simulations.</p

Behavioral data on the task switching paradigm for patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls.

<p>Behavioral data on the task switching paradigm for patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls.</p

The letter/digit task switching paradigm.

<p>In this example (consecutive trials are running from top-left to bottom-right) the events-of-interest are displayed. Subjects are presented two stimuli on each trial, i.e. a letter and a digit, for 4000 ms maximally. Subjects select either stimulus by pressing the left or right button on a button box, after which a fixation cross is presented for 500 ms. Each letter/digit pair is presented in either blue or red color. The trial color cues the task to be performed. In the letter task, subjects indicate whether the letter presented is a vowel or a consonant. In the digit task, subjects indicate whether the digit presented is odd or even. Two consecutive trials never contain the same letter or digit. Trial color changes, and therefore task switching, occurs randomly after 4–6 trials to avoid predictability. The first trials immediately after task switching are defined ‘switch events’ (SEs), all other trials as ‘repeat events’ (REs). Color-task and stimulus-response associations were counterbalanced across participants.</p

Group x task interaction effects on the task switching paradigm for the group of patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls. All activations at p<.001 uncorrected.

<p>Group x task interaction effects on the task switching paradigm for the group of patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls. All activations at p<.001 uncorrected.</p