EEG/ECoG/EMG publications

Considerable work suggests the dominant syllable rhythm of the acoustic envelope is remarkably similar across languages (∼4–5 Hz) and that oscillatory brain activity tracks these quasiperiodic rhythms to facilitate speech processing. However, whether this fundamental periodicity represents a common organizing principle in both auditory and motor systems involved in speech has not been explicitly tested. To evaluate relations between entrainment in the perceptual and production domains, we measured individuals’ (i) neuroacoustic tracking of the EEG to speech trains and their (ii) simultaneous and non-simultaneous productions synchronized to syllable rates between 2.5 and 8.5 Hz. Productions made without concurrent auditory presentation isolated motor speech functions more purely. We show that neural synchronization flexibly adapts to the heard stimuli in a rate-dependent manner, but that phase locking is boosted near ∼4.5 Hz, the purported dominant rate of speech. Cued speech productions (recruit sensorimotor interaction) were optimal between 2.5 and 4.5 Hz, suggesting a low-frequency constraint on motor output and/or sensorimotor integration. In contrast, “pure” motor productions (without concurrent sound cues) were most precisely generated at rates of 4.5 and 5.5 Hz, paralleling the neuroacoustic data. Correlations further revealed strong links between receptive (EEG) and production synchronization abilities; individuals with stronger auditory-perceptual entrainment better matched speech rhythms motorically. Together, our findings support an intimate link between exogenous and endogenous rhythmic processing that is optimized at 4–5 Hz in both auditory and motor systems. Parallels across modalities could result from dynamics of the speech motor system coupled with experience-dependent tuning of the perceptual system via the sensorimotor interface.

Human cognitive abilities naturally vary along a spectrum, even among those we call "neurotypical". Individuals differ in their ability to selectively attend to goal-relevant auditory stimuli. We sought to characterize this variability in a cohort of people with diverse attentional functioning. We recruited both neurotypical (N = 20) and ADHD (N = 25) young adults, all with normal hearing. Participants listened to one of three concurrent, spatially separated speech streams and reported the order of the syllables in that stream while we recorded electroencephalography (EEG). We tested both the ability to sustain attentional focus on a single "Target" stream and the ability to monitor the Target but flexibly either ignore or switch attention to an unpredictable "Interrupter" stream from another direction that sometimes appeared. Although differences in both stimulus structure and task demands affected behavioral performance, ADHD status did not. In both groups, the Interrupter evoked larger neural responses when it was to be attended compared to when it was irrelevant, including for the P3a "reorienting" response previously described as involuntary. This attentional modulation was weaker in ADHD listeners, even though their behavioral performance was the same. Across the entire cohort, individual performance correlated with the degree of top-down modulation of neural responses. These results demonstrate that listeners differ in their ability to modulate neural representations of sound based on task goals, while suggesting that adults with ADHD may have weaker volitional control of attentional processes than their neurotypical counterparts.

RESUMO Objetivo analisar o efeito do mascaramento estável e modulado no Potencial Evocado Auditivo Cortical com estímulo de fala em adultos-jovens. Método participaram 14 indivíduos com idades entre 19 e 28 anos de ambos os sexos e sem perda auditiva. O exame de Potencial Evocado Auditivo Cortical foi realizado com estímulo de fala sintética /ba/ simultâneo ao ruído Speech Shaped Noise apresentado em três condições: ruído estável com intensidade de 30 dB NPSpe (ruído estável fraco), ruído estável com intensidade de 65 dB NPSpe (ruído estável forte) e ruído modulado em intensidade de 30 dB NPSpe e 65 dB NPSpe em 25Hz e com período de modulação de 40 ms. Resultados foram observadas maiores latências nos componentes corticais, exceto P2, na condição de ruído estável forte e medidas mais robustas de amplitude dos componentes corticais P1, N1 e P2 na condição de ruído modulado com diferença estatística significativa na comparação com a condição de ruído estável forte. Houve pior morfologia na condição de ruído estável forte, quando comparado aos demais registros. Os limiares eletrofisiológicos médios para as condições de ruído estável forte e ruído modulado foram 60 dB NPSpe e 49 dB NPSpe, respectivamente, mostrando 11,7 dB de diferença média. Conclusão podemos inferir que houve um menor efeito mascarante do ruído modulado, comparado à condição de ruído estável forte, nas medidas de amplitude dos componentes corticais e uma diferença média de 11,7 dB entre os limiares eletrofisiológicos (interpretado como a medida do Benefício do Mascaramento Modulado).

