Modulation of brain activity in brain-injured patients with a disorder of consciousness in intensive care with repeated 10-Hz transcranial alternating current stimulation (tACS): a randomised controlled trial protocol.

INTRODUCTION: Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. METHODS AND ANALYSES: The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current's frequency targets alpha brain oscillations (8-13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8-13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers' burden. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l'Île-de-Montréal (Project ID 2021-2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial's results will be published on a public trial registry database (ClinicalTrials.gov). TRIAL REGISTRATION NUMBER: NCT05833568.

Uninterrupted in vivo cerebral microdialysis measures of the acute neurochemical response to a single or repeated concussion in a rat model combining force and rotation.

Altered extracellular amino acid concentrations following concussion or mild traumatic brain injury can result in delayed neuronal damage through overactivation of NMDA glutamatergic receptors. However, the consequences of repeated concussions prior to complete recovery are not well understood. In this study, we utilized in vivo cerebral microdialysis and a weight-drop model to investigate the acute neurochemical response to single and repeated concussions in adult rats that were fully conscious. A microdialysis probe was inserted into the hippocampus and remained in place during impact. Primary outcomes included concentrations of glutamate, GABA, taurine, glycine, glutamine, and serine, while secondary outcomes were righting times and excitotoxic indices. Compared to sham injury, the first concussion resulted in significant increases in glutamate, GABA, taurine, and glycine levels, longer righting times, and higher excitotoxic indices. Following the second concussion, righting times were significantly longer, suggesting cumulative effects of repeated concussion while only partial increases were observed in glutamate and taurine levels. GABA and glycine levels, and excitotoxic indices were comparable to sham injury. These findings suggest that single and repeated concussions may induce acute increases in several amino acids, while repeated concussions could exacerbate neurological symptoms despite less pronounced neurochemical changes.

The Contribution of Sleep Quality and Psychological Factors to the Experience of Within-Day Pain Fluctuations Among Individuals With Temporomandibular Disorders.

We assessed the impact of day-to-day sleep quality and psychological variables (catastrophizing, negative affect, and positive affect) to within-day pain fluctuations in 42 females with painful temporomandibular disorders (TMD) using electronic diaries. More specifically, we examined the contribution of these variables to the likelihood of experiencing pain exacerbations defined as 1) an increase of 20 points (or more) in pain intensity on a 0 to 100 visual analog scale from morning to evening, and/or 2) a transition from mild-to-moderate pain over the course of the day; and pain decreases defined as 3) a decrease of 20 points (or more) in pain intensity (visual analog scale) from morning to evening, and/or 4) a reduction from moderate-to-mild pain over the day. The results indicated significantly main effects of sleep on both pain exacerbation outcomes (both P's < .05), indicating that nights with better sleep quality were less likely to be followed by clinically meaningful pain exacerbations on the next day. The results also indicated that days characterized by higher levels of catastrophizing were associated with a greater likelihood of pain exacerbations on the same day (both P's < .05). Daily catastrophizing was the only variable significantly associated with within-day pain decrease indices (both P's < .05). None of the other variables were associated with these outcomes (all P's > .05). These results underscore the importance of addressing patients' sleep quality and psychological states in the management of painful TMD. PERSPECTIVES: These findings highlight the significance of sleep quality and pain catastrophizing in the experience of within-day pain fluctuations among individuals with TMD. Addressing these components through tailored interventions may help to alleviate the impact of pain fluctuations and enhance the overall well-being of TMD patients.

A 10-day theta burst stimulation intervention facilitates the clinical rehabilitation of patients following an isolated limb fracture: A longitudinal SHAM-controlled pilot study.

OBJECTIVE: We investigated if theta burst stimulation (TBS) could enhance recovery by reducing key symptoms when implemented acutely post-fracture in participants with an isolated upper limb fracture (IULF). METHODS/DESIGN: This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous TBS protocol. Two main groups were included: I) participants with IULF receiving active TBS; and II) patients with IULF receiving SHAM/placebo. Another group (III) of healthy individuals were the reference group. Disability and pain intensity were collected through questionnaires (DASH & NRA) at three timepoints (baseline; 72 h post-intervention & 3 months post-injury). Group III completed the baseline assessment. RESULTS: 79 participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between Intervention and Time approached significance (F = 2.33; p = 0.11), whereas it was significant for pain (F = 3.42; p = 0.04). At 3 months post-injury, the ACTIVE group reported reduced disability (F = 4.71; p = 0.04) and pain (F = 5.84; p = 0.02) at three months post-injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. CONCLUSIONS: In IULF patients, a 10-day TBS intervention implemented acutely post-trauma had beneficial effects on symptoms of functional recovery and pain at 3 months post-trauma.

