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Augmented neural activity during executive control processing following diffuse axonal injury

From the Rotman Research Institute (G.R.T., B.L.), Baycrest Centre for Geriatric Care, Toronto; and the Departments of Psychology (G.R.T., B.L.) and Medicine (Neurology) (B.L.), University of Toronto, Ontario, Canada.

Address correspondence and reprint requests to Dr. Brian Levine, Rotman Research Institute, Baycrest Center for Geriatric Care, 3560 Bathurst St., Toronto, ON, M6A 2E1, Canada blevine{at}rotman-baycrest.on.ca

Background: Deficits in working memory are commonly observed after traumatic brain injury (TBI), with executive control processes preferentially impacted relative to storage and rehearsal. Previous activation functional neuroimaging investigations of working memory in patients with TBI have reported altered functional recruitment, but methodologic issues including sample heterogeneity (e.g., variability in injury mechanism, severity, neuropathology or chronicity), underspecified definitions of "working memory," and behavioral differences between TBI and control groups have hindered interpretation of these changes.

Methods: Executive control processing in working memory was explicitly engaged during fMRI in a sample of carefully selected chronic-stage, moderate-to-severe TBI patients with diffuse axonal injury (DAI) but without focal lesions.

Results: Despite equivalent task performance, we observed a pattern of greater recruitment of interhemispheric and intrahemispheric regions of prefrontal cortex (PFC) and posterior cortices in our DAI sample. Enhanced activations were recorded in the left dorsolateral PFC (middle frontal gyrus), right ventrolateral PFC (inferior frontal gyrus), bilateral posterior parietal cortices, and left temporo-occipital junction. Region-of-interest analyses confirmed that these effects were robust across individual patients and could not be attributed to load factors or slowed speed of processing.

Conclusions: Augmented functional recruitment in the context of normal behavioral performance may be a neural marker of capacity or efficiency limits that can affect functional outcome after traumatic brain injury with diffuse injury.

Abbreviations: BA = Brodmann area; BOLD = blood oxygen level–dependent; DAI = diffuse axonal injury; DLPFC = dorsolateral prefrontal function; GCS = Glasgow Coma Scale; IFG = inferior frontal gyrus; ITI = intertrial interval; MFG = middle frontal gyrus; NA = not applicable; NS = not significant; PFC = prefrontal cortex; ROI = region of interest; TBI = traumatic brain injury.

Supplemental data at www.neurology.org

Supported by a grant from the NIH–National Institute of Child Health and Human Development (no. HD42385-01) to B.L.

Disclosure: The authors report no disclosures.

Received January 8, 2008. Accepted in final form May 30, 2008.