Direct Activation of Cortical Neurons in the Primary Somatosensory Cortex of the Rat in Vivo Using Focused Ultrasound
Kush Tripathi, Tongsheng Zhang, Nathan McDannold, Yong-Zhi Zhang, Gösta Ehnholm, Yoshio Okada
Ultrasound in Medicine & Biology 2020 · 10.1016/j.ultrasmedbio.2020.06.003
Abstract
We address the recent controversy over whether focused ultrasound (FUS) activates cortical neurons directly or indirectly by initially activating auditory pathways. We obtained two types of evidence that FUS can directly activate cortical neurons. The depth profile of the local field potential (LFP) in the barrel cortex of the rat in vivo indicated a generator was located within the cortical gray matter. The onset and peak latencies of the initial component p1 were 3.2 ± 0.25 ms (mean ± standard error of the mean) and 7.6 ± 0.12 ms, respectively, for the direct cortical response (DCR), 6.8 ± 0.40 and 14.3 ± 0.54 ms for the FUS-evoked LFP (4 MHz, 3.2 MPa, 50 or 300 µs/pulse, 1-20 pulses at 1 kHz) and 6.9 ± 0.51 and 15.8 ± 0.94 ms for the LFP evoked by 1-ms deflection of the C2 whisker projecting to the same area. The peak latency of the FUS p1 was statistically (t-test) longer than the DCR, but shorter than the whisker p1 at p < 0.005.
Abstract via europepmc.
Exposures
Exposure 1: FUS to barrel column C2 of primary somatosensory cortex (skull removed)
Target: primary somatosensory cortex — “barrel column C2 (S1 barrel cortex)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 4,000 | ✓✓✓ |
| Pulse duration (ms) | 0.05, 0.3swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 0.00000125, 0.02swept | ✓✓✓ |
| Free-field pressure (kPa) | 3,300 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 355 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.00015, 0.036, 0.714swept | ✓✓✓⚑ |
It produced a train of FUS pulses (each pulse varied between 1.25 and 300 ms depending on the experiment, containing multiple cycles of sinusoidally varying 4-MHz ultrasound). The pulse duration was 50 or 300 ms in most of the experiments. The number of pulses ranged between 1 and 20 at a pulse repetition frequency (PRF) of 1 kHz. Elsewhere the paper labels the shortest pulse duration in microseconds (e.g. '1.25-μs pulse'), so it is unclear whether pulse durations are in ms or μs (see flag).
Flags from extraction
exposures[0].timing.pulse_duration_ms— Pulse duration is stated inconsistently: 'The pulse duration was 50 or 300 ms in most of the experiments' and the Figure 3 caption states '1.25 300 ms', yet elsewhere the same intensity calculation labels the shortest duration '1.25-μs pulse', and a 300 ms pulse is physically impossible at the stated 1 kHz PRF (1 ms period). Left not_reported because the correct unit (ms vs μs) cannot be resolved from the text.exposures[0].in_situ.isppa_w_cm2— The paper labels 355 W/cm2 as a 'derated' Isptp value 'at the location of interest for measurement (0-3 mm below the cortex)', but this is numerically identical to the intensity value obtained from beam measurements with the lens in place (see free_field discussion elsewhere in Methods), raising doubt about whether true tissue derating was performed or whether this is simply the same water-measured value re-labelled.exposures[0].in_situ.ispta_w_cm2— The three listed Ispta values are tied to pulse-duration labels that mix ms and μs inconsistently in the source text (see pulse_duration_ms flag); recorded as stated with unresolved unit ambiguity.n_subjects— The paper gives the total number of animals used across all experiments in the study (whisker mapping, DCR, and FUS comparisons combined), not a count restricted to animals that received FUS specifically.