Cognitive safety of dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression

Abstract

The most widely used target for repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD) is the dorsolateral prefrontal cortex (DLPFC). Despite convergent evidence that the dorsomedial prefrontal cortex (DMPFC) may be a promising alternative target for rTMS in TRD, its cognitive safety profile has not previously been assessed. Here, we applied 20 sessions of rTMS to the DMPFC in 21 TRD patients. Before and after treatment, a battery of neuropsychological tasks was administered to evaluate changes in cognition across three general cognitive domains: learning and memory, attention and processing speed, and cognitive flexibility. Subjects also completed the 17-item Hamilton Rating Scale for Depression (HamD17) prior to and following treatment to measure changes in severity of depressive symptoms, and to assess the relationship between mood and cognitive performance over the course of treatment. No serious adverse effects or significant deterioration in cognitive performance were observed. Overall, subjects improved significantly on Stroop Inhibition/Switching and on Trails B, and this improvement was independent of the degree of improvement in depression symptoms. No domains or items significantly predicted clinical outcome, with the exception of baseline performance on Visual Elevator Accuracy. Clinical improvement correlated to improved performance in the overall domain of attention and processing speed, although this effect was not evident following covariate adjustment. DMPFC-rTMS did not produce any detectable cognitive adverse effects during treatment of TRD. Performance did not deteriorate significantly on any measures. Taken together, the present findings support the tolerability and cognitive safety of DMPFC-rTMS in refractory depression.