Faculty Bibliography

People with blindness and low vision (pBLV) encounter substantial challenges when it comes to comprehensive scene recognition and precise object identification in unfamiliar environments. Additionally, due to the vision loss, pBLV have difficulty in accessing and identifying potential tripping hazards independently. Previous assistive technologies for the visually impaired often struggle in real-world scenarios due to the need for constant training and lack of robustness, which limits their effectiveness, especially in dynamic and unfamiliar environments, where accurate and efficient perception is crucial. Therefore, we frame our research question in this paper as: How can we assist pBLV in recognizing scenes, identifying objects, and detecting potential tripping hazards in unfamiliar environments, where existing assistive technologies often falter due to their lack of robustness? We hypothesize that by leveraging large pretrained foundation models and prompt engineering, we can create a system that effectively addresses the challenges faced by pBLV in unfamiliar environments. Motivated by the prevalence of large pretrained foundation models, particularly in assistive robotics applications, due to their accurate perception and robust contextual understanding in real-world scenarios induced by extensive pretraining, we present a pioneering approach that leverages foundation models to enhance visual perception for pBLV, offering detailed and comprehensive descriptions of the surrounding environment and providing warnings about potential risks. Specifically, our method begins by leveraging a large-image tagging model (i.e., Recognize Anything Model (RAM)) to identify all common objects present in the captured images. The recognition results and user query are then integrated into a prompt, tailored specifically for pBLV, using prompt engineering. By combining the prompt and input image, a vision-language foundation model (i.e., InstructBLIP) generates detailed and comprehensive descriptions of the environment and identifies potential risks in the environment by analyzing environmental objects and scenic landmarks, relevant to the prompt. We evaluate our approach through experiments conducted on both indoor and outdoor datasets. Our results demonstrate that our method can recognize objects accurately and provide insightful descriptions and analysis of the environment for pBLV.

APOE^ε4 is the major genetic risk factor for sporadic Alzheimer's disease (AD). Although APOE^ε4 is known to promote Aβ pathology, recent data also support an effect of APOE polymorphism on phosphorylated Tau (pTau) pathology. To elucidate these potential effects, the pTau interactome was analyzed across APOE genotypes in the frontal cortex of 10 advanced AD cases (n = 5 APOE^ε3/ε3 and n = 5 APOE^ε4/ε4), using a combination of anti-pTau pS396/pS404 (PHF1) immunoprecipitation (IP) and mass spectrometry (MS). This proteomic approach was complemented by an analysis of anti-pTau PHF1 and anti-Aβ 4G8 immunohistochemistry, performed in the frontal cortex of 21 advanced AD cases (n = 11 APOE^ε3/ε3 and n = 10 APOE^ε4/ε4). Our dataset includes 1130 and 1330 proteins enriched in IP_PHF1 samples from APOE^ε3/ε3 and APOE^ε4/ε4 groups (fold change ≥ 1.50, IP_PHF1 vs IP_{IgG ctrl}). We identified 80 and 68 proteins as probable pTau interactors in APOE^ε3/ε3 and APOE^ε4/ε4 groups, respectively (SAINT score ≥ 0.80; false discovery rate (FDR) ≤ 5%). A total of 47/80 proteins were identified as more likely to interact with pTau in APOE^ε3/ε3 vs APOE^ε4/ε4 cases. Functional enrichment analyses showed that they were significantly associated with the nucleoplasm compartment and involved in RNA processing. In contrast, 35/68 proteins were identified as more likely to interact with pTau in APOE^ε4/ε4 vs APOE^ε3/ε3 cases. They were significantly associated with the synaptic compartment and involved in cellular transport. A characterization of Tau pathology in the frontal cortex showed a higher density of plaque-associated neuritic crowns, made of dystrophic axons and synapses, in APOE^ε4 carriers. Cerebral amyloid angiopathy was more frequent and severe in APOE^ε4/ε4 cases. Our study supports an influence of APOE genotype on pTau-subcellular location in AD. These results suggest a facilitation of pTau progression to Aβ-affected brain regions in APOE^ε4 carriers, paving the way to the identification of new therapeutic targets.

