Neural complexity and the spectral slope characterise auditory processing in wakefulness and sleep.

Auditory processing and the complexity of neural activity can both indicate residual consciousness levels and differentiate states of arousal. However, how measures of neural signal complexity manifest in neural activity following environmental stimulation and, more generally, how the electrophysiological characteristics of auditory responses change in states of reduced consciousness remain under-explored. Here, we tested the hypothesis that measures of neural complexity and the spectral slope would discriminate stages of sleep and wakefulness not only in baseline electroencephalography (EEG) activity but also in EEG signals following auditory stimulation. High-density EEG was recorded in 21 participants to determine the spatial relationship between these measures and between EEG recorded pre- and post-auditory stimulation. Results showed that the complexity and the spectral slope in the 2-20 Hz range discriminated between sleep stages and had a high correlation in sleep. In wakefulness, complexity was strongly correlated to the 20-40 Hz spectral slope. Auditory stimulation resulted in reduced complexity in sleep compared to the pre-stimulation EEG activity and modulated the spectral slope in wakefulness. These findings confirm our hypothesis that electrophysiological markers of arousal are sensitive to sleep/wake states in EEG activity during baseline and following auditory stimulation. Our results have direct applications to studies using auditory stimulation to probe neural functions in states of reduced consciousness.

Sleep and cardiac autonomic modulation in older adults: Insights from an at-home study with auditory deep sleep stimulation.

The autonomic nervous system regulates cardiovascular activity during sleep, likely impacting cardiovascular health. Aging, a primary cardiovascular risk factor, is associated with cardiac autonomic disbalance and diminished sleep slow waves. Therefore, slow waves may be linked to aging, autonomic activity and cardiovascular health. However, it is unclear how sleep and slow waves are linked to cardiac autonomic profiles across multiple nights in older adults. We conducted a randomized, crossover trial involving healthy adults aged 62-78 years. Across 2 weeks, we applied auditory stimulation to enhance slow waves and compared it with a SHAM period. We measured sleep parameters using polysomnography and derived heart rate, heart rate variability approximating parasympathetic activity, and blood pulse wave approximating sympathetic activity from a wearable. Here, we report the results of 14 out of 33 enrolled participants, and show that heart rate, heart rate variability and blood pulse wave within sleep stages differ between the first and second half of sleep. Furthermore, baseline slow-wave activity was related to cardiac autonomic activity profiles during sleep. Moreover, we found auditory stimulation to reduce heart rate variability, while heart rate and blood pulse wave remained unchanged. Lastly, within subjects, higher heart rate coincided with increased slow-wave activity, indicating enhanced autonomic activation when slow waves are pronounced. Our study shows the potential of cardiac autonomic markers to offer insights into participants' baseline slow-wave activity when recorded over multiple nights. Furthermore, we highlight that averaging cardiac autonomic parameters across a night may potentially mask dynamic effects of auditory stimulation, potentially playing a role in maintaining a healthy cardiovascular system.

Closed-loop auditory stimulation of slow-wave sleep in chronic insomnia: a pilot study.

Insomnia is a prevalent and disabling condition whose treatment is not always effective. This pilot study explores the feasibility and effects of closed-loop auditory stimulation (CLAS) as a potential non-invasive intervention to improve sleep, its subjective quality, and memory consolidation in patients with insomnia. A total of 27 patients with chronic insomnia underwent a crossover, sham-controlled study with 2 nights of either CLAS or sham stimulation. Polysomnography was used to record sleep parameters, while questionnaires and a word-pair memory task were administered to assess subjective sleep quality and memory consolidation. The initial analyses included 17 patients who completed the study, met the inclusion criteria, and received CLAS. From those, 10 (58%) received only a small number of stimuli. In the remaining seven (41%) patients with sufficient CLAS, we evaluated the acute and whole-night effect on sleep. CLAS led to a significant immediate increase in slow oscillation (0.5-1 Hz) amplitude and activity, and reduced delta (1-4 Hz) and sigma/sleep spindle (12-15 Hz) activity during slow-wave sleep across the whole night. All these fundamental sleep rhythms are implicated in sleep-dependent memory consolidation. Yet, CLAS did not change sleep-dependent memory consolidation or sleep macrostructure characteristics, number of arousals, or subjective perception of sleep quality. Results showed CLAS to be feasible in patients with insomnia. However, a high variance in the efficacy of our automated stimulation approach suggests that further research is needed to optimise stimulation protocols to better unlock potential CLAS benefits for sleep structure and subjective sleep quality in such clinical settings.

