Effects of Repetitive Transcranial Magnetic Stimulation on Working Memory Performance and Brain Structure in People With Schizophrenia Spectrum Disorders: A Double-Blind, Randomized, Sham-Controlled Trial

Background: There are currently no approved treatments for working memory deficits in schizophrenia spectrum disorders (SSDs). The objective of the present study was to assess whether repetitive transcranial magnetic stimulation (rTMS) to the bilateral dorsolateral prefrontal cortex (DLPFC) in people with SSDs 1) improves working memory deficits and 2) changes brain structure.

Methods: We conducted a double-blind, parallel, randomized, sham-controlled study at the Centre for Addiction and Mental Health in Toronto, Canada. We randomized 83 participants with SSDs to receive either active 20 Hz rTMS applied to the bilateral DLPFC or sham rTMS for 4 weeks. The participants also completed pre/posttreatment magnetic resonance imaging. Clinical and cognitive assessments were performed at baseline, treatment end, and 1 month later. The primary outcome was change in verbal n-back working memory performance accuracy (d-prime). The secondary outcome measures were change in DLPFC thickness and fractional anisotropy of white matter tracts connecting to the DLPFC. Prespecified exploratory outcome measures were changes in general cognition; positive, negative, and depressive symptoms.

Results: Compared with sham treatment, active rTMS did not lead to significant change in working memory performance; it was associated with an increase in right DLPFC thickness but not fractional anisotropy. Prespecified exploratory analysis showed a significant decrease in depressive symptoms in the active group; the decrease in depressive symptoms was correlated with an increase in right DLPFC thickness.

Conclusions: Although rTMS applied to the bilateral DLPFC was not efficacious in treating working memory deficits in SSDs, it did increase right DLPFC thickness and decrease depressive symptoms. These findings deserve further study given the lack of efficacy of antidepressant medications in SSDs.