Faculty Bibliography

INTRODUCTION:Validity indicators embedded within standard neuropsychological tests have received increasing attention as more efficient measures for sampling performance validity throughout an evaluation. This cross-sectional study examined multiple performance validity tests (PVTs) embedded in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Working Memory (WMI) and Processing Speed (PSI) Indices for detecting invalid test performance. METHOD:This cross-sectional study examined data from a mixed clinical neuropsychiatric sample of 110 patients referred for outpatient evaluation. The sample was composed of 85 patients with valid neuropsychological performance and 25 with invalid performance based on multiple independent criterion PVTs. Among the patients with valid performance, 54% were cognitively impaired, whereas 46% were cognitively unimpaired. RESULTS: CONCLUSION:Overall, results indicated that embedded WAIS-IV WMI and PSI are useful embedded PVTs in conditions in which cognitive impairment is not expected; however, these embedded PVTs demonstrated questionable utility among patients with cognitive impairment due to poor sensitivity, if adequate specificity is maintained, suggesting limited efficacy among patients with cognitive impairment due to risk of false-positive classification.

BACKGROUND:Mobile health, predominantly wearable technology and mobile apps, have been considered in Parkinson disease to provide valuable ecological data between face-to-face visits and improve monitoring of motor symptoms remotely. OBJECTIVE:We explored the feasibility of using a technology-based mHealth platform comprising a smartphone in combination with a smartwatch and a pair of smart insoles, described in the this study as the PD_manager system, to collect clinically meaningful data. We also explored outcomes and disease-related factors that are important determinants to establish feasibility. Finally, we further validated a tremor evaluation method with data collected while patients performed their daily activities. METHODS:PD_manager trial was an open-label parallel group randomized study. The mHeath platform consists of a wristband, a pair of sensor insoles, and a smartphone (with dedicated mobile Android apps and a knowledge platform) serving as the cloud backend. Compliance was assessed with statistical analysis and the factors affecting it using appropriate regression analysis. The correlation of the scores of our previous algorithm for tremor evaluation and the respective Unified Parkinson's Disease Rating Scale estimations by clinicians were explored. RESULTS:Of the 75 study participants, 65 (87%) completed the protocol. They used the PD_manager system for a median 11.57 (SD 3.15) days. Regression analysis suggests that the main factor associated with high use was caregivers' burden. Motor Aspects of Experiences of Daily Living and patients' self-rated health status also influence the system's use. Our algorithm provided clinically meaningful data for the detection and evaluation of tremor. CONCLUSIONS:We found that PD patients, regardless of their demographics and disease characteristics, used the system for 11 to 14 days. The study further supports that mHealth can be an effective tool for the ecologically valid, passive, unobtrusive monitoring and evaluation of symptoms. Future studies will be required to demonstrate that an mHealth platform can improve disease management and care. INTERNATIONAL REGISTERED REPORT/UNASSIGNED:RR2-10.1186/s13063-018-2767-4.

Neuroimaging software methods are complex, making it a near certainty that some implementations will contain errors. Modern computational techniques (i.e., public code and data repositories, continuous integration, containerization) enable the reproducibility of the analyses and reduce coding errors, but they do not guarantee the scientific validity of the results. It is difficult, nay impossible, for researchers to check the accuracy of software by reading the source code; ground truth test datasets are needed. Computational reproducibility means providing software so that for the same input anyone obtains the same result, right or wrong. Computational validity means obtaining the right result for the ground-truth test data. We describe a framework for validating and sharing software implementations, and we illustrate its usage with an example application: population receptive field (pRF) methods for functional MRI data. The framework is composed of three main components implemented with containerization methods to guarantee computational reproducibility. In our example pRF application, those components are: (1) synthesis of fMRI time series from ground-truth pRF parameters, (2) implementation of four public pRF analysis tools and standardization of inputs and outputs, and (3) report creation to compare the results with the ground truth parameters. The framework was useful in identifying realistic conditions that lead to imperfect parameter recovery in all four pRF implementations, that would remain undetected using classic validation methods. We provide means to mitigate these problems in future experiments. A computational validation framework supports scientific rigor and creativity, as opposed to the oft-repeated suggestion that investigators rely upon a few agreed upon packages. We hope that the framework will be helpful to validate other critical neuroimaging algorithms, as having a validation framework helps (1) developers to build new software, (2) research scientists to verify the software's accuracy, and (3) reviewers to evaluate the methods used in publications and grants.

OBJECTIVES/OBJECTIVE:We sought to (1) identify the countries in the Latin America/Caribbean Group of the United Nations (GRULAC) that have protocols for brain death/death by neurologic criteria (BD/DNC) and (2) review the similarities and differences between these protocols. MATERIALS AND METHODS/METHODS:Between January 2018 and April 2019, we obtained and reviewed BD/DNC protocols from countries in GRULAC. RESULTS:We communicated with contacts in 30/33 countries in GRULAC (91 % of countries) and found that 16 (53 % of countries with contacts, 48 % of Latin American/Caribbean countries) had BD/DNC protocols. Of the 13 protocols that provided a definition of death, 10 (77 %) referred to whole brain death. The number of exams/examiners, prerequisites for BD/DNC, and descriptions of the clinical assessment and apnea test were inconsistent among protocols. Although Brazil and Panama required an ancillary test, the indications for ancillary testing, and the types of accepted ancillary tests, varied by country. CONCLUSION/CONCLUSIONS:BD/DNC determination protocols in the countries in GRULAC are inconsistent. Acknowledging the fact that there are diverse cultural, legal and religious perspectives on death, and human and technological resources differ by region, we recommend that attempts be made to harmonize protocols on BD/DNC both regionally and worldwide.

