Faculty Bibliography

Different theories explain how subjective experience arises from brain activity^1,2. 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 consortium^11-13. 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 here^14-17. 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.

OBJECTIVE:This study was undertaken to investigate diagnostic delay in adolescent onset focal epilepsy, including reasons for longer delays and associated morbidities. METHODS:Secondary analysis was done using enrollment data from the Human Epilepsy Project, a multi-institutional cohort including 34 sites in the USA, Canada, Finland, Austria, and Australia (2012-2017). Participants were aged 11-64 years at enrollment and within 4 months of treatment initiation for newly diagnosed focal epilepsy. Participants with seizure onset at age ≤ 21 years were evaluated. Data included seizure diaries documenting onset, frequency, and characteristics of seizures, reasons for diagnostic delays, and prediagnosis morbidities, including injuries, suicidal ideation, and self-injurious behaviors. RESULTS: = 7.04, p = .008). SIGNIFICANCE/CONCLUSIONS:This study highlights significant delays in diagnosing adolescent onset focal epilepsy, especially in cases with nonmotor seizures. These delays, often due to lack of recognition by patients and health care providers, are linked to more frequent seizures, higher injury rates, and increased suicidal ideation and self-injury. Early recognition and diagnosis may mitigate adverse outcomes and improve quality of life for adolescents with epilepsy.

OBJECTIVE:This study was undertaken to investigate diagnostic delay in adolescent onset focal epilepsy, including reasons for longer delays and associated morbidities. METHODS:Secondary analysis was done using enrollment data from the Human Epilepsy Project, a multi-institutional cohort including 34 sites in the USA, Canada, Finland, Austria, and Australia (2012-2017). Participants were aged 11-64 years at enrollment and within 4 months of treatment initiation for newly diagnosed focal epilepsy. Participants with seizure onset at age ≤ 21 years were evaluated. Data included seizure diaries documenting onset, frequency, and characteristics of seizures, reasons for diagnostic delays, and prediagnosis morbidities, including injuries, suicidal ideation, and self-injurious behaviors. RESULTS: = 7.04, p = .008). SIGNIFICANCE/CONCLUSIONS:This study highlights significant delays in diagnosing adolescent onset focal epilepsy, especially in cases with nonmotor seizures. These delays, often due to lack of recognition by patients and health care providers, are linked to more frequent seizures, higher injury rates, and increased suicidal ideation and self-injury. Early recognition and diagnosis may mitigate adverse outcomes and improve quality of life for adolescents with epilepsy.

BACKGROUND AND IMPORTANCE/BACKGROUND:Rhino-orbital cerebral mucormycosis (ROCM) is an aggressive fungal infection involving the paranasal sinuses, orbit, and intracranial cavity, with a propensity for vascular invasion. This can lead to complications such as internal carotid artery (ICA) thrombosis and occlusion, presenting major neurosurgical challenges. Although surgical debridement and antifungal therapy are the mainstays of treatment, cases with significant neurovascular involvement require specialized intervention. We report a case of ROCM with severe flow-limiting ICA stenosis treated by direct extracranial-intracranial bypass. CLINICAL PRESENTATION/METHODS:tA 65-year-old man with diabetes presented with progressive left-sided blindness and facial numbness. Imaging revealed a left orbital mass extending into the paranasal sinuses and intracranially. Empiric antifungal therapy was started. Pathology confirmed Rhizopus species. Despite extensive surgical debridement and antifungal therapy, the patient developed progressive severe cavernous ICA stenosis, leading to watershed territory strokes. To restore cerebral perfusion, protect from distal emboli, and prepare for potential aggressive debridement, a flow-replacing direct (superficial temporal artery-middle cerebral artery (M2)) bypass was performed, and the supraclinoid carotid was trapped. Intraoperative angiography confirmed robust flow through the bypass. The patient was discharged on antifungal therapy and aspirin. At 6-month follow-up, the patient was neurologically intact with an modified Rankin Scale score of 1. Computed tomography angiography and transcranioplasty Doppler ultrasonography confirmed good flow through the bypass. CONCLUSION/CONCLUSIONS:In addition to antifungal therapy and surgical debridement, superficial temporal artery-middle cerebral artery bypass can be a lifesaving intervention in the management of ROCM with severe cerebrovascular compromise. This case highlights the critical role of cranial bypass in preserving cerebral perfusion in patients with flow-limiting ROCM-associated ICA invasion.

