EEG/ECoG/EMG publications

A 'pattern alternation paradigm' has been previously used in human ERP recordings to investigate the brain encoding of complex auditory regularities, but prior studies on regularity encoding in animal models to examine mechanisms of adaptation of auditory neuronal responses have used primarily oddball stimulus sequences to study stimulus-specific adaptation alone. In order to examine the sensitivity of neuronal adaptation to expected and unexpected events embedded in a complex sound sequence, we used a similar patterned sequence of sounds. We recorded single unit activity and compared neuronal responses in the rat inferior colliculus (IC) to sound stimuli conforming to pattern alternation regularity with those to stimuli in which occasional sound repetitions violated that alternation. Results show that some neurons in the rat inferior colliculus are sensitive to the history of patterned stimulation and to violations of patterned regularity, demonstrating that there is a population of subcortical neurons, located as early as the level of the midbrain, that can detect more complex stimulus regularities than previously supposed and that are as sensitive to complex statistics as some neurons in primary auditory cortex. Our findings indicate that these pattern-sensitive neurons can extract temporal and spectral regularities between successive acoustic stimuli. This is important because the extraction of regularities from the sound sequences will result in the development of expectancies for future sounds and hence, the present results are compatible with predictive coding models. Our results demonstrate that some collicular neurons, located as early as in the midbrain level, are involved in the generation and shaping of prediction errors in ways not previously considered and thus, the present findings challenge the prevailing view that perceptual organization of sound only emerges at the auditory cortex level.

The frequency-specific tone-evoked auditory brainstem response (ABR) is an indispensable tool in both the audiology clinic and research laboratory. Most frequently, the toneburst ABR is used to estimate hearing thresholds in infants, toddlers, and other patients for whom behavioral testing is not feasible. Therefore, results of the ABR exam form the basis for decisions regarding interventions and hearing habilitation with implications extending far into the child’s future. Currently, responses are elicited by periodic sequences of toneburst stimuli presented serially to one ear at a time, which take a long time to measure multiple frequencies and intensities, and provide incomplete information if the infant wakes up early. Here, we describe a new method, the parallel ABR (pABR), which uses randomly timed toneburst stimuli to simultaneously acquire ABR waveforms to five frequencies in both ears. Here, we describe the pABR and quantify its effectiveness in addressing the greatest drawback of current methods: test duration. We show that in adults with normal hearing the pABR yields high-quality waveforms over a range of intensities, with similar morphology to the standard ABR in a fraction of the recording time. Furthermore, longer latencies and smaller amplitudes for low frequencies at a high intensity evoked by the pABR versus serial ABR suggest that responses may have better place specificity due to the masking provided by the other simultaneous toneburst sequences. Thus, the pABR has substantial potential for facilitating faster accumulation of more diagnostic information that is important for timely identification and treatment of hearing loss.

Evaluation of patients who are unable to provide behavioral responses on standard clinical measures is challenging due to the lack of standard objective (non-behavioral) clinical audiological measures that assess the outcome of an intervention (e.g., hearing aids). Brainstem responses to short consonant-vowel stimuli (speech-auditory brainstem responses [speech-ABRs]) have been proposed as a measure of subcortical encoding of speech, speech detection, and speech-in-noise performance in individuals with normal hearing. Here, we investigated the potential application of speech-ABRs as an objective clinical outcome measure of speech detection, speech-in-noise detection and recognition, and self-reported speech understanding in 98 adults with sensorineural hearing loss. We compared aided and unaided speech-ABRs, and speech-ABRs in quiet and in noise. In addition, we evaluated whether speech-ABR F0 encoding (obtained from the complex cross-correlation with the 40 ms [da] fundamental waveform) predicted aided behavioral speech recognition in noise or aided self-reported speech understanding. Results showed that (a) aided speech-ABRs had earlier peak latencies, larger peak amplitudes, and larger F0 encoding amplitudes compared to unaided speech-ABRs; (b) the addition of background noise resulted in later F0 encoding latencies but did not have an effect on peak latencies and amplitudes or on F0 encoding amplitudes; and (c) speech-ABRs were not a significant predictor of any of the behavioral or self-report measures. These results show that speech-ABR F0 encoding is not a good predictor of speech-in-noise recognition or self-reported speech understanding with hearing aids. However, our results suggest that speech-ABRs may have potential for clinical application as an objective measure of speech detection with hearing aids.

