Biology subjects

Cleveland, R. O.

Publications and source records attributed to Cleveland, R. O..

3 recordsLinked to original sources

bioRxiv2025

Non-invasive in vivo acoustoelectric neuromodulation and its contribution to ultrasound stimulation

Non-invasive brain stimulation offers therapeutic potential without the risks of surgery, yet current electrical approaches lack spatial precision and depth due to the long wavelengths of electric fields. Here we demonstrate that the acoustoelectric interaction--the nonlinear coupling between applied acoustic and electric fields--can overcome these limitations to achieve spatially focused, non-invasive neuromodulation. Using in vitro and in vivo rodent electrophysiology, we show motor-evoked potentials that depend on both the amplitude and frequency of the acoustoelectric field, with artefactual controls excluding purely acoustic or electrical origins. We further identify an acoustoelectric contribution to conventional ultrasound stimulation, arising from the interaction between ultrasound-induced electrical signals and propagating acoustic waves. These findings establish acoustoelectric neuromodulation as a distinct mechanism of neural activation and a significant contributor to how ultrasound stimulation influences brain activity, opening new directions for precise, non-invasive neuromodulation and neurotherapeutic development.

neuroscience↗

bioRxiv2025

Low-intensity focused ultrasound to human amygdala reveals a causal role in ambiguous emotion processing and alters local and network-level activity

The amygdala is a core region changed in depression, a disorder characterized by compromised emotion, motivation and learning processes. However, lesion studies in humans examining amygdala function have largely focused on its role in processing fear. It currently remains unclear what causal role the human amygdala plays in more complex emotion, motivation and learning processes in daily life. This is because it has not been possible to reversibly modulate amygdala activity non-invasively in humans. Here, we used transcranial focused ultrasound stimulation (TUS) to bilaterally perturb neural activity in the basolateral amygdala (BLA). In separate sessions (n = 87), 29 healthy volunteers received offline-TUS to bilateral BLA, mid-insula or sham before playing a novel emotional learning task validated in an independent large cohort online (n = 210). 7T-resting-state and metabolite signals clearly demonstrated target engagement. BLA-TUS reduced the BLAs connectivity fingerprint and decreased its excitation/inhibition balance, suggesting an inhibitory effect of our TUS protocol on BLA activity. In behaviour, BLA-TUS caused a stimulation volume-dependent increase in the tendency to approach neutral, emotionally ambiguous faces, treating them more similarly to happy faces, and a slowing of reaction times for those two emotion categories. These effects were functionally and regionally specific and suggest a causal role for the amygdala in resolving emotional ambiguity. Our results provide important insights for future studies into mood disorders where ambiguous situations might be harder to resolve, which could contribute to existing emotional and learning biases.

neuroscience↗

bioRxiv2020

Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked

BackgroundTranscranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways. ObjectiveWe aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal. MethodsIn 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 {degrees}C at the target and <3 {degrees}C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS. ResultsWe found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound. ConclusionFuture studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.

neuroscience↗