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

Abstract Background There are currently no approved treatments for working memory deficits in schizophrenia spectrum disorders(SSD). The objective of the present study was to assess whether repetitive transcranial magnetic stimulation(rTMS) to bilateral dorsolateral prefrontal cortex(DLPFC) in people with SSD a) improves working memory deficits and b) 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. 83 participants with SSD were randomized to either active 20Hz rTMS applied to bilateral DLPFC or sham rTMS for four weeks. Participant also completed a ‘pre/post’ MRI. Clinical and cognitive assessments were performed at baseline, treatment end, and one 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(FA) of white matter tracts connecting to DLPFC. Pre-specified exploratory outcome measures were changes in general cognition; positive, negative, and depressive symptoms. Results Compared to sham, active rTMS did not lead to significant change in working memory performance; it was associated with increase in right DLPFC thickness but not FA. Pre-specified exploratory analysis showed significant decrease in depressive symptoms in the active group; decrease in depressive symptoms was correlated with increase in right DLPFC thickness. Conclusions rTMS applied to bilateral DLPFC is not efficacious to treat working memory deficits in SSD. However, it increases right DLPFC thickness and decreases depressive symptoms. These findings deserve further study given the lack of efficacy of antidepressant medications in SSD.