Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)

Summary

Traumatic brain injury (TBI) is a significant public health problem, with 1.5-2.0 million Americans injured each year. Cognitive deficits, particularly in the domains of memory and attention are frequently the source of lingering disability after TBI and a source of enormous distress to the injured individuals and their family/caregivers. To date, interventions to ameliorate chronic cognitive deficits have been directed at either pharmacological interventions or cognitive rehabilitation. We propose to (1) To compare the efficacy of three interventions: memory and attention training (MAAT), methylphenidate, and memory/attention training in combination with methylphenidate and (2) use functional MRI (fMRI) to characterize changes in activation of the neural circuitry of memory and attention due to MAAT alone, methylphenidate alone, and MAAT in combination with methylphenidate. This is a two by two design with medication (methylphenidate/placebo) and cognitive therapy (Memory and Attention Training (MAAT) or an Attention control intervention) as possible interventions. Using a randomized, placebo-controlled, double-blind design, 200 individuals with persistent cognitive deficits 6-12 months after MTBI will be randomized to receive a six week trial of either (1) MAAT and placebo, (2) MAAT and methylphenidate (0.3 mg/kg BID), (3) attention control intervention and methylphenidate (0.3 mg/kg BID), or (4) attention control intervention and placebo. Symptom distress, attention and memory performance, and activation patterns of the neural circuitry of attention and memory while undergoing fMRI will be characterized at baseline, and after the four treatment conditions. This study will provide important information on three interventions for the most disabling sequelae of an enormous public health problem. Further, it will help to clarify underlying neural mechanisms and suggest additional treatment possibilities.

Timeline

Start

2007-02

Primary completion

2013-05

Completion

2013-05

Publications

• Background McAllister TW, Flashman LA, McDonald BC, Saykin AJ. Mechanisms of working memory dysfunction after mild and moderate TBI: evidence from functional MRI and neurogenetics. J Neurotrauma. 2006 Oct;23(10):1450-67. doi: 10.1089/neu.2006.23.1450.
• Background Neurobehavioral Guidelines Working Group; Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, Drake A, Gentry T, Jagoda A, Katz DI, Kraus J, Labbate LA, Ryan LM, Sparling MB, Walters B, Whyte J, Zapata A, Zitnay G. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006 Oct;23(10):1468-501. doi: 10.1089/neu.2006.23.1468.
• Background McAllister TW, Rhodes CH, Flashman LA, McDonald BC, Belloni D, Saykin AJ. Effect of the dopamine D2 receptor T allele on response latency after mild traumatic brain injury. Am J Psychiatry. 2005 Sep;162(9):1749-51. doi: 10.1176/appi.ajp.162.9.1749.
• Background McAllister TW, Flashman LA, Sparling MB, Saykin AJ. Working memory deficits after traumatic brain injury: catecholaminergic mechanisms and prospects for treatment -- a review. Brain Inj. 2004 Apr;18(4):331-50. doi: 10.1080/02699050310001617370.
• Background McAllister TW, Ferrell RB. Evaluation and treatment of psychosis after traumatic brain injury. NeuroRehabilitation. 2002;17(4):357-68.
• Background Flashman LA, McAllister TW. Lack of awareness and its impact in traumatic brain injury. NeuroRehabilitation. 2002;17(4):285-96.
• Background McAllister TW, Arciniegas D. Evaluation and treatment of postconcussive symptoms. NeuroRehabilitation. 2002;17(4):265-83.
• Background McAllister TW. Evaluation and treatment of neurobehavioral complications of traumatic brain injury--have we made any progress? NeuroRehabilitation. 2002;17(4):263-4. No abstract available.
• Background McAllister TW, Sparling MB, Flashman LA, Saykin AJ. Neuroimaging findings in mild traumatic brain injury. J Clin Exp Neuropsychol. 2001 Dec;23(6):775-91. doi: 10.1076/jcen.23.6.775.1026.
• Background McAllister TW, Sparling MB, Flashman LA, Guerin SJ, Mamourian AC, Saykin AJ. Differential working memory load effects after mild traumatic brain injury. Neuroimage. 2001 Nov;14(5):1004-12. doi: 10.1006/nimg.2001.0899.
• 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 McAllister TW. Traumatic Brain Injury and Psychosis: What Is the Connection? Semin Clin Neuropsychiatry. 1998 Jul;3(3):211-223.
• Background Flashman LA, Amador X, McAllister TW. Lack of Awareness of Deficits in Traumatic Brain Injury. Semin Clin Neuropsychiatry. 1998 Jul;3(3):201-210.
• Background McAllister TW, Green RL. Traumatic Brain Injury: A Model of Acquired Psychiatric Illness? Semin Clin Neuropsychiatry. 1998 Jul;3(3):158-159. No abstract available.
• Background McAllister TW. Evaluation of brain injury related behavioral disturbances in community mental health centers. Community Ment Health J. 1997 Aug;33(4):341-58; discussion 359-64. doi: 10.1023/a:1025055426260.
• Background Silver JM, McAllister TW. Forensic issues in the neuropsychiatric evaluation of the patient with mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1997 Winter;9(1):102-13. doi: 10.1176/jnp.9.1.102. No abstract available.
• Background McAllister TW. Neuropsychiatric sequelae of head injuries. Psychiatr Clin North Am. 1992 Jun;15(2):395-413.

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