The effect of HF-rTMS over the left DLPFC on stress regulation as measured by cortisol and heart rate variability

Abstract

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This preregistered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M=21.05, SD=2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to the stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis.

Perceived Stress, Cortical GABA, and Functional Connectivity Correlates: A Hypothesis-Generating Preliminary Study

“…However, we did not observe a significant relationship between perceived stress and RSFC. The DLPFC is thought to play an inhibitory role in the physiological response to stress via regulation of amygdala projections to hypothalamus, a key region of the HPA-axis known to be modulated by GABAergic activity in response to stress (23,51,52). The DLPFC has been targeted in neurostimulation treatment aimed at improving stress-related cognitive impairments and physiological responses.…”

Stress and aging: A neurovisceral integration perspective

“…Given that the PFC tonically inhibits subcortical sympathoexcitatory circuits (e.g., Thayer et al., 2009), it was hypothesized that inactivation of the dlPFC using transcranial magnetic stimulation (TMS) should be associated with greater HR, lower HRV, and larger cortisol responses to a perseverative cognition induction compared to inactivations of a motor brain region or sham stimulation. These researchers indeed found that dlPFC inactivation was associated with higher HR, lower vagally mediated HRV, and greater cortisol responses that extended into the recovery period compared to the other conditions (see also Angius et al., 2019; De Witte et al., 2020; Pulopulos et al., 2020). These findings provide compelling evidence for the relationships among the PFC, and autonomic and endocrine stress responses.…”

Feasibility of Combining Transcranial Direct Current Stimulation and Active Fully Embodied Virtual Reality for Visual Height Intolerance: A Double-Blind Randomized Controlled Study

“…Concerning the objective biological salivary cortisol measurements, our results did not show differential effects in both groups. Most of the studies focused on left dorsolateral prefrontal cortex stimulation and suggested rTMS [69,70] or tDCS [71] could reduce the neuroendocrine response to stress in healthy subjects. Nevertheless, recently, a study evaluating a single session of tDCS on the left dlPFC in healthy subjects showed that tDCS was probably responsible for an attenuation of the autonomic response to stress (heart rate variability) without a significant reduction in cortisol concentration [72].…”

“…Starting from the ground, participants were invited to get into the elevator and were asked to rise as high as possible. At each floor (1,3,5,13,22,35,55,70 and 99, for a total of 9 levels and a 150 m maximum height), the door opened, and participants had to cross a wooden plank between two platforms in order to access the elevator of the second part of the skyscraper and be able to go up to the next floor (Figure 5). Once the board was crossed, participants had to observe their environment for 30 s before rating the SUD twice with a 30 s interval between both.…”