Restoration of Cognitive Function With TDCS and Training in Schizophrenia

Development of interventions that can effectively target and remediate the cognitive and
functional impairment associated with schizophrenia is a treatment priority. Transcranial
direct current stimulation (tDCS) is a safe, non-invasive neuromodulation technique that is
capable of stimulating brain activity to facilitate learning. The primary objective of this
study is to evaluate the pairing of two therapeutic techniques, cognitive remediation and
tDCS, as a cognitively enhancing intervention. This study is designed to address four
questions. Is cognitive remediation paired with tDCS more efficacious than cognitive
remediation delivered with sham stimulation? Is it possible to predict responsiveness to the
intervention? Is intervention-induced cognitive change sustainable? Are there barriers to
implementing this intervention in clinical practice?

To examine the incremental benefit of pairing tDCS with cognitive remediation, a 110
clinically stable outpatients between the ages of 18-60 who have a diagnosis of schizophrenia
or schizoaffective disorder will be enrolled in a double-blind, double-baseline,
sham-controlled clinical trial. Participants will be randomized in a 1:1 ratio to receive
either tDCS or sham stimulation concurrent with working memory focused cognitive remediation.
Training will be offered to participants in a small group format. Training will consist of 48
sessions, with 2-3 sessions scheduled in a week. Each training session will last 2 hours. One
hour will be spent completing cognitive exercises that require working memory skills on a
computer. TDCS or sham stimulation will be offered concurrent with the first 20 minutes of
training with a StarStim neuromodulator. One mA of anodal stimulation will be applied to the
left dorsal lateral prefrontal cortex and the cathodal electrode will be placed in the
contralateral supraorbital position. Upon completion of working memory training, participants
will transition to a 30-minute discussion group. The discussion will focus on application of
cognitive skills in everyday life. Effective strategies for approaching cognitive tasks will
be described and practiced. Participant experience with aspects of the training will be
monitored with self-report measures of motivation, mood, and physical reactions. To assess
intervention-induced change, working memory, other aspects of cognition, functional capacity,
and community functioning will be assessed pre- and post-intervention. Cognitive outcomes
will be assessed with training tasks as well as tasks that are unfamiliar to participants. A
performance-based measure will be used to assess functional capacity for everyday living
skills and a self-report instrument will be used to assess community functioning. Potential
confounds such as symptom severity, medication changes, outside treatment hours, and
significant life stressors will be assessed individually every 2 weeks during the
intervention phase of the study. Sustainability of intervention-induced change will be
assessed with assessment sessions 6 weeks and 6 months post-intervention. Change in
performance during the first 12 training sessions on two working memory training tasks, a
n-back task and a complex span task, will be used to determine if early response to treatment
is predictive of post-intervention outcomes. An intent-to-treat analysis will be used to
analyze intervention-induced change. Regression analyses will be conducted to identify
predictors of treatment response.

Achieving the proposed objectives will yield important information about the efficacy,
durability, and efficiency of a novel pairing of cognitively enhancing interventions.
Findings will inform treatment development for patients with schizophrenia as well for
patients with other cognitively compromising illnesses.