Characterization of Running Intensity in Canadian Football Based on Tactical Position.

This study aimed to use a data-driven approach to identify individualized speed thresholds to characterize running demands and athlete workload during games and practices in skill and linemen football players. Data were recorded from wearable sensors over 28 sessions from 30 male Canadian varsity football athletes, resulting in a total of 287 performances analyzed, including 137 games and 150 practices, using a global positioning system. Speed zones were identified for each performance by fitting a 5-dimensional Gaussian mixture model (GMM) corresponding to 5 running intensity zones from minimal (zone 1) to maximal (zone 5). Skill players had significantly higher (p < 0.001) speed thresholds, percentage of time spent, and distance covered in maximal intensity zones compared to linemen. The distance covered in game settings was significantly higher (p < 0.001) compared to practices. This study highlighted the use of individualized speed thresholds to determine running intensity and athlete workloads for American and Canadian football athletes, as well as compare running performances between practice and game scenarios. This approach can be used to monitor physical workload in athletes with respect to their tactical positions during practices and games, and to ensure that athletes are adequately trained to meet in-game physical demands.

Short-term changes in the physiology of the primary motor cortex following head impact exposure during a Canadian football game.

OBJECTIVE: This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). METHODS: Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations. RESULTS: Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05). CONCLUSIONS: Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

One session of repetitive transcranial magnetic stimulation induces mild and transient analgesic effects among female individuals with painful temporomandibular disorders.

OBJECTIVE: Temporomandibular disorders (TMD) are characterised by chronic pain and dysfunction in the jaw joint and masticatory muscles. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential non-invasive treatment for chronic pain; however, its effectiveness in individuals with TMD has not been thoroughly investigated. This study aimed to evaluate the immediate and sustained (over seven consecutive days) effects of a single session of active rTMS compared to sham stimulation on pain intensity and pain unpleasantness in individuals with TMD. METHODS: A randomised, double-blind, sham-controlled trial enrolled 41 female participants with chronic TMD. Pain intensity and pain unpleasantness were assessed immediately pre- and post-intervention, as well as twice daily for 21 days using electronic diaries. Secondary outcomes included pain interference, sleep quality, positive and negative affect and pain catastrophizing. Adverse effects were monitored. Repeated measures ANOVA and multilevel modelling regression analyses were employed for data analysis. RESULT: Active rTMS demonstrated a significant immediate mild reduction in pain intensity and pain unpleasantness compared to sham stimulation. However, these effects were not sustained over the 7-day post-intervention period. No significant differences were observed between interventions for pain interference, sleep quality and negative affect. A minority of participants reported minor and transient side effects, including headaches and fatigue. CONCLUSION: A single session of active rTMS was safe and led to immediate mild analgesic effects in individuals with TMD compared to sham stimulation. However, no significant differences were observed between interventions over the 7-day post-intervention period. Based on this study, rTMS stimulation appears to be a promising safe approach to be tested in TMD patients with longer stimulation protocols.

Females with painful temporomandibular disorders present higher intracortical facilitation relative to pain-free controls.

OBJECTIVES: This study aimed to investigate cortical excitability differences in the primary motor cortex (M1) hand representation between individuals with temporomandibular disorders (TMD) and healthy controls. We assessed resting motor thresholds, motor-evoked potentials (MEPs), intracortical inhibition, and intracortical facilitation and explored potential associations with clinical and psychosocial characteristics in the TMD group. MATERIALS AND METHODS: We recruited 36 female participants with TMD and 17 pain-free controls. Transcranial magnetic stimulation (TMS) was used to assess M1 cortical excitability. Correlations between clinical and psychosocial factors and cortical excitability measures were also evaluated. RESULTS: Patients with TMD showed significantly higher intracortical facilitation at 12 ms (z = 1.98, p = 0.048) and 15 ms (z = 2.65, p = 0.008) when compared to controls. Correlations revealed associations between intracortical facilitation and pain interference, sleep quality, depressive symptoms, and pain catastrophizing in the TMD group. CONCLUSIONS: Females with TMD exhibit heightened motor cortex intracortical facilitation in the hand representation, potentially indicating altered cortical excitability beyond the motor face area. This suggests a role for cortical excitability in TMD pathophysiology, influenced by psychosocial factors. CLINICAL RELEVANCE: Understanding cortical excitability in TMD may inform targeted interventions. Psychosocial variables may play a role in cortical excitability, emphasizing the multidimensional nature of TMD-related pain. Further research is needed to confirm and expand upon these findings, with potential implications for the management of TMD and related pain conditions.

Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice.

In Parkinson's disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due to the ability of many motor behaviors to be sustained through a diffuse basal tone of DA; but experimental evidence for this is limited. Here we show that conditional deletion of the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (Syt1 cKODA mice) abrogates most activity-dependent axonal DA release in the striatum and mesencephalon, leaving somatodendritic (STD) DA release intact. Strikingly, Syt1 cKODA mice showed intact performance in multiple unconditioned DA-dependent motor tasks and even in a task evaluating conditioned motivation for food. Considering that basal extracellular DA levels in the striatum were unchanged, our findings suggest that activity-dependent DA release is dispensable for such tasks and that they can be sustained by a basal tone of extracellular DA. Taken together, our findings reveal the striking resilience of DA-dependent motor functions in the context of a near-abolition of phasic DA release, shedding new light on why extensive loss of DA innervation is required to reveal motor dysfunctions in PD.

The Putative Role of Neuroinflammation in the Interaction between Traumatic Brain Injuries, Sleep, Pain and Other Neuropsychiatric Outcomes: A State-of-the-Art Review.

Sleep disturbances are widely prevalent following a traumatic brain injury (TBI) and have the potential to contribute to numerous post-traumatic physiological, psychological, and cognitive difficulties developing chronically, including chronic pain. An important pathophysiological mechanism involved in the recovery of TBI is neuroinflammation, which leads to many downstream consequences. While neuroinflammation is a process that can be both beneficial and detrimental to individuals' recovery after sustaining a TBI, recent evidence suggests that neuroinflammation may worsen outcomes in traumatically injured patients, as well as exacerbate the deleterious consequences of sleep disturbances. Additionally, a bidirectional relationship between neuroinflammation and sleep has been described, where neuroinflammation plays a role in sleep regulation and, in turn, poor sleep promotes neuroinflammation. Given the complexity of this interplay, this review aims to clarify the role of neuroinflammation in the relationship between sleep and TBI, with an emphasis on long-term outcomes such as pain, mood disorders, cognitive dysfunctions, and elevated risk of Alzheimer's disease and dementia. In addition, some management strategies and novel treatment targeting sleep and neuroinflammation will be discussed in order to establish an effective approach to mitigate long-term outcomes after TBI.

Transcranial Alternating Current Stimulation to Modulate Alpha Activity: A Systematic Review.

BACKGROUND: Transcranial alternating current stimulation (tACS) has been one of numerous investigation methods used for their potential to modulate brain oscillations; however, such investigations have given contradictory results and a lack of standardization. OBJECTIVES: In this systematic review, we aimed to assess the potential of tACS to modulate alpha spectral power. The secondary outcome was the identification of tACS methodologic key parameters, adverse effects, and sensations. MATERIALS AND METHODS: Studies in healthy adults who were receiving active and sham tACS intervention or any differential condition were included. The main outcome assessed was the increase/decrease of alpha spectral power through either electroencephalography or magnetoencephalography. Secondary outcomes were methodologic parameters, sensation reporting, and adverse effects. Risks of bias and the study quality were assessed with the Cochrane assessment tool. RESULTS: We obtained 1429 references, and 20 met the selection criteria. A statistically significant alpha-power increase was observed in nine studies using continuous tACS stimulation and two using intermittent tACS stimulation set at a frequency within the alpha range. A statistically significant alpha-power increase was observed in three more studies using a stimulation frequency outside the alpha range. Heterogeneity among stimulation parameters was recognized. Reported adverse effects were mild. The implementation of double blind was identified as challenging using tACS, in part owing to electrical artifacts generated by stimulation on the recorded signal. CONCLUSIONS: Most assessed studies reported that tACS has the potential to modulate brain alpha power. The optimization of this noninvasive brain stimulation method is of interest mostly for its potential clinical applications with neurological conditions associated with perturbations in alpha brain activity. However, more research efforts are needed to standardize optimal parameters to achieve lasting modulation effects, develop methodologic alternatives to reduce experimental bias, and improve the quality of studies using tACS to modulate brain activity.

