Quantifying Sharpness and Nonlinearity in Neonatal Seizure Dynamics.

The integration of multiple electrophysiological biomarkers is crucial for monitoring neonatal seizure dynamics. The present study aimed to characterize the temporal dynamics of neonatal seizures by analyzing intrinsic waveforms of epileptic electroencephalogram (EEG) signals. We proposed a complementary set of methods considering envelope power, focal sharpness changes, and nonlinear patterns of EEG signals of 79 neonates with seizures. Features derived from EEG signals were used as input to the machine learning classifier. All three characteristics were significantly elevated during seizure events, as agreed upon by all viewers (P < 0.0001). Envelope power was elevated in the entire seizure period, and the degree of nonlinearity rose at the termination of a seizure event. Epileptic sharpness effectively characterizes an entire seizure event, complementing the role of envelope power in identifying its onset. However, the degree of nonlinearity showed superior discriminability for the termination of a seizure event. The proposed computational methods for intrinsic sharp or nonlinear EEG patterns evolving during neonatal seizure could share some features with envelope power. Current findings may be helpful in developing strategies to improve neonatal seizure monitoring.

A pilot study on a patient with refractory headache: Personalized deep brain stimulation through stereoelectroencephalography.

The integration of stereoelectroencephalography with therapeutic deep brain stimulation (DBS) holds immense promise as a viable approach for precise treatment of refractory disorders, yet it has not been explored in the domain of headache or pain management. Here, we implanted 14 electrodes in a patient with refractory migraine and integrated clinical assessment and electrophysiological data to investigate personalized targets for refractory headache treatment. Using statistical analyses and cross-validated machine-learning models, we identified high-frequency oscillations in the right nucleus accumbens as a critical headache-related biomarker. Through a systematic bipolar stimulation approach and blinded sham-controlled survey, combined with real-time electrophysiological data, we successfully identified the left dorsal anterior cingulate cortex as the optimal target for the best potential treatment. In this pilot study, the concept of the herein-proposed data-driven approach to optimizing precise and personalized treatment strategies for DBS may create a new frontier in the field of refractory headache and even pain disorders.

A Novel Sleep Staging Method Based on EEG and ECG Multimodal Features Combination.

Accurate sleep staging evaluates the quality of sleep, supporting the clinical diagnosis and intervention of sleep disorders and related diseases. Although previous attempts to classify sleep stages have achieved high classification performance, little attention has been paid to integrating the rich information in brain and heart dynamics during sleep for sleep staging. In this study, we propose a generalized EEG and ECG multimodal feature combination to classify sleep stages with high efficiency and accuracy. Briefly, a hybrid features combination in terms of multiscale entropy and intrinsic mode function are used to reflect nonlinear dynamics in multichannel EEGs, along with heart rate variability measures over time/frequency domains, and sample entropy across scales are applied for ECGs. For both the max-relevance and min-redundancy method and principal component analysis were used for dimensionality reduction. The selected features were classified by four traditional machine learning classifiers. Macro-F1 score, macro-geometric mean, and Cohen kappa value are adopted to evaluate the classification performance of each class in an imbalanced dataset. Experimental results show that EEG features contribute more to wake stage classification while ECG features contribute more to deep sleep stages. The proposed combination achieves the highest accuracy of 84.3% and the highest kappa value of 0.794 on the support vector machine in the ISRUC-S3 dataset, suggesting the proposed multimodal features combination is promising in accuracy and efficiency compared to other state-of-the-art methods.

Brain Complexity Predicts Response to Adrenocorticotropic Hormone in Infantile Epileptic Spasms Syndrome: A Retrospective Study.

