title: Alpha-2 adrenergic challenge with guanfacine one month after mild traumatic brain injury: altered working memory and BOLD response.
abstract: Alterations in working memory (WM) are common after traumatic brain injury (TBI). Frontal catecholaminergic systems, including the alpha-2 adrenergic system, modulate WM function and may be affected in TBI. We hypothesized that administration of an alpha-2 adrenergic agonist might improve WM after mild TBI (MTBI). Thirteen individuals with MTBI 1month after injury and 14 healthy controls (HC) were challenged with guanfacine and placebo prior to administration of a verbal WM functional MRI task. Guanfacine was associated with improved WM performance in the MTBI but not the HC group. On guanfacine the MTBI group showed increased activation within a WM task-specific region of interest. Findings are consistent with the hypothesis that alterations in WM after MTBI may be improved with the alpha-2 agonist guanfacine.
authors.affiliation: Section of Neuropsychiatry, Department of Psychiatry, Dartmouth Medical School, Lebanon, NH 03756, USA. thomas.w.mcallister@dartmouth.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McAllister
authors.forename: Brenna C
authors.initials: BC
authors.lastname: McDonald
authors.forename: Laura A
authors.initials: LA
authors.lastname: Flashman
authors.forename: Richard B
authors.initials: RB
authors.lastname: Ferrell
authors.forename: Tor D
authors.initials: TD
authors.lastname: Tosteson
authors.forename: Norman N
authors.initials: NN
authors.lastname: Yanofsky
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Grove
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000328:Adult; D001921:Brain / Q000098:blood supply* / Q000187:drug effects*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D016316:Guanfacine / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008570:Memory, Short-Term / Q000187:drug effects*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D015599:Trauma Severity Indices; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016316:Guanfacine; D010100:Oxygen