Understanding cortical processing of spectrally degraded speech in normal-hearing subjects may provide insights into how sound information is processed by cochlear implant (CI) users. This study investigated electrocorticographic (ECoG) responses to noise-vocoded speech and related these responses to behavioral performance in a phonemic identification task. Subjects were neurosurgical patients undergoing chronic invasive monitoring for medically refractory epilepsy. Stimuli were utterances /aba/ and /ada/, spectrally degraded using a noise vocoder (1-4 bands). ECoG responses were obtained from Heschl's gyrus (HG) and superior temporal gyrus (STG), and were examined within the high gamma frequency range (70-150 Hz). All subjects performed at chance accuracy with speech degraded to 1 and 2 spectral bands, and at or near ceiling for clear speech. Inter-subject variability was observed in the 3- and 4-band conditions. High gamma responses in posteromedial HG (auditory core cortex) were similar for all vocoded conditions and clear speech. A progressive preference for clear speech emerged in anterolateral segments of HG, regardless of behavioral performance. On the lateral STG, responses to all vocoded stimuli were larger in subjects with better task performance. In contrast, both behavioral and neural responses to clear speech were comparable across subjects regardless of their ability to identify degraded stimuli. Findings highlight differences in representation of spectrally degraded speech across cortical areas and their relationship to perception. The results are in agreement with prior non-invasive results. The data provide insight into the neural mechanisms associated with variability in perception of degraded speech and potentially into sources of such variability in CI users.

Before primary motor cortex (M1) develops its motor functions, it functions like a somatosensory area. Here, by recording from neurons in the forelimb representation of M1 in postnatal day (P) 8–12 rats, we demonstrate a rapid shift in its sensory responses. At P8-10, M1 neurons respond overwhelmingly to feedback from sleep-related twitches of the forelimb, but the same neurons do not respond to wake-related movements. By P12, M1 neurons suddenly respond to wake movements, a transition that results from opening the sensory gate in the external cuneate nucleus. Also at P12, fewer M1 neurons respond to individual twitches, but the full complement of twitch-related feedback observed at P8 is unmasked through local disinhibition. Finally, through P12, M1 sensory responses originate in the deep thalamorecipient layers, not primary somatosensory cortex. These findings demonstrate that M1 initially establishes a sensory framework upon which its later-emerging role in motor control is built.

Objectives: The purpose of this study was to obtain an electrophysiological analog of masking release using speech-evoked cortical potentials in steady and modulated maskers and to relate this masking release to behavioral measures for the same stimuli. The hypothesis was that the evoked potentials can be tracked to a lower stimulus level in a modulated masker than in a steady masker and that the magnitude of this electrophysiological masking release is of the same order as that of the behavioral masking release for the same stimuli. Design: Cortical potentials evoked by an 80-ms /ba/ stimulus were measured in two steady maskers (30 and 65 dB SPL), and in a masker that modulated between these two levels at a rate of 25 Hz. In each masker, a level series was undertaken to determine electrophysiological threshold. Behavioral detection thresholds were determined in the same maskers using an adaptive tracking procedure. Masking release was defined as the difference between signal thresholds measured in the steady 65-dB SPL masker and the modulated masker. A total of 23 normal-hearing adults participated. Results: Electrophysiological thresholds were uniformly elevated relative to behavioral thresholds by about 6.5 dB. However, the magnitude of masking release was about 13.5 dB for both measurement domains. Conclusions: Electrophysiological measures of masking release using speech-evoked cortical auditory evoked potentials correspond closely to behavioral estimates for the same stimuli. This suggests that objective measures based on electrophysiological techniques can be used to reliably gauge aspects of temporal processing ability.

