EEG/ECoG/EMG publications

A noninvasive sleep screen uncovers a Vamp2 mouse mutation with synaptic deficits underlying substantial sleep disturbances.

Unsupervised learning of visual temporal statistics drives postnatal development of position invariance in visual cortex.

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.

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.

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.

The role of the claustrum in consciousness and vigilance states was proposed more than two decades ago; however, its role in anesthesia is not yet understood, and this requires more investigation. The aim of our study was to assess the impact of claustrum electrical stimulation during isoflurane anesthesia in adult rats. The claustrum in the left hemisphere was electrically stimulated using a bipolar tungsten electrode inserted stereotaxically. In order to monitor the anesthetic depth, the electrocorticogram (ECoG) was recorded before, during, and after claustrum stimulation using frontal and parietal epidural electrodes placed over the left hemisphere. After reaching stabilized slow-wave isoflurane anesthesia, twenty stimuli, each of one second duration with ten seconds interstimulus duration, were applied. ECoG analysis has shown that, after a delay from the beginning of stimulation, the slow-wave ECoG signal changed to a transient burst suppression (BS) pattern. Our results show that electrical stimulation of the claustrum area during slow-wave isoflurane anesthesia induces a transitory increase in anesthetic depth, documented by the appearance of a BS ECoG pattern, and suggests a potential role of claustrum in anesthesia.

Spatial attention may be used to select target speech in one location while suppressing irrelevant speech in another. However, if perceptual resolution of spatial cues is weak, spatially focused attention may work poorly, leading to difficulty communicating in noisy settings. In electroencephalography (EEG), the distribution of alpha (8–14 Hz) power over parietal sensors reflects the spatial focus of attention [Banerjee, Snyder, Molholm, and Foxe (2011). J. Neurosci. 31, 9923–9932; Foxe and Snyder (2011). Front. Psychol. 2, 154.] If spatial attention is degraded, however, alpha may not be modulated across parietal sensors. A previously published behavioral and EEG study found that, compared to normal-hearing (NH) listeners, hearing-impaired (HI) listeners often had higher interaural time difference thresholds, worse performance when asked to report the content of an acoustic stream from a particular location, and weaker attentional modulation of neural responses evoked by sounds in a mixture [Dai, Best, and Shinn-Cunningham (2018). Proc. Natl. Acad. Sci. U. S. A. 115, E3286]. This study explored whether these same HI listeners also showed weaker alpha lateralization during the previously reported task. In NH listeners, hemispheric parietal alpha power was greater when the ipsilateral location was attended; this lateralization was stronger when competing melodies were separated by a larger spatial difference. In HI listeners, however, alpha was not lateralized across parietal sensors, consistent with a degraded ability to use spatial features to selectively attend.

The ability to selectively attend to speech in the presence of other competing talkers is critical for everyday communication; yet the neural mechanisms facilitating this process are poorly understood. Here, we use electroencephalography (EEG) to study how a mixture of two speech streams is represented in the brain as subjects attend to one stream or the other. To characterize the speech-EEG relationships and how they are modulated by attention, we estimate the statistical association between each canonical EEG frequency band (delta, theta, alpha, beta, low-gamma, and high-gamma) and the envelope of each of ten different frequency bands in the input speech. Consistent with previous literature, we find that low-frequency (delta and theta) bands show greater speech-EEG coherence when the speech stream is attended compared to when it is ignored. We also find that the envelope of the low-gamma band shows a similar attention effect, a result not previously reported with EEG. This is consistent with the prevailing theory that neural dynamics in the gamma range are important for attention-dependent routing of information in cortical circuits. In addition, we also find that the greatest attention-dependent increases in speech-EEG coherence are seen in the mid-frequency acoustic bands (0.5–3 kHz) of input speech and the temporal-parietal EEG sensors. Finally, we find individual differences in the following: (1) the specific set of speech-EEG associations that are the strongest, (2) the EEG and speech features that are the most informative about attentional focus, and (3) the overall magnitude of attentional enhancement of speech-EEG coherence.

