EEG/ECoG/EMG publications

The ability to dynamically change motor outputs, such as stopping an initiated response, is an important aspect of human behavior. A hyperdirect pathway between the inferior frontal gyrus and subthalamic nucleus is hypothesized to mediate movement inhibition, but there is limited evidence for this in humans. We recorded high spatial and temporal resolution field potentials from both the inferior frontal gyrus and subthalamic nucleus in 21 subjects. Cortical potentials evoked by subthalamic stimulation revealed short latency events indicative of monosynaptic connectivity between the inferior frontal gyrus and ventral subthalamic nucleus. During a stop signal task, stopping-related potentials in the cortex preceded stopping-related activity in the subthalamic nucleus, and synchronization between these task-evoked potentials predicted the stop signal reaction time. Thus, we show that a prefrontal-subthalamic hyperdirect pathway is present in humans and mediates rapid stopping. These findings may inform therapies to treat disorders featuring perturbed movement inhibition.

Objective: Top-down spatial attention is effective at selecting a target sound from a mixture. However, nonspatial features often distinguish sources in addition to location. This study explores whether redundant nonspatial features are used to maintain selective auditory attention for a spatially defined target. Design: We recorded electroencephalography while subjects focused attention on one of three simultaneous melodies. In one experiment, subjects (n = 17) were given an auditory cue indicating both the location and pitch of the target melody. In a second experiment (n = 17 subjects), the cue only indicated target location, and we compared two conditions: one in which the pitch separation of competing melodies was large, and one in which this separation was small. Results: In both experiments, responses evoked by onsets of events in sound streams were modulated by attention, and we found no significant difference in this modulation between small and large pitch separation conditions. Therefore, the evoked response reflected that target stimuli were the focus of attention, and distractors were suppressed successfully for all experimental conditions. In all cases, parietal alpha was lateralized following the cue, but before melody onset, indicating that subjects initially focused attention in space. During the stimulus presentation, this lateralization disappeared when pitch cues were strong but remained significant when pitch cues were weak, suggesting that strong pitch cues reduced reliance on sustained spatial attention. Conclusions: These results demonstrate that once a well-defined target stream at a known location is selected, top-down spatial attention plays a weak role in filtering out a segregated competing stream.

There are several technical challenges to obtaining high-quality recordings of cochlear potentials in human electrocochleography (ECochG). These challenges include electrical artifacts from devices such as acoustic transducers, biological artifacts from excessive myogenic and electroencephalographic potentials, and issues associated with the placement of a tympanic membrane (TM) electrode on the eardrum. This article presents approaches for dealing with these challenges for ECochG measurement using a TM electrode. Emphasis is placed on eliminating stimulus artifact, optimizing the placement of the electrode, and comparing a custom-made electrode with a commercially-available electrode. This comparison revealed that the custom-made electrode results in greater subject comfort, superior ease of placing the electrode on the eardrum, and larger compound action potential (CAP) amplitudes.

Do noises wake you up at night? Blame your locus coeruleus.

Objective: Electrical stimulation of the human brain is commonly used for eliciting and inhibiting neural activity for clinical diagnostics, modifying abnormal neural circuit function for therapeutics, and interrogating cortical connectivity. However, recording electrical signals with concurrent stimulation results in dominant electrical artifacts that mask the neural signals of interest. Here we develop a method to reproducibly and robustly recover neural activity during concurrent stimulation. We concentrate on signal recovery across an array of electrodes without channel-wise fine-tuning of the algorithm. Our goal includes signal recovery with trains of stimulation pulses, since repeated, high-frequency pulses are often required to induce desired effects in both therapeutic and research domains. We have made all of our code and data publicly available. Approach: We developed an algorithm that automatically detects templates of artifacts across many channels of recording, creating a dictionary of learned templates using unsupervised clustering. The artifact template that best matches each individual artifact pulse is subtracted to recover the underlying activity. To assess the success of our method, we focus on whether it extracts physiologically interpretable signals from real recordings. Main results: We demonstrate our signal recovery approach on invasive electrophysiologic recordings from human subjects during stimulation. We show the recovery of meaningful neural signatures in both electrocorticographic (ECoG) arrays and deep brain stimulation (DBS) recordings. In addition, we compared cortical responses induced by the stimulation of primary somatosensory (S1) by natural peripheral touch, as well as motor cortex activity with and without concurrent S1 stimulation. Significance: Our work will enable future advances in neural engineering with simultaneous stimulation and recording.

