Sensor-Assisted Analysis of Autonomic and Cerebrovascular Dysregulation following Concussion in an Individual with a History of Ten Concussions: A Case Study.

INTRODUCTION: Concussion is known to cause transient autonomic and cerebrovascular dysregulation that generally recovers; however, few studies have focused on individuals with an extensive concussion history. METHOD: The case was a 26-year-old male with a history of 10 concussions, diagnosed for bipolar type II disorder, mild attention-deficit hyperactivity disorder, and a history of migraines/headaches. The case was medicated with Valproic Acid and Escitalopram. Sensor-based baseline data were collected within six months of his injury and on days 1-5, 10, and 14 post-injury. Symptom reporting, heart rate variability (HRV), neurovascular coupling (NVC), and dynamic cerebral autoregulation (dCA) assessments were completed using numerous biomedical devices (i.e., transcranial Doppler ultrasound, 3-lead electrocardiography, finger photoplethysmography). RESULTS: Total symptom and symptom severity scores were higher for the first-week post-injury, with physical and emotional symptoms being the most impacted. The NVC response showed lowered activation in the first three days post-injury, while autonomic (HRV) and autoregulation (dCA) were impaired across all testing visits occurring in the first 14 days following his concussion. CONCLUSIONS: Despite symptom resolution, the case demonstrated ongoing autonomic and autoregulatory dysfunction. Larger samples examining individuals with an extensive history of concussion are warranted to understand the chronic physiological changes that occur following cumulative concussions through biosensing devices.

Heart Rate Variability and Pulse Rate Variability: Do Anatomical Location and Sampling Rate Matter?

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20-100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown. Further, due to different autonomic innervation, it is unknown if PRV metrics are harmonious between the cerebral and peripheral vasculature. Cardiac activity via electrocardiography (ECG) and PPG were obtained concurrently in 54 participants (29 females) in an upright orthostatic position. PPG data were collected at three anatomical locations: left third phalanx, middle cerebral artery, and posterior cerebral artery using a Finapres NOVA device and transcranial Doppler ultrasound. Data were sampled for five minutes at 1000 Hz and downsampled to frequencies ranging from 20 to 500 Hz. HRV (via ECG) and PRV (via PPG) were quantified and compared at 1000 Hz using Bland-Altman plots and coefficient of variation (CoV). A sampling frequency of ~100-200 Hz was required to produce PRV metrics with a bias of less than 2%, while a sampling rate of ~40-50 Hz elicited a bias smaller than 20%. At 1000 Hz, time- and frequency-domain PRV measures were slightly elevated compared to those derived from HRV (mean bias: ~1-8%). In conjunction with previous reports, PRV and HRV were not surrogate biomarkers due to the different nature of the collected waveforms. Nevertheless, PRV estimates displayed greater validity at a lower sampling rate compared to HRV estimates.

A systematic review, meta-analysis, and meta-regression amalgamating the driven approaches used to quantify dynamic cerebral autoregulation.

Numerous driven techniques have been utilized to assess dynamic cerebral autoregulation (dCA) in healthy and clinical populations. The current review aimed to amalgamate this literature and provide recommendations to create greater standardization for future research. The PubMed database was searched with inclusion criteria consisting of original research articles using driven dCA assessments in humans. Risk of bias were completed using Scottish Intercollegiate Guidelines Network and Methodological Index for Non-Randomized Studies. Meta-analyses were conducted for coherence, phase, and gain metrics at 0.05 and 0.10 Hz using deep-breathing, oscillatory lower body negative pressure (OLBNP), sit-to-stand maneuvers, and squat-stand maneuvers. A total of 113 studies were included, with 40 of these incorporating clinical populations. A total of 4126 participants were identified, with younger adults (18-40 years) being the most studied population. The most common techniques were squat-stands (n = 43), deep-breathing (n = 25), OLBNP (n = 20), and sit-to-stands (n = 16). Pooled coherence point estimates were: OLBNP 0.70 (95%CI:0.59-0.82), sit-to-stands 0.87 (95%CI:0.79-0.95), and squat-stands 0.98 (95%CI:0.98-0.99) at 0.05 Hz; and deep-breathing 0.90 (95%CI:0.81-0.99); OLBNP 0.67 (95%CI:0.44-0.90); and squat-stands 0.99 (95%CI:0.99-0.99) at 0.10 Hz. This review summarizes clinical findings, discusses the pros/cons of the 11 unique driven techniques included, and provides recommendations for future investigations into the unique physiological intricacies of dCA.

