Sébastien Tremblay

Acute and Chronic Changes in Diffusivity Measures after Sports Concussion

Despite negative neuroimaging findings in concussed athletes, studies indicate that the acceleration and deceleration of the brain after concussive impacts result in metabolic and electrophysiological alterations that may be attributable to changes in white matter resulting from biomechanical strain. In the present study we investigated the effects of sports concussion on white matter using three different diffusion tensor imaging (DTI) measures: fractional anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD). We compared a group of 10 non-concussed athletes with a group of 18 concussed athletes of the same age (mean age 22.5 years) and education (mean 16 years) using a voxel-based approach (VBA) in both the acute and chronic post-injury phases. All concussed athletes were scanned 1-6 days post-concussion and again 6 months later in a 3T Siemens Trio(™) MRI. Three 2×2 repeated-measures analyses of variance (ANOVAs) were conducted, one for each measure of DTI used in the current study. There was a main group effect of FA, which was increased in dorsal regions of both corticospinal tracts (CST) and in the corpus callosum in concussed athletes at both time points. There was a main group effect of AD in the right CST, where concussed athletes showed elevated values relative to controls at both time points. MD values were decreased in concussed athletes, in whom analyses revealed significant group differences in the CST and corpus callosum at both time points. Although the use of VBA does limit the analyses to large tracts, and it has clinical limitations with regard to individual analyses, our results nevertheless indicate that sports concussions do result in changes in diffusivity in the corpus callosum and CST that are not detected using conventional neuroimaging techniques.

Neurometabolic Changes in the Acute Phase after Sports Concussions Correlate with Symptom Severity

Sports concussion is a major problem that affects thousands of people in North America every year. Despite negative neuroimaging findings, many athletes display neurophysiological alterations and post-concussion symptoms such as headaches and sensitivity to light and noise. It is suspected that neurometabolic changes may underlie these changes. In this study we investigated the effects of sports concussion on brain metabolism using (1)H-MR spectroscopy by comparing a group of 12 non-concussed athletes with a group of 12 concussed athletes of the same age (mean 22.5 years) and education (mean 16 years). All athletes were scanned 1-6 days post-concussion in a 3T Siemens MRI, and were administered a symptom scale to evaluate post-concussion symptomatology. Participants also completed a neuropsychological test battery to assess verbal memory, visual memory, information processing speed, and reaction time, and no group differences were detected relative to controls. Concussed athletes showed a higher number of symptoms than non-concussed athletes, and they also showed a significant decrease in glutamate in the primary motor cortex (M1), as well as significant decreases in N-acetylaspartate in the prefrontal and primary motor cortices. No changes were observed in the hippocampus. Furthermore, the metabolic changes in M1 correlated with self-reported symptom severity despite equivalent neuropsychological performance. These results confirm cortical neurometabolic changes in the acute post-concussion phase, and demonstrate for the first time a correlation between subjective self-reported symptoms and objective physical changes that may be related to increased vulnerability of the concussed brain.

Sports Concussions and Aging: A Neuroimaging Investigation

Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

Altered Bidirectional Plasticity and Reduced Implicit Motor Learning in Concussed Athletes

Persistent motor/cognitive alterations and increased prevalence of Alzheimers disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. To test the hypothesis that increased GABAergic inhibition after repeated concussions suppresses LTP/LTD and contributes to learning impairments, we used a paired associative stimulation (PAS) protocol to induce LTP/LTD-like effects in primary motor cortex (M1) jointly with an implicit motor learning task (serial reaction time task, SRTT). Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.

Persistent Motor System Abnormalities in Formerly Concussed Athletes

CONTEXT The known detrimental effects of sport concussions on motor system function include balance problems, slowed motor execution, and abnormal motor cortex excitability. OBJECTIVE To assess whether these concussion-related alterations of motor system function are still evident in collegiate football players who sustained concussions but returned to competition more than 9 months before testing. DESIGN Case-control study. SETTING University laboratory. PATIENTS OR OTHER PARTICIPANTS A group of 21 active, university-level football players who had experienced concussions was compared with 15 university football players who had not sustained concussions. INTERVENTION(S) A force platform was used to assess center-of-pressure (COP) displacement and COP oscillation regularity (approximate entropy) as measures of postural stability in the upright position. A rapid alternating-movement task was also used to assess motor execution speed. Transcranial magnetic stimulation over the motor cortex was used to measure long-interval intracortical inhibition and the cortical silent period, presumably reflecting y-aminobutyric acid subtype B receptor-mediated intracortical inhibition. MAIN OUTCOME MEASURE(S) COP displacement and oscillation regularity, motor execution speed, long-interval intracortical inhibition, cortical silent period. RESULTS Relative to controls, previously concussed athletes showed persistently lower COP oscillation randomness, normal performance on a rapid alternating-movement task, and more M1 intracortical inhibition that was related to the number of previous concussions. CONCLUSIONS Sport concussions were associated with pervasive changes in postural control and more M1 intracortical inhibition, providing neurophysiologic and behavioral evidence of lasting, subclinical changes in motor system integrity in concussed athletes.

