An EEG Study of Reward Processing and Memory Dysfunction in Schizophrenia

The overall goal of the proposed project is to improve the care of Veterans with schizophrenia. Deficits
in initiating and sustaining goal-oriented behavior, termed avolition, is a hallmark feature of schizophrenia that
has cascading effects on interpersonal relationships, occupational functioning, and psychological well-being.
There is widespread consensus that adequate interventions for avolition do not exist. The development of
effective and tailored interventions for avolition depends on a clearer understanding of its neurobiological
underpinnings in concert with translational models that bridge with pre-clinical research. Recent models have
posited several mechanisms that contribute to avolition, including failures to sufficiently recall past personal
experiences when imagining and evaluating future gains, reduced capacity to anticipate reward from future
outcomes, and indecision when preparing movements towards a goal. To date, there has been no thorough
test of how these various processes contribute to avolition in the context of schizophrenia. Animal models of
goal pursuit show that core brain rhythms orchestrate memory and reward functioning; similar oscillatory
patterns support memory and reward processing in humans and are often deficient in schizophrenia. Taken
together, avolition in schizophrenia could arise, in part, from neural oscillatory signals that can be compared to
preclinical models. Noninvasive neurostimulation methods are a safe and promising avenue to try to augment
these oscillatory signals in Veterans with schizophrenia, in an effort to reduce avolition. Mounting evidence
shows that stimulation applied to a novel episodic memory-related brain target enhances memory in healthy
individuals. Whether targeting this same region remediates memory-related oscillatory deficits in
schizophrenia, and corresponding behavioral sequalae, is unknown.
This proposal aims to address these gaps in the literature by isolating a set of mechanisms related to
avolition, and by testing whether a single session of transient, noninvasive neurostimulation can augment the
neural signals associated with these mechanisms in Veterans with schizophrenia. This study will combine
electroencephalography (EEG) recordings and theta burst stimulation (TBS), a noninvasive neurostimulation
method, to achieve three specific aims: 1) to investigate the contributions of episodic memory, reward
anticipation, and motor preparation processes in the prediction of clinical avolition in schizophrenia using a
translational reward task; 2) to identify episodic-memory neural oscillatory deficits in Veterans with
schizophrenia using EEG, and evaluate relationships between oscillatory dysfunction with reward anticipation,
motor preparation, and clinical avolition; and finally, 3) to examine whether memory-related oscillatory activity
in Veterans with schizophrenia can be enhanced with a brief TBS protocol applied to a novel memory-related
brain target. The proposed work will leverage the temporal precision of EEG and the efficiency of TBS.
Knowledge gained from this study could provide important insights into the pathophysiology of
schizophrenia. In turn, these findings could facilitate the identification of neurophysiological targets for novel
interventions specifically aimed at ameliorating avolition, thereby improving functional outcomes in Veterans
with schizophrenia.

Grant Number: 5IK2CX002355-04
NIH Institute/Center: VA
Principal Investigator: Samantha Abram