PROJECT SUMMARY/ABSTRACT Cognitive control deficits are associated with poor functioning in schizophrenia (SZ). These deficits include an impaired ability to maintain task-relevant goals and attention to a task over time, and are connected to impaired functioning of the dorsolateral prefrontal cortex (DLPFC), a key hub in the neural network supporting cognitive control. The proposed research uses a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS) to test a set of mechanistic hypotheses about the role of the DLPFC in cognitive control deficits in SZ, focusing on stimulation-induced changes in neural oscillations and DLPFC GABA levels. To do so, we will use DLPFC-targeted tDCS in combination with electrophysiology (EEG) and magnetic resonance spectroscopy (MRS) methods to examine stimulation-induced changes in neural activity related to cognitive control in SZ. Preliminary data from our lab suggests that DLPFC-targeted anodal tDCS can enhance neural oscillations that support goal maintenance in both healthy controls and individuals with SZ. This neurostimulation approach offers an exciting new avenue for understanding the neural mechanisms underlying impaired cognition in SZ, which we propose to utilize with three specific aims. Aim 1: Compare the effects of task-engaged versus resting tDCS in order to optimize the impact of tDCS on goal maintenance related neural oscillatory activity and task performance in SZ. Aim 2: Establish the regional specificity of the impact of DLPFC tDCS (compared to Occipital tDCS) effects on brain circuitry underlying goal maintenance in SZ. Aim 3: Test hypotheses about relationships between tDCS effects on DLPFC GABA levels, DLPFC-related oscillatory activity and cognitive performance in SZ. Successful completion of these Aims will address critical gaps in the literature on cognitive disability in SZ, which has, to date, relied on correlative approaches and will provide new insights into the role of disrupted DLPFC related brain circuity in SZ and its underlying pathophysiological mechanisms. It will also provide important new insights into the mechanisms of tDCS effects on brain and cognition in this illness.