Investigation of multi-site micro recordings of subthalamic nucleus neurons using machine learning MER with DBS in Parkinson`s – A simulation study

Multineural spikes were acquired with a multisite electrode placed in the hippocampus pyramidal cell layer of non-primate anesthetized snitch animals. If the impedance of each electrode-site is relatively low and the distance amongst electrode sites is appropriately miniatured, a spike generated by a neuron is parallelly recorded at multielectrode sites with different amplitudes. The covariance between the spike of the at each electrode-point and a template was computed as a damping-factor due to the volume conduction of the spike from the neuron to electrode-site. Computed damping factors were vectorized and analyzed by simple but elegant hierarchical-clustering using a multidimensional statistical-test. Since a cluster of damping vectors was shown to correspond to an antidromically identified neuron, spikes of distinct neurons are classified by suggesting to the scatterings of damping vectors. Errors in damping vector computing due to partially overlapping spikes were minimized by successively subtracting preceding spikes from raw data. Clustering errors due to complex-spike-bursts (i.e., spikes with variable-amplitudes) were prevented by detecting such bursts and using only the first spike of a burst for clustering.

The Role of Electrode-Site Placement in the Long-Term Stability of Intracortical Microstimulation

Intracortical microelectrodes are neuroprosthetic devices used in brain-machine interfaces to both record and stimulate neural activity in the brain. These technologies have been improved by advances in microfabrication, which have led to the creation of subcellular and high-density microelectrodes. The greater number of independent stimulation channels in these devices allows for improved neuromodulation selectivity, compared to single-site microelectrodes. Elements of electrode design such as electrode-site placement can influence the long-term performance of neuroprostheses. Previous studies have shown that electrode-sites placed on the edge of a planar microelectrode have greater chronic recording functionality than sites placed in the center. However, the effect of electrode-site placement on long-term intracortical microstimulation (ICMS) is still unknown. Here, we show that, in rats chronically implanted with custom-made planar silicon microelectrodes, electrode-sites on the tip of the device outperformed those on both the edge and center in terms of the effect per charge delivered, though there is still a slight advantage to using edge sites over center sites for ICMS. Longitudinal analysis of ICMS detection thresholds over a 16-week period revealed that while all sites followed a similar trend over time, the tip and edge sites consistently elicited the behavioral response with less charge compared to center sites. Furthermore, we quantified channel activity over time and found that edge sites remained more active than center sites over time, though the rate of decay of active sites for center and edge sites was comparable. Our results demonstrate that electrode-site placement plays an important role in the long-term stability of intracortical microstimulation and could be a potential factor to consider in the design of future intracortical electrodes.

Age-related differences in the error-related negativity and error positivity in children and adolescents are moderated by sample and methodological characteristics: A meta-analysis

The error-related negativity (ERN) and the error positivity (Pe) are electrophysiological components associated with error processing that are thought to exhibit distinctive developmental trajectories from childhood to adulthood. To investigate the age and age moderation effects on the ERN and the Pe strength during development, we conducted a preregistered three-level meta-analysis synthesizing 120 and 41 effect sizes across 18 group comparison studies and 19 correlational studies, respectively. The meta-analysis included studies with mean age range between 3.6 to 28.7 years for age-group comparisons and 6.1 to 18.7 years for age correlations. Results showed that age was associated with a more negative ERN (SMD = -.433, r = -.230). No statistically significant association between age and the Pe was found (SMD = .059, r = -.091), except for in a group comparison between younger and older adolescents. The age effects were not significantly moderated by whether a Flanker or a Go/No-Go task was used, whereas studies that used other tasks found larger age effects on the Pe. There was a moderating effect of electrode site, whereby the Fz and Cz electrode sites yielded stronger negative associations between age and the ERN and the Pe, respectively. The results confirm that the ERN and the Pe show differential development courses and suggest that sample and methodological characteristics influence the age effects, and lay the foundation for investigations of developmental patterns of error processing in relation to psychopathology and early genetic and environmental risk factors.

Photobiological Neuromodulation of Resting-State EEG and Steady-State Visual-Evoked Potentials by 40 Hz Violet Light Optical Stimulation in Healthy Individuals

Photobiological neuromodulation and its clinical application has been investigated in recent years. The response of the gamma-oscillation to human visual stimuli is known to be both burst and resonant in nature, and the coupling between alpha and gamma oscillations may play a functional role in visual processing. To date, there is no study that examined the effects of gamma-frequency violet light (VL) stimulation on human electroencephalography (EEG). In this study, we investigated the neurophysiological changes induced by light stimulation using EEG. The purpose of this study was to evaluate the specific effects of 40 Hz gamma-frequency VL stimulation on EEG activity by comparing the effects of white light (WL) with the same condition. Twenty healthy participants (10 females: 37.5 ± 14.3 years; 10 males: 38.0 ± 13.3 years) participated in this study and the following results were observed. First, when compared with the power spectrum density (PSD) of baseline EEG, 40 Hz-WL induced significant increase of PSD in theta band. Second, compared the PSDs between EEG with 40 Hz-VL and EEG with 40 Hz-WL, 40 Hz-VL induced significantly lower enhancement in delta and theta bands than 40 Hz-WL. Third, when focused on the occipital area, negative peak of VEP with 40 Hz-VL was smaller than that of 40 Hz-WL. Fourth, 40 Hz-VL induced an increase of alpha-gamma coupling during the VEP at the F5 electrode site as well as post-EEG at the C4 electrode site, compared with baseline EEG. Thus, the present study suggested that 40 Hz-VL stimulation may induce unique photobiological neuromodulations on human EEG activity.