Spinal cord injury (SCI) frequently results in complete, permanent paralysis. Although it is possible to reverse the effects of incomplete paralysis, complete paralysis effects are permanent. At present, there is no cure for SCI, but engineers can bypass the spinal cord and restore the connection from the brain to the muscles through brain-machine or brain-computer interfaces (BMIs or BCIs). These experiments initially began with rodents and non-human primates (NHPs), which were trained to move cursors, joysticks or robots with their minds beginning in the 20th century. Research progressed to human clinical trials in the late 20th century. In this paper, I present the work done to train a new NHP model for behavioural experiments, how these NHPs were trained, and the neurophysiology involved in training BMI algorithms. With this knowledge, we then moved to non-invasive human clinical trials, in which 8 SCI and 6 control subjects were able to control the opening and closing of their hands with a BCI system using electroencephalographic (EEG) signals from the motor cortex. Finally, we used these algorithms with a SCI subject in an invasive human clinical trial. The subject successfully completed activities of daily living (ADLs) and was able to control an ambulatory device that enabled him to walk upright. The overall accuracy for the BMI was approximately 90% for the upper extremity task and 85% for the lower extremity task. In addition, the subject improved in performance and speed on the Jebsen Hand Function Test (JHFT) during the 20 weeks of the study. Our subject was then sent home with a mechanical glove to continue performing upper-extremity ADLs in the home environment.

Broadly congruent mirror neurons, responding to any grasp movement, and strictly congruent mirror neurons, responding only to specific grasp movements, have been reported in single-cell studies with primates. Delineating grasp properties in humans is essential to understand the human mirror neuron system with implications for behavior and social cognition. We analyzed electrocorticography data from a natural reach-and-grasp movement observation and delayed imitation task with 3 different natural grasp types of everyday objects. We focused on the classification of grasp types from high-frequency broadband mirror activation patterns found in classic mirror system areas, including sensorimotor, supplementary motor, inferior frontal, and parietal cortices. Classification of grasp types was successful during movement observation and execution intervals but not during movement retention. Our grasp type classification from combined and single mirror electrodes provides evidence for grasp-congruent activity in the human mirror neuron system potentially arising from strictly congruent mirror neurons.

Evoked neural responses to sensory stimuli have been extensively investigated in humans and animal models both to enhance our understanding of brain function and to aid in clinical diagnosis of neurological and neuropsychiatric conditions. Recording and imaging techniques such as electroencephalography (EEG), magnetoencephalography (MEG), local field potentials (LFPs), and calcium imaging provide complementary information about different aspects of brain activity at different spatial and temporal scales. Modeling and simulations provide a way to integrate these different types of information to clarify underlying neural mechanisms. In this study, we aimed to shed light on the neural dynamics underlying auditory evoked responses by fitting a rate-based model to LFPs recorded via multi-contact electrodes which simultaneously sampled neural activity across cortical laminae. Recordings included neural population responses to best-frequency (BF) and non-BF tones at four representative sites in primary auditory cortex (A1) of awake monkeys. The model considered major neural populations of excitatory, parvalbumin-expressing (PV), and somatostatin-expressing (SOM) neurons across layers 2/3, 4, and 5/6. Unknown parameters, including the connection strength between the populations, were fitted to the data. Our results revealed similar population dynamics, fitted model parameters, predicted equivalent current dipoles (ECD), tuning curves, and lateral inhibition profiles across recording sites and animals, in spite of quite different extracellular current distributions. We found that PV firing rates were higher in BF than in non-BF responses, mainly due to different strengths of tonotopic thalamic input, whereas SOM firing rates were higher in non-BF than in BF responses due to lateral inhibition. In conclusion, we demonstrate the feasibility of the model-fitting approach in identifying the contributions of cell-type specific population activity to stimulus-evoked LFPs across cortical laminae, providing a foundation for further investigations into the dynamics of neural circuits underlying cortical sensory processing.