Hearing impairment disrupts processes of selective attention that help listeners attend to one sound source over competing sounds in the environment. Hearing prostheses (hearing aids and cochlear implants, CIs), do not fully remedy these issues. In normal hearing, mechanisms of selective attention arise through the facilitation and suppression of neural activity that represents sound sources. However, it is unclear how hearing impairment affects these neural processes, which is key to understanding why listening difficulty remains. Here, severely-impaired listeners treated with a CI, and age-matched normal-hearing controls, attended to one of two identical but spatially separated talkers while multichannel EEG was recorded. Whereas neural representations of attended and ignored speech were differentiated at early (~ 150 ms) cortical processing stages in controls, differentiation of talker representations only occurred later (~250 ms) in CI users. CI users, but not controls, also showed evidence for spatial suppression of the ignored talker through lateralized alpha (7–14 Hz) oscillations. However, CI users’ perceptual performance was only predicted by early-stage talker differentiation. We conclude that multi-talker listening difficulty remains for impaired listeners due to deficits in early-stage separation of cortical speech representations, despite neural evidence that they use spatial information to guide selective attention.

In rats, forelimb movements are evoked from two cortical regions, the caudal and rostral forelimb areas (CFA and RFA, respectively). These areas are densely interconnected and RFA induces complex and powerful modulations of CFA outputs. CFA and RFA also have interhemispheric connections, and these areas from both hemispheres send projections to common targets along the motor axis, providing multiple potential sites of interactions for movement production. Our objective was to characterize how CFA and RFA in one hemisphere can modulate motor outputs of the opposite hemisphere. To do so, we used paired-pulse protocols with intracortical microstimulation techniques (ICMS), while recording electromyographic (EMG) activity of forelimb muscles in sedated rats. A subthreshold conditioning stimulation was applied in either CFA or RFA in one hemisphere simultaneously or before a suprathreshold test stimulation in either CFA or RFA in the opposite hemisphere. Both CFA and RFA tended to facilitate motor outputs with short (0–2.5 ms) or long (20–35 ms) delays between the conditioning and test stimuli. In contrast, they tended to inhibit motor outputs with intermediate delays, in particular 10 ms. When comparing the two areas, we found that facilitatory effects from RFA were more frequent and powerful than the ones from CFA. In contrast, inhibitory effects from CFA on its homolog were more frequent and powerful than the ones from RFA. Our results demonstrate that interhemispheric modulations from CFA and RFA share some similarities but also have clear differences that could sustain specific functions these cortical areas carry for the generation of forelimb movements. NEW & NOTEWORTHY We show that caudal and rostral forelimb areas (CFA and RFA) have distinct effects on motor outputs from the opposite hemisphere, supporting that they are distinct nodes in the motor network of rats. However, the pattern of interhemispheric modulations from RFA has no clear equivalent among premotor areas in nonhuman primates, suggesting they contribute differently to the generation of ipsilateral hand movements. Understanding these interspecies differences is important given the common use of rodent models in motor control and recovery studies.