Cumulative effects of concussions in athletes revealed by electrophysiological abnormalities on visual working memory

Event-related potentials (ERPs) have been useful to detect subtle, pervasive alterations of cognition-related waveforms in athletes with multiple concussions. This study used the sustained posterior contralateral negativity (SPCN) waveform component recorded while participants performed a visual short-term memory task to investigate how working memory (WM) storage capacity was affected among athletes who differed according to their history of sports concussions. Fifty-five university-level football players were assigned to three groups: 1–2 concussion athletes; 3+ concussion athletes; non-concussed athletes. The main finding of the present study was that athletes with a history of three concussions or more exhibited significantly attenuated SPCN amplitude relative to both concussed athletes with only one or two prior concussions and athletes without concussions. The latter finding adds to previous evidence of disproportionately worse outcome in athletes presenting with a history of three or more concussions relative to those with fewer concussions. In addition, SPCN amplitude was found to correlate significantly with a visual memory capacity estimate (K), but this K value did not significantly differ across groups. This suggests that attenuated SPCN amplitude after three or more concussions did not interfere with apparent WM function. Taken together, these findings suggest that the altered neurophysiological index of WM storage might be a more sensitive measure of a latent WM function abnormality which may well worsen with aging, or perhaps additional brain insults.

Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions

Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.

Multimodal assessment of primary motor cortex integrity following sport concussion in asymptomatic athletes

OBJECTIVE Recent studies have shown, in asymptomatic concussed athletes, metabolic disruption in the primary motor cortex (M1) and abnormal intracortical inhibition lasting for more than six months. The present study aims to assess if these neurochemical and neurophysiological alterations are persistent and linked to M1 cortical thickness. METHODS Sixteen active football players who sustained their last concussion, on average, three years prior to testing and 14 active football players who never sustained a concussion were recruited for a single session of proton magnetic resonance spectroscopy ((1)H-MRS) and transcranial magnetic stimulation (TMS). Measures of M1 and whole brain cortical thickness were acquired, and (1)H-MRS data were acquired from left M1 using a MEGA-PRESS sequence. Cortical silent period (CSP) and long-interval intracortical inhibition (LICI) were measured with TMS applied over left M1. RESULTS No significant group differences were observed for metabolic concentrations, TMS measures, and cortical thickness. However, whereas GABA and glutamate levels were positively correlated in control athletes, this relationship was absent in concussed athletes. CONCLUSION These data suggest the general absence of neurophysiologic, neurometabolic and neuroanatomical disruptions in M1 three years following the last concussive event. However, correlational analyses suggest the presence of a slight metabolic imbalance between GABA and glutamate concentrations in the primary motor cortex of concussed athletes. SIGNIFICANCE The present study highlights the importance of multimodal assesments of the impacts of sport concussions.

Motor system alterations in retired former athletes: the role of aging and concussion history

BackgroundRetired athletes with a history of sports concussions experience cognitive and motor declines with aging, and the risk of severe neurodegenerative conditions is magnified in this population. The present study investigated the effects of aging on motor system metabolism and function in former university-level athletes who sustained their last concussion several decades prior to testing.MethodsTo test the hypothesis that age and remote concussions induce functional as well as metabolic alterations of the motor system, we used proton magnetic resonance spectroscopy to detect metabolic abnormalities in the primary motor cortex and the serial reaction time task (SRTT) to evaluate motor learning.ResultsOur results indicate that motor learning is significantly reduced in former concussed athletes relative to controls. In addition, glutamate/H2O ratio in M1 was disproportionately reduced in concussed athletes with advancing age and was found to strongly correlate with motor learning impairments.ConclusionFindings from this study provide evidence that the acquisition of a repeated motor sequence is compromised in the aging concussed brain and that its physiological underpinnings could implicate disproportionate reductions of M1 glutamate concentrations with advancing age.

Long-Term Effects of Sports Concussions: Bridging the Neurocognitive Repercussions of the Injury with the Newest Neuroimaging Data

Little is known of the long-term effects of sports-related concussion. Within the scientific literature, conclusions vary substantially where some work suggests there are no long-term consequences at all and other studies show rampant neurodegeneration thought to be caused by sometimes even a single concussive blow to the head. There is growing evidence that supports multiple long-term outcomes, showing both subclinical and clinically relevant changes in the brains of athletes, young and old alike. This article reviews the pathohistology of cerebral concussions and examines the extant literature with a focus on electrophysiological and neuroimaging findings. Neurobehavioral and neurocognitive changes are also reviewed, particularly as they are related to chronic traumatic encephalopathy. Lacunae within the literature are explored, and future research directions are proposed.