Novel murine closed-loop auditory stimulation paradigm elicits macrostructural sleep benefits in neurodegeneration.

Boosting slow-wave activity (SWA) by modulating slow waves through closed-loop auditory stimulation (CLAS) might provide a powerful non-pharmacological tool to investigate the link between sleep and neurodegeneration. Here, we established mouse CLAS (mCLAS)-mediated SWA enhancement and explored its effects on sleep deficits in neurodegeneration, by targeting the up-phase of slow waves in mouse models of Alzheimer's disease (AD, Tg2576) and Parkinson's disease (PD, M83). We found that tracking a 2 Hz component of slow waves leads to highest precision of non-rapid eye movement (NREM) sleep detection in mice, and that its combination with a 30° up-phase target produces a significant 15-30% SWA increase from baseline in wild-type (WTAD) and transgenic (TGAD) mice versus a mock stimulation group. Conversely, combining 2 Hz with a 40° phase target yields a significant increase ranging 30-35% in WTPD and TGPD mice. Interestingly, these phase-target-triggered SWA increases are not genotype dependent but strain specific. Sleep alterations that may contribute to disease progression and burden were described in AD and PD lines. Notably, pathological sleep traits were rescued by mCLAS, which elicited a 14% decrease of pathologically heightened NREM sleep fragmentation in TGAD mice, accompanied by a steep decrease in microarousal events during both light and dark periods. Overall, our results indicate that model-tailored phase targeting is key to modulate SWA through mCLAS, prompting the acute alleviation of key neurodegeneration-associated sleep phenotypes and potentiating sleep regulation and consolidation. Further experiments assessing the long-term effect of mCLAS in neurodegeneration may majorly impact the establishment of sleep-based therapies.

The Development of a Wearable Biofeedback System to Elicit Temporal Gait Asymmetry using Rhythmic Auditory Stimulation and an Assessment of Immediate Effects.

Temporal gait asymmetry (TGA) is commonly observed in individuals facing mobility challenges. Rhythmic auditory stimulation (RAS) can improve temporal gait parameters by promoting synchronization with external cues. While biofeedback for gait training, providing real-time feedback based on specific gait parameters measured, has been proven to successfully elicit changes in gait patterns, RAS-based biofeedback as a treatment for TGA has not been explored. In this study, a wearable RAS-based biofeedback gait training system was developed to measure temporal gait symmetry in real time and deliver RAS accordingly. Three different RAS-based biofeedback strategies were compared: open- and closed-loop RAS at constant and variable target levels. The main objective was to assess the ability of the system to induce TGA with able-bodied (AB) participants and evaluate and compare each strategy. With all three strategies, temporal symmetry was significantly altered compared to the baseline, with the closed-loop strategy yielding the most significant changes when comparing at different target levels. Speed and cadence remained largely unchanged during RAS-based biofeedback gait training. Setting the metronome to a target beyond the intended target may potentially bring the individual closer to their symmetry target. These findings hold promise for developing personalized and effective gait training interventions to address TGA in patient populations with mobility limitations using RAS.

The Brain Selectively Tunes to Unfamiliar Voices during Sleep.

