EEG/ECoG/EMG publications

The glutamate transporter GLT-1 is responsible for the largest proportion of total glutamate transport. Recently, it has been demonstrated that ceftriaxone (CEF) robustly increases GLT-1 expression. In addition, physiological studies have shown that GLT-1 up-regulation strongly affects synaptic plasticity, and leads to an impairment of the prepulse inhibition, a simple form of information processing, thus suggesting that GLT-1 over-expression may lead to dysfunctions of large populations of neurons. To test this possibility, we assessed whether CEF affects cortical electrical activity by using chronic electroencephalographic (EEG) recordings in male WKY rats. Spectral analysis showed that 8 days of CEF treatment resulted in a delayed reduction in EEG theta power (7-9 Hz) in both frontal and parietal derivations. This decrease peaked at day 10, i.e., 2 days after the end of treatment, and disappeared by day 16. In addition, we found that the same CEF treatment increased motor activity, especially when EEG changes are more prominent. Taken together, these data indicate that GLT-1 up-regulation, by modulating glutamatergic transmission, impairs the activity of widespread neural circuits. In addition, the increased motor activity and prepulse inhibition alterations previously described suggest that neural circuits involved in sensorimotor control are particularly sensitive to GLT-1 up-regulation.

The aim of this paper is twofold: first, to introduce a neural field model motivated by a well-known neural mass model; second, to show how one can estimate model parameters pertaining to spatial (anatomical) properties of neuronal sources based on EEG or LFP spectra using Bayesian inference. Specifically, we consider neural field models of cortical activity as generative models in the context of dynamic causal modeling (DCM). This paper considers the simplest case of a single cortical source modeled by the spatiotemporal dynamics of hidden neuronal states on a bounded cortical surface or manifold. We build this model using multiple layers, corresponding to cortical lamina in the real cortical manifold. These layers correspond to the populations considered in classical (Jansen and Rit) neural mass models. This allows us to formulate a neural field model that can be reduced to a neural mass model using appropriate constraints on its spatial parameters. In turn, this enables one to compare and contrast the predicted responses from equivalent neural field and mass models respectively. We pursue this using empirical LFP data from a single electrode to show that the parameters controlling the spatial dynamics of cortical activity can be recovered, using DCM, even in the absence of explicit spatial information in observed data.

Memories are thought to be encoded as a distributed representation in the neocortex. The medial prefrontal cortex (mPFC) has been shown to support the expression of memories that initially depend on the hippocampus (HPC), yet the mechanisms by which the HPC and mPFC access the distributed representations in the neocortex are unknown. By measuring phase synchronization of local field potential (LFP) oscillations, we found that learning initiated changes in neuronal communication of the HPC and mPFC with the lateral entorhinal cortex (LEC), an area that is connected with many other neocortical regions. LFPs were recorded simultaneously from the three brain regions while rats formed an association between an auditory stimulus (CS) and eyelid stimulation (US) in a trace eyeblink conditioning paradigm, as well as during retention 1 month following learning. Over the course of learning, theta oscillations in the LEC and mPFC became strongly synchronized following presentation of the CS on trials in which rats exhibited a conditioned response (CR), and this strengthened synchronization was also observed during remote retention. In contrast, CS-evoked theta synchronization between the LEC and HPC decreased with learning. Our results suggest that communication between the LEC and mPFC are strengthened with learning whereas the communication between the LEC and HPC are concomitantly weakened, suggesting that enhanced LEC-mPFC communication may be a neuronal correlate for theoretically proposed neocortical reorganization accompanying encoding and consolidation of a memory.

