Prognostic value of quantitative EEG in early hours of life for neonatal encephalopathy and neurodevelopmental outcomes.

BACKGROUND: The ability to determine severity of encephalopathy is crucial for early neuroprotective therapies and for predicting neurodevelopmental outcome. The objective of this study was to assess a novel brain state of newborn (BSN) trend to distinguish newborns with presence of hypoxic ischemic encephalopathy (HIE) within hours after birth and predict neurodevelopmental outcomes at 2 years of age. METHOD: This is a prospective cohort study of newborns at 36 weeks' gestation or later with and without HIE at birth. The Total Sanart Score (TSS) was calculated based on a modified Sarnat exam within 6 h of life. BSN was calculated from electroencephalogram (EEG) measurements initiated after birth. The primary outcome at 2 year of age was a diagnosis of death or disability using the Bayley Scales of Infant Development III. RESULTS: BSN differentiated between normal and abnormal neurodevelopmental outcomes throughout the entire recording period from 6 h of life. Additionally, infants with lower BSN values had higher odds of neurodevelopmental impairment and HIE. BSN distinguished between normal (n = 86) and HIE (n = 46) and showed a significant correlation with the concomitant TSS. CONCLUSION: BSN is a sensitive real-time marker for monitoring dynamic progression of encephalopathy and predicting neurodevelopmental impairment. IMPACT: This is a prospective cohort study to investigate the ability of brain state of newborn (BSN) trend to predict neurodevelopmental outcome within the first day of life and identify severity of encephalopathy. BSN predicts neurodevelopmental outcomes at 2 years of age and the severity of encephalopathy severity. It also correlates with the Total Sarnat Score from the modified Sarnat exam. BSN could serve as a promising bedside trend aiding in accurate assessment and identification of newborns who may benefit from additional neuroprotection therapies.

Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation.

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the prefrontal cortex (PFC). Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

Simultaneous MEG and EEG source imaging of electrophysiological activity in response to acute transcranial photobiomodulation.

Introduction: Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique that improves human cognition. The effects of tPBM of the right forehead on neurophysiological activity have been previously investigated using EEG in sensor space. However, the spatial resolution of these studies is limited. Magnetoencephalography (MEG) is known to facilitate a higher spatial resolution of brain source images. This study aimed to image post-tPBM effects in brain space based on both MEG and EEG measurements across the entire human brain. Methods: MEG and EEG scans were concurrently acquired for 6 min before and after 8-min of tPBM delivered using a 1,064-nm laser on the right forehead of 25 healthy participants. Group-level changes in both the MEG and EEG power spectral density with respect to the baseline (pre-tPBM) were quantified and averaged within each frequency band in the sensor space. Constrained modeling was used to generate MEG and EEG source images of post-tPBM, followed by cluster-based permutation analysis for family wise error correction (p < 0.05). Results: The 8-min tPBM enabled significant increases in alpha (8-12 Hz) and beta (13-30 Hz) powers across multiple cortical regions, as confirmed by MEG and EEG source images. Moreover, tPBM-enhanced oscillations in the beta band were located not only near the stimulation site but also in remote cerebral regions, including the frontal, parietal, and occipital regions, particularly on the ipsilateral side. Discussion: MEG and EEG results shown in this study demonstrated that tPBM modulates neurophysiological activity locally and in distant cortical areas. The EEG topographies reported in this study were consistent with previous observations. This study is the first to present MEG and EEG evidence of the electrophysiological effects of tPBM in the brain space, supporting the potential utility of tPBM in treating neurological diseases through the modulation of brain oscillations.

Neurovascular coupling in the attention during visual working memory processes.

Focusing attention in visual working memory (vWM) depends on the ability to filter distractors and expand the scope of targets. Although many properties of attention processes in vWM have been well documented, it remains unclear how the mechanisms of neurovascular coupling (NVC) function during attention processes in vWM. Here, we show simultaneous multimodal data that reveal the similar temporal and spatial features of attention processes during vWM. These similarities lead to common NVC outcomes across individuals. When filtering out distractors, the electroencephalography (EEG)-informed NVC displayed broader engagement across the frontoparietal network. A negative correlation may exist between behavioral metrics and EEG-informed NVC strength related to attention control. On a dynamic basis, NVC features exhibited higher discriminatory power in predicting behavior than other features alone. These results underscore how multimodal approaches can advance our understanding of the role of attention in vWM, and how NVC fluctuations are associated with actual behavior.

Temporal and spectral analyses of EEG microstate reveals neural effects of transcranial photobiomodulation on the resting brain.

