White matter integrity of the medial forebrain bundle and attention and working memory deficits following traumatic brain injury.

BACKGROUND AND OBJECTIVE: The medial forebrain bundle (MFB) contains ascending catecholamine fibers that project to the prefrontal cortex (PFC). Damage to these fibers following traumatic brain injury (TBI) may alter extracellular catecholamine levels in the PFC and impede attention and working memory ability. This study investigated white matter microstructure of the medial MFB, specifically the supero-lateral branch (slMFB), following TBI, and its association with performance on attention and working memory tasks. METHOD: Neuropsychological measures of attention and working memory were administered to 20 moderate-severe participants with TBI (posttraumatic amnesia M = 40.05 ± 37.10 days, median time since injury 10.48 months, range 3.72-87.49) and 20 healthy controls. Probabilistic tractography was used to obtain fractional anisotropy (FA) and mean diffusivity (MD) values for 17 participants with TBI and 20 healthy controls. RESULTS: When compared to controls, participants with TBI were found to have significantly lower FA (p < .001) and higher MD (p < .001) slMFB values, and they were slower to complete tasks including Trail Making Task-A, Hayling, selective attention task, n-back, and Symbol Digit Modalities Test. CONCLUSION: This study was the first to demonstrate microstructural white matter damage within the slMFB following TBI. However, no evidence was found for an association of alterations to this tract and performance on attentional tasks.

The efficacy and safety of extended-release methylphenidate following traumatic brain injury: a randomised controlled pilot study.

OBJECTIVE: To investigate the feasibility, safety and efficacy of extended-release methylphenidate in enhancing processing speed, complex attentional functioning and everyday attentional behaviour after traumatic brain injury. DESIGN: Seven week randomised, placebo-controlled, double-blind, parallel pilot study. SETTING: Inpatient and outpatient Acquired Brain Injury Rehabilitation Program. PARTICIPANTS: Eleven individuals with reduced processing speed and/or attention deficits following complicated mild to severe traumatic brain injury. INTERVENTIONS: Participants were allocated using a blocked randomisation schedule to receive daily extended-release methylphenidate (Ritalin® LA at a dose of 0.6 mg/kg) or placebo (lactose) in identical capsules. MAIN OUTCOMES: Tests of processing speed and complex attention, and ratings of everyday attentional behaviour were completed at baseline, week 7 (on-drug), week 8 (off-drug) and 9 months follow-up. Vital signs and side effects were monitored from baseline to week 8. RESULTS: Three percent ( n = 11) of individuals screened participated (mean post-traumatic amnesia duration = 63.80 days, SD = 45.15). Results were analysed for six and four individuals on methylphenidate and placebo, respectively. Groups did not differ on attentional test performance or relative/therapist ratings of everyday attentional behaviour. One methylphenidate participant withdrew due to difficulty sleeping. Methylphenidate was associated with trends towards increased blood pressure and reported anxiety. CONCLUSION: Methylphenidate was not associated with enhanced processing speed, attentional functioning or everyday attentional behaviour after traumatic brain injury. Alternative treatments for attention deficits after traumatic brain injury should be explored given the limited feasibility of methylphenidate in this population.