Increased myelination plays a central role in white matter neuroplasticity.

White matter (WM) neuroplasticity in the human brain has been tracked non-invasively using advanced magnetic resonance imaging techniques, with increasing evidence for improved axonal transmission efficiency as a central mechanism. The current study is the culmination of a series of studies, which characterized the structure-function relationship of WM transmission efficiency in the cortico-spinal tract (CST) during motor learning. Here, we test the hypothesis that increased transmission efficiency is linked directly to increased myelination using myelin water imaging (MWI). MWI was used to evaluate neuroplasticity-related improvements in the CST. The MWI findings were then compared to diffusion tensor imaging (DTI) results, with the secondary hypothesis that radial diffusivity (RD) would have a stronger relationship than axial diffusivity (AD) if the changes were due to increased myelination. Both MWI and RD data showed the predicted pattern of significant results, strongly supporting that increased myelination plays a central role in WM neuroplasticity.

A Method for Estimating Longitudinal Change in Motor Skill from Individualized Functional-Connectivity Measures.

Pragmatic, objective, and accurate motor assessment tools could facilitate more frequent appraisal of longitudinal change in motor function and subsequent development of personalized therapeutic strategies. Brain functional connectivity (FC) has shown promise as an objective neurophysiological measure for this purpose. The involvement of different brain networks, along with differences across subjects due to age or existing capabilities, motivates an individualized approach towards the evaluation of FC. We advocate the use of EEG-based resting-state FC (rsFC) measures to address the pragmatic requirements. Pertaining to appraisal of accuracy, we suggest using the acquisition of motor skill by healthy individuals that could be quantified at small incremental change. Computer-based tracing tasks are a good candidate in this regard when using spatial error in tracing as an objective measure of skill. This work investigates the application of an individualized method that utilizes Partial Least Squares analysis to estimate the longitudinal change in tracing error from changes in rsFC. Longitudinal data from participants yielded an average accuracy of 98% (standard deviation of 1.2%) in estimating tracing error. The results show potential for an accurate individualized motor assessment tool that reduces the dependence on the expertise and availability of trained examiners, thereby facilitating more frequent appraisal of function and development of personalized training programs.

Proceedings From the Ice Hockey Summit III: Action on Concussion.

OBJECTIVES: The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these 5 objectives: (1) describe sport related concussion (SRC) epidemiology; (2) classify prevention strategies; (3) define objective, diagnostic tests; (4) identify treatment; and (5) integrate science and clinical care into prioritized action plans and policy. METHODS: Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. RESULTS: To (1) establish a national and international hockey database for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care; and (6) mandate baseline testing to improve concussion diagnosis for all age groups. CONCLUSIONS: Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

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.

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.

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).

Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: a high-density MEG case study.

BACKGROUND: In a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits. METHODS: Canadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program. RESULTS: Combining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27 Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes. CONCLUSIONS: The findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.

The Feasibility of Longitudinal Upper Extremity Motor Function Assessment Using EEG.

Motor function assessment is crucial in quantifying motor recovery following stroke. In the rehabilitation field, motor function is usually assessed using questionnaire-based assessments, which are not completely objective and require prior training for the examiners. Some research groups have reported that electroencephalography (EEG) data have the potential to be a good indicator of motor function. However, those motor function scores based on EEG data were not evaluated in a longitudinal paradigm. The ability of the motor function scores from EEG data to track the motor function changes in long-term clinical applications is still unclear. In order to investigate the feasibility of using EEG to score motor function in a longitudinal paradigm, a convolutional neural network (CNN) EEG model and a residual neural network (ResNet) EEG model were previously generated to translate EEG data into motor function scores. To validate applications in monitoring rehabilitation following stroke, the pre-established models were evaluated using an initial small sample of individuals in an active 14-week rehabilitation program. Longitudinal performances of CNN and ResNet were evaluated through comparison with standard Fugl-Meyer Assessment (FMA) scores of upper extremity collected in the assessment sessions. The results showed good accuracy and robustness with both proposed networks (average difference: 1.22 points for CNN, 1.03 points for ResNet), providing preliminary evidence for the proposed method in objective evaluation of motor function of upper extremity in long-term clinical applications.