Spatial selective attention greatly affects our processing of complex visual scenes, yet the way in which the brain selects relevant objects while suppressing irrelevant objects is still unclear. Evidence of these processes has been found using non-invasive electroencephalography (EEG). However, few studies have characterized these measures during attention to dynamic stimuli, and little is known regarding how these measures change with increased scene complexity. Here, we compared attentional modulation of the EEG N1 and alpha power (oscillations between 8-14 Hz) across three visual selective attention tasks. The tasks differed in the number of irrelevant stimuli presented, but all required sustained attention to the orientation trajectory of a lateralized stimulus. In scenes with few irrelevant stimuli, top-down control of spatial attention is associated with strong modulation of both the N1 and alpha power across parietal-occipital channels. In scenes with many irrelevant stimuli in both hemifields, however, top-down control is no longer represented by strong modulation of alpha power, and N1 amplitudes are overall weaker. These results suggest that as a scene becomes more complex, requiring suppression in both hemifields, the neural signatures of top-down control degrade, likely reflecting some limitation in EEG to represent this suppression.

Humans engagement in music rests on underlying elements such as the listeners’ cultural background and interest in music. These factors modulate how listeners anticipate musical events, a process inducing instantaneous neural responses as the music confronts these expectations. Measuring such neural correlates would represent a direct window into high-level brain processing. Here we recorded cortical signals as participants listened to Bach melodies. We assessed the relative contributions of acoustic versus melodic components of the music to the neural signal. Melodic features included information on pitch progressions and their tempo, which were extracted from a predictive model of musical structure based on Markov chains. We related the music to brain activity with temporal response functions demonstrating, for the first time, distinct cortical encoding of pitch and note-onset expectations during naturalistic music listening. This encoding was most pronounced at response latencies up to 350 ms, and in both planum temporale and Heschl’s gyrus.

Nowadays, the majority of the progress in the development of implantable neuroprostheses has been achieved by improving the knowledge of brain functions so as to restore sensorial impairments. Intracortical microstimulation (ICMS) is a widely used technique to investigate site-specific cortical responses to electrical stimuli. Herein, we investigated the neural modulation induced in the primary auditory cortex (A1) by an acousto-electric transduction of ultrasonic signals using a bio-inspired intracortical microstimulator. The developed electronic system emulates the transduction of ultrasound signals in the cochlea, providing bio-inspired electrical stimuli. Firstly, we identified the receptive fields in the primary auditory cortex devoted to encoding ultrasonic waves at different frequencies, mapping each area with neurophysiological patterns. Subsequently, the activity elicited by bio-inspired ICMS in the previously identified areas, bypassing the sense organ, was investigated. The observed evoked response by microstimulation resulted as highly specific to the stimuli, and the spatiotemporal dynamics of neural oscillatory activity in the alpha, beta, and gamma waves were related to the stimuli preferred by the neurons at the stimulated site. The alpha waves modulated cortical excitability only during the activation of the specific tonotopic neuronal populations, inhibiting neural responses in unrelated areas. Greater neuronal activity in the posterior area of A1 was observed in the beta band, whereas a gamma rhythm was induced in the anterior A1. The results evidence that the proposed bio-inspired acousto-electric ICMS triggers high-frequency oscillations, encoding information about the stimulation sites and involving a large-scale integration in the brain.

We investigated whether the categorical perception (CP) of speech might also provide a mechanism that aids its perception in noise. We varied signal-to-noise ratio (SNR) [clear, 0 dB, -5 dB] while listeners classified an acoustic-phonetic continuum (/u/ to /a/). Noise-related changes in behavioral categorization were only observed at the lowest SNR. Event-related brain potentials (ERPs) differentiated category vs. category-ambiguous speech by the P2 wave (~180-320 ms). Paralleling behavior, neural responses to speech with clear phonetic status (i.e., continuum endpoints) were robust to noise down to -5 dB SNR, whereas responses to ambiguous tokens declined with decreasing SNR. Results demonstrate that phonetic speech representations are more resistant to degradation than corresponding acoustic representations. Findings suggest the mere process of binning speech sounds into categories provides a robust mechanism to aid figure-ground speech perception by fortifying abstract categories from the acoustic signal and making the speech code more resistant to external interferences.

