Biology subjects

Raiff, L.

Publications and source records attributed to Raiff, L..

3 recordsLinked to original sources

bioRxiv2026

Motor signals modulate cortical but not subcortical processing of self-initiated sounds

When we produce sounds ourselves, the brain modulates the auditory neural response through an efference copy mechanism, allowing us to distinguish between self-initiated and externally generated auditory inputs. However, the precise level of the auditory pathway at which this attenuation occurs remains unclear. While evidence from animal models suggests that early auditory processing of self-generated sounds may be modulated by corticofugal signaling, localized cortical modulation would preserve the high-fidelity subcortical sound encoding while allowing flexible, context-dependent processing at higher levels. To probe potential motor influences in the early auditory system, we collected scalp-recorded frequency following responses (FFRs) from 33 normal-hearing adults during active (self-initiated) and passive (externally presented) listening conditions using a 170 ms speech stimulus. Data were collected with a vertical montage that emphasizes subcortical generators of the FFR. We observed no significant differences in the FFR between active and passive conditions in spectral power, response amplitude, pitch tracking, onset latency, or phase consistency. In contrast, cortical event-related potentials showed motor-induced suppression (MIS): reduced early peak amplitudes in the active condition after correcting for motor signals, increased phase consistency prior to auditory feedback, and more precise phase consistency at sound offset. In addition to indicating FFRs can be collected during a wider range of behavioral tasks without substantial motor contamination, our observation of the canonical MIS in cortical signals but not in FFRs suggests that MIS of self-initiated sounds primarily affects later stages of auditory processing rather than the early encoding reflected in the FFR.

neuroscience↗

bioRxiv2025

Transcranial ultrasound stimulation modulates neuronal membrane potentials across broad timescales in the awake mammalian brain

BackgroundTranscranial ultrasound stimulation (TUS) offers noninvasive neuromodulation with high spatial and temporal precision, but its cellular-level effects in the awake brain remain poorly understood. ObjectiveWe investigated how low-intensity TUS modulates membrane voltage dynamics in single cortical neurons in awake mice. MethodsUsing the genetically encoded voltage indicator SomArchon, we performed high-speed kilohertz voltage imaging in awake head-fixed mice. TUS was delivered with a 0.35 MHz transducer at 10 or 40 Hz pulse repetition frequency with a 20% duty cycle, at intensities below the estimated threshold for auditory brainstem activation. We analyzed changes in membrane potential (Vm), spiking, and coordination across simultaneously recorded neurons. ResultsTUS evoked rapid (<10 ms) Vm depolarizations in 42.8% of neurons, while only 20.5% showed increased spiking, highlighting a direct effect of TUS on modulating synaptic inputs. Many neurons were entrained at both PRFs (20.8% at 10 Hz; 12.7% at 40 Hz) with Vm exhibiting significant phase-locking to individual TUS pulses. Vm entrainment was accompanied by increased temporal coordination across neurons and reset network synchrony. Furthermore, TUS-evoked cellular responses adapted over time, often transitioning from membrane depolarization to hyperpolarization upon repeated exposures, demonstrating prominent response depression. ConclusionBy resolving single-neuron responses, our results demonstrate that TUS directly activates individual cortical neuron with a latency shorter than 10 ms. TUS pulsed at physiologically relevant frequencies of 10 and 40 Hz robustly entrains neural dynamics, alters network coordination and evokes neuronal plasticity. These results highlight the therapeutic potential of designing TUS pulsing patterns to target specific neural circuit dynamics.

neuroscience↗

bioRxiv2024

Ultrasound pulse repetition frequency preferentially activates different neuron populations independent of cell type

Transcranial ultrasound activates mechanosensitive cellular signaling and modulates neural dynamics. Given that intrinsic neuronal activity is limited to a couple hundred hertz and often exhibits frequency preference, we examined whether pulsing ultrasound at physiologic pulse repetition frequencies (PRFs) could selectively influence neuronal activity in the mammalian brain. We performed calcium imaging of individual motor cortex neurons, while delivering 0.35 MHz ultrasound at PRFs of 10, 40, and 140 Hz in awake mice. We found that most neurons were preferentially activated by only one of the three PRFs, highlighting unique cellular effects of physiologic PRFs. Further, ultrasound evoked responses were similar between excitatory neurons and parvalbumin positive interneurons regardless of PRFs, indicating that individual cell sensitivity dominates ultrasound-evoked effects, consistent with the heterogeneous mechanosensitive channel expression we found across single neurons in mice and humans. These results highlight the feasibility of tuning ultrasound neuromodulation effects through varying PRFs.

neuroscience↗