Glassy carbon (GC) has high potential to serve as a biomaterial in neural applications because it is biocompatible, electrochemically inert and can be incorporated in polyimide-based implantable devices. Miniaturization and applicability of GC is, however, thought to be partially limited by its electrical conductivity. For this study, ultra-conformable polyimide-based electrocorticography (ECoG) devices with different-diameter GC electrodes were fabricated and tested in vitro and in rat models. For achieving conformability to the rat brain, polyimide was patterned in a finger-like shape and its thickness was set to 8 µm. To investigate different electrode sizes, each ECoG device was assigned electrodes with diameters of 50, 100, 200 and 300 µm. They were electrochemically characterized and subjected to 10 million biphasic pulses—for achieving a steady-state—and to X-ray photoelectron spectroscopy, for examining their elemental composition. The electrodes were then implanted epidurally to evaluate the ability of each diameter to detect neural activity. Results show that their performance at low frequencies (up to 300 Hz) depends on the distance from the signal source rather than on the electrode diameter, while at high frequencies (above 200 Hz) small electrodes have higher background noises than large ones, unless they are coated with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS).

In week-old rats, somatosensory input arises predominantly from external stimuli or from sensory feedback (reafference) associated with myoclonic twitches during active sleep. A previous study suggested that the brainstem motor structures that produce twitches also send motor copies (or corollary discharge, CD) to the cerebellum. We tested this possibility by recording from two precerebellar nuclei—the inferior olive (IO) and lateral reticular nucleus (LRN). In most IO and LRN neurons, twitch-related activity peaked sharply around twitch onset, consistent with CD. Next, we identified twitch-production areas in the midbrain that project independently to the IO and LRN. Finally, we blocked calcium-activated slow potassium (SK) channels in the IO to explain how broadly tuned brainstem motor signals can be transformed into precise CD signals. We conclude that the precerebellar nuclei convey a diversity of sleep-related neural activity to the developing cerebellum to enable processing of convergent input from CD and reafferent signals.

Significance Musicianship is widely reported to enhance auditory brain processing related to speech–language function. Such benefits could reflect true experience-dependent plasticity, as often assumed, or innate, preexisting differences in auditory system function (i.e., nurture vs. nature). By recording speech-evoked electroencephalograms, we show that individuals who are naturally more adept in listening tasks but possess no formal music training (“musical sleepers”) have superior neural encoding of clear and noise-degraded speech, mirroring enhancements reported in trained musicians. Our findings provide clear evidence that certain individuals have musician-like auditory neurobiological function and temper assumptions that music-related neuroplasticity is solely experience-driven. These data reveal that formal music experience is neither necessary nor sufficient to enhance the brain’s neural encoding and perception of sound.

Under the predictive coding hypothesis, specific spatiotemporal patterns of cortical activation are postulated to occur during sensory processing as expectations generate feedback predictions and prediction errors generate feedforward signals. Establishing experimental evidence for this information flow within cortical hierarchy has been difficult, especially in humans, due to spatial and temporal limitations of non-invasive measures of cortical activity. This study investigated cortical responses to auditory novelty using the local/global deviant paradigm, which engages the hierarchical network underlying auditory predictive coding over short ('local deviance'; LD) and long ('global deviance'; GD) time scales. Electrocorticographic responses to auditory stimuli were obtained in neurosurgical patients from regions of interest (ROIs) including auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed in averaged evoked potential (AEP) and high gamma (70-150 Hz) signals, the former likely dominated by local synaptic currents and the latter largely reflecting local spiking activity. AEP LD effects were distributed across all ROIs, with greatest percentage of significant sites in core and non-core auditory cortex. High gamma LD effects were localized primarily to auditory cortex in the superior temporal plane and on the lateral surface of the superior temporal gyrus (STG). LD effects exhibited progressively longer latencies in core, non-core, auditory-related and prefrontal cortices, consistent with feedforward signaling. The spatial distribution of AEP GD effects overlapped that of LD effects, but high gamma GD effects were more restricted to non-core areas. High gamma GD effects had shortest latencies in STG and preceded AEP GD effects in most ROIs. This latency profile, along with the paucity of high gamma GD effects in the superior temporal plane, suggest that the STG plays a prominent role in initiating novelty detection signals over long time scales. Thus, the data demonstrate distinct patterns of information flow in human cortex associated with auditory novelty detection over multiple time scales.