Humans perceptual judgments are imprecise, as repeated exposures to the same physical stimulation (e.g. audio-visual inputs separated by a constant temporal offset) can result in different decisions. Moreover, there can be marked individual differences – precise judges will repeatedly make the same decision about a given input, whereas imprecise judges will make different decisions. The causes are unclear. We examined this using audio-visual (AV) timing and confidence judgments, in conjunction with electroencephalography (EEG) and multivariate pattern classification analyses. One plausible cause of differences in timing precision is that it scales with variance in the dynamics of evoked brain activity. Another possibility is that equally reliable patterns of brain activity are evoked, but there are systematic differences that scale with precision. Trial-by-trial decoding of input timings from brain activity suggested precision differences may not result from variable dynamics. Instead, precision was associated with evoked responses that were exaggerated (more different from baseline) ~300 ms after initial physical stimulations. We suggest excitatory and inhibitory interactions within a winner-take-all neural code for AV timing might exaggerate responses, such that evoked response magnitudes post-stimulation scale with encoding success.

A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (∼10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (>40 ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms. SIGNIFICANCE STATEMENT Reduced behavioral responsiveness to sensory stimulation is at the core of sleep's definition, but it is still unclear how the sleeping brain responds differently to sensory stimuli. In the current study, we recorded neuronal spiking responses to sounds along the cortical processing hierarchy of rats during wakefulness and natural sleep. Responses in auditory cortex only showed modest changes during sleep, whereas sleep robustly attenuated the responses of neurons in high-level perirhinal cortex. We also found that, during NREM sleep, the response latency predicts the degree of sleep attenuation in individual neurons above and beyond their anatomical location. These results provide anatomical and temporal signatures of sensory disconnection during sleep and pave the way to understanding the underlying mechanisms.

Binaural beating is a perceptual auditory illusion occurring when presenting two neighboring frequencies to each ear separately. Several controversial claims have been attributed to binaural beats regarding their ability to entrain human brain activity and mood, in both the scientific literature and the marketing realm. Here, we sought to address those questions in a robust fashion using a single-blind, active-controlled protocol. To do so, we compared the effects of binaural beats with a control beat stimulation (monaural beats, known to entrain brain activity but not mood) across four distinct levels in the human auditory pathway: subcortical and cortical entrainment, scalp-level functional connectivity and self-reports. Both stimuli elicited standard subcortical responses at the pure tone frequencies of the stimulus [i.e., frequency following response (FFR)], and entrained the cortex at the beat frequency [i.e., auditory steady state response (ASSR)]. Furthermore, functional connectivity patterns were modulated differentially by both kinds of stimuli, with binaural beats being the only one eliciting cross-frequency activity. Despite this, we did not find any mood modulation related to our experimental manipulation. Our results provide evidence that binaural beats elicit cross frequency connectivity patterns, but weakly entrain the cortex when compared with monaural beat stimuli. Whether binaural beats have an impact on cognitive performance or other mood measurements remains to be seen and can be further investigated within the proposed methodological framework.

Objective . Categorical perception (CP) is an inherent property of speech perception. The response time (RT) of listeners’ perceptual speech identification is highly sensitive to individual differences. While the neural correlates of CP have been well studied in terms of the regional contributions of the brain to behavior, functional connectivity patterns that signify individual differences in listeners’ speed (RT) for speech categorization is less clear. In this study, we introduce a novel approach to address these questions. Approach . We applied several computational approaches to the EEG, including graph mining, machine learning (i.e., support vector machine), and stability selection to investigate the unique brain states (functional neural connectivity) that predict the speed of listeners’ behavioral decisions. Main results . We infer that (i) the listeners’ perceptual speed is directly related to dynamic variations in their brain connectomics, (ii) global network assortativity and efficiency distinguished fast, medium, and slow RTs, (iii) the functional network underlying speeded decisions increases in negative assortativity (i.e., became disassortative) for slower RTs, (iv) slower categorical speech decisions cause excessive use of neural resources and more aberrant information flow within the CP circuitry, (v) slower responders tended to utilize functional brain networks excessively (or inappropriately) whereas fast responders (with lower global efficiency) utilized the same neural pathways but with more restricted organization. Significance . Findings show that neural classifiers (SVM) coupled with stability selection correctly classify behavioral RTs from functional connectivity alone with over 92% accuracy (AUC = 0.9). Our results corroborate previous studies by supporting the engagement of similar temporal (STG), parietal, motor, and prefrontal regions in CP using an entirely data-driven approach.