The Use of Electroencephalography as an Informative Tool in Assisting Early Clinical Management after Sport-Related Concussion: a Systematic Review.

Sport-related concussion (SRC) is managed primarily through serial clinical evaluations throughout recovery. However, studies suggest that clinical measures may not be suitable to detect subtle alterations in functioning and are limited by numerous internal and external factors. Electroencephalography (EEG) has been used for over eight decades to discern altered function following illnesses and injuries, including traumatic brain injury. This study evaluated the associations between EEG measures and clinical presentation within three-months following SRC. A systematic review of the literature was performed in Medline, Embase, PsycINFO, CINAHL and Web of Science databases following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines, yielding a total of 13 peer-reviewed articles. Most studies showed low to moderate bias and moderate to high quality. The majority of the existing literature on the impact of concussion within the first 3 months post-injury suggests that individuals with concussion show altered brain function, with EEG abnormalities outlasting clinical dysfunction. Of all EEG biomarkers evaluated, P300 shows the most promise and should be explored further. Despite the relatively high quality of included articles, significant limitations are still present within this body of literature, including potential conflicts of interest and proprietary algorithms, making it difficult to draw strong and meaningful conclusions on the use of EEG in the early stages of SRC. Therefore, further exploration of the relationship between EEG measures and acute clinical presentation is warranted to determine if EEG provides additional benefits over current clinical assessments and is a feasible tool in clinical settings.

Traumatic brain injuries are ignored or discriminated in prospective clinical trials on shoulder fractures: a systematic review.

PURPOSE: Current literature suggests a significant epidemiological association between traumatic brain injury (TBI) and proximal upper limb fractures in addition to major clinical consequences. A systematic review was conducted to assess how TBI is taken into consideration in interventional studies on shoulder fractures. METHODS: The following data sources were used: MEDLINE, EMBASE, EBM Reviews, CINAHL, and OpenGrey databases. Study selection included interventional randomized clinical trials and prospective cohort studies on shoulder fractures published in English or French between 2008 and 2020. Studies on pathologic fractures, chronic fracture complications, nonhuman subjects, and biomechanics were excluded. Articles were reviewed by two independent authors according to the PRISMA guidelines. Baseline characteristics, exclusion criteria, and input relevant to TBI were recorded. Methodological quality was assessed with the Cochrane risk of bias tool for randomized clinical trials and the Newcastle-Ottawa Scale for cohort studies. RESULTS: One-hundred-thirteen studies met the inclusion criteria. None discussed the possible impact of TBI on their results. Only three (2.7%) studies considered TBI relevant and included these patients in their cohort. Furthermore, 43/113 (38.1%) excluded patients with injuries or mechanisms strongly related to traumatic brain injuries: head injuries (4); moderate and/or severe TBI (7); high energy traumas (3); Polytrauma subjects (33). CONCLUSION: TBI are ignored or discriminated in prospective clinical trials on shoulder fractures. The exclusion of these cases impacts generalizability as their prevalence is significant. Considering the major impact of TBI on important outcomes, its presence should always be assessed to ensure high quality evidence. LEVEL OF EVIDENCE: Systematic Review, Therapeutic Level II.

Effects of emotion and emotional ambiguity on early visual event-related potentials.

The modulation of early sensory event-related potentials such as the P1, N1, and N170 by emotion and emotional ambiguity is still controversial. Some studies have found a modulation of one or all of these components by one or both of these factors, whereas others have failed to show such results. The objective of this study was to investigate the effects of emotion and ambiguity on the behavioral and electrophysiological responses to a morphed emotion recognition task. Thirty-seven healthy participants (19 men) completed an emotion recognition task where photographs of a male face expressing the six basic emotions morphed with another emotion (in a proportion ranging from 26% to 74%) were randomly presented while electroencephalography was recorded. After each face presentation, participants were asked to identify the facial emotion. We found an emotional effect on the P1, N1, and N170, with greater amplitudes for some emotional facial expressions than for others. However, we found no significant emotional ambiguity effect or interaction between emotion and ambiguity for any of these components. These findings suggest that computation of emotional facial expressions (regardless of their ambiguity) occurs from the early stages of brain processing. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

TractoInferno - A large-scale, open-source, multi-site database for machine learning dMRI tractography.