Stomach Region Stimulated Determines Effects on Duodenal Motility in Rats

Gastric electrical stimulation (GES) is used clinically to promote proximal GI emptying and motility. In acute experiments, we measured duodenal motor responses elicited by GES applied at 141 randomly chosen electrode sites on the stomach serosal surface. Overnight-fasted (H2O available) anesthetized male rats (n = 81) received intermittent biphasic GES for 5 min (20s-on/40s-off cycles; I = 0.3mA; pw = 0.2ms; 10 Hz). A strain gauge on the serosal surface of the proximal duodenum of each animal was used to evaluate baseline motor activity and the effect of GES. Using ratios of time blocks compared to a 15-min pre-stimulation baseline, we evaluated the effects of the 5-min stimulation on concurrent activity; on the 10-min immediately after the stimulation, and on the 15-min period beginning with the onset of stimulation. We mapped the magnitude of the duodenal response (3 different motility indices) elicited from the 141 stomach sites. Post hoc electrode site maps associated with duodenal responses suggested three zones similar to the classic regions of forestomach, corpus and antrum. Maximal excitatory duodenal motor responses were elicited from forestomach sites, whereas inhibitory responses occurred with stimulation of the corpus. Moderate excitatory duodenal responses occurred with stimulation of the antrum. Complex, weak inhibitory/excitatory responses were produced by stimulation at boundaries between stomach regions. Patterns of GES efficacies coincided with distributions of previously mapped vagal afferents, suggesting that excitation of the duodenum is strongest when GES electrodes are situated over stomach concentrations of vagal intramuscular arrays, putative stretch receptors in the muscle wall.

Application of Referencing Techniques in EEG-Based Recordings of Contact Heat Evoked Potentials (CHEPS)

Evoked potentials in the amplitude-time spectrum of the electroencephalogram are commonly used to assess the extent of brain responses to stimulation with noxious contact heat. The magnitude of the N- and P-waves are used as a semi-objective measure of the response to the painful stimulus: the higher the magnitude, the more painful the stimulus has been perceived. The strength of the N-P-wave response is also largely dependent on the chosen reference electrode site. The goal of this study was to examine which reference technique excels both in practical and theoretical terms when analyzing noxious contact heat evoked potentials (CHEPS) in the amplitude-time spectrum. We recruited 21 subjects (10 male, 11 female, mean age of 55.79 years). We applied seven noxious contact heat stimuli using two temperatures, 51°C, and 54°C, to each subject. During EEG analysis, we aimed to identify the referencing technique which produces the highest N-wave and P-wave amplitudes with as little artifactual influence as possible. For this purpose, we applied the following six referencing techniques: mathematically linked A1/A2 (earlobes), average reference, REST, AFz, Pz, and mathematically linked PO7/PO8. We evaluated how these techniques impact the N-P amplitudes of CHEPS based on our data from healthy subjects. Considering all factors, we found that mathematically linked earlobes to be the ideal referencing site to use when displaying and evaluating CHEPS in the amplitude-time spectrum.

NMDA receptor ion channel activation detected in vivo with [18F]GE-179 PET after electrical stimulation of rat hippocampus

The positron emission tomography (PET) tracer [18F]GE-179 binds to the phencyclidine (PCP) site in the open N-methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [18F]GE-179 uptake by active NMDAR-ICs and that this can be blocked by the PCP antagonist S-ketamine, 15 rats had an electrode unilaterally implanted in their ventral hippocampus. Seven rats had no stimulation, five received pulsed 400 µA supra-threshold 60 Hz stimulation alone, and three received intravenous S-ketamine injection prior to stimulation. Six other rats were not implanted. Each rat had a 90 min [18F]GE-179 PET scan. Stimulated rats had simultaneous depth-EEG recordings of induced seizure activity. [18F]GE-179 uptake (volume of distribution, VT) was compared between hemispheres and between groups. Electrical stimulation induced a significant increase in [18F]GE-179 uptake at the electrode site compared to the contralateral hippocampus (mean 22% increase in VT, p = 0.0014) and to non-stimulated comparator groups. Rats injected with S-ketamine prior to stimulation maintained non-stimulated levels of [18F]GE-179 uptake during stimulation. In conclusion, PET visualisation of focal [18F]GE-179 uptake during electrically activated NMDAR-ICs and the demonstration of specificity for PCP sites by blockade with S-ketamine support the in vivo utility of [18F]GE-179 PET as a use-dependent marker of NMDAR-IC activation.