Auditory speech comprehension is the result of neural computations that occur in a broad network that includes the temporal lobe auditory cortex and the left inferior frontal cortex. It remains unclear how representations in this network differentially contribute to speech comprehension. Here, we recorded high-density direct cortical activity during a sine-wave speech (SWS) listening task to examine detailed neural speech representations when the exact same acoustic input is comprehended versus not comprehended. Listeners heard SWS sentences (pre-exposure), followed by clear versions of the same sentences, which revealed the content of the sounds (exposure), and then the same SWS sentences again (post-exposure). Across all three task phases, high-gamma neural activity in the superior temporal gyrus was similar, distinguishing different words based on bottom-up acoustic features. In contrast, frontal regions showed a more pronounced and sudden increase in activity only when the input was comprehended, which corresponded with stronger representational separability among spatiotemporal activity patterns evoked by different words. We observed this effect only in participants who were not able to comprehend the stimuli during the pre-exposure phase, indicating a relationship between frontal high-gamma activity and speech understanding. Together, these results demonstrate that both frontal and temporal cortical networks are involved in spoken language understanding, and that under certain listening conditions, frontal regions are involved in discriminating speech sounds.

The selection of behaviorally relevant information from cluttered visual scenes (often referred to as “attention”) is mediated by a cortical large-scale network consisting of areas in occipital, temporal, parietal, and frontal cortex that is organized into a functional hierarchy of feedforward and feedback pathways. In the human brain, little is known about the temporal dynamics of attentional processing from studies at the mesoscopic level of electrocorticography (ECoG), that combines millisecond temporal resolution with precise anatomical localization of recording sites. We analyzed high-frequency broadband responses (HFB) responses from 626 electrodes implanted in 8 epilepsy patients who performed a spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system. HFB responses showed high spatial selectivity and tuning, constituting ECoG response fields (RFs), within and outside the topographic visual system. In accordance with monkey physiology studies, both RF widths and onset latencies increased systematically across the visual processing hierarchy. We used the spatial specificity of HFB responses to quantitatively study spatial attention effects and their temporal dynamics to probe a hierarchical top-down model suggesting that feedback signals back propagate the visual processing hierarchy. Consistent with such a model, the strengths of attentional modulation were found to be greater and modulation latencies to be shorter in posterior parietal cortex, middle temporal cortex and ventral extrastriate cortex compared with early visual cortex. However, inconsistent with such a model, attention effects were weaker and more delayed in anterior parietal and frontal cortex. SIGNIFICANCE STATEMENT In the human brain, visual attention has been predominantly studied using methods with high spatial, but poor temporal resolution such as fMRI, or high temporal, but poor spatial resolution such as EEG/MEG. Here, we investigate temporal dynamics and attention effects across the human visual system at a mesoscopic level that combines precise spatial and temporal measurements by using electrocorticography in epilepsy patients performing a classical spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system, thereby relating them to topography and processing hierarchy. We demonstrate regional differences in temporal dynamics across the attention network. Our findings do not fully support a top-down model that promotes influences on visual cortex by reversing the processing hierarchy.