The brain continues to respond selectively to environmental stimuli during sleep. However, the functional role of such responses, and whether they reflect information processing or rather sensory inhibition, is not fully understood. Here, we present 17 human sleepers (14 females) with their own name and two unfamiliar first names, spoken by either a familiar voice (FV) or an unfamiliar voice (UFV), while recording polysomnography during a full night of sleep. We detect K-complexes, sleep spindles, and microarousals, and assess event-related and frequency responses as well as intertrial phase synchronization to the different stimuli presented during nonrapid eye movement (NREM) sleep. We show that UFVs evoke more K-complexes and microarousals than FVs. When both stimuli evoke a K-complex, we observe larger evoked potentials, more precise time-locking of brain responses in the delta band (1-4 Hz), and stronger activity in the high frequency (>16 Hz) range, in response to UFVs relative to FVs. Crucially, these differences in brain responses disappear completely when no K-complexes are evoked by the auditory stimuli. Our findings highlight discrepancies in brain responses to auditory stimuli based on their relevance to the sleeper and propose a key role for K-complexes in the modulation of sensory processing during sleep. We argue that such content-specific, dynamic reactivity to external sensory information enables the brain to enter a sentinel processing mode in which it engages in the important internal processes that are ongoing during sleep while still maintaining the ability to process vital external sensory information.SIGNIFICANCE STATEMENT Previous research has shown that sensory processing continues during sleep. Here, we studied the capacity of the sleeping brain to extract and process relevant sensory information. We presented sleepers with their own names and unfamiliar names spoken by either an FV or a UFV. During NREM sleep, UFVs elicited more K-complexes and microarousals than FVs. By contrasting stimuli that evoked K-complexes, we demonstrate that UFVs evoked larger, more synchronized brain responses as well as stronger power at high frequencies (>16 Hz) relative to FVs. These differences in brain responses disappeared when no K-complexes were evoked. Our results suggest a pivotal role for K-complexes in the selective processing of relevant information during NREM sleep.

Feasibility, efficacy, and functional relevance of automated auditory closed-loop suppression of slow-wave sleep in humans.

Slow-wave sleep (SWS) is a fundamental physiological process, and its modulation is of interest for basic science and clinical applications. However, automatised protocols for the suppression of SWS are lacking. We describe the development of a novel protocol for the automated detection (based on the whole head topography of frontal slow waves) and suppression of SWS (through closed-loop modulated randomised pulsed noise), and assessed the feasibility, efficacy and functional relevance compared to sham stimulation in 15 healthy young adults in a repeated-measure sleep laboratory study. Auditory compared to sham stimulation resulted in a highly significant reduction of SWS by 30% without affecting total sleep time. The reduction of SWS was associated with an increase in lighter non-rapid eye movement sleep and a shift of slow-wave activity towards the end of the night, indicative of a homeostatic response and functional relevance. Still, cumulative slow-wave activity across the night was significantly reduced by 23%. Undisturbed sleep led to an evening to morning reduction of wake electroencephalographic theta activity, thought to reflect synaptic downscaling during SWS, while suppression of SWS inhibited this dissipation. We provide evidence for the feasibility, efficacy, and functional relevance of a novel fully automated protocol for SWS suppression based on auditory closed-loop stimulation. Future work is needed to further test for functional relevance and potential clinical applications.

Rhythmic auditory stimulation incorporated in training improved movements in individuals with psychotic-like experiences.

Movement abnormalities, including movement slowing and irregular muscle contraction, exist in individuals with psychotic-like experiences (PLEs) and serve as vulnerable factors of developing psychotic diseases in the psychosis continuum. To date scarce studies have developed early intervention programs tackling these initial impairments, which may be caused by basal ganglia alterations, in the early stage of the psychosis course. Rhythmic auditory stimulation (RAS) is a technique of neurological music therapy and has been proved effective in inducing faster movements in patients with psychotic diseases. This pilot study examined if RAS incorporated in functional movement training reduced severity of movement slowing and irregular muscle contraction in individuals with PLEs. Seventeen individuals with PLEs were randomly allocated to receiving RAS or receiving no RAS and underwent daily 40-min movement training (picking up beans) for three weeks. This study used motion analysis to measure movement performance at pretest and posttest. Eighteen age- and gender-matched individuals without PLEs were also recruited to provide data of intact movements. Results showed that RAS may reduce severity of movement slowing and irregular muscle contraction in individuals with PLEs. This pilot study is one of the pioneering studies validating effectiveness of early intervention programs tackling movement abnormalities, which are initial impairments in the psychosis continuum, in individuals with PLEs.

