Executive functions (EFs) are cognitive control processes that include flexibility in problem solving, planning, allocation of attention, maintenance and manipulation of information over time, and self-regulation. EFs, which deploy specific cognitive skills such as declarative memory and other domains such as perceptuomotor skills, are mediated by prefrontal cortex and its circuitry. EFs are frequently impaired after traumatic brain injury (TBI), thus contributing to disability and reduced quality of life. Working memory and inhibition are fundamental processes of EFs which have been associated with prefrontal cortex and its network. Although the prefrontal region is vulnerable to injury by acceleration/deceleration and blunt trauma, structural brain imaging is limited in understanding the neurobiology of EF deficits after TBI. Using functional magnetic resonance imaging (fMRI), the Aims 9 of this 3 center project are to (1) Investigate whether the extent of cortical activation during working memory (N-back for faces) and inhibition (left-right incompatibility of arrows) tasks in adults 3 months following moderate to severe TBI differs from that of adults who have sustained extracranial injury; (2) Examine longitudinal changes in activation of prefrontal and related cortical regions during performance of working memory and inhibition tasks in TBI patients reimaged at I year postinjury; (3) Investigate the relationship between patterns of brain activation during working memory and inhibition tasks at 3 months and 1 year postinjury and performance on laboratory, clinical, and everyday measures of EF; (4) In an ongoing study of a separate cohort of moderate to severe TBI patients, evaluate the effects of methylphenidate (MPH) taken for 1 month on prefrontal activation during performance of working memory and inhibition tasks and the associated changes in performance on EF measures. Moderate to severe TBI patients (total n= 180) and general trauma patients (total n=60) will be recruited from the neurosurgery and surgery services at 3 centers.
Aims 1 -3 will be addressed by fMRI and EF assessment at 3 months and 1 year postinjury.
Aim 4 will involve fMRI and EF assessment of TBI patients with working memory deficit who are treated for 28 days with MPH 15 in- bid beginning between 3 and 12 months postinjury. Patients studied for Aim 4 will undergo fMRI and EF assessment before beginning MPH and 1 hour after their final dose of MPH. Laboratory EF measures include dual task performance, subject ordered pointing, N-back letters task, selective learning, and risk taking; the revised Neurobehavioral Rating Scale provides clinical ratings of EFs; and assessment of EFs in everyday activities will include measures of dysexecutive functioning and planning. Analyses will test TBI-related alterations in brain activation at 3 months postinjury, changes on reimaging at 1 year, relationship to EFs, and MPH effects.
