Neurophysiological impact of theta burst stimulation followed by cognitive exercise in treatment of youth depression

Abstract

• Changes in cortical reactivity following bilateral DLPFC TBS combined with cognitive exercise treatment were assessed in youth with depression. • Cortical reactivity was modulated at cortical sites both local and distal to the site of TBS application. • Modulation of cortical reactivity at different sites was associated with improvement in both depression and rumination scores. • TBS combined with cognitive exercise may exert its therapeutic effect by modulating the neurophysiology of sites both local and distal to the stimulation sites. Targeting the dorsolateral prefrontal cortex (DLPFC) with repeated sessions of theta-burst stimulation (TBS) is a promising treatment for youth depression. However, it remains unclear whether TBS selectively acts upon inhibitory and/or excitatory measures. Such insight could aid with the development of biomarker driven approaches to delivering TBS in depressed youth. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) was used to assess the neurophysiological impact of a 4-week bilateral DLPFC-targeted TBS trial followed by a cognitive exercise for the treatment of depression in youth. In 26 youth with depression (aged 16 – 24 years old), TMS-evoked potentials (TEPs) were assessed at baseline and after treatment completion from the bilateral DLPFC and intraparietal lobules (IPL). Following treatment, there were significant changes in TEPs both local and distal to the stimulated treatment sites. The amplitude of the left DLPFC N100 response was significantly reduced. Also, there was a significant association between changes in the right DLPFC N45 response and reduction in depressive and rumination scores. Additionally, the amplitude of the right IPL N100 response was reduced. Moreover, the modulation of the right IPL N100 response was significantly associated with a reduction in depressive scores. The primary limitation was the lack of a sham treatment arm. Bilateral DLPFC TBS may exert its therapeutic impact by modulating the neurophysiology of regions and networks both local and distal to the treatment site. Collectively, our findings offer novel insight into the potential therapeutic mechanisms of TBS for the treatment of youth depression.