Rhythmic musical-electrical trigeminal nerve stimulation improves impaired consciousness

Figures

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  Fig. 1. Study design and experimental procedure. (A). Schematic of assessments and musical-electrical TNS. DOC patients’ consciousness was assessed by two experienced blinded clinicians using the CRS-R. Long-term outcomes were assessed using the GOSE. Patients’ brain activity was assessed by measuring 64-channel EEG during the presentation of continuous rhythmic auditory Chinese speech. The rhythmic musical-electrical TNS involved the simultaneous application of auditory music via earphones and electrical current via electrodes attached to the middle and lower parts of the patient’s face (see green and orange squares). Both acoustic and electrical stimulation were amplitude-modulated at gamma frequency (40 Hz, gamma-stimulation group) or beta frequency (28 Hz, beta-stimulation group), or their intensities were set to zero after a short (30 s) initial stimulation interval (sham-stimulation group). (B). Experimental procedure. Each patient underwent a 15-day long experimental procedure consisting of three 5-day long consecutive phases (pretest, stimulation, and posttest,) and a follow-up assessment approximately-one year after the initial CRS-R assessment. The treatment phase involved…

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  Fig. 2. Consciousness level in DOC patients before and after rhythmic musical-electrical TNS or sham stimulation. (A). CRS-R total scores of DOC patients in pretest (gray) and posttest (hue). The leftmost pair of boxes represents the consciousness level of the group of DOC patients who underwent gamma stimulation (gamma-stimulation group). The two other pairs represent results of matched patient groups receiving beta stimulation (beta-stimulation group) and sham stimulation (sham-stimulation group). Gamma stimulation and beta stimulation, but not sham stimulation, had positive effects on patients’ consciousness. (B). Percentage of DOC patients showing improved diagnosis (blue) after gamma stimulation (left), beta stimulation (center), or sham stimulation (right). Gamma stimulation and beta stimulation, but not sham stimulation, had positive effects on patients’ diagnosis. Overall, approximately-one third of the patients who received rhythmic musical-electrical TNS showed improved diagnosis. (C). Estimated effect of gamma stimulation (left) and beta stimulation (right) on patients’ consciousness level (after correcting for sham stimulation-related changes; see Methods). Beta stimulation…

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  Fig. 3. Rhythmic brain responses to amplitude-modulated speech in DOC patients before and after rhythmic musical-electrical TNS or sham stimulation. (A). Spectral response to beta (28 Hz, left) or gamma (40 Hz, center) amplitude-modulated speech in pretest (gray) and posttest (orange) for the gamma-stimulation group. Asterisks indicate significant responses at the test frequency relative to the noise floor (average responses in the surrounding frequency bins), reflecting robust phase-locked cortical responses to the amplitude modulation of the auditory speech stimuli (one-tailed paired t-test, FDR-corrected). The two peaks surrounding the test frequency arise from the isochronous nature of the speech stimuli, which had a word rate of 2 Hz (see Methods). The bar plot on the right shows the ASSR (amplitude at test frequency relative to noise floor), a measure of rhythmic brain activity, in pretest and posttest. It can be seen that ASSR at gamma frequency was significantly enhanced after vs before gamma stimulation. No such effect is observable on ASSR at beta frequency. (B). Same as (A) but for the beta-stimulation group. (C). Same as (A) but for the sham-stimulation group. (D). Estimated…

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  Fig. 4. Relation between changes in consciousness and changes in rhythmic brain activity in DOC patients. The scatterplot shows results from a correlation analysis testing for a functional coupling between changes in consciousness and changes in rhythmic brain activity. Correlation coefficient rho (ρ) and p-value describe, respectively, the strength and statistical significance of the coupling (linear regression line) across all patients. Orange, green, and magenta dots respectively represent patients in the gamma, beta, and sham-stimulation group.