EEG/ECoG/EMG publications

The “non-specific” ventromedial thalamic nucleus (VM) has long been considered a candidate for mediating cortical arousal due to its diffuse, superficial projections, but direct evidence was lacking. Here, we show in mice that the activity of VM calbindin1-positive matrix cells is high in wake and REM sleep and low in NREM sleep, and increases before cortical activity at the sleep-to-wake transition. Optogenetic stimulation of VM cells rapidly awoke all mice from NREM sleep and consistently caused EEG activation during slow wave anesthesia, while arousal did not occur from REM sleep. Conversely, chemogenetic inhibition of VM decreased wake duration. Optogenetic activation of the “specific” ventral posteromedial nucleus (VPM) did not cause arousal from either NREM or REM sleep. Thus, matrix cells in VM produce arousal and broad cortical activation during NREM sleep and slow wave anesthesia in a way that accounts for the effects classically attributed to “non-specific” thalamic nuclei.

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation.

Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones, have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones-independent of them being epileptogenic-are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILβ1, TNFα and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed.

The acoustic change complex (ACC) is a scalp-recorded cortical evoked potential complex generated in response to changes (e.g., frequency, amplitude) in an auditory stimulus. The ACC has been well studied in humans, but to our knowledge, no animal model has been evaluated. In particular, it was not known whether the ACC could be recorded under the conditions of sedation that likely would be necessary for recordings from animals. For that reason, we tested the feasibility of recording ACC from sedated cats in response to changes of frequency and amplitude of pure-tone stimuli. Cats were sedated with ketamine and acepromazine, and subdermal needle electrodes were used to record electroencephalographic (EEG) activity. Tones were presented from a small loudspeaker located near the right ear. Continuous tones alternated at 500-ms intervals between two frequencies or two levels. Neurometric functions were created by recording neural response amplitudes while systematically varying the magnitude of steps in frequency centered in octave frequency around 2, 4, 8, and 16 kHz, all at 75 dB SPL, or in decibel level around 75 dB SPL tested at 4 and 8 kHz. The ACC could be recorded readily under this ketamine/azepromazine sedation. In contrast, ACC could not be recorded reliably under any level of isoflurane anesthesia that was tested. The minimum frequency (expressed as Weber fractions (df/f)) or level steps (expressed in dB) needed to elicit ACC fell in the range of previous thresholds reported in animal psychophysical tests of discrimination. The success in recording ACC in sedated animals suggests that the ACC will be a useful tool for evaluation of other aspects of auditory acuity in normal hearing and, presumably, in electrical cochlear stimulation, especially for novel stimulation modes that are not yet feasible in humans.

Laboratory and clinical studies have demonstrated that therapeutic hypothermia (TH), when applied as soon as possible after resuscitation from cardiac arrest (CA), results in better neurological outcome. This study tested the hypothesis that TH would promote cerebral blood flow (CBF) restoration and its maintenance after return of spontaneous circulation (ROSC) from CA. Twelve Wistar rats resuscitated from 7-min asphyxial CA were randomized into two groups: hypothermia group (7 H, n = 6), treated with mild TH (33–34℃) immediately after ROSC and normothermia group (7 N, n = 6,37.0 ± 0.5℃). Multiple parameters including mean arterial pressure, CBF, electroencephalogram (EEG) were recorded. The neurological outcomes were evaluated using electrophysiological (information quantity, IQ, of EEG) methods and a comprehensive behavior examination (neurological deficit score, NDS). TH consistently promoted better CBF restoration approaching the baseline levels in the 7 H group as compared with the 7 N group. CBF during the first 5–30 min post ROSC of the two groups was 7 H:90.5% ± 3.4% versus 7 N:76.7% ± 3.5% ( P < 0.01). Subjects in the 7 H group showed significantly better IQ scores after ROSC and better NDS scores at 4 and 24 h. Early application of TH facilitates restoration of CBF back to baseline levels after CA, which in turn results in the restoration of brain electrical activity and improved neurological outcome.