BACKGROUND:Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. METHODS:RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. DISCUSSION/CONCLUSIONS:This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

OBJECTIVES/OBJECTIVE:(1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity. METHODS:Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. RESULTS:The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity. INTERPRETATION/CONCLUSIONS:Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.

INTRODUCTION/UNASSIGNED:Alzheimer's Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent. METHODS/UNASSIGNED: = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus. RESULTS/UNASSIGNED:SCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD. DISCUSSION/UNASSIGNED:The diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.

BACKGROUND:We examined drivers of self and study partner reports of memory loss in mild cognitive impairment (MCI) from Alzheimer (AD-MCI) and vascular disease (Va-MCI). METHODS:We performed retrospective cross-sectional analyses of participants with AD-MCI (n=2874) and Va-MCI (n=376) from the National Alzheimer's Coordinating Center data set. Statistical analysis utilized 2-sided t test or the Fisher exact test. RESULTS:Compared with AD-MCI, Va-MCI subjects (24.5% vs. 19.7%, P=0.031) and study partners (31.4% vs. 21.6%, P<0.0001) were more likely to deny memory loss. Black/African Americans were disproportionately represented in the group denying memory loss in AD-MCI (20.0% vs. 13.2%, P<0.0001) and Va-MCI (33.7% vs. 18.0%, P=0.0022). Study partners of participants with these features also disproportionately denied memory loss: female (AD-MCI: 60.1% vs. 51.7%, P=0.0002; Va-MCI: 70.3% vs. 52.3%, P=0.0011), Black/African American (AD-MCI: 23.5% vs. 11.98%, P<0.0001; Va-MCI: 48.8% vs. 26.5%, P=0.0002), and <16 years of education (AD-MCI only: 33.9% vs. 16.3%, P=0.0262). In AD-MCI and Va-MCI, participants with anxiety were disproportionately represented in the group endorsing memory loss (AD: 28.2% vs. 17.4%, P<0.0001; Va: 31.5% vs. 16.1%, P=0.0071), with analogous results with depression. CONCLUSION/CONCLUSIONS:The findings would suggest extra vigilance in interview-based MCI detection of persons at-risk for self-based or informant-based misreport.

BACKGROUND AND PURPOSE/OBJECTIVE:Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS/METHODS:Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS:Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS:This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.

OBJECTIVE:Epilepsy patients often report memory deficits despite normal objective testing, suggesting that available measures are insensitive or that non-mnemonic factors are involved. The Visual Paired Comparison Task (VPCT) assesses novelty preference, the tendency to fixate on novel images rather than previously viewed items, requiring recognition memory for the "old" images. As novelty preference is a sensitive measure of hippocampal-dependent memory function, we predicted impaired VPCT performance in epilepsy patients compared to healthy controls. METHODS:We assessed 26 healthy adult controls and 31 epilepsy patients (16 focal-onset, 13 generalized-onset, 2 unknown-onset) with the VPCT using delays of 2 or 30 s between encoding and recognition. Fifteen healthy controls and 17 epilepsy patients (10 focal-onset, 5 generalized-onset, 2 unknown-onset) completed the task at 2-, 5-, and 30-minute delays. Subjects also performed standard memory measures, including the Medical College of Georgia (MCG) Paragraph Test, California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visual Memory Test-Revised (BVMT-R). RESULTS:The epilepsy group was high functioning, with greater estimated IQ (p = 0.041), greater years of education (p = 0.034), and higher BVMT-R scores (p = 0.024) compared to controls. Both the control group and epilepsy cohort, as well as focal- and generalized-onset subgroups, had intact novelty preference at the 2- and 30-second delays (p-values ≤ 0.001) and declined at 30 min (p-values > 0.05). Only the epilepsy patients had early declines at 2- and 5-minute delays (controls with intact novelty preference at p = 0.003 and p ≤ 0.001, respectively; epilepsy groups' p-values > 0.05). CONCLUSIONS:Memory for the "old" items decayed more rapidly in overall, focal-onset, and generalized-onset epilepsy groups. The VPCT detected deficits while standard memory measures were largely intact, suggesting that the VPCT may be a more sensitive measure of temporal lobe memory function than standard neuropsychological batteries.