We measured the fast temporal dynamics of face processing simultaneously across the human temporal cortex (TC) using intracranial recordings in eight participants. We found sites with selective responses to faces clustered in the ventral TC, which responded increasingly strongly to marine animal, bird, mammal, and human faces. Both face-selective and face-active but non-selective sites showed a posterior to anterior gradient in response time and selectivity. A sparse model focusing on information from the human face-selective sites performed as well as, or better than, anatomically distributed models when discriminating faces from non-faces stimuli. Additionally, we identified the posterior fusiform site (pFUS) as causally the most relevant node for inducing distortion of conscious face processing by direct electrical stimulation. These findings support anatomically discrete but temporally distributed response profiles in the human brain and provide a new common ground for unifying the seemingly contradictory modular and distributed modes of face processing.

Unlike the sensory thalamus, studies on the functional organization of the midline and intralaminar nuclei are scarce, and this has hindered the establishment of conceptual models of the function of this brain region. We investigated the functional organization of the paraventricular nucleus of the thalamus (PVT), a midline thalamic structure that is increasingly being recognized as a critical node in the control of diverse processes such as arousal, stress, emotional memory and motivation, in mice. We identify two major classes of PVT neurons-termed type I and type II-that differ in terms of gene expression, anatomy and function. In addition, we demonstrate that type II neurons belong to a previously neglected class of PVT neurons that convey arousal-related information to corticothalamic neurons of the infralimbic cortex. Our results uncover the existence of an arousal-modulated thalamo-corticothalamic loop that links the PVT and the ventromedial prefrontal cortex.

Human perception requires the many-to-one mapping between continuous sensory elements and discrete categorical representations. This grouping operation underlies the phenomenon of categorical perception (CP)-the experience of perceiving discrete categories rather than gradual variations in signal input. Speech perception requires CP because acoustic cues do not share constant relations with perceptual-phonetic representations. Beyond facilitating perception of unmasked speech, we reasoned CP might also aid the extraction of target speech percepts from interfering sound sources (i.e., noise) by generating additional perceptual constancy and reducing listening effort. Specifically, we investigated how noise interference impacts cognitive load and perceptual identification of unambiguous (i.e., categorical) vs. ambiguous stimuli. Listeners classified a speech vowel continuum (/u/-/a/) at various signal-to-noise ratios (SNRs [unmasked, 0 and -5 dB]). Continuous recordings of pupil dilation measured processing effort, with larger, later dilations reflecting increased listening demand. Critical comparisons were between time-locked changes in eye data in response to unambiguous (i.e., continuum endpoints) tokens vs. ambiguous tokens (i.e., continuum midpoint). Unmasked speech elicited faster responses and sharper psychometric functions, which steadily declined in noise. Noise increased pupil dilation across stimulus conditions, but not straightforwardly. Noise-masked speech modulated peak pupil size (i.e., [0 and -5 dB] > unmasked). In contrast, peak dilation latency varied with both token and SNR. Interestingly, categorical tokens elicited earlier pupil dilation relative to ambiguous tokens. Our pupillary data suggest CP reconstructs auditory percepts under challenging listening conditions through interactions between stimulus salience and listeners' internalized effort and/or arousal.

Sleep-wake transitions are modulated through extensive subcortical networks although the precise roles of their individual components remain elusive. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterised by a reduced propensity to transition between all sleep states while a profound loss in total REM sleep time was evident. The causative mutation, an Ile102Asn substitution in VAMP2, was associated with substantial synaptic changes while in vitro electrophysiological investigations with fluorescence imaging revealed a diminished probability of vesicular release in mutants. We conclude that the synaptic efficiency of the entire subcortical brain network determines the likelihood that an animal transitions from one vigilance state to the next.