We present a new class of carbon-based neural probes that consist of homogeneous glassy carbon (GC) microelectrodes, interconnects and bump pads. These electrodes have purely capacitive behavior with exceptionally high charge storage capacity (CSC) and are capable of sustaining more than 3.5 billion cycles of bi-phasic pulses at charge density of 0.25 mC/cm 2 . These probes enable both high SNR (>16) electrical signal recording and remarkably high-resolution real-time neurotransmitter detection, on the same platform. Leveraging a new 2-step, double-sided pattern transfer method for GC structures, these probes allow extended long-term electrical stimulation with no electrode material corrosion. Cross-section characterization through FIB and SEM imaging demonstrate strong attachment enabled by hydroxyl and carbonyl covalent bonds between GC microstructures and top insulating and bottom substrate layers. Extensive in-vivo and in-vitro tests confirmed: (i) high SNR (>16) recordings, (ii) highest reported CSC for non-coated neural probe (61.4 ± 6.9 mC/cm 2 ), (iii) high-resolution dopamine detection (10 nM level - one of the lowest reported so far), (iv) recording of both electrical and electrochemical signals, and (v) no failure after 3.5 billion cycles of pulses. Therefore, these probes offer a compelling multi-modal platform for long-term applications of neural probe technology in both experimental and clinical neuroscience.

Objectives: This study was designed to evaluate binaural temporal processing in young and older adults using a binaural masking level difference (BMLD) paradigm. Using behavioral and electrophysiological measures within the same listeners, a series of stimulus manipulations was used to evaluate the relative contribution of binaural temporal fine-structure and temporal envelope cues. We evaluated the hypotheses that age-related declines in the BMLD task would be more strongly associated with temporal fine-structure than envelope cues and that age-related declines in behavioral measures would be correlated with cortical auditory evoked potential (CAEP) measures. Design: Thirty adults participated in the study, including 10 young normal-hearing, 10 older normal-hearing, and 10 older hearing-impaired adults with bilaterally symmetric, mild-to-moderate sensorineural hearing loss. Behavioral and CAEP thresholds were measured for diotic (So) and dichotic (Sπ) tonal signals presented in continuous diotic (No) narrowband noise (50-Hz wide) maskers. Temporal envelope cues were manipulated by using two different narrowband maskers; Gaussian noise (GN) with robust envelope fluctuations and low-noise noise (LNN) with minimal envelope fluctuations. The potential to use temporal fine-structure cues was controlled by varying the signal frequency (500 or 4000 Hz), thereby relying on the natural decline in phase-locking with increasing frequency. Results: Behavioral and CAEP thresholds were similar across groups for diotic conditions, while the masking release in dichotic conditions was larger for younger than for older participants. Across all participants, BMLDs were larger for GN than LNN and for 500-Hz than for 4000-Hz conditions, where envelope and fine-structure cues were most salient, respectively. Specific age-related differences were demonstrated for 500-Hz dichotic conditions in GN and LNN, reflecting reduced binaural temporal fine-structure coding. No significant age effects were observed for 4000-Hz dichotic conditions, consistent with similar use of binaural temporal envelope cues across age in these conditions. For all groups, thresholds and derived BMLD values obtained using the behavioral and CAEP methods were strongly correlated, supporting the notion that CAEP measures may be useful as an objective index of age-related changes in binaural temporal processing. Conclusions: These results demonstrate an age-related decline in the processing of binaural temporal fine-structure cues with preserved temporal envelope coding that was similar with and without mild-to-moderate peripheral hearing loss. Such age-related changes can be reliably indexed by both behavioral and CAEP measures in young and older adults.

Sleep-wake history, wake behaviors, lighting conditions, and circadian time influence sleep, but neither their relative contribution nor the underlying mechanisms are fully understood. The dynamics of electroencephalogram (EEG) slow-wave activity (SWA) during sleep can be described using the two-process model, whereby the parameters of homeostatic Process S are estimated using empirical EEG SWA (0.5-4 Hz) in nonrapid eye movement sleep (NREMS), and the 24 hr distribution of vigilance states. We hypothesized that the influence of extrinsic factors on sleep homeostasis, such as the time of day or wake behavior, would manifest in systematic deviations between empirical SWA and model predictions. To test this hypothesis, we performed parameter estimation and tested model predictions using NREMS SWA derived from continuous EEG recordings from the frontal and occipital cortex in mice. The animals showed prolonged wake periods, followed by consolidated sleep, both during the dark and light phases, and wakefulness primarily consisted of voluntary wheel running, learning a new motor skill or novel object exploration. Simulated SWA matched empirical levels well across conditions, and neither waking experience nor time of day had a significant influence on the fit between data and simulation. However, we consistently observed that Process S declined during sleep significantly faster in the frontal than in the occipital area of the neocortex. The striking resilience of the model to specific wake behaviors, lighting conditions, and time of day suggests that intrinsic factors underpinning the dynamics of Process S are robust to extrinsic influences, despite their major role in shaping the overall amount and distribution of vigilance states across 24 hr.

