Kelsey Bryk

Where's Waldo? The utility of a complicated visual search paradigm for transcranial Doppler-based assessments of neurovascular coupling.

BACKGROUND The concept of neurovascular coupling has been postulated since the late 1800s and has been demonstrated most commonly in humans using visual stimuli (e.g. reading, checkerboards). These traditional paradigms evoke only a moderate cerebral blood flow response due to the relative simplicity of the visual stimuli. NEW METHOD Forty subjects completed three visual paradigms each challenging the visual processing areas to a different extent: reading text, complicated visual searching (new method: Wheres Waldo) and viewing coloured dots. Posterior and middle cerebral artery (PCA, MCA) velocities were recorded using transcranial Doppler ultrasound during each visual paradigm. RESULTS Prior to the presentation of the visual stimuli there were no differences in mean arterial pressure, or PCA or MCA velocities for the three paradigms. All three paradigms led to an elevation in PCA and MCA velocities after a delay (∼1.1s). Whereas velocity elevation was consistent across the three paradigms in the MCA, it was markedly larger during the Wheres Waldo task in the PCA. Thus, although the onset of the neurovascular coupling response was similar across the three visual paradigms, its overall magnitude was stimulus-dependent. COMPARISON WITH EXISTING METHODS Given that PCA velocity can be affected by blood pressure or carbon dioxide alterations, traditional neurovascular coupling paradigms (e.g. reading, checkerboards) appear to have a lower signal-to-noise ratio than that observed in complicated visual search tasks such as Wheres Waldo. CONCLUSIONS We recommend complicated visual search paradigms such as Wheres Waldo be considered for future transcranial Doppler-based neurovascular coupling studies.

Sport-Related Concussion Alters Indices of Dynamic Cerebral Autoregulation

Sport-related concussion is known to affect a variety of brain functions. However, the impact of this brain injury on cerebral autoregulation (CA) is poorly understood. Thus, the goal of the current study was to determine the acute and cumulative effects of sport-related concussion on indices of dynamic CA. Toward this end, 179 elite, junior-level (age 19.6 ± 1.5 years) contact sport (ice hockey, American football) athletes were recruited for preseason testing, 42 with zero prior concussions and 31 with three or more previous concussions. Eighteen athletes sustained a concussion during that competitive season and completed follow-up testing at 72 h, 2 weeks, and 1 month post injury. Beat-by-beat arterial blood pressure (BP) and middle cerebral artery blood velocity (MCAv) were recorded using finger photoplethysmography and transcranial Doppler ultrasound, respectively. Five minutes of repetitive squat–stand maneuvers induced BP oscillations at 0.05 and 0.10 Hz (20- and 10-s cycles, respectively). The BP–MCAv relationship was quantified using transfer function analysis to estimate Coherence (correlation), Gain (amplitude ratio), and Phase (timing offset). At a group level, repeated-measures ANOVA indicated that 0.10 Hz Phase was significantly reduced following an acute concussion, compared to preseason, by 23% (−0.136 ± 0.033 rads) at 72 h and by 18% (−0.105 ± 0.029 rads) at 2 weeks post injury, indicating impaired autoregulatory functioning; recovery to preseason values occurred by 1 month. Athletes were cleared to return to competition after a median of 14 days (range 7–35), implying that physiologic dysfunction persisted beyond clinical recovery in many cases. When comparing dynamic pressure buffering between athletes with zero prior concussions and those with three or more, no differences were observed. Sustaining an acute sport-related concussion induces transient impairments in the capabilities of the cerebrovascular pressure-buffering system that may persist beyond 2 weeks and may be due to a period of autonomic dysregulation. Athletes with a history of three or more concussions did not exhibit impairments relative to those with zero prior concussions, suggesting recovery of function over time. Findings from this study support the potential need to consider physiological recovery in deciding when patients should return to play following a concussion.

