Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
Total Results:
23548
Adversarial testing of global neuronal workspace and integrated information theories of consciousness
Different theories explain how subjective experience arises from brain activity1,2. These theories have independently accrued evidence, but have not been directly compared3. Here we present an open science adversarial collaboration directly juxtaposing integrated information theory (IIT)4,5 and global neuronal workspace theory (GNWT)6-10 via a theory-neutral consortium11-13. The theory proponents and the consortium developed and preregistered the experimental design, divergent predictions, expected outcomes and interpretation thereof12. Human participants (n = 256) viewed suprathreshold stimuli for variable durations while neural activity was measured with functional magnetic resonance imaging, magnetoencephalography and intracranial electroencephalography. We found information about conscious content in visual, ventrotemporal and inferior frontal cortex, with sustained responses in occipital and lateral temporal cortex reflecting stimulus duration, and content-specific synchronization between frontal and early visual areas. These results align with some predictions of IIT and GNWT, while substantially challenging key tenets of both theories. For IIT, a lack of sustained synchronization within the posterior cortex contradicts the claim that network connectivity specifies consciousness. GNWT is challenged by the general lack of ignition at stimulus offset and limited representation of certain conscious dimensions in the prefrontal cortex. These challenges extend to other theories of consciousness that share some of the predictions tested here14-17. Beyond challenging the theories, we present an alternative approach to advance cognitive neuroscience through principled, theory-driven, collaborative research and highlight the need for a quantitative framework for systematic theory testing and building.
PMID: 40307561
ISSN: 1476-4687
CID: 5833912
Using Virtual Reality to Enhance Mobility, Safety, and Equity for Persons with Vision Loss in Urban Environments
This study explores the use of virtual reality (VR) as an innovative tool to enhance awareness, understanding of accessibility for persons with vision loss (VL), and acceptance. Through a VR-based workshop developed in collaboration with New York City's Department Of Transportation, participants experienced immersive simulations of VL and related immersive mobility challenges. The methodology included the development of a VR environment, simulations of vision loss, testing with the DOT team during the workshop, and an assessment of changes in participants' knowledge, confidence in addressing accessibility challenges, and overall perception through pre- and post-intervention questionnaires. Participants included urban planners, designers, and architects. Results showed a significant increase in awareness of VL-related challenges that affect design guidelines, as well as improved confidence in addressing such challenges. Participants also expressed strong support for VR as a pedagogical tool, noting its potential for reshaping professional practices, improving capacity building, and enhancing inclusive design. The study demonstrates the effectiveness of VR as an experiential learning platform, fostering empathy and a long-term commitment to integrating VL considerations into urban design. These findings highlight the transformative potential of VR in advancing equity and accessibility in urban environments.
PMID: 40014220
ISSN: 1468-2869
CID: 5801222
Education Research: A Behavioral Intervention to Improve Group-Based Diagnostic Quality and Educational Experience Among Neurology Trainees: A Feasibility Study
BACKGROUND AND OBJECTIVES/UNASSIGNED:"Brain-writing" is a technique in which group members write down ideas individually, before a group discussion, to improve idea generation and individual engagement in group discussions. We assessed the feasibility of studying the impact of brain-writing on diagnostic quality and educational experience among neurology residents in a small case-based learning environment. METHODS/UNASSIGNED:We conducted a repeated-measures study, conducted over 6 sessions consisting of groups of 3 to 5 neurology residents from different years of training. During each session, 3 cases were treated as control, "brainstorming," cases, and 3 were intervention, "brain-writing," cases, in which the group wrote down possible diagnoses and tests before engaging in a group discussion. Tests and diagnoses from the brain-writing exercise and group discussion as well as a post case survey on participant experience were recorded through a Qualtrics survey, and video recordings were reviewed to determine speaking order and number of tests and diagnoses verbalized by each member. Feasibility was determined by recruitment and ability to complete the study procedures in a pragmatic fashion that incorporated resident education. The primary outcome was accuracy of diagnoses, and secondary outcomes included number of tests and diagnoses generated, percent of "can't miss diagnoses mentioned," speaking order and psychological reactions of group members. RESULTS/UNASSIGNED:= 0.07). Junior residents spoke later and verbalized significantly fewer diagnoses and tests than senior residents in both brainstorming and brain-writing groups. There was no statistically significant difference in psychological outcomes of junior and senior residents in each group. DISCUSSION/UNASSIGNED:It is feasible to examine the impact of a behavioral-based intervention among medical trainees in a small case-based learning environment. This study, limited by a small sample size, did not find that brain-writing improved decision quality.
