Personalized depth‐specific neuromodulation of the human primary motor cortex via ultrasound

Abstract

Non-invasive brain stimulation has the potential to boost neuronal plasticity in the primary motor cortex (M1), but it remains unclear whether the stimulation of both superficial and deep layers of the human motor cortex can effectively promote M1 plasticity. Here, we leveraged transcranial ultrasound stimulation (TUS) to precisely target M1 circuits at depths of approximately 5 mm and 16 mm from the cortical surface. Initially, we generated computed tomography images from each participant's individual anatomical magnetic resonance images (MRI), which allowed for the generation of accurate acoustic simulations. This process ensured that personalized TUS was administered exactly to the targeted depths within M1 for each participant. Using long-term depression and long-term potentiation (LTD/LTP) theta-burst stimulation paradigms, we examined whether TUS over distinct depths of M1 could induce LTD/LTP plasticity. Our findings indicated that continuous theta-burst TUS-induced LTD-like plasticity with both superficial and deep M1 stimulation, persisting for at least 30 min. In comparison, sham TUS did not significantly alter M1 excitability. Moreover, intermittent theta-burst TUS did not result in the induction of LTP- or LTD-like plasticity with either superficial or deep M1 stimulation. These findings suggest that the induction of M1 plasticity can be achieved with ultrasound stimulation targeting distinct depths of M1, which is contingent on the characteristics of TUS. KEY POINTS: The study integrated personalized transcranial ultrasound stimulation (TUS) with electrophysiology to determine whether TUS targeting superficial and deep layers of the human motor cortex (M1) could elicit long-term depression (LTD) or long-term potentiation (LTP) plastic changes. Utilizing acoustic simulations derived from individualized pseudo-computed tomography scans, we ensured the precision of TUS delivery to the intended M1 depths for each participant. Continuous theta-burst TUS targeting both the superficial and deep layers of M1 resulted in the emergence of LTD-like plasticity, lasting for at least 30 min. Administering intermittent theta-burst TUS to both the superficial and deep layers of M1 did not lead to the induction of LTP- or LTD-like plastic changes. We suggest that theta-burst TUS targeting distinct depths of M1 can induce plasticity, but this effect is dependent on specific TUS parameters.

Abstract via europepmc.

Flags from extraction

• exposures[0] — Superficial (~5 mm, grey matter) and deep (~16 mm, white matter) stimulation both target M1 at the same 500 kHz frequency and are combined into one exposure per the target x frequency rule; the two depths are described in the target label and protocol_description rather than as separate exposures.
• exposures[0].timing.pulse_duration_ms — The paper states a 0.2 s 'burst' duration with a 10% duty cycle repeated at a 5 Hz theta frequency; pulse_duration_ms=20 ms is derived from duty_cycle/PRF (10%/5Hz) per the burst rule, since no separate explicit pulse duration is given.
• exposures[0].timing.sonication_duration_s — 80 s is the total duration of the continuous theta-burst protocol and 2 s is the individual train duration in the intermittent protocol; both protocols report 8 s of cumulative active sonication, described in protocol_description.
• blinding — The paper does not use the word 'blind' explicitly; single-blinding of participants to condition is inferred from the sham design (transducer on scalp, no ultrasound delivered) and the statement that study objectives were not revealed to participants.