Introduction: The quantification of electroencephalography (EEG) microstates is an effective method for analyzing synchronous neural firing and assessing the temporal dynamics of the resting state of the human brain. Transcranial photobiomodulation (tPBM) is a safe and effective modality to improve human cognition. However, it is unclear how prefrontal tPBM neuromodulates EEG microstates both temporally and spectrally. Methods: 64-channel EEG was recorded from 45 healthy subjects in both 8-min active and sham tPBM sessions, using a 1064-nm laser applied to the right forehead of the subjects. After EEG data preprocessing, time-domain EEG microstate analysis was performed to obtain four microstate classes for both tPBM and sham sessions throughout the pre-, during-, and post-stimulation periods, followed by extraction of the respective microstate parameters. Moreover, frequency-domain analysis was performed by combining multivariate empirical mode decomposition with the Hilbert-Huang transform. Results: Statistical analyses revealed that tPBM resulted in (1) a significant increase in the occurrence of microstates A and D and a significant decrease in the contribution of microstate C, (2) a substantial increase in the transition probabilities between microstates A and D, and (3) a substantial increase in the alpha power of microstate D. Discussion: These findings confirm the neurophysiological effects of tPBM on EEG microstates of the resting brain, particularly in class D, which represents brain activation across the frontal and parietal regions. This study helps to better understand tPBM-induced dynamic alterations in EEG microstates that may be linked to the tPBM mechanism of action for the enhancement of human cognition.

Unilateral Mitochondrial-Hemodynamic Coupling and Bilateral Connectivity in the Prefrontal Cortices of Young and Older Healthy Adults.

A recent study demonstrated that noninvasive measurements of cortical hemodynamics and metabolism in the resting human prefrontal cortex can facilitate quantitative metrics of unilateral mitochondrial-hemodynamic coupling and bilateral connectivity in infraslow oscillation frequencies in young adults. The infraslow oscillation includes three distinct vasomotions with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. The goal of this study was to prove the hypothesis that there are significant differences between young and older adults in the unilateral coupling (uCOP) and bilateral connectivity (bCON) in the prefrontal cortex. Accordingly, we performed measurements from 24 older adults (67.2 ± 5.9 years of age) using the same two-channel broadband near-infrared spectroscopy (bbNIRS) setup and resting-state experimental protocol as those in the recent study. After quantification of uCOP and bCON in three E/N/M frequencies and statistical analysis, we demonstrated that older adults had significantly weaker bilateral hemodynamic connectivity but significantly stronger bilateral metabolic connectivity than young adults in the M band. Furthermore, older adults exhibited significantly stronger unilateral coupling on both prefrontal sides in all E/N/M bands, particularly with a very large effect size in the M band (>1.9). These age-related results clearly support our hypothesis and were well interpreted following neurophysiological principles. The key finding of this paper is that the neurophysiological metrics of uCOP and bCON are highly associated with age and may have the potential to become meaningful features for human brain health and be translatable for future clinical applications, such as the early detection of Alzheimer's disease.

Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation.

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the PFC. Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

Repeated Transcranial Photobiomodulation with Light-Emitting Diodes Improves Psychomotor Vigilance and EEG Networks of the Human Brain.

Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. The repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improves human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in a 4-week study. Topographical maps of the EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data processing framework combining the group's singular value decomposition (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of the PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during a 10 min LED-tPBM while the participants performed the PVT task. We also found that the theta, beta, and gamma EEG powers significantly increased overall after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that a 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.

Evaluation of neurovascular coupling during neuroprotective therapies: A single site HEAL ancillary study.

BACKGROUND: There is a critical need for development of physiological biomarkers in infants with birth asphyxia to identify the physiologic response to therapies in real time. This is an ancillary single site study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (Wu et al., 2022 [1]) to measure neurovascular coupling (NVC) non-invasively during an ongoing blinded randomized trial. METHODS: Neonates who randomized in the HEAL enrolled at a single-center Level III Neonatal Intensive Care Unit were recruited between 2017 and 2019. Neurodevelopmental impairment was blinded and defined as any of the following: cognitive score <90 on Bayley Scales of Infant Toddler Development, third edition (BSID-III), Gross Motor Function Classification Score (GMFCS) ≥1. RESULTS: All twenty-seven neonates enrolled in HEAL were recruited and 3 died before complete recording. The rank-based analysis of covariance models demonstrated lack of difference in NVC between the two groups (Epo versus Placebo) that was consistent with the observed lack of effect on neurodevelopmental outcomes. CONCLUSION: We demonstrate no difference in neurovascular coupling after Epo administration. These findings are consistent with overall negative trial results. Physiological biomarkers can help elucidate mechanisms of neuroprotective therapies in real time in future trials.

