Faculty Bibliography

Background/Objectives/UNASSIGNED:Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. Methods/UNASSIGNED:We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. Results/UNASSIGNED:= 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. Conclusion/UNASSIGNED:Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.

Purpose/UNASSIGNED:Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine. Methods/UNASSIGNED:In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities. Results/UNASSIGNED:Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions. Conclusion/UNASSIGNED:tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

Background: Fatigue is among the most frequent and disabling symptoms in RMS patients.
Objective(s): To measure multiple sclerosis (MS) fatigue and its impact on daily life in a real-world population using a survey including the relapsing MS (RMS)-specific Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS).
Method(s): This is an ongoing noninterventional prospective study of RMS patients recruited across the USA via an online survey. Participants completed questionnaires including disease history, disease status, sleep, social and emotional functioning, and the FSIQ-RMS, administered daily for 7 days. The FSIQ-RMS measures self-reported fatigue, and scores range from 0-100 (higher score = greater severity). The impact of fatigue on several aspects of patient's life was rated from 0 (no impact) to 10 (very high impact).
Result(s): A total of 300 RMS participants completed the 7-day assessment: mean age: 43.0 yrs; 88% women; mean diagnosis age: 32 yrs. Fatigue was reported as the symptom with the greatest impact on daily functioning. Participants with lower disability rated fatigue as the most impactful symptom on daily life. Fatigue was rated as severe, with a mean score: 57.3 for the FSIQ-RMS symptom domain; 3 impact sub-domain scores were 42.3, 43.4 and 50.1 (physical, cognitive/emotional, and coping). Fatigue severity did not vary among patients receiving high efficacy disease modifying therapy (DMT) vs other DMTs (44% [n=111] vs 56% [n=143], with score of 57.8?}17.6 vs 55.9?}19.8). Impact of ability to perform daily activities was rated as the highest (6.9/10) in terms of impact on patient's life. Because of MS, 44% of participants did not work. Among those who were working currently (48%), the impact of fatigue on professional life was rated as 4.5/10. Nearly half of the participants (49% of 300) discussed fatigue at each visit with their neurologists and 35% discussed at most visits, with 'impact of fatigue on quality of life' being the most discussed topic (65% of 289). Participants used different approaches to manage their fatigue including avoided heat exposure (77%), took breaks (65%), managed their energy (59%), took non-medicinal products (58%); however, only 6% (of 293) were totally satisfied with these strategies.
Conclusion(s): In this survey including the novel RMS specific FSIQ-RMS, fatigue occurred in most MS participants and adversely influenced patient's daily functioning and life. Fatigue remains a major concern for those with MS

Background: The corticoreticulospinal tract (CReST) is a major descending motor pathway in humans, but little is known about its relative innervation of proximal versus distal upper extremity (UE) muscles. In addition, CReST is believed to reorganize after corticospinal injury, but changes in its projections to different paretic muscles remain unknown. Here, we used transcranial magnetic stimulation (TMS) to probe the functional connectivity of the contralesional CReST to an arm muscle (biceps (BIC)) and an intrinsic hand muscle (first dorsal interosseous (FDI)) in healthy and stroke subjects.
Method(s): In this cross-sectional observational study, we examined 15 healthy (F: 7; mean age: 54 (44-81) years; mean UE Fugl-Meyer Assessment (FMA) score: 65 (63-66)) and 16 chronic stroke subjects (F: 10; mean age 62 (44-85) years; mean UE FMA score: 49 (23-64); mean time since stroke: 5 (0.5-14.4) years). We applied TMS to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs). We measured contralesional CReST functional connectivity (iMEP presence/absence) and projection strength (iMEP size; mV*ms) to the paretic BIC and FDI. We also measured paretic muscle maximum voluntary contraction and segmental FMA subscores. We examined differences in CReST projections between muscles and subject groups using Fisher's exact tests and general linear mixed models, and examined neurophysiologicalbehavioral relationships with Pearson's and Spearman's correlations.
Result(s): The contralesional CReST made functional connections to both muscles of most subjects (iMEP presence/absence: healthy BIC 14/1, healthy FDI 15/0; stroke BIC 11/5, stroke FDI 15/1). CReST functional connectivity did not differ between muscles in either healthy or stroke subjects (all p>0.172), and did not differ between subject groups for either muscle (all p=1.0). However, CReST projection strength for the muscles diverged between subject groups, manifesting as larger iMEPs in FDIs than BICs in healthy subjects (1.9 mV*ms, p=0.042) and larger iMEPs in BICs than FDIs in stroke subjects (1.0 mV*ms, p=0.042). Muscle iMEP sizes did not significantly differ between healthy and stroke subjects. Muscle strength related to iMEP size in only the paretic BIC of stroke subjects (r(6)=0.853, p=0.007). There was no relationship between FMA subscores and iMEP size for either muscle in either subject group.
Conclusion(s): Our findings indicate that the contralesional CReST has readily identifiable connections to the paretic BIC and FDI. In healthy subjects, the identification of a stronger CReST projection strength to the FDI challenges the notion of a proximal innervation bias by the reticulospinal tract. The shift in projection strength to the BIC after stroke reinforces the concept that the CReST reorganizes after CST injury, with circumscribed behavioral relevance. To confirm a recovery role of the CReST, a longitudinal observation of recovering behavior relating to changing CReST neurophysiology is required.

Recent findings challenge the prior notion that the cerebellum remains unaffected by Alzheimer's disease (AD). Yet, it is unclear whether AD exacerbates age-related cerebellar grey matter decline or engages distinct structural and functional territories. We performed a meta-analysis of cerebellar grey matter loss in normal ageing and AD. We mapped voxels with structural decline onto established brain networks, functional parcellations, and along gradients that govern the functional organisation of the cerebellum. Importantly, these gradients track continuous changes in cerebellar specialisation providing a more nuanced measure of the functional profile of regions vulnerable to ageing and AD. Gradient 1 progresses from motor to cognitive territories; Gradient 2 isolates attentional processing; Gradient 3 captures lateralisation differences in cognitive functions. We identified bilateral and right-lateralised posterior cerebellar atrophy in ageing and AD, respectively. Age- and AD-related structural decline only showed partial spatial overlap in right lobule VI/Crus I. Despite the seemingly distinct patterns of AD- and age-related atrophy, the functional profiles of these regions were similar. Both participate in the same macroscale networks (default mode, frontoparietal, attention), support executive functions and language processing, and did not exhibit a difference in relative positions along Gradients 1 or 2. However, Gradient 3 values were significantly different in ageing vs. AD, suggesting that the roles of left and right atrophied cerebellar regions exhibit subtle functional differences despite their membership in similar macroscale networks. These findings provide an unprecedented characterisation of structural and functional differences and similarities in cerebellar grey matter loss between normal ageing and AD.