Loudness dependence of auditory evoked potentials (LDAEP) is a widely used EEG-based biomarker for central serotonergic activity. Serotonin has been shown to be associated with different psychiatric disorders such as depression and schizophrenia. Despite its clinical significance, the underlying neurochemical mechanism of this promising marker is not fully understood, and further research is needed to improve its validity. Other neurotransmitters might have a significant impact on this measure. Thus, we assessed the inhibitory action through individual GABA/H20 concentrations and GABA/glutamate ratios by means of magnetic resonance spectroscopy at 3T in healthy subjects. The measurements were assessed in the primary auditory cortex to investigate the association with the LDAEP, whose generators are mainly in the primary auditory cortex. For the first time, this study examines the link between GABAergic neurotransmission and LDAEP, and the data preliminary show that GABA may not contribute to the generation of EEG-based LDAEP.

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.

Purpose Our study aimed to explore the feasibility of manganese‐enhanced magnetic resonance imaging ( MEMRI ) combined with visual evoked potentials ( VEP ) and auditory evoked visual cortex responses ( AVR ) in evaluating for the establishment of visual/auditory compensatory pathways after monocular blindness. Materials and Methods A total of 14 healthy neonatal male Sprague‐Dawley rats were randomly divided into two groups ( n = 7 for Groups A and B). Right optic nerve ( ON ) transection was performed on the 7 rats of Group A to obtain a monocularly blind model, and the 7 rats of Group B were chosen as the control group. Four months later, 400 mmol MnCl 2 was injected into the left eye in both groups via intravitreal injection. The changes in the visual pathways projected from the blind eye and the remaining eye in Group A and the normal eyes in Group B were compared to determine if new visual compensatory pathways were established. Additionally, VEP tests were performed to determine complete blindness, and AVR examinations were performed to help identify the generation of auditory compensatory function. Results The VEP test indicated complete visual loss after ON transection. In the monocularly blind rats, the contrast‐to‐noise ratio ( CNR ) of ON , optic tract ( OT ), lateral geniculate nucleus ( LGN ), superior colliculus ( SC ), optic radiation ( OR ) and visual cortex ( VC ) of visual pathway projected from the left eye was significantly higher than that of the right pathway ( p < .001). Moreover, the CNR of ON , OT , LGN , SC , OR and VC in the visual pathway projected from the left eye of monocularly blind rats was significantly lower than those of normal rats ( p < .05). The AVR results revealed that the corresponding bilateral visual cortex in monocularly blind rats did not respond to the auditory stimulus or showed dissimilation with the low frequency. Conclusion MEMRI combined with electrophysiology, including VEP and AVR , may be potentially helpful in the evaluation of the possible generation of new visual/auditory compensatory pathways after monocular blindness.

Tinnitus chronically affects between 10–15% of the population but, despite its prevalence, the underlying mechanisms are still not properly understood. One experimental model involves administration of high doses of sodium salicylate, as this is known to reliably induce tinnitus in both humans and animals. Guinea pigs were implanted with chronic electrocorticography ( EC oG) electrode arrays, with silver‐ball electrodes placed on the dura over left and right auditory cortex. Two more electrodes were positioned over the cerebellum to monitor auditory brainstem responses ( ABR s). We recorded resting‐state and auditory evoked neural activity from awake animals before and 2 h following salicylate administration (350 mg/kg; i.p.). Large increases in click‐evoked responses (> 100%) were evident across the whole auditory cortex, despite significant reductions in wave I ABR amplitudes (in response to 20 kHz tones), which are indicative of auditory nerve activity. In the same animals, significant decreases in 6–10 Hz spontaneous oscillations (alpha waves) were evident over dorsocaudal auditory cortex. We were also able to demonstrate for the first time that cortical evoked potentials can be inhibited by a preceding gap in background noise [gap‐induced pre‐pulse inhibition ( PPI )], in a similar fashion to the gap‐induced inhibition of the acoustic startle reflex that is used as a behavioural test for tinnitus. Furthermore, 2 h following salicylate administration, we observed significant deficits in PPI of cortical responses that were closely aligned with significant deficits in behavioural responses to the same stimuli. Together, these data are suggestive of neural correlates of tinnitus and oversensitivity to sound (hyperacusis).

Neural correlates of movement planning onset and direction may be present in human electrocorticography in the signal dynamics of both motor and non-motor cortical regions. We use a three-stage model of jPCA reduced-rank hidden Markov model (jPCA-RR-HMM), regularized shrunken-centroid discriminant analysis (RDA), and LASSO regression to extract direction-sensitive planning information and movement onset in an upper-limb 3D isometric force task in a human subject. This mode achieves a relatively high true positive force-onset prediction rate of 60% within 250ms, and an above-chance 36% accuracy (17% chance) in predicting one of six planned 3D directions of isometric force using pre-movement signals. We also find direction-distinguishing information up to 400ms before force onset in the pre-movement signals, captured by electrodes placed over the limb-ipsilateral dorsal premotor regions. This approach can contribute to more accurate decoding of higher-level movement goals, at earlier timescales, and inform sensor placement. Our results also contribute to further understanding of the spatiotemporal features of human motor planning.

Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.

A unique sound that deviates from a repetitive background sound induces signature neural responses, such as mismatch negativity and novelty P3 response in electro-encephalography studies. Here we show that a deviant auditory stimulus induces a human pupillary dilation response (PDR) that is sensitive to the stimulus properties and irrespective whether attention is directed to the sounds or not. In an auditory oddball sequence, we used white noise and 2000-Hz tones as oddballs against repeated 1000-Hz tones. Participants' pupillary responses were recorded while they listened to the auditory oddball sequence. In Experiment 1, they were not involved in any task. Results show that pupils dilated to the noise oddballs for approximately 4 s, but no such PDR was found for the 2000-Hz tone oddballs. In Experiments 2, two types of visual oddballs were presented synchronously with the auditory oddballs. Participants discriminated the auditory or visual oddballs while trying to ignore stimuli from the other modality. The purpose of this manipulation was to direct attention to or away from the auditory sequence. In Experiment 3, the visual oddballs and the auditory oddballs were always presented asynchronously to prevent residuals of attention on to-be-ignored oddballs due to the concurrence with the attended oddballs. Results show that pupils dilated to both the noise and 2000-Hz tone oddballs in all conditions. Most importantly, PDRs to noise were larger than those to the 2000-Hz tone oddballs regardless of the attention condition in both experiments. The overall results suggest that the stimulus-dependent factor of the PDR appears to be independent of attention.

In Parkinson's disease patients in the OFF medication state, basal ganglia local field potentials exhibit changes in beta and gamma oscillations that correlate with reduced voluntary movement, manifested as rigidity and akinesia. However, magnetoencephalography and low-resolution electrocorticography (ECoG) studies in Parkinson's patients suggest that changes in sensorimotor cortical oscillations differ from those of the basal ganglia. To more clearly define the role of sensorimotor cortex oscillatory activity in Parkinson's, we performed intraoperative, high-resolution (4 mm spacing) ECoG recordings in 10 Parkinson's patients (2 females, ages 47-72) undergoing deep brain stimulation (DBS) lead placement in the awake, OFF medication state. We analyzed ECoG potentials during a computer-controlled reaching task designed to separate movement preparation from movement execution and compared findings to similar invasive recordings in eight patients with essential tremor (3 females, ages 59-78), a condition not associated with rigidity or akinesia. We show that (1) cortical beta spectral power at rest does not differ between Parkinson's and essential tremor patients (p = 0.85), (2) early motor preparation in Parkinson's patients in the OFF medication state is associated with a larger beta desynchronization compared to patients with essential tremor (p = 0.0061), and (3) cortical broadband gamma power is elevated in Parkinson's patients compared to essential tremor patients during both rest and task recordings (p = 0.004). Our findings suggest an oscillatory profile in sensorimotor cortex of Parkinson's patients that, in contrast to the basal ganglia, may act to promote movement to oppose the anti-kinetic bias of the dopamine-depleted state.

Multiple components of "γ-oscillations" between 30-170 Hz in the CA1 region of the hippocampus have been described, based on their coherence with oscillations in other brain regions and on their cross-frequency coupling with local θ-oscillations. However, it remains unclear whether the different sub-bands are generated by a single broadband oscillator coupled to multiple external inputs, or by separate oscillators that incorporate distinct circuit elements. To distinguish between these possibilities, we used high-density linear array recording electrodes in awake behaving mice to examine the spatiotemporal characteristics of γ-oscillations and their responses to midazolam and atropine. We characterized oscillations using current source density (CSD) analysis, and measured θ-γ phase-amplitude coupling by cross frequency coupling (CFC) analysis. Prominent peaks were present in the CSD signal in the mid- and distal apical dendritic layers at all frequencies, and at stratum pyramidale for γ(slow) (30-45 Hz) and γ(mid) (50-90 Hz), but not γ(fast) (90-170 Hz) oscillations. Differences in the strength and timing of θ-γ(slow) and θ-γ(mid) cross frequency coupling, and a lack of coupling at the soma and mid-apical region for γ(fast) oscillations, indicated that separate circuit components generate the three sub-bands. Midazolam altered CSD amplitudes and cross-frequency coupling in a lamina- and frequency specific manner, providing further evidence for separate generator circuits. Atropine altered CSD amplitudes and θ-γ CFC uniformly at all locations. Simulations using a detailed compartmental model were consistent with γ(slow) and γ(mid) oscillations driven primarily by inputs at the mid-apical dendrites, and γ(fast) at the distal apical dendrite. Our results indicate that multiple distinct local circuits generate γ-oscillations in the CA1 region of the hippocampus, and provide detailed information about their spatiotemporal characteristics.

Music perception builds on expectancy in harmony, melody, and rhythm. Neural responses to the violations of such expectations are observed in event-related potentials (ERPs) measured using electroencephalography. Most previous ERP studies demonstrating sensitivity to musical violations used stimuli that were temporally regular and musically structured, with less-frequent deviant events that differed from a specific expectation in some feature such as pitch, harmony, or rhythm. Here, we asked whether expectancies about Western musical scale are strong enough to elicit ERP deviance components. Specifically, we explored whether pitches inconsistent with an established scale context elicit deviant components even though equally rare pitches that fit into the established context do not, and even when their timing is unpredictable. We used Markov chains to create temporally irregular pseudo-random sequences of notes chosen from one of two diatonic scales. The Markov pitch-transition probabilities resulted in sequences that favored notes within the scale, but that lacked clear melodic, harmonic, or rhythmic structure. At the random positions, the sequence contained probe tones that were either within the established scale or were out of key. Our subjects ignored the note sequences, watching a self-selected silent movie with subtitles. Compared to the in-key probes, the out-of-key probes elicited a significantly larger P2 ERP component. Results show that random note sequences establish expectations of the "first-order" statistical property of musical key, even in listeners not actively monitoring the sequences.

Upper-limb movements are often composed of regular submovements, and neural correlates of submovement frequencies between 1 and 4 Hz have been found in the motor cortex. The temporal profile of movements is usually assumed to be determined by extrinsic factors such as limb biomechanics and feedback delays, but another possibility is that an intrinsic rhythmicity contributes to low frequencies in behavior. We used multielectrode recordings in monkeys performing an isometric movement task to reveal cyclic activity in primary motor cortex locked to submovements, and a distinct oscillation in premotor cortex. During ketamine sedation and natural sleep, cortical activity traversed similar cycles and became synchronized across areas. Because the same cortical dynamics are coupled to submovements and also observed in the absence of behavior, we conclude that the motor networks controlling the upper limb exhibit an intrinsic periodicity at submovement frequencies that is reflected in the speed profile of movements.