Evaluation of the non-auditory responses in individuals with auditory brainstem implant.

OBJECTIVES: After auditory brainstem implant (ABI) surgery, stimulation of certain cranial nerves may result in a non-auditory response, and the electrodes that stimulate these nerves may be deactivated. The goals of this study are to compare the number of active electrodes in the initial activation and the last fitting, to investigate non-auditory response types and their frequency as a result of non-auditory stimulation, to compare the placements of deactivated electrodes as a result of non-auditory stimulation in the initial activation and the last fitting. METHODS: The computer software system was used to perform a retrospective analysis of the fitting data of 69 ABI users who underwent auditory brainstem implant surgery between January 1997 and January 2019. The non-auditory response types, deactive electrodes, and the positioning of the deactive electrodes horizontally and vertically were recorded in these users during the initial activation and the last fitting. RESULTS: There was no statistically significant difference between the number of active electrodes in the initial activation and the last fitting. The proportion of the users with deactive electrodes in the initial activation and the last fitting was not statistically significant different. In the horizontal and vertical placement classification, the placement of the deactive electrodes was not statistically different between initial activation and last fitting. The most common type of non-auditory response was facial nerve stimulation at the initial activation and no auditory perception at the last fitting. According to the difference between the number of active and deactive electrodes in the initial activation and the last fitting, as well as the auditory and non-auditory responses, it was found that the ABI users were statistically different between the initial activation and the last fitting. CONCLUSION: The results of this study show that not only auditory but also non-auditory responses occur in most ABI users. In addition, to the best of our knowledge, this study is the first to examine the frequencies of non-auditory response types, and the placement of the electrodes that cause these responses according to horizontal and vertical classifications.

Closed-Loop Auditory Stimulation to Guide Respiration: Preliminary Study to Evaluate the Effect on Time Spent in Sleep Initiation during a Nap.

Various stimulation systems to modulate sleep structure and function have been introduced. However, studies on the time spent in sleep initiation (TSSI) are limited. This study proposes a closed-loop auditory stimulation (CLAS) to gradually modulate respiratory rhythm linked to the autonomic nervous system (ANS) activity directly associated with sleep. CLAS is continuously updated to reflect the individual's current respiratory frequency and pattern. Six participants took naps on different days with and without CLAS. The average values of the TSSI are 14.00 ± 4.24 and 9.67 ± 5.31 min in the control and stimulation experiments (p < 0.03), respectively. Further, the values of respiratory instability and heart rate variability differ significantly between the control and stimulation experiments. Based on our findings, CLAS supports the individuals to gradually modulate their respiratory rhythms to have similar characteristics observed near sleep initiation, and the changed respiratory rhythms influence ANS activities, possibly influencing sleep initiation. Our approach aims to modulate the respiratory rhythm, which can be controlled intentionally. Therefore, this method can probably be used for sleep initiation and daytime applications.

Effect of Music Based Therapy Rhythmic Auditory Stimulation (RAS) Using Wearable Device in Rehabilitation of Neurological Patients: A Systematic Review.