The selective effectiveness of adrenocorticotropic hormone (ACTH) in treating infantile spasms suggests an underlying neuroinflammation. Because neuroinflammation is mediated by activated microglia, which express translocator protein (TSPO), we imaged neuroinflammation in children with infantile spasms using positron emission tomography (PET) with ¹¹C-PK11195 (PK), which selectively binds to TSPO. Children were studied prospectively before and following treatment with Acthar Gel (repository corticotropin injection). We hypothesized that PK-PET would show neuroinflammation (increased PET uptake) in cortical and/or subcortical structures before treatment, and that this inflammation will be abolished/reduced following Acthar Gel treatment. Eight children with infantile spasms (5 males; mean age 1.8±1.1, range 0.9-4.1 years) were recruited. After clinical and video electroencephalograph (EEG) evaluation and dynamic PK-PET scan, children underwent treatment with Acthar Gel over 4 weeks, followed by repeat clinical evaluation/video-EEG 2 weeks after initiation of treatment and repeat PK-PET 2 weeks after treatment completion. Visual and quantitative analysis of PK-PET scans were performed. We calculated regional binding potential (measure of receptor-ligand binding) using a reference tissue model. Focal areas of increased PK-binding were found in the pretreatment PK-PET in 5 children. Following treatment, these increases were either reduced or normalized and were associated with cessation (n=4) or significant reduction (n=1) of spasms and complete disappearance of hypsarrhythmia. One child showed increased binding potential in basal ganglia and thalamus, despite normalization of cortical binding potential; however, these increases were likely associated with death-related causes. This study suggests Acthar Gel-responsive neuroinflammatory changes in children with infantile spasms, supporting a potential role of neuroinflammation in the pathogenesis of infantile spasms.

Physician-patient collaboration was recognized as a critical core of participatory medicine more than a century ago. However, the subsequent focus on scientific research to enable cures and increased dominance of physicians in health care subordinated patients to a passive role. This paternalistic model weakened in the past 50 years-as women, minorities, and the disabled achieved greater rights, and as incurable chronic diseases and unrelieved pain disorders became more prevalent-promoting a more equitable role for physicians and patients. By 2000, a shared decision-making model became the pinnacle for clinical decisions, despite a dearth of data on health outcomes, or the model's reliance on single patient or solo practitioner studies, or evidence that no single model could fit all clinical situations. We report about a young woman with intractable epilepsy due to a congenital brain malformation whose family and medical specialists used a collaborative decision-making approach. This model positioned the health professionals as supporters of the proactive family, and enabled them all to explore and co-create knowledge beyond the clinical realm. Together, they involved other members of the community in the decisions, while harnessing diverse relationships to allow all family members to achieve positive levels of health, despite the resistance of the seizures to medical treatment and the incurable nature of the underlying disease.

To become a unifying theory of brain function, predictive processing (PP) must accommodate its rich representational diversity. Gilead et al. claim such diversity requires a multi-process theory, and thus is out of reach for PP, which postulates a universal canonical computation. We contend this argument and instead propose that PP fails to account for the experiential level of representations.

Introduction/UNASSIGNED:Recognition of faces of family members, friends, and colleagues is an important skill essential for everyday life. Individuals affected by prosopagnosia (face blindness) have difficulty recognizing familiar individuals. The prevalence of prosopagnosia has been estimated to be as high as 3%. Prosopagnosia can severely impact the quality of life of those affected, and it has been suggested to co-occur with conditions such as depression and anxiety. Methods/UNASSIGNED:To determine real-world diagnostic frequency of prosopagnosia and the spectrum of its comorbidities, we utilized a large database of more than 7.5 million de-identified electronic health records (EHRs) from patients who received care at major academic health centers and Federally Qualified Health Centers in New York City. We designed a computable phenotype to search the database for diagnosed cases of prosopagnosia, revealing a total of n = 902 cases. In addition, data from a randomly sampled matched control population (n = 100,973) were drawn from the database for comparative analyses to study the condition's comorbidity landscape. Diagnostic frequency of prosopagnosia, epidemiological characteristics, and comorbidity landscape were assessed. Results/UNASSIGNED:We observed prosopagnosia diagnoses at a rate of 0.012% (12 per 100,000 individuals). We discovered elevated frequency of prosopagnosia diagnosis for individuals who carried certain comorbid conditions, such as personality disorder, depression, epilepsy, and anxiety. Moreover, prosopagnosia diagnoses increased with the number of comorbid conditions. Conclusions/UNASSIGNED:Results from this study show a wide range of comorbidities and suggest that prosopagnosia is vastly underdiagnosed. Findings imply important clinical consequences for the diagnosis and management of prosopagnosia as well as its comorbid conditions.

Anti-CD20 therapies have established efficacy in the treatment of immune-mediated neurological and non-neurological diseases. Rituximab, one of the first B-cell-directed therapies, is relatively inexpensive compared to newer anti-CD20 molecules, is available in many countries, and has been used off-label in pediatric patients with neuroimmune conditions. The objective of this paper is to describe the experience with rituximab in pediatric multiple sclerosis and other inflammatory immune-mediated disorders of the central nervous system (CNS), and to define a protocol for its use in clinical practice, in particular addressing doses, interval of administration, duration of treatment, and tests to perform at baseline and during follow-up.