Brain vital signs as a quantitative measure of cognition: Methodological implementation in a care home environment.

Introduction: Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function. Taking advantage of point-of-care accessibility, the current study evaluated the methodological feasibility, the assessment of whether a particular research method can be successfully implemented, of quantitatively measuring cognition of care home residents using brain vital signs. Secondarily, the current study examined the relationship between brain vital signs, specifically the cognitive processing associated N400 component, and MMSE scores in care home residents. Materials and methods: Brain vital signs used the established N100 (auditory sensation), P300 (basic attention), and N400 (cognitive processing) event-related potential (ERP) components. A total of 52 residents were enrolled, with all participants evaluated using the MMSE. Participants were assigned into homogeneous groups based on their MMSE scores, and were categorized into low (n = 14), medium (n = 17), and high (n = 13) MMSE groups. Both brain vital sign measures and underlying ERP waveforms were examined. Statistical analyses used partial least squares correlation (PLS) analyses in which both MMSE and age were included as factors, as well as jackknife approaches, to test for significant brain vital sign changes. Results: The current study successfully measured and analyzed standardized, quantifiable brain vital signs in a care home setting. ERP waveform data showed specific N400 changes between MMSE groups as a function of MMSE score. PLS analyses confirmed significant MMSE-related and age-related differences in the N400 amplitude (p < 0.05, corrected). Similarly, the jackknife approach emphasized the N400 latency difference between the low and high MMSE groups. Discussion and conclusion: It was possible to acquire brain vital signs measures in care home residents. Additionally, the current study evaluated brain vital signs relative to MMSE in this group. The comparison revealed significant decreasing in N400 response amplitude (cognitive processing) as a function of both MMSE score and age, as well as a slowing of N400 latency. The findings indicate that objective neurophysiological measures of impairment are detectable in care home residents across the span of MMSE scores. Direct comparison to MMSE- and age-related variables represents a critical initial step ahead of future studies that will investigate relative improvements in sensitivity, validity, reliability and related advantages of brain vital sign monitoring.

Brain vital sign monitoring of sleep deprivation detects situational cognitive impairment.

Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring.

Real world evidence of improved attention and cognition during physical therapy paired with neuromodulation: a brain vital signs study.

Background: Non-invasive neuromodulation using translingual neurostimulation (TLNS) has been shown to advance rehabilitation outcomes, particularly when paired with physical therapy (PT). Together with motor gains, patient-reported observations of incidental improvements in cognitive function have been noted. Both studies in healthy individuals and case reports in clinical populations have linked TLNS to improvements in attention-related cognitive processes. We investigated if the use of combined TLNS/PT would translate to changes in objective neurophysiological cognitive measures in a real-world clinical sample of patients from two separate rehabilitation clinics. Methods: Brain vital signs were derived from event-related potentials (ERPs), specifically auditory sensation (N100), basic attention (P300), and cognitive processing (N400). Additional analyses explored the attention-related N200 response given prior evidence of attention effects from TLNS/PT. The real-world patient sample included a diverse clinical group spanning from mild-to-moderate traumatic brain injury (TBI), stroke, Multiple Sclerosis (MS), Parkinson's Disease (PD), and other neurological conditions. Patient data were also acquired from a standard clinical measure of cognition for comparison. Results: Results showed significant N100 variation between baseline and endpoint following TLNS/PT treatment, with further examination showing condition-specific significant improvements in attention processing (i.e., N100 and N200). Additionally, CogBAT composite scores increased significantly from baseline to endpoint. Discussion: The current study highlighted real-world neuromodulation improvements in neurophysiological correlates of attention. Overall, the real-world findings support the concept of neuromodulation-related improvements extending beyond physical therapy to include potential attention benefits for cognitive rehabilitation.

Event Related Potential Signal Capture Can Be Enhanced through Dynamic SNR-Weighted Channel Pooling.