Site-specific effects of 800- and 850-nm forehead transcranial photobiomodulation on prefrontal bilateral connectivity and unilateral coupling in young adults.

Significance: Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulation method that facilitates the improvement of human cognition. However, limited information is available in the literature on the wavelength- and site-specific effects of prefrontal tPBM. Moreover, 2-channel broadband near-infrared spectroscopy (2-bbNIRS) is a new approach for quantifying infra-slow oscillations (ISO; 0.005 to 0.2 Hz) of neurophysiological networks in the resting human brain in vivo. Aim: We aim to prove the hypothesis that the hemodynamic and metabolic activities of the resting prefrontal cortex are significantly modulated by tPBM and that the modulation is wavelength- and site-specific in different ISO bands. Approach: Noninvasive 8-min tPBM with an 800- or 850-nm laser or sham was delivered to either side of the forehead of 26 healthy young adults. A 2-bbNIRS unit was used to record prefrontal ISO activity 7 min before and after tPBM/sham. The measured time series were analyzed in the frequency domain to determine the coherence of hemodynamic and metabolic activities at each of the three ISO frequency bands. Sham-controlled coherence values represent tPBM-induced effects on neurophysiological networks. Results: Prefrontal tPBM by either wavelength and on either lateral side of the forehead (1) increased ipsilateral metabolic-hemodynamic coupling in the endogenic band and (2) desynchronized bilateral activity of metabolism in the neurogenic band and vascular smooth-muscle hemodynamics in the myogenic band. Site-specific effects of laser tPBM were also observed with significant enhancement of bilateral hemodynamic and metabolic connectivity by the right prefrontal 800-nm tPBM. Conclusions: Prefrontal tPBM can significantly modulate neurophysiological networks bilaterally and coupling unilaterally in the human prefrontal cortex. Such modulation effects are site- and wavelength-specific for each ISO band.

Recent Mechanisms of Neurodegeneration and Photobiomodulation in the Context of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease and the world's primary cause of dementia, a condition characterized by significant progressive declines in memory and intellectual capacities. While dementia is the main symptom of Alzheimer's, the disease presents with many other debilitating symptoms, and currently, there is no known treatment exists to stop its irreversible progression or cure the disease. Photobiomodulation has emerged as a very promising treatment for improving brain function, using light in the range from red to the near-infrared spectrum depending on the application, tissue penetration, and density of the target area. The goal of this comprehensive review is to discuss the most recent achievements in and mechanisms of AD pathogenesis with respect to neurodegeneration. It also provides an overview of the mechanisms of photobiomodulation associated with AD pathology and the benefits of transcranial near-infrared light treatment as a potential therapeutic solution. This review also discusses the older reports and hypotheses associated with the development of AD, as well as some other approved AD drugs.

Revisiting Transcranial Light Stimulation as a Stroke Therapeutic-Hurdles and Opportunities.

Near-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. While the NEST trials failed to show the efficacy of light therapy in human stroke patients, there are many lingering questions and lessons that can be learned. In this review, we summarize the putative mechanism of light stimulation in the setting of stroke, highlight barriers, and challenges during the translational process, and evaluate light stimulation parameters, dosages and safety issues, choice of outcomes, effect size, and patient selection criteria. In the end, we propose potential future opportunities with transcranial light stimulation as a cerebroprotective or restorative tool for future stroke treatment.

Transcranial photobiomodulation enhances visual working memory capacity in humans.

Transcranial photobiomodulation (tPBM) is a safe and noninvasive intervention that has shown promise for improving cognitive performance. Whether tPBM can modulate brain activity and thereby enhance working memory (WM) capacity in humans remains unclear. In this study, we found that 1064-nm tPBM applied to the right prefrontal cortex (PFC) improves visual working memory capacity and increases occipitoparietal contralateral delay activity (CDA). The CDA set-size effect during retention mediated the effect between the 1064-nm tPBM and subsequent WM capacity. The behavioral benefits and the corresponding changes in the CDA set-size effect were absent with tPBM at a wavelength of 852 nm or with stimulation of the left PFC. Our findings provide converging evidence that 1064-nm tPBM applied to the right PFC can improve WM capacity.

Frequency-specific electrogastrography as a non-invasive tool to measure gastrointestinal maturity in preterm infants.