Cardiac arrest (CA) remains the leading cause of coma, and early arousal recovery indicators are needed to allocate critical care resources properly. High-frequency oscillations (HFOs) of somatosensory evoked potentials (SSEPs) have been shown to indicate responsive wakefulness days following CA. Nonetheless, their potential in the acute recovery phase, where the injury is reversible, has not been tested. We hypothesize that time-frequency (TF) analysis of HFOs can determine arousal recovery in the acute recovery phase. To test our hypothesis, eleven adult male Wistar rats were subjected to asphyxial CA (five with 3-min mild and six with 7-min moderate to severe CA) and SSEPs were recorded for 60 min post-resuscitation. Arousal level was quantified by the neurological deficit scale (NDS) at 4 h. Our results demonstrated that continuous wavelet transform (CWT) of SSEPs localizes HFOs in the TF domain under baseline conditions. The energy dispersed immediately after injury and gradually recovered. We proposed a novel TF-domain measure of HFO: the total power in the normal time-frequency space (NTFS) of HFO. We found that the NTFS power significantly separated the favorable and unfavorable outcome groups. We conclude that the NTFS power of HFOs provides earlier and objective determination of arousal recovery after CA.

Microglia are critical regulators of brain development that engulf synaptic proteins during postnatal synapse remodeling. However, the mechanisms through which microglia sense the brain environment are not well defined. Here, we characterized the regulatory program downstream of interleukin-33 (IL-33), a cytokine that promotes microglial synapse remodeling. Exposing the developing brain to a supraphysiological dose of IL-33 altered the microglial enhancer landscape and increased binding of stimulus-dependent transcription factors including AP-1/FOS. This induced a gene expression program enriched for the expression of pattern recognition receptors, including the scavenger receptor MARCO. CNS-specific deletion of IL-33 led to increased excitatory/inhibitory synaptic balance, spontaneous absence-like epileptiform activity in juvenile mice, and increased seizure susceptibility in response to chemoconvulsants. We found that MARCO promoted synapse engulfment, and Marco-deficient animals had excess thalamic excitatory synapses and increased seizure susceptibility. Taken together, these data define coordinated epigenetic and functional changes in microglia and uncover pattern recognition receptors as potential regulators of postnatal synaptic refinement.

Extended wakefulness is associated with reduced performance and the build-up of sleep pressure. In the cortex, this manifests as changes in network activity. These changes show local variation depending on the waking experience, and their underlying mechanisms represent targets for overcoming the effects of tiredness. Here, we reveal a central role for intracellular chloride regulation, which sets the strength of postsynaptic inhibition via GABAA receptors in cortical pyramidal neurons. Wakefulness results in depolarizing shifts in the equilibrium potential for GABAA receptors, reflecting local activity-dependent processes during waking and involving changes in chloride cotransporter activity. These changes underlie electrophysiological and behavioral markers of local sleep pressure within the cortex, including the levels of slow-wave activity during non-rapid eye movement sleep and low-frequency oscillatory activity and reduced performance levels in the sleep-deprived awake state. These findings identify chloride regulation as a crucial link between sleep-wake history, cortical activity and behavior.