Sensory training therapies for tinnitus are based on the assumption that, notwithstanding neural changes related to tinnitus, auditory training can alter the response properties of neurons in auditory pathways. To assess this assumption, we investigated whether brain changes induced by sensory training in tinnitus sufferers and measured by electroencephalography (EEG) are similar to those induced in age and hearing loss matched individuals without tinnitus trained on the same auditory task. Auditory training was given using a 5 kHz 40-Hz amplitude-modulated (AM) sound that was in the tinnitus frequency region of the tinnitus subjects and enabled extraction of the 40-Hz auditory steady-state response (ASSR) and P2 transient response known to localize to primary and non-primary auditory cortex, respectively. P2 amplitude increased over training sessions equally in participants with tinnitus and in control subjects, suggesting normal remodeling of non-primary auditory regions in tinnitus. However, training-induced changes in the ASSR differed between the tinnitus and control groups. In controls the phase delay between the 40-Hz response and stimulus waveforms reduced by about 10° over training, in agreement with previous results obtained in young normal hearing individuals. However, ASSR phase did not change significantly with training in the tinnitus group, although some participants showed phase shifts resembling controls. On the other hand, ASSR amplitude increased with training in the tinnitus group, whereas in controls this response (which is difficult to remodel in young normal hearing subjects) did not change with training. These results suggest that neural changes related to tinnitus altered how neural plasticity was expressed in the region of primary but not non-primary auditory cortex. Auditory training did not reduce tinnitus loudness although a small effect on the tinnitus spectrum was detected.

Studies on the maturation of auditory motion processing in children have yielded inconsistent reports. The present study combines subjective and objective measurements to investigate how the auditory perceptual abilities of children change during development and whether these changes are paralleled by changes in the event-related brain potential (ERP). We employed the mismatch negativity (MMN) to determine maturational changes in the discrimination of interaural time differences (ITDs) that generate lateralized moving auditory percepts. MMNs were elicited in children, teenagers, and adults, using a small and a large ITD at stimulus offset with respect to each subject's discrimination threshold. In adults and teenagers large deviants elicited prominent MMNs, whereas small deviants at the behavioral threshold elicited only a marginal or no MMN. In contrast, pronounced MMNs for both deviant sizes were found in children. Behaviorally, however, most of the children showed higher discrimination thresholds than teens and adults. Although automatic ITD detection is functional, active discrimination is still limited in children. The lack of MMN deviance dependency in children suggests that unlike in teenagers and adults, neural signatures of automatic auditory motion processing do not mirror discrimination abilities. The study critically accounts for advanced understanding of children's central auditory development.

Slow cortical potentials (SCPs) are currently of great interest in the hearing aid fitting process for infants; however, there is conflicting evidence in the literature concerning the use of SCPs for this purpose. The current study investigated SCP amplitudes and latencies in young normal-hearing listeners in response to a 60 ms duration tonal stimulus (1000 Hz) presented at three intensities (30, 50, and 70 dB SPL) in aided and unaided conditions using three hearing aids (Analog, DigitalA, and DigitalB) with two gain settings (20 and 40 dB). Results showed that SCP amplitudes were smaller for the digital hearing aids compared with the analog hearing aid, and none of the hearing aids resulted in a reliable increase in response amplitude relative to the unaided across conditions. SCP latencies in analog conditions were not significantly different from latencies in the unaided conditions; however, both digital hearing aids resulted in significantly delayed SCP latencies. The results of the current study (as well as several previous studies) indicate that the SCP may not accurately reflect the amplified stimulus expected from the prescribed hearing aids. Thus, “aided-SCP” results must be interpreted with caution, and more research is required concerning possible clinical use of this technique.

An extensive photosensitive-polyimide (PSPI)-based method for designing and fabricating various neural electrode architectures was developed. The method aims to broaden the design flexibility and expand the fabrication capability for neural electrodes to improve the quality of recorded signals and integrate other functions. After characterizing PSPI's properties for micromachining processes, we successfully designed and fabricated various neural electrodes even on a non-flat substrate using only one PSPI as an insulation material and without the time-consuming dry etching processes. The fabricated neural electrodes were an electrocorticogram (ECoG) electrode, a mesh intracortical electrode with a unique lattice-like mesh structure to fixate neural tissue, and a guide cannula electrode with recording microelectrodes placed on the curved surface of a guide cannula as a microdialysis probe. In vivo neural recordings using anesthetized rats demonstrated that these electrodes can be used to record neural activities repeatedly without any breakage and mechanical failures, which potentially promises stable recordings for long periods of time. These successes make us believe that this PSPI-based fabrication is a powerful method, permitting flexible design, and easy optimization of electrode architectures for a variety of electrophysiological experimental research with improved neural recording performance.