Evidence for intrinsic functional connectivity (FC) within the human brain is largely from neuroimaging studies of hemodynamic activity. Data are lacking from anatomically precise electrophysiological recordings in the most widely studied nodes of human brain networks. Here we used a combination of fMRI and electrocorticography (ECoG) in five human neurosurgical patients with electrodes in the canonical “default” (medial prefrontal and posteromedial cortex), “dorsal attention” (frontal eye fields and superior parietal lobule), and “frontoparietal control” (inferior parietal lobule and dorsolateral prefrontal cortex) networks. In this unique cohort, simultaneous intracranial recordings within these networks were anatomically matched across different individuals. Within each network and for each individual, we found a positive, and reproducible, spatial correlation for FC measures obtained from resting-state fMRI and separately recorded ECoG in the same brains. This relationship was reliably identified for electrophysiological FC based on slow (<1 Hz) fluctuations of high-frequency broadband (70–170 Hz) power, both during wakeful rest and sleep. A similar FC organization was often recovered when using lower-frequency (1–70 Hz) power, but anatomical specificity and consistency were greatest for the high-frequency broadband range. An interfrequency comparison of fluctuations in FC revealed that high and low-frequency ranges often temporally diverged from one another, suggesting that multiple neurophysiological sources may underlie variations in FC. Together, our work offers a generalizable electrophysiological basis for intrinsic FC and its dynamics across individuals, brain networks, and behavioral states. SIGNIFICANCE STATEMENT The study of human brain networks during wakeful “rest”, largely with fMRI, is now a major focus in both cognitive and clinical neuroscience. However, little is known about the neurophysiology of these networks and their dynamics. We studied neural activity during wakeful rest and sleep within neurosurgical patients with directly implanted electrodes. We found that network activity patterns showed striking similarities between fMRI and direct recordings in the same brains. With improved resolution of direct recordings, we also found that networks were best characterized with specific activity frequencies and that different frequencies show different profiles of within-network activity over time. Our work clarifies how networks spontaneously organize themselves across individuals, brain networks, and behavioral states.

The posterior auricular muscle (PAM) reflex to sounds has been used clinically to determine hearing threshold as an alternative to other audiological diagnostic measures such as the auditory brainstem response. We have shown that the PAM response is also sensitive to interaural timing differences in normally hearing adults. PAM responses were evoked by both ipsilateral/ contralateral monaural stimulation and by binaural stimulation. Introducing sound delays ipsilaterally or contralaterally decreased the PAM response amplitude and increased its latency. The PAM response in this study shows a qualitatively similar pattern to that seen by the binaural interaction component (BIC) of the auditory brainstem potential to binaural clicks described in previous studies, in that both: have their shortest latency and maximal amplitudes centred around zero interaural timing differences, have response latencies increase with increasing interaural delays up to 1.2 ms and have response amplitudes decrease with increasing interaural delays of up to 1.2 ms. Our data show that the PAM response may be useful in measuring binaural integration in humans non-invasively for diagnostic or research studies.

Parsing simultaneous speech requires listeners use pitch-guided segregation which can be affected by the signal-to-noise ratio (SNR) in the auditory scene. The interaction of these two cues may occur at multiple levels within the cortex. The aims of the current study were to assess the correspondence between oscillatory brain rhythms and determine how listeners exploit pitch and SNR cues to successfully segregate concurrent speech. We recorded electrical brain activity while participants heard double-vowel stimuli whose fundamental frequencies (F0s) differed by zero or four semitones (STs) presented in either clean or noise-degraded (+5 dB SNR) conditions. We found that behavioral identification was more accurate for vowel mixtures with larger pitch separations but F0 benefit interacted with noise. Time-frequency analysis decomposed the EEG into different spectrotemporal frequency bands. Low-frequency (θ, β) responses were elevated when speech did not contain pitch cues (0ST > 4ST) or was noisy, suggesting a correlate of increased listening effort and/or memory demands. Contrastively, γ power increments were observed for changes in both pitch (0ST > 4ST) and SNR (clean > noise), suggesting high-frequency bands carry information related to acoustic features and the quality of speech representations. Brain-behavior associations corroborated these effects; modulations in low-frequency rhythms predicted the speed of listeners' perceptual decisions with higher bands predicting identification accuracy. Results are consistent with the notion that neural oscillations reflect both automatic (pre-perceptual) and controlled (post-perceptual) mechanisms of speech processing that are largely divisible into high- and low-frequency bands of human brain rhythms.

