Theta-burst stimulation and frontotemporal regulation of cardiovascular autonomic outputs: The role of state anxiety.

Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying top-down control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of top-down neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation.