Targeting fear behaviour using non-invasive neuromodulation

Anxious individuals show impaired control over emotional behavior, resulting in excessive fear and avoidance. This impairment likely reflects disrupted regulation of emotional actions by the lateral frontopolar cortex (FPl), mediated through its connections with the amygdala and sensorimotor systems. In highly anxious individuals, FPl hyperexcitability is associated with stronger amygdalofugal projections and reduced functional recruitment when control is required, indicating altered fronto-limbic dynamics as a potential intervention target. Building on this framework, we investigated two neuromodulatory approaches. First, dual-site, phase-coupled transcranial alternating current stimulation (tACS) was used to modulate prefrontal–sensorimotor coupling, improving emotion control and indirectly influencing amygdala circuitry. Second, transcranial ultrasonic stimulation (TUS) was applied to directly target bilateral amygdala circuits. Across two controlled threat-conditioning experiments, amygdala-targeted TUS—unlike hippocampal stimulation—selectively modulated learning by slowing initial threat acquisition while enhancing subsequent extinction. Together, these findings refine our understanding of amygdala circuit function and underscore the potential of targeted neuromodulation as a translational strategy for improving therapeutic outcomes.

1. Bramson B, Meijer S, van Nuland Toni I, Roelofs K (2023). Anxious individuals shift emotion control from lateral frontal pole to dorsolateral prefrontal cortex. Nature Communications 14, 4880. https://doi.org/10.1038/s41467-023-40666-3

2. Meijer S, Bramson B, Toni, I Roelofs K (2026). Improving emotion control in social anxiety by targeting rhythmic brain circuits. Journal of Neuroscience, e0769252026, DOI: https://doi.org/10.1523/JNEUROSCI.0769-25.2026

3. Meijer S, Carpino, E, Kop B, Lam J, Roelofs K*, Verhagen L* (2026). The human amygdala in threat learning and extinction. Science Advances. 12,eaea8233. https://www.science.org/doi/10.1126/sciadv.aea8233

Bio

Karin Roelofs is Professor of Experimental Psychopathology at Radboud University and Chair of the Affective Neuroscience group at the Donders Institute for Brain, Cognition and Behaviour. Her research focuses on the neural mechanisms of stress vulnerability and resilience, combining behavioural and autonomic phenotyping with advanced neuroimaging (fMRI, MEG) and neuromodulation techniques, including transcranial ultrasound stimulation (TUS). She also leads prospective longitudinal studies on emotional action control and decision-making in both typical and at-risk populations, translating resilience markers into targeted interventions. Roelofs is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW) and serves on the board of ALLEA (All European Academies); she is also a former president of the International Resilience Alliance (INTRESA). In 2026, she joined the Scientific Council of the European Research Council (ERC). She has received numerous national and international awards, including three ERC grants, and was awarded the Evens Science Prize in 2020 for her contributions to stress resilience and cognitive neuroscience.