Epidural Recordings Research Articles

Epidural Spinal Cord Recordings (ESRs): sources of neural-appearing artifact in stimulation evoked compound action potentials.

Evoked compound action potentials (ECAPs) measured during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain and inform closed-loop control of SCS. Previous studies have used ECAPs to characterize neural responses to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model.
We characterized sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode™ lead. Spinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby muscles of the back, and motion artifact. The capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. EMG bleed-through can have phase shifts across the electrode array, similar to the phase shift anticipated by propagation of an evoked A-beta fiber response. The short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in CSF between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of recorded ECAPs. 
Controls must be implemented to separate neural signal from sources of artifact in SCS ECAPs. We suggest experimental procedures and reporting requirements necessary to disambiguate underlying neural response from these confounds. These data are important to better understand the framework for recorded ESRs, with components such as ECAPs, EMG, and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.

The role of spinal cord neuroanatomy in the variances of epidural spinal recordings

BackgroundSpinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone.MethodTwo electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs.ResultsReconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an ‘off-disc’ stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds.ConclusionThe results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Multifunctional Nanomesh Enables Cellular-Resolution, Elastic Neuroelectronics.

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing. Nanomesh elastic neuroelectronics are validated using single-unit recording from the small and curvilinear epidural surface of mouse dorsal root ganglia (DRG) with device self-conformed and superior recording quality compared to plastic control devices requiring manual pressing is demonstrated. Electrode scaling studies from in vivo epidural recording further revealed the need for cellular resolution for high-fidelity recording of single-unit activities and compound action potentials. In addition to creating a minimally invasive device to effectively interface with DRG sensory afferents at a single-cell resolution, this study establishes nanomeshing as a practical pathway to leverage traditional electrode materials for a new class of elastic neuroelectronics.

Human Cervical Epidural Spinal Electrogram Topographically Maps Distinct Volitional Movements.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4-8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements.

Clinical utility of intraoperative direct wave monitoring in patients with pre-operative motor deficits: Case series

Introduction and importanceD-wave (Direct waves) are Motor Evoked Potentials (MEPs) generated by a single transcranial stimulation and captured by attaching an epidural recording electrode caudal to the vulnerable area. Intraoperative neurophysiologic monitoring (IONM) is widely used in neurosurgery to recognize important neurological structures but can be challenging in the pediatric population due to incomplete neural development. Case presentationCase 1: A 48-year-old female presented to the outpatient department with complaints of difficulty walking for the past six months, numbness and weakness in bilateral lower limbs with recurrent falls for the past 1 month. Case 2: A 12-year-old boy presented to the emergency room with a history of inability to use both upper and lower limbs on the right side with tremulousness. Clinical discussionMagnetic resonance imaging (MRI) Spine in the first case revealed a D9-D10 calcified meningioma with significant spinal cord compression. In the second case, MRI Spine showed C1-C2 Intramedullary Space Occupying Lesion (SOL) and was planned for C1-C2 laminectomy with midline myelotomy. The first case was planned for microsurgical excision of the lesion under IONM guidance. The procedure went smoothly. Microsurgical gross total resection (GTR) of the intramedullary SOL under IONM Guidance was done for the second case. Postoperatively, the first patient showed no neurological compromise or complications. In the second case, following surgery, the child recovered gradually from surgery. ConclusionThis case series demonstrates the successful surgical management of two cases of spinal cord tumors through an IONM-guided surgery and the effective use of D waves in such challenging cases.

Novel Evoked Synaptic Activity Potentials (ESAPs) Elicited by Spinal Cord Stimulation.