Differentiation of epileptic regions from voluntary high-gamma activation via interictal cross-frequency windowed power-power correlation

OBJECTIVEElectrocorticography is an indispensable tool in identifying the epileptogenic zone in the presurgical evaluation of many epilepsy patients. Traditional electrocorticographic features (spikes, ictal onset changes, and recently high-frequency oscillations [HFOs]) rely on the presence of transient features that occur within or near epileptogenic cortex. Here the authors report on a novel corticography feature of epileptogenic cortex—covariation of high-gamma and beta frequency band power profiles. Band-limited power was measured from each recording site based on native physiological signal differences without relying on clinical ictal or interictal epileptogenic features. In this preliminary analysis, frequency windowed power correlation appears to be a specific marker of the epileptogenic zone. The authors’ overall aim was to validate this observation with the location of the eventual resection and outcome.METHODSThe authors conducted a retrospective analysis of 13 adult patients who had undergone electrocorticography for surgical planning at their center. They quantified the correlation of high-gamma (70–200 Hz) and beta (12–18 Hz) band frequency power per electrode site during a cognitive task. They used a sliding window method to correlate the power of smoothed, Hilbert-transformed high-gamma and beta bands. They then compared positive and negative correlations between power in the high-gamma and beta bands in the setting of a hand versus a tongue motor task as well as within the resting state. Significant positive correlations were compared to surgically resected areas and outcomes based on reviewed records.RESULTSPositive high-gamma and beta correlations appeared to predict the area of eventual resection and, preliminarily, surgical outcome independent of spike detection. In general, patients with the best outcomes had well-localized positive correlations (high-gamma and beta activities) to areas of eventual resection, while those with poorer outcomes displayed more diffuse patterns.CONCLUSIONSData in this study suggest that positive high-gamma and beta correlations independent of any behavioral metric may have clinical applicability in surgical decision-making. Further studies are needed to evaluate the clinical potential of this methodology. Additional work is also needed to relate these results to other methods, such as HFO detection or connectivity with other cortical areas.

Hippocampal CA1 and CA3 neural recording in the human brain: validation of depth electrode placement through high-resolution imaging and electrophysiology

OBJECTIVEIntracranial human brain recordings typically utilize recording systems that do not distinguish individual neuron action potentials. In such cases, individual neurons are not identified by location within functional circuits. In this paper, verified localization of singly recorded hippocampal neurons within the CA3 and CA1 cell fields is demonstrated.METHODSMacro-micro depth electrodes were implanted in 23 human patients undergoing invasive monitoring for identification of epileptic seizure foci. Individual neurons were isolated and identified via extracellular action potential waveforms recorded via macro-micro depth electrodes localized within the hippocampus. A morphometric survey was performed using 3T MRI scans of hippocampi from the 23 implanted patients, as well as 46 normal (i.e., nonepileptic) patients and 26 patients with a history of epilepsy but no history of depth electrode placement, which provided average dimensions of the hippocampus along typical implantation tracks. Localization within CA3 and CA1 cell fields was tentatively assigned on the basis of recording electrode site, stereotactic positioning of the depth electrode in comparison with the morphometric survey, and postsurgical MRI. Cells were selected as candidate CA3 and CA1 principal neurons on the basis of waveform and firing rate characteristics and confirmed within the CA3-to-CA1 neural projection pathways via measures of functional connectivity.RESULTSCross-correlation analysis confirmed that nearly 80% of putative CA3-to-CA1 cell pairs exhibited positive correlations compatible with feed-forward connection between the cells, while only 2.6% exhibited feedback (inverse) connectivity. Even though synchronous and long-latency correlations were excluded, feed-forward correlation between CA3-CA1 pairs was identified in 1071 (26%) of 4070 total pairs, which favorably compares to reports of 20%–25% feed-forward CA3-CA1 correlation noted in published animal studies.CONCLUSIONSThis study demonstrates the ability to record neurons in vivo from specified regions and subfields of the human brain. As brain-machine interface and neural prosthetic research continues to expand, it is necessary to be able to identify recording and stimulation sites within neural circuits of interest.

Study on Situation Awareness under Different Mental Workloads

The aim of the present study was to examine the situation awareness (SA) changes under various mental workloads and to explore the sensitive physiological indicators to SA under this circumstance. Twenty-four participants were recruited to perform tasks under three kinds of mental workload based on the Multi Attribute Task Battery (MATB) Ⅱ platform. Performance measures, situational awareness global assessment technology (SAGAT), three dimensions situation awareness rating technology (3D-SART), eye movement and electroencephalograph (EEG) data were recorded. Results indicated that, the SAGAT scores and 3D-SART scores decreased significantly with the increasing of mental workload. In addition, the two scores both have a medium negative relationship with the National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores. The SAGAT scores have a medium positive relationship with the high alpha relative power at C4 electrode site. What's more, The SAGAT scores have a medium negative relationship with the Nearest Neighbor Index (NNI) under high mental workload condition. In conclusion, under different mental workload levels, (1) Mental workload has a medium negative relationship with SA. (2) NNI and high alpha relative power may be possible sensitive indicators to SA. The present study can provide a reference for designing the display and control interface in cockpit and for optimization of man-machine functional allocation.