Faculty Bibliography
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school:SOM
Department/Unit:Neurology
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22948
Image processing and analysis methods for the Adolescent Brain Cognitive Development Study
The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.
PMID: 31415884
ISSN: 1095-9572
CID: 4042682
Mineralocorticoid receptor antagonist use after hospitalization of patients with heart failure and post-discharge outcomes: a single-center retrospective cohort study
BACKGROUND:Mineralocorticoid receptor antagonists (MRA) are an underutilized therapy for heart failure with a reduced ejection fraction (HFrEF), but the current impact of hospitalization on MRA use is not well characterized. The objective of this study was to describe contemporary MRA prescription for heart failure patients before and after the full scope of hospitalizations and the association between MRA discharge prescription and post-hospitalization outcomes. METHODS:We conducted a retrospective cohort study at an academic hospital system in 2013-2016. Among 1500 included hospitalizations of 1009 unique patients with HFrEF and without MRA contraindication, the mean age was 71.9 ± 13.6 years and 443 (29.5%) were female. We compared MRA prescription before and after hospitalizations with McNemar's test and between patients with principal and secondary diagnoses of HFrEF with the chi-square test, and association of MRA discharge prescription with 30-day and 180-day mortality and readmissions using generalized estimating equations. RESULTS:MRA prescriptions increased from 303 (20.2%) to 375 (25.0%) at discharge (+4.8%, p < 0.0001). More patients with principal diagnosis of HFrEF compared to those hospitalized for other reasons received MRA (34.9% versus 21.3%, p < 0.0001) and had them initiated (21.8% versus 9.7%, p < 0.0001). MRA prescription at discharge was not associated with mortality or readmission at 30 and 180 days, and there was no interaction with principal/secondary diagnosis. CONCLUSIONS:Among hospitalized HFrEF patients, 75% did not receive MRA before or after hospitalization, and nearly 90% of eligible patients did not have MRA initiated. As we found no signal for short-term harm after discharge, hospitalization may represent an opportunity to initiate guideline-directed heart failure therapy.
PMID: 31399059
ISSN: 1471-2261
CID: 4034482
Patients with dorsolateral prefrontal cortex lesions are capable of discriminatory threat learning but appear impaired in cognitive regulation of subjective fear
Humans are able to cognitively regulate emotions by changing their thoughts. Neuroimaging studies show correlations between dorsolateral prefrontal cortex (dlPFC) activity and cognitive regulation of emotions. Here our objective was to investigate whether dlPFC damage is associated with impaired cognitive regulation of emotion. We therefore tested the ability of patients with dlPFC lesions (N = 6) and matched control participants (N = 19) to utilize a laboratory version of cognitive regulation training (CRT) to regulate subjective fear and autonomic threat responses following Pavlovian threat conditioning. We found that patients with dlPFC lesions were able to acquire conditioned threat but seemed impaired in their ability to utilize CRT to cognitively regulate subjective fear to a threatening stimulus. Despite inclusion of a limited number of lesion patients, our results suggest that the dlPFC is important for the cognitive regulation of subjective fear.
PMID: 31119295
ISSN: 1749-5024
CID: 3920792
Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome
Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B, a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B-encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.
