Marne White¹ (), Yoojeong Choo¹, Alena Zheng¹, Joshua MacMillan², Jason Smith¹, Ines Violante³, Alexander Shackman¹, Weizhen Xie¹; ¹Department of Psychology, University of Maryland, College Park, ²A. James Clark School of Engineering, University of Maryland, College Park, ³School of Biomedical Engineering and Imaging Sciences, King’s College London

Deep circuits such as the amygdala-hippocampus complex play a key role in higher-level visual cognition and affective processing, yet they remain difficult to study and modulate noninvasively in humans. Limitations in the spatiotemporal resolution of existing methods constrain efforts to test causal links between subcortical dynamics and visual cognitive functions. Temporal interference (TI) stimulation is an emerging noninvasive technique that leverages the interaction of two high-frequency electrical currents (e.g., 2000 Hz and 2010 Hz), each too fast to elicit neuronal firing on its own, to generate a lower-frequency envelope (e.g., 10 Hz) in deeper tissue, offering a potential avenue for subcortical modulation without invasive intervention. Here, we examine the feasibility of TI stimulation in modulating amygdala-related pupillary responses during threat anticipation in a double-blinded, sham-controlled study. Participants performed a threat-anticipation task previously shown in fMRI work to engage the amygdala. On each trial, a geometric cue signaled that a threatening or neutral image-sound pair might occur unpredictably, eliciting high versus low levels of anticipatory anxiety. In our pupillometry adaptation, real-time pupil dilation provided a continuous physiological marker of this anticipatory state, devoid of low-level visual confounds (Experiment 1). We next applied 10 Hz TI stimulation targeting the amygdala circuit during the anticipation period in a randomized, blocked design (Experiment 2). Preliminary results indicate that 10 Hz TI stimulation attenuates pupil dilation to threat cues relative to neutral cues, whereas sham stimulation preserves the original threat-related pupil dilation. A high-frequency control study using a 0 Hz envelope (Experiment 3) provided further evidence for the specificity of the 10 Hz effect. Together, these findings highlight TI stimulation as a viable noninvasive approach for modulating deep subcortical circuits central to visual-affective processing.