EEG/ECoG/EMG publications

Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POA GAD2 →TMN neurons) are crucial for the homeostatic regulation of REMs. POA GAD2 →TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POA GAD2 →TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POA GAD2 →TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

Introduction Benzodiazepines (BDZs) are commonly used to treat the symptoms of movement disorders; however, deep brain stimulation (DBS) has become a popular treatment for these disorders. Previous studies have investigated the effects of BDZ on cortical activity, no data are currently available on their effects on deep brain regions, nor on these regions’ responses to DBS. How the BDZ affects the thalamus and basal ganglia in dystonia patients remains unknown. Methods DBS recordings were performed in ventral oralis anterior/posterior (VoaVop), ventral intermediate (VIM) and ventral anterior (VA) thalamic subnuclei, as well as globus pallidus interna (GPi) and subthalamic nucleus (STN). Evoked potentials (EP) and frequency domain analysis were performed to determine the BDZ effect on neural activities compared to the control condition (off-BDZ). Three male pediatric patients with dystonia treated with BDZ and undergoing depth electrode evaluation for clinical targeting were recruited for the study. Stimulation was administered at 25 and 55 Hz frequencies and recordings were simultaneously gathered through pairs of externalized stereoelectroencephalography (sEEG) electrodes. EP amplitude and the effect of stimulation on the frequency spectrum of activity were compared at baseline and following clinical administration of BDZ. Results Frequency analysis showed consistent reductions in activity during BDZ treatment in all studied brain regions for all patients. Evoked potential (EP) analysis showed increased subthalamic nucleus (STN) EP amplitude and decreased ventral intermediate (VIM) and STN EP amplitude during BDZ treatment. Interpretation BDZs reduce thalamic and basal ganglia activity in multiple regions and alter the efficacy of transmission between these regions. While the mechanism is unknown our results confirm the known widespread effects of this class of medications and identify specific areas within the motor system that are directly affected.

Social decision making requires the integration of reward valuation and social cognition systems, both dependent on the orbitofrontal cortex (OFC). How these two OFC functions interact is largely unknown. We recorded intracranial activity from the OFC of ten patients making choices in a social context where reward inequity with a social counterpart varied and could be either advantageous or disadvantageous. We find that OFC high-frequency activity (HFA; 70-150 Hz) encodes self-reward, consistent with previous reports. We also observe encoding of the social counterpart's reward, as well as the type of inequity being experienced. Additionally, we find evidence of inequity-dependent reward encoding: depending on the type of inequity, electrodes rapidly and reversibly switch between different reward-encoding profiles. These results provide direct evidence for encoding of self- and other rewards in the human OFC and highlight the dynamic nature of encoding in the OFC as a function of social context.

So-called duplex speech stimuli with perceptually ambiguous spectral cues to one ear and isolated low- versus high-frequency third formant “chirp” to the opposite ear yield a coherent percept supporting their phonetic categorization. Critically, such dichotic sounds are only perceived categorically upon binaural integration. Here, we used frequency-following responses (FFRs), scalp-recorded potentials reflecting phase-locked subcortical activity, to investigate brainstem responses to fused speech percepts and to determine whether FFRs reflect binaurally integrated category-level representations. We recorded FFRs to diotic and dichotic stop-consonants (/da/, /ga/) that either did or did not require binaural fusion to properly label along with perceptually ambiguous sounds without clear phonetic identity. Behaviorally, listeners showed clear categorization of dichotic speech tokens confirming they were heard with a fused, phonetic percept. Neurally, we found FFRs were stronger for categorically perceived speech relative to category-ambiguous tokens but also differentiated phonetic categories for both diotically and dichotically presented speech sounds. Correlations between neural and behavioral data further showed FFR latency predicted the degree to which listeners labeled tokens as “da” versus “ga.” The presence of binaurally integrated, category-level information in FFRs suggests human brainstem processing reflects a surprisingly abstract level of the speech code typically circumscribed to much later cortical processing.