Over the past decade, numerous neuroimaging studies based on hemodynamic markers of brain activity have examined the feeling of body ownership using perceptual body-illusions in humans. However, the direct electrophysiological correlates of body ownership at the cortical level remain unexplored. To address this, we studied the rubber hand illusion in 5 patients (3 males and 2 females) implanted with intracranial electrodes measuring cortical surface potentials. Increased high-γ (70–200 Hz) activity, an index of neuronal firing rate, in premotor and intraparietal cortices reflected the feeling of ownership. In both areas, high-γ increases were intimately coupled with the subjective illusion onset and sustained both during and in-between touches. However, intraparietal activity was modulated by tactile stimulation to a higher degree than the premotor cortex through effective connectivity with the hand-somatosensory cortex, which suggests different functional roles. These findings constitute the first intracranial electrophysiological characterization of the rubber hand illusion and extend our understanding of the dynamic mechanisms of body ownership.

This work started from the hypothesis that the physiological processes giving rise to the vestibular evoked myogenic potential (VEMP) can be induced not only by transient sounds but also by a continuous stimulation with a stochastic signal. The hypothesis is based on the idea that the number of motor unit action potentials (MUAPs) decreases after a momentary amplitude increase of the effective stimulus, whereas a momentary amplitude decrease has the opposite effect. This concept was theoretically analyzed by assuming that the effective stimulus is closely related to the envelope of the stimulus actually presented. The analysis led to the prediction that the cross-correlation function of the effective stimulus and the measured electromyogram (EMG) has VEMP-like properties. Experiments confirmed this prediction, thus providing evidence of a novel electrophysiological response: the vestibular evoked myographic correlation (VEMCorr). The methodological approach corresponded to a conventional VEMP study, except that the stimulus (delivered with a hand-held minishaker) comprised not only a series of 500-Hz tone pulses (classical VEMP measurement, for comparison) but also sequences of narrow-band noise with a center frequency of 500 Hz (VEMCorr measurement). Each of the 12 test persons showed a clear VEMCorr. Moreover, VEMP and VEMCorr largely resembled each other, as predicted. Apparently they are two different expressions of a more general mechanism that leads to a roughly linear relationship between stimulus envelope and expectation of the EMG. Future applications of the VEMCorr could exploit that a continuous-stimulation paradigm allows for varying the center frequency of the stimulus without changing the relative bandwidth.

The ability to capture the most relevant information from everyday experiences without constantly learning unimportant details is vital to survival and mental health. While decreased activity of the medial prefrontal cortex (mPFC) is associated with failed or inflexible encoding of relevant events in the hippocampus, mechanisms used by the mPFC to discern behavioral relevance of events are not clear. To address this question, we chemogenetically activated excitatory neurons in the mPFC of male rats and examined its impact on local network activity and differential associative learning dependent on the hippocampus. Rats were exposed to two neutral stimuli in two environments whose contingency with an aversive stimulus changed systematically across days. Over 2 weeks of differential and reversal learning, theta band activity began to ramp up toward the expected onset of the aversive stimulus, and this ramping activity tracked the subsequent shift of the set (stimulus modality to environment) predictive of the aversive stimulus. With chemogenetic mPFC activation, the ramping activity emerged within a few sessions of differential learning, which paralleled faster learning and stronger correlations between the ramping activity and conditioned responses. Chemogenetic mPFC activity, however, did not affect the adjustment of ramping activity or behavior during reversal learning or set-shifting, suggesting that the faster learning was not because of a general enhancement of attention, sensory, or motor processing. Thus, the dynamics of the mPFC network activation during events provide a relevance-signaling mechanism through which the mPFC exerts executive control over the encoding of those events in the hippocampus.