TractoInferno is the world's largest open-source multi-site tractography database, including both research- and clinical-like human acquisitions, aimed specifically at machine learning tractography approaches and related ML algorithms. It provides 284 samples acquired from 3 T scanners across 6 different sites. Available data includes T1-weighted images, single-shell diffusion MRI (dMRI) acquisitions, spherical harmonics fitted to the dMRI signal, fiber ODFs, and reference streamlines for 30 delineated bundles generated using 4 tractography algorithms, as well as masks needed to run tractography algorithms. Manual quality control was additionally performed at multiple steps of the pipeline. We showcase TractoInferno by benchmarking the learn2track algorithm and 5 variations of the same recurrent neural network architecture. Creating the TractoInferno database required approximately 20,000 CPU-hours of processing power, 200 man-hours of manual QC, 3,000 GPU-hours of training baseline models, and 4 Tb of storage, to produce a final database of 350 Gb. By providing a standardized training dataset and evaluation protocol, TractoInferno is an excellent tool to address common issues in machine learning tractography.

Conditioning to Enhance the Effects of Repetitive Transcranial Magnetic Stimulation on Experimental Pain in Healthy Volunteers.

Objective: In this proof-of-concept study we sought to explore whether the combination of conditioning procedure based on a surreptitious reduction of a noxious stimulus (SRPS) could enhance rTMS hypoalgesic effects [i.e., increase heat pain threshold (HPT)] and augment intervention expectations in a healthy population. Methods: Forty-two healthy volunteers (19-35 years old) were enrolled in a randomized crossover-controlled study and were assigned to one of two groups: (1) SRPS and (2) No SRPS. Each participant received two consecutive sessions of active or sham rTMS over the M1 area of the right hand on two visits (1) active, (2) sham rTMS separated by at least one-week interval. HPT and the temperature needed to elicit moderate heat pain were measured before and after each rTMS intervention on the right forearm. In the SRPS group, conditioning consisted of deliberately decreasing thermode temperature by 3°C following intervention before reassessing HPT, while thermode temperature was held constant in the No SRPS group. Intervention expectations were measured before each rTMS session. Results: SRPS conditioning procedure did not enhance hypoalgesic effects of rTMS intervention, neither did it modify intervention expectations. Baseline increases in HPT were found on the subsequent intervention session, suggesting variability of this measure over time, habituation or a possible "novelty effect." Conclusion: Using a SRPS procedure in healthy volunteers did not enhance rTMS modulating effects on experimental pain sensation (i.e., HPT). Future studies are therefore needed to come up with a conditioning procedure which allows significant enhancement of rTMS pain modulating effects in healthy volunteers.

Pupil Light Reflex for the Assessment of Analgesia in Critically Ill Sedated Patients With Traumatic Brain Injury: A Preliminary Study.

ABSTRACT: BACKGROUND: Analgesia monitoring is essential to preserve comfort in critically ill sedated patients with traumatic brain injury (TBI). Although pupil dilation (PD) and pain behaviors can be used to assess analgesia, these indicators require application of noxious stimulations for elicitation. Recently, the pupillary light reflex (PLR) has emerged as a nonnoxious parameter that may be used to predict analgesia requirements in non-brain-injured patients. Here, we explored whether PLR can be used for the purpose of analgesia monitoring in critically ill sedated TBI patients. METHODS: Fifteen mechanically ventilated TBI patients (11 men; 54 ± 20 years) under continuous analgesia and sedation infusions were assessed at predefined time within 72 hours of intensive care unit admission. Data collection was performed using video-pupillometry and the Behavioral Pain Scale. At each assessment, pupil size and PLR at rest were recorded followed immediately by the documentation of PD and pain behaviors elicited by a calibrated noxious stimulus. Blood concentrations of analgesics/sedatives were monitored. RESULTS: One hundred three assessments were completed. PLR resulted in an average decrease of 19% in pupil diameter, and PD resulted in an average increase of 10% in pupil diameter. Variations in PLR and PD were more pronounced in subjects who showed a Behavioral Pain Scale score greater than 3 (a recognized sign of subanalgesia) compared with those with no behavioral reaction. Multiple regression analyses suggest a significant overlap between fluctuations in pupillary reflexes and blood levels of fentanyl, not propofol. CONCLUSION: In our sample, percentages of variation in PLR and PD were found to be directly representative of TBI patients' fentanyl blood concentration. Considering information about blood drug concentration is generally not available at bedside, PLR could be used as a proxy to assess analgesia requirements before a nociceptive procedure in critically ill sedated TBI patients who are vulnerable to stress.

Efficacy of prophylactic versus therapeutic administration of the NMDA receptor antagonist MK-801 on the acute neurochemical response to a concussion in a rat model combining force and rotation.

OBJECTIVE: Alterations in amino acid concentrations are a major contributor to the persistent neurological and behavioral effects induced by concussions and mild traumatic brain injuries (TBIs). Glutamate, the most abundant excitatory amino acid in the CNS, has a major role in the pathophysiological process of concussion. The indiscriminate liberation of glutamate immediately after a concussion triggers an excitotoxic response that leads to cell death, neuronal damage, and the dysfunction of surviving neurons, largely by overactivation of N-methyl-d-aspartate (NMDA) glutamatergic receptors. The aim of the present study was to investigate the efficacy of prophylactic versus therapeutic administration of MK-801, a promising NMDA receptor antagonist, on the acute changes in amino acid extracellular concentrations involved in excitotoxicity resulting from a concussive trauma. METHODS: The immediate neurochemical response to a concussion cannot be characterized in humans. Therefore, the authors used their previously validated combination of a weight-drop concussion rat model and in vivo cerebral microdialysis. The microdialysis probe was inserted inside the hippocampus and left inserted at impact to allow uninterrupted sampling of amino acids of interest immediately after concussion. The primary outcome included amino acid concentrations and the secondary outcome included righting time. Samples were taken in 10-minute increments for 60 minutes before, during, and 60 minutes after impact, and analyzed for glutamate, gamma-aminobutyric acid, taurine, glycine, glutamine, and serine using high-performance liquid chromatography. Righting time was acquired as a neurological restoration indicator. Physiological saline or 10 mg/kg MK-801 was administrated intraperitoneally 60 minutes before or immediately following induction of sham injury or concussion. RESULTS: Following induction of concussion, glutamate, taurine, and glycine levels as well as righting times in cases from the MK-801 treatment group were comparable to those of vehicle-treated animals. In contrast, righting times and amino acid concentrations observed within the first 10 minutes after induction of concussion in cases assigned to the MK-801 prophylaxis group were comparable to those of sham-injured animals. CONCLUSIONS: These results suggest that presynaptic actions and peak availability of MK-801 following prophylactic administration significantly inhibit the immediate and indiscriminate release of glutamate, taurine, and glycine in extracellular fluid after a concussion.

Effects of Music Intervention on Stress in Concussed and Non-Concussed Athletes.

Sport-related concussion is a serious public health issue affecting millions of individuals each year. Among the many negative side effects, emotional symptoms, such as stress, are some of the most common. Stress management is repeatedly cited by expert groups as an important intervention for this population. It was shown that music has relaxing effects, reducing stress through the activation of brain areas involved in emotions and pleasure. The objective of this study was to explore the effects of a music-listening intervention compared with silence on experimentally induced stress in concussed and non-concussed athletes. To this aim, four groups of athletes (non-concussed music, non-concussed silence, concussed music, and concussed silence) performed the Trier Social Stress Test, for which both physiological (skin conductance level) and self-reported stress measurements were taken. No significant difference was found in the pattern of stress recovery for self-reported measurements. However, the skin conductance results showed greater and faster post-stress recovery after listening to music compared with silence for concussed athletes only. Taken together, these results suggest that music could be an efficient stress management tool to implement in the everyday life of concussed athletes to help them prevent stress accumulation.

Relevance of Sleep Disturbances to Orthopaedic Surgery: A Current Concepts Narrative and Practical Review.

➤: Sleep disturbances can increase the risk of falls and motor vehicle accidents and may reduce bone density. ➤: Poor sleep can lead to worse outcomes after fracture, such as chronic pain and delayed recovery. ➤: Orthopaedic surgeons can play an important role in the screening of sleep disorders among their patients.