Objective: The proposed study will determine the efficacy of methylphenidate (MPH) for the treatment of epilepsy-related attentional dysfunction. Epilepsy patients often have attention and other cognitive deficits, which can impair quality of life. The causes are typically multifactorial, including frequent seizures, interictal discharges, brain lesions, and antiseizure medication side effects. The comorbidity of attentional dysfunction and epilepsy may be partially explained by abnormalities in ascending reticular activating system networks. There are no FDA-approved medical therapies for epilepsy-related cognitive deficits, and rehabilitation strategies provide limited benefit. MPH is a stimulant, FDA-approved for the treatment of attention deficit hyperactivity disorder (ADHD). It is unknown, however, if stimulants would be of benefit for epilepsy-related cognitive dysfunction. Studies of MPH in children with epilepsy and ADHD suggest efficacy and safety. Further, large database and registry studies found beneficial effects of MPH on seizure risk in children with and without epilepsy. Small, single-dose and open label trials of MPH in adults with epilepsy and attentional dysfunction suggest benefit and safety, but longer-duration, controlled trials with larger numbers of subjects are needed. The proposed study is a multi-site, randomized, double-blind, placebo-controlled trial of MPH, with an open- label extension period, to determine the efficacy of MPH for adult epilepsy-related attentional dysfunction. The study will also establish the effects of MPH on other attention-dependent cognitive processes ({i.e., a combined measure of} memory, psychomotor speed, and executive function) and quality of life. The hypothesis is that subjects will have improved cognitive function and quality of life with MPH compared to placebo. Secondary analyses will determine the impact of MPH on mood and subjective cognitive abilities, efficacy over an open-label period, and safety, including effects on seizure frequency. Research Plan/Methods: Subjects will include {186} adults with epilepsy and self-reported cognitive deficits, recruited from the Manhattan, Portland, Miami, and Boston VA hospitals. In the blinded phase, subjects will {be randomly assigned to} receive either placebo or MPH (titrated to 20 mg twice daily) for 8 weeks. Subjects will then receive open-label MPH for 8 weeks (titrated to 20 mg twice daily). Cognitive testing will be administered at baseline, the end of blinded treatment (Week 8), and the end of the open-label period (Week 16). The cognitive battery will include tests of attention (Continuous Performance Test), memory (MCG Paragraph Test), psychomotor speed (Symbol Digit Modalities Test), and a combined measure of divided attention, psychomotor speed, and response inhibition (Stroop Color Word Interference Test). Additional measures will include quality of life (Quality of Life in Epilepsy Patient Inventory-89), side effects (Adverse Ev...