Comparative analysis of sleep parameters and structures derived from wearable flexible electrode sleep patches and polysomnography in young adults.

Polysomnography (PSG) is the gold standard for clinical sleep monitoring, but its cost, discomfort, and limited suitability for continuous use present challenges. The flexible electrode sleep patch (FESP) emerges as an economically viable and patient-friendly solution, offering lightweight, simple operation, and self-applicable. Nevertheless, its utilization in young individuals remains uncertain. The objective of this study was to compare sleep data obtained by FESP and PSG in healthy young individuals and analyze agreement for sleep parameters and structure classification. Overnight monitoring with FESP and PSG recordings in 48 participants (mean age: 23 yr) was done. Correlation analysis, Bland-Altman plots, and Cohen's kappa coefficient assessed consistency. Sensitivity, specificity, and predictive values compared classification against PSG. FESP showed strong correlation and consistency with PSG for sleep monitoring. Bland-Altman plots indicated small errors and high consistency. Kappa values (0.70-0.84) suggested substantial agreement for sleep stage classification. Pearson correlation coefficient values for sleep stages (0.75-0.88) and sleep parameters (0.80-0.96) confirm that FESP has a strong application. Intraclass correlation coefficient yielded values between 0.65 and 0.97. In addition, FESP demonstrated an impressive accuracy range of 84.12-93.47% for sleep stage classification. The FESP also features a wearable self-test program with an error rate of no more than 8% for both deep sleep and wake. In young adults, FESP demonstrated reliable monitoring capabilities comparable to PSG. With its low cost and user-friendly design, FESP is a potential alternative for portable sleep assessment in clinical and research applications. Further studies involving larger populations are needed to validate its diagnostic potential.NEW & NOTEWORTHY By comparison with PSG, this study confirmed the reliability of an efficient, objective, low-cost, and noninvasive portable automatic sleep-monitoring device FESP, which provides effective information for long-term family sleep disorder diagnosis and sleep quality monitoring.

EEG Connectivity Diversity Differences between Children with Autism and Typically Developing Children: A Comparative Study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, and repetitive or stereotyped behaviors. Previous studies have reported altered brain connectivity in ASD children compared to typically developing children. In this study, we investigated the diversity of connectivity patterns between children with ASD and typically developing children using phase lag entropy (PLE), a measure of the variability of phase differences between two time series. We also developed a novel wavelet-based PLE method for the calculation of PLE at specific scales. Our findings indicated that the diversity of connectivity in ASD children was higher than that in typically developing children at Delta and Alpha frequency bands, both within brain regions and across hemispheric brain regions. These findings provide insight into the underlying neural mechanisms of ASD and suggest that PLE may be a useful tool for investigating brain connectivity in ASD.

Transcranial Direct Current Stimulation Modulates EEG Microstates in Low-Functioning Autism: A Pilot Study.

Autism spectrum disorder (ASD) is a heterogeneous disorder that affects several behavioral domains of neurodevelopment. Transcranial direct current stimulation (tDCS) is a new method that modulates motor and cognitive function and may have potential applications in ASD treatment. To identify its potential effects on ASD, differences in electroencephalogram (EEG) microstates were compared between children with typical development (n = 26) and those with ASD (n = 26). Furthermore, children with ASD were divided into a tDCS (experimental) and sham stimulation (control) group, and EEG microstates and Autism Behavior Checklist (ABC) scores before and after tDCS were compared. Microstates A, B, and D differed significantly between children with TD and those with ASD. In the experimental group, the scores of microstates A and C and ABC before tDCS differed from those after tDCS. Conversely, in the control group, neither the EEG microstates nor the ABC scores before the treatment period (sham stimulation) differed from those after the treatment period. This study indicates that tDCS may become a viable treatment for ASD.

Abnormalities of EEG Functional Connectivity and Effective Connectivity in Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that interferes with normal brain development. Brain connectivity may serve as a biomarker for ASD in this respect. This study enrolled a total of 179 children aged 3-10 years (90 typically developed (TD) and 89 with ASD). We used a weighted phase lag index and a directed transfer function to investigate the functional and effective connectivity in children with ASD and TD. Our findings indicated that patients with ASD had local hyper-connectivity of brain regions in functional connectivity and simultaneous significant decrease in effective connectivity across hemispheres. These connectivity abnormalities may help to find biomarkers of ASD.

Development of EEG connectivity from preschool to school-age children.