Enteral feeding is challenging in preterm infants because of gastrointestinal (GI) immaturity. Electrogastrography (EGG) is a non-invasive technology that measures gastric myoelectrical activity and can be utilized to measure changes that occur with maturation at different gestational ages (GA). Three gastric rhythms (GR) exist between 0.5-9 cycles per minute (cpm), namely, bradygastria (0.5 ≤ GR < 2 cpm), normogastria (2 ≤ GR < 4 cpm), and tachygastria (4 ≤ GR < 9 cpm). We aimed to characterize EGG-derived parameters for different GA by quantifying (1) power spectral density (PSD) and its spectral means at three GR bands (i.e., mPSDGR) and (2) the percent (%) time spent in each band. Data analyzed was from a longitudinal cohort of preterm infants (n = 51) born at early, mid, and term GA of < 29, 29-33, and ≥ 37 weeks, respectively. Weekly EGG monitoring was performed until 40 weeks' postmenstrual age or discharge. Pre-, during, and post-feed data were analyzed for mPSDGR at each GR band. Also, % bradygastria, % normogastria, and % tachygastria were calculated by continuous wavelet transform analysis. Results showed (1) mPSD values in normogastria and tachygastria during feeding increased with advancing GA, and (2) % normogastria increased with advancing GA regardless of GR ranges, suggesting EGG may measure GI maturity in preterm infants.

Neuromodulation of brain power topography and network topology by prefrontal transcranial photobiomodulation.

Objective.Transcranial photobiomodulation (tPBM) has shown promising benefits, including cognitive improvement, in healthy humans and in patients with Alzheimer's disease. In this study, we aimed to identify key cortical regions that present significant changes caused by tPBM in the electroencephalogram (EEG) oscillation powers and functional connectivity in the healthy human brain.Approach. A 64-channel EEG was recorded from 45 healthy participants during a 13 min period consisting of a 2 min baseline, 8 min tPBM/sham intervention, and 3 min recovery. After pre-processing and normalizing the EEG data at the five EEG rhythms, cluster-based permutation tests were performed for multiple comparisons of spectral power topographies, followed by graph-theory analysis as a topological approach for quantification of brain connectivity metrics at global and nodal/cluster levels.Main results. EEG power enhancement was observed in clusters of channels over the frontoparietal regions in the alpha band and the centroparietal regions in the beta band. The global measures of the network revealed a reduction in synchronization, global efficiency, and small-worldness of beta band connectivity, implying an enhancement of brain network complexity. In addition, in the beta band, nodal graphical analysis demonstrated significant increases in local information integration and centrality over the frontal clusters, accompanied by a decrease in segregation over the bilateral frontal, left parietal, and left occipital regions.Significance.Frontal tPBM increased EEG alpha and beta powers in the frontal-central-parietal regions, enhanced the complexity of the global beta-wave brain network, and augmented local information flow and integration of beta oscillations across prefrontal cortical regions. This study sheds light on the potential link between electrophysiological effects and human cognitive improvement induced by tPBM.

Repeated transcranial photobiomodulation improves working memory of healthy older adults: behavioral outcomes of poststimulation including a three-week follow-up.

Significance: Decline in cognitive ability is a significant issue associated with healthy aging. Transcranial photobiomodulation (tPBM) is an emerging non-invasive neuromodulation technique and has shown promise to overcome this challenge. Aim: This study aimed to investigate the effects of seven-day repeated tPBM, compared to those of single tPBM and baseline, on improving N -back working memory in healthy older adults and to evaluate the persistent efficacy of repeated tPBM. Approach: In a sham-controlled and within-subject design, 61 healthy older adults were recruited to participate in a longitudinal study involving an experimental baseline, seven days of tPBM treatment (12 min daily, 1064-nm laser, 250 mW / cm 2 ) in the left dorsolateral prefrontal cortex and three weeks of follow-ups. Behavioral performance in the N -back ( N = 1,2 , 3 ) was recorded poststimulation during the baseline, the first and seventh days of the tPBM session, and the three weekly follow-ups. A control group with 25 participants was included in this study to rule out the practice and placebo effects. The accuracy rate and response time were used in the statistical analysis. Results: Repeated and single tPBM significantly improved accuracy rate in 1- and 3-back tasks and decreased response time in 3-back compared to the baseline. Moreover, the repeated tPBM resulted in a significantly higher improvement in accuracy rate than the single tPBM. These improvements in accuracy rate and response time lasted at least three weeks following repeated tPBM. In contrast, the control group showed no significant improvement in behavioral performance. Conclusions: This study demonstrated that seven-day repeated tPBM improved the working memory of healthy older adults more efficiently, with the beneficial effect lasting at least three weeks. These findings provide fundamental evidence that repeated tPBM may be a potential intervention for older individuals with memory decline.