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL-PFC interactions underlie working memory for everyday experiences.

Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture. SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we performed chronic electrophysiological recordings of cortical neural activity during waking, sleep, and after sleep deprivation from young and older mice. We found that all main hallmarks of cortical activity during spontaneous sleep and recovery sleep after sleep deprivation were largely intact in older mice, suggesting that the well-described age-related changes in global sleep are unlikely to arise from a disruption of local network dynamics within the neocortex.

Significance Listeners with hearing loss have trouble communicating in many social settings. In such situations, listeners with normal hearing suppress the neural representation of competing sounds, a process known as auditory selective attention. We compared hearing-impaired (HI) and normal-hearing (NH) listeners on a spatial selective attention task while measuring neural responses using electroencephalography. Compared with NH listeners, HI listeners have poorer sensitivity to spatial cues, perform more poorly on the selective attention task, and show weaker neural suppression of competing sounds. Moreover, these different measures are correlated both for HI and for NH listeners. These results suggest that poor spatial acuity produces problems with selective attention. These findings have implications both for basic science and for development of next-generation hearing aids.

Natural sound is composed of various frequencies. Although the core region of the primate auditory cortex has functionally defined sound frequency preference maps, how the map is organized in the auditory areas of the belt and parabelt regions is not well known. In this study, we investigated the functional organizations of the core, belt, and parabelt regions encompassed by the lateral sulcus and the superior temporal sulcus in the common marmoset ( Callithrix jacchus ). Using optical intrinsic signal imaging, we obtained evoked responses to band-pass noise stimuli in a range of sound frequencies (0.5–16 kHz) in anesthetized adult animals and visualized the preferred sound frequency map on the cortical surface. We characterized the functionally defined organization using histologically defined brain areas in the same animals. We found tonotopic representation of a set of sound frequencies (low to high) within the primary (A1), rostral (R), and rostrotemporal (RT) areas of the core region. In the belt region, the tonotopic representation existed only in the mediolateral (ML) area. This representation was symmetric with that found in A1 along the border between areas A1 and ML. The functional structure was not very clear in the anterolateral (AL) area. Low frequencies were mainly preferred in the rostrotemplatal (RTL) area, while high frequencies were preferred in the caudolateral (CL) area. There was a portion of the parabelt region that strongly responded to higher sound frequencies (>5.8 kHz) along the border between the rostral parabelt (RPB) and caudal parabelt (CPB) regions.

Objective . Recent research has characterized the anatomical and functional basis of speech perception in the human auditory cortex. These advances have made it possible to decode speech information from activity in brain regions like the superior temporal gyrus, but no published work has demonstrated this ability in real-time, which is necessary for neuroprosthetic brain–computer interfaces. Approach . Here, we introduce a real-time neural speech recognition (rtNSR) software package, which was used to classify spoken input from high-resolution electrocorticography signals in real-time. We tested the system with two human subjects implanted with electrode arrays over the lateral brain surface. Subjects listened to multiple repetitions of ten sentences, and rtNSR classified what was heard in real-time from neural activity patterns using direct sentence-level and HMM-based phoneme-level classification schemes. Main results . We observed single-trial sentence classification accuracies of 90 % or higher for each subject with less than 7 minutes of training data, demonstrating the ability of rtNSR to use cortical recordings to perform accurate real-time speech decoding in a limited vocabulary setting. Significance . Further development and testing of the package with different speech paradigms could influence the design of future speech neuroprosthetic applications.