Maximizing the Reliability and Precision of Measures of Prefrontal Cortical Oxygenation Using Frequency-Domain Near-Infrared Spectroscopy.

Frequency-domain near-infrared spectroscopy (FD-NIRS) has been used for non-invasive assessment of cortical oxygenation since the late 1990s. However, there is limited research demonstrating clinical validity and general reproducibility. To address this limitation, recording duration for adequate validity and within- and between-day reproducibility of prefrontal cortical oxygenation was evaluated. To assess validity, a reverse analysis of 10-min-long measurements (n = 52) at different recording durations (1-10-min) was quantified via coefficients of variation and Bland-Altman plots. To assess within- and between-day within-subject reproducibility, participants (n = 15) completed 2-min measurements twice a day (morning/afternoon) for five consecutive days. While 1-min recordings demonstrated sufficient validity for the assessment of oxygen saturation (StO2) and total hemoglobin concentration (THb), recordings ≥4 min revealed greater clinical utility for oxy- (HbO) and deoxyhemoglobin (HHb) concentration. Females had lower StO2, THb, HbO, and HHb values than males, but variability was approximately equal between sexes. Intraclass correlation coefficients ranged from 0.50-0.96. The minimal detectable change for StO2 was 1.15% (95% CI: 0.336-1.96%) and 3.12 µM for THb (95% CI: 0.915-5.33 µM) for females and 2.75% (95%CI: 0.807-4.70%) for StO2 and 5.51 µM (95%CI: 1.62-9.42 µM) for THb in males. Overall, FD-NIRS demonstrated good levels of between-day reliability. These findings support the application of FD-NIRS in field-based settings and indicate a recording duration of 1 min allows for valid measures; however, data recordings of ≥4 min are recommended when feasible.

Transcranial Doppler Ultrasound and Concussion-Supplemental Symptoms with Physiology: A Systematic Review.

Sport-related concussion (SRC) can impair the cerebrovasculature both acutely and chronically. Transcranial Doppler (TCD) ultrasound assessment has the potential to illuminate the mechanisms of impairment and provide an objective evaluation of SRC. The current systematic review investigated studies employing TCD ultrasound assessment of intracranial arteries across three broad categories of cerebrovascular regulation: neurovascular coupling (NVC), cerebrovascular reactivity (CVR), and dynamic cerebral autoregulation (dCA). The current review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021275627). The search strategy was applied to PubMed, as this database indexes all biomedical journals. Original articles on TCD for athletes with medically diagnosed SRC were included. Title/abstract and full-text screening were completed by three authors. Two authors completed data extraction and risk of bias using the Methodological Index for Non-Randomized Studies and Scottish Intercollegiate Guideline Network checklists. Of the 141 articles identified, 14 met the eligibility criteria. One article used an NVC challenge, eight assessed CVR, and six investigated dCA. Methodologies varied widely among studies, and results were heterogeneous. There was evidence of cerebrovascular impairment in all three domains roughly 2 days post-SRC, but the magnitude and recovery of these impairments were not clear. There was evidence that clinical symptom resolution occurred before cerebrovascular function, indicating that physiological deficits may persist despite clinical recovery and return to play. Collectively, this emphasizes an opportunity for the use of TCD to illuminate the cerebrovascular deficits caused by SRC. It also highlights that there is need for consistent methodological rigor when employing TCD in a SRC population.

Letter to the editor: Deriving transfer function analysis metrics from driven methods.

Driven and spontaneous methods have been used to quantify the cerebral pressure-flow relationship via transfer function analysis (TFA). Commonly, TFA derived estimates are assessed using band averages within the very-low (0.02-0.07 Hz) and low (0.07-0.20 Hz) frequency during spontaneous oscillations but are quantified at frequencies of interest where blood pressure oscillations are driven (e.g., 0.05 and/or 0.10 Hz). Driven estimates more closely resemble the autoregulatory challenges individuals experience on a daily basis, while also eliciting higher levels of reliability. While driven estimates with point-estimates are not feasible for all clinical populations, these approaches increase the ability to understand pathophysiological changes.

Validity and reliability of deriving the autoregulatory plateau through projection pursuit regression from driven methods.