Background Autism spectrum disorders (ASD) encompass a wide array of debilitating symptoms, including sensory dysfunction and delayed language development. Auditory temporal processing is crucial for speech perception and language development. Abnormal development of temporal processing may account for the language impairments associated with ASD. Very little is known about the development of temporal processing in any animal model of ASD. Methods In the current study, we quantify auditory temporal processing throughout development in the Fmr1 knock-out (KO) mouse model of Fragile X Syndrome (FXS), a leading genetic cause of intellectual disability and ASD-associated behaviors. Using epidural electrodes in awake and freely moving wildtype (WT) and KO mice, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (gap-ASSR) paradigm. Mice were recorded at three different ages in a cross sectional design: postnatal (p)21, p30 and p60. Recordings were obtained from both auditory and frontal cortices. The gap-ASSR requires underlying neural generators to synchronize responses to gaps of different widths embedded in noise, providing an objective measure of temporal processing across genotypes and age groups. Results We present evidence that the frontal, but not auditory, cortex shows significant temporal processing deficits at p21 and p30, with poor ability to phase lock to rapid gaps in noise. Temporal processing was similar in both genotypes in adult mice. ERP amplitudes were larger in Fmr1 KO mice in both auditory and frontal cortex, consistent with ERP data in humans with FXS. Conclusions These data indicate cortical region-specific delays in temporal processing development in Fmr1 KO mice. Developmental delays in the ability of frontal cortex to follow rapid changes in sounds may shape language delays in FXS, and more broadly in ASD.

Deformable semi-solid liquid metal particles (LMP) have emerged as a promising substitute for rigid conductive fillers due to their excellent electrical properties and stable conductance under strain. However, achieving a compact and robust coating of LMP on fibers remains a persistent challenge, mainly due to the incompatibility of conventional coating techniques with LMP. Additionally, the limited durability and absence of initial electrical conductivity of LMP restrict their widespread application. In this study, we propose a solution process that robustly and compactly assembles mechanically durable and initially conductive LMP on fibers. Specifically, we present a shearing-based deposition of polymer-attached LMP followed by additional coating with CNT-attached LMP to create bi-layer LMP composite with exceptional durability, electrical conductivity, stretchability, and biocompatibility on various fibers. The versatility and reliability of this manufacturing strategy for 1D electronics are demonstrated through the development of sewn electrical circuits, smart clothes, stretchable biointerfaced fiber, and multifunctional fiber probes.

Theories of consciousness suggest that brain mechanisms underlying transitions into and out of unconsciousness are conserved no matter the context or precipitating conditions. We compared signatures of these mechanisms using intracranial electroencephalography in neurosurgical patients during propofol anesthesia and overnight sleep and found strikingly similar reorganization of human cortical networks. We computed the “effective dimensionality” of the normalized resting state functional connectivity matrix to quantify network complexity. Effective dimensionality decreased during stages of reduced consciousness (anesthesia unresponsiveness, N2 and N3 sleep). These changes were not region-specific, suggesting global network reorganization. When connectivity data were embedded into a low-dimensional space in which proximity represents functional similarity, we observed greater distances between brain regions during stages of reduced consciousness, and individual recording sites became closer to their nearest neighbors. These changes corresponded to decreased differentiation and functional integration and correlated with decreases in effective dimensionality. This network reorganization constitutes a neural signature of states of reduced consciousness that is common to anesthesia and sleep. These results establish a framework for understanding the neural correlates of consciousness and for practical evaluation of loss and recovery of consciousness.

Insufficient sleep is commonplace in modern lifestyle and can lead to grave outcomes, yet the changes in neuronal activity accumulating over hours of extended wakefulness remain poorly understood. Specifically, which aspects of cortical processing are affected by sleep deprivation (SD), and whether they also affect early sensory regions, remain unclear. Here, we recorded spiking activity in the rat auditory cortex along with polysomnography while presenting sounds during SD followed by recovery sleep. We found that frequency tuning, onset responses, and spontaneous firing rates were largely unaffected by SD. By contrast, SD decreased entrainment to rapid (≥20 Hz) click trains, increased population synchrony, and increased the prevalence of sleep-like stimulus-induced silent periods, even when ongoing activity was similar. Recovery NREM sleep was associated with similar effects as SD with even greater magnitude, while auditory processing during REM sleep was similar to vigilant wakefulness. Our results show that processes akin to those in NREM sleep invade the activity of cortical circuits during SD, even in the early sensory cortex.