(1) Background: Even though music therapy is acknowledged to have positive benefits in neurology, there is still a lack of knowledge in the literature about the applicability of music treatments in clinical practice with a neurological population using wearable devices. (2) Methods: a systematic review was conducted following PRISMA 2020 guidelines on the 29 October 2022, searching in five databases: PubMed, PEDro, Medline, Web of Science, and Science Direct. (3) Results: A total of 2964 articles were found, including 413 from PubMed, 248 from Web of Science, 2110 from Science Direct, 163 from Medline, and none from PEDro. Duplicate entries, of which there were 1262, were eliminated. In the first screening phase, 1702 papers were screened for title and abstract. Subsequently, 1667 papers were removed, based on population, duplicate, outcome, and poor study design. Only 15 studies were considered after 35 papers had their full texts verified. Results showed significant values of spatiotemporal gait parameters in music-based therapy rhythmic auditory stimulation (RAS), including speed, stride length, cadence, and ROM. (4) Conclusions: The current findings confirm the value of music-based therapy RAS as a favorable and effective tool to implement in the health care system for the rehabilitation of patients with movement disorders.

Variable Cadence Gait Training Outcomes Using Rhythmic Auditory Stimulation Embedded in Older Adults' Preferred Music.

Older adults must have the ability to walk at variable speeds/distances to meet community demands. This single group pre-post test study's purposes were to examine if actual cadences after 7 weeks of rhythmic auditory stimulation gait training matched target cadences, improved walking distance, duration, velocity, maximum cadence, balance, enjoyment, and/or changed spatial/temporal gait parameters. Fourteen female adults (72.6 ± 4.4 years) participated in 14 sessions, while variable cadences were progressively introduced. Eleven older adult responders walked faster (3.8 steps/min) than one target cadence (-10% pace) while matching the target cadences for the other paces when walking with rhythmic auditory stimulation. Two nonresponders walked near their baseline cadence with little variability while one walked at faster cadences; all three did not appear to adjust to the beat of the music. After training, participants increased their walking distance, 90.8 ± 46.5 m; t(1, 13) = -7.3; p ≤ .005, velocity, 0.36 ± 0.15 m/s; t(1, 40) = -15.4; p < .001, and maximum cadence, 20.6 ± 9.1 steps/min; t(1, 40) = -14.6; p < .001; changes exceeded minimal clinically important differences. Twelve of 14 expressed enjoyment. Walk with rhythmic auditory stimulation training is a promising activity for older adults, which may translate to an individual's ability to adapt walking speeds to various community demands.

Effects of maternal sound stimulation on preterm infants: A systematic review and meta-analysis.

AIMS: To evaluate the effects of maternal sound stimulation on preterm infants. BACKGROUND: With an increased focus of studies on maternal sound stimulation for preterm infants, there is a need for an up-to-date systematic review and meta-analysis of randomized controlled trials to measure the effects of maternal sound stimulation on preterm infants. DESIGN: A systematic review and meta-analysis. DATA SOURCES: We searched PubMed, EMBASE, the Cochrane Library, CINAHL Complete, VIP Journal Integration Platform, China National Knowledge Infrastructure, Wanfang Data and China Biology Medicine disc from database establishment to 28 April 2021. REVIEW METHODS: We conducted the meta-analysis using Review Manager 5.3. Integrative description was used for data that were not suitable for meta-analysis. RESULTS: A total of 380 studies between 1979 and 2021 were retrieved and 26 were included in this systematic review. Maternal sound stimulation could significantly reduce the pain level and increase the comfort level of preterm infants during a painful procedure. Compared with routine care, maternal sound stimulation could help preterm infants achieve better physiological stability by reducing their heart rate and increasing their oxygen saturation. CONCLUSION: Maternal sound stimulation is a feasible and effective intervention for preterm infants, which is highly recommended in the clinical setting.

Impact of natural and artificial prenatal stimulation on the behavioural profile of Japanese quail.

