Investigating the Effects of Priming Theta Burst Stimulation in Healthy and Subclinically Depressed Populations

Background Repetitive transcranial magnetic stimulation and its patterned form, intermittent theta- burst stimulation (iTBS) (rTMS) is a clinically effective treatment for neuropsychiatric disorders, including depression [1]. The mechanism of action of therapeutic iTBS is proposed to involve a change in cortical excitability and the induction of neuroplastic changes [2]. However, the effects of iTBS vary across participants [3]. Priming stimulation is a highly promising tool to enhance the effects of iTBS on brain activity through the mechanism of metaplasticity [4]. The potentiating effects of priming stimulation, however, depend on the time interval between the priming and the test stimulation. Objective The objective of this study was to systematically investigate the effects of priming TBS on the excitability of left dorsolateral prefrontal cortex (DLPFC) – one of the main targets for therapeutic rTMS – in individuals with subclinical depression and healthy participants. Method A total of 87 right-handed young adults participated in this study, including 49 individuals with subclinical depression and 38 healthy controls. The priming protocol comprised priming continuous TBS (cTBS) followed by subsequent iTBS. The experimental conditions included real or sham cTBS followed by iTBS, real cTBS followed by iTBS after a 10-minute delay, and real cTBS followed by iTBS after a 20- minute delay. TBS was delivered to the lDLPFC at the intensity of 70% of their individual resting motor threshold. The function of lDLPFC was assessed using a verbal fluency task directly before and after stimulation. Results Our results revealed significant group differences in prefrontal function between healthy individuals and those with subclinical depression (p=0.015). Furthermore, a significant interaction effect (group by condition) (p =0.044) was observed, indicating that the metaplasticity response to iTBS differed between the two populations. However, the time interval between priming cTBS and subsequent iTBS did not show a significant effect on prefrontal function (p = 0.205). Conclusions The present study provides novel insights into the differential effects of priming stimulation on prefrontal excitability in healthy individuals and individuals with subclinical depression. The observed group differences and the interaction effect suggest that the neuroplastic response to iTBS may be influenced by underlying population characteristics. References 1.Machado, S., et al., Repetitive transcranial magnetic stimulation for clinical applications in neurological and psychiatric disorders: an overview. Eurasian J Med, 2013. 45(3): p. 191-206. 2.Huang, Y.-Z., et al., Theta Burst Stimulation of the Human Motor Cortex. Neuron, 2005. 45(2): p. 201- 206. 3.Suppa, A., et al., Ten Years of Theta Burst Stimulation in Humans: Established Knowledge, Unknowns and Prospects. Brain Stimul, 2016. 9(3): p. 323-335. 4.Iyer, M.B., N. Schleper, and E.M. Wassermann, Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation. J Neurosci, 2003. 23(34): p. 10867-72.