INTRODUCTION: Infantile epileptic spasms syndrome (IESS) is an age-specific and severe epileptic encephalopathy. Although adrenocorticotropic hormone (ACTH) is currently considered the preferred first-line treatment, it is not always effective and may cause side effects. Therefore, seeking a reliable biomarker to predict the treatment response could benefit clinicians in modifying treatment options. METHODS: In this study, the complexities of electroencephalogram (EEG) recordings from 15 control subjects and 40 patients with IESS before and after ACTH therapy were retrospectively reviewed using multiscale entropy (MSE). These 40 patients were divided into responders and nonresponders according to their responses to ACTH. RESULTS: The EEG complexities of the patients with IESS were significantly lower than those of the healthy controls. A favorable response to treatment showed increasing complexity in the γ band but exhibited a reduction in the ß/α-frequency band, and again significantly elevated in the δ band, wherein the latter was prominent in the parieto-occipital regions in particular. Greater reduction in complexity was significantly linked with poorer prognosis in general. Occipital EEG complexities in the γ band revealed optimized performance in recognizing response to the treatment, corresponding to the area under the receiver operating characteristic curves as 0.8621, while complexities of the δ band served as a fair predictor of unfavorable outcomes globally. CONCLUSION: We suggest that optimizing frequency-specific complexities over critical brain regions may be a promising strategy to facilitate predicting treatment response in IESS.

Cross-Frequency Coupling and Intelligent Neuromodulation.

Cross-frequency coupling (CFC) reflects (nonlinear) interactions between signals of different frequencies. Evidence from both patient and healthy participant studies suggests that CFC plays an essential role in neuronal computation, interregional interaction, and disease pathophysiology. The present review discusses methodological advances and challenges in the computation of CFC with particular emphasis on potential solutions to spurious coupling, inferring intrinsic rhythms in a targeted frequency band, and causal interferences. We specifically focus on the literature exploring CFC in the context of cognition/memory tasks, sleep, and neurological disorders, such as Alzheimer's disease, epilepsy, and Parkinson's disease. Furthermore, we highlight the implication of CFC in the context and for the optimization of invasive and noninvasive neuromodulation and rehabilitation. Mainly, CFC could support advancing the understanding of the neurophysiology of cognition and motor control, serve as a biomarker for disease symptoms, and leverage the optimization of therapeutic interventions, e.g., closed-loop brain stimulation. Despite the evident advantages of CFC as an investigative and translational tool in neuroscience, further methodological improvements are required to facilitate practical and correct use in cyborg and bionic systems in the field.

Frequency Nesting Interactions in the Subthalamic Nucleus Correlate With the Step Phases for Parkinson's Disease.

Gait disturbance in Parkinson's disease (PD) can be ameliorated by sound stimulation. Given that excessive ß synchronization in basal ganglia is linked to motor impairment in PD, whether the frequency nesting interactions are associated with the gait problem is far from clear. To this end, the masking phase-amplitude coupling (PAC) method was proposed to overcome the trade-off between intrinsic nonlinearity/non-stationarity and demand for predetermined frequencies, normally extracted by the filter. In this study, we analyzed LFPs recorded from 13 patients (one female) with PD during stepping with bilateral deep brain electrodes implanted in the subthalamic nucleus (STN). We found that not only high-frequency oscillation (100-300 Hz) was modulated by ß (13-30 Hz) but also ß and γ amplitude were modulated by their low-frequency components in δ/θ/α and δ/θ/α/ß bands. These PAC values were suppressed by sound stimulation, along with an improvement in gait. We also showed that gait-related high-ß (Hß) modulation in the STN was sensitive to auditory cues, and Hß gait-phase modulation increased with a metronome. Meanwhile, phase-locking values (PLVs) across all frequencies were significantly suppressed around contralateral heel strikes, manifesting the contralateral step as a critical gait phase in gait initiation for PD. Only the PLVs around contralateral steps were sensitive to auditory cues. Our results support masking PAC as an effective method in exploring frequency nesting interactions in LFPs and reveal the linkages between sound stimulation and couplings related to gait phases in the STN. These findings raise the possibility that nesting interactions in the STN work as feasible biomarkers in alleviating gait disorders.

A Novel Framework in Quantifying Oscillatory Coupling to Gait Disturbance in Parkinson's Disease.