PMCID:6684583
PMID: 31388001
ISSN: 2041-1723
CID: 4033212
Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089)
OBJECTIVE:To evaluate the effect of cenobamate in patients with photoparoxysmal-EEG response (PPR) to intermittent photic stimulation (IPS) as proof of principle of efficacy in patients with epilepsy. METHODS:In this multicenter, single-blind study, adults with photosensitive epilepsy, with/without concomitant antiepileptic drug therapy, underwent IPS under 3 eye conditions after a single dose of placebo (day -1, day 2) or cenobamate (day 1; 100, 250, or 400 mg). Complete suppression was a standardized photosensitivity range reduction to 0 over ≥1 time points for all eye conditions. Partial suppression was a ≥3-point reduction over ≥3 testing times vs the same time points on day -1 in ≥1 eye condition. Pharmacokinetics and safety were assessed. RESULTS:Of 6 evaluable patients, 5 reentered to receive higher doses. Cenobamate 100 mg produced partial suppression in 1 of 3 patients; 250 mg produced complete suppression in 1 of 4 and partial suppression in 4 of 4 patients; and 400 mg produced complete suppression in 1 of 4 and partial suppression in 2 of 4 patients. PPR was consistently reduced on days 1 and 2 (>24 hours after cenobamate) vs day -1 (placebo) with the 250- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 μg/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence. CONCLUSIONS:This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy. CLINICALTRIALSGOV IDENTIFIER/UNASSIGNED:NCT00616148. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.
PMID: 31292226
ISSN: 1526-632x
CID: 3976662
Introduction. Primary and secondary infections of the brain
PMID: 31370012
ISSN: 1092-0684
CID: 4622712
Prevention of surgical site infections after brain surgery: the prehistoric period to the present
In this historical vignette, the authors discuss the prevention of surgical site infections (SSIs) after brain surgery from the prehistoric period to the present. Although the mechanism for infection was not fully understood until the 19th century, records demonstrate that as early as 10,000 bc, practitioners used gold, a biocidal material, for cranioplasties and attempted to approximate wounds by tying a patient's hair across the incision. Written records from the Egyptian and Babylonian period depict the process of soaking head dressings in alcohol, an antibacterial agent. In the Greek and Early Byzantine period, Hippocrates argued against the formation of pus in wounds and continued to champion the use of wine in wound management. In the 16th century, intracranial silver drains were first utilized in an effort to prevent postoperative infections. The turning point of SSI prevention was in 1867, when Joseph Lister illustrated the connection between Louis Pasteur's discovery of the fermentation process and the suppuration of wounds. Today, there are ongoing investigations and debates about the optimal techniques to prevent SSI after brain surgery. Although tremendous progress in the field of SSI prevention since the prehistoric period has been made, SSI continues to affect morbidity and mortality after brain surgery.
PMID: 31370023
ISSN: 1092-0684
CID: 4015402
Long-term test-retest reliability of event-related potential (ERP) recordings during treadmill walking using the mobile brain/body imaging (MoBI) approach
Advancements in acquisition technology and signal-processing techniques have spurred numerous recent investigations on the electro-cortical signals generated during whole-body motion. This approach, termed Mobile Brain/Body Imaging (MoBI), has the potential to elucidate the neural correlates of perceptual and cognitive processes during real-life activities, such as locomotion. However, as of yet, no one has assessed the long-term stability of event-related potentials (ERPs) recorded under these conditions. Therefore, the objective of the current study was to evaluate the test-retest reliability of cognitive ERPs recorded while walking. High-density EEG was acquired from 12 young adults on two occasions, separated by an average of 2.3years, as they performed a Go/No-Go response inhibition paradigm. During each testing session, participants performed the task while walking on a treadmill and seated. Using the intraclass correlation coefficient (ICC) as a measure of agreement, we focused on two well-established neurophysiological correlates of cognitive control, the N2 and P3 ERPs. Following ICA-based artifact rejection, the earlier N2 yielded good to excellent levels of reliability for both amplitude and latency, while measurements for the later P3 component were generally less robust but still indicative of adequate to good levels of stability. Interestingly, the N2 was more consistent between walking sessions, compared to sitting, for both hits and correct rejection trials. In contrast, the P3 waveform tended to have a higher degree of consistency during sitting conditions. Overall, these results suggest that the electro-cortical signals obtained during active walking are representative of stable indices of neurophysiological function.
