Faculty Bibliography

Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are learned without considering behavior. We develop preferential subspace identification (PSID), which is an algorithm that models neural activity while dissociating and prioritizing its behaviorally relevant dynamics. Modeling data in two monkeys performing three-dimensional reach and grasp tasks, PSID revealed that the behaviorally relevant dynamics are significantly lower-dimensional than otherwise implied. Moreover, PSID discovered distinct rotational dynamics that were more predictive of behavior. Furthermore, PSID more accurately learned behaviorally relevant dynamics for each joint and recording channel. Finally, modeling data in two monkeys performing saccades demonstrated the generalization of PSID across behaviors, brain regions and neural signal types. PSID provides a general new tool to reveal behaviorally relevant neural dynamics that can otherwise go unnoticed.

Background/UNASSIGNED:The Symbol Digit Modalities Test (SDMT) is the gold standard for cognitive screening in multiple sclerosis (MS). Objective/UNASSIGNED:Due to the recent COVID-19 pandemic and the increased need for virtual clinical visits, we examined the reliability of remote administration of the SDMT vs. standard in-person administration to individuals with MS. Methods/UNASSIGNED:Pearson's correlation analysis was performed between SDMT scores on the in-person and remote administrations. Results/UNASSIGNED: = .000). Conclusion/UNASSIGNED:Remote administration of the SDMT is a reliable cognitive screening approach in MS.

Despite support for the role of self-medication alcohol use in the etiology and maintenance of comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), theoretical and empirical models of PTSD-AUD rarely account for the role of common comorbidities in risk processes, such as major depressive disorder (MDD). The current study examined the main and interactive effects of PTSD and depressive symptoms on patterns of trauma and alcohol cue reactivity to elucidate potential influences of depression on conditioned craving responses to trauma memories. It was hypothesized that depressive symptoms would be associated with greater cue reactivity (i.e., craving and salivation) to personalized trauma cues, above and beyond the influence of PTSD symptoms. Participants were 184 trauma-exposed young adults (50% female) endorsing current weekly alcohol use. Patterns of craving and salivation were assessed in response to four combinations of narrative (trauma vs. neutral) and beverage (alcohol vs. water) cues. Forward-fitted linear mixed effects models with deviance testing were conducted to ascertain the impact of the within-subjects factors (narrative and beverage cues) and covariates (PTSD and depressive symptoms) on self-reported and physiological (salivation) alcohol craving. Depressive symptoms were associated with elevated drinking coping motives, AUD symptom severity, and alcohol use problems at baseline; however, depressive symptoms did not show main or interactive effects with narrative or beverage cues to predict craving or salivation, p's > 0.05. Results suggest that, in the context of PTSD symptoms, depressive symptoms may not exacerbate alcohol craving responses to trauma reminders or alcohol cues.

BACKGROUND AND PURPOSE/OBJECTIVE:Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. MATERIALS AND METHODS/METHODS:This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. RESULTS:< .003). CONCLUSIONS:Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.

Objective: A recent clinical trial with 0.7mg/kg/day of fenfluramine (FFA) showed 62.3% (IC 95%: -47.7%; -72.8%; p<0.001) reduction in convulsive seizure frequency (CSF) compared to placebo. However, the impact of the disease on the patient and their caregivers may depend on other variables. This alternative analysis value the impact of other results.
Method(s): After a baseline period of 6 weeks patients with DS ages 2 to 18 years, was randomized to FFA 0.7 or 0.2mg/kg/day or placebo added. Time to new event (time required to experience the same number of crisis as in the reference period [TTE]) was analyzed. Intervals without crisis and number of days without crisis was analyzed too.
Result(s): 119 patients with DS receiving FFA 0.7mg/kg/day; FFA0.2mg/kg/day; or placebo. TTE was significantly longer in active groups. Placebo: 6 weeks, FFA 0.2mg/kg/day:8 weeks and FFA 0.7mg/kg/day: >12 weeks (p<0.001; ~60% of patients in the FFA 0.7mg/kg/day group never reached their baseline seizure count and were censored). The number of days without crisis was higher in groups treated with FFA: 33 and 20 days without additional crisis counted in the active groups. The longest average without crisis was higher with FFA 0.7mg/kg/day (25 days; p<0.001) and FFA 0.2mg/kg/day (15 days; Px0.035) than with placebo (9.5 days).
Conclusion(s): FFA extended TTE and provided significantly more days without crisis and longer periods without crisis than placebo. Our analysis can help assess the ability of a treatment to reduce the burden of seizures in patients with SD and their caregivers

Mural cells (smooth muscle cells and pericytes) are integral components of brain blood vessels that play important roles in vascular formation, blood-brain barrier maintenance, and regulation of regional cerebral blood flow (rCBF). These cells are implicated in conditions ranging from developmental vascular disorders to age-related neurodegenerative diseases. Here we present complementary tools for cell labeling with transgenic mice and organic dyes that allow high-resolution intravital imaging of the different mural cell subtypes. We also provide detailed methodologies for imaging of spontaneous and neural activity-evoked calcium transients in mural cells. In addition, we describe strategies for single- and two-photon optogenetics that allow manipulation of the activity of individual and small clusters of mural cells. Together with measurements of diameter and flow in individual brain microvessels, calcium imaging and optogenetics allow the investigation of pericyte and smooth muscle cell physiology and their role in regulating rCBF. We also demonstrate the utility of these tools to investigate mural cells in the context of Alzheimer's disease and cerebral ischemia mouse models. Thus, these methods can be used to reveal the functional and structural heterogeneity of mural cells in vivo, and allow detailed cellular studies of the normal function and pathophysiology of mural cells in a variety of disease models. The implementation of this protocol can take from several hours to days depending on the intended applications.