Spinal cord stimulation (SCS) evokes fast epidural evoked compound action potential (ECAP) that represent activity of dorsal column axons, but not necessarily a spinal circuit response. Using a multimodal approach, we identified and characterized a delayed and slower potential evoked by SCS that reflects synaptic activity within the spinal cord. Anesthetized female Sprague Dawley rats were implanted with an epidural SCS lead, epidural motor cortex stimulation electrodes, an epidural spinal cord recording lead, an intraspinal penetrating recording electrode array, and intramuscular electromyography (EMG) electrodes in the hindlimb and trunk. We stimulated the motor cortex or the epidural spinal cord and recorded epidural, intraspinal, and EMG responses. SCS pulses produced characteristic propagating ECAPs (composed of P1, N1, and P2 waves with latencies <2 ms) and an additional wave ("S1") starting after the N2. We verified the S1-wave was not a stimulation artifact and was not a reflection of hindlimb/trunk EMG. The S1-wave has a distinct stimulation-intensity dose response and spatial profile compared with ECAPs. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX; a selective competitive antagonist of AMPA receptors (AMPARs)] significantly diminished the S1-wave, but not ECAPs. Furthermore, cortical stimulation, which did not evoke ECAPs, produced epidurally detectable and CNQX-sensitive responses at the same spinal sites, confirming epidural recording of an evoked synaptic response. Finally, applying 50-Hz SCS resulted in dampening of S1-wave but not ECAPs. Therefore, we hypothesize that the S1-wave is synaptic in origin, and we term the S1-wave type responses: evoked synaptic activity potentials (ESAPs). The identification and characterization of epidurally recorded ESAPs from the dorsal horn may elucidate SCS mechanisms.

Decoding violated sensory expectations from the auditory cortex of anaesthetised mice: Hierarchical recurrent neural network depicts separate 'danger' and 'safety' units.

The ability to respond appropriately to sensory information received from the external environment is among the most fundamental capabilities of central nervous systems. In the auditory domain, processes underlying this behaviour are studied by measuring auditory‐evoked electrophysiology during sequences of sounds with predetermined regularities. Identifying neural correlates of ensuing auditory novelty responses is supported by research in experimental animals. In the present study, we reanalysed epidural field potential recordings from the auditory cortex of anaesthetised mice during frequency and intensity oddball stimulation. Multivariate pattern analysis (MVPA) and hierarchical recurrent neural network (RNN) modelling were adopted to explore these data with greater resolution than previously considered using conventional methods. Time‐wise and generalised temporal decoding MVPA approaches revealed previously underestimated asymmetry between responses to sound‐level transitions in the intensity oddball paradigm, in contrast with tone frequency changes. After training, the cross‐validated RNN model architecture with four hidden layers produced output waveforms in response to simulated auditory inputs that were strongly correlated with grand‐average auditory‐evoked potential waveforms (r 2 > .9). Units in hidden layers were classified based on their temporal response properties and characterised using principal component analysis and sample entropy. These demonstrated spontaneous alpha rhythms, sound onset and offset responses and putative ‘safety’ and ‘danger’ units activated by relatively inconspicuous and salient changes in auditory inputs, respectively. The hypothesised existence of corresponding biological neural sources is naturally derived from this model. If proven, this could have significant implications for prevailing theories of auditory processing.

Non-invasive recording of high-frequency signals from the human spinal cord

Throughout the somatosensory system, neuronal ensembles generate high-frequency signals in the range of several hundred Hertz in response to sensory input. High-frequency signals have been related to neuronal spiking, and could thus help clarify the functional architecture of sensory processing. Recording high-frequency signals from subcortical regions, however, has been limited to clinical pathology whose treatment allows for invasive recordings. Here, we demonstrate the feasibility to record 200–1200 Hz signals from the human spinal cord non-invasively, and in healthy individuals. Using standard electroencephalography equipment in a cervical electrode montage, we observed high-frequency signals between 200 and 1200 Hz in a time window between 8 and 16 ms after electric median nerve stimulation (n = 15). These signals overlapped in latency, and, partly, in frequency, with signals obtained via invasive, epidural recordings from the spinal cord in a patient with neuropathic pain. Importantly, the observed high-frequency signals were dissociable from classic spinal evoked responses. A spatial filter that optimized the signal-to-noise ratio of high-frequency signals led to submaximal amplitudes of the evoked response, and vice versa, ruling out the possibility that high-frequency signals are merely a spectral representation of the evoked response. Furthermore, we observed spontaneous fluctuations in the amplitude of high-frequency signals over time, in the absence of any concurrent, systematic change to the evoked response. High-frequency, “spike-like” signals from the human spinal cord thus carry information that is complementary to the evoked response. The possibility to assess these signals non-invasively provides a novel window onto the neurophysiology of the human spinal cord, both in a context of top-down control over perception, as well as in pathology.