Mammalian sleep consists of distinct rapid eye movement (REM) and non-REM (NREM) states. The midbrain region ventrolateral periaqueductal gray (vlPAG) is known to be important for gating REM sleep, but the underlying neuronal mechanism is not well understood. Here, we show that activating vlPAG GABAergic neurons in mice suppresses the initiation and maintenance of REM sleep while consolidating NREM sleep, partly through their projection to the dorsolateral pons. Cell-type-specific recording and calcium imaging reveal that most vlPAG GABAergic neurons are strongly suppressed at REM sleep onset and activated at its termination. In addition to the rapid changes at brain state transitions, their activity decreases gradually between REM sleep and is reset by each REM episode in a duration-dependent manner, mirroring the accumulation and dissipation of REM sleep pressure. Thus, vlPAG GABAergic neurons powerfully gate REM sleep, and their firing rate modulation may contribute to the ultradian rhythm of REM/NREM alternation.

Whereas the neurophysiology of respiration has traditionally focused on automatic brain stem processes, higher brain mechanisms underlying the cognitive aspects of breathing are gaining increasing interest. Therapeutic techniques have used conscious control and awareness of breathing for millennia with little understanding of the mechanisms underlying their efficacy. Using direct intracranial recordings in humans, we correlated cortical and limbic neuronal activity as measured by the intracranial electroencephalogram (iEEG) with the breathing cycle. We show this to be the direct result of neuronal activity, as demonstrated by both the specificity of the finding to the cortical gray matter and the tracking of breath by the gamma-band (40–150 Hz) envelope in these structures. We extend prior observations by showing the iEEG signal to track the breathing cycle across a widespread network of cortical and limbic structures. We further demonstrate a sensitivity of this tracking to cognitive factors by using tasks adapted from cognitive behavioral therapy and meditative practice. Specifically, volitional control and awareness of breathing engage distinct but overlapping brain circuits. During volitionally paced breathing, iEEG-breath coherence increases in a frontotemporal-insular network, and during attention to breathing, we demonstrate increased coherence in the anterior cingulate, premotor, insular, and hippocampal cortices. Our findings suggest that breathing can act as an organizing hierarchical principle for neuronal oscillations throughout the brain and detail mechanisms of how cognitive factors impact otherwise automatic neuronal processes during interoceptive attention. NEW & NOTEWORTHY Whereas the link between breathing and brain activity has a long history of application to therapy, its neurophysiology remains unexplored. Using intracranial recordings in humans, we show neuronal activity to track the breathing cycle throughout widespread cortical/limbic sites. Volitional pacing of the breath engages frontotemporal-insular cortices, whereas attention to automatic breathing modulates the cingulate cortex. Our findings imply a fundamental role of breathing-related oscillations in driving neuronal activity and provide insight into the neuronal mechanisms of interoceptive attention.

Electrophysiology and neuroimaging provide conflicting evidence for the neural contributions to target detection. Scalp electroencephalography (EEG) studies localize the P3b event-related potential component mainly to parietal cortex, whereas neuroimaging studies report activations in both frontal and parietal cortices. We addressed this discrepancy by examining the sources that generate the target-detection process using electrocorticography (ECoG). We recorded ECoG activity from cortex in 14 patients undergoing epilepsy monitoring, as they performed an auditory or visual target-detection task. We examined target-related responses in 2 domains: high frequency band (HFB) activity and the P3b. Across tasks, we observed a greater proportion of electrodes that showed target-specific HFB power relative to P3b over frontal cortex, but their proportions over parietal cortex were comparable. Notably, there was minimal overlap in the electrodes that showed target-specific HFB and P3b activity. These results revealed that the target-detection process is characterized by at least 2 different neural markers with distinct cortical distributions. Our findings suggest that separate neural mechanisms are driving the differential patterns of activity observed in scalp EEG and neuroimaging studies, with the P3b reflecting EEG findings and HFB activity reflecting neuroimaging findings, highlighting the notion that target detection is not a unitary phenomenon.

Speech is an ecologically essential signal, whose processing crucially involves the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses in human listeners under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electroencephalography (EEG) and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal-to-noise ratios signal-to-noise ratio has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tone-bursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response (ABR) to ongoing, naturally uttered speech, using EEG to record from human listeners. We found a high degree of morphological similarity between the speech-derived ABRs and the standard click-evoked ABR, in particular, a preserved Wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks that recapitulate the canonical ABR, at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to measure the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the potential effects of cognitive processes like language and attention on brainstem processing.