title: Altered inhibition-related frontolimbic connectivity in obsessive-compulsive disorder.
abstract: BACKGROUND
  Recent studies have shown that response inhibition is impaired in patients with obsessive-compulsive disorder and their unaffected siblings, suggesting that these deficits may be considered a cognitive endophenotype of obsessive-compulsive disorder. Structural and functional neural correlates of altered response inhibition have been identified in patients and siblings. This study aims to examine the functional integrity of the response inhibition network in patients with obsessive-compulsive disorder and their unaffected siblings.
  
  
  METHODS
  Forty-one unmedicated patients with obsessive-compulsive disorder, 17 of their unaffected siblings and 37 healthy controls performed a stop signal task during functional magnetic resonance imaging. Psycho-physiological interaction analysis was used to examine functional connectivity between the following regions of interest: the bilateral inferior frontal gyri, presupplementary motor area, subthalamic nuclei, inferior parietal lobes, anterior cingulate cortex, and amygdala. We then used dynamic causal modeling to investigate the directionality of the networks involved.
  
  
  RESULTS
  Patients, and to a lesser extent also their unaffected siblings, show altered connectivity between the inferior frontal gyrus and the amygdala during response inhibition. The follow-up dynamic causal modeling suggests a bottom-up influence of the amygdala on the inferior frontal gyrus in healthy controls, whereas processing occurs top-down in patients with obsessive-compulsive, and in both directions in siblings.
  
  
  CONCLUSIONS
  Our findings suggest that amygdala activation in obsessive-compulsive disorder interferes differently with the task-related recruitment of the inhibition network, underscoring the role of limbic disturbances in cognitive dysfunctions in obsessive-compulsive disorder.
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, the Netherlands.
authors.forename: Laura S
authors.initials: LS
authors.lastname: van Velzen
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, the Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Stella J
authors.initials: SJ
authors.lastname: de Wit
authors.affiliation: Department of Neuroscience, Neuroimaging Center, University Medical Centre Groningen, Groningen, the Netherlands.
authors.forename: Branislava
authors.initials: B
authors.lastname: Ćurĉić-Blake
authors.affiliation: Altrecht Academic Anxiety Center, Utrecht, the Netherlands.|Division of Clinical and Health Psychology, Utrecht University, Utrecht, the Netherlands.
authors.forename: Daniëlle C
authors.initials: DC
authors.lastname: Cath
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, the Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Froukje E
authors.initials: FE
authors.lastname: de Vries
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, the Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Neuroscience Campus Amsterdam (NCA), Amsterdam, the Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, the Netherlands.|Netherlands Institute for Neuroscience, Netherlands Academy of Sciences, Amsterdam, the Netherlands.
authors.forename: Ysbrand D
authors.initials: YD
authors.lastname: van der Werf
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.|Neuroscience Campus Amsterdam (NCA), Amsterdam, the Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
mesh_terms: D000328:Adult; D001931:Brain Mapping; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D007839:Functional Laterality; D006801:Humans; D007266:Inhibition, Psychological; D008032:Limbic System / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology; D009415:Nerve Net / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D011597:Psychomotor Performance; D011999:Recruitment, Neurophysiological
keywords: dynamic causal modeling; effective connectivity; obsessive-compulsive disorder; psycho-physiological interaction; response inhibition