Effects of HF-rTMS over left and right DLPFC on worry and parasympathetic cardiac control

The dorsolateral prefrontal cortex (DLPFC) is central to regulating intrusive thoughts and worry, yet the lateralization and neurophysiological mechanisms underlying these processes remain unclear. Parasympathetic cardiac control, indexed by heart rate variability (HRV), has been proposed to correlate with prefrontal control over brain regions involved in emotional, cognitive, and autonomic regulation, but empirical evidence linking these domains is mixed. In this preregistered, single-blind, sham-controlled, within-subject study, we examined the effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left and right DLPFC on parasympathetic cardiac control, worry, and intrusive thoughts in 31 healthy participants. HRV was assessed at rest and during a breathing focus task (BFT), a validated paradigm that measures attentional focus, spontaneous intrusive thoughts, and worry. Contrary to predictions, active stimulation did not differ from sham in modulating HRV, intrusive thoughts, or worry. However, right compared with left DLPFC stimulation was associated with higher self-reported worry and lower RMSSD. Exploratory analyses suggested that these differences in RMSSD were not present at baseline and were observed following stimulation. Notably, changes in HRV were not associated with changes in worry, indicating that the effects of HF-rTMS on worry co-occur with, though are not directly explained by, changes in parasympathetic cardiac control, challenging straightforward interpretations of HRV as a correlate of prefrontal regulatory control. Together, these findings provide evidence for hemispheric asymmetries in prefrontal contributions to autonomic and worry-related processes and may inform understanding of the effects of inhibitory right- or excitatory left-DLPFC stimulation protocols on worry-related symptoms.