As the sensory systems of vertebrates develop prenatally, embryos perceive many environmental stimuli that can influence the ontogeny of their behaviour. Whether the nature and intensity of prenatal stimuli affect this ontogeny differently remains to be investigated. In this context, this study aimed to analyse the effects of prenatal auditory stimulation (natural stimulation, NS; predator vocalisations or artificial stimulation, AS; metallic sounds) on the subsequent behaviour of young Japanese quail (Coturnix coturnix japonica). For this, behavioural variables recorded during ethological tests evaluating emotional and social reactivity were analysed using a principal component analysis. This analysis revealed significant differences between the behavioural profile of stimulated chicks and that of non-exposed chicks. Indeed, chicks exposed to NS expressed more intense emotional responses in fearful situations, but less neophobia when exposed to a novel environment or object, whereas chicks exposed to AS appeared more sensitive to social isolation. Our results show that the acoustic environment of embryos can influence the way young birds subsequently interact with their social and physical environment after hatching, and face challenges in changing living conditions.

Auditory closed-loop stimulation on sleep slow oscillations using in-ear EEG sensors.

Acoustic stimulation synchronized to slow oscillations in scalp electroencephalograms has been shown to enhance sleep features, which makes it promising in boosting cognitive functions as well as in the treatment of some sleep disturbances. Nevertheless, scalp electrode sensors are resource intensive and poorly tolerated by sleeping patients. The aim of this study was to investigate the potential usability of in-the-ear electroencephalography to implement auditory closed-loop stimulation during sleep. For this, we evaluated the agreement between slow oscillation recordings obtained through the in-ear sensor and those obtained simultaneously from standard scalp electrodes during naps of 13 healthy subjects. We found that in-ear activity provided enough information to automatically detect sleep slow oscillations in real-time. Based on this, we successfully enhanced scalp slow oscillations using auditory single-cycle closed-loop brain-state-dependent stimulation based on in-ear signals acquired in 11 further subjects. We conclude that in-ear sensors provide a feasible technology for the enhancement of sleep patterns, and could pave the way for new clinical applications in the near future.

Optimising sounds for the driving of sleep oscillations by closed-loop auditory stimulation.

Recent studies have shown that slow oscillations (SOs) can be driven by rhythmic auditory stimulation, which deepens slow-wave sleep (SWS) and improves memory and the immune-supportive hormonal milieu related to this sleep stage. While different attempts have been made to optimise the driving of the SOs by changing the number of click stimulations, no study has yet investigated the impact of applying more than five clicks in a row. Likewise, the importance of the type of sounds in eliciting brain responses is presently unclear. In a study of 12 healthy young participants (10 females; aged 18-26 years), we applied an established closed-loop stimulation method, which delivered sequences of 10 pink noises, 10 pure sounds (B note of 247 Hz), 10 pronounced "a" vowels, 10 sham, 10 variable sounds, and 10 "oddball" sounds on the up phase of the endogenous SOs. By analysing area under the curve, amplitude, and event related potentials, we explored whether the nature of the sound had a differential effect on driving SOs. We showed that every stimulus in a 10-click sequence, induces a SO response. Interestingly, all three types of sounds that we tested triggered SOs. However, pink noise elicited a more pronounced response compared to the other sounds, which was explained by a broader topographical recruitment of brain areas. Our data further suggest that varying the sounds may partially counteract habituation.

Targeted memory reactivation has a sleep stage-specific delayed effect on dream content.

Although new learning is known to reappear in later dream scenarios, the timing of such reappearances remains unclear. Sometimes, references to new learning occur relatively quickly, 1 day post-learning (day-residue effect); at other times there may be a substantive delay, 5-7 days, before such references appear (dream-lag effect). We studied temporal delays in dream reactivation following the learning of a virtual reality (VR) flying task using 10-day home sleep/dream logs, and how these might be influenced by targeted memory reactivation (TMR). Participants were exposed twice to a VR task in the sleep laboratory; once before and once after a 2-hr opportunity to nap (n = 65) or to read (n = 32). Auditory cues associated with the VR task were replayed in either wake, rapid eye movement (REM) sleep, slow-wave sleep (SWS) or were not replayed. Although we previously showed that TMR cueing did not have an immediate effect on dream content, in the present study we extend these results by showing that TMR in sleep has instead a delayed effect on task-dream reactivations: participants dreamed more about the task 1-2 days later when TMR was applied in REM sleep and 5-6 days later when it was applied in SWS sleep, compared to participants with no cueing. Findings may help explain the temporal relationships between dream and memory reactivations and clarify the occurrence of day-residue and dream-lag phenomena.