Impaired neural conductivity shown by delayed latency and reduced amplitude of characteristic peaks in somatosensory evoked potentials (SSEPs), has been used to monitor hypoxic-ischemic brain injury after cardiac arrest (CA). However, rather than characteristic peak deferral and suppression, the time jitter of the peak in SSEP related with time-variant neurological abnormalities is diminished by the commonly used ensemble average method. This paper utilizes the second order blind identification (SOBI) technique to extract characteristic peak information from one trial of SSEPs. Sixteen male Wistar rats were subjected to 7 or 9 min of asphyxial CA (n=8 per group). The SSEPs from median nerve stimulation were recorded for 4h after CA and then for 15 min periods at 24, 48 and 72 h. Neurological outcomes were evaluated by neurologic deficit score (NDS) at 72 h post-CA. The SSEP signal was analyzed offline with SOBI processing in Matlab. The N10 feature of SSEP was compared between good (NDS≥50) and bad (NDS<50) outcomes. After processed by SOBI, the N10 detection rate was significantly increased (p<0.001) from 90 min post-CA. Statistical difference of the latency variance of the N10 between good and bad outcome groups existed at 24, 48 and 72 h post-CA (p≤0.001). Our study is the first application using SOBI detecting variance in neural signals like SSEP. N10 latency variance, related with neurophysiological dysfunction, increased after hypoxic-ischemic injury. The SOBI technique is an efficient method in the identification of peak detection and offers a favorable alternative to reveal the neural transmission variation.

The whisker-to-barrel cortex is widely used to study neurovascular coupling, but the cellular basis that underlies the perfusion changes is still largely unknown. Here, we identified neurons recruited by whisker stimulation in the rat somatosensory cortex using double immunohistochemistry for c-Fos and markers of glutamatergic and GABAergic neurons, and investigated in vivo their contribution along with that of astrocytes in the evoked perfusion response. Whisker stimulation elicited cerebral blood flow (CBF) increases concomitantly with c-Fos upregulation in pyramidal cells that coexpressed cyclooxygenase-2 (COX-2) and GABA interneurons that coexpressed vasoactive intestinal polypeptide and/or choline acetyltransferase, but not somatostatin or parvalbumin. The evoked CBF response was decreased by blockade of NMDA (MK-801, -37%), group I metabotropic glutamate (MPEP+LY367385, -40%), and GABA-A (picrotoxin, -31%) receptors, but not by GABA-B, VIP, or muscarinic receptor antagonism. Picrotoxin decreased stimulus-induced somatosensory evoked potentials and CBF responses. Combined blockade of GABA-A and NMDA receptors yielded an additive decreasing effect (-61%) of the evoked CBF compared with each antagonist alone, demonstrating cooperation of both excitatory and inhibitory systems in the hyperemic response. Blockade of prostanoid synthesis by inhibiting COX-2 (indomethacin, NS-398), expressed by ∼40% of pyramidal cells but not by astrocytes, impaired the CBF response (-50%). The hyperemic response was also reduced (-40%) after inhibition of astroglial oxidative metabolism or epoxyeicosatrienoic acids synthesis. These results demonstrate that changes in pyramidal cell activity, sculpted by specific types of inhibitory GABA interneurons, drive the CBF response to whisker stimulation and, further, that metabolically active astrocytes are also required.

The human temporal lobe is well known to be critical for language comprehension. Previous physiological research has focused mainly on non-invasive neuroimaging and electrophysiological techniques with each approach requiring averaging across many trials and subjects. The results of these studies have implicated extended anatomical regions in peri-sylvian cortex in speech perception. These non-invasive studies typically report a spatially homogenous functional pattern of activity across several centimeters of cortex. We examined the spatiotemporal dynamics of word processing using electrophysiological signals acquired from high-density electrode arrays (4mm spacing) placed directly on the human temporal lobe. Electrocorticographic (ECoG) activity revealed a rich mosaic of language activity, which was functionally distinct at four mm separation. Cortical sites responding specifically to word and not phoneme stimuli were surrounded by sites that responded to both words and phonemes. Other sub-regions of the temporal lobe responded robustly to self-produced speech and minimally to external stimuli while surrounding sites at 4mm distance exhibited an inverse pattern of activation. These data provide evidence for temporal lobe specificity to words as well as self-produced speech. Furthermore, the results provide evidence that cortical processing in the temporal lobe is not spatially homogenous over centimeters of cortex. Rather, language processing is supported by independent and spatially distinct functional sub-regions of cortex at a resolution of at least 4mm.

