Outcomes and Mechanisms Associated With Selective Thalamic Neuronal Loss in Chronic Traumatic Brain Injury.

Importance: The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes.

Objective: To determine whether tissues that appear healthy on routine imaging can be investigated for selective neuronal loss using [11C]flumazenil (FMZ) positron emission tomography (PET) and to examine whether this neuronal loss is associated with long-term outcomes.

Design, Setting, And Participants: In this cross-sectional study, data were collected prospectively from 2 centers (University of Cambridge in the UK and Weill Cornell Medicine in the US) between September 1, 2004, and May 31, 2021.

The Use of Methylphenidate During Inpatient Rehabilitation After Pediatric Traumatic Brain Injury: Population Characteristics and Prescribing Patterns.

Objective: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation.

Setting: Inpatient pediatric rehabilitation.

Participants: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not.

Brain Fluid Clearance After Traumatic Brain Injury Measured Using Dynamic Positron Emission Tomography.

Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case C-flumazenil) is cleared from ventricular cerebrospinal fluid (CSF), we estimated the overall efficiency of brain fluid clearance in humans who had experienced complicated-mild or moderate TBI 3-6 months before neuroimaging ( = 7) as compared to healthy controls ( = 9).

Brain vital signs as a quantitative measure of cognition: Methodological implementation in a care home environment.

Introduction: Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function.

Screening for Delirium During Pediatric Brain Injury Rehabilitation.

Objective: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes.

Design: Retrospective study.

Setting: Pediatric inpatient rehabilitation unit.

Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS) to Assess Effects of Age, Sex, and Head Size on Interstitial Fluid Dynamics in Healthy Subjects.

Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer's disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects.

Brain-Computer Interfaces for Communication in Patients with Disorders of Consciousness: A Gap Analysis and Scientific Roadmap.

Background: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment.

Methods: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question.

Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.

Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed.

Glymphatic clearance estimated using diffusion tensor imaging along perivascular spaces is reduced after traumatic brain injury and correlates with plasma neurofilament light, a biomarker of injury severity.

The glymphatic system is a perivascular fluid clearance system, most active during sleep, considered important for clearing the brain of waste products and toxins. Glymphatic failure is hypothesized to underlie brain protein deposition in neurodegenerative disorders like Alzheimer's disease. Preclinical evidence suggests that a functioning glymphatic system is also essential for recovery from traumatic brain injury, which involves release of debris and toxic proteins that need to be cleared from the brain.

Objective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.

Background And Objectives: Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development.

Cognitive-Motor Dissociation Following Pediatric Brain Injury: What About the Children?

Background And Objectives: Following severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence.

Methods: We applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively.

Tau PET following acute TBI: Off-target binding to blood products, tauopathy, or both?

Repeated mild Traumatic Brain Injury (TBI) is a risk factor for Chronic Traumatic Encephalopathy (CTE), characterized pathologically by neurofibrillary tau deposition in the depths of brain sulci and surrounding blood vessels. The mechanism by which TBI leads to CTE remains unknown but has been posited to relate to axonal shear injury leading to release and possibly deposition of tau at the time of injury. As part of an IRB-approved study designed to learn how processes occurring acutely after TBI may predict later proteinopathy and neurodegeneration, we performed tau PET using 18F-MK6240 and MRI within 14 days of complicated mild TBI in three subjects.

Prescribing Patterns of Amantadine During Pediatric Inpatient Rehabilitation After Traumatic Brain Injury: A Multicentered Retrospective Review From the Pediatric Brain Injury Consortium.

Objectives: To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation units.

Setting: Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium.

Participants: Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI.

Quantitative Electroencephalographic Markers of Delirium in the Pediatric Intensive Care Unit: Insights From a Heterogenous Convenience Sample.

Objective: Little is known about the underlying neurophysiology of pediatric delirium. In adult patients, the sensitivity of EEG to clinical symptoms of delirium has been noted, with a slowing of background activity (alpha) and an increase in slow-wave activity (delta-theta). In this pilot study, the authors extended this investigation to a pediatric cohort.