To compare the construct validity and between-day reliability of projection pursuit regression (PPR) from oscillatory lower body negative pressure (OLBNP) and squat-stand maneuvers (SSMs). Nineteen participants completed 5 min of OLBNP and SSMs at driven frequencies of 0.05 and 0.10 Hz across two visits. Autoregulatory plateaus were derived at both point-estimates and across the cardiac cycle. Between-day reliability was assessed with intraclass correlation coefficients (ICCs), Bland-Altman plots with 95% limits of agreement (LOA), coefficient of variation (CoV), and smallest real differences. Construct validity between OLBNP-SSMs were quantified with Bland-Altman plots and Cohen's d. The expected autoregulatory curve with positive rising and negative falling slopes were present in only ~23% of the data. The between-day reliability for the ICCs were poor-to-good with the CoV estimates ranging from ~50% to 70%. The 95% LOA were very wide with an average spread of ~450% for OLBNP and ~350% for SSMs. Plateaus were larger from SSMs compared to OLBNPs (moderate-to-large effect sizes). The cerebral pressure-flow relationship is a complex regulatory process, and the "black-box" nature of this system can make it challenging to quantify. The current data reveals PPR analysis does not always elicit a clear-cut central plateau with distinctive rising/falling slopes.

Adolescent Sport-Related Concussion and the Associated Neurophysiological Changes: A Systematic Review.

BACKGROUND: Sport-related concussion (SRC) has been shown to induce cerebral neurophysiological deficits, quantifiable with electroencephalography (EEG). As the adolescent brain is undergoing rapid neurodevelopment, it is fundamental to understand both the short- and long-term ramifications SRC may have on neuronal functioning. The current systematic review sought to amalgamate the literature regarding both acute/subacute (≤28 days) and chronic (>28 days) effects of SRC in adolescents via EEG and the diagnostic accuracy of this tool. METHODS: The review was registered within the Prospero database (CRD42021275256). Search strategies were created and input into the PubMed database, where three authors completed all screening. Risk of bias assessments were completed using the Scottish Intercollegiate Guideline Network and Methodological Index for Non-Randomized Studies. RESULTS: A total of 128 articles were identified; however, only seven satisfied all inclusion criteria. The studies ranged from 2012 to 2021 and included sample sizes of 21 to 81 participants, albeit only ∼14% of the included athletes were females. The studies displayed low-to-high levels of bias due to the small sample sizes and preliminary nature of most investigations. Although heterogeneous methods, tasks, and analytical techniques were used, 86% of the studies found differences compared with control athletes, in both the symptomatic and asymptomatic phases of SRC. One study used raw EEG data as a diagnostic indicator demonstrating promise; however, more research and standardization are a necessity. CONCLUSIONS: Collectively, the findings highlight the utility of EEG in assessing adolescent SRC; however, future studies should consider important covariates including biological sex, maturation status, and development.

Youth Preseason Performance on the Sport Concussion Assessment Tool 5 Across Multiple Sports.

OBJECTIVE: To examine preseason Sport Concussion Assessment Tool 5 (SCAT5) performance of adolescent sport participants by environment (in-person/virtual), sex, age, concussion history, collision/noncollision sport participation, and self-reported medical diagnoses. DESIGN: Cross-sectional. SETTING: Canadian community and high-school sport settings. PARTICIPANTS: Three thousand eight hundred five adolescent (2493 male, 1275 female, and 37 did not disclose; 11- to 19-year-old) sport participants. ASSESSMENT OF RISK FACTORS: Sport Concussion Assessment Tool 5 administration method (in-person/virtual), sex (male/female/unreported), age (years), concussion history (0/1/2/3+), collision/noncollision sport participant, and self-reported medical diagnoses [attention deficit disorder or attention-deficit/hyperactivity disorder, headache/migraine, learning disability, and psychiatric disorder (ie, anxiety/depression/other)]. OUTCOME MEASURES: Preseason SCAT5 outcomes including total number of symptoms (TNS; /22), symptom severity score (SSS; /132), Standardized Assessment of Concussion (SAC; /50), and modified Balance Error Scoring System (mBESS; /30). RESULTS: Multiple multilevel linear or Poisson regression complete case analyses adjusting for clustering and robust standard errors, with ß-coefficients (95% CI) back-transformed to indicate an increase/decrease in SCAT5 subdomains when relevant for clinical interpretation. Virtual (V) performance was associated with fewer symptoms reported [TNS Difference V-IP = -1.53 (95% CI, -2.22 to -0.85)], lower SSS [-2.49 (95% CI, -4.41 to -0.58)], and fewer mBESS errors (IP) [-0.52 (95% CI, -0.77 to -0.27)] compared with in-person. For every one-year increase in age, more symptoms [TNS = 0.22 (95% CI, 0.01-0.44)], higher SSS [0.52 (95% CI, 0.01-1.06)], higher SAC [0.27 (95% CI, 0.15-0.38), and poorer balance [mBESS = -0.19 (-0.28 to -0.09)] were observed. Differences between males and females were also seen across all SCAT5 outcomes. Individuals reporting any medical diagnosis or 3+ concussion history also reported more symptoms (TNS) and higher SSS than those who did not. CONCLUSIONS: Administration environment, sex, age, concussion history, and medical diagnoses were associated with SCAT5 subdomains and are important considerations when interpreting the SCAT5 results.