Movement-assist devices such as neuromuscular stimulation systems can be used to generate movements in people with chronic hand paralysis due to stroke. If detectable, motor planning activity in the cortex could be used in real time to trigger a movement-assist device and restore a person's ability to perform many of the activities of daily living. Additionally, re-coupling motor planning in the cortex with assisted movement generation in the periphery may provide an even greater benefit-strengthening relevant synaptic connections over time to promote natural motor recovery. This study examined the potential for using electroencephalograms (EEGs) as a means of rapidly detecting the intent to open the hand during movement planning in individuals with moderate chronic hand paralysis following a subcortical ischemic stroke. On average, attempts to open the hand could be detected from EEGs approximately 100-500 ms prior to the first signs of movement onset. This earlier detection would minimize device activation delays and allow for tighter coupling between initial formation of the motor plan in the cortex and augmentation of that plan in the periphery by a movement-assist device. This tight temporal coupling may be important or even essential for strengthening synaptic connections and enhancing natural motor recovery.

Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli—albeit not consciously perceived—had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.

Brain-machine interfaces (BMIs) use signals from the brain to control a device such as a computer cursor. Various types of signals have been used as BMI inputs, from single-unit action potentials to scalp potentials. Recently, intermediate-level signals such as subdural field potentials have also shown promise. These different signal types are likely to provide different amounts of information, but we do not yet know what signal types are necessary to enable a particular BMI function, such as identification of reach target location, control of a two-dimensional cursor or the dynamics of limb movement. Here we evaluated the performance of field potentials, measured either intracortically (local field potentials, LFPs) or epidurally (epidural field potential, EFPs), in terms of the ability to decode reach direction. We trained rats to move a joystick with their forepaw to control the motion of a sipper tube to one of the four targets in two dimensions. We decoded the forelimb reach direction from the field potentials using linear discriminant analysis. We achieved a mean accuracy of 69 ± 3% with EFPs and 57 ± 2% with LFPs, both much better than chance. Signal quality remained good up to 13 months after implantation. This suggests that using epidural signals could provide BMI inputs of high quality with less risk to the patient than using intracortical recordings.

Objective: There is interest in using cortical auditory evoked potentials (CAEPs) to evaluate hearing aid fittings and experience-related plasticity associated with amplification; however, little is known about hearing aid signal processing effects on these responses. The purpose of this study was to determine the effect of clinically relevant hearing aid gain settings, and the resulting in-the-canal signal-to-noise ratios (SNRs), on the latency and amplitude of P1, N1, and P2 waves. DESIGN & SAMPLE: Evoked potentials and in-the-canal acoustic measures were recorded in nine normal-hearing adults in unaided and aided conditions. In the aided condition, a 40-dB signal was delivered to a hearing aid programmed to provide four levels of gain (0, 10, 20, and 30 dB). As a control, unaided stimulus levels were matched to aided condition outputs (i.e. 40, 50, 60, and 70 dB) for comparison purposes. Results: When signal levels are defined in terms of output level, aided CAEPs were surprisingly smaller and delayed relative to unaided CAEPs, probably resulting from increases to noise levels caused by the hearing aid. Discussion: These results reinforce the notion that hearing aids modify stimulus characteristics such as SNR, which in turn affects the CAEP in a way that does not reliably reflect hearing aid gain.

In an awake state, neurons in the cerebral cortex fire irregularly and electroencephalogram (EEG) recordings display low-amplitude, high-frequency fluctuations. During sleep, neurons oscillate between 'on' periods, when they fire as in an awake brain, and 'off' periods, when they stop firing altogether and the EEG displays high-amplitude slow waves. However, what happens to neuronal firing after a long period of being awake is not known. Here we show that in freely behaving rats after a long period in an awake state, cortical neurons can go briefly 'offline' as in sleep, accompanied by slow waves in the local EEG. Neurons often go offline in one cortical area but not in another, and during these periods of 'local sleep', the incidence of which increases with the duration of the awake state, rats are active and display an 'awake' EEG. However, they are progressively impaired in a sugar pellet reaching task. Thus, although both the EEG and behaviour indicate wakefulness, local populations of neurons in the cortex may be falling asleep, with negative consequences for performance.

