The dynamic role of the left dlPFC in neurovisceral integration: Differential effects of theta burst stimulation on vagally mediated heart rate variability and cognitive-affective processing.

Adapting to the ever-changing demands of the environment requires a complex interplay between cognitive-affective, neuronal, and autonomic processes. Vagally mediated heart rate variability (vmHRV) is positively associated with both cognitive-affective functioning and prefrontal cortex (PFC) activity. Accordingly, the Neurovisceral Integration Model has posited a shared role of the PFC in the regulation of cognitive-affective processes and autonomic nervous system (ANS) activity. While there are numerous correlational findings in this regard, no study so far has investigated whether the manipulation of PFC activity induces changes in vmHRV and cognitive-affective processing in an inter-dependent manner. In a sample of 64 participants, we examined the effects of continuous (cTBS; n = 21) and intermittent theta-burst stimulation (iTBS; n = 20) compared to sham stimulation (n = 23) over the left dorsolateral PFC (dlPFC) on vmHRV and cognitive-affective processing within an emotional stop-signal task (ESST). Our results revealed that both resting vmHRV and vmHRV reactivity predicted cognitive-affective processing. Furthermore, we found a dampening effect of cTBS on resting and on-task vmHRV, as well as an enhancing effect of iTBS on ESST performance. Our results show no direct association between vmHRV changes and ESST performance alterations following stimulation. We interpret our results in the light of a hierarchical model of neurovisceral integration, suggesting a dynamical situation-dependent recruitment of higher-order cortical areas like the dlPFC in the regulation of the ANS. In conclusion, our results highlight the complex interplay between PFC activity, autonomic regulation, and cognitive-affective processing, emphasizing the need for further research to understand the causal dynamics of the underlying neural mechanisms.

Tonic and phasic cardiac vagal activity predict cognitive-affective processing in an emotional stop-signal task.

Both the Neurovisceral Integration Model and the Vagal Tank Theory propose cardiac vagal activity (CVA) as proxy for self-regulatory or processing resources required for attentional and top-down control as key mechanisms in executive functioning or emotion-regulation. These resources have, according to the Dual Competition Model, limited capacity and are prioritized for processing the most salient of different competing stimuli. As such, emotional and especially negative or threatening stimuli attract these self-regulatory/processing resources, and may thus interfere with ongoing cognitive processes if not integrated adaptively. Here, we investigated whether tonic and phasic CVA represent self-regulatory/processing resources and thus predict response inhibition in an emotional stop-signal task as a measure of cognitive-affective integration. Thereby, we examined not only the independent effects of tonic and phasic CVA, but whether and how the interaction of both variables predicts response inhibition. We assumed that the effects of CVA on response inhibition would be more pronounced in negatively-valenced trials compared to positive or neutral ones. Our results show that CVA significantly predicted response inhibition, with higher tonic CVA predicting faster, and larger phasic withdrawal CVA predicting slower stop-signal reaction times. The interactive effects of tonic and phasic CVA revealed that high tonic CVA levels prevented the negative effects of CVA withdrawal on response inhibition. Contrary to our assumption, we did not find differential effects of tonic and phasic CVA on trials with different valences. Our results support the notion of CVA as index for self-regulatory/processing resources. However, further research is needed to investigate how CVA is related to specific neural processes of cognitive-affective processing.

The effects of noninvasive brain stimulation on heart rate and heart rate variability: A systematic review and meta-analysis.

Noninvasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation and transcranial direct current stimulation are widely used to test the involvement of specific cortical regions in various domains such as cognition and emotion. Despite the capability of stimulation techniques to test causal directions, this approach has been only sparsely used to examine the cortical regulation of autonomic nervous system (ANS) functions such as heart rate (HR) and heart rate variability (HRV) and to test current models in this regard. In this preregistered (PROSPERO) systematic review and meta-analysis, we aimed to investigate, based on meta-regression, whether NIBS represents an effective method for modulating HR and HRV measures, and to evaluate whether the ANS is modulated by cortical mechanisms affected by NIBS. Here we have adhered to the PRISMA guidelines. In a series of four meta-analyses, a total of 131 effect sizes from 35 sham-controlled trials were analyzed using robust variance estimation random-effects meta-regression technique. NIBS was found to effectively modulate HR and HRV with small to medium effect sizes. Moderator analyses yielded significant differences in effects between stimulation of distinct cortical areas. Our results show that NIBS is a promising tool to investigate the cortical regulation of ANS, which may add to the existing brain imaging and animal study literature. Future research is needed to identify further factors modulating the size of effects. As many of the studies reviewed were found to be at high risk of bias, we recommend that methods to reduce potential risk of bias be used in the design and conduct of future studies.

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

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 pre-registered 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 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.

Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil.

The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27%) in contrast to the DC coil (about 15%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil.