Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields

Abstract

Understanding the cellular mechanisms of kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation including forms of transcranial electrical stimulation, interferential stimulation, and high-rate spinal cord stimulation (SCS). Yet, the well-established low-pass filtering by neuronal membranes suggests minimal neuronal polarization in respond to charge-balanced kHz stimulation. The hippocampal brain slice model is among the most studied systems in neuroscience and exhaustively characterized in screening the effects of electrical stimulation. High-frequency electric fields of varied amplitudes (1–150 V/m), waveforms (sinusoidal, symmetrical pule, asymmetrical pulse) and frequencies (1 and10 kHz) were tested. Changes in single or paired-pulse field EPSPs (fEPSP) in CA1 were measured in response to radial-directed and tangential-directed electric fields, with brief (30 s) or long (30 min) application times. The effects of kHz stimulation on ongoing endogenous network activity were tested in carbachol-induced γ oscillation of CA3a and CA3c. Across 23 conditions evaluated, no significant changes in fEPSP were resolved, while responses were detected for within-slice control direct current (DC) fields; 1-kHz sinusoidal and pulse stimulation (≥60 V/m), but not 10 kHz, induced changes in oscillating neuronal network. We thus report no responses to low-amplitude 1-kHz or any 10-kHz fields, suggesting that any brain sensitivity to these fields is via yet to be-determined mechanism(s) of action which were not identified in our experimental preparation.

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions

“…Our results duplicate the functional separation between brain oscillations at 20 and 70 Hz. The functional separation between 70 Hz (2,000 and 2,070 Hz) and 20 Hz (2,000 and 2,020 Hz) TI stimulation also supports the hypothesis that electric fields of high-frequency carriers (2,000 Hz) may have little contribution to the results because of the intrinsic feature of the neural membrane that filters electrical signals in a low-pass manner ( Hutcheon and Yarom, 2000 ; Esmaeilpour et al, 2020 ). Additional studies could explore the effects of carrier frequency and envelope frequency more deeply.…”

Excitatory effect of biphasic kHz field stimulation on CA1 pyramidal neurons in slices

“…It seems that minimization of kHz-current shunted through ACSF in experiments with submerged slices is essential for obtaining a measurable neuronal response. When stimulating wire electrodes were placed in the bath on the sides of a slice but mainly were contacting the ACSF, no significant field effect was observed in the experiments of [24] and in our pilot experiments (not shown). Passing stimulating kHz-currents between parallel bare wires 5 mm long and 5 mm apart located above the slice also did not elicit any response at 3 mA (Fig.2), although in the setup used in the current study the kHz-FS of this amplitude was superthreshold at all frequencies.…”

“…Second, in the reported current-clamp whole-cell recordings during kHz-field application in a slice the intracellular voltage was masked by a strong high-frequency noise and an artifactual hyperpolarizing shift was observed due to the absence of the voltage follower in the headstage [23]. Third, measurements of population postsynaptic activity in the hippocampal slice before and after short (1s) or long (up to 30 min) kHz-frequency electric field application did not reveal significant effects either immediately or 30 and 60 min after termination of stimulation [24]. This is in contrast with the long lasting effects of kHz stimulation to produce peripheral axonal conduction block [25-27], or to produce central nervous system changes after spinal cord stimulation [28] and deep brain stimulation in in vivo experiments [14].…”

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions

“…Meanwhile, tACS at 20 Hz has been reported to improve the performance of implicit learning of SRTT in previous studies [22,52]. These findings [70,71]. Additional studies could explore the effects of carrier frequency and envelope frequency more deeply.…”