Prefrontal cortical connectivity and coupling of infraslow oscillation in the resting human brain: a 2-channel broadband NIRS study.

The resting-state infraslow oscillation (ISO) of the cerebral cortex reflects the neurophysiological state of the human brain. ISO results from distinct vasomotion with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. Quantification of prefrontal ISO in cortical hemodynamics and metabolism in the resting human brain may facilitate the identification of objective features that are characteristic of certain brain disorders. The goal of this study was to explore and quantify the prefrontal ISO of the cortical concentration changes of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics in all 3 E/N/M bands. Two-channel broadband near-infrared spectroscopy (2-bbNIRS) enabled measurements of the forehead of 26 healthy young participants in a resting state once a week for 5 weeks. After quantifying the ISO spectral amplitude (SA) and coherence at each E/N/M band, several key and statistically reliable metrics were obtained as features: (i) SA of Δ[HbO] at all E/N/M bands, (ii) SA of Δ[CCO] in the M band, (iii) bilateral connectivity of hemodynamics and metabolism across the E and N bands, and (iv) unilateral hemodynamic-metabolic coupling in each of the E and M bands. These features have promising potential to be developed as objective biomarkers for clinical applications in the future.

Mapping and understanding of correlated electroencephalogram (EEG) responses to the newsvendor problem.

Decision-making is one of the most critical activities of human beings. To better understand the underlying neurocognitive mechanism while making decisions under an economic context, we designed a decision-making paradigm based on the newsvendor problem (NP) with two scenarios: low-profit margins as the more challenging scenario and high-profit margins as the less difficult one. The EEG signals were acquired from healthy humans while subjects were performing the task. We adopted the Correlated Component Analysis (CorrCA) method to identify linear combinations of EEG channels that maximize the correlation across subjects ([Formula: see text]) or trials ([Formula: see text]). The inter-subject or inter-trial correlation values (ISC or ITC) of the first three components were estimated to investigate the modulation of the task difficulty on subjects' EEG signals and respective correlations. We also calculated the alpha- and beta-band power of the projection components obtained by the CorrCA to assess the brain responses across multiple task periods. Finally, the CorrCA forward models, which represent the scalp projections of the brain activities by the maximally correlated components, were further translated into source distributions of underlying cortical activity using the exact Low Resolution Electromagnetic Tomography Algorithm (eLORETA). Our results revealed strong and significant correlations in EEG signals among multiple subjects and trials during the more difficult decision-making task than the easier one. We also observed that the NP decision-making and feedback tasks desynchronized the normalized alpha and beta powers of the CorrCA components, reflecting the engagement state of subjects. Source localization results furthermore suggested several sources of neural activities during the NP decision-making process, including the dorsolateral prefrontal cortex, anterior PFC, orbitofrontal cortex, posterior cingulate cortex, and somatosensory association cortex.

Feasibility of EEG Phase-Amplitude Coupling to Stratify Encephalopathy Severity in Neonatal HIE Using Short Time Window.

Goal: It is challenging to clinically discern the severity of neonatal hypoxic ischemic encephalopathy (HIE) within hours after birth in time for therapeutic decision-making for hypothermia. The goal of this study was to determine the shortest duration of the EEG based PAC index to provide real-time guidance for clinical decision-making for neonates with HIE. Methods: Neonates were recruited from a single-center Level III NICU between 2017 and 2019. A time-dependent, PAC-frequency-averaged index, tPACm, was calculated to characterize intrinsic coupling between the amplitudes of 12−30 Hz and the phases of 1−2 Hz oscillation from 6-h EEG data at electrode P3 during the first day of life, using different sizes of moving windows including 10 s, 20 s, 1 min, 2 min, 5 min, 10 min, 20 min, 30 min, 60 min, and 120 min. Time-dependent receiver operating characteristic (ROC) curves were generated to examine the performance of the accurate window tPACm as a neurophysiologic biomarker. Results: A total of 33 neonates (mild-HIE, n = 15 and moderate/severe HIE, n = 18) were enrolled. Mixed effects models demonstrated that tPACm between the two groups was significantly different with window time segments of 3−120 min. By observing the estimates of group differences in tPACm across different window sizes, we found 20 min was the shortest window size to optimally distinguish the two groups (p < 0.001). Time-varying ROC showed significant average area-under-the-curve of 0.82. Conclusions: We demonstrated the feasibility of using tPACm with a 20 min EEG time window to differentiate the severity of HIE and facilitate earlier diagnosis and treatment initiation.