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

Heritability by minor allele frequency.

<p>The x-axis represents all minor allele frequency bins tested while the y-axis represents resultant heritability in a given bin. Blue bars indicate TS and red bars indicate OCD. Error bars are shown.</p

GWAS and imputed heritability partitioned by minor allele frequency.

<p>Legend: MAF: minor allele frequency; GWAS: genome-wide association study; se: standard error; SNPs: single nucleotide polymorphisms.</p

Overall heritability analysis of obsessive-compulsive disorder and Tourette syndrome.

<p>Legend: se: standard error; SNPs: single nucleotide polymorphisms; TS: Tourette syndrome; OCD: Obsessive-compulsive disorder;</p>*<p>Average of 10 analyses of permuted phenotypes.</p>**<p>Sample size reduced to match size of TS sample.</p

Tourette Syndrome heritability by chromosome.

<p>Heritability (y-axis) per chromosome is plotted against chromosome length (x-axis). The red line represents heritability regressed on chromosome length and the 95% confidence interval around the slope of the regression model is represented by the red dashed lines. The black line represents the expected heritability per chromosome (based on size) regressed on chromosome length. Chromosomes 2, 5, 11, 12, 16, and 20 fall outside of the 95% confidence interval and appear to account for more heritability than expected based on chromosome length.</p

Obsessive-compulsive disorder heritability by chromosome.

<p>Heritability (y-axis) per chromosome is plotted against chromosome length (x-axis). The red line represents heritability regressed on chromosome length and the 95% confidence interval around the slope of the regression model is represented by the red dashed lines. The black line represents the expected heritability per chromosome (based on size) regressed on chromosome length. Chromosome 15 is shown in red to highlight its extreme deviation from the expected heritability based on chromosome length. Chromosomes 3, 10, 13, and 17 are also outside of the 95% interval and appear to account for more heritability than expected based on chromosome length.</p