title: Cell-Type-Selective Effects of Intramembrane Cavitation as a Unifying Theoretical Framework for Ultrasonic Neuromodulation.
abstract: Diverse translational and research applications could benefit from the noninvasive ability to reversibly modulate (excite or suppress) CNS activity using ultrasound pulses, however, without clarifying the underlying mechanism, advanced design-based ultrasonic neuromodulation remains elusive. Recently, intramembrane cavitation within the bilayer membrane was proposed to underlie both the biomechanics and the biophysics of acoustic bio-effects, potentially explaining cortical stimulation results through a neuronal intramembrane cavitation excitation (NICE) model. Here, NICE theory is shown to provide a detailed predictive explanation for the ability of ultrasonic (US) pulses to also suppress neural circuits through cell-type-selective mechanisms: according to the predicted mechanism T-type calcium channels boost charge accumulation between short US pulses selectively in low threshold spiking interneurons, promoting net cortical network inhibition. The theoretical results fit and clarify a wide array of earlier empirical observations in both the cortex and thalamus regarding the dependence of ultrasonic neuromodulation outcomes (excitation-suppression) on stimulation and network parameters. These results further support a unifying hypothesis for ultrasonic neuromodulation, highlighting the potential of advanced waveform design for obtaining cell-type-selective network control.
authors.affiliation: Faculty of Biomedical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology , Haifa 32000, Israel.
authors.forename: Michael
authors.identifier: 0000-0002-2826-9461
authors.initials: M
authors.lastname: Plaksin
authors.affiliation: Faculty of Biomedical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology , Haifa 32000, Israel.
authors.forename: Eitan
authors.identifier: 0000-0001-6114-4196
authors.initials: E
authors.lastname: Kimmel
authors.affiliation: Faculty of Biomedical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology , Haifa 32000, Israel.
authors.forename: Shy
authors.identifier: 0000-0003-0376-3495
authors.initials: S
authors.lastname: Shoham
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D020747:Calcium Channels, T-Type / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010812:Physical Stimulation; D013788:Thalamus / Q000166:cytology / Q000502:physiology; D000069453:Ultrasonic Waves
chemical_list: D020747:Calcium Channels, T-Type
keywords: Hodgkin and Huxley; T-type calcium channels; action potential; model; neurons; ultrasound