To obtain combined behavioural and electrophysiological measures of pitch perception, we presented harmonic complexes, bandpass filtered to contain only high-numbered harmonics, to normal-hearing listeners. These stimuli resemble bandlimited pulse trains and convey pitch using a purely temporal code. A core set of conditions consisted of six stimuli with baseline pulse rates of 94, 188 and 280 pps, filtered into a HIGH (3365–4755 Hz) or VHIGH (7800–10,800 Hz) region, alternating with a 36% higher pulse rate. Brainstem and cortical processing were measured using the frequency following response (FFR) and auditory change complex (ACC), respectively. Behavioural rate change difference limens (DLs) were measured by requiring participants to discriminate between a stimulus that changed rate twice (up-down or down-up) during its 750-ms presentation from a constant-rate pulse train. FFRs revealed robust brainstem phase locking whose amplitude decreased with increasing rate. Moderate-sized but reliable ACCs were obtained in response to changes in purely temporal pitch and, like the psychophysical DLs, did not depend consistently on the direction of rate change or on the pulse rate for baseline rates between 94 and 280 pps. ACCs were larger and DLs lower for stimuli in the HIGH than in the VHGH region. We argue that the ACC may be a useful surrogate for behavioural measures of rate discrimination, both for normal-hearing listeners and for cochlear-implant users. We also showed that rate DLs increased markedly when the baseline rate was reduced to 48 pps, and compared the behavioural and electrophysiological findings to recent cat data obtained with similar stimuli and methods.

The human brain networks responsible for selectively listening to a voice amid other talkers remain to be clarified. The present study aimed to investigate relationships between cortical activity and performance in a speech-in-speech task, before (Experiment I) and after training-induced improvements (Experiment II). In Experiment I, 74 participants performed a speech-in-speech task while their cortical activity was measured using a functional near infrared spectroscopy (fNIRS) device. One target talker and one masker talker were simultaneously presented at three different target-to-masker ratios (TMRs): adverse, intermediate and favorable. Behavioral results show that performance may increase monotonically with TMR in some participants and failed to decrease, or even improved, in the adverse-TMR condition for others. On the neural level, an extensive brain network including the frontal (left prefrontal cortex, right dorsolateral prefrontal cortex and bilateral inferior frontal gyri) and temporal (bilateral auditory cortex) regions was more solicited by the intermediate condition than the two others. Additionally, bilateral frontal gyri and left auditory cortex activities were found to be positively correlated with behavioral performance in the adverse-TMR condition. In Experiment II, 27 participants, whose performance was the poorest in the adverse-TMR condition of Experiment I, were trained to improve performance in that condition. Results show significant performance improvements along with decreased activity in bilateral inferior frontal gyri, the right dorsolateral prefrontal cortex, the left inferior parietal cortex and the right auditory cortex in the adverse-TMR condition after training. Arguably, lower neural activity reflects higher efficiency in processing masker inhibition after speech-in-speech training. As speech-in-noise tasks also imply frontal and temporal regions, we suggest that regardless of the type of masking (speech or noise) the complexity of the task will prompt the implication of a similar brain network. Furthermore, the initial significant cognitive recruitment will be reduced following a training leading to an economy of cognitive resources.

Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Intractable facial paralysis has a poor prognosis, and new treatments are required. Facial paralysis results in the decline in the generation of facial expressions and is attributed to several causes. Reactive oxygen species can inhibit peripheral nerve regeneration after injury. Therefore, the administration of an appropriate antioxidant can promote nerve regeneration. Silicon (Si)-based agents can react with water to generate antioxidant hydrogen. Oral administration of Si-based agents can effectively alleviate symptoms of disease models associated with oxidative stress. Thus, we orally administered a Si-based agent to a facial paralysis model mice to investigate whether promotion of nerve regeneration occurred. The combined administration of methylcobalamin (MeCbl) with the Si-based agent was also investigated. The Si-based agent improved the clinical score evaluation of facial paralysis. Electroneuronography and immunostaining showed that the Si-based agent promoted myelination and recovery of facial nerve function. Furthermore, in the drug-administered group, oxidative stress associated with facial nerve injury was reduced more than that in the non-administered group. The clinical score evaluation, neuroregeneration effect, and reduction of oxidative stress were improved in the combination group compared to the single administration group. The Si-based agent could rapidly improve the disappearance of facial expressions by promoting myelin sheath formation and alleviating oxidative stress. Combination therapy with a Si-based agent and MeCbl should improve the prognosis and treatment of intractable facial paralysis.

