Efficacy of Pharmacological Treatment of Working Memory Impairment After Traumatic Brain Injury: Evaluation With fMRI

Summary

This study is designed to examine the effects of a wake-promoting agent (Modafinil) on working memory (WM) in persons with moderate to severe TBI utilizing a double blinded placebo controlled methodology. Our approach is to evaluate participants with BOLD fMRI and a limited neuropsychological battery to examine WM performance before and after pharmacological intervention. Hypotheses 1. Because increased cognitive effort (as a function of decreased efficiency after TBI) is presumed to underlie fMRI activation dispersion that is seen during central executive WM tasks, we anticipate an attenuation of cerebral activation in prefrontal cortex during pharmacological intervention with Modafinil when compared to placebo administration on the mPASAT and vigilance testing. 2. There will be a correlation between the decreased dispersion of the fMRI signal on scans and improvement in neuropsychological measures when individuals are on Modafinil that is not seen when they are taking placebo.

Timeline

Start

2003-08

Primary completion

—

Completion

2008-12

Publications

• Background Baddeley A. Working memory. Science. 1992 Jan 31;255(5044):556-9. doi: 10.1126/science.1736359.
• Background Levin HS, Gary HE Jr, Eisenberg HM, Ruff RM, Barth JT, Kreutzer J, High WM Jr, Portman S, Foulkes MA, Jane JA, et al. Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank. J Neurosurg. 1990 Nov;73(5):699-709. doi: 10.3171/jns.1990.73.5.0699.
• Background McDowell S, Whyte J, D'Esposito M. Working memory impairments in traumatic brain injury: evidence from a dual-task paradigm. Neuropsychologia. 1997 Oct;35(10):1341-53. doi: 10.1016/s0028-3932(97)00082-1.
• Background Ponsford J, Kinsella G. Attentional deficits following closed-head injury. J Clin Exp Neuropsychol. 1992 Sep;14(5):822-38. doi: 10.1080/01688639208402865.
• Background Stuss DT, Ely P, Hugenholtz H, Richard MT, LaRochelle S, Poirier CA, Bell I. Subtle neuropsychological deficits in patients with good recovery after closed head injury. Neurosurgery. 1985 Jul;17(1):41-7. doi: 10.1227/00006123-198507000-00007.
• Background McAllister TW, Saykin AJ, Flashman LA, Sparling MB, Johnson SC, Guerin SJ, Mamourian AC, Weaver JB, Yanofsky N. Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology. 1999 Oct 12;53(6):1300-8. doi: 10.1212/wnl.53.6.1300.
• Background Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE. Traumatic brain injury in the United States: A public health perspective. J Head Trauma Rehabil. 1999 Dec;14(6):602-15. doi: 10.1097/00001199-199912000-00009.
• Background Schootman M, Fuortes LJ. Ambulatory care for traumatic brain injuries in the US, 1995-1997. Brain Inj. 2000 Apr;14(4):373-81. doi: 10.1080/026990500120664.
• Background Guerrero JL, Thurman DJ, Sniezek JE. Emergency department visits associated with traumatic brain injury: United States, 1995-1996. Brain Inj. 2000 Feb;14(2):181-6.
• Background Smith EE, Jonides J, Koeppe RA. Dissociating verbal and spatial working memory using PET. Cereb Cortex. 1996 Jan-Feb;6(1):11-20. doi: 10.1093/cercor/6.1.11.

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