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex.

To clarify speech-elicited response patterns within auditory-responsive cortex of the posterolateral superior temporal (PLST) gyrus, time-frequency analyses of event-related band power in the high gamma frequency range (75-175 Hz) were performed on the electrocorticograms recorded from high-density subdural grid electrodes in 8 patients undergoing evaluation for medically intractable epilepsy. Stimuli were 6 stop consonant-vowel (CV) syllables that varied in their consonant place of articulation (POA) and voice onset time (VOT). Initial augmentation was maximal over several centimeters of PLST, lasted about 400 ms, and was often followed by suppression and a local outward expansion of activation. Maximal gamma power overlapped either the Nα or Pβ deflections of the average evoked potential (AEP). Correlations were observed between the relative magnitudes of gamma band responses elicited by unvoiced stop CV syllables (/pa/, /ka/, /ta/) and their corresponding voiced stop CV syllables (/ba/, /ga/, /da/), as well as by the VOT of the stimuli. VOT was also represented in the temporal patterns of the AEP. These findings, obtained in the passive awake state, indicate that PLST discriminates acoustic features associated with POA and VOT and serve as a benchmark upon which task-related speech activity can be compared.

A long debate in selective attention research is whether attention enhances sensory response or sharpens neural tuning by suppressing response to non-target input. In fact, both processes may occur as a function of load: an uncertain listener might use a broad attentional filter to enhance responses to all inputs (i.e., vigilance), yet employ sharpened tuning to focus on hard to discriminate targets. The present work used the greater signal gain, anatomical precision, and laterality separation of intracranial electrophysiological recordings (electrocorticograms) to investigate these competing effects. Data were recorded from acoustically-responsive cortex in the perisylvian region of a single hemisphere in five neurosurgery patients. Patients performed a dichotic listening task in which they alternately attended toward, away from, or completely ignored (silent reading) tones presented to designated ears at varying presentation rates. Comparisons between the grand-averaged event-related potential (ERP) waveforms show a striking change in the effect of selective auditory attention with attentional load. At slower presentation rates (low-load), ERPs were overall enhanced in response to both input channels and regardless of attended ear, including a significant enhancement of ipsilateral input. This result supports a broadly enhancing model of attention under low perceptual load conditions. At the fastest rate, however, only responses to attended inputs contralateral to grid location remained enhanced. This result supports an increasing suppression, or "sharpening," of neural responses to non-targets with increasing attentional load. These data provide support for an elastic model of attention in which attentional scope narrows with increasing load.

This study examines the feasibility of using electroencephalograms (EEGs) to rapidly detect the intent to open one's hand in individuals with complete hand paralysis following a subcortical ischemic stroke. If detectable, this motor-planning activity could be used in real time to trigger a motorized hand exoskeleton or an electrical stimulation device that opens/closes the hand. While EEG-triggered movement-assist devices could restore function, they may also promote recovery by reinforcing the use of remaining cortical circuits. EEGs were recorded while participants were cued to either relax or attempt to extend their fingers. Linear-discriminant analysis was used to detect onset of finger-extension from the EEGs in a leave-one-trial-out cross-validation process. In each testing trial, the classifier was applied in pseudo-real-time starting from an initial hand-relaxed phase, through movement planning, and into the initial attempted-finger-extension phase (finger-extension phase estimated from typical time-to-movement-onset measured in the unaffected hand). The classifiers detected attempted-finger-extension at a significantly higher rate during both motor-planning and early attempted execution compared to rest. To reduce inappropriate triggering of a movement-assist device during rest, the classification threshold could be adjusted to require more certainty about one's intent to move before triggering a device. Additionally, a device could be set to activate only after multiple time samples in a row were classified as finger-extension events. These options resulted in some sessions with no false triggers while the person was resting, but moderate-to-high true trigger rates during attempted-movements.