Intracranial electrodes are a vital component of implantable neurodevices, both for acute diagnostics and chronic treatment with open and closed-loop neuromodulation. Their performance is hampered by acute implantation trauma and chronic inflammation in response to implanted materials and mechanical mismatch between stiff synthetic electrodes and pulsating, natural soft host neural tissue. Flexible electronics based on thin polymer films patterned with microscale conductive features can help alleviate the mechanically induced trauma; however, this strategy alone does not mitigate inflammation at the device-tissue interface. In this study, we propose a biomimetic approach that integrates microscale extracellular matrix (ECM) coatings on microfabricated flexible subdural microelectrodes. Taking advantage of a high-throughput process employing micro-transfer molding and excimer laser micromachining, we fabricate multi-channel subdural microelectrodes primarily composed of ECM protein material and demonstrate that the electrochemical and mechanical properties match those of standard, uncoated controls. In vivo ECoG recordings in rodent brain confirm that the ECM microelectrode coatings and the protein interface do not alter signal fidelity. Astrogliotic, foreign body reaction to ECM coated devices is reduced, compared to uncoated controls, at 7 and 30 days, after subdural implantation in rat somatosensory cortex. We propose microfabricated, flexible, biomimetic electrodes as a new strategy to reduce inflammation at the device-tissue interface and improve the long-term stability of implantable subdural electrodes.

Epidural electrical stimulation (EES) of the spinal cord restores locomotion in animal models of spinal cord injury but is less effective in humans. Here we hypothesized that this interspecies discrepancy is due to interference between EES and proprioceptive information in humans. Computational simulations and preclinical and clinical experiments reveal that EES blocks a significant amount of proprioceptive input in humans, but not in rats. This transient deafferentation prevents modulation of reciprocal inhibitory networks involved in locomotion and reduces or abolishes the conscious perception of leg position. Consequently, continuous EES can only facilitate locomotion within a narrow range of stimulation parameters and is unable to provide meaningful locomotor improvements in humans without rehabilitation. Simulations showed that burst stimulation and spatiotemporal stimulation profiles mitigate the cancellation of proprioceptive information, enabling robust control over motor neuron activity. This demonstrates the importance of stimulation protocols that preserve proprioceptive information to facilitate walking with EES.

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event‐related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex.

Translational comparison of rodent models of neurological and neuropsychiatric diseases to human electroencephalography (EEG) biomarkers in these conditions will require multisite rodent EEG on the skull surface, rather than local area electrocorticography (ECoG) or multisite local field potential (LFP) recording. We have developed a technique for planar multielectrode array (MEA) implantation on the mouse skull surface, which enables multisite EEG in awake and freely moving mice and reusability of the MEA probes. With this method, we reliably obtain 30-channel low-noise EEG from awake mice. Baseline and stimulus-evoked EEG recordings can be readily obtained and analyzed. For example, we have demonstrated EEG responses to auditory stimuli. Broadband noise elicits reliable 30-channel auditory event-related potentials (ERPs), and chirp stimuli induce phase-locked EEG responses just as in human sound presentation paradigms. This method is unique in achieving chronic implantation of novel MEA technology onto the mouse skull surface for chronic multisite EEG recordings. Furthermore, we demonstrate a reliable method for reusing MEA probes for multiple serial implantations without loss of EEG quality. This skull surface MEA methodology can be used to obtain simultaneous multisite EEG recordings and to test EEG biomarkers in diverse mouse models of human neurological and neuropsychiatric diseases. Reusability of the MEA probes makes it more cost-effective to deploy this system for various studies.

Electrical nerve recording and stimulation technologies are critically needed to monitor and modulate nerve activity to treat a variety of neurological diseases. However, current neuromodulation technologies presented in the literature or commercially available products cannot support simultaneous recording and stimulation on the same nerve. To solve this problem, a new bidirectional neuromodulation system-on-chip (SoC) is proposed in this paper, which includes a frequency-shaping neural recorder and a fully integrated neural stimulator with charge balancing capability. In addition, auxiliary circuits consisting of power management and data transmission circuits are designed to provide the necessary power supply for the SoC and the bidirectional data communication between the SoC and an external computer via a universal serial bus (USB) interface, respectively. To achieve sufficient low input noise for sensing nerve activity at a sub-10 μ V range, several noise reduction techniques are developed in the neural recorder. The designed SoC was fabricated in a 0.18 μ m high-voltage Bipolar CMOS DMOS (BCD) process technology that was described in a previous publication and it has been recently tested in animal experiments that demonstrate the proposed SoC is capable of achieving reliable and simultaneous electrical stimulation and recording on the same nerve.