Comparison of the Buffalo Concussion Treadmill Test With a Physiologically Informed Cycle Test: Calgary Concussion Cycle Test.

BACKGROUND: Sport-related concussions are a complex injury requiring multifaceted assessment, including physical exertion. Currently, concussion testing relies primarily on a treadmill-based protocol for assessing exertion-related symptoms in persons after concussion. This study compared a modified cycle protocol (Calgary Concussion Cycle Test [CCCT]) with the clinically adopted standard, the Buffalo Concussion Treadmill Test (BCTT), across multiple physiological parameters. HYPOTHESIS: Treadmill and cycle matched workload protocols would produce similar results for cerebral blood velocity, mean arterial pressure (MAP), and end-tidal carbon dioxide partial pressure (PETCO2), but heart rate (HR) and oxygen consumption (VO2) would be higher on the treadmill than the cycle modality. STUDY DESIGN: Crossover study design. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 17 healthy adults (8 men, 9 women; age, 26 ± 3 years; body mass index, 23.8 ± 2.7 kg/m2) completed the BCTT and CCCT protocols, 7 days apart in a randomized order. During both exertional protocols, the physiological parameters measured were middle cerebral artery mean blood velocity (MCAv), MAP, PETCO2, VO2, and HR. Analysis of variance with effect size computations, coefficient of variation, and Bland-Altman plots with 95% limits of agreement were used to compare exercise tests. RESULTS: The BCTT and CCCT produced comparable results for both male and female participants with no significant differences for average MCAv, MAP, and PETCO2 (all P > 0.05; all generalized eta squared [η2G] < 0.02 [negligible]; P value range, 0.29-0.99) between stages. When accounting for exercise stage and modality, VO2 (P < 0.01) and HR (P < 0.01) were higher on the treadmill compared with the cycle. Aside from the final few stages, all physiology measures displayed good-to-excellent agreeability/variability. CONCLUSION: The CCCT was physiologically similar to the BCTT in terms of MCAv, PETCO2, and MAP; however, HR and VO2 differed between modalities. CLINICAL RELEVANCE: Providing a cycle-based modality to exertional testing after injury mayincrease accessibility to determine symptom thresholds in the future.

Influence of sex on the reliability of cerebral blood velocity regulation during lower body negative pressure and supine cycling with considerations of the menstrual cycle.

Objective.To evaluate sex differences in the reliability of absolute and relative cerebral blood velocity (CBv) during concurrent supine cycling with lower body negative pressure (LBNP).Approach. A total of 19 participants (11 females; aged 20-33 years) completed five testing sessions, occurring on 7 d intervals. Visit 1 was a maximal-ramp-cycle test to ascertain peak CBv wattage. During visits 2-5, supine cycling protocol occurred at individualized peak CBv wattages with progressive decreases in LBNP from 0 to -20, -40, -60, -70, and -80 Torr. Menstrual cycle day was self-reported via the Rhinessa Women's Questionnaire. Transcranial Doppler ultrasound insonated bilateral middle cerebral artery velocity (MCAv). Two-way ANOVA assessed potential day- and sex-differences at each LBNP stage. Reliability was determined using intraclass correlation coefficients (ICC) and coefficient of variation (CoV).Main results. For all physiological measures, no main-effects were present for day- or interaction-terms (p> 0.067; negligible-to-small effect sizes), while sex differences were noted for MCAv, blood pressure, and heart rate (p< 0.046). Across visits, males and females displayed excellent and good-to-excellent levels of reliability for MCAv metrics, respectively (ICC range: 0.745-0.999; CoV range: 0.33%-9.90%).Significance. During the current investigation, both relative and absolute CBv demonstrated high reliability in both male and female participants during a supine LBNP cycling protocol. An exploratory analysis revealed increased variance was found in female participants dependent on contraceptive use. Despite this, results indicate future LBNP studies may include females at any menstrual cycle stage.

