Faculty Bibliography

It is important to consider antisynthetase syndrome in the differential diagnosis of patients presenting with weakness, respiratory distress, and a constellation of complaints spanning multiple organ systems, as this will change clinical management.

BACKGROUND AND PURPOSE/OBJECTIVE:With the surge of critically ill COVID-19 patients, neurology and neurosurgery residents and advanced practice providers (APPs) were deployed to intensive care units (ICU). These providers lacked relevant critical care training. We investigated whether a focused video-based learning curriculum could effectively teach high priority intensive care topics in this unprecedented setting to these neurology providers. METHODS:Neurocritical care clinicians led a multidisciplinary team in developing a 2.5-hour lecture series covering the critical care management of COVID-19 patients. We examined whether provider confidence, stress, and knowledge base improved after viewing the lectures. RESULTS:A total of 88 residents and APPs participated across 2 academic institutions. 64 participants (73%) had not spent time as an ICU provider. After viewing the lecture series, the proportion of providers who felt moderately, quite, or extremely confident increased from 11% to 72% (60% difference, 95% CI 49-72%) and the proportion of providers who felt nervous/stressed, very nervous/stressed, or extremely nervous/stressed decreased from 78% to 48% (38% difference, 95% CI 26-49%). Scores on knowledge base questions increased an average of 2.5 out of 12 points (SD 2.1; p < 0.001). CONCLUSION/CONCLUSIONS:A targeted, asynchronous curriculum on critical care COVID-19 management led to significantly increased confidence, decreased stress, and improved knowledge among resident trainees and APPs. This curriculum could serve as an effective didactic resource for neurology providers preparing for the COVID-19 ICU.

Negative symptoms in the motivational domain are strongly correlated with deficits in social and occupational functioning in schizophrenia. However, the neural substrates underlying these symptoms remain largely unknown. Twenty-eight adults with schizophrenia and twenty healthy volunteers underwent functional magnetic resonance while completing a lottery game designed to capture reward-related cognitive processes. Each trial demanded an initial investment of effort in form of key presses to increase the odds of winning. Brain activity in response to different reward cues (1 euro versus 1 cent) was compared between groups. Whereas controls invested more effort in improving their chances to win 1 euro compared to 1 cent in the lottery game, patients invested similarly high amounts of effort in both reward conditions. The neuroimaging analysis revealed lower neural activity in the bilateral caudate and cingulo-opercular circuits and decreased effective connectivity between reward-associated areas and neural nodes in the frontoparietal and salience network in response to high- versus low-reward conditions in schizophrenia patients compared to controls. Effective connectivity differences across conditions were associated with amotivation symptoms in patients. Overall, our data provide the evidence of alterations in neural activity in the caudate and cingulo-opercular "task maintenance" circuits and frontoparietal effective connectivity with reward-associated nodes as possible underlying mechanisms of reward value discrimination deficits affecting effort computation in schizophrenia.

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.

Adolescents with anxiety disorders exhibit excessive emotional and somatic arousal. Neuroimaging studies have shown abnormal cerebral cortical activation and connectivity in this patient population. The specific role of cerebellar output circuitry, specifically the dentate nuclei (DN), in adolescent anxiety disorders remains largely unexplored. Resting-state functional connectivity analyses have parcellated the DN, the major output nuclei of the cerebellum, into three functional territories (FTs) that include default-mode, salience-motor, and visual networks. The objective of this study was to understand whether FTs of the DN are implicated in adolescent anxiety disorders. Forty-one adolescents (mean age 15.19 ± 0.82, 26 females) with one or more anxiety disorders and 55 age- and gender-matched healthy controls completed resting-state fMRI scans and a self-report survey on anxiety symptoms. Seed-to-voxel functional connectivity analyses were performed using the FTs from DN parcellation. Brain connectivity metrics were then correlated with State-Trait Anxiety Inventory (STAI) measures within each group. Adolescents with an anxiety disorder showed significant hyperconnectivity between salience-motor DN FT and cerebral cortical salience-motor regions compared to controls. Salience-motor FT connectivity with cerebral cortical sensorimotor regions was significantly correlated with STAI-trait scores in HC (R² = 0.41). Here, we report DN functional connectivity differences in adolescents diagnosed with anxiety, as well as in HC with variable degrees of anxiety traits. These observations highlight the relevance of DN as a potential clinical and sub-clinical marker of anxiety.

OBJECTIVE:The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia. METHODS:We used the magnetic resonance imaging (MRI) dataset from the Shanghai At Risk for Psychosis study that included subjects at high risk to develop schizophrenia (N = 144), with longitudinal follow-up to determine which subjects developed a psychotic episode within 1 year of their functional magnetic resonance imaging (fMRI) scan (converters N = 23). Analysis used the 3 functional parcels (default-mode, salience-motor, and visual territory) from the DN as seed regions of interest for whole-brain RsFc analysis. RESULTS:RsFc analysis revealed abnormalities at baseline in high-risk individuals who developed psychosis, compared to high-risk individuals who did not develop psychosis. The nature of the observed abnormalities was found to be anatomically specific such that abnormal RsFc was localized predominantly in cerebral cortical networks that matched the 3 functional territories of the DN that were evaluated. CONCLUSIONS:We show for the first time that abnormal RsFc of the DN may precede the onset of psychosis. This new evidence highlights the role of the cerebellum as a potential target for psychosis prediction and prevention.

Mapping the structural and functional connectivity of the central nervous system has become a key area within neuroimaging research. While detailed network structures across the entire brain have been probed using animal models, non-invasive neuroimaging in humans has thus far been dominated by cortical investigations. Beyond the cortex, subcortical nuclei have traditionally been less accessible due to their smaller size and greater distance from radio frequency coils. However, major neuroimaging developments now provide improved signal and the resolution required to study these structures. Here, we present an overview of the connectivity between the amygdala, brainstem, cerebellum, spinal cord and the rest of the brain. While limitations to their imaging and analyses remain, we also provide some recommendations and considerations for mapping brain connectivity beyond the cortex.