Introduction: Many studies have collected normative developmental EEG data to better understand brain function in early life and associated changes during both aging and pathology. Higher cognitive functions of the brain do not normally stem from the workings of a single brain region that works but, rather, on the interaction between different brain regions. In this regard studying the connectivity between brain regions is of great importance towards understanding higher cognitive functions and its underlying mechanisms. Methods: In this study, EEG data of children (N = 253; 3-10 years old; 113 females, 140 males) from pre-school to schoolage was collected, and the weighted phase delay index and directed transfer function method was used to find the electrophysiological indicators of both functional connectivity and effective connectivity. A general linear model was built between the indicators and age, and the change trend of electrophysiological indicators analyzed for age. Results: The results showed an age trend for the functional and effective connectivity of the brain of children. Discussion: The results are of importance in understanding normative brain development and in defining those conditions that deviate from typical growth trajectories.

Impact of repetitive transcranial magnetic stimulation on the directed connectivity of autism EEG signals: a pilot study.

To compare the differences in directed connectivity between typically developing (TD) and autism spectrum disorder (ASD) children and identify the potential effects of repetitive transcranial magnetic stimulation (rTMS) on brain connectivity and behavior of children with ASD; 26 TD children (18 males/8 females; the average age was 6.34 ± 0.45) and 30 ASD children (21 males/9 females; the average age was 6.42 ± 0.17) participated in the experiment. ASD children were divided randomly into an experimental group and a control group. The experimental group received 18 rTMS sessions (twice a week for nine weeks), whereas the control group received the same procedures with sham stimulation. Directed transfer function (DTF) was used to calculate the effective connectivity as a way of investigating differences between ASD and TD children while simultaneously evaluating the effectiveness of rTMS for ASD. The results illustrate that the DTF of TD children in the frontal lobe (Fp1, Fp2, F7, F8) and temporal lobe (T7, T8) is higher than that of ASD children in all frequency bands; however, the DTF of ASD children is higher than TD in the midline (Fz, Cz), central lobe (C3, C4), and parietal lobe (P3, P4). In the experimental group of ASD children, the effective connectivity decreased from O1 to T7 and from P7 to Fp1 in the alpha band and from Pz to T8 in the gamma band after stimulation. Significant changes in Autism Behavior Checklist (ABC) scores were also found in social behaviors. Effective connectivity derived from DTF distinguishes ASD from TD children. rTMS provides changes in connectivity and behavior, suggesting its potential use as a viable treatment option for ASD individuals.

The Significance of EEG Alpha Oscillation Spectral Power and Beta Oscillation Phase Synchronization for Diagnosing Probable Alzheimer Disease.

Alzheimer disease (AD) is the most common cause of dementia in geriatric population. At present, no effective treatments exist to reverse the progress of AD, however, early diagnosis and intervention might delay its progression. The search for biomarkers with good safety, repeatable detection, reliable sensitivity and community application is necessary for AD screening and early diagnosis and timely intervention. Electroencephalogram (EEG) examination is a non-invasive, quantitative, reproducible, and cost-effective technique which is suitable for screening large population for possible AD. The power spectrum, complexity and synchronization characteristics of EEG waveforms in AD patients have distinct deviation from normal elderly, indicating these EEG features can be a promising candidate biomarker of AD. However, current reported deviation results are inconsistent, possibly due to multiple factors such as diagnostic criteria, sample sizes and the use of different computational measures. In this study, we collected two neurological tests scores (MMSE and MoCA) and the resting-state EEG of 30 normal control elderly subjects (NC group) and 30 probable AD patients confirmed by Pittsburgh compound B positron emission tomography (PiB-PET) inspection (AD group). We calculated the power spectrum, spectral entropy and phase synchronization index features of these two groups' EEG at left/right frontal, temporal, central and occipital brain regions in 4 frequency bands: δ oscillation (1-4 Hz), θ oscillation (4-8 Hz), α oscillation (8-13 Hz), and ß oscillation (13-30 Hz). In most brain areas, we found that the AD group had significant differences compared to NC group: (1) decreased α oscillation power and increased θ oscillation power; (2) decreased spectral entropy in α oscillation and elevated spectral entropy in ß oscillation; and (3) decrease phase synchronization index in δ, θ, and ß oscillation. We also found that α oscillation spectral power and ß oscillation phase synchronization index correlated well with the MMSE/MoCA test scores in AD groups. Our study suggests that these two EEG features might be useful metrics for population screening of probable AD patients.

Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f.