Documentation, coding, and billing (claims submission) are foundational to neurologic practice in the United States, enabling accurate reimbursement, effective communication, and data-driven advancements in patient care, research, and education. Neurologists navigate complex regulatory frameworks and evolving payer guidelines, requiring meticulous attention to diagnostic coding, evaluation and management (E/M) services, and procedure-specific requirements. This chapter examines critical aspects of neurologic billing and coding, including ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) for diagnostic accuracy, updated E/M guidelines emphasizing medical decision-making and time, and new telemedicine codes. It highlights the best practices for procedure coding and the use of digital health technologies. The challenges posed by prior authorization are explored, alongside potential solutions like artificial intelligence-driven tools and policy reform. By prioritizing precision, compliance, and technological adaptation, neurologists can enhance patient outcomes, support practice sustainability, and contribute to the broader goals of equitable, efficient, and innovative neurologic care.

BACKGROUND AND IMPORTANCE/BACKGROUND:Rhino-orbital cerebral mucormycosis (ROCM) is an aggressive fungal infection involving the paranasal sinuses, orbit, and intracranial cavity, with a propensity for vascular invasion. This can lead to complications such as internal carotid artery (ICA) thrombosis and occlusion, presenting major neurosurgical challenges. Although surgical debridement and antifungal therapy are the mainstays of treatment, cases with significant neurovascular involvement require specialized intervention. We report a case of ROCM with severe flow-limiting ICA stenosis treated by direct extracranial-intracranial bypass. CLINICAL PRESENTATION/METHODS:tA 65-year-old man with diabetes presented with progressive left-sided blindness and facial numbness. Imaging revealed a left orbital mass extending into the paranasal sinuses and intracranially. Empiric antifungal therapy was started. Pathology confirmed Rhizopus species. Despite extensive surgical debridement and antifungal therapy, the patient developed progressive severe cavernous ICA stenosis, leading to watershed territory strokes. To restore cerebral perfusion, protect from distal emboli, and prepare for potential aggressive debridement, a flow-replacing direct (superficial temporal artery-middle cerebral artery (M2)) bypass was performed, and the supraclinoid carotid was trapped. Intraoperative angiography confirmed robust flow through the bypass. The patient was discharged on antifungal therapy and aspirin. At 6-month follow-up, the patient was neurologically intact with an modified Rankin Scale score of 1. Computed tomography angiography and transcranioplasty Doppler ultrasonography confirmed good flow through the bypass. CONCLUSION/CONCLUSIONS:In addition to antifungal therapy and surgical debridement, superficial temporal artery-middle cerebral artery bypass can be a lifesaving intervention in the management of ROCM with severe cerebrovascular compromise. This case highlights the critical role of cranial bypass in preserving cerebral perfusion in patients with flow-limiting ROCM-associated ICA invasion.

The International League Against Epilepsy (ILAE) has updated the operational classification of epileptic seizures, building upon the framework established in 2017. This revision, informed by the implementation experience, involved a working group appointed by the ILAE Executive Committee. Comprising 37 members from all ILAE regions, the group utilized a modified Delphi process, requiring a consensus threshold of more than two thirds for any proposal. Following public comments, the Executive Committee appointed seven additional experts to the revision task force to address and incorporate the issues raised, as appropriate. The updated classification maintains four main seizure classes: Focal, Generalized, Unknown (whether focal or generalized), and Unclassified. Taxonomic rules distinguish classifiers, which are considered to reflect biological classes and directly impact clinical management, from descriptors, which indicate other important seizure characteristics. Focal seizures and those of unknown origin are further classified by the patient's state of consciousness (impaired or preserved) during the seizure, defined operationally through clinical assessment of awareness and responsiveness. If the state of consciousness is undetermined, the seizure is classified under the parent term, that is, the main seizure class (focal seizure or seizure of unknown origin). Generalized seizures are grouped into absence seizures, generalized tonic-clonic seizures, and other generalized seizures, now including recognition of negative myoclonus as a seizure type. Seizures are described in the basic version as with or without observable manifestations, whereas an expanded version utilizes the chronological sequence of seizure semiology. This updated classification comprises four main classes and 21 seizure types. Special emphasis was placed on ensuring translatability into languages beyond English. Its aim is to establish a common language for all health care professionals involved in epilepsy care, from resource-limited areas to highly specialized centers, and to provide accessible terms for patients and caregivers.

