title: Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity.
abstract: A recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity.
  
  
  
  Multiecho resting-state acquisition, combined with micromovement correction by blood oxygen level-dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects. We measured cognitive flexibility (attentional set-shifting) and goal-directed performance (planning of sequential response sequences) by means of well-validated, standardized behavioral cognitive paradigms. Functional connectivity strength of striatal seed regions was related to cognitive flexibility and goal-directed performance. To gain insights into fundamental network alterations, graph theoretical models of brain networks were derived.
  
  
  
  Reduced functional connectivity between the caudate and the ventrolateral prefrontal cortex was selectively associated with reduced cognitive flexibility. In contrast, goal-directed performance was selectively related to reduced functional connectivity between the putamen and the dorsolateral prefrontal cortex in OCD patients, as well as to symptom severity. Whole-brain data-driven graph theoretical analysis disclosed that striatal regions constitute a cohesive module of the community structure of the functional connectome in OCD patients as nodes within the basal ganglia and cerebellum were more strongly connected to one another than in healthy control subjects.
  
  
  
  These data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable frontostriatal circuits and those cognitive processes underlying OCD symptoms.
authors: Departments of Psychology, University of Cambridge, Cambridge; Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge. Electronic address: matilde.vaghi@gmail.com.
authors: Matilde M
authors: MM
authors: Vaghi
authors: Psychiatry, University of Cambridge, Cambridge; Brain Mapping Unit, University of Cambridge, Cambridge.
authors: Petra E
authors: PE
authors: Vértes
authors: Psychiatry, University of Cambridge, Cambridge; Brain Mapping Unit, University of Cambridge, Cambridge.
authors: Manfred G
authors: MG
authors: Kitzbichler
authors: Psychiatry, University of Cambridge, Cambridge; Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge.
authors: Annemieke M
authors: AM
authors: Apergis-Schoute
authors: Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge.
authors: Febe E
authors: FE
authors: van der Flier
authors: Hertfordshire Partnership University National Health Service Foundation Trust, Hertfordshir; University of Hertfordshire, Hertfordshire.
authors: Naomi A
authors: NA
authors: Fineberg
authors: Cumbria Partnership National Health Service Foundation Trust, National Health Service, Penrith, Cumbria, United Kingdom.
authors: Akeem
authors: A
authors: Sule
authors: Psychiatry, University of Cambridge, Cambridge.
authors: Rashid
authors: R
authors: Zaman
authors: Psychiatry, University of Cambridge, Cambridge; Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge.
authors: Valerie
authors: V
authors: Voon
authors: Brain Imaging Center and Translational, Icahn Institute of Medicine at Mt. Sinai, New York, New York; Molecular Imaging Institute, Icahn Institute of Medicine at Mt. Sinai, New York, New York.
authors: Prantik
authors: P
authors: Kundu
authors: Psychiatry, University of Cambridge, Cambridge; Brain Mapping Unit, University of Cambridge, Cambridge.
authors: Edward T
authors: ET
authors: Bullmore
authors: Departments of Psychology, University of Cambridge, Cambridge; Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge.
authors: Trevor W
authors: TW
authors: Robbins
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D003342:Corpus Striatum / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006040:Goals; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012720:Severity of Illness Index
keywords: Cognitive flexibility; Frontostriatal circuits; Functional connectivity; Goal-directed planning; Obsessive-compulsive disorder; Resting state