The Inhibitory Thermal Effects of Focused Ultrasound on an Identified, Single Motoneuron

Abstract

Focused ultrasound (US) is an emerging neuromodulation technology that has gained much attention due to its ability to modulate, noninvasively, neuronal activity in a variety of animals, including humans. However, there has been considerable debate about exactly which types of neurons can be influenced and what underlying mechanisms are in play. Are US-evoked motor changes driven indirectly by activated mechanosensory inputs, or more directly via central interneurons or motoneurons?Although it has been shown that US can mechanically depolarize mechanosensory neurons, there are no studies that have yet tested how identified motoneurons respond directly to US and what the underlying mechanism might be. Here, we examined the effects of US on a single, identified motoneuron within a well-studied and tractable invertebrate preparation, the medicinal leech, Hirudo verbana. Our approach aimed to clarify single neuronal responses to US, which may be obscured in other studies whereby US is applied across a diverse population of cells. We found that US has the ability to inhibit tonic spiking activity through a predominately thermal mechanism. USevoked effects persisted after blocking synaptic inputs, indicating that its actions were direct. Experiments also revealed that US-comparable heating blocked the axonal conduction of spontaneous action potentials. Finally, we found no evidence that US had significant mechanical effects on the neurons tested, a finding counter to prevailing views. We conclude that a non-sensory neuron can be directly inhibited via a thermal mechanism, a finding that holds promise for clinical neuromodulatory applications.

Induction of Human Motor Cortex Plasticity by Theta Burst Transcranial Ultrasound Stimulation

“…50 Moreover, an increase in tissue temperature would reduce but not enchance its excitability. 51,52 Therefore, the observed effects of tbTUS over the motor cortex are likely related to nonthermal effect. Although how tbTUS excites neurons via mechanical forces is not fully understood, it may induce activation of mechanosensitive voltage-gated sodium and calcium channels.…”

Comparison of Transcranial Focused Ultrasound and Transcranial Pulse Stimulation for Neuromodulation: A Computational Study

“…[20][21][22][23] The influence of mechanical vs thermal mechanisms of acoustic stimulation is debated, but it could be a differentiating factor between tFUS and TPS. [24][25][26][27] Future studies could investigate this directly. With respect to model interpretation, the consideration of intensity as a proxy for neuromodulation is rational because it indicates regions in the brain directly affected by ultrasound stimulation.…”

Neurostimulation success rate of repetitive‐pulse focused ultrasound in an in vivo giant axon model: An acoustic parametric study

“…However, as previously mentioned, lower NSRs at 3.3 MHz may be due to difficulties in properly positioning the focal spot on the neural structure. Furthermore, it is important to consider that local temperature elevations of a few degrees may produce an inhibitory effect and thus contribute to lowering the NSR for FUS applied at 3.3 MHz 55,56 . In particular, a recent study by Collins et al.…”

“…Furthermore, it is important to consider that local temperature elevations of a few degrees may produce an inhibitory effect and thus contribute to lowering the NSR for FUS applied at 3.3 MHz. 55,56 In particular, a recent study by Collins et al on an invertebrate medicinal leech model showed that ultrasound parameters capable of generating heat (2-3 • C) induced an inhibitory response as demonstrated by a reduction of close to 43%, on average, in the firing rate of a single motoneuron. 56 Nonetheless, when studying the effects of changing the PRF and number of pulses per FUS stimulus, significant jumps in NSR were observed for very low differences in thermal elevations.…”