Cognitive loading via mental arithmetic modulates effects of blink-related oscillations on precuneus and ventral attention network regions.

Blink-related oscillations (BROs) have been linked with environmental monitoring processes associated with blinking, with cortical activations in the bilateral precuneus. Although BROs have been described under resting and passive fixation conditions, little is known about their characteristics under cognitive loading. To address this, we investigated BRO effects during both mental arithmetic (MA) and passive fixation (PF) tasks using magnetoencephalography (n =20), while maintaining the same sensory environment in both tasks. Our results confirmed the presence of BRO effects in both MA and PF tasks, with similar characteristics including blink-related increase in global field power and blink-related activation of the bilateral precuneus. In addition, cognitive loading due to MA also modulated BRO effects by decreasing BRO-induced cortical activations in key brain regions including the bilateral anterior precuneus. Interestingly, blinking during MA-but not PF-activated regions of the ventral attention network (i.e., right supramarginal gyrus and inferior frontal gyrus), suggesting possible recruitment of these areas for blink processing under cognitive loading conditions. Time-frequency analysis revealed a consistent pattern of BRO-related effects in the precuneus in both tasks, but with task-related functional segregation within the anterior and posterior subregions. Based on these findings, we postulate a potential neurocognitive mechanism for blink processing in the precuneus. This study is the first investigation of BRO effects under cognitive loading, and our results provide compelling new evidence for the important cognitive implications of blink-related processing in the human brain.

Human translingual neurostimulation alters resting brain activity in high-density EEG.

BACKGROUND: Despite growing evidence of a critical link between neuromodulation technologies and neuroplastic recovery, the underlying mechanisms of these technologies remain elusive. OBJECTIVE: To investigate physiological evidence of central nervous system (CNS) changes in humans during translingual neurostimulation (TLNS). METHODS: We used high-density electroencephalography (EEG) to measure changes in resting brain activity before, during, and after high frequency (HF) and low frequency (LF) TLNS. RESULTS: Wavelet power analysis around Cz and microstate analysis revealed significant changes after 20 min of stimulation compared to baseline. A secondary effect of exposure order was also identified, indicating a differential neuromodulatory influence of HF TLNS relative to LF TLNS on alpha and theta signal power. CONCLUSIONS: These results further our understanding of the effects of TLNS on underlying resting brain activity, which in the long-term may contribute to the critical link between clinical effect and changes in brain activity.

Proceedings from the Ice Hockey Summit III: Action on Concussion.

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Detecting white matter activity using conventional 3 Tesla fMRI: An evaluation of standard field strength and hemodynamic response function.

Detection of functional magnetic resonance imaging (fMRI) activation in white matter has been increasingly reported despite historically being controversial. Much of the development work to-date has used high-field 4 T MRI and specialized pulse sequences. In the current study, we utilized conventional 3 T MRI and a commonly applied gradient-echo-planar imaging sequence to evaluate white matter (WM) fMRI sensitivity within a common framework. Functional WM activity was replicated in target regions of interest within the corpus callosum, at the group and individual levels. As expected there was a reduction in overall WM activation sensitivity. Individual analyses revealed that 8 of the 13 individuals showed white matter activation, showing a lower percentage of individuals with WM activation detected. Importantly, WM activation results were sensitive to analyses that applied alternate hemodynamic response functions, with an increase in the group level cluster when hemodynamic response function (HRF) onset slope was reduced. The findings supported the growing evidence that WM activation is detectable, with activation levels are closer to thresholds used for routine 3T MRI studies. Optimization factors, such as the HRF model, appear to be important to further enhance the characterization of WM activity in fMRI.

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.

Improving fMRI reliability in presurgical mapping for brain tumours.

PURPOSE: Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps. METHODS: Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel. RESULTS: The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively). CONCLUSIONS: We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping.

Asymmetric Weighting to Optimize Regional Sensitivity in Combined fMRI-MEG Maps.

