Assessing the distinct contributions of rostral and dorsomedial prefrontal cortex to cognitive control using temporal interference brain stimulation

The medial prefrontal cortex has been strongly implicated in a diverse array of cognitive functions in humans, including cognitive control and emotion regulation. Numerous studies have further proposed distinct functions for dorsomedial and rostromedial areas, but direct evidence from neuromodulation studies in healthy humans has been lacking due to the limitations of commonly used non-invasive neuromodulation techniques. Temporal interference (TI) stimulation is a recently developed technique for non-invasive deep brain stimulation that utilizes the frequency difference {Delta}[f] between pairs of high frequency electric fields to stimulate brain regions at depth and with improved precision compared to traditional techniques. Despite its theoretical potential, however, TI applications in humans have remained limited. Here, we examined the effects of TI stimulation to dorsomedial prefrontal cortex (dmPFC) and rostromedial prefrontal cortex (rmPFC) on cognitive control. Healthy adult participants (n = 32) were recruited and administered 20 Hz {Delta}[f] TI stimulation and 0 Hz {Delta}[f] sham stimulation in interleaved blocks while completing two variants of the Stroop Task, a well-established paradigm intended to measure cognitive control: the Color-Word and Affective Number Stroop. During the Color-Word Stroop, we found that 20 Hz {Delta}[f] TI stimulation of dmPFC and rmPFC relative to sham stimulation slowed down reaction times, with a significantly more pronounced slowing effect specific to incongruent trials for dmPFC stimulation as well as reduced accuracy. Importantly, effects of TI on dmPFC targets localized with fMRI differed markedly from dmPFC targeting based on a generic model, highlighting the importance of individualized targeting. For the Affective Stroop, we found that stimulation of dmPFC relative to sham stimulation facilitated increased reaction times in a valence specific-manner. This research provides novel evidence for distinct effects of neuromodulation in sub-regions of medial prefrontal cortex in healthy humans and sheds light on the strengths of TI as a non-invasive stimulation method for human cognitive neuroscience.