title: Acute deep brain stimulation changes in regional cerebral blood flow in obsessive-compulsive disorder.
abstract: OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Darin D
authors.initials: DD
authors.lastname: Dougherty
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.|Department of Psychology, Harvard University, Cambridge.
authors.forename: Tina
authors.initials: T
authors.lastname: Chou
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Corse
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Arulpragasam
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.|Picower Institute for Learning & Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Alik S
authors.initials: AS
authors.lastname: Widge
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cusin
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Karleyton C
authors.initials: KC
authors.lastname: Evans
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Butler Hospital and Brown Medical School, Providence, Rhode Island; and.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Greenberg
authors.affiliation: Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: Haber
authors.affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Thilo
authors.initials: T
authors.lastname: Deckersbach
mesh_terms: D000328:Adult; D002560:Cerebrovascular Circulation; D003430:Cross-Sectional Studies; D046690:Deep Brain Stimulation; D006801:Humans; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*
keywords: 15O-PET = oxygen-15 positron emission tomography; ACC = anterior cingulate cortex; DBS = deep brain stimulation; FDG = fluorodeoxyglucose; FWHM = full width at half maximum; HAM-D = Hamilton Depression Rating Scale; MGH = Massachusetts General Hospital; MNI = Montreal Neurological Institute; OCD = obsessive-compulsive disorder; OFC = orbitofrontal cortex; ROI = region of interest; VC/VS = ventral capsule/ventral striatum; Y-BOCS = Yale-Brown Obsessive Compulsive Scale; cortico-striatal-thalamic-cortical circuit; dACC = dorsal anterior cingulate cortex; deep brain stimulation; functional neurosurgery; obsessive-compulsive disorder; positron emission tomography; rCBF = regional cerebral blood flow; ventral capsule/ventral striatum; vmPFC = ventromedial prefrontal cortex