Down-phase auditory stimulation is not able to counteract pharmacologically or physiologically increased sleep depth in traumatic brain injury rats.

Modulation of slow-wave activity, either via pharmacological sleep induction by administering sodium oxybate or sleep restriction followed by a strong dissipation of sleep pressure, has been associated with preserved posttraumatic cognition and reduced diffuse axonal injury in traumatic brain injury rats. Although these classical strategies provided promising preclinical results, they lacked the specificity and/or translatability needed to move forward into clinical applications. Therefore, we recently developed and implemented a rodent auditory stimulation method that is a scalable, less invasive and clinically meaningful approach to modulate slow-wave activity by targeting a particular phase of slow waves. Here, we assessed the feasibility of down-phase targeted auditory stimulation of slow waves and evaluated its comparative modulatory strength in relation to the previously employed slow-wave activity modulators in our rat model of traumatic brain injury. Our results indicate that, in spite of effectively reducing slow-wave activity in both healthy and traumatic brain injury rats via down-phase targeted stimulation, this method was not sufficiently strong to counteract the boost in slow-wave activity associated with classical modulators, nor to alter concomitant posttraumatic outcomes. Therefore, the usefulness and effectiveness of auditory stimulation as potential standalone therapeutic strategy in the context of traumatic brain injury warrants further exploration.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Technical feasibility of using auditory phase-targeted stimulation after pediatric severe traumatic brain injury in an intensive care setting.

BACKGROUND: Supplementary treatment options after pediatric severe traumatic brain injury (TBI) are needed to improve neurodevelopmental outcome. Evidence suggests enhancement of brain delta waves via auditory phase-targeted stimulation might support neuronal reorganization, however, this method has never been applied in analgosedated patients on the pediatric intensive care unit (PICU). Therefore, we conducted a feasibility study to investigate this approach: In a first recording phase, we examined feasibility of recording over time and in a second stimulation phase, we applied stimulation to address tolerability and efficacy. METHODS: Pediatric patients (> 12 months of age) with severe TBI were included between May 2019 and August 2021. An electroencephalography (EEG) device capable of automatic delta wave detection and sound delivery through headphones was used to record brain activity and for stimulation (MHSL-SleepBand version 2). Stimulation tolerability was evaluated based on report of nurses, visual inspection of EEG data and clinical signals (heart rate, intracranial pressure), and whether escalation of therapy to reduce intracranial pressure was needed. Stimulation efficacy was investigated by comparing EEG power spectra of active stimulation versus muted stimulation (unpaired t-tests). RESULTS: In total, 4 out of 32 TBI patients admitted to the PICU (12.5%) between 4 and 15 years of age were enrolled in the study. All patients were enrolled in the recording phase and the last one also to the stimulation phase. Recordings started within 5 days after insult and lasted for 1-4 days. Overall, 23-88 h of EEG data per patient were collected. In patient 4, stimulation was enabled for 50 min: No signs of patient stress reactions were observed. Power spectrums between active and muted stimulation were not statistically different (all P > .05). CONCLUSION: Results suggests good feasibility of continuously applying devices needed for auditory stimulation over multiple days in pediatric patients with TBI on PICU. Very preliminary evidence suggests good tolerability of auditory stimuli, but efficacy of auditory stimuli to enhance delta waves remains unclear and requires further investigation. However, only low numbers of severe TBI patients could be enrolled in the study and, thus, future studies should consider an international multicentre approach.