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.

Methylphenidate Ameliorates Behavioural and Neurobiological Deficits in Executive Function for Patients with Chronic Traumatic Brain Injury.

(1) : Traumatic brain injury (TBI) often results in cognitive impairments, including in visuospatial planning and executive function. Methylphenidate (MPh) demonstrates potential improvements in several cognitive domains in patients with TBI. The Tower of London (TOL) is a visuospatial planning task used to assess executive function.

In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems.

Distributed harmonic patterns of structure-function dependence orchestrate human consciousness.

A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human structural connectome. We show that structure-function coupling is a generalisable indicator of consciousness that is under bi-directional neuromodulatory control.

Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study.

Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. We studied the chronic effect of COVID-19 on cerebrovascular health, in relation to acute severity, adverse clinical outcomes and in contrast to control group data.

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity.

Post-acute blood biomarkers and disease progression in traumatic brain injury.

There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI.

Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem.

Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years.

Background: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials.

Objective: To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling.

Methods: Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years.

Methylphenidate-mediated motor control network enhancement in patients with traumatic brain injury.

Primary Objective: To investigate functional improvement late (>6 months) after traumatic brain injury (TBI). To this end, we conducted a double-blind, placebo-controlled experimental medicine study to test the hypothesis that a widely used cognitive enhancer would benefit patients with TBI.

Research Design: We focused on motor control function using a sequential finger opposition fMRI paradigm in both patients and age-matched controls.

Neural correlates of visual memory in patients with diffuse axonal injury.

Primary Objective: To investigate the neural substrates of visual memory in a sample of patients with traumatic brain injury (TBI). We hypothesized that patients with decreased grey and white matter volume in frontal and parietal cortices as well as medial temporal and occipital lobes would perform poorly on the tests of visual memory analysed.

Methods And Procedures: 39 patients and 53 controls were assessed on tests of visual memory and learning from the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate.

Traumatic brain injury (TBI) often results in cognitive impairments for patients. The aim of this proof of concept study was to establish the nature of abnormalities, in terms of activity and connectivity, in the working memory network of TBI patients and how these relate to compromised behavioral outcomes. Further, this study examined the neural correlates of working memory improvement following the administration of methylphenidate.

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task.

Depression following traumatic brain injury: A functional connectivity perspective.

Introduction: Despite the mounting evidence that depression is one of the most common psychiatric sequelae in survivors of traumatic brain injury (TBI), no studies so far have attempted to provide an explanation in terms of functional network integrity. This proof of concept study investigated the association between the severity of depressive symptoms and resting network integrity in a sample of patients with TBI and a group of healthy controls.

Methods: We first examined the association between depression symptomatology and global functional connectivity and then attempted to characterize the extent of differences in functional network integrity.

Cognitive Flexibility: A Default Network and Basal Ganglia Connectivity Perspective.

The intra/extradimensional set-shifting task (IED) provides a reliable assessment of cognitive flexibility, the shifting of attention to select behaviorally relevant stimuli in a given context. Impairments in this domain were previously reported in patients with altered neurotransmitter systems such as schizophrenia and Parkinson's disease. Consequently, corticostriatal connections were implicated in the mediation of this function.

Default Mode Dynamics for Global Functional Integration.

Unlabelled: The default mode network (DMN) has been traditionally assumed to hinder behavioral performance in externally focused, goal-directed paradigms and to provide no active contribution to human cognition. However, recent evidence suggests greater DMN activity in an array of tasks, especially those that involve self-referential and memory-based processing. Although data that robustly demonstrate a comprehensive functional role for DMN remains relatively scarce, the global workspace framework, which implicates the DMN in global information integration for conscious processing, can potentially provide an explanation for the broad range of higher-order paradigms that report DMN involvement.

Microstructural basis of contusion expansion in traumatic brain injury: insights from diffusion tensor imaging.

Traumatic brain injury (TBI) is often exacerbated by events that lead to secondary brain injury, and represent potentially modifiable causes of mortality and morbidity. Diffusion tensor imaging was used to characterize tissue at-risk in a group of 35 patients scanned at a median of 50 hours after injury. Injury progression was assessed in a subset of 16 patients with two scans.

Mapping traumatic axonal injury using diffusion tensor imaging: correlations with functional outcome.

Background: Traumatic brain injury is a major cause of morbidity and mortality worldwide. Ameliorating the neurocognitive and physical deficits that accompany traumatic brain injury would be of substantial benefit, but the mechanisms that underlie them are poorly characterized. This study aimed to use diffusion tensor imaging to relate clinical outcome to the burden of white matter injury.