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are neuroimaging techniques that measure inherently different physiological processes, resulting in complementary estimates of brain activity in different regions. Combining the maps generated by each technique could thus provide a richer understanding of brain activation. However, present approaches to integration rely on a priori assumptions, such as expected patterns of brain activation in a task, or use fMRI to bias localization of MEG sources, diminishing fMRI-invisible sources. We aimed to optimize sensitivity to neural activity by developing a novel method of integrating data from the two imaging techniques. We present a data-driven method of integration that weights fMRI and MEG imaging data by estimates of data quality for each technique and region. This method was applied to a verbal object recognition task. As predicted, the two imaging techniques demonstrated sensitivity to activation in different regions. Activity was seen using fMRI, but not MEG, throughout the medial temporal lobes. Conversely, activation was seen using MEG, but not fMRI, in more lateral and anterior temporal lobe regions. Both imaging techniques were sensitive to activation in the inferior frontal gyrus. Importantly, integration maps retained activation from individual activation maps, and showed an increase in the extent of activation, owing to greater sensitivity of the integration map than either fMRI or MEG alone.

Simulation-based training for burr hole surgery instrument recognition.

BACKGROUND: The use of simulation training in postgraduate medical education is an area of rapidly growing popularity and research. This study was designed to assess the impact of simulation training for instrument knowledge and recognition among neurosurgery residents. METHODS: This was a randomized control trial of first year residents from neurosurgery residency training programs across Canada. Eighteen neurosurgery trainees were recruited to test two simulation-based applications: PeriopSim™ Instrument Trainer and PeriopSim™ for Burr Hole Surgery. The intervention was game-based simulation training for learning neurosurgical instruments and applying this knowledge to identify correct instruments during a simulated burr hole surgery procedure. RESULTS: Participants showed significant overall improvement in total score (p < 0.0005), number of errors (p = 0.019) and time saved (p < 0.0005), over three testing sessions when using the PeriopSim™ Instrument Trainer. Participants demonstrated further performance-trained improvements when using PeriopSim™ Burr Hole Surgery. CONCLUSIONS: Training in the recognition and utilization of simulated surgical instruments by neurosurgery residents improved significantly with repetition when using PeriopSim™ Instrument Trainer and PeriopSim™ for Burr Hole Surgery.

Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women.

INTRODUCTION: Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. METHODS: We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). RESULTS: In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance (P < .0001), executive functioning (P = .026), and overall cognition (P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes-related, APOE ε4, and inflammatory potential confounders. Attention/working memory (P = .532) and episodic memory (P = .144) were not associated with waist circumference. These correlations were not found in men. DISCUSSION: These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia.

Investigating female versus male differences in white matter neuroplasticity associated with complex visuo-motor learning.

Magnetic resonance imaging (MRI) has increasingly been used to characterize structure-function relationships during white matter neuroplasticity. Biological sex differences may be an important factor that affects patterns of neuroplasticity, and therefore impacts learning and rehabilitation. The current study examined a participant cohort before and after visuo-motor training to characterize sex differences in microstructural measures. The participants (N = 27) completed a 10-session (4 week) complex visuo-motor training task with their non-dominant hand. All participants significantly improved movement speed and their movement speed variability over the training period. White matter neuroplasticity in females and males was examined using fractional anisotropy (FA) and myelin water fraction (MWF) along the cortico-spinal tract (CST) and the corpus callosum (CC). FA values showed significant differences in the middle portion of the CST tract (nodes 38-51) across the training period. MWF showed a similar cluster in the inferior portion of the tract (nodes 18-29) but did not reach significance. Additionally, at baseline, males showed significantly higher levels of MWF measures in the middle body of the CC. Combining data from females and males would have resulted in reduced sensitivity, making it harder to detect differences in neuroplasticity. These findings offer initial insights into possible female versus male differences in white matter neuroplasticity during motor learning. This warrants investigations into specific patterns of white matter neuroplasticity for females versus males across the lifespan. Understanding biological sex-specific differences in white matter neuroplasticity may have significant implications for the interpretation of change associated with learning or rehabilitation.

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.