Towards single-trial classification of invasively recorded auditory evoked potentials in cochlear implant users

Objective. One promising approach towards further improving cochlear implants (CI) is to use brain signals controlling the device in order to close the auditory loop. Initial electroencephalography (EEG) studies have already shown promising results. However, they are based on noninvasive measurements, whereas implanted electrodes are expected to be more convenient in terms of everyday-life usability. If additional measurement electrodes were implanted during CI surgery, then invasive recordings should be possible. Furthermore, implantation will provide better signal quality, higher robustness to artefacts, and thus enhanced classification accuracy. Approach. In an initial project, three additional epidural electrodes were temporarily implanted during the surgical procedure. After surgery, different auditory evoked potentials (AEPs) were recorded both invasively (epidural) and using surface electrodes, with invasively recorded signals demonstrated as being markedly superior. In this present analysis, cortical evoked response audiometry (CERA) signals recorded in seven patients were used for single-trial classification of sounds with different intensities. For classification purposes, we used shrinkage-regularized linear discriminant analysis (sLDA). Clinical speech perception scores were also investigated. Main results. Analysis of CERA data from different subjects showed single-trial classification accuracies of up to 99.2% for perceived vs. non-perceived sounds. Accuracies of up to 89.1% were achieved in classification of sounds perceived at different intensities. Highest classification accuracies were achieved by means of epidural recordings. Required loudness differences seemed to correspond to speech perception in noise. Significance. The proposed epidural recording approach showed good classification accuracy into sound perceived and not perceived when the best-performing electrodes were selected. Classifying different levels of sound stimulation accurately proved more challenging. At present, the methods explored in this study would not be sufficiently reliable to allow automated closed-loop control of CI parameters. However, our findings are an important initial contribution towards improving applicability of closed auditory loops and for next-generation automatic fitting approaches.

Utilization of Epidural Electrodes as a Diagnostic Tool in Intractable Epilepsy-A Technical Note.

The utilization of epidural electrodes in the preoperative evaluation of intractable epilepsy is a valuable but underrepresented tool. In recent years, we have adapted the use of cylindrical epidural 1-contact electrodes (1-CE) instead of Peg electrodes. 1-CEs are more versatile since their explantation is a possible bedside procedure. Here we report our experience with 1-CEs as well as associated technical nuances. This retrospective analysis included 56 patients with intractable epilepsy who underwent epidural electrode placement for presurgical evaluation at the Department of Neurosurgery at the Charité University Hospital from September 2011 to July 2021. The median age at surgery was 36.3 years (range: 18–87), with 30 (53.6%) female and 26 (46.4%) male patients. Overall, 507 electrodes were implanted: 93 Fo electrodes, 33 depth electrodes, and 381 epidural electrodes, with a mean total surgical time of 100.5 ± 38 min and 11.8 ± 5 min per electrode. There was a total number of 24 complications in 21 patients (8 Fo electrode dislocations, 6 CSF leaks, 6 epidural electrode dislocations or malfunction, 3 wound infections, and 2 hemorrhages); 11 of these required revision surgery. The relative electrode complication rates were 3/222 (1.4%) in Peg electrodes and 3/159 (1.9%) in 1-CE. In summary, epidural recording via 1-CE is technically feasible, harbours an acceptable complication rate, and adequately replaces Peg electrodes.

