Faculty Bibliography

BACKGROUND:The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure. METHODS:71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8 weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP. RESULTS: = 0.486, p < 0.001). CONCLUSIONS:Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis.

OBJECTIVES/OBJECTIVE:To characterise psychological distress during the COVID-19 pandemic among collegiate athletes and assess whether racial and ethnic differences in psychological distress are attenuated when accounting for inequitable exposure to structural and social determinants of health. METHODS:Participants were collegiate athletes on teams competing in the National Collegiate Athletic Association (n=24 246). An electronic questionnaire was distributed by email, open for completion 6 October to 2 November 2020. Multivariable linear regression models were used to assess the cross-sectional associations between meeting basic needs, death or hospitalisation due to COVID-19 of a close contact, race and ethnicity, and psychological distress. RESULTS:Athletes racialised as Black had higher levels of psychological distress than their white peers (B=0.36, 95% CI 0.08 to 0.64). Psychological distress was higher among athletes who had more difficulties meeting basic needs, and who had a close contact die or be hospitalised with COVID-19. After adjusting for these structural and social factors, Black athletes experienced less psychological distress than white peers (B=-0.27, 95% CI -0.54 to -0.01). CONCLUSIONS:The present findings provide further evidence of how inequitable structural and social exposures are associated with racial and ethnic differences in mental health outcomes. Sports organisations should ensure the mental health services available for their athletes are appropriate for meeting the needs of individuals experiencing complex and traumatic stressors. Sports organisations should also consider whether there are opportunities to screen for social needs (eg, related to food or housing insecurity), and to connect athletes with resources to help meet those needs.

In 2019, the International Olympic Committee (IOC) published a consensus statement outlining the principles for recording and reporting injury and illness in elite sport. The authors encouraged sport federations to adapt the framework to their sport-specific context. Since this publication, several sports have published extensions to the IOC consensus statement.In response to a paucity of epidemiological data on athlete mental health, the IOC mental health working group adapted the IOC consensus statement on injury and illness surveillance to improve the capturing of athlete mental health data. In addition to the members of the working group, other experts and athlete representatives joined the project team to address gaps in expertise, and to add stakeholder perspective, respectively. Following an in-person meeting, the authors worked remotely, applying the scientific literature on athlete mental health to the IOC injury and illness surveillance framework. A virtual meeting was held to reach consensus on final recommendations.Practical outcomes based on the analysis of the scientific literature are provided with respect to surveillance design, data collection and storage, data analysis and reporting of athlete mental health data. Mental health-specific report forms for athlete and health professional utilisation are included for both longitudinal and event-specific surveillance.Ultimately, this publication should encourage the standardisation of surveillance methodology for mental health symptoms and disorders among athletes, which will improve consistency in study designs, thus facilitating the pooling of data and comparison across studies. The goal is to encourage systematic surveillance of athlete mental health.

PURPOSE/OBJECTIVE:Remote patient monitoring (RPM) is a tool for patients to share data collected outside of office visits. RPM uses technology and the digital transmission of data to inform clinician decision-making in patient care. Using RPM to track routine physical activity is feasible to operationalize, given contemporary consumer-grade devices that can sync to the electronic health record. Objective monitoring through RPM can be more reliable than patient self-reporting for physical activity. DESIGN AND METHODS/METHODS:This article reports on four pilot studies that highlight the utility and practicality of RPM for physical activity monitoring in outpatient clinical care. Settings include endocrinology, cardiology, neurology, and pulmonology settings. RESULTS:The four pilot use cases discussed demonstrate how RPM is utilized to monitor physical activity, a shift that has broad implications for prediction, prevention, diagnosis, and management of chronic disease and rehabilitation progress. CLINICAL RELEVANCE/CONCLUSIONS:If RPM for physical activity is to be expanded, it will be important to consider that certain populations may face challenges when accessing digital health services. CONCLUSION/CONCLUSIONS:RPM technology provides an opportunity for clinicians to obtain objective feedback for monitoring progress of patients in rehabilitation settings. Nurses working in rehabilitation settings may need to provide additional patient education and support to improve uptake.

BACKGROUND:Deep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics. METHODS:The c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification. FINDINGS/RESULTS:The application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6). INTERPRETATION/CONCLUSIONS:Our results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation. FUNDING/BACKGROUND:The specific funding of this article is provided in the acknowledgements section.

INTRODUCTION/BACKGROUND:Cerebrovascular pathology is an early and causal hallmark of Alzheimer's disease (AD), in need of effective therapies. METHODS:Based on the success of our previous in vitro studies, we tested for the first time in a model of AD and cerebral amyloid angiopathy (CAA), the carbonic anhydrase inhibitors (CAIs) methazolamide and acetazolamide, Food and Drug Administration-approved against glaucoma and high-altitude sickness. RESULTS:Both CAIs reduced cerebral, vascular, and glial amyloid beta (Aβ) accumulation and caspase activation, diminished gliosis, and ameliorated cognition in TgSwDI mice. The CAIs also improved microvascular fitness and induced protective glial pro-clearance pathways, resulting in the reduction of Aβ deposition. Notably, we unveiled that the mitochondrial carbonic anhydrase-VB (CA-VB) is upregulated in TgSwDI brains, CAA and AD+CAA human subjects, and in endothelial cells upon Aβ treatment. Strikingly, CA-VB silencing specifically reduces Aβ-mediated endothelial apoptosis. DISCUSSION/CONCLUSIONS:This work substantiates the potential application of CAIs in clinical trials for AD and CAA.

BACKGROUND:) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. PURPOSE:estimation. STUDY TYPE:Retrospective. POPULATION:A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. FIELD STRENGTH/SEQUENCE:A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. ASSESSMENT:were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. STATISTICAL TESTS:Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P ≤ 0.05. RESULTS:(r = 0.705). DATA CONCLUSION:may underestimate CVR and could exaggerate CCD. EVIDENCE LEVEL:4. TECHNICAL EFFICACY:Stage 3.

OBJECTIVE:Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. METHODS:Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. RESULTS:The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05-0.4; RTX: 0.03 μg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. INTERPRETATION:These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.

We used the forepaw barrel subfield (FBS), that normally receives input from the forepaw skin surface, in rat primary somatosensory cortex as a model system to study rapid and delayed lower jaw-to-forepaw cortical reorganization. Single and multi-unit recording from FBS neurons was used to examine the FBS for the presence of "new" lower jaw input following deafferentations that include forelimb amputation, brachial plexus nerve cut, and brachial plexus anesthesia. The major findings are as follows: (1) immediately following forelimb deafferentations, new input from the lower jaw becomes expressed in the anterior FBS; (2) 7-27 weeks after forelimb amputation, new input from the lower jaw is expressed in both anterior and posterior FBS; (3) evoked response latencies recorded in the deafferented FBS following electrical stimulation of the lower jaw skin surface are significantly longer in both rapid and delayed deafferents compared to control latencies for input from the forepaw to reach the FBS or for input from lower jaw to reach the LJBSF; (4) the longer latencies suggest that an additional relay site is imposed along the somatosensory pathway for lower jaw input to access the deafferented FBS. We conclude that different sources of input and different mechanisms underlie rapid and delayed reorganization in the FBS and suggest that these findings are relevant, as an initial step, for developing a rodent animal model to investigate phantom limb phenomena.

RATIONALE/BACKGROUND:The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS:Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS:The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS:These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.