GCaMP6f is among the most widely used genetically encoded calcium indicators for monitoring neuronal activity. Applications are at both the cellular and population levels. Here, we explore two important and under-explored issues. First, we have tested if GCaMP6f is sensitive enough for the detection of population activity with sparse firing, similar to the sensitivity of the local field potential (LFP). Second, we have tested if GCaMP6f is fast enough for the detection of fast network oscillations critical for the encoding and consolidation of memory. We have focused this study on the activity of the hippocampal network including sharp waves (SWs), carbachol-induced theta oscillations, and interictal-like spikes. We compare simultaneous LFP and optical GCaMP6f fluorescent recordings in Thy1-GCaMP6f mouse hippocampal slices. We observe that SWs produce a clear population GCaMP6f signal above noise with an average magnitude of 0.3% ΔF/F. This population signal is highly correlated with the LFP, albeit with a delay of 40.3 ms (SD 10.8 ms). The population GCaMP6f signal follows the LFP evoked by 20 Hz stimulation with high fidelity, while electrically evoked oscillations up to 40 Hz were detectable with reduced amplitude. GCaMP6f and LFP signals showed a large amplitude discrepancy. The amplitude of GCaMP6f fluorescence increased by a factor of 28.9 (SD 13.5) between spontaneous SWs and carbachol-induced theta bursts, while the LFP amplitude increased by a factor of 2.4 (SD 1.0). Our results suggest that GCaMP6f is a useful tool for applications commonly considered beyond the scope of genetically encoded calcium indicators. In particular, population GCaMP6f signals are sensitive enough for detecting synchronous network events with sparse firing and sub-threshold activity, as well as asynchronous events with only a nominal LFP. In addition, population GCaMP6f signals are fast enough for monitoring theta and beta oscillations (<25 Hz). Faster calcium indicators (e.g., GCaMP7) will further improve the frequency response for the detection of gamma band oscillations. The advantage of population optical over LFP recordings are that they are non-contact and free from stimulation artifacts. These features may be particularly useful for high-throughput recordings and applications sensitive to stimulus artifact, such as monitoring responses during continuous stimulation.

Localization of Epileptogenic Zone Based on Cortico-Cortical Evoked Potential (CCEP): A Feature Extraction and Graph Theory Approach.

OBJECTIVE: Epilepsy is a chronic brain disease, which is prone to relapse and affects individuals of all ages worldwide, particularly the very young and elderly. Up to one-third of these patients are medically intractable and require resection surgery. However, the outcomes of epilepsy surgery rely upon the clear identification of epileptogenic zone (EZ). The combination of cortico-cortical evoked potential (CCEP) and electrocorticography (ECoG) provides an opportunity to observe the connectivity of human brain network and more comprehensive information that may help the clinicians localize the epileptogenic focus more precisely. However, there is no standard analysis method in the clinical application of CCEPs, especially for the quantitative analysis of abnormal connectivity of epileptic networks. The aim of this paper was to present an approach on the batch processing of CCEPs and provide information relating to the localization of EZ for clinical study. METHODS: Eight medically intractable epilepsy patients were included in this study. Each patient was implanted with subdural grid electrodes and electrical stimulations were applied directly to their cortex to induce CCEPs. After signal preprocessing, we constructed three effective brain networks at different spatial scales for each patient, regarding the amplitudes of CCEPs as the connection weights. Graph theory was then applied to analyze the brain network topology of epileptic patients, and the topological metrics of EZ and non-EZ (NEZ) were compared. RESULTS: The effective connectivity network reconstructed from CCEPs was asymmetric, both the number and the amplitudes of effective CCEPs decreased with increasing distance between stimulating and recording sites. Besides, the distribution of CCEP responses was associated with the locations of EZ which tended to have higher degree centrality (DC) and nodal shortest path length (NLP) than NEZ. CONCLUSION: Our results indicated that the brain networks of epileptics were asymmetric and mainly composed of short-distance connections. The DC and NLP were highly consistent to the distribution of the EZ, and these topological parameters have great potential to be readily applied to the clinical localization of the EZ.

Automated Detection of High-Frequency Oscillations in Epilepsy Based on a Convolutional Neural Network.

Epilepsy is one of the most common chronic neurological diseases. High-frequency oscillations (HFOs) have emerged as promising biomarkers for the epileptogenic zone. However, visual marking of HFOs is a time-consuming and laborious process. Several automated techniques have been proposed to detect HFOs, yet these are still far from being suitable for application in a clinical setting. Here, ripples and fast ripples from intracranial electroencephalograms were detected in six patients with intractable epilepsy using a convolutional neural network (CNN) method. This approach proved more accurate than using four other HFO detectors integrated in RIPPLELAB, providing a higher sensitivity (77.04% for ripples and 83.23% for fast ripples) and specificity (72.27% for ripples and 79.36% for fast ripples) for HFO detection. Furthermore, for one patient, the Cohen's kappa coefficients comparing automated detection and visual analysis results were 0.541 for ripples and 0.777 for fast ripples. Hence, our automated detector was capable of reliable estimates of ripples and fast ripples with higher sensitivity and specificity than four other HFO detectors. Our detector may be used to assist clinicians in locating epileptogenic zone in the future.