Breathing is dynamically modulated by metabolic needs as well as by emotional states. Even though rodents are invaluable models for investigating the neural control of respiration, current literature lacks systematic characterization of breathing dynamics across a broad spectrum of rodent behaviors. Here we uncover a wide diversity in breathing patterns across spontaneous, attractive odor-, stress-, and fear-induced behaviors in mice. Direct recordings of intranasal pressure afford more detailed respiratory information than more traditional whole-body plethysmography. K-means clustering groups 11 well-defined behavioral states into four clusters with distinct key respiratory features. Furthermore, we implement RUSBoost (random undersampling boost) classification, a supervised machine learning model, and find that breathing patterns can separate these behaviors with an accuracy of 80%. Taken together, our findings highlight the tight relationship between breathing and behavior and the potential use of breathing patterns to aid in distinguishing similar behaviors and inform about their internal states.

Performance on auditory change detection tasks can be improved by training. We examined the stimulus specificity of these training effects in behavior and ERPs. A flicker change detection task was employed in which spatialized auditory scenes were alternated until a "change" or "same" response was made. For half of the trials, scenes were identical. The other half contained changes in the spatial locations of objects from scene to scene. On Day 1, participants were either trained on this auditory change detection task (trained group), or trained on a non-auditory change detection task (control group). On Day 2, all participants were tested on the flicker task while EEG was recorded. The trained group showed greater change detection accuracy than the control group. They were less biased to respond "same" and showed full generalization of learning from trained to novel auditory objects. ERPs for "change" compared to "same" trials showed more negative going P1, N1, and P2 amplitudes, as well as a larger P3b amplitude. The P3b amplitude also differed between the trained and control group, with larger amplitudes for the trained group. Analysis of ERPs to scenes viewed prior to a decision revealed build-up of a difference between "change" and "same" trials in N1 and P2. Results demonstrate that training has an impact early in the "same" versus "change" decision-making process, and that the flicker paradigm combined with the ERP method can be used to study the build-up of change detection in auditory scenes.

Although sleep and anesthesia are predicted to share common neural signatures of transitions into and out of unconsciousness, supportive evidence has been elusive. We identified these signatures using intracranial electroencephalography in neurosurgical patients. We applied diffusion map embedding to map cortical location into a space where proximity indicates functional similarity using a normalized connectivity (‘diffusion’) matrix, itself a rich source of information about network properties. During reduced consciousness, diffusion matrices exhibited decreased effective dimensionality, reflecting reduced network entropy. Furthermore, functional brain regions exhibited tighter clustering in embedding space with greater distances between regions, corresponding to decreased differentiation and functional integration. These changes were not region-specific, suggesting global network reorganization. These results strongly suggest common neural substrates for loss and recovery of consciousness during anesthesia and sleep, providing a systems-level mechanistic understanding within an intuitive geometric context and laying the foundation for evaluation of cortical state transitions in clinical settings.

The cerebral cortex is spontaneously active during sleep, yet it is unclear how this global cortical activity is spatiotemporally organized, and whether such activity not only reflects sleep states but also contributes to sleep state switching. Here we report that cortex-wide calcium imaging in mice revealed distinct sleep stage-dependent spatiotemporal patterns of global cortical activity, and modulation of such patterns could regulate sleep state switching. In particular, elevated activation in the occipital cortical regions (including the retrosplenial cortex and visual areas) became dominant during rapid-eye-movement (REM) sleep. Furthermore, such pontogeniculooccipital (PGO) wave-like activity was associated with transitions to REM sleep, and optogenetic inhibition of occipital activity strongly promoted deep sleep by suppressing the NREM-to-REM transition. Thus, whereas subcortical networks are critical for initiating and maintaining sleep and wakefulness states, distinct global cortical activity also plays an active role in controlling sleep states.

