A longitudinal, randomized experimental pilot study to investigate the effects of airborne ultrasound on human mental health, cognition, and brain structure

Abstract

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants’ bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.Trial registration: The trial was registered at NIH www.clinicaltrials.gov, trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183.

Air-conducted ultrasound below the hearing threshold elicits functional changes in the cognitive control network

“…In addition, the fact that IFG has also been implicated in contrast-enhancement for cases of low auditory discriminability [ 77 , 84 , 85 ] and that auditory change detection can be recorded for consciously imperceptible stimulus differences [ 86 , 87 ] suggests that auditory stimulation does not necessarily have to produce a clear and distinct hearing impression to affect the CNS. Importantly, a similar conclusion can be drawn from Ascone et al‘s study [ 16 ], who showed that prolonged exposure to inaudible US at SPLs well below the HT was associated with significant grey matter volume reductions in large frontal clusters (including bilateral IFG), even though participants were asleep during most of the exposure. Apart from that, it remains unclear why 9 out of 10 participants who reported hearing the stimuli during ATC also had a hearing impression during BTC, while reporting correctly that no stimulation had occurred when the sound source was switched off (NTC).…”

“…Previous studies have reported various subjective symptoms in response to US exposure, such as ‘annoyance’, ’inability to concentrate’ [ 8 , 15 ], ‘vertigo’ or ‘tingling in the limbs’ [ 1 , 98 ]. The findings of this study add to the existing body of research, by suggesting that in addition to brain structure [ 16 ], US can also affect brain activity in areas involved in executive functions such attentional control and inhibition. Referencing evidence from various lines of research, the authors argued that bilateral IFG activation could reflect an increase in cognitive demand, mediated by attentional mechanisms in the presence of unpleasant and/or distractive stimuli.…”

“…Interestingly, while stimulation per se did not cause any adverse symptoms, the authors reported that (false) expectations about the presence of US led to small nocebo effects (i.e., slightly higher ratings for ‘ear pain’, ‘dizziness’, and ‘tinnitus’). In a recent fMRI-study, Ascone et al [ 16 ] also investigated potential adverse effects of inaudible US vs. sham by installing commercially available US sources capable of producing sound at about 22.4 kHz in participants’ bedrooms. The authors reported that prolonged US exposure over a period of 28 consecutive nights had no influence on any of the behavioral domains studied (such as sound sensitivity, quality of sleep or cognitive performance), while sham stimulation was again associated with minor nocebo-effects (i.e., increased somatization and phasic alertness).…”

Validity of the 1984 Interim Guidelines on Airborne Ultrasound and Gaps in the Current Knowledge

“…The few observations published to date consistently report that ultrasound is often perceived as displeasing or unpleasant as soon as the sound is heard, which suggests (but does not necessarily prove) that potentially adverse non-specific symptoms will only manifest if the sound is heard. This is supported by the few wellcontrolled blinded studies with inaudible ultrasound, in which no ultrasound-induced effects were reported at low SPLs (Fletcher et al 2018b;Ascone et al 2021).…”

“…The nocebo effect size appears to be small compared to some of the self-reported effects in observational studies, although the transfer from an experimental setting with a short exposure time to a long-term exposure setting of observational studies is clearly limited. In a single-blind randomized study, Ascone et al (2021) investigated whether exposure to inaudible ultrasound from commercial devices for 28 nights (22.4 kHz, target level below 90 dB SPL) or sham exposure is associated with self-reported behavioral effects, including non-specific symptoms and sleep quality. The authors reported no consistent evidence of ultrasound effects on self-reported behavior but there were instances of symptoms in the sham condition pointing to a possible nocebo effect driven by the expectation of being exposed.…”