A method for focused ultrasound (FUS) neuromodulation with simultaneous electroencephalogram recordings in awake, head-fixed mice with temporal lobe epilepsy
Carena Cornelssen, Braden Brown, Eli Finlinson, Skyler Blair, Sharayu Senthilkumar, Jan Kubanek, Karen S. Wilcox
2024 · 10.1101/2024.03.20.585988
Abstract
Transcranial focused ultrasound (FUS) may be a promising neuromodulation technology for treating people with epilepsy whose seizures are drug resistant. Prior studies have shown seizure suppression in animal studies using FUS. However, most of these studies were performed in evoked seizure models and not in animal models of epilepsy. Evoked seizure models do not exhibit the pathophysiology of epilepsy and do not exhibit spontaneous recurrent seizures, which define epilepsy. For translation to humans, there is a critical need to determine the specific FUS stimulation parameters that reduce spontaneous recurrent seizures in a chronic disease model of epilepsy. To achieve this goal, we developed and optimized an approach to determine the effects of ultrasonic stimulation on metrics of seizure-like events (SLEs) in awake, head-fixed mice within the intrahippocampal kainate (IHK) mouse model of temporal lobe epilepsy (TLE). A proof-of-principle study demonstrated that two target (bilateral and contralateral to the kainic acid injection site) stimulation conditions and two FUS parameter sets (low and high pressure) could be combined with the ability to simultaneously record hippocampal electroencephalograms. We also provide a method for analysis of the effects of FUS stimulation on the metrics of SLEs (interevent duration, SLE duration, and spike frequency).
Abstract via europepmc.
Exposures
Exposure 1: Low (0.2 MPa, 50% DC) and High (1.0 MPa, 10% DC) parameter sets; bilateral and contralateral hippocampal targets
Target: hippocampus — “bilateral and contralateral hippocampi relative to the kainic acid injection site”
Device: Olympus / Panametrics · Olympus · 18-0018-P ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 50, 10swept | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 200, 1,000swept | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 1.33, 3.33swept | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.0667, 0.333swept | ✓✓✓⚑ |
500 Hz PRF pulse trains of 0.2 s repeated with an interpulse train interval of 1.8 s, delivered for a 40-minute stimulation session with 1 h EEG before and after.
Flags from extraction
exposures[0].unspecified_domain.isppa_w_cm2— Text gives I_SPPA in mW/cm2 (1.33, 3.33) but the Table 1 column header gives W/cm2; recorded the table unit. Values do not obviously agree with the stated pressure and duty cycle.exposures[0].unspecified_domain.ispta_w_cm2— Table 1 and text give I_SPTA in mW/cm2 (66.67, 333.33); converted to W/cm2.exposures[0].timing.sonication_duration_s— Table calls 0.2 s the 'pulse train interval'; the Figure 10 legend calls it the pulse train duration of 200 ms, which was recorded as the sonication (train) duration. Pulse duration not stated; not computed.exposures[0].target— Two target conditions (bilateral and contralateral to the injection site) both at hippocampus, and two pressure/duty-cycle sets, were listed in one exposure. Only 2 mice were stimulated.n_subjects— 17 mice had surgery; only 2 IHK mice received FUS (proof-of-principle).