Quantification of dynamic cerebral autoregulation: welcome to the jungle!

PURPOSE: Patients with dysautonomia often experience symptoms such as dizziness, syncope, blurred vision and brain fog. Dynamic cerebral autoregulation, or the ability of the cerebrovasculature to react to transient changes in arterial blood pressure, could be associated with these symptoms. METHODS: In this narrative review, we go beyond the classical view of cerebral autoregulation to discuss dynamic cerebral autoregulation, focusing on recent advances pitfalls and future directions. RESULTS: Following some historical background, this narrative review provides a brief overview of the concept of cerebral autoregulation, with a focus on the quantification of dynamic cerebral autoregulation. We then discuss the main protocols and analytical approaches to assess dynamic cerebral autoregulation, including recent advances and important issues which need to be tackled. CONCLUSION: The researcher or clinician new to this field needs an adequate comprehension of the toolbox they have to adequately assess, and interpret, the complex relationship between arterial blood pressure and cerebral blood flow in healthy individuals and clinical populations, including patients with autonomic disorders.

Cerebral blood velocity during concurrent supine cycling, lower body negative pressure, and head-up tilt challenges: implications for concussion rehabilitation.

Introduction. The effect of concurrent head-up tilt and lower body negative pressure (LBNP) have been examined on middle cerebral artery velocity (MCAv) at rest; however, it is unknown the superimposed effect these factors have on blunting the elevation in cerebral blood velocity associated with moderate-intensity exercise.Methods. 23 healthy adults (11 females / 12 males, 20-33 years) completed three visits. The first consisted of a maximal ramp supine cycling test to identify the wattage associated with individualized maximal MCAv. Subsequent visits included randomized no LBNP (control) or LBNP at -40 Torr (experimental) with successively increasing head-up tilt stages of 0, 15, 30, and 45 degrees during the pre-described individualized wattage. Transcranial Doppler ultrasound was utilized to quantify MCAv. Two-factorial repeated measures analysis of variance with effect sizes were used to determine differences between days and tilt stages.Results. Between-day baseline values for MCAv, heart rate, and blood pressure displayed low variability with <5% variation. With no LBNP, MCAv was above baseline on average for all participants; however, 15 degrees and 30 degrees tilt with concurrent -40 Torr LBNP was sufficient to return MCAv to 100% of baseline values in females and males, respectively. Body-weight did not impact the association between tilt and pressure (R2range: 0.01-0.12).Conclusion. Combined LBNP and tilt were sufficient to reduce the increase in MCAv associated with moderate-intensity exercise. This exercise modality shows utility to enable individuals with a concussion to obtain the positive physiological adaptions associated with exercise while minimizing symptom exacerbation due to the notion of the Monro-Kellie doctrine.

The temporal neurovascular coupling response remains intact during sinusoidal hypotensive and hypertensive challenges.

Introduction. Neurovascular coupling (NVC) describes the coupling of neuronal metabolic demand to blood supply, which has shown to be impaired with chronic hypertension, as well as with prolonged hypotension. However, it is unknown the extent the NVC response remains intact during transient hypo- and hyper-tensive challenges.Methods. Fifteen healthy participants (9 females/6 males) completed a visual NVC task ('Where's Waldo?') over two testing sessions, consisting of cyclical 30 s eyes closed and opened portions. The Waldo task was completed at rest (8 min) and concurrently during squat-stand maneuvers (SSMs; 5 min) at 0.05 Hz (10 s squat/stand) and 0.10 Hz (5 s squat-stand). SSMs induce 30-50 mmHg blood pressure oscillations, resulting in cyclical hypo- and hyper-tensive swings within the cerebrovasculature, allowing for the quantification of the NVC response during transient hypo- and hyper-tension. Outcome NVC metrics included baseline, peak, relative increase in cerebral blood velocity (CBv), and area-under-the-curve (AUC30) within the posterior and middle cerebral arteries indexed via transcranial Doppler ultrasound. Within-subject, between-task comparisons were conducted using analysis of variance with effect size calculations.Results. Differences were noted between rest and SSM conditions in both vessels for peak CBv (allp< 0.045) and the relative increase in CBv (allp <0.049) with small-to-large effect sizes. AUC30 metrics were similar between all tasks (allp> 0.090) with negligible-to-small effect sizes.Conclusions. Despite the SSMs eliciting ∼30-50 mmHg blood pressure oscillations, similar levels of activation occurred within the neurovascular unit across all conditions. This demonstrated the signaling of the NVC response remained intact during cyclical blood pressure challenges.