The rate model of basal ganglia function predicts that muscle activity in dystonia is due to disinhibition of thalamus resulting from decreased inhibitory input from pallidum. We seek to test this hypothesis in children with dyskinetic cerebral palsy undergoing evaluation for deep brain stimulation (DBS) to analyze movement-related activity in different brain regions. The results revealed prominent beta-band frequency peaks in the globus pallidus interna (GPi), ventral oralis anterior/posterior (VoaVop) subnuclei of the thalamus, and subthalamic nucleus (STN) during movement but not at rest. Connectivity analysis indicated stronger coupling between STN-VoaVop and STN-GPi compared to GPi-STN. These findings contradict the hypothesis of decreased thalamic inhibition in dystonia, suggesting that abnormal patterns of inhibition and disinhibition, rather than reduced GPi activity, contribute to the disorder. Additionally, the study implies that correcting abnormalities in GPi function may explain the effectiveness of DBS targeting the STN and GPi in treating dystonia.

The P2 component of the auditory evoked potential is commonly thought to reflect acoustic stimulus properties as well as prior exposure to the materials, rather than change-related cortical activity. Here, we challenge this view by showing that the P2 is strongly increased in response to voice pitch changes with a stepwise pattern compared to changes in dynamic pitch contours typical for natural speech, and also reflects the magnitude of these pitch changes. Furthermore, it is demonstrated that neither the P2 nor any other component are affected by the harmonicity of the materials. Despite no prior exposure, artificially created inharmonic versions of the speech materials elicited similar activity throughout auditory cortex. This suggests that so-called harmonic template neurons observed in animal studies are either absent or do not exist in sufficient number in human auditory cortex to detect their activity extracranially. Crucially, both morphology and source reconstructions of the EEG data showed that the P2 appears to consist of two separate subcomponents. Whereas source activity for the “P2a” was strongest in right auditory cortex, the subsequent “P2b” included generators spread across auditory cortex and association areas, bilaterally. The two subcomponents thus likely reflect processing at different stages of the auditory pathway.

Neurophysiological studies suggest that intrinsic brain oscillations influence sensory processing, especially of rhythmic stimuli like speech. Prior work suggests that brain rhythms may mediate perceptual grouping and selective attention to speech amidst competing sound, as well as more linguistic aspects of speech processing like predictive coding. However, we know of no prior studies that have directly tested, at the single-trial level, whether brain oscillations relate to speech-in-noise outcomes. Here, we combined electroencephalography while simultaneously measuring intelligibility of spoken sentences amidst two different interfering sounds: multi-talker babble or speech-shaped noise. We find that induced parieto-occipital alpha (7–15 Hz; thought to modulate attentional focus) and frontal beta (13–30 Hz; associated with maintenance of the current sensorimotor state and predictive coding) oscillations covary with trial-wise percent-correct scores; importantly, alpha and beta power provide significant independent contributions to predicting single-trial behavioral outcomes. These results can inform models of speech processing and guide noninvasive measures to index different neural processes that together support complex listening.

Recent studies have shown that the feasibility of speech brain-computer interfaces (BCIs) as a clinically valid treatment in helping nontonal language patients with communication disorders restore their speech ability. However, tonal language speech BCI is challenging because additional precise control of laryngeal movements to produce lexical tones is required. Thus, the model should emphasize the features from the tonal-related cortex. Here, we designed a modularized multistream neural network that directly synthesizes tonal language speech from intracranial recordings. The network decoded lexical tones and base syllables independently via parallel streams of neural network modules inspired by neuroscience findings. The speech was synthesized by combining tonal syllable labels with nondiscriminant speech neural activity. Compared to commonly used baseline models, our proposed models achieved higher performance with modest training data and computational costs. These findings raise a potential strategy for approaching tonal language speech restoration.

