Preliminary Data on Nrem Sleep Duration Changes Post-thalamic Focused Ultrasound Stimulation

Research Objectives: Currently, there are few therapies to improve consciousness after severe brain injury. Thalamic focused ultrasound stimulation (tFUS) has been studied as a non-invasive neuromodulation approach. Sleep elements such as K-complexes and sleep spindles, which have generators in the thalamus, have been related to better outcomes in sABI. This study assessed whether tFUS to the thalamus could increase patients' behavioral responsiveness, akin to non-REM (nREM) sleep, in this population.

Design: Nocturnal polysomnography (PSG) was recorded and automatically scored using the Dreem2 headband based on frontal (Fp1, F7, F8) and occipital (O1, O2) electrodes. On average, recordings had a quality index of 70%, a sleep duration above 5h. Percentage of sleep spent in nREM were compared pre/post tFUS using a paired t-test. The changes in nREM sleep percentage were also correlated to changes in Coma Recovery Scale-Revised (CRS-R) scores after tFUS.

Setting: Casa Colina Hospital and Centers for healthcare

Participants: Fourteen patients (age range: 21-70 years) classified as being in a minimally conscious states (MCS; ie, 11 MCS+, 2 MCS-) or vegetative state (VS; n=1) based on the CRS-R were included in this study. Etiologies included traumatic brain injuries (n = 6), anoxia (n = 7), and stroke (n=1). Time since injury ranged from one to six years.

Interventions: one session (10min) of tFUS applied on the left temporal bone using Brainsonix BX Pulsar 1002.

Main Outcome Measures: Percentage of sleep spent in nREM as well as CRS-R scores and subscores.

Results: Using a paired t-test, a significant increase was observed in: 1) The CRS-R total scores (t=7.1;p <.001) and in the following subscores: Visual (Z=2.7;p=.004), Auditory (Z=1.8;p=.04), Communication (Z=1.8;p=.04), and Arousal (Z=1.7;p=.04); 2) The amount of nREM sleep, more exactly, N2 sleep stage % (t= 2.5, p =.03) with an increase of 12% on average. However, no significant correlation was found between the changes in CRS-R (total scores) and N2 (%). Factors such as age, etiology, and time since injury did not seem to significantly affect the percent change in N2 sleep stage.

Conclusions: These preliminary data reveal a significant increase in behavioral responses following tLIFUP as well as an increase in nREM/N2 sleep stage which is characterized by sleep spindles mainly generated by the thalamus and thalamo-cortical loops. Our data suggests potential synergistic effects as well as preliminary therapeutic effects of tLIFUP in prolonged DOC patients. However, our study had a small sample size and was open label. A randomized sham-controlled clinical trial should be performed in the future.

Author(s) Disclosures: Nihil