Clinical recovery from concussion-return to school and sport: a systematic review and meta-analysis.

OBJECTIVE: To define the time frames, measures used and modifying factors influencing recovery, return to school/learn (RTL) and return to sport (RTS) after sport-related concussion (SRC). DESIGN: Systematic review and meta-analysis. DATA SOURCES: 8 databases searched through 22 March 2022. ELIGIBILITY CRITERIA: Studies with diagnosed/suspected SRC and interventions facilitating RTL/RTS or investigating the time and modifying factors for clinical recovery. Outcomes included days until symptom free, days until RTL and days until RTS. We documented study design, population, methodology and results. Risk of bias was evaluated using a modified Scottish Intercollegiate Guidelines Network tool. RESULTS: 278 studies were included (80.6% cohort studies and 92.8% from North America). 7.9% were considered high-quality studies, while 23.0% were considered high risk of bias and inadmissible. The mean days until symptom free was 14.0 days (95% CI: 12.7, 15.4; I2=98.0%). The mean days until RTL was 8.3 (95% CI: 5.6, 11.1; I2=99.3%), with 93% of athletes having a full RTL by 10 days without new academic support. The mean days until RTS was 19.8 days (95% CI: 18.8, 20.7; I2=99.3%), with high heterogeneity between studies. Several measures define and track recovery, with initial symptom burden remaining the strongest predictor of longer days until RTS. Continuing to play and delayed access to healthcare providers were associated with longer recovery. Premorbid and postmorbid factors (eg, depression/anxiety, migraine history) may modify recovery time frames. Though point estimates suggest that female sex or younger age cohorts take longer to recover, the heterogeneity of study designs, outcomes and overlap in CIs with male sex or older age cohorts suggests that all have similar recovery patterns. CONCLUSION: Most athletes have full RTL by 10 days but take twice as long for an RTS. PROSPERO REGISTRATION NUMBER: CRD42020159928.

Rest and exercise early after sport-related concussion: a systematic review and meta-analysis.

OBJECTIVE: To synthesise the evidence regarding the risks and benefits of physical activity (PA), prescribed aerobic exercise treatment, rest, cognitive activity and sleep during the first 14 days after sport-related concussion (SRC). DESIGN: Meta-analysis was performed for PA/prescribed exercise interventions and a narrative synthesis for rest, cognitive activity and sleep. Risk of bias (ROB) was determined using the Scottish Intercollegiate Guidelines Network and quality assessed using Grading of Recommendations, Assessment, Development and Evaluations. DATA SOURCES: MEDLINE, Embase, APA PsycInfo, Cochrane Central Register of Controlled Trials, CINAHL Plus and SPORTDiscus. Searches were conducted in October 2019 and updated in March 2022. ELIGIBILITY CRITERIA: Original research articles with sport-related mechanism of injury in >50% of study sample and that evaluated how PA, prescribed exercise, rest, cognitive activity and/or sleep impact recovery following SRC. Reviews, conference proceedings, commentaries, editorials, case series, animal studies and articles published before 1 January 2001 were excluded. RESULTS: 46 studies were included and 34 had acceptable/low ROB. Prescribed exercise was assessed in 21 studies, PA in 15 studies (6 PA/exercise studies also assessed cognitive activity), 2 assessed cognitive activity only and 9 assessed sleep. In a meta-analysis of seven studies, PA and prescribed exercise improved recovery by a mean of -4.64 days (95% CI -6.69, -2.59). After SRC, early return to light PA (initial 2 days), prescribed aerobic exercise treatment (days 2-14) and reduced screen use (initial 2 days) safely facilitate recovery. Early prescribed aerobic exercise also reduces delayed recovery, and sleep disturbance is associated with slower recovery. CONCLUSION: Early PA, prescribed aerobic exercise and reduced screen time are beneficial following SRC. Strict physical rest until symptom resolution is not effective, and sleep disturbance impairs recovery after SRC. PROSPERO REGISTRATION NUMBER: CRD42020158928.