Syllables are an essential building block of speech. We recently showed that tactile stimuli linked to the perceptual centers of syllables in continuous speech can improve speech comprehension. The rate of syllables lies in the theta frequency range, between 4 and 8 Hz, and the behavioural effect appears linked to multisensory integration in this frequency band. Because this neural activity may be oscillatory, we hypothesized that a behavioural effect may also occur not only while but also after this activity has been evoked or entrained through vibrotactile pulses. Here we show that audiotactile integration regarding the perception of single syllables, both on the neural and on the behavioural level, is consistent with this hypothesis. We first stimulated subjects with a series of vibrotactile pulses and then presented them with a syllable in background noise. We show that, at a delay of 200 ms after the last vibrotactile pulse, audiotactile integration still occurred in the theta band and syllable discrimination was enhanced. Moreover, the dependence of both the neural multisensory integration as well as of the behavioral discrimination on the delay of the audio signal with respect to the last tactile pulse was consistent with a damped oscillation. In addition, the multisensory gain is correlated with the syllable discrimination score. Our results therefore evidence the role of the theta band in audiotactile integration and provide evidence that these effect may involve oscillatory activity that still persists after the tactile stimulation.

The perception of pitch is a fundamental percept, which is mediated by the auditory system, requiring the abstraction of stimulus properties related to the spectro-temporal structure of sound. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to species differences or differences in the recording measures and choices of stimuli used in previous studies. Moreover, it was unknown whether the human brain contains pitch neurons and how distributed such neurons might be. Here, we present the first study to measure multiunit neural activity in response to pitch stimuli in the auditory cortex of intracranially implanted humans. The stimulus sets were regular-interval noise with a pitch strength that is related to the temporal regularity and a pitch value determined by the repetition rate and harmonic complexes. Specifically, we demonstrate reliable responses to these different pitch-inducing paradigms that are distributed throughout Heschl’s gyrus, rather than being localized to a particular region, and this finding was evident regardless of the stimulus presented. These data provide a bridge across animal and human studies and aid our understanding of the processing of a critical percept associated with acoustic stimuli.

Previous work has demonstrated that performance in an auditory selective attention task can be enhanced or impaired, depending on whether a task-irrelevant visual stimulus is temporally coherent with a target auditory stream or with a competing distractor. However, it remains unclear how audiovisual (AV) temporal coherence and auditory selective attention interact at the neurophysiological level. Here, we measured neural activity using EEG while human participants (men and women) performed an auditory selective attention task, detecting deviants in a target audio stream. The amplitude envelope of the two competing auditory streams changed independently, while the radius of a visual disk was manipulated to control the AV coherence. Analysis of the neural responses to the sound envelope demonstrated that auditory responses were enhanced largely independently of the attentional condition: both target and masker stream responses were enhanced when temporally coherent with the visual stimulus. In contrast, attention enhanced the event-related response evoked by the transient deviants, largely independently of AV coherence. These results provide evidence for dissociable neural signatures of bottom-up (coherence) and top-down (attention) effects in AV object formation. SIGNIFICANCE STATEMENT Temporal coherence between auditory stimuli and task-irrelevant visual stimuli can enhance behavioral performance in auditory selective attention tasks. However, how audiovisual temporal coherence and attention interact at the neural level has not been established. Here, we measured EEG during a behavioral task designed to independently manipulate audiovisual coherence and auditory selective attention. While some auditory features (sound envelope) could be coherent with visual stimuli, other features (timbre) were independent of visual stimuli. We find that audiovisual integration can be observed independently of attention for sound envelopes temporally coherent with visual stimuli, while the neural responses to unexpected timbre changes are most strongly modulated by attention. Our results provide evidence for dissociable neural mechanisms of bottom-up (coherence) and top-down (attention) effects on audiovisual object formation.

Our continuous visual experience in daily life is dominated by change. Previous research has focused on visual change due to stimulus motion, eye movements or unfolding events, but not their combined impact across the brain, or their interactions with semantic novelty. We investigate the neural responses to these sources of novelty during film viewing. We analyzed intracranial recordings in humans across 6328 electrodes from 23 individuals. Responses associated with saccades and film cuts were dominant across the entire brain. Film cuts at semantic event boundaries were particularly effective in the temporal and medial temporal lobe. Saccades to visual targets with high visual novelty were also associated with strong neural responses. Specific locations in higher-order association areas showed selectivity to either high or low-novelty saccades. We conclude that neural activity associated with film cuts and eye movements is widespread across the brain and is modulated by semantic novelty.

