Blink-Related Oscillations Provide Naturalistic Assessments of Brain Function and Cognitive Workload within Complex Real-World Multitasking Environments.

BACKGROUND: There is a significant need to monitor human cognitive performance in complex environments, with one example being pilot performance. However, existing assessments largely focus on subjective experiences (e.g., questionnaires) and the evaluation of behavior (e.g., aircraft handling) as surrogates for cognition or utilize brainwave measures which require artificial setups (e.g., simultaneous auditory stimuli) that intrude on the primary tasks. Blink-related oscillations (BROs) are a recently discovered neural phenomenon associated with spontaneous blinking that can be captured without artificial setups and are also modulated by cognitive loading and the external sensory environment-making them ideal for brain function assessment within complex operational settings. METHODS: Electroencephalography (EEG) data were recorded from eight adult participants (five F, M = 21.1 years) while they completed the Multi-Attribute Task Battery under three different cognitive loading conditions. BRO responses in time and frequency domains were derived from the EEG data, and comparisons of BRO responses across cognitive loading conditions were undertaken. Simultaneously, assessments of blink behavior were also undertaken. RESULTS: Blink behavior assessments revealed decreasing blink rate with increasing cognitive load (p < 0.001). Prototypical BRO responses were successfully captured in all participants (p < 0.001). BRO responses reflected differences in task-induced cognitive loading in both time and frequency domains (p < 0.05). Additionally, reduced pre-blink theta band desynchronization with increasing cognitive load was also observed (p < 0.05). CONCLUSION: This study confirms the ability of BRO responses to capture cognitive loading effects as well as preparatory pre-blink cognitive processes in anticipation of the upcoming blink during a complex multitasking situation. These successful results suggest that blink-related neural processing could be a potential avenue for cognitive state evaluation in operational settings-both specialized environments such as cockpits, space exploration, military units, etc. and everyday situations such as driving, athletics, human-machine interactions, etc.-where human cognition needs to be seamlessly monitored and optimized.

Towards ubiquitous and nonintrusive measurements of brain function in the real world: assessing blink-related oscillations during simulated flight using portable low-cost EEG.

Blink-related oscillations (BRO) are newly discovered neurophysiological phenomena associated with spontaneous blinking and represent cascading neural mechanisms including visual sensory, episodic memory, and information processing responses. These phenomena have been shown to be present at rest and during tasks and are modulated by cognitive load, creating the possibility for brain function assessments that can be integrated seamlessly into real-world settings. Prior works have largely examined the BRO phenomenon within controlled laboratory environments using magnetoencephalography and high-density electroencephalography (EEG) that are ill-suited for real-world deployment. Investigating BROs using low-density EEG within complex environments reflective of the real-world would further our understanding of how BRO responses can be utilized in real-world settings. We evaluated whether the BRO response could be captured in a high-fidelity flight simulation environment using a portable, low-density wireless EEG system. The effects of age and task demands on BRO responses were also examined. EEG data from 30 licensed pilots (age 43.37 +/- 17.86, 2 females) were collected during simulated flights at two cognitive workload levels. Comparisons of signal amplitudes were undertaken to confirm the presence of BRO responses and mixed model ANOVAs quantified the effects of workload and age group on BRO amplitudes. Significant increases in neural activity were observed post-blink compared to the baseline period (p < 0.05), confirming the presence of BRO responses. In line with prior studies, results showed BRO time-domain responses from the delta band (0.5-4 Hz) consisting of an early negative peak followed by a positive peak post-blink in temporal and parietal electrodes. Additionally, task workload and age-related effects were also found, with observations of the enhancement of BRO amplitudes with older age and attenuation of BRO responses in high workloads (p < 0.05). These findings demonstrate that it is possible to capture BRO responses within simulated flight environments using portable, low-cost, easy-to-use EEG systems. Furthermore, biological and task salience were reflected in these BRO responses. The successful detection and demonstration of both task-and age-related modulation of BRO responses in this study open the possibility of assessing human brain function across the lifespan with BRO responses in complex and realistic environments.

White Matter Neuroplasticity: Motor Learning Activates the Internal Capsule and Reduces Hemodynamic Response Variability.

Numerous studies have noted the importance of white matter changes in motor learning, but existing literature only focuses on structural and microstructural MRI changes, as there are limited tools available for in vivo investigations of white matter function. One method that has gained recent prominence is the application of blood oxygen level dependent (BOLD) fMRI to white matter, with high-field scanners now being able to better detect the smaller hemodynamic changes present in this tissue type compared to those in the gray matter. However, fMRI techniques have yet to be applied to investigations of neuroplastic change with motor learning in white matter. White matter function represents an unexplored component of neuroplasticity and is essential for gaining a complete understanding of learning-based changes occurring throughout the whole brain. Twelve healthy, right-handed participants completed fine motor and gross motor tasks with both hands, using an MRI compatible computer mouse. Using a crossover design along with a prior analysis approach to establish WM activation, participants received a baseline scan followed by 2 weeks of training, returning for a midpoint and endpoint scan. The motor tasks were designed to be selectively difficult for the left hand, leading to a training effect only in that condition. Analysis targeted the comparison and detection of training-associated right vs left hand changes. A statistically significant improvement in motor task score was only noted for the left-hand motor condition. A corresponding change in the temporal characteristics of the white matter hemodynamic response was shown within only the right corticospinal tract. The hemodynamic response exhibited a reduction in the dispersion characteristics after the training period. To our knowledge, this is the first report of MRI detectable functional neuroplasticity in white matter, suggesting that modifications in temporal characteristics of white matter hemodynamics may underlie functional neuroplasticity in this tissue.