PMCID:11985166
PMID: 40212892
ISSN: 2771-9979
CID: 5824292
The cerebellum in epilepsy
The cerebellum, a subcortical structure, is traditionally linked to sensorimotor integration and coordination, although its role in cognition and affective behavior, as well as epilepsy, is increasingly recognized. Cerebellar dysfunction in patients with epilepsy can result from genetic disorders, antiseizure medications, seizures, and seizure-related trauma. Impaired cerebellar function, regardless of cause, can cause ataxia (imbalance, impaired coordination, unsteady gait), tremor, gaze-evoked nystagmus, impaired slow gaze pursuit and saccade accuracy, as well as speech deficits (slurred, scanning, or staccato). We explore how cerebellar dysfunction can contribute to epilepsy, reviewing data on genetic, infectious, and neuroinflammatory disorders. Evidence of cerebellar dysfunction in epilepsy comes from animal studies as well as human neuropathology and structural magnetic resonance imaging (MRI), functional and diffusion tensor MRI, positron emission and single photon emission computerized tomography, and depth electrode electro-encephalography studies. Cerebellar lesions can infrequently cause epilepsy, with focal motor, autonomic, and focal to bilateral tonic-clonic seizures. Antiseizure medication-resistant epilepsy typically presents in infancy or before age 1 year with hemifacial clonic or tonic seizures ipsilateral to the cerebellar mass. Lesions are typically asymmetric benign or low-grade tumors in the floor of the fourth ventricle involving the cerebellar peduncles and extending to the cerebellar hemisphere. Electrical stimulation of the cerebellum has yielded conflicting results on efficacy, although methodological issues confound interpretation. Epilepsy-related comorbidities including cognitive and affective disorders, falls, and sudden unexpected death in epilepsy may also be impacted by cerebellar dysfunction. We discuss how cerebellar dysfunction may drive seizures and how genetic epilepsies, seizures and seizure therapies may drive cerebellar dysfunction, and how our understanding of epilepsy-related comorbidities through basic neuroscience, animals models and patient studies can advance our understanding and improve patient outcomes.
PMID: 40079849
ISSN: 1528-1167
CID: 5808732
Minimum Technical Preanalytical, Patient, and Clinical Context Data Elements for Cerebrospinal Fluid Liquid Biopsy: Recommendations for Public Database Submissions
PURPOSE/OBJECTIVE:Blood-based liquid biopsy has enabled minimally invasive molecular profiling in patients with solid tumors. For cancers of the CNS, however, the use of peripheral blood for cell-free DNA (cfDNA) detection and sequencing has proved challenging because of scant levels of tumor-derived material shed into systemic circulation. An alternative is to use cerebrospinal fluid (CSF), which contains a greater concentration of tumor-derived cfDNA in patients with brain tumors (BTs). CSF liquid biopsy is a relatively nascent field, with critical unanswered questions regarding preanalytical variables that may affect assay performance. In an effort to identify and standardize key preanalytical variables, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium launched a BT Working Group in 2022. METHODS:We reviewed protocols for CSF sample collection and processing used by expert Working Group members at their respective academic institutions and diagnostic companies, as well as the available literature on CSF liquid biopsy. Through a collaborative and iterative process, we developed a list of key preanalytical variables for cfDNA-based CSF liquid biopsy in patients with primary and metastatic brain malignancies. RESULTS:The Working Group agreed on a recommended list of preanalytical minimum technical data elements, clinical context data elements, and patient context data elements for cfDNA-based CSF liquid biopsy in patients with CNS malignancies. A subset of variables were considered to be of critical priority and are designated as required annotations to submissions of cfDNA-based CSF liquid biopsy sample data into the BLOODPAC Data Commons. CONCLUSION/CONCLUSIONS:We propose a list of preanalytical variables relevant for cfDNA-based CSF liquid biopsy, with the overarching goal of encouraging routine collection and reporting of these variables in future studies.
PMID: 40570259
ISSN: 2473-4284
CID: 5962032
Considerations and recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 3-Ex vivo imaging: Data processing, comparisons with microscopy, and tractography
Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high SNR images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work concludes a three-part series of recommendations and considerations for preclinical dMRI. Herein, we describe best practices for dMRI of ex vivo tissue, with a focus on image pre-processing, data processing, and comparisons with microscopy. In each section, we attempt to provide guidelines and recommendations but also highlight areas for which no guidelines exist (and why), and where future work should lie. We end by providing guidelines on code sharing and data sharing and point toward open-source software and databases specific to small animal and ex vivo imaging.