There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and “real-world” listening environments and stimuli. Speech in the real world is often accompanied by visual cues, background environmental noise, and is generally in a conversational context, all factors that could affect listening demand. Thus, our objectives were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high-density electroencephalogram (EEG) while CI users listened/watched a naturalistic stimulus (i.e., the television show, “The Office”). We used continuous EEG to quantify “speech neural tracking” (i.e., TRFs, temporal response functions) to the show’s soundtrack and 8–12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show, mimicking a natural noisy environment. The task also included an audio-only (no video) condition. After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they understood. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). Increasing background noise affected speech neural tracking at a group level, in addition to eliciting strong individual differences. Mixed effect modeling showed that listening demand and conversation understanding were correlated to early cortical speech tracking, such that high demand and low conversation understanding occurred with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power, where higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between clinical speech perception and quality-of-life in CI users. However, physiological responses to complex natural speech may provide an objective measure of aspects of quality-of-life measures like self-perceived listening demand.

In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupts sleep by increasing brief arousals (microarousals [MAs]), reducing sleep spindles, and impairing infraslow oscillations in the spindle band of the electroencephalogram during NREMs, while reducing REMs. This poor sleep quality was reflected in an increased number of calcium transients in the activity of noradrenergic (NE) neurons in the locus coeruleus (LC) during NREMs. Opto- and chemogenetic LC-NE activation in naïve mice is sufficient to change the sleep microarchitecture similar to stress. Conversely, chemogenetically inhibiting LC-NE neurons reduced MAs during NREMs and normalized their number after stress. Specifically inhibiting LC-NE neurons projecting to the preoptic area of the hypothalamus (POA) decreased MAs and enhanced spindles and REMs after stress. Optrode recordings revealed that stimulating LC-NE fibers in the POA indeed suppressed the spiking activity of POA neurons that are activated during sleep spindles and REMs and inactivated during MAs. Our findings reveal that changes in the dynamics of the stress-regulatory LC-NE neurons during sleep negatively affect sleep quality, partially through their interaction with the POA.

Active recall of short-term memory (STM) is known to last for a few hours, but whether STM has long-term functions is unknown. Here we show that STM can be optogenetically retrieved at a time point during which natural recall is not possible, uncovering the long-term existence of an STM engram. Moreover, re-training within 3 days led to natural long-term recall, indicating facilitated consolidation. Inhibiting offline CA1 activity during non-rapid eye movement (NREM) sleep, N-methyl-D-aspartate receptor (NMDAR) activity, or protein synthesis after first exposure to the STM-forming event impaired the future re-exposure-facilitated consolidation, which highlights a role of protein synthesis, NMDAR and NREM sleep in the long-term storage of an STM trace. These results provide evidence that STM is not completely lost within hours and demonstrates a possible two-step STM consolidation, first long-term storage as a behaviorally inactive engram, then transformation into an active state by recurrence within 3 days.

Experimental evidence in animals demonstrates cortical neurons innervate subcortex bilaterally to tune brainstem auditory coding. Yet, the role of the descending (corticofugal) auditory system in modulating earlier sound processing in humans during speech perception remains unclear. Here, we measured EEG activity as listeners performed speech identification tasks in different noise backgrounds designed to tax perceptual and attentional processing. We hypothesized brainstem speech coding might be tied to attention and arousal states (indexed by cortical α power) that actively modulate the interplay of brainstem-cortical signal processing. When speech-evoked brainstem frequency-following responses (FFRs) were categorized according to cortical α states, we found low α FFRs in noise were weaker, correlated positively with behavioral response times, and were more "decodable" via neural classifiers. Our data provide new evidence for online corticofugal interplay in humans and establish that brainstem sensory representations are continuously yoked to (i.e., modulated by) the ebb and flow of cortical states to dynamically update perceptual processing.