Curbs serve as vital borders that delineate safe pedestrian zones from potential vehicular traffic hazards. Curbs also represent a primary spatial hazard during dynamic navigation with significant stumbling potential. Such vulnerabilities are particularly exacerbated for persons with blindness and low vision (PBLV). Accurate visual-based discrimination of curbs is paramount for assistive technologies that aid PBLV with safe navigation in urban environments. Herein, we investigate the efficacy of curb segmentation for foundation models. We introduce the largest curb segmentation dataset to date to benchmark leading foundation models. Our results show that state-of-the-art foundation models face significant challenges in curb segmentation. This is due to their low precision and recall with poor performance distinguishing curbs from curb-like objects or non-curb areas, such as sidewalks. In addition, the best-performing model averaged a 3.70-s inference time, underscoring problems in providing real-time assistance. In response, we propose solutions including filtered bounding box selections to achieve more accurate curb segmentation. Overall, despite the immediate flexibility of foundation models, their application for practical assistive technology applications still requires refinement. This research highlights the critical need for specialized datasets and tailored model training to address navigation challenges for PBLV and underscores implicit weaknesses in foundation models.

BACKGROUND AND PURPOSE/OBJECTIVE:Cerebrovascular reactivity (CVR) is a widely studied biomarker of cerebral hemodynamics, commonly used in risk stratification and treatment planning in patients with steno-occlusive disease (SOD). Conventional use relies on normalization of estimates to contralateral hemisphere reference values, which is unsuitable for bilateral or indeterminate distributions of disease. We report upon a custom data-driven approach leveraging random forest classifiers (RFc) to identify candidate voxels for normalization in order to facilitate interrogation outside conditions of known unilateral SOD MATERIALS AND METHODS: We retrospectively analyzed 16 patients with unilateral SOD who underwent acetazolamide-augmented BOLD-MRI and DSC perfusion. Three RFc models were trained using leave-one-out cross-validation (LOOCV) to identify candidate voxels brain-wide whose CVR were within 10% of the normal hemispheric median: i. all voxels; ii. gray matter only; and iii. white matter only. Model input features included time-to-maximum (Tmax), mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) from contemporaneous DSC. The median model-predicted reference CVR (CVRref) was compared to ground-truth medians in LOOCV, and its impact on threshold-based volumetric classification of CVR reduction assessed. RESULTS:RFc models effectively predicted ground-truth CVR voxels, achieving median absolute percent differences of 12.8% (IQR: 5.0%-18.9%) using all voxels, 11.3% (IQR: 9.3%-16.1%) for gray matter, and 9.8% (IQR: 4.4%-16.9%) for white matter. Volumetric estimates of CVR reduction across thresholds for the models revealed excellent agreement between ground-truth and model estimates without statistically significant differences (p>0.01), excepting lowest white matter CVR thresholds. Model use in a small pilot deployment of bilateral SOD cases demonstrated the potential utility, enabling voxel-wise CVR assessment without reliance on contralateral reference. CONCLUSIONS:We present a novel data-driven approach for normalizing CVR maps in patients with bilateral or indeterminate SOD. Using an RFc, our method provides an individualized, brain-wide reference CVR, expanding the utility of CVR estimates beyond the typical constraints of unilateral disease, and with potential application to other, similarly constrained scenarios such as for SPECT or PET hemodynamic studies. ABBREVIATIONS/BACKGROUND:CVR = cerebrovascular reactivity; RFc = random forest classifier; SOD = steno-occlusive disease.

BACKGROUND:Neurofibromatosis 1 (NF1) is a rare, neurogenetic disorder predisposing individuals to multiple tumors and other issues requiring expert care and regular health monitoring. We sought to assess U.S. patients' access to specialized NF1 clinics and receipt of evidence-informed health surveillance. METHODS:An online survey was distributed to NF Registry participants in May 2021. Rate of NF1 clinic attendance and self-reported receipt of health surveillance amongst NF Registry participants was estimated using inverse propensity scores. Differences in these outcomes based on participant demographics were assessed using weighted logistic regression and robust linear regression, respectively. RESULTS:322 individuals responded (160 adults, 162 parents; 4.7% overall response rate). We estimate that 51.7% of children and 35.6% of adults attend NF1 clinics. Younger children were more likely to attend an NF1 clinic, as were adults living in urban areas, with a college degree or higher, or with a household income ≥ $130,000 (all ps < 0.05). Completion rates for each individual health surveillance evaluation ranged from 41 to 79% for children and 33-61% for adults. Higher rates of recommended evaluations were reported by both adults and children who attend a specialized NF1 clinic, non-Hispanic White adults, and adults with commercial or Medicare insurance (all ps < 0.05). CONCLUSIONS:Adults with NF1 experience significant sociodemographic disparities in care, and patients of all ages attending NF1 specialty clinics receive more recommended health surveillance. Given the limited access to specialty NF clinics, quality improvement efforts are needed to increase access for underserved adults and improve provision of recommended health surveillance outside specialty clinics.