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.

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).

Point-of-care brain injury evaluation of conscious awareness: wide scale deployment of portable HCS EEG evaluation.

Survivors of severe brain injury may remain in a decreased state of conscious awareness for an extended period of time. Clinical scales are used to describe levels of consciousness but rely on behavioural responses, precipitating misdiagnosis. We have previously utilized event-related potentials (ERPs) to circumvent reliance on behavioural responses. However, practical implementation barriers limit the clinical utility of ERP assessment at point-of-care (POC). To address this challenge, we developed the Halifax Consciousness Scanner (HCS)-a rapid, semi-automated electroencephalography system. The current study evaluated: (i) HCS feasibility in sub-acute, POC settings nationwide; (ii) ERP P300 responses in patients with acquired brain injury versus healthy controls; and (iii) correlations within and between clinical measures and P300 latencies. We assessed 28 patients with severe, chronic impairments from brain injuries and contrasted the results with healthy control data (n = 100). Correlational analyses examined relationships between P300 latencies and the commonly used clinical scales. P300 latencies were significantly delayed in patients compared to healthy controls (P < 0.05). Clinical assessment scores were significantly inter-correlated and correlated significantly with P300 latencies (P < 0.05). In sub-acute and chronic care settings, the HCS provided a physiological measure of neurocognitive processing at POC for patients with severe acquired brain injury, including those with disorders of consciousness.

Multimodal characterization of the semantic N400 response within a rapid evaluation brain vital sign framework.

BACKGROUND: For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as "brain vital signs" that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings-thereby enabling its translation into brain vital signs applications. METHODS: Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected. RESULTS: The N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90). CONCLUSION: The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.

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.

Spontaneous Blinks Activate the Precuneus: Characterizing Blink-Related Oscillations Using Magnetoencephalography.

Spontaneous blinking occurs 15-20 times per minute. Although blinking has often been associated with its physiological role of corneal lubrication, there is now increasing behavioral evidence suggesting that blinks are also modulated by cognitive processes such as attention and information processing. Recent low-density electroencephalography (EEG) studies have reported so-called blink-related oscillations (BROs) associated with spontaneous blinking at rest. Delta-band (0.5-4 Hz) BROs are thought to originate from the precuneus region involved in environmental monitoring and awareness, with potential clinical utility in evaluation of disorders of consciousness. However, the neural mechanisms of BROs have not been elucidated. Using magnetoencephalography (MEG), we characterized delta-band BROs in 36 healthy individuals while controlling for background brain activity. Results showed that, compared to pre-blink baseline, delta-band BROs resulted in increased global field power (p < 0.001) and time-frequency spectral power (p < 0.05) at the sensor level, peaking at ~250 ms post-blink maximum. Source localization showed that spontaneous blinks activated the bilateral precuneus (p < 0.05 FWE), and source activity within the precuneus was also consistent with sensor-space results. Crucially, these effects were only observed in the blink condition and were absent in the control condition, demonstrating that results were due to spontaneous blinks rather than as part of the inherent brain activity. The current study represents the first MEG examination of BROs. Our findings suggest that spontaneous blinks activate the precuneus regions consistent with environmental monitoring and awareness, and provide important neuroimaging support for the cognitive role of spontaneous blinks.

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.

Long-Term Motor Recovery After Severe Traumatic Brain Injury: Beyond Established Limits.

OBJECTIVE: To report neural plasticity changes after severe traumatic brain injury. SETTING: Case-control study. PARTICIPANTS: Canadian soldier, Captain Trevor Greene survived a severe open-traumatic brain injury during a 2006 combat tour in Afghanistan. DESIGN: Longitudinal follow-up for more than 6 years. MAIN MEASURES: Twelve longitudinal functional magnetic imaging (fMRI) examinations were conducted to investigate lower limb activation changes in association with clinical examination. Trevor Greene's lower limb fMRI activation was compared with control fMRI activation of (1) mental imagery of similar movement and (2) matched control subject data. RESULTS: Trevor Greene's motor recovery and corresponding fMRI activation increased significantly over time (F = 32.54, P < .001). Clinical measures of functional recovery correlated strongly with fMRI motor activation changes (r = 0.81, P = .001). By comparison, while Trevor Greene's mental imagery activated similar motor regions, there was no evidence of fMRI activation change over time. While comparable, control motor activation did not change over time and there was no significant mental imagery activation. CONCLUSION: Motor function recovery can occur beyond 6 years after severe traumatic brain injury, both in neural plasticity and clinical outcome. This demonstrates that continued benefits in physical function due to rehabilitative efforts can be achieved for many years following injury. The finding challenges current practices and assumptions in rehabilitation following traumatic brain injury.