Alpha-2 adrenergic challenge with guanfacine one month after mild traumatic brain injury: Altered working memory and BOLD response

• Published in: International journal of psychophysiology Vol. 82; no. 1; pp. 107 - 114
• Main Authors: McAllister, Thomas W., McDonald, Brenna C., Flashman, Laura A., Ferrell, Richard B., Tosteson, Tor D., Yanofsky, Norman N., Grove, Margaret R., Saykin, Andrew J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.10.2011; Elsevier
• Subjects: Adrenergic alpha-2 Receptor Agonists - therapeutic use; Adult; Adult and adolescent clinical studies; Alpha-2 adrenergic agonist; Behavioral psychophysiology; Biological and medical sciences; Brain - blood supply; Brain - drug effects; Brain Injuries - complications; Brain Injuries - drug therapy; Brain Injuries - pathology; Brain Mapping; Cognition Disorders - diagnosis; Cognition Disorders - etiology; Double-Blind Method; Female; Functional MRI; Fundamental and applied biological sciences. Psychology; Guanfacine; Guanfacine - therapeutic use; Humans; Image Processing, Computer-Assisted; Injuries of the nervous system and the skull. Diseases due to physical agents; Magnetic Resonance Imaging; Male; Medical sciences; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory, Short-Term - drug effects; Neuropsychological Tests; Organic mental disorders. Neuropsychology; Oxygen - blood; Prospective Studies; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Trauma Severity Indices; Traumas. Diseases due to physical agents; Traumatic brain injury; Working memory; Young Adult; Functional MRI; Traumatic brain injury; Working memory; Guanfacine; Alpha-2 adrenergic agonist; α2-Adrenergic receptor; Memory disorder; Nervous system diseases; Agonist; Cognitive disorder; Guanidines; Nuclear magnetic resonance imaging; Functional magnetic resonance imaging; Antihypertensive agent; α-Adrenergic receptor agonist; Head trauma
• ISSN: 0167-8760; 1872-7697
• DOI: 10.1016/j.ijpsycho.2011.06.022

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 1 month 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. ► Individuals with MTBI differed from controls in response to guanfacine. ► The MTBI group showed improved working memory (WM) performance on guanfacine. ► Improved WM performance was associated with increased activation of frontal WM cortex.