BACKGROUND: Electroencephalography (EEG)-derived event-related potentials (ERPs) provide information about a variety of brain functions, but often suffer from low inherent signal-to-noise ratio (SNR). To overcome the low SNR, techniques that pool data from multiple sensors have been applied. However, such pooling implicitly assumes that the SNR among sensors is equal, which is not necessarily valid. This study presents a novel approach for signal pooling that accounts for differential SNR among sensors. METHODS: The new technique involves pooling together signals from multiple EEG channels weighted by their respective SNRs relative to the overall SNR of all channels. We compared ERP responses derived using this new technique with those derived using both individual channels as well as traditional averaged-based channel pooling. The outcomes were evaluated in both simulated data and real data from healthy adult volunteers (n = 37). Responses corresponding to a range of ERP components indexing auditory sensation (N100), attention (P300) and language processing (N400) were evaluated. RESULTS: Simulation results demonstrate that, compared to traditional pooling technique, the new SNR-weighted channel pooling technique improved ERP response effect size in cases of unequal noise among channels (p's < 0.001). Similarly, results from real-world experimental data showed that the new technique resulted in significantly greater ERP effect sizes compared to either traditional pooling or individual channel approach for all three ERP components (p's < 0.001). Furthermore, the new channel pooling approach also resulted in larger ERP signal amplitudes as well as greater differences among experimental conditions (p's < 0.001). CONCLUSION: These results suggest that the new technique improves the capture of ERP responses relative to traditional techniques. As such, SNR-weighted channel pooling can further enable widespread applications of ERP techniques, especially those that require rapid assessments in noisy out-of-laboratory environments.

Brain Vital Signs in Elite Ice Hockey: Towards Characterizing Objective and Specific Neurophysiological Reference Values for Concussion Management.

Background: Prior concussion studies have shown that objective neurophysiological measures are sensitive to detecting concussive and subconcussive impairments in youth ice-hockey. These studies monitored brain vital signs at rink-side using a within-subjects design to demonstrate significant changes from pre-season baseline scans. However, practical clinical implementation must overcome inherent challenges related to any dependence on a baseline. This requires establishing the start of normative reference data sets. Methods: The current study collected specific reference data for N = 58 elite, youth, male ice-hockey players and compared these with a general reference dataset from N = 135 of males and females across the lifespan. The elite hockey players were recruited to a select training camp through CAA Hockey, a management agency for players drafted to leagues such as the National Hockey League (NHL). The statistical analysis included a test-retest comparison to establish reliability, and a multivariate analysis of covariance to evaluate differences in brain vital signs between groups with age as a covariate. Findings: Test-retest assessments for brain vital signs evoked potentials showed moderate-to-good reliability (Cronbach's Alpha > 0.7, Intraclass correlation coefficient > 0.5) in five out of six measures. The multivariate analysis of covariance showed no overall effect for group (p = 0.105), and a significant effect of age as a covariate was observed (p < 0.001). Adjusting for the effect of age, a significant difference was observed in the measure of N100 latency (p = 0.022) between elite hockey players and the heterogeneous control group. Interpretation: The findings support the concept that normative physiological data can be used in brain vital signs evaluation in athletes, and should additionally be stratified for age, skill level, and experience. These can be combined with general norms and/or individual baseline assessments where appropriate and/or possible. The current results allow for brain vital sign evaluation independent of baseline assessment, therefore enabling objective neurophysiological evaluation of concussion management and cognitive performance optimization in ice-hockey.

Differential neural processing of spontaneous blinking under visual and auditory sensory environments: An EEG investigation of blink-related oscillations.

