A tool for monitoring cell type–specific focused ultrasound neuromodulation and control of chronic epilepsy

Abstract

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.

Abstract via europepmc.

Flags from extraction

• n_subjects — Group sizes vary by experiment (n = 5 to 8, PET n = 5 and n = 3, epilepsy n = 5) and animals may be shared across experiments; no total is stated.
• exposures[0].in_situ — 0.62 MPa peak negative pressure and 12.3 W/cm2 ISPPA were measured through an explanted skull at 220 peak volts (device characterisation), not for the 4.5 W/cm2 protocol.
• exposures[0].unspecified_domain.isppa_w_cm2 — The 4.5 W/cm2 ISPPA of the 900 Hz protocol is not said to be in water or in situ; the Methods describe ISPPA derived from hydrophone pressure through a skull with an assumed brain impedance, but do not tie that to this value.
• exposures[0].timing — Pulse duration is not stated; DC/PRF is not computed. Waveform mixes continuous 200 ms pulses and a 900 Hz pulsed protocol (and a 1 Hz, 8 % protocol in PET). The PRF and duty-cycle lists cover the pulsed protocols only. Quote for the lists is the 1 Hz sentence; the 900 Hz / 20 % values are in the sentence quoted for exposures[1].
• exposures[0].timing.sonication_duration_s — 200 ms from the continuous-wave experiment and 5 s from the 900 Hz and 1 Hz protocols.
• exposures[2].timing — Target stated as the centromedial nucleus of the thalamus (CMT); mapped to centromedian_nucleus as nearest term. Fig. 3 caption labels the CMT panel as VTA but the text assigns it to CMT.
• exposures[3].timing — Intensities given only in figure; no numeric pressure or intensity in text for these pulses.
• exposures[0].device — Piezoelectric ring from Thorlabs assembled in-house with balsa and magnesium layers; driving electronics (Agilent 33210A, ENI 2100L amplifier) do not set the family.
• sham_type — Off-target stimulation 3 mm dorsal in CMT; PET compared stimulated with unstimulated hemisphere and with a 1 Hz protocol; no powered-off arm.
• auditory_control — Off-target (cortex/skull) stimulation response was 55 % of on-target, used to argue audible sound is not substantial; no masking.
• readout_timing — Photometry online; PET FDG uptake over 30 min stimulation with scan afterwards; LFP spikes analysed after stimulation.
• exposures[0].timing.pulse_repetition_frequency_hz — 1 Hz protocol in PET gave no significant FDG increase; 900 Hz is the main protocol.