INTRODUCTION: Clinicians caring for critically-ill patients must be able to discuss prognosis and deliver bad news. To teach Neurology residents how to do this, we designed an objective structured clinical examination (OSCE) case in which trainees discussed prognosis with a standardized patient (SP).
METHOD(S): In 2017, in conjunction with the NYU School of Medicine Simulation Center, neurology faculty designed an OSCE case in which a resident was tasked with informing a SP her father had severe global hypoxic ischemic injury. The SP was instructed to assess the resident's ability to 1) explain the neurologic findings and 2) to respond to an emotional outburst. A neurology attending observed the encounter via one-way glass. After a 10-minute encounter, the resident was provided 5 minutes of feedback. The residents were surveyed on how prepared they felt for the OSCE, how useful it was, how they rated their performance, and how much they learned from the activity via a Likert scale from 1 (worst) to 5 (best) and free text response. The SP completed a behavioral anchored checklist to assess the residents' ability to gather information, develop a relationship, provide education and counseling, present bad news, and maintain professionalism.
RESULT(S): 57 third and fourth year neurology residents completed the case from 2018-2020, 54 (95%) of whom completed the post-OSCE survey. Residents reported feeling moderately prepared (mean Likert score 3.7/5) and rated their performance as average (3.4/5). Overall they found the case to be very helpful (4.6/5). Several reported difficultly with 1) addressing a complex medical case in a limited amount of time 2) reacting appropriately to an emotional family member and 3) avoiding medical jargon. The SP reported that residents performed well in the realms of non-verbal behavior enriched communication, being non-judgmental, not interrupting, acknowledging emotion, and avoiding medical jargon. Areas in which there was room for improvement included collaborating with the SP to decide upon next steps, identifying a support system, and asking "what is going through your mind right now?".
CONCLUSION(S): OSCE cases can be used to teach clinicians how to discuss prognosis and break bad news. Feedback about this simulation was positive, however its efficacy has yet to be evaluated

PURPOSE OF REVIEW/OBJECTIVE:The mental health toll on populations exposed to COVID-19 is alarming, and there is a need to address this with urgency. This current review provides insights on how individuals, communities, and specific populations, such as healthcare workers and patients are leveraging pre-COVID-19 and peri-COVID-19 factors to reinforce their psychological resilience during the global public health crisis. RECENT FINDINGS/RESULTS:Examination of the extant literature indicated that populations around the world rely often on support from their loved-ones, closed significant others, outdoor and physical activities, and spirituality to cope with the COVID-19-related distress. Increased sense of meaning/purpose since the COVID-19 pandemic was also reported. SUMMARY/CONCLUSIONS:A portion of publications provided intervention models to reinforce resilience among specific populations during the COVID-19 pandemic. Nevertheless, it is not convincing that some of these models can be applied universally. Additionally, it is important to note that in this category, translational data was scarce.

OBJECTIVE:Intraoperative neuromonitoring (IONM) techniques aim to identify and potentially prevent nerve injury during surgeries. Prior studies into the efficacy of recurrent laryngeal nerve (RLN) IONM convey mixed results, with some claiming equivalence between IONM and no monitoring at all. The goal of the current study was to compare continuous RLN monitoring using the laryngeal adductor reflex (LAR) to intermittent RLN monitoring (intermittent IONM) to determine whether continuous monitoring reduces the incidence of intraoperative RLN injury during neck endocrine surgeries. METHODS:In this observational, historical case-control study, a historical cohort of patients monitored with intermittent-IONM (group 1, n = 130) were compared to prospectively collected data from consecutive nerves-at-risk monitored continuously with the LAR (LAR-CIONM, group 2, n = 205), at a single center by a single surgeon. The test benefit ratio and relative risk reduction (RRR) for LAR-CIONM over intermittent IONM were calculated. RESULTS:For group 1, nine nerves at risk exhibited intraoperative LOS with transient postoperative vocal fold (VF) hypomobility (n = 2) or immobility (VFI, n = 7). For group 2, two nerves at risk (0.98%) had sudden intraoperative LAR LOS following bipolar cautery, resulting in postoperative transient VFI (P = .004). In each group, there was one case of permanent postoperative VFI. The test benefit rate ratio for LAR-CIONM demonstrated a dramatic effect at 5.23, with an RRR of 81.0%. CONCLUSION/CONCLUSIONS:LAR-CIONM significantly decreased rates of postoperative transient VF paralysis and paresis over intermittent IONM alone (P = .004). Surgeons should be aware of the benefits and limitations of intermittent IONM versus CIONM. Intermittent IONM, although useful in nerve mapping and intraoperative decision making, has minimal benefit for the prevention of nerve injury, whereas CIONM can potentially reduce nerve injury rates and improve patient outcomes. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2020.