Phase-amplitude coupling (PAC) based on the uniform phase empirical mode decomposition (UPEMD) is proposed to improve the accuracy of PAC assessment. The framework is applied to investigate the mechanism and improvement measure of gait disturbance for Parkinson's disease (PD). Hß modulation is suppressed at the time of contralateral heel strikes and rebounds when the contralateral foot rests on the ground and the ipsilateral foot is raised. Prominent PACs exist between δ and Lß/Hß activities. Auditory cue improves the gait; meanwhile, it enhances the Hß modulation, and suppresses the δ-Lß/Hß PACs, which may rebound toward the before-cue stage afterward. Our findings suggest the proposed UPEMD-PAC is a useful framework in quantifying PAC with pre-determined frequencies, whereas the δ-Lß/Hß PACs in the subthalamic nucleus serve as potential biomarkers for gait disturbance in PD. Clinical Relevance- This manifests the efficacy of auditory cues on gait disturbance. The proposed framework may be useful in diagnosing the severity of motor impairment.

Integration of multiscale entropy and BASED scale of electroencephalography after adrenocorticotropic hormone therapy predict relapse of infantile spasms.

BACKGROUND: Even though adrenocorticotropic hormone (ACTH) demonstrated powerful efficacy in the initially successful treatment of infantile spasms (IS), nearly half of patients have experienced a relapse. We sought to investigate whether features of electroencephalogram (EEG) predict relapse in those IS patients without structural brain abnormalities. METHODS: We retrospectively reviewed data from children with IS who achieved initial response after ACTH treatment, along with EEG recorded within the last two days of treatment. The recurrence of epileptic spasms following treatment was tracked for 12 months. Subjects were categorized as either non-relapse or relapse groups. General clinical and EEG recordings were collected, burden of amplitudes and epileptiform discharges (BASED) score and multiscale entropy (MSE) were carefully explored for cross-group comparisons. RESULTS: Forty-one patients were enrolled in the study, of which 26 (63.4%) experienced a relapse. The BASED score was significantly higher in the relapse group. MSE in the non-relapse group was significantly lower than the relapse group in the γ band but higher in the lower frequency range (δ, θ, α). Sensitivity and specificity were 85.71% and 92.31%, respectively, when combining MSE in the δ/γ frequency of the occipital region, plus BASED score were used to distinguish relapse from non-relapse groups. CONCLUSIONS: BASED score and MSE of EEG after ACTH treatment could be used to predict relapse for IS patients without brain structural abnormalities. Patients with BASED score ≥ 3, MSE increased in higher frequency, and decreased in lower frequency had a high risk of relapse.

Assessing Risk for Relapse among Children with Infantile Spasms Using the Based Score after ACTH Treatment: A Retrospective Study.

INTRODUCTION: Even though adrenocorticotropic hormone (ACTH) demonstrated powerful efficacy in the initially successful treatment of infantile spasms (IS), nearly one-half of patients whose spasms were once suppressed experienced relapse. There is currently no validated method for the prediction of the risk of relapse. The Burden of Amplitudes and Epileptiform Discharges (BASED) score is an electroencephalogram (EEG) grading scale for children with infantile spasms. We sought to determine whether an association exists between the BASED score after ACTH treatment and relapse after initial response with ACTH. METHODS: Children with IS who achieved initial response after ACTH treatment were selected as the study subjects. Those who experienced relapse within 12 months after ACTH treatment were categorized as the relapse group, and those who did not were categorized as the non-relapse group. Their general clinical data and EEG data (using BASED scoring) after ACTH treatment were collected, and compared between groups. Cox proportional hazards models were fit to determine factors associated with relapse. RESULTS: A total of 64 children with IS were enrolled in the study, of which 37 (57.8%) experienced a relapse, and the median duration after ACTH treatment was 3 (1.5, 6) months. The BASED score was significantly higher in the relapse group than in the non-relapse group. Cox modeling demonstrated that BASED score was independently associated with relapse. The patients with a score greater than or equal to 3 showed a high rate (89.3%) of relapse. The relapse group had stronger, more stable EEG functional networks than the non-relapse group, and there were obvious correlations between BASED score and functional connectivity. CONCLUSION: This study suggests the BASED score after ACTH treatment has potential value as a predictor for relapse after initial response. Children with IS who have a BASED score greater than or equal to 3 after the initial response of ACTH carry a high risk of relapse within 1 year.