Cerebellar Transcranial Alternating Current Stimulation in the Theta Band Prevents Recall of the Initial Fear...

Although the neural network underlying fear extinction has been extensively studied, the cerebellum's role has received little attention - despite its well-established involvement in associative learning. Our study therefore aimed to provide additional evidence that the cerebellum is part of the circuitry supporting fear-extinction processes, and to get a better understanding of how the cerebellum may contribute to fear extinction learning. In this study, 6 Hz cerebellar transcranial alternating current stimulation (ctACS) or sham stimulation was applied during extinction training in a two-day differential fear conditioning paradigm in young, healthy participants undergoing 3T fMRI, using a double-blind randomized design. Acquisition and extinction training occurred on day 1, followed by extinction recall on day 2. Skin conductance responses showed that 6 Hz ctACS applied during extinction training reduced spontaneous fear recovery during recall. During extinction training, differential fMRI activation (CS+ > CS-) was significantly higher in the occipital cortex in the verum compared to the sham group. During recall, differential fMRI activation was significantly higher in the precentral gyrus in the sham compared to the verum group at the time the aversive unconditioned response (US) was expected but did not occur. Furthermore, in recall, parametric modulation based on trial-by-trial model-derived prediction errors for no-US events revealed significantly higher activation in frontal cortical areas, including the anterior cingulate cortex, and parietal cortical areas in the sham compared to the verum group. Volume of interest analyses showed significantly higher beta values towards the CS+ compared to the CS- in the sham group, but not in the verum group in the right insula related to the prediction of the US and its unexpected omission in early recall. Although direct stimulation effects cannot be ruled out, 6 Hz ctACS-related increases in activation in visual regions during extinction training may indicate enhanced attention to CS-related visual and/or contextual cues. Furthermore, 6 Hz ctACS facilitated the downregulation of brain regions involved in fear conditioning during recall, potentially reducing spontaneous recovery. Future studies are warranted to further evaluate whether enhancement of cerebellar theta oscillations can help to stabilize extinction effects and therefore support exposure therapy.