There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [11C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [11C]DPA-713 binding to TSPO, may be linked to history of NFL play. [11C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play.

IMPORTANCE Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. OBJECTIVE To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution

Objective: To quantitatively synthesize results from neuroimaging studies that evaluated patterns of resting functional activity in patients with disorders of consciousness (DOC).Methods: We performed a systematic review and coordinate-based meta-analysis of studies published up to May 2014. Studies were included if they compared resting-state functional neuroimaging data acquired in patients with DOC (coma, minimally conscious state, emergence from minimally conscious state, or vegetative state) with a group of healthy controls. Coordinate-based meta-analysis was performed in studies that included voxel-based comparisons at the whole-brain level and if analysis was accomplished with data-driven approaches.Results: A total of 36 studies (687 patients, 637 healthy controls) were included in the systematic review. Reported DOC were vegetative state (43.2%), coma (23.4%), minimally conscious state (22.8%), and emergence from minimally conscious state (1.6%); the most common etiologies of DOC were traumatic brain injury (37.7%) and anoxic brain injury (36.9%). Functional neuroimaging was accomplished using fMRI (16 studies), PET (15 studies), SPECT (4 studies), and both PET and SPECT in one study. Meta-analysis in 13 studies (272 patients, 259 healthy controls) revealed consistently reduced activity in patients with DOC in bilateral medial dorsal nucleus of the thalamus, left cingulate, posterior cingulate, precuneus, and middle frontal and medial temporal gyri. Conclusions:In patients with DOC evaluated in the resting state, functional neuroimaging indicates markedly reduced activity within midline cortical and subcortical sites, anatomical structures that have been linked to the default-mode network. Studies are needed to determine the relation between activation (and coherence) within these structures and the emergence of conscious awareness. Neurology ® 2015;84:1272-1280 GLOSSARY ALE 5 activation likelihood estimate; ALFF 5 amplitude of low-frequency fluctuations; BOLD 5 blood oxygen level-dependent; CRS-R 5 Coma Recovery Scale-Revised; DMN 5 default mode network; DOC 5 disorders of consciousness; EMCS 5 emergence from minimally conscious state; FDG 5 fluorodeoxyglucose; HC 5 healthy control; ICA 5 independent component analysis; MCS 5 minimally conscious state; MNI 5 Montreal Neurological Institute; PCC 5 posterior cingulate cortex; ReHo 5 regional homogeneity; ROI 5 region of interest; TBI 5 traumatic brain injury; VS 5 vegetative state.Coma is a cardinal sign of brain injury resulting from trauma, stroke, cardiac arrest, infection, or metabolic causes. While coma is a transient state from which the majority of subjects awaken, a subset of patients develop a more prolonged impairment in consciousness, such as the vegetative state (VS) or minimally conscious state (MCS). Despite considerable research, states such as coma, VS, and MCS-collectively termed disorders of consciousness (DOC)-remain poorly understood regarding their neural basis, clinical recognition, and long-term outcome.1,2 Neurophysiologic...