PMID: 28532853
ISSN: 1872-6240
CID: 3075642
Negative affect is associated with increased stress-eating for women with high perceived life stress
Perceived life stress (PLS) and cognitive restraint are associated with increased comfort food intake under stress and lead to weight gain and obesity, but the mechanisms by which they do so remain unclear. Stress and negative affect (NA) are associated with increased reward-driven comfort food intake as a means to 'feel better', particularly for individuals with higher PLS and cognitive restraint. Thus, we propose that PLS and cognitive restraint increase stress-eating by strengthening the relationship between stress-induced NA and comfort food intake. Upon comfort eating, individuals with higher PLS show greater reductions in the negative consequences of stress (e.g. NA). The rewarding effects of this 'emotional relief' may promote future stress-induced comfort eating, but this has yet to be examined. Thus, we investigate the pathways by which PLS or cognitive restraint increase snack intake under stress by proposing that 1) stress-induced NA is a stronger predictor of increased snack intake for women with greater PLS and cognitive restraint, and 2) greater PLS will be associated with greater reductions in NA upon snacking under stress (i.e. emotional relief). Forty-three healthy women were given snacks (chips, golden oreos, and M&Ms) to eat after a Trier Social Stress Test or rest period on separate days in counterbalanced order. Following linear regression analyses, we determined that stress-induced NA predicted more snack intake for women with higher PLS, and that higher PLS was associated with heightened emotional relief upon snacking under stress. Future studies are needed to directly assess whether greater emotional relief following stress-eating reinforces the learned association between stress-induced NA and intake, and ultimately explains greater stress-eating and obesity in women with higher PLS. This work may lead clinicians to focus on NA in the treatment of obesity-and stress-related illnesses for women with higher PLS.
PMID: 31377311
ISSN: 1873-507x
CID: 4032602
International journal of radiation oncology biology physics. 2019:104(5):1106-1113.DOI: 10.1016/j.ijrobp.2019.04.008
Correlation of Tumor Treating Fields Dosimetry to Survival Outcomes in Newly Diagnosed Glioblastoma: A Large-Scale Numerical Simulation-Based Analysis of Data from the Phase 3 EF-14 Randomized Trial
INTRODUCTION/BACKGROUND:Tumor Treating Fields (TTFields) are approved for glioblastoma based on improved overall survival (OS) and progression-free survival (PFS) in the phase 3 EF-14 trial of newly diagnosed glioblastoma. To test the hypothesis that increasing TTFields dose at the tumor site improves patient outcomes, we performed a simulation-based study investigating the association between TTFields dose and survival (OS and PFS) in patients treated with TTFields in EF-14. METHODS AND MATERIALS/METHODS:EF-14 patient cases (NÂ =Â 340) were included. Realistic head models were derived from T1-contrast images captured at baseline. The transducer array layout on each patient was obtained from EF-14 records; average compliance (fraction of time patient was on active treatment) and average electrical current delivered to the patient were derived from log files of the TTFields devices used by patients. TTFields intensity distributions and power densities were calculated using the finite element method. Local minimum dose density (LMiDD) was defined as the product of TTFields intensity, tissue-specific conductivities, and patient compliance. The average LMiDD within a tumor bed comprising the gross tumor volume and the 3-mm-wide peritumoral boundary zone was calculated. RESULTS:: OS was 25.2 versus 20.4Â months (PÂ =Â .003, hazard ratio [HR]Â =Â 0.611) and PFS was 8.5 versus 6.7Â months (PÂ =Â .02, HRÂ =Â 0.699). The median OS and PFS were longer when the average TTFields intensity was >1.06Â V/cm: OS was 24.3 versus 21.6Â months (PÂ =Â .03, HRÂ =Â 0.705) and PFS was 8.1 versus 7.9Â months (PÂ =Â .03, HRÂ =Â 0.721). CONCLUSIONS:In this study we present the first reported analysis demonstrating patient-level dose responses to TTFields. We provide a rigorous definition for TTFields dose and set a conceptual framework for future work on TTFields dosimetry and treatment planning.
PMID: 31026557
ISSN: 1879-355x
CID: 4096982