Cognitive Recovery During Inpatient Rehabilitation Following Pediatric Traumatic Brain Injury: A Pediatric Brain Injury Consortium Study.

Objectives: To characterize the demographics, clinical course, and predictors of cognitive recovery among children and young adults receiving inpatient rehabilitation following pediatric traumatic brain injury (TBI).

Design: Retrospective observational, multicenter study.

Setting: Eight acute pediatric inpatient rehabilitation facilities in the United States with specialized programs for treating patients with TBI.

Acute Imaging Findings Predict Recovery of Cognitive and Motor Function after Inpatient Rehabilitation for Pediatric Traumatic Brain Injury: A Pediatric Brain Injury Consortium Study.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children; survivors experience long-term cognitive and motor deficits. To date, studies predicting outcome following pediatric TBI have primarily focused on acute behavioral responses and proxy measures of injury severity; unsurprisingly, these measures explain very little of the variance following heterogenous injury. In adults, certain acute imaging biomarkers help predict cognitive and motor recovery following moderate to severe TBI.

Quantitative multimodal imaging in traumatic brain injuries producing impaired cognition.

Purpose Of Review: Cognitive impairments are a devastating long-term consequence following traumatic brain injury (TBI). This review provides an update on the quantitative mutimodal neuroimaging studies that attempt to elucidate the mechanism(s) underlying cognitive impairments and their recovery following TBI.

Recent Findings: Recent studies have linked individual specific behavioural impairments and their changes over time to physiological activity and structural changes using EEG, PET and MRI.

Focal Electroencephalographic Changes Index Post-Traumatic Confusion and Outcome.

While the duration and severity of post-traumatic confusional state (PTCS) after traumatic brain injury have well-established implications for long-term outcomes, little is known about the underlying pathophysiology and their role in functional outcomes. Here, we analyzed the delta-to-alpha frequency band power ratios (DAR) from localized scalp areas derived from standard resting electroencephalographic (EEG) data recorded during eyes closed state in 49 patients diagnosed with PTCS. Higher global, occipital, parietal, and temporal DARs were significantly associated with the severity of PTCS, as assessed by the Confusion Assessment Protocol (CAP) observed on the same day, after controlling for injury severity.

Executive attention deficits after traumatic brain injury reflect impaired recruitment of resources.

Deficits in attention are a common and devastating consequence of traumatic brain injury (TBI), leading to functional impairments, rehabilitation barriers, and long-term disability. While such deficits are well documented, little is known about their underlying pathophysiology hindering development of effective and targeted interventions. Here we evaluate the integrity of brain systems specific to attentional functions using quantitative assessments of electroencephalography recorded during performance of the Attention Network Test (ANT), a behavioral paradigm that separates alerting, orienting, and executive components of attention.

Central thalamic deep brain stimulation for cognitive neuromodulation - a review of proposed mechanisms and investigational studies.

We review the history of efforts to apply central thalamic deep brain stimulation (CT/DBS) to restore consciousness in patients in a coma or vegetative state by changing the arousal state. Early experimental and clinical studies, and the results of a recent single-subject human study that demonstrated both immediate behavioral facilitation and carry-over effects of CT/DBS are reviewed. We consider possible mechanisms underlying CT/DBS effects on cognitively-mediated behaviors in conscious patients in light of the anatomical connectivity and physiological specializations of the central thalamus.

Modulation of arousal regulation with central thalamic deep brain stimulation.

To investigate the effects of central thalamic deep brain stimulation (CT/DBS) on behavior and frontal cortical function, we conducted experiments in an awake, behaving macaque monkey performing tasks that required sustained attention and working memory. Results of this preliminary study revealed that CT/DBS can lead to an improvement, a decrement, a mixed or have no effect on behavior.

A Bayesian statistical analysis of behavioral facilitation associated with deep brain stimulation.

Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large.