Longitudinal alterations in gamma-aminobutyric acid (GABAA) receptor availability over ∼ 1 year following traumatic brain injury.

Longitudinal alterations of gamma-aminobutyric acid (GABAA) receptor availability following traumatic brain injury have remained uncharacterized and may reflect changes in neuronal structure and function linked to cognitive recovery. We measured GABAA receptor availability using the tracer [11C]flumazenil in nine adults with traumatic brain injury (3-6 months after injury, subacute scan) and in 20 non-brain-injured individuals. A subset of subjects with traumatic brain injury (n = 7) were scanned at a second chronic time-point, 7-13 months after their first scan; controls (n = 9) were scanned for a second time, 5-11 months after the first scan. After accounting for atrophy in subjects with traumatic brain injury, we find broad decreases in GABAA receptor availability predominantly within the frontal lobes, striatum, and posterior-medial thalami; focal reductions were most pronounced in the right insula and anterior cingulate cortex (p < 0.05). Greater relative increase, compared to controls, in global GABAA receptor availability appeared between subacute and chronic scans. At chronic scan (>1 year post-injury), we find increased pallidal receptor availability compared to controls. Conversely, receptor availability remained depressed across the frontal cortices. Longitudinal improvement in executive attention correlated with increases in receptor availability across bilateral fronto-parietal cortical regions and the anterior-lateral aspects of the thalami. The specific observations of persistent bi-frontal lobe reductions and bilateral pallidal elevation are consistent with the anterior forebrain mesocircuit hypothesis for recovery of consciousness following a wide range of brain injuries; our results provide novel correlative data in support of specific cellular mechanisms underlying persistent cognitive deficits. Collectively, these measurements support the use of [11C]flumazenil to track recovery of large-scale network function following brain injuries and measure response to therapeutics.

Cerebral [18 F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

An exploration of clinical dementia phenotypes among individuals with and without traumatic brain injury.

OBJECTIVE: To characterize the clinical profiles of individuals with dementia who do and do not report a history of TBI. INTRODUCTION: Some evidence suggests that a history of traumatic brain injury (TBI) is associated with an increased risk of dementia later in life. The clinical features of dementia associated with TBI have not been well investigated. While there is some evidence that TBI is associated with increased risk of Alzheimer's disease (AD), there are also indications that dementia associated with TBI has prominent behavioral, affective, and motor symptoms, making it distinct from AD. METHODS: The current study involves secondary analysis of baseline data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS). RESULTS: Individuals with dementia who reported a history of TBI had higher fluency and verbal memory scores and later onset of decline, but they are on more medications, had worse cardiovascular and cerebrovascular health, were more likely to have received medical attention for depression, and were more likely to have a gait disorder, falls, and motor slowness. CONCLUSION: These findings suggest that dementia among individuals with a history of TBI may represent a unique clinical phenotype that is distinct from known dementia subtypes.

Behavioral effects of serotonin and serotonin agonists in two crayfish species, Procambarus clarkii and Orconectes rusticus.

Exogenous serotonin elicits several behaviors in Procambarus clarkii, including a flexed, elevated posture, reduced locomotion, and changes in aggressive behavior. We conducted experiments to determine if several serotonin agonists mimicked the behavioral effects of serotonin in two crayfish species, P. clarkii and Orconectes rusticus. Drugs tested were 1-(3-Chlorophenyl)-piperazine dihydrochloride (mCPP), Oxymetazoline, 2,5-dimethoxy-4-iodoamphetamine (DOI), CGS-12066A, and (+/-)-8-hydroxy-2-(di-n-dipropylamino) tetralin (8-OH-DPAT). In P. clarkii, mCPP most closely mimicked the effects of serotonin, significantly increasing the performance of the flexed, elevated posture and reducing locomotion; 8-OH-DPAT significantly reduced locomotion as well. Both of these drugs produced significant increases in elevated posture and decreases in locomotion in O. rusticus, and in this species, the drugs at test concentrations were more effective in eliciting these effects than serotonin. The effects of the drugs on behaviors performed during fighting bouts were variable. In both species, only 8-OH-DPAT significantly reduced several agonistic behaviors, and no agonist or 5-HT itself produced significant increases in agonistic behavior.