Sensory cortical disinhibition is required for long-term fear memory in humans

Brown, J. A.; Ma, Y.; Wang, Y.; Massa, J. J.; Cheng, P. K.-H.; Chen, C.; Ding, M.; Schmidt, N. B.; Milad, M. R.; Soares, J. C.; Dolan, R. J.; You, C.; Li, W.

doi:10.64898/2026.08.28.745592

bioRxiv · 10.64898/2026.08.28.745592

Sensory cortical disinhibition is required for long-term fear memory in humans

Brown, J. A.·Ma, Y.·Wang, Y.·Massa, J. J.·Cheng, P. K.-H.·Chen, C.·Ding, M.·Schmidt, N. B.·Milad, M. R.·Soares, J. C.·Dolan, R. J.·You, C.·Li, W.

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Abstract

The transformation of transient threats into enduring memories is fundamental to survival, yet how the human brain constructs long-term fear memory remains elusive. Early sensory cortex, traditionally viewed as a passive feature analyzer, is increasingly recognized as an active participant in fear processing. Here, using a multimodal approach combining high-definition -frequency transcranial alternating current stimulation (HD -tACS) with simultaneous EEG-fMRI and transformer-based neural decoding, we tracked fear memory development across early formation, consolidation, and long-term retention stages (assessed at 15 min, 24 h, and 7 days post-conditioning). Spatiotemporal memory representations were evident at all three time points, beginning at an early sensory stage (40-60 ms post-stimulus). Conditioning potentiated occipital -oscillation desynchronization (a marker of visual cortical disinhibition), which predicted the strength of subsequent long-term memory traces. Critically, targeted -tACS over early visual cortex induced V1/V2 inhibition, abolished conditioning-potentiated desynchronization, and selectively disrupted fear-memory consolidation and retention while leaving initial acquisition intact. These findings establish sensory cortical disinhibition as a necessary mechanism for long-term fear memory in humans and identify early sensory cortex as a causal node for interventions targeting persistent maladaptive fear.

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Brown, J. A., Ma, Y., Wang, Y., Massa, J. J., Cheng, P. K.-H., Chen, C., Ding, M., Schmidt, N. B., Milad, M. R., Soares, J. C., Dolan, R. J., You, C., Li, W.. 2026-09-03. Sensory cortical disinhibition is required for long-term fear memory in humans. https://doi.org/10.64898/2026.08.28.745592

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