Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex
Nardin Samuel, Ke Zeng, Irene E. Harmsen, Mandy Yi Rong Ding, Ghazaleh Darmani, Can Sarica, Brendan Santyr, Artur Vetkas, Aditya Pancholi, Anton Fomenko, Vanessa Milano, Kazuaki Yamamoto, Utpal Saha, Richard Wennberg, Nathan C. Rowland, Robert Chen, Andres M. Lozano
Brain Stimulation 2022, 15, 1337-1347 · 10.1016/j.brs.2022.10.001
Abstract
Introduction There is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects. Objective The aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity. Methods An 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated. Results tbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence. Conclusion The findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.
Abstract via europepmc.
Exposures
Exposure 1: Theta-burst TUS (tbTUS) to left primary motor cortex
Target: primary motor cortex — “left motor cortex (FDI hotspot in M1)”
Device: Sonic Concepts · Sonic Concepts Inc. · H246 ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 2.26 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | 0.23 | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
The theta burst TUS (tbTUS) paradigm consists of an 80s train of pulses with pulse repetition frequency (PFR) of 5 Hz, pulse duration of 20 ms, ultrasonic stimulus duration of 200 ms, and duty cycle of 10%, for a total number of 400 pulses. The power of ultrasound was set as 20W. For sham tbTUS, the transducer was flipped so that the inactive face of the transducer was in contact with the scalp and ultrasonic energy was directed away from the head.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— ISPPA/ISPTA values were taken from field measurements made in water in a previous study (Zeng et al. 2022), not measured in the present cohort; assigned to free_field domain since the text explicitly states measurements were 'made in water'.n_sessions_per_subject— Set to 2 (one active + one sham tbTUS visit); paper describes a third visit for an MRI scan only, not counted as a TUS session.readout_timing— TMS/EMG and MEG measures were all collected before and after (not during) tbTUS administration.