Blink-related oscillations (BROs) are a recently discovered neurophysiological response associated with spontaneous blinking, distinct from the well-known oculomotor and visual suppression effects. BROs strongly activate the bilateral precuneus along with other cortical regions involved in visuospatial processing and associative episodic memory, and are believed to represent environmental monitoring processes that occur following blink-induced visual interruptions. Although these responses have been reported across multiple imaging modalities under both resting and cognitive loading conditions, it is yet unknown whether these responses also exist under external sensory stimulation conditions. To address this, we investigated BRO responses in healthy adults using 64-channel electroencephalography (EEG), while participants underwent passive external auditory and visual stimulation. Our results showed that BRO responses are present under both auditory and visual stimulation conditions (p â€‹< â€‹0.05), with similar temporal and spectral features compared to rest. However, visual stimulation did result in decreased BRO amplitude compared to auditory and resting conditions (p â€‹< â€‹0.05), suggesting decreased neuronal resources for processing blink-related information in the visual but not auditory environment. There were also additional pre-blink spectral changes in the visual condition compared to rest (p â€‹< â€‹0.05), which suggest that passive visual stimulation induces neural preparatory processes occurring in anticipation of the upcoming blink event. Together, these findings provide new and compelling evidence that blink-related neural processes are modulated not only by the internal cognitive loading due to simultaneous task demands, but also by competing external sensory requirements. This highlights the link between blinking and cognition, and further demonstrates the importance of BROs as a new window into brain function.

Distant Sensor Prediction of Event-Related Potentials.

OBJECTIVE: The ability to measure event-related potentials (ERPs) as practical, portable brain vital signs is limited by the physical locations of electrodes. Standard electrode locations embedded within the hair result in challenges to obtaining quality signals in a rapid manner. Moreover, these sites require electrode gel, which can be inconvenient. As electrical activity in the brain is spatially volume distributed, it should be possible to predict ERPs from distant sensor locations at easily accessible mastoid and forehead scalp regions. METHODS: An artificial neural network was trained on ERP signals recorded from below hairline electrode locations (Tp9, Tp10, Af7, Af8 referenced to Fp1, Fp2) to predict signals recorded at the ideal Cz location. RESULTS: The model resulted in mean improvements in intraclass correlation coefficient relative to control for all stimulus types (Standard Tones: +9.74%, Deviant Tones: +3.23%, Congruent Words: +15.25%, Incongruent Words: +25.43%) and decreases in RMS Error (Standard Tones: -26.72%, Deviant Tones: -17.80%, Congruent Words: -28.78%, Incongruent Words: -29.61%) compared to the individual distant channels. Measured vs predicted ERP amplitudes were highly and significantly correlated with control for the N100 (R = 0.5, padj < 0.05), P300 (R = 0.75, padj < 0.01), and N400 (R = 0.75, padj < 0.01) ERPs. CONCLUSION: ERP waveforms at distant channels can be combined using a neural network autoencoder to model the control channel features with better precision than those at individual distant channels. This is the first demonstration of feasibility of predicting evoked potentials and brain vital signs using signals recorded from more distant, practical locations. SIGNIFICANCE: This solves a key engineering challenge for applications that require portability, comfort, and speed of measurement as design priorities for measurement of event-related potentials across a range of individuals, settings, and circumstances.

Novel Signal Processing Technique for Capture and Isolation of Blink-Related Oscillations Using a Low-Density Electrode Array for Bedside Evaluation of Consciousness.

OBJECTIVE: Blink-related oscillations derived from electroencephalography (EEG) have recently emerged as an important measure of awareness. Combined with portable EEG hardware with low-density electrode arrays, this neural marker may crucially augment the existing bedside assessments of consciousness in unresponsive patients. Nonetheless, the close relationship between signal characteristics of the neural response of interest and blink-induced oculomotor artifacts poses particular challenges when measuring blink-related oscillations using a point-of-care platform. This study presents a novel denoising approach based on time-frequency (TF) filtering that exploits the differential temporal and spectral features to isolate the neural response from ocular artifact in a low-density array. METHODS: We investigated the effectiveness of the TF filtering technique using 64-channel EEG data collected in healthy adults, with focal analysis of the Pz and POz channels. RESULTS: TF filtering showed comparable performance in denoising the signal relative to the established gold-standard independent component analysis approach, with strong similarities in morphological characteristics as measured by intraclass correlations (p < 0.001), extent of artifact rejection based on the ocular contamination index (p < 0.006), as well as time- and frequency-domain signal capture (p < 0.05). Results are robust at the individual and group levels, and are crucially validated using raw data from only four electrodes comprising Pz, POz, Fp2, and T7. CONCLUSION: These results demonstrate for the first time that TF filtering enables the successful capture and isolation of the blink-related oscillations response using a four-electrode array. SIGNIFICANCE: This significantly advances the translation of the blink-related oscillations marker to a point-of-care platform for eventual bedside applications.

Brain vital signs detect concussion-related neurophysiological impairments in ice hockey.

There is a growing demand for objective evaluations of concussion. We developed a portable evoked potential framework to extract 'brain vital signs' using electroencephalography. Brain vital signs were derived from well established evoked responses representing auditory sensation (N100), basic attention (P300), and cognitive processing (N400) amplitudes and latencies, converted to normative metrics (six total). The study evaluated whether concussion-related neurophysiological impairments were detected over the duration of ice hockey seasons using brain vital signs. Forty-seven Tier III, Junior A, male ice hockey players were monitored over two seasons. Twelve sustained concussions after baseline testing then completed post-injury and return-to-play assessments. Twenty-three were not diagnosed with a concussion during the season and completed both baseline and post-season testing. Scores were evaluated using a repeated-measures analysis of variance with post hoc two-tailed paired t-tests. Concussion resulted in significantly increased amplitude and delayed latency scores for all six brain vital signs (P < 0.0001). Importantly, significant changes at return-to-play were also detected in basic attention (P300) amplitude, indicating persistent subclinical impairment. In the non-concussed group, there was also a significant change between baseline and post-season (P = 0.0047), with specific decreases in cognitive processing (N400) speed (P = 0.011) and overall total score (P = 0.002).

Brain Vital Signs: Expanding From the Auditory to Visual Modality.

The critical need for rapid objective, physiological evaluation of brain function at point-of-care has led to the emergence of brain vital signs-a framework encompassing a portable electroencephalography (EEG) and an automated, quick test protocol. This framework enables access to well-established event-related potential (ERP) markers, which are specific to sensory, attention, and cognitive functions in both healthy and patient populations. However, all our applications to-date have used auditory stimulation, which have highlighted application challenges in persons with hearing impairments (e.g., aging, seniors, dementia). Consequently, it has become important to translate brain vital signs into a visual sensory modality. Therefore, the objectives of this study were to: 1) demonstrate the feasibility of visual brain vital signs; and 2) compare and normalize results from visual and auditory brain vital signs. Data were collected from 34 healthy adults (33 ± 13 years) using a 64-channel EEG system. Visual and auditory sequences were kept as comparable as possible to elicit the N100, P300, and N400 responses. Visual brain vital signs were elicited successfully for all three responses across the group (N100: F = 29.8380, p < 0.001; P300: F = 138.8442, p < 0.0001; N400: F = 6.8476, p = 0.01). Initial auditory-visual comparisons across the three components showed attention processing (P300) was found to be the most transferrable across modalities, with no group-level differences and correlated peak amplitudes (rho = 0.7, p = 0.0001) across individuals. Auditory P300 latencies were shorter than visual (p < 0.0001) but normalization and correlation (r = 0.5, p = 0.0033) implied a potential systematic difference across modalities. Reduced auditory N400 amplitudes compared to visual (p = 0.0061) paired with normalization and correlation across individuals (r = 0.6, p = 0.0012), also revealed potential systematic modality differences between reading and listening language comprehension. This study provides an initial understanding of the relationship between the visual and auditory sequences, while importantly establishing a visual sequence within the brain vital signs framework. With both auditory and visual stimulation capabilities available, it is possible to broaden applications across the lifespan.

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time.

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential "brain vital signs." This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22-82 years). Results confirmed specific ERPs at the individual level (86.81-98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia.