Long-term effects of sports concussion

Questions : Cette thèse visait à répondre à deux questions fondamentales : 1) Est-ce que les athlètes qui présentent un historique de commotions cérébrales du sport en conservent des effets délétères à long terme? ; et 2) Est-ce que les effets néfastes des commotions cérébrales récurrentes sur le fonctionnement tant cognitif que moteur sont cumulatifs? Devis expérimental : À l’aide d’un plan d’investigation double-cohorte réalisé avec un groupe d’athlètes évoluant au niveau universitaire et un autre formé d’anciens athlètes universitaires testés plus de trois décennies plus tard, les quatre études qui composent cette thèse ont employé des méthodes raffinées d’investigation des fonctions cognitives et motrices pour en déceler des atteintes persistantes. Méthodologie : Les potentiels évoqués cognitifs ainsi que les tests neuropsychologiques ont permis de sonder le fonctionnement cognitif de ces athlètes alors que la stimulation magnétique transcrânienne, une plateforme de force permettant de mesurer la stabilité posturale ainsi qu’un système d’enregistrement tridimensionnel des mouvements rapides alternatifs ont servi à l’évaluation de l’intégrité du système moteur. Résultats : Cette thèse a permis de déceler des altérations persistentes et cumulatives des fonctions cognitives et motrices. De plus, ces subtiles atteintes observées chez les jeunes athlètes, affectant essentiellement des marqueurs neurophysiologiques sous-cliniques du fonctionnement cognitif et moteur, s’étaient accentuées chez les anciens athlètes universitaires qui montraient un déclin quantifiable tant des fonctions cognitives que motrices. Discussion : Ces résultats suggèrent d’une part que les commotions cérébrales du sport entraînent des altérations cognitives et motrices chroniques qui s’accentuent en fonction du nombre de commotions cérébrales subies. D’autre part, les effets délétères des commotions cérébrales du sport sur le fonctionnement cognitif et moteur combinés à ceux associés au processus de vieillissement entraînent un déclin cognitif et moteur quantifiable en comparaison aux anciens athlètes n’ayant jamais subi de commotions cérébrales.Question: This thesis aimed to address two fundamental issues: 1) Are there long-lasting effects of sports-related concussion on cognitive and motor functions? and 2) Are the adverse effects of recurrent concussions cumulative? Experimental Design: The cross-sectional thesis design included a group of active university-level athletes as well as a group of former athletes recruited more than three decades after their university years who were tested on neurophysiological measures of both cognitive and motor system functions. Methods: Event-Related potentials and neuropsychological tests were used to assess cognitive functions while transcranial magnetic paradigms were used to assess motor cortex excitability, a force platform was used to assess postural stability and a 3-dimensional recording device was used to track hand position when performing a rapid alternating movement task. Results: This thesis disclosed persistent and cumulative alterations of both cognitive and motor functions after sports concussions. Furthermore, subclinical, neurophysiological alterations found in young concussed athletes were exacerbated in former athletes with concussions who displayed quantifiable cognitive and motor functions decline more than three decades post-concussion. Discussion: These results suggest that sports concussions induce cognitive and motor functions abnormalities that worsen as a function of the number of concussions sustained. Moreover, findings from the present thesis indicate that the deleterious effects of sports concussion on cognitive and motor system functions combined to those associated with the aging process lead to quantifiable decline on both cognition and motor functions

Electrophysiological impact of multiple concussions in asymptomatic athletes: a re-analysis based on alpha activity during a visual-spatial attention task

Most EEG studies used event-related potentials to assess long-term and cumulative effects of sport-related concussions on brain activity. Time-frequency methods provide another approach that allows the detection of subtle shifts in types and patterns of brain oscillations. We sought to discover whether event-related alpha activity would be significantly affected in asymptomatic multi-concussed athletes. We measured the amplitude of alpha activity (8–12 Hz) from the EEG recorded during a visual-spatial attention task to compare event-related alpha perturbations in 13 multi-concussed athletes and 14 age-equivalent, non-concussed teammates. Relative to non-concussed athletes, multi-concussed athletes showed significantly less event-related perturbations time-locked to stimulus presentation. Alpha activity alterations were closely related to the number of concussions sustained. Event-related alpha activity differed in asymptomatic multi-concussed athletes when compared to controls. Our study suggests that low-level neurophysiological underpinnings of the deployment of visual-spatial attention are affected in multi-concussed athletes even though their last concussion occurred on average 30 months prior to testing

Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

Alzheimer's disease (AD)—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE), the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD

Parallel recovery of consciousness and sleep in acute traumatic brain injury.

OBJECTIVE: To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI). METHODS: This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score. RESULTS: Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses. CONCLUSIONS: Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI

Motor Learning Improvement Remains 3 Months After a Multisession Anodal tDCS Intervention in an Aging Population

Healthy aging is associated with decline of motor function that can generate serious consequences on the quality of life and safety. Our studies aim to explore the 3-month effects of a 5-day multisession anodal transcranial direct current stimulation (a-tDCS) protocol applied over the primary motor cortex (M1) during motor sequence learning in elderly. The present sham-controlled aging study investigated whether tDCS-induced motor improvements previously observed 1 day after the intervention persist beyond 3 months. A total of 37 cognitively-intact aging participants performed five consecutive daily 20-min sessions of the serial-reaction time task (SRTT) concomitant with either anodal (n = 18) or sham (n = 19) tDCS over M1. All participants performed the Purdue Pegboard Test and transcranial magnetic stimulation (TMS) measures of cortical excitability were collected before, 1 day after and 3 months after the intervention. The last follow-up session also included the execution of the trained SRTT. The main findings are the demonstration of durable effects of a 5-day anodal tDCS intervention at the trained skill, while the active intervention did not differ from the sham intervention at both the untrained task and on measures of M1-disinhibition. Thus, the current article revealed for the first time the durability of functional effects of a-tDCS combined with motor training after only 5 days of intervention in an aging population. This finding provides evidence that the latter treatment alternative is effective in achieving our primary motor rehabilitation goal, that is to allow durable motor training effects in an aging population

Investigating the incidence and magnitude of heterotopic ossification with and without joints involvement in patients with a limb fracture and mild traumatic brain injury

Objectives: This study seeks to evaluate the incidence rate of heterotopic ossification (HO) formation in patients afflicted by an isolated limb fracture (ILF) and a concomitant mild traumatic brain injury (mTBI). Methods: The current study is an observational study including ILF patients with or without a concomitant mTBI recruited from an orthopedic clinic of a Level 1 Trauma Hospital. Patients were diagnosed with a mTBI according to the American Congress of Rehabilitation Medicine (ACRM) criteria. Radiographs taken on average 3 months post-trauma were analyzed separately by two distinct specialists for the presence of HO proximally to the fracture site (joints or extra joints). Both raters referred to Brooker's and Della's Valle's classification to establish signs of HO. First, analyses were conducted for the full sample. Secondly, a matched cohort was used in order to control for specific factors, namely age, sex, type of injury, and time elapsed between the accident and the analyzed radiograph. Results: The full sample included a total of 183 patients with an ILF (94 females; 47.5 years old), of which 50 had a concomitant mTBI and 133 without. Radiographic evidence of HO was significantly higher in patients with an ILF and a mTBI compared to ILF patients (X2 = 6.50; p = 0.01). The matched cohort consisted of 94 participants (i.e.; 47 patients from the ILF + mTBI group and 47 patients from the ILF group). Again, ILF + mTBI patients presented significantly higher rates of HO signs in comparison to ILF patients (X2 = 3.69; p = 0.04). Presence of HO was associated with prolonged delays to return to work (RTW) only in ILF + mTBI patients (F = 4.055; p = 0.05) but not in ILF patients (F = 0.823; p = 0.37). Conclusions: Study findings suggest that rates of HO are significantly higher proximally to fracture sites when ILF patients sustain a concomitant mTBI, even after controlling for factors known to influence HO. Moreover, results show that HO is associated with a prolonged RTW only in ILF patients with a concomitant mTBI but not in ILFonly patients. The impact of mTBI on HO formation warrants further attention to detect early signs of HO, to identify shared physiopathological mechanisms and, ultimately, to design targeted therapies

Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults

Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed with neuroimaging. Objectives: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals. Methods: Seventy-one subjects (ages: 55 to 76; apnea–hypopnea index: 0.2 to 96.6 events/h) were evaluated with magnetic resonance imaging. Two techniques were used: 1) voxel-based morphometry, which measures gray matter volume and concentration; 2) FreeSurfer automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, sleep fragmentation). Measurements and Main Results: Subjects had few symptoms, i.e. sleepiness, depression, anxiety and cognitive deficits. While no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume while more severe sleep fragmentation was associated with increased thickness of the inferior frontal gyrus. Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea

BDNF Val66Met polymorphism interacts with sleep consolidation to predict ability to create new declarative memories

It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (β-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (β-values from -0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (β = -0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition

Moderate to severe acute pain disturbs motor cortex intracortical inhibition and facilitation in orthopedic trauma patients : a TMS study

Objective Primary motor (M1) cortical excitability alterations are involved in the development and maintenance of chronic pain. Less is known about M1-cortical excitability implications in the acute phase of an orthopedic trauma. This study aims to assess acute M1-cortical excitability in patients with an isolated upper limb fracture (IULF) in relation to pain intensity. Methods Eighty-four (56 IULF patients <14 days post-trauma and 28 healthy controls). IULF patients were divided into two subgroups according to pain intensity (mild versus moderate to severe pain). A single transcranial magnetic stimulation (TMS) session was performed over M1 to compare groups on resting motor threshold (rMT), short-intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval cortical inhibition (LICI). Results Reduced SICI and ICF were found in IULF patients with moderate to severe pain, whereas mild pain was not associated with M1 alterations. Age, sex, and time since the accident had no influence on TMS measures. Discussion These findings show altered M1 in the context of acute moderate to severe pain, suggesting early signs of altered GABAergic inhibitory and glutamatergic facilitatory activities

Cerebral white matter diffusion properties and free‐water with obstructive sleep apnea severity in older adults

Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty‐five adults aged 55 to 85 were recruited and divided into three groups: control (apnea‐hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract‐Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free‐water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p < .05 corrected) and lower FW fraction (p < .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p < .05 corrected). No between‐group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics