EEG/ECoG/EMG publications

The subthalamic nucleus (STN) is hypothesized to play a central role in the rapid stopping of movement in reaction to a stop signal. Single-unit recording evidence for such a role is sparse, however, and it remains uncertain how that role relates to the disparate functions described for anatomic subdivisions of the STN. Here we address that gap in knowledge using non-human primates and a task that distinguishes reactive and proactive action inhibition, switching and skeletomotor functions. We found that specific subsets of STN neurons have activity consistent with causal roles in reactive action stopping or switching. Importantly, these neurons were strictly segregated to a ventromedial region of STN. Neurons in other subdivisions encoded task dimensions such as movement per se and proactive control. We propose that the involvement of STN in reactive control is restricted to its ventromedial portion, further implicating this STN subdivision in impulse control disorders.

Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive. Here, we investigated to what extent modulation of complex spike firing is reflected in the temporal patterns of seizures. Extracellular single-unit recordings in awake, head-restrained homozygous tottering mice, which suffer from a mutation in the voltage-gated CaV2.1 calcium channel, revealed that a substantial proportion of Purkinje cells (26%) showed increased complex spike activity and rhythmicity during GSWDs. Moreover, Purkinje cells, recorded either electrophysiologically or by using Ca2+-imaging, showed a significant increase in complex spike synchronicity for both adjacent and remote Purkinje cells during ictal events. These seizure-related changes in firing frequency, rhythmicity and synchronicity were most prominent in the lateral cerebellum, a region known to receive cerebral input via the inferior olive. These data indicate profound and widespread changes in olivary firing that are most likely induced by seizure-related activity changes in the thalamocortical network, thereby highlighting the possibility that olivary neurons can compensate for pathological brain-state changes by dampening oscillations.

Electrocorticogram (ECoG) has great potential as a source signal, especially for clinical BMI. Until recently, ECoG electrodes were commonly used for identifying epileptogenic foci in clinical situations, and such electrodes were low-density and large. Increasing the number and density of recording channels could enable the collection of richer motor/sensory information, and may enhance the precision of decoding and increase opportunities for controlling external devices. Several reports have aimed to increase the number and density of channels. However, few studies have discussed the actual validity of high-density ECoG arrays. In this study, we developed novel high-density flexible ECoG arrays and conducted decoding analyses with monkey somatosensory evoked potentials (SEPs). Using MEMS technology, we made 96-channel Parylene electrode arrays with an inter-electrode distance of 700 μm and recording site area of 350 μm2. The arrays were mainly placed onto the finger representation area in the somatosensory cortex of the macaque, and partially inserted into the central sulcus. With electrical finger stimulation, we successfully recorded and visualized finger SEPs with a high spatiotemporal resolution. We conducted offline analyses in which the stimulated fingers and intensity were predicted from recorded SEPs using a support vector machine. We obtained the following results: (1) Very high accuracy (~98%) was achieved with just a short segment of data (~15 ms from stimulus onset). (2) High accuracy (~96%) was achieved even when only a single channel was used. This result indicated placement optimality for decoding. (3) Higher channel counts generally improved prediction accuracy, but the efficacy was small for predictions with feature vectors that included time-series information. These results suggest that ECoG signals with high spatiotemporal resolution could enable greater decoding precision or external device control.

Facial paralysis can be a devastating condition, causing disfiguring facial droop, slurred speech, eye dryness, scarring and blindness. This study investigated the utility of closed-loop functional electric stimulation (FES) for reanimating paralyzed facial muscles in a quantitative rodent model. The right buccal and marginal mandibular branches of the rat facial nerve were transected for selective, unilateral paralysis of whisker muscles. Microwire electrodes were implanted bilaterally into the facial musculature for FES and electromyographic (EMG) recording. With the rats awake and head-fixed, whisker trajectories were tracked bilaterally with optical micrometers. First, the relationship between EMG and volitional whisker movement was quantified on the intact side of the face. Second, the effect of FES on whisker trajectories was quantified on the paralyzed side. Third, closed-loop experiments were performed in which the EMG signal on the intact side triggered FES on the paralyzed side to restore symmetric whisking. The results demonstrate a novel in vivo platform for developing control strategies for neuromuscular facial prostheses.

We report on the superior electrochemical properties, in-vivo performance and long term stability under electrical stimulation of a new electrode material fabricated from lithographically patterned glassy carbon. For a direct comparison with conventional metal electrodes, similar ultra-flexible, micro-electrocorticography (μ-ECoG) arrays with platinum (Pt) or glassy carbon (GC) electrodes were manufactured. The GC microelectrodes have more than 70% wider electrochemical window and 70% higher CTC (charge transfer capacity) than Pt microelectrodes of similar geometry. Moreover, we demonstrate that the GC microelectrodes can withstand at least 5 million pulses at 0.45 mC/cm 2 charge density with less than 7.5% impedance change, while the Pt microelectrodes delaminated after 1 million pulses. Additionally, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was selectively electrodeposited on both sets of devices to specifically reduce their impedances for smaller diameters (<60 μm). We observed that PEDOT-PSS adhered significantly better to GC than Pt, and allowed drastic reduction of electrode size while maintaining same amount of delivered current. The electrode arrays biocompatibility was demonstrated through in-vitro cell viability experiments, while acute in vivo characterization was performed in rats and showed that GC microelectrode arrays recorded somatosensory evoked potentials (SEP) with an almost twice SNR (signal-to-noise ratio) when compared to the Pt ones.

Auditory selective attention paradigms are powerful tools for elucidating the various stages of speech processing. This study examined electrocorticographic activation during target detection tasks within and beyond auditory cortex. Subjects were nine neurosurgical patients undergoing chronic invasive monitoring for treatment of medically refractory epilepsy. Four subjects had left hemisphere electrode coverage, four had right coverage and one had bilateral coverage. Stimuli were 300 ms complex tones or monosyllabic words, each spoken by a different male or female talker. Subjects were instructed to press a button whenever they heard a target corresponding to a specific stimulus category (e.g., tones, animals, numbers). High gamma (70-150 Hz) activity was simultaneously recorded from Heschl's gyrus (HG), superior, middle temporal and supramarginal gyri (STG, MTG, SMG), as well as prefrontal cortex (PFC). Data analysis focused on: (1) task effects (non-target words in tone detection vs. semantic categorization task); and (2) target effects (words as target vs. non-target during semantic classification). Responses within posteromedial HG (auditory core cortex) were minimally modulated by task and target. Non-core auditory cortex (anterolateral HG and lateral STG) exhibited sensitivity to task, with a smaller proportion of sites showing target effects. Auditory-related areas (MTG and SMG) and PFC showed both target and, to a lesser extent, task effects, that occurred later than those in the auditory cortex. Significant task and target effects were more prominent in the left hemisphere than in the right. Findings demonstrate a hierarchical organization of speech processing during auditory selective attention.

Current models of cortical speech and language processing include multiple regions within the temporal lobe of both hemispheres. Human communication, by necessity, involves complex interactions between regions subserving speech and language processing with those involved in more general cognitive functions. To assess these interactions, we utilized an ecologically salient conversation-based approach. This approach mandates that we first clarify activity patterns at the earliest stages of cortical speech processing. Therefore, we examined high gamma (70-150 Hz) responses within the electrocorticogram (ECoG) recorded simultaneously from Heschl's gyrus (HG) and lateral surface of the superior temporal gyrus (STG). Subjects were neurosurgical patients undergoing evaluation for treatment of medically intractable epilepsy. They performed an expanded version of the Mini-mental state examination (MMSE), which included additional spelling, naming, and memory-based tasks. ECoG was recorded from HG and the STG using multicontact depth and subdural electrode arrays, respectively. Differences in high gamma activity during listening to the interviewer and the subject's self-generated verbal responses were quantified for each recording site and across sites within HG and STG. The expanded MMSE produced widespread activation in auditory cortex of both hemispheres. No significant difference was found between activity during listening to the interviewer's questions and the subject's answers in posteromedial HG (auditory core cortex). A different pattern was observed throughout anterolateral HG and posterior and middle portions of lateral STG (non-core auditory cortical areas), where activity was significantly greater during listening compared to speaking. No systematic task-specific differences in the degree of suppression during speaking relative to listening were found in posterior and middle STG. Individual sites could, however, exhibit task-related variability in the degree of suppression during speaking compared to listening. The current study demonstrates that ECoG recordings can be acquired in time-efficient dialog-based paradigms, permitting examination of language and cognition in an ecologically salient manner. The results obtained from auditory cortex serve as a foundation for future studies addressing patterns of activity beyond auditory cortex that subserve human communication.

In humans, listening to speech evokes neural responses in the motor cortex. This has been controversially interpreted as evidence that speech sounds are processed as articulatory gestures. However, it is unclear what information is actually encoded by such neural activity. We used high-density direct human cortical recordings while participants spoke and listened to speech sounds. Motor cortex neural patterns during listening were substantially different than during articulation of the same sounds. During listening, we observed neural activity in the superior and inferior regions of ventral motor cortex. During speaking, responses were distributed throughout somatotopic representations of speech articulators in motor cortex. The structure of responses in motor cortex during listening was organized along acoustic features similar to auditory cortex, rather than along articulatory features as during speaking. Motor cortex does not contain articulatory representations of perceived actions in speech, but rather, represents auditory vocal information.

Although resting-state functional connectivity is a commonly used neuroimaging paradigm, the underlying mechanisms remain unknown. Thalamo-cortical and cortico-cortical circuits generate oscillations at different frequencies during spontaneous activity. However, it remains unclear how the various rhythms interact and whether their interactions are lamina-specific. Here we investigated intra- and inter-laminar spontaneous phase-amplitude coupling (PAC). We recorded local-field potentials using laminar probes inserted in the forelimb representation of rat area S1. We then computed time-series of frequency-band- and lamina-specific current source density (CSD), and PACs of CSD for all possible pairs of the classical frequency bands in the range of 1-150 Hz. We observed both intra- and inter-laminar spontaneous PAC. Of 18 possible combinations, 12 showed PAC, with the highest measures of interaction obtained for the pairs of the theta/gamma and delta/gamma bands. Intra- and inter-laminar PACs involving layers 2/3-5a were higher than those involving layer 6. Current sinks (sources) in the delta band were associated with increased (decreased) amplitudes of high-frequency signals in the beta to fast gamma bands throughout layers 2/3-6. Spontaneous sinks (sources) of the theta and alpha bands in layers 2/3-4 were on average linked to dipoles completed by sources (sinks) in layer 6, associated with high (low) amplitudes of the beta to fast-gamma bands in the entire cortical column. Our findings show that during spontaneous activity, delta, theta, and alpha oscillations are associated with periodic excitability, which for the theta and alpha bands is lamina-dependent. They further emphasize the differences between the function of layer 6 and that of the superficial layers, and the role of layer 6 in controlling activity in those layers. Our study links theories on the involvement of PAC in resting-state functional connectivity with previous work that revealed lamina-specific anatomical thalamo-cortico-cortical connections.

Spectro-Temporal Receptive Fields (STRFs) were estimated from both multi-unit sorted clusters and high-gamma power responses in human auditory cortex. Intracranial electrophysiological recordings were used to measure responses to a random chord sequence of Gammatone stimuli. Traditional methods for estimating STRFs from single-unit recordings, such as spike-triggered-averages, tend to be noisy and are less robust to other response signals such as local field potentials. We present an extension to recently advanced methods for estimating STRFs from generalized linear models (GLM). A new variant of regression using regularization that penalizes non-zero coefficients is described, which results in a sparse solution. The frequency-time structure of the STRF tends toward grouping in different areas of frequency-time and we demonstrate that group sparsity-inducing penalties applied to GLM estimates of STRFs reduces the background noise while preserving the complex internal structure. The contribution of local spiking activity to the high-gamma power signal was factored out of the STRF using the GLM method, and this contribution was significant in 85 percent of the cases. Although the GLM methods have been used to estimate STRFs in animals, this study examines the detailed structure directly from auditory cortex in the awake human brain. We used this approach to identify an abrupt change in the best frequency of estimated STRFs along posteromedial-to-anterolateral recording locations along the long axis of Heschl's gyrus. This change correlates well with a proposed transition from core to non-core auditory fields previously identified using the temporal response properties of Heschl's gyrus recordings elicited by click-train stimuli.

Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

Neural micro-electrode arrays that are transparent over a broad wavelength spectrum from ultraviolet to infrared could allow for simultaneous electrophysiology and optical imaging, as well as optogenetic modulation of the underlying brain tissue. The long-term biocompatibility and reliability of neural micro-electrodes also require their mechanical flexibility and compliance with soft tissues. Here we present a graphene-based, carbon-layered electrode array (CLEAR) device, which can be implanted on the brain surface in rodents for high-resolution neurophysiological recording. We characterize optical transparency of the device at >90% transmission over the ultraviolet to infrared spectrum and demonstrate its utility through optical interface experiments that use this broad spectrum transparency. These include optogenetic activation of focal cortical areas directly beneath electrodes, in vivo imaging of the cortical vasculature via fluorescence microscopy and 3D optical coherence tomography. This study demonstrates an array of interfacing abilities of the CLEAR device and its utility for neural applications.

Speech perception requires that sounds be transformed into speech-related objects with lexical and semantic meaning. It is unclear at what level in the auditory pathways this transformation emerges. Primary auditory cortex has been implicated in both representation of acoustic sound attributes and sound objects. While non-primary auditory cortex located on the posterolateral superior temporal gyrus (PLST) is clearly involved in acoustic-to-phonetic pre-lexical representations, it is unclear what role this region plays in auditory object formation. Additional data support the importance of prefrontal cortex in the formation of auditory objects, while other data would implicate this region in auditory object selection. To help clarify the respective roles of auditory and auditory-related cortex in the formation and selection of auditory objects, we examined high gamma activity simultaneously recorded directly from Heschl's gyrus (HG), PLST and prefrontal cortex, while subjects performed auditory semantic detection tasks. Subjects were patients undergoing evaluation for treatment of medically intractable epilepsy. We found that activity in posteromedial HG and early activity on PLST was robust to sound stimuli regardless of their context, and minimally modulated by tasks. Later activity on PLST could be strongly modulated by semantic context, but not by behavioral performance. Activity within prefrontal cortex also was related to semantic context, and did co-vary with behavior. We propose that activity in posteromedial HG and early activity on PLST primarily reflect the representation of spectrotemporal sound attributes. Later activity on PLST represents a pre-lexical processing stage and is an intermediate step in the formation of word objects. Activity in prefrontal cortex appears directly involved in word object selection. The roles of other auditory and auditory-related cortical areas in the formation of word objects remain to be explored.

Improving performance in motor skill acquisition is proposed to be supported by tuning of neural networks. To address this issue we investigated changes of phase-amplitude cross-frequency coupling (paCFC) in neuronal networks during motor performance improvement. We recorded intracranially from subdural electrodes (electrocorticogram; ECoG) from 6 patients who learned 3 distinct motor tasks requiring coordination of finger movements with an external cue (serial response task, auditory motor coordination task, go/no-go). Performance improved in all subjects and all tasks during the first block and plateaued in subsequent blocks. Performance improvement was paralled by increasing neural changes in the trial-to-trial paCFC between theta ([Formula: see text]; 4-8 Hz) phase and high gamma (HG; 80-180 Hz) amplitude. Electrodes showing this covariation pattern (Pearson's r ranging up to .45) were located contralateral to the limb performing the task and were observed predominantly in motor brain regions. We observed stable paCFC when task performance asymptoted. Our results indicate that motor performance improvement is accompanied by adjustments in the dynamics and topology of neuronal network interactions in the [Formula: see text] and HG range. The location of the involved electrodes suggests that oscillatory dynamics in motor cortices support performance improvement with practice.

Dysregulated endoplasmic reticulum (ER) calcium (Ca(2+)) signaling is reported to play an important role in Alzheimer disease (AD) pathogenesis. The role of ER Ca(2+) release channels, the ryanodine receptors (RyanRs), has been extensivelys tudied in AD models and RyanR expression and activity are upregulated in the brains of various familial AD (FAD) models.The objective of this study was to utilize a genetic approach to evaluate the importance of RyanR type 3 (RyanR3) in the context of AD pathology.The expression of RyanR3 was also elevated in hippocampus of APPPS1 mice (Thy1-APPKM670/671NL, Thy1-PS1L166P).In young (≤ 3 mo) APPPS1 mice, the deletion of RyanR3 increased hippocampal neuronal network excitability and accelerated AD pathology, leading to mushroom spine loss and increased amyloid accumulation. In contrast, deletion of RyanR3 in older APPPS1 mice (≥ 6 mo) rescued network excitability and mushroom spine loss, reduced amyloid plaque load and reduced spontaneous seizure occurrence.Our data suggests a dual role for RyanR3 in AD pathology. In young AD neurons, RyanR3 protects AD neurons from synaptic and network dysfunction. In older AD neurons, increased RyanR3 activity contributes to pathology. These results imply that blockade of RyanR3 may be beneficial for those in the later stages of the disease, but RyanR activators may be beneficial when used prior to disease onset or in its initial stages. Caffeine is an activator of RyanRs and our results may help to explain a complex epidemiological connection between coffee consumption in mid-life and risk of AD development in old age.

Here we propose a methodology to analyze volumetric electrical activity of neuronal masses in the somatosensory barrel field of Wistar rats. The key elements of the proposed methodology are a three-dimensional microelectrode array, which was customized by our group to observe extracellular recordings from an extended area of the barrel field, and a novel method for the current source density analysis. By means of this methodology, we were able to localize single barrels from their event-related responses to single whisker deflection. It was also possible to assess the spatiotemporal dynamics of neuronal aggregates in several barrels at the same time with the resolution of single neurons. We used simulations to study the robustness of our methodology to unavoidable physiological noise and electrode configuration. We compared the accuracy to reconstruct neocortical current sources with that obtained with a previous method. This constitutes a type of electrophysiological microscopy with high spatial and temporal resolution, which could change the way we analyze the activity of cortical neurons in the future.

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.

It was recently shown that rhythmic entrainment, long considered a human-specific mechanism, can be demonstrated in a selected group of bird species, and, somewhat surprisingly, not in more closely related species such as nonhuman primates. This observation supports the vocal learning hypothesis that suggests rhythmic entrainment to be a by-product of the vocal learning mechanisms that are shared by several bird and mammal species, including humans, but that are only weakly developed, or missing entirely, in nonhuman primates. To test this hypothesis we measured auditory event-related potentials (ERPs) in two rhesus monkeys (Macaca mulatta), probing a well-documented component in humans, the mismatch negativity (MMN) to study rhythmic expectation. We demonstrate for the first time in rhesus monkeys that, in response to infrequent deviants in pitch that were presented in a continuous sound stream using an oddball paradigm, a comparable ERP component can be detected with negative deflections in early latencies (Experiment 1). Subsequently we tested whether rhesus monkeys can detect gaps (omissions at random positions in the sound stream; Experiment 2) and, using more complex stimuli, also the beat (omissions at the first position of a musical unit, i.e. the 'downbeat'; Experiment 3). In contrast to what has been shown in human adults and newborns (using identical stimuli and experimental paradigm), the results suggest that rhesus monkeys are not able to detect the beat in music. These findings are in support of the hypothesis that beat induction (the cognitive mechanism that supports the perception of a regular pulse from a varying rhythm) is species-specific and absent in nonhuman primates. In addition, the findings support the auditory timing dissociation hypothesis, with rhesus monkeys being sensitive to rhythmic grouping (detecting the start of a rhythmic group), but not to the induced beat (detecting a regularity from a varying rhythm).