Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions.

Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.

Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer's Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study.

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.

Physiological separation of Alzheimer's disease and Alzheimer's disease with significant levels of cerebrovascular symptomology and healthy controls.

Most dementia patients with a mixed dementia (MxD) diagnosis have a mix of Alzheimer's disease (AD) and vascular dementia. Electrovestibulography (EVestG) records vestibuloacoustic afferent activity. We hypothesize EVestG recordings of AD and MxD patients are different. All patients were assessed with the Montreal cognitive assessment (MoCA) and Hachinski ischemic scale (HIS) (> 4 HIS score < 7 is representative of MxD cerebrovascular symptomology). EVestG recordings were made from 26 AD, 21 MxD and 44 healthy (control) participants. Features were derived from the EVestG recordings of the average field potential and field potential interval histogram to classify the AD, MxD and control groups. Multivariate analysis was used to test the features' significance. Using a leave-one-out cross-validated linear discriminant analysis with 3 EVestG features yielded accuracies > 80% for separating pairs of AD/MxD/control. Using the MoCA assessment and 2 EVestG features, a best accuracy of 81 to 91% depending on the classifier was obtained for the 3-way identification of AD, MxD and controls. EVestG measures provide a physiological basis for identifying AD from MxD. EVestG measures are hypothesized to be partly related to channelopathies and changes in the descending input to the vestibular periphery. Four of the five AD or MxD versus control features used had significant correlations with the MoCA. This supports assertions that the pathologic changes associated with AD impact the vestibular system and further are suggestive that the postulated physiological changes behind these features have an association with cognitive decline severity.

Correlation between Ocular and Vestibular Abnormalities and Convergence Insufficiency in Post-Concussion Syndrome.

The vestibular and oculomotor/visual systems are commonly affected in post-concussion syndrome (PCS). Convergence insufficiency (CI) is the most common ocular abnormality after concussion. Electrovestibulography (EVestG) is a relatively new non-invasive method that measures the peripheral vestibular responses; it has shown abnormal vestibular responses in a PCS. Here, we report the results of investigating the correlation between the vestibular and oculomotor systems in PCS population using EVestG and CI measures. Forty-eight PCS patients were tested using EVestG, out of which 20 also completed the Rivermead post-concussion questionnaire (RPQ). An EVestG feature (Field Potential (FP)-area) was extracted from the stationary part of the EVestG signals. A neuro-ophthalmologist (author BM) measured participants' CI at near vision using cross-cover examination and a prism-bar. Results indicate: (1) vestibular abnormality (i.e. FP-area) and CI values are significantly correlated in PCS (R = 0.68, p < .01), and (2) there are significant correlations between severity of concussion (i.e. RPQ3) and CI (R = 0.70, p < .01) and between RPQ3 and FP-area (R = -0.56, p < .02). To the best of our knowledge, this is the first study that objectively demonstrates a significant positive correlation between the CI and vestibular systems' abnormality. These findings are scientifically important as they help localise the pathology of PCS, and are clinically valuable as they help physicians in their decision-making about PCS diagnosis and rehabilitation strategies.

Post-Concussion Syndrome and Sleep Apnea: A Retrospective Study.

BACKGROUND: Concussion symptoms typically resolve within 7-10 days, but 10%-25% of patients do not fully recover. They can develop post-concussion syndrome (PCS), which includes sleep abnormalities such as obstructive sleep apnea. It is unclear how specific sleep problems manifest in PCS and how it relates to cognition and symptomology. METHODS: A retrospective chart review was conducted on PCS patients seen at the University Health Network (UHN) Concussion Clinic and sent for sleep study. Neuropsychology tests, concussion features, PCS symptoms, and demographics were abstracted from clinical charts. Sleep measures were abstracted from the overnight sleep study. Data were analyzed using chi-squared tests and linear regression. RESULTS: Fifty-one patients completed the sleep study; 78% of these were diagnosed with sleep apnea. Patients with sleep apnea reported significantly more memory symptoms. A trend existed for higher total symptom number. Age was significantly different between the two groups. Women and men were equally at risk of being diagnosed with sleep apnea. CONCLUSIONS: Sleep apnea is common in PCS patients complaining of non-restorative sleep and/or waking up with headaches. Sleep apnea was associated with more memory symptoms. PCS patients are at higher risk for sleep apnea and sleep study should be considered if complaining of non-restorative sleep and/or waking up with headaches, regardless of sex and other known risk factors.

