Interhemispheric cortico-cortical paired associative stimulation of the prefrontal cortex jointly modulates frontal asymmetry and emotional reactivity

Background: As advances in neuroimaging further our understanding of the brain's functional connectivity, neuropsychology has moved away from a regional approach of attributing behavior to a specific region towards a network approach, attributing behavior to interconnected regions. A prime example of this is the suggested relevance of frontal asymmetry of the lateral prefrontal cortex (LPFC) in emotional processing. Yet, while neuroimaging defines relevant networks, it can only establish correlations and not causality.

Objective: We address this deficiency by applying cortico-cortical paired associative stimulation (ccPAS) to twenty-seven healthy, human participants (both genders represented equally). ccPAS involves TMS applied to two brain regions contemporaneously, changing the connectivity via Hebbian mechanisms.

Methods: We evaluate modifications in connectivity following ccPAS between the right and left LPFC that are dependent on the direction of ccPAS, i.e., which hemisphere is stimulated first. Participants performed an emotional reactivity task, assessed by measuring attentional bias, and brain activity was recorded with electroencephalogram (EEG) both at rest and in response to TMS pulses.

Results: We find that ccPAS modulates attentional bias bidirectionally depending on the order of stimulation. Furthermore, this modulation is accompanied by a change in frontal asymmetry. Measuring the direction of the information flow using TMS evoked potentials provides evidence that ccPAS strengthens inhibition from the hemisphere stimulated first to the hemisphere stimulated second.

Conclusions: Our findings provide causal evidence for the role of frontal asymmetry in emotional processing and establish ccPAS combined with the EEG measures as a tool to causally characterize functionality of neuronal circuits.