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bioRxiv · 10.1101/2025.04.28.651079

Continuous theta-burst stimulation of the prefrontal cortex in the macaque monkey: no evidence for within-target inhibition or cross-hemisphere disinhibition of neural activity

Lehmann, S. J.·Corneil, B. D.
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Abstract

BackgroundContinuous theta-burst stimulation (cTBS) can perturb neural activity and behavior by inducing effects that persist beyond the relatively short stimulation period. Although widely used in basic research and clinical settings, there lacks an understanding of the neurophysiological and behavioural effects of cTBS. Objectives/HypothesisTwo assumptions motivating the use of cTBS are that it will i) inhibit neural activity in the targeted area, and ii) consequently disinhibit neural activity in the mirroring region in the contralateral cortex. Here, we test these assumptions in the oculomotor system of healthy rhesus macaques. MethodsIn two macaques, we delivered cTBS between blocks of trials where they performed a delayed pro-/anti-saccade task, delivered cTBS to the right PFC (areas 8Ar and 46, which includes the frontal eye fields; 32 cTBS-PFC sessions), to the air as a SHAM control (27 cTBS-SHAM sessions), or to the nearby primary motor cortex as a brain control (21 cTBS-M1 sessions). Across these different types of sessions, we compared changes in oculomotor behavior (reaction times, error rates, peak saccade velocity), and changes in neural activity recorded from the left, contralateral PFC. ResultsDespite multiple lines of evidence consistent with TMS influencing neural activity in the cTBS-PFC and cTBS-M1 sessions, we found no behavioral evidence for inhibition of the right PFC in the cTBS-PFC sessions, nor any evidence for contralateral disinhibition in the left PFC. ConclusionsOur results call into question some of the fundamental assumptions underlying the application of cTBS. HighlightsO_LIcTBS widely used in lab and clinic to rebalance activity across cortex C_LIO_LIWe tested this in a monkey model, delivering cTBS to the prefrontal cortex C_LIO_LINo behavioural evidence for inhibition of brain area targeted by cTBS C_LIO_LINo evidence for disinhibition of spiking activity in mirroring, contralateral cortex C_LIO_LIResults question key assumptions about how cTBS influences network activity C_LI

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Lehmann, S. J., Corneil, B. D.. 2025-04-29. Continuous theta-burst stimulation of the prefrontal cortex in the macaque monkey: no evidence for within-target inhibition or cross-hemisphere disinhibition of neural activity. https://doi.org/10.1101/2025.04.28.651079

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