The subthalamic nucleus (STN) is hypothesized to play a central role in neural processes that regulate self-control. Still uncertain, however, is how that brain structure participates in the dynamically evolving estimation of value that underlies the ability to delay gratification and wait patiently for a gain. To address that gap in knowledge, we studied the spiking activity of neurons in the STN of monkeys during a task in which animals were required to remain motionless for varying periods of time in order to obtain food reward. At the single-neuron and population levels, we found a cost–benefit integration between the desirability of the expected reward and the imposed delay to reward delivery, with STN signals that dynamically combined both attributes of the reward to form a single integrated estimate of value. This neural encoding of subjective value evolved dynamically across the waiting period that intervened after instruction cue. Moreover, this encoding was distributed inhomogeneously along the antero-posterior axis of the STN such that the most dorso-posterior-placed neurons represented the temporal discounted value most strongly. These findings highlight the selective involvement of the dorso-posterior STN in the representation of temporally discounted rewards. The combination of rewards and time delays into an integrated representation is essential for self-control, the promotion of goal pursuit, and the willingness to bear the costs of time delays.

Growing evidence suggests that brain activity during sleep, as well as sleep regulation, are tightly linked with synaptic function and network excitability at the local and global levels. We previously reported that a mutation in synaptobrevin 2 ( Vamp2 ) in restless ( rlss ) mice results in a marked increase of wakefulness and suppression of sleep, in particular REM sleep (REMS) as well as increased consolidation of sleep and wakefulness. In the current study, using finer-scale in vivo electrophysiology recordings, we report that spontaneous cortical activity in rlss mice during NREM sleep (NREMS) is characterised by an occurrence of abnormally prolonged periods of complete neuronal silence (OFF-periods), often lasting several seconds, similar to the burst suppression pattern typically seen under deep anaesthesia. Increased incidence of prolonged network OFF-periods was not specific to NREMS, but also present in REMS and wake in rlss mice. Slow-wave activity (SWA) was generally increased in rlss mice, while higher frequencies including theta-frequency activity were decreased, further resulting in diminished differences between vigilance states. The relative increase in SWA after sleep deprivation was attenuated in rlss mice, suggesting either that rlss mice experience persistently elevated sleep pressure, or, alternatively, that the intrusion of sleep-like patterns of activity into awake state diminishes the accumulation of sleep drive. We propose that deficit in global synaptic neurotransmitter release leads to ‘state inertia’, reflected in an abnormal propensity of brain networks to enter and remain in a persistent ‘default state’ resembling coma or deep anaesthesia.

Biocompatible and plastic neural interface devices allow for minimally invasive recording of brain activity. Increasing electrode density in such devices is essential for high-resolution neural recordings. Superimposing conductive leads in devices can help multiply the number of recording sites while keeping probes width small and suitable for implantation. However, because of leads' vertical proximity, this can create capacitive coupling (CC) between overlapping channels, which leads to crosstalk. Here, we present a thorough investigation of CC phenomenon in multi-gold layer thin-film multi-electrode arrays with a parylene C (PaC) insulation layer between superimposed leads. We also propose a guideline on the design, fabrication, and characterization of such type of neural interface devices for high spatial resolution recording. Our results demonstrate that the capacitance created through CC between superimposed tracks decreases non-linearly and then linearly with the increase of insulation thickness. We identify an optimal PaC insulation thickness that leads to a drastic reduction of CC between superimposed gold channels while not significantly increasing the overall device thickness. Finally, we show that double gold layer electrocorticography probes with the optimal insulation thickness exhibit similar performances in vivo when compared to single-layer devices. This confirms that these probes are adequate for high-quality neural recordings.

We report on the power spectral analysis of multiunit activity (MUA) of lumbar spinal interneurons during a locomotor task. In line with prior studies, we found evidence of greater power at the frequency of locomotion in high lumbar segments and during the flexion phase. Our results also confirm prior observations from our laboratory that the rhythmically active MUA behaves as a longitudinal standing wave of neural activation that is flexor dominant.