Acute sport-related concussion induces transient impairment in dynamic cerebral auto regulation that is related to scat3 performance

Objective Examine how the frequency-dependent relationship between blood pressure (BP) and cerebral blood velocity (CBV) is affected by acute sport-related concussion. Design Prospective Cohort. Setting Laboratory. Participants: 136 male contact-sport athletes (19.1±1.4 years) recruited, subset of 14 sustained concussions (19±1.4 years). Intervention Participants completed baseline (T0) and post-injury testing at 72-hours (T1), 2-weeks (T2), and 1-month (T3). BP was monitored via finger photoplethysmography, and transcranial Doppler ultrasound indexed CBV in the middle cerebral artery. Squat-stand manoeuvers were performed at 0.05 and 0.10Hz to enhance BP variation. RM-ANOVA independent variables included time (4) and frequency (2). Outcome measures Transfer function analysis point estimates quantified coherence (correlation), phase (synchronisation) and gain (amplitude buffer) metrics between BP and CBV waveforms. Results Significant frequency-time interactions for phase (p=0.007) and gain (p=0.049). Simple effects analysis revealed time effects for phase at 0.10 Hz, indicating reductions at T1 (95% CI: 0.033 – 0.24 rads, p=0.008) and T2 (95% CI: 0.014–0.196 rads, p=0.02) compared to T0. On average, return-to-play occurred at T2 (median 14 days). Phase reductions at T1 were correlated with Standardised Assessment of Concussion performance (r=0.659, p=0.02). Conclusions These results reveal transient post-concussion impairments in the capacity of the cerebrovasculature to buffer BP oscillations, which exceeded clinical recovery duration. Phase reductions at 0.10Hz suggest the presence of a cerebrovascular autonomic dysregulation, which could leave the brain less protected to BP surges. This key finding may help explain why the brain is more vulnerable to additional trauma during the post-injury recovery period. Competing interests None.

Systolic and Diastolic Regulation of the Cerebral Pressure-Flow Relationship Differentially Affected by Acute Sport-Related Concussion

OBJECTIVE To determine whether acute sports-related concussion (SRC) exerts differential effects on cerebral autoregulatory properties during systole versus diastole. MATERIALS AND METHODS One hundred and thirty-six contact-sport athletes tested preseason; 14 sustained a concussion and completed follow-up testing at 72 hours, 2 weeks, and 1 month post-injury. Five minutes of repetitive squat-stand maneuvers induced blood pressure (BP) oscillations at both 0.05 and 0.10 Hz. Beat-by-beat peak-systolic and end-diastolic BP (sysBP/ diasBP) and middle cerebral artery blood velocity (sysMCAv/diasMCAv) were recorded using finger photoplethysmography and transcranial Doppler ultrasound, respectively. Relationships between sysBP-sysMCAv and diasBP-diasMCAv were quantified using transfer function analysis to estimate coherence (correlation), gain (response magnitude), and phase (response latency). RESULTS Significant main effects of the cardiac cycle were observed across all outcome metrics. A significant main effect of SRC was observed for 0.10 Hz phase: systolic and diastolic phases were reduced at 72 h (21.8 ± 5.2%) and 2 weeks (22.7 ± 7.1%) compared to preseason but recovered by 1 month. Concussion significantly impaired diastolic, but not systolic, gain: 0.10 Hz diastolic gain was increased (27.2 ± 7.7%) at 2 weeks, recovering by 1 month. CONCLUSIONS Impairments in autoregulatory capacity, observed for a transient period following SRC that persist beyond symptom resolution and clinical recovery, appear to be differentially affected across the cardiac cycle. Similar patterns of impairment were observed for systolic and diastolic phases (response latency); however, normalized gain (response magnitude) impairments were identified only in diastole. These findings may explain the increased cerebral vulnerability as well as exercise-induced symptom exacerbation observed post-SRC.

