Compensatory Frontoparietal Activity During Working Memory: An Endophenotype of Obsessive-Compulsive Disorder

• Published in: Biological psychiatry (1969) Vol. 76; no. 11; pp. 878 - 887
• Main Authors: de Vries, Froukje E, de Wit, Stella J, Cath, Danielle C, van der Werf, Ysbrand D, van der Borden, Vionne, van Rossum, Thomas B, van Balkom, Anton J.L.M, van der Wee, Nic J.A, Veltman, Dick J, van den Heuvel, Odile A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2014; Elsevier
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; Anxiety disorders. Neuroses; Biological and medical sciences; Brain Mapping; Endophenotype; Endophenotypes; Female; fMRI; Frontal Lobe - physiopathology; frontoparietal; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Memory, Short-Term - physiology; Middle Aged; n-back; obsessive-compulsive disorder; Obsessive-Compulsive Disorder - physiopathology; Obsessive-compulsive disorders; Parietal Lobe - physiopathology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Siblings; Spatial Memory - physiology; working memory; Young Adult; fMRI; n-back; working memory; frontoparietal; obsessive-compulsive disorder; Endophenotype; Obsessive compulsive disorder; Central nervous system; Anxiety disorder; Activity; Cognition; Frontal cortex; Nuclear magnetic resonance imaging; Encephalon; Compensation; Parietal cortex; Functional magnetic resonance imaging; Medical imagery; Working memory; Functional imaging
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2013.11.021

Background Subtle deficits in executive functioning are present in patients with obsessive-compulsive disorder (OCD) and their first-degree relatives, suggesting involvement of the frontoparietal circuits. The neural correlates of working memory may be a neurocognitive endophenotype of OCD. Methods Forty-three unmedicated OCD patients, 17 unaffected siblings, and 37 matched comparison subjects performed a visuospatial n-back task, with a baseline condition (N0) and three working memory load levels (N1, N2, N3) during functional magnetic resonance imaging. Task-related brain activity was compared between groups in frontoparietal regions of interest. Generalized psychophysiological interaction analyses were used to study task-related changes in functional connectivity. Results Obsessive-compulsive disorder patients, compared with comparison subjects and siblings, showed increased error rates at N3. Compared with comparison subjects, OCD patients showed task-related hyperactivation in left dorsal frontal areas and left precuneus associated with better task performance. Siblings exhibited hyperactivation in a bilateral frontoparietal network. Increased task load was associated with increased task-related brain activity, but in OCD patients and siblings this increase was smaller from load N2 to N3 than in comparison subjects. Obsessive-compulsive disorder patients, compared with siblings and comparison subjects, showed increased task-related functional connectivity between frontal regions and bilateral amygdala. Conclusions These findings indicate that compensatory frontoparietal brain activity in OCD patients and their unaffected relatives preserves task performance at low task loads but is insufficient to maintain performance at high task loads. Frontoparietal dysfunction may constitute a neurocognitive endophenotype for OCD, possibly reflecting limbic interference with and neural inefficiency within the frontoparietal network.