Emotion regulation is crucial for mental health and adaptive social behavior. One effective strategy for voluntary emotion regulation is cognitive reappraisal, which refers to the deliberate reinterpretation of emotional stimuli to manage and regulate emotional responses in various contexts. A clear understanding of the brain processes involved in cognitive reappraisal may be valuable in developing targeted and effective interventions for disorders of emotion regulation, such as depression, anxiety, and borderline personality disorder.

Emerging evidence from functional imaging and neuromodulation studies has implicated specific frontal cortical regions in cognitive reappraisal. Functional magnetic resonance imaging (fMRI) studies suggest that cognitive reappraisal engages the ventrolateral prefrontal cortex (VLPFC) and its interactions with subcortical affective regions, primarily the insula and amygdala (Ochsner et al., 2012; Buhle et al., 2014; Hart et al., 2018). Moreover, the use of neuromodulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, has suggested a causal role of the VLPFC in emotion regulation (Cao et al., 2021). Without concurrent assessment of stimulation-related changes in brain activity, evidence from studies using neuromodulation alone cannot directly establish a causal relationship between activity in VLPFC circuitry and cognitive reappraisal.

It is possible that the VLPFC directly modulates subcortical activity during cognitive reappraisal. However, it has also been proposed that the ventromedial prefrontal cortex (VMPFC), which is interconnected with both VLPFC and subcortical affective regions, serves as an intermediary between the VLPFC and subcortical areas (Hiser and Koenigs, 2018). Thus, the involvement of VMPFC in voluntary emotion regulation needs to be clarified.

Combining TMS with fMRI is a powerful approach for establishing the role of specific brain regions and their downstream targets in a given brain function. Delivering TMS during MRI involves technical challenges, however (Mizutani-Tiebel et al., 2022). For example, the TMS …

Correspondence should be addressed to Jennifer Lissemore at jenlissstanford.edu.