Selective Colour Vision Deficits in Multiple Sclerosis at Different Temporal Stages.

Multiple sclerosis (MS) without optic neuritis causes color-vision deficit but the evidence for selective color deficits in parvocellular-Red/Green (PC-RG) and koniocellular-Blue/Yellow (KC-BY) pathways is inconclusive. We investigated selective color-vision deficits at different MS stages. Thirty-one MS and twenty normal participants were tested for achromatic, red-green and blue-yellow sinewave-gratings (0.5 and 2 cycles-per-degree (cpd)) contrast orientation discrimination threshold. Red-green mean threshold at 0.5cpd in established-MS and blue-yellow mean threshold in all MS participants were abnormal. These findings show blue-yellow versus red-green color test is useful in differentiating MS chronicity, which helps to better understand the mechanism of colour-vision involvement in MS.

Neuroprotective effect of dimethyl fumarate in stroke: The role of nuclear factor erythroid 2-related factor 2.

Background: There is evidence that supports the neuroprotective effects of dimethyl fumarate (DMF) in stroke. Nuclear factor erythroid 2-related factor 2 (Nrf2) has both anti-oxidant and anti-inflammatory mechanisms. We investigated the neuroprotective effects of DMF via Nrf2 activation in the cortex, striatum, and diencephalon in a middle cerebral artery occlusion (MCAO) model of stroke. Methods: 22 Sprague-Dawley male rats were randomized into 3 groups. In DMF-treated group (n = 8), rats received 15 mg/kg oral DMF twice daily by gavage from day 0 to 14 after a 60-minute MCAO. The vehicle group (n = 7) underwent MCAO and were given methocel/H2O, using the same method and schedule. In the sham group (n = 7), neck was opened, but neither middle cerebral artery (MCA) was occluded nor any drug was administered. After 14 days, the animals were sacrificed. The infarct volume were assessed by stereology method. Nrf2 expression was evaluated in the cortex, striatum, and diencephalon by immunohistochemistry method. Results: Ratio of infarct to total brain volume was significantly lower in the DMF-treated group (5.76%) in comparison with the vehicle group (22.39%) (P < 0.0001). Nrf2 expression was higher in DMF-treated group in comparison with both the vehicle and sham groups in cortex, striatum, diencephalon, and total brain (P < 0.0001). In the DMF-treated group, significant negative correlation between Nrf2 expression and infarct volume was observed in cortex, striatum, diencephalon, and total brain. Conclusion: DMF induces Nrf2 expression and its neuroprotective effects in different brain anatomical regions.

Molybdenum coated SU-8 microneedle electrodes for transcutaneous electrical nerve stimulation.

Electrophysiological devices are connected to the body through electrodes. In some applications, such as nerve stimulation, it is needed to minimally pierce the skin and reach the underneath layers to bypass the impedance of the first layer called stratum corneum. In this study, we have designed and fabricated surface microneedle electrodes for applications such as electrical peripheral nerve stimulation. We used molybdenum for microneedle fabrication, which is a biocompatible metal; it was used for the conductive layer of the needle array. To evaluate the performance of the fabricated electrodes, they were compared with the conventional surface electrodes in nerve conduction velocity experiment. The recorded signals showed a much lower contact resistance and higher bandwidth in low frequencies for the fabricated microneedle electrodes compared to those of the conventional electrodes. These results indicate the electrode-tissue interface capacitance and charge transfer resistance have been increased in our designed electrodes, while the contact resistance decreased. These changes will lead to less harmful Faradaic current passing through the tissue during stimulation in different frequencies. We also compared the designed microneedle electrodes with conventional ones by a 3-dimensional finite element simulation. The results demonstrated that the current density in the deep layers of the skin and the directivity toward a target nerve for microneedle electrodes were much more than those for the conventional ones. Therefore, the designed electrodes are much more efficient than the conventional electrodes for superficial transcutaneous nerve stimulation purposes.