Electrically Evoked Compound Action Potentials in Spinal Cord Stimulation: Implications for Preclinical Research Models

ObjectivesThe study aimed to assess the feasibility of recording electrically evoked compound action potentials (ECAPs) from the rat spinal cord. To achieve this, we characterized electrophysiological responses of dorsal column (DC) axons from electrical stimulation and quantified the relationship between ECAP and motor thresholds (ECAPTs and MTs). Material and MethodsNaïve, anesthetized, and freely behaving rats were implanted with a custom-made epidural spinal cord stimulation (SCS) lead. Epidural stimulation and recordings were performed on the same lead using specifically designed equipment. ResultsThe ECAPs recorded from the rat spinal cord demonstrated the expected triphasic morphology. Using 20 μsec pulse duration and 2 Hz frequency rate, the current required in anesthetized rats to generate ECAPs was 0.13 ± 0.02 mA, while the average current required to observe MT was 1.49 ± 0.14 mA. In unanesthetized rats, the average current required to generate ECAPs was 0.09 ± 0.02 mA, while the average current required to observe MT was 0.27 ± 0.04 mA. Thus, there was a significant difference between the ECAPT and MT in both anesthetized and unanesthetized rats (MT was 13.39 ± 2.40 and 2.84 ± 0.33 times higher than ECAPT, respectively). Signal analysis revealed average conduction velocities (CVs) suggesting that predominantly large, myelinated fibers were activated. In addition, a morphometric evaluation of spinal cord slices indicated that the custom-made lead may preferentially activate DC axons. ConclusionsThis is the first evidence demonstrating the feasibility of recording ECAPs from the rat spinal cord, which may be more useful in determining parameters of SCS in preclinical SCS models than MTs. Thus, this approach may allow for the development of a novel model of SCS in rats with chronic pain that will translate better between animals and humans.

Epidural Spinal Electrogram Provides Direct Spinal Recordings in Awake Human Participants.

Little is known about the electrophysiological activity of the spinal cord during voluntary movement control in humans. We present a novel method for recording electrophysiological activity from the human spinal cord using implanted epidural electrodes during naturalistic movements including overground walking. Spinal electrograms (SEGs) were recorded from epidural electrodes implanted as part of a test trial for patients with chronic pain undergoing evaluation for spinal cord stimulation. Externalized ends of the epidural leads were connected to an external amplifier to capture SEGs. Electromyographic and accelerometry data from the upper and lower extremities were collected using wireless sensors and synchronized to the SEG data. Patients were instructed to perform various arm and leg movements while SEG and kinematic data were collected. This study proves the safety and feasibility of performing epidural spinal recordings from human subjects performing movement tasks.

Model-based prediction of muscarinic receptor function from auditory mismatch negativity responses

Drugs affecting neuromodulation, for example by dopamine or acetylcholine, take centre stage among therapeutic strategies in psychiatry. These neuromodulators can change both neuronal gain and synaptic plasticity and therefore affect electrophysiological measures. An important goal for clinical diagnostics is to exploit this effect in the reverse direction, i.e., to infer the status of specific neuromodulatory systems from electrophysiological measures.In this study, we provide proof-of-concept that the functional status of cholinergic (specifically muscarinic) receptors can be inferred from electrophysiological data using generative (dynamic causal) models. To this end, we used epidural EEG recordings over two auditory cortical regions during a mismatch negativity (MMN) paradigm in rats. All animals were treated, across sessions, with muscarinic receptor agonists and antagonists at different doses. Together with a placebo condition, this resulted in five levels of muscarinic receptor status. Using a dynamic causal model - embodying a small network of coupled cortical microcircuits - we estimated synaptic parameters and their change across pharmacological conditions. The ensuing parameter estimates associated with (the neuromodulation of) synaptic efficacy showed both graded muscarinic effects and predictive validity between agonistic and antagonistic pharmacological conditions.This finding illustrates the potential utility of generative models of electrophysiological data as computational assays of muscarinic function. In application to EEG data of patients from heterogeneous spectrum diseases, e.g. schizophrenia, such models might help identify subgroups of patients that respond differentially to cholinergic treatments. Significance StatementIn psychiatry, the vast majority of pharmacological treatments affect actions of neuromodulatory transmitters, e.g. dopamine or acetylcholine. As treatment is largely trial-and-error based, one of the goals for computational psychiatry is to construct mathematical models that can serve as “computational assays” and infer the status of specific neuromodulatory systems in individual patients. This translational neuromodeling strategy has great promise for electrophysiological data in particular but requires careful validation. The present study demonstrates that the functional status of cholinergic (muscarinic) receptors can be inferred from electrophysiological data using dynamic causal models of neural circuits. While accuracy needs to be enhanced and our results must be replicated in larger samples, our current results provide proof-of-concept for computational assays of muscarinic function using EEG.