Pacing Hippocampal Sharp-Wave Ripples With Weak Electric Stimulation.

Sharp-wave ripples (SWRs) are spontaneous neuronal population events that occur in the hippocampus during sleep and quiet restfulness, and are thought to play a critical role in the consolidation of episodic memory. SWRs occur at a rate of 30-200 events per minute. Their overall abundance may, however, be reduced with aging and neurodegenerative disease. Here we report that the abundance of SWR within murine hippocampal slices can be increased by paced administration of a weak electrical stimulus, especially when the spontaneously occurring rate is low or compromised. Resultant SWRs have large variations in amplitude and ripple patterns, which are morphologically indistinguishable from those of spontaneous SWRs, despite identical stimulus parameters which presumably activate the same CA3 neurons surrounding the electrode. The stimulus intensity for reliably pacing SWRs is weaker than that required for inducing detectable evoked field potentials in CA1. Moreover, repetitive ~1 Hz stimuli with low intensity can reliably evoke thousands of SWRs without detectable LTD or "habituation." Our results suggest that weak stimuli may facilitate the spontaneous emergence of SWRs without significantly altering their characteristics. Pacing SWRs with weak electric stimuli could potentially be useful for restoring their abundance in the damaged hippocampus.

'Blue' voltage-sensitive dyes for studying spatiotemporal dynamics in the brain: visualizing cortical waves.

Among many distinct contributions made by Amiram Grinvald's group, the "Blue dyes" is a special gift for visualizing cortical population neuronal activity. The excitation wavelength of blue dyes has minimal overlap with the absorption of hemoglobin, and hence has minimal pulsation artifacts. This advantage leads to high signal-to-noise ratio optical recordings of cortical activity, with sensitivity as good as that of local field potential recordings. High sensitivity imaging allows for recording of spontaneous and evoked activity in single trials without spatial or temporal averaging, and has benefitted many scientists in their research projects. Single trial recording is particularly important for studying the cortex, because spontaneous and ongoing activities interact with sensory evoked events, creating rich dynamics in the wave patterns. Signal averaging in space and time would diminish the dynamic components in the patterns. Here, we discuss how the blue dyes help to achieve high-sensitivity voltage-sensitive dye imaging of spontaneous and evoked cortical activities. Spontaneous cortical activity has a constantly changing spatial pattern and temporal frequency, making it impossible to average in space and time. Amiran Grinvald's invention of blue dyes made it possible to examine the spatiotemporal patterns of cortical dynamics, about 15 years before the first useful genetically coded voltage proteins became available.

Emergence of dominant initiation sites for interictal spikes in rat neocortex.

Neuronal populations with unbalanced inhibition can generate interictal spikes (ISs), where each IS starts from a small initiation site and then spreads activation across a larger area. We used in vivo voltage-sensitive dye imaging to map the initiation site of ISs in rat visual cortex disinhibited by epidural application of bicuculline methiodide. Immediately after the application of bicuculline, the IS initiation sites were widely distributed over the entire disinhibited area. After ∼ 10 min, a small number of sites became "dominant" and initiated the majority of the ISs throughout the course of imaging. Such domination also occurred in cortical slices, which lack long-range connections between the cortex and subcortical structures. This domination of IS initiation sites may allow timing-related plasticity mechanisms to provide a spatial organization where connections projecting outward from the dominant initiation site become strengthened. Understanding the spatiotemporal organization of IS initiation sites may contribute to our understanding of epileptogenesis in its very early stages, because a dominant IS initiation site with strengthened outward connectivity may ultimately develop into a seizure focus.

Monitoring Population Membrane Potential Signals from Neocortex.

Voltage-sensitive dyes (VSDs) and optical imaging are useful tools for studying spatiotemporal patterns of population neuronal activity in cortex. Because fast VSDs respond to membrane potential changes with microsecond temporal resolution, these are better suited than calcium indicators for recording rapid neural signals. Here we describe methods for using a 464 element photodiode array and fast VSDs to record signals ranging from large scale network activity in brain slices and in vivo mammalian preparations with sensitivity comparable to local field potential (LFP) recordings. With careful control of dye bleaching and phototoxicity, long recording times can be achieved. Absorption dyes have less photo-toxicity than fluorescent dyes. In brain slices, the total recording time in each slice can be 1,000-2,000 s, which can be divided into hundreds of short recording trials over several hours. In intact brains when fluorescent dyes are used, reduced light intensity can also increase recording time. In this chapter, we will discuss technical details for the methods to achieve reliable VSD imaging with high sensitivity and long recording time.