PMID: 40008460
ISSN: 1522-2594
CID: 5800922
X-chromosome-wide association study for Alzheimer's disease
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-
PMID: 39633006
ISSN: 1476-5578
CID: 5804132
The history of Down syndrome-associated Alzheimer's disease; past, present, and future [Historical Article]
The landscape of Down syndrome-associated Alzheimer's disease (DSAD) research reflects decades of scientific endeavor and collaborative effort, charting a remarkable journey from initial observations to the elucidation of complex genetic and molecular mechanisms. This perspective article chronicles key milestones and breakthroughs, paying homage to the pioneering scientists and advancements that have shaped the field. A thorough review of historical and contemporary literature offers a comprehensive narrative, highlighting the evolution of knowledge surrounding DSAD, from early recognition to the characterization of clinical presentation and natural history. The unique challenges and ethical considerations associated with DSAD populations are also examined, underscoring the importance of tailoring research and clinical approaches. By reflecting on the field's trajectory, this work celebrates past achievements while emphasizing the critical need for sustained research efforts. As part of a special issue, this article provides a foundation for appreciating the challenges and opportunities that lie ahead in advancing DSAD understanding and care. HIGHLIGHTS: This article provides a comprehensive overview of Down syndrome-associated Alzheimer's disease (DSAD) history, from early descriptions to its recognition as a genetic form of AD. It reflects on historical challenges faced by individuals with intellectual disabilities in achieving inclusion in scientific research. This historical perspective highlights the critical contributions of individuals with DS in advancing understanding of AD natural history. It explores pivotal milestones and efforts that have driven progress in DSAD research. Finally, it provides context to understand challenges and opportunities in DSAD research and its future directions.
PMCID:12138279
PMID: 40469048
ISSN: 1552-5279
CID: 5862592
Dravet syndrome: From neurodevelopmental to neurodegenerative disease?
OBJECTIVE:Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency in the majority of cases. Caregivers of adults with DS often complain about the loss of previously acquired skills. We set out to explore these perceptions and determine whether abnormalities reported were detectable in validated tests. We also investigated possible correlations between symptoms, age, and exposure to sodium channel blockers (SCBs). METHODS:This cross-sectional, multicenter study used the Vineland Adaptive Behavior Scales, 3rd edition (raw scores) for behavior analyses and Moss-Psychiatric Assessment Schedules checklist to screen for psychiatric symptoms. The Social Communication Questionnaire screened for social communication deficits. Parkinsonian features were evaluated with the modified Unified Parkinson's Disease Rating Scale. For gait evaluation, we validated the use of home videos, using instrumental gait analysis in a subgroup of patients, and then used the home videos for the remainder. RESULTS:A total of 92 patients were enrolled (age range = 18-51 years, mean = 27.93 ± 8.59 years). Sixty percent of caregivers observed a decline in previously acquired skills, including intelligence, speech, interaction with others, ability to climb stairs and walk without support, and hand coordination. Adaptive skills, parkinsonian symptoms, and gait were worse in older patients and those exposed to SCBs for longer periods of time. Fourteen percent of patients screened positive for affective disorders, 11.6% for dementia, and 10.5% for a psychotic disorder. Fifty-three percent screened positive for social communication deficits. SIGNIFICANCE/CONCLUSIONS:This is the largest group of adults with DS to be systematically evaluated. They had severe nonseizure symptoms. Older age and longer use of SCBs were associated with worse adaptive skills, gait, and parkinsonism. Some older adults screened positive for depression and dementia. Caregivers identified functional decline in activities of daily living (ADLs). Taken together, the risk of dementia, parkinsonian gait, and decline in ability to perform previously mastered ADLs support that some adults with DS may be developing a neurodegenerative disorder.
PMID: 40034086
ISSN: 1528-1167
CID: 5842702
Autoimmune encephalitis-associated epilepsy
Autoimmune encephalitis (AE), defined by clinical criteria and its frequent association with neural autoantibodies, often manifests with seizures, which usually stop with immunotherapy. However, a subset of encephalitic conditions present with recurrent seizures that are resistant to immunotherapy. Three primary neurological constellations that fall within this subset are discussed in this Perspective: temporal lobe epilepsy with antibodies against glutamic acid decarboxylase, epilepsy in the context of high-risk paraneoplastic antibodies, and epilepsy following adequately treated surface antibody-mediated AE. These entities all share a common mechanism of structural injury and potentially epileptogenic focal neural loss, often induced by cytotoxic T cells. Recently, we have proposed conceptualizing these conditions under the term autoimmune encephalitis-associated epilepsy (AEAE). Here, we discuss the new concept of AEAE as an emerging field of study. We consider the clinical characteristics of patients who should be investigated for AEAE and highlight the need for judicious use of traditional epilepsy therapeutics alongside immunotherapeutic considerations that are of uncertain and incomplete efficacy for this group of disorders. Last, we discuss future efforts needed to diagnose individuals before structural epileptogenesis has superseded inflammation and to develop improved therapeutics that target the specific immunological or functional disturbances in this entity.
PMID: 40316743
ISSN: 1759-4766
CID: 5834592