Spike-wave discharges in absence epilepsy: segregation of electrographic components reveals distinct pathways of seizure activity.

The major electrophysiological hallmarks of absence seizures are spike and wave discharges (SWDs), consisting of a sharp spike component and a slow wave component. In a widely accepted scheme, these components are functionally coupled and reflect an iterative progression of neuronal excitation during the spike and post-excitatory silence during the wave. In a genetic rat model of absence epilepsy, local pharmacological inhibition of the centromedian thalamus (CM) selectively suppressed the spike component, leaving self-contained waves in epidural recordings. Thalamic inputs induced activity in cortical microcircuits underlying the spike component, while intracortical oscillations generated the wave component. Based on these findings, we propose a model in which oscillatory waves provide adequate time windows for integration of thalamocortical inputs and feedback responses during generation of a synchronized SWD. Spike and wave discharges (SWDs) are the electrographic hallmark of absence seizures and the major diagnostic criterion for childhood absence epilepsy (CAE). In a widely accepted scheme, the alternating sequence of spikes and waves reflects an iterative progression of neuronal excitation during the spike component and post-excitatory silence during the wave component. Here we challenge this view by showing that these two components are not necessarily coupled. In a genetic rat model of CAE, self-contained waves occurred in motor cortex in synchrony with SWDs in the somatosensory system during blockade of afferent input from the thalamus. Current-source density analyses of multi-site local field potentials (LFPs) revealed layer-specific activity, in which thalamic inputs induced a sequence of cellular-synaptic events underlying the spike component, while intracortical oscillations generated the wave component. These findings indicate novel principles of SWDs, where oscillatory cortical waves provide adequate time windows for integration of thalamocortical inputs and feedback responses during generation of seizure activity.

Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice.

Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epileptic treatments. Besides spontaneous seizures, these mice also display frequent epileptic spiking in epidural EEG recordings, and these have provided a means to test potential drug treatment to AD-related epilepsy. However, the origin of EEG spikes in transgenic AD model mice has remained elusive, which makes it difficult to relate electrophysiology with underlying pathology at the cellular and molecular level. Using multiple cortical and subcortical electrodes in freely moving APP/PS1 transgenic mice and their wild-type littermates, we identified several types of epileptic spikes among over 15 800 spikes visible with cortical screw electrodes based on their source localization. Cortical spikes associated with muscle twitches, cortico-hippocampal spikes, and spindle and fast-spindle associated spikes were present equally often in both APP/PS1 and wild-type mice, whereas pure cortical spikes were slightly more common in APP/PS1 mice. In contrast, spike-wave discharges, cortico-hippocampal spikes with after hyperpolarization and giant spikes were seen almost exclusively in APP/PS1 mice but only in a subset of them. Interestingly, different subtypes of spikes responded differently to anti-epileptic drugs ethosuximide and levetiracetam. From the translational point most relevant may be the giant spikes generated in the hippocampus that reached an amplitude up to ± 5 mV in the hippocampal channel. As in AD patients, they occurred exclusively during sleep. Further, we could demonstrate that a high number of giant spikes in APP/PS1 mice predicts seizures. These data show that by only adding a pair of hippocampal deep electrodes and EMG to routine cortical epidural screw electrodes and by taking into account underlying cortical oscillations, one can drastically refine the analysis of cortical spike data. This new approach provides a powerful tool to preclinical testing of potential new treatment options for AD related epilepsy.

