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We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. We sought to characterize the neuroimaging, cognitive, pathological and metabolomic changes in a mouse model of rmTBI. Using a closed-skull model of mTBI that when scaled to human leads to rotational and linear accelerations far below what has been reported for sports concussion athletes, we found that 5 daily mTBIs triggered two temporally distinct types of pathological changes. First, during the first days and weeks after injury, the rmTBI produced diffuse axonal injury, a transient inflammatory response and changes in diffusion tensor imaging (DTI) that resolved with time. Second, the rmTBI led to pathological changes that were evident months after the injury including: changes in magnetic resonance spectroscopy (MRS), altered levels of synaptic proteins, behavioural deficits in attention and spatial memory, accumulations of pathologically phosphorylated tau, altered blood metabolomic profiles and white matter ultrastructural abnormalities. These results indicate that exceedingly mild rmTBI, in mice, triggers processes with pathological consequences observable months after the initial injury. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01161-2.

Ageing is associated with a decline in motor function that critically interferes with activities of daily living involving manual dexterity. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that has been shown to enhance manual dexterity in healthy aging adults. The supplementary motor area (SMA) is involved in motor preparation and bimanual control; therefore, bihemispheric tDCS incorporating the SMA may preferentially enhance bimanual motor movements in healthy older adults. The aim of the current study was to determine if tDCS incorporating SMA could improve manual dexterity in older adults. Twenty-four adults, aged 67–84 participated in this double-blind, randomized, cross over design, pilot study. One group of participants (n = 17) were randomized to receive stimulation or sham on their first visit and received the contrary on their second visit, seven days later. A second group of participants (n = 10) received three consecutive days of tDCS while performing a motor task. Participants performed unimanual and bimanual hand movements while receiving 2 mA of tDCS. The total time for participants to complete three trials of each task was recorded. No significant differences in performance times were observed between single or tri session tDCS and sham conditions. However, tDCS had opposing effects on the motor consolidation of anti-phase and in-phase bimanual tasks. During the tri session paradigm, older adults improved performance learning of antiphase bimanual movements more quickly than inphase bimanual movements, suggesting a different mechanism of action of these two movements.

The purpose of this study was to use non-invasive proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) to monitor changes in prefrontal white matter metabolite levels and tissue microstructure in female rugby players with and without concussion (ages 18-23, n = 64). Evaluations including clinical tests and 3 T MRI were performed at the beginning of a season (in-season) and followed up at the end of the season (off-season). Concussed athletes were additionally evaluated 24-72 hr (n = 14), three months (n = 11), and six months (n = 8) post-concussion. Reduced glutamine at 24-72 hr and three months post-concussion, and reduced glutamine/creatine at three months post-concussion were observed. In non-concussed athletes (n = 46) both glutamine and glutamine/creatine were lower in the off-season compared to in-season. Within the MRS voxel, an increase in fractional anisotropy (FA) and decrease in radial diffusivity (RD) were also observed in the non-concussed athletes, and correlated with changes in glutamine and glutamine/creatine. Decreases in glutamine and glutamine/creatine suggest reduced oxidative metabolism. Changes in FA and RD may indicate neuroinflammation or re-myelination. The observed changes did not correlate with clinical test scores suggesting these imaging metrics may be more sensitive to brain injury and could aid in assessing recovery of brain injury from concussion.

Objective:To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes.Methods:Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n = 26) and longitudinally in concussed athletes within 24 to 72 hours (n = 17) and 3 months (n = 14) after a diagnosed concussion.Results:There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption.Conclusions:Changes persisted well after players' clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated.

A short echo time (TE ) is commonly used for brain glutamate measurement by 1 H MRS to minimize drawbacks of long TE such as signal modulation due to J evolution and T2 relaxation. However, J coupling causes the spectral patterns of glutamate to change with TE , and the shortest achievable TE may not produce the optimal glutamate measurement. The purpose of this study was to determine the optimal TE for glutamate measurement at 7 T using semi-LASER (localization by adiabatic selective refocusing). Time-domain simulations were performed to model the TE dependence of glutamate signal energy, a measure of glutamate signal strength, and were verified against measurements made in the human sensorimotor cortex (five subjects, 2 × 2 × 2 cm3 voxel, 16 averages) on a 7 T MRI scanner. Simulations showed a local maximum of glutamate signal energy at TE = 107 ms. In vivo, TE = 105 ms produced a low Cramer-Rao lower bound of 6.5 ± 2.0% across subjects, indicating high-quality fits of the prior knowledge model to in vivo data. TE = 105 ms also produced the greatest glutamate signal energy with the smallest inter-subject glutamate-to-creatine ratio (Glu/Cr) coefficient of variation (CV), 4.6%. Using these CVs, we performed sample size calculations to estimate the number of participants per group required to detect a 10% change in Glu/Cr between two groups with 95% confidence. 13 were required at TE = 45 ms, the shortest achievable echo time on our 7 T MRI scanner, while only 5 were required at TE = 105 ms, indicating greater statistical power. These results indicate that TE = 105 ms is optimum for in vivo glutamate measurement at 7 T with semi-LASER. Using long TE decreases power deposition by allowing lower maximum RF pulse amplitudes in conjunction with longer RF pulses. Importantly, long TE minimizes macromolecule contributions, eliminating the requirement for acquisition of separate macromolecule spectra or macromolecule fitting techniques, which add additional scan time or bias the estimated glutamate fit.