Cerebral Autoregulation Is Disrupted Following a Season of Contact Sports Participation

Repetitive subconcussive head impacts across a season of contact sports participation are associated with a number of deficits in brain function. To date, no research has investigated the effect of such head impact exposure on dynamic cerebral autoregulation (dCA). To address this issue, 179 elite, junior-level (age 19.6 ± 1.5 years) contact sport (ice hockey, American football) athletes were recruited for pre-season testing. Fifty-two non-concussed athletes returned for post-season testing. Fifteen non-contact sport athletes (age 20.4 ± 2.2) also completed pre- and postseason testing. dCA was assessed via recordings of beat-by-beat mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) using finger photoplethysmography and transcranial Doppler ultrasound, respectively, during repetitive squat-stand maneuvers at 0.05 and 0.10 Hz. Transfer function analysis was used to determine Coherence (correlation), Gain (response amplitude), and Phase (response latency) of the MAP-MCAv relationship. Results showed that in contact sport athletes, Phase was reduced (p = 0.027) and Gain increased (p < 0.001) at post-season compared to pre-season during the 0.10 Hz squat-stand maneuvers, indicating cerebral autoregulatory impairment in both the latency and magnitude of the response. Changes in Phase were greater in athletes experiencing higher numbers and severity of head impacts. By contrast, no changes in dCA were observed in non-contact sport controls. Taken together, these results demonstrate that repetitive subconcussive head impacts occurring across a season of contact sports participation are associated with exposure-dependent impairments in the cerebrovascular pressure-buffering system capacity. It is unknown how long these deficits persist or if they accumulate year-over-year.

Exposure to rotational acceleration over the course of one athletic season is related to impairments in an index of dynamic cerebral autoregulation

Objective To examine the relationship between cerebral autoregulation changes and impact exposuresthroughout a season of contact sports (hockey or football). Design Prospective Cohort. Setting Laboratory. Participants 40 male contact sport athletes (19.4±1.2 years); to date, 3 cross-country athletes (20.0±1.0 years) have completed testing (non-contact controls). Intervention Participants completed testing prior to the start of their athletic seasons (T1), and again after the conclusion of each season (T2). Blood pressure (BP) oscillations were driven by stand-squat manoeuvres at 0.05 and 0.10 Hz. BP and cerebral blood velocity (CBV) in the middle cerebral artery were indexed non-invasively using finger photoplethysmography and transcranial Doppler ultrasound, respectively. RM-ANOVA independent variables included time (2) and frequency (2). Outcome measures Point-estimates of coherence (correlation), phase (synchronisation), and gain (amplitude buffer) transfer function analysis metrics were calculated. Biomechanical data on head-impact exposure was estimated in a subset of contact-sport athletes (n=29) using the xPatch (X2 Biosystems), affixed to the right mastoid. Results Significant frequency-time interaction for gain in contact-sport athletes (p=0.048) but not controls (p=0.213). Simple effects analysis revealed a time effect at 0.10 Hz (p<0.001), whereby gain increased at T2 (95% CI: 0.070–0.229%/%). The Δgain T2-T1 at 0.10 Hz was correlated withestimated cumulativerotational acceleration exposure (r=0.462, p=0.015). Conclusions These findings suggest cumulative exposure to the rotational component of sustained head-impactsduring participation in a season of contact-sport (hockey or football) impairs the ability of the cerebrovasculature to buffer BP challenges experienced during everyday activities. Competing interests None.

A history of multiple concussions does not confer long-term impairments to dynamic cerebral autoregulation

Objective To examine the effects of concussion history on an index of cerebral autoregulation in a healthy athlete population. Design Retrospective Cohort. Setting Laboratory. Participants 136 male contact sport athletes (19.1±1.4 years, 66 football, 70 hockey) were recruited; 39 presented with 0 previous concussions, 16 with 3+ previous concussions; exclusion criteria included history of concussion within 6 months. Intervention Participants completed baseline testing prior to the athletic season. Squat-stand manoeuvres at 0.05 and 0.10 Hz were used to enhance