Epidural recordings in cochlear implant users

Objective. In the long term it is desirable for CI users to control their device via brain signals. A possible strategy is the use of auditory evoked potentials (AEPs). Several studies have shown the suitability of auditory paradigms for such an approach. However, these investigations are based on non-invasive recordings. When thinking about everyday life applications, it would be more convenient to use implanted electrodes for signal acquisition. Ideally, the electrodes would be directly integrated into the CI. Further it is to be expected that invasively recorded signals have higher signal quality and are less affected by artifacts. Approach. In this project we investigated the feasibility of implanting epidural electrodes temporarily during CI surgery and the possibility to record AEPs in the course of several days after implantation. Intraoperatively, auditory brainstem responses were recorded, whereas various kinds of AEPs were recorded postoperatively. After a few days the epidural electrodes were removed. Main results. Data sets of ten subjects were obtained. Invasively recorded potentials were compared subjectively and objectively to clinical standard recordings using surface electrodes. Especially the cortical evoked response audiometry depicted clearer N1 waves for the epidural electrodes which were also visible at lower stimulation intensities compared to scalp electrodes. Furthermore the signal was less disturbed by artifacts. The objective quality measure (based on data sets of six patients) showed a significant better signal quality for the epidural compared to the scalp recordings. Significance. Altogether the approach revealed to be feasible and well tolerated by the patients. The epidural recordings showed a clearly better signal quality than the scalp recordings with AEPs being clearer recognizable. The results of the present study suggest that including epidural recording electrodes in future CI systems will improve the everyday life applicability of auditory closed loop systems for CI subjects.

Correlates of Spreading Depolarization, Spreading Depression, and Negative Ultraslow Potential in Epidural Versus Subdural Electrocorticography.

Spreading depolarizations (SDs) are characterized by near-complete breakdown of the transmembrane ion gradients, neuronal oedema and activity loss (=depression). The SD extreme in ischemic tissue, termed ‘terminal SD,’ shows prolonged depolarization, in addition to a slow baseline variation called ‘negative ultraslow potential’ (NUP). The NUP is the largest bioelectrical signal ever recorded from the human brain and is thought to reflect the progressive recruitment of neurons into death in the wake of SD. However, it is unclear whether the NUP is a field potential or results from contaminating sensitivities of platinum electrodes. In contrast to Ag/AgCl-based electrodes in animals, platinum/iridium electrodes are the gold standard for intracranial direct current (DC) recordings in humans. Here, we investigated the full continuum including short-lasting SDs under normoxia, long-lasting SDs under systemic hypoxia, and terminal SD under severe global ischemia using platinum/iridium electrodes in rats to better understand their recording characteristics. Sensitivities for detecting SDs or NUPs were 100% for both electrode types. Nonetheless, the platinum/iridium-recorded NUP was 10 times smaller in rats than humans. The SD continuum was then further investigated by comparing subdural platinum/iridium and epidural titanium peg electrodes in patients. In seven patients with either aneurysmal subarachnoid hemorrhage or malignant hemispheric stroke, two epidural peg electrodes were placed 10 mm from a subdural strip. We found that 31/67 SDs (46%) on the subdural strip were also detected epidurally. SDs that had longer negative DC shifts and spread more widely across the subdural strip were more likely to be observed in epidural recordings. One patient displayed an SD-initiated NUP while undergoing brain death despite continued circulatory function. The NUP’s amplitude was -150 mV subdurally and -67 mV epidurally. This suggests that the human NUP is a bioelectrical field potential rather than an artifact of electrode sensitivity to other factors, since the dura separates the epidural from the subdural compartment and the epidural microenvironment was unlikely changed, given that ventilation, arterial pressure and peripheral oxygen saturation remained constant during the NUP. Our data provide further evidence for the clinical value of invasive electrocorticographic monitoring, highlighting important possibilities as well as limitations of less invasive recording techniques.

A piecewise probabilistic regression model to decode hand movement trajectories from epidural and subdural ECoG signals

Objective. The primary concern of this study is to develop a probabilistic regression method that would improve the decoding of the hand movement trajectories from epidural ECoG as well as from subdural ECoG signals. Approach. The model is characterized by the conditional expectation of the hand position given the ECoG signals. The conditional expectation of the hand position is then modeled by a linear combination of the conditional probability density functions defined for each segment of the movement. Moreover, a spatial linear filter is proposed for reducing the dimension of the feature space. The spatial linear filter is applied to each frequency band of the ECoG signals and extract the features with highest decoding performance. Main results. For evaluating the proposed method, a dataset including 28 ECoG recordings from four adult Japanese macaques is used. The results show that the proposed decoding method outperforms the results with respect to the state of the art methods using this dataset. The relative kinematic information of each frequency band is also investigated using mutual information and decoding performance. The decoding performance shows that the best performance was obtained for high gamma bands from 50 to 200 Hz as well as high frequency ECoG band from 200 to 400 Hz for subdural recordings. However, the decoding performance was decreased for these frequency bands using epidural recordings. The mutual information shows that, on average, the high gamma band from 50 to 200 Hz and high frequency ECoG band from 200 to 400 Hz contain significantly more information than the average of the rest of the frequency bands for both subdural and epidural recordings. The results of high resolution time-frequency analysis show that ERD/ERS patterns in all frequency bands could reveal the dynamics of the ECoG responses during the movement. The onset and offset of the movement can be clearly identified by the ERD/ERS patterns. Significance. Reliable decoding the kinematic information from the brain signals paves the way for robust control of external devices.

A convex-shaped, PDMS-parylene hybrid multichannel ECoG-electrode array.

Long-term electrode implant is a challenge for successful brain-computer interfaces (BCIs). It is well known that electrocorticography (ECoG) using flexible planar electrodes is more suitable for long-term implants than intracortical neural recordings using penetrative electrodes. In this study, we propose a convex-shaped, PDMS-parylene hybrid multi-electrode array for long-term stable ECoG recording on the brain or the spinal cord. The electrode array consists of 10 gold recording sites which show impedance values between 50 and 70 kOhm at 1 kHz with a diameter of 100 μm. It is designed like octopus's leg to tightly adhere to the ellipsoidal brain. To assess its performance, epidural ECoG recordings were performed from the main olfactory bulb (MOB) of an anesthetized rat during odor stimulation. The odor-evoked response was shown with an increase of the power in the beta band.

The Anticonvulsant Effect of Transcutaneous AuricularVagus Nerve Stimulation is Associated with Balancingthe Autonomic Dysfunction in Rats

Objective: The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats. Methods: Healthy adult male Sprague-Dawley rats were anesthetized with an intraperitoneal injection of 10% urethane. Seizures were evoked by intraperitoneal injection of pentylenetetrazol (PTZ, 60 mg/kg). Femoral vein catheterization was performed for injection of sympathetic agonist and antagonists. Bipolar globe silver electrodes were utilized for epidural EEG recording. Three needles were inserted separately in subcutaneous muscles of left anterior limb, right anterior limb, and left hind limb to record ECG signals. ta-VNS was performed at auricular concha. Results: In comparison with preictal state, the mean heart rate (HR) increased slightly during epileptic seizures (P Conclusion: The results showed that autonomic dysfunction occurred in epileptic rats characterized by enhanced sympathetic nerve activity. Epileptic seizures in EEG traces decreased, HR decreased and HF increased after ta-VNS, which indicated that ta-VNS may suppress epileptic seizures via balancing the autonomic dysfunction. Abbreviations: SUDEP: sudden unexpected death; HRV: Heart rate variability; HR: heart rate; EEG: electroencephalograph; ECG: electrocardiograph; LF: low-frequency; HF: high-frequency; VNS: vagus nerve stimulation; ta-VNS: transcutaneous auricular vagus nerve stimulation; NTS: nucleus tractus solitaries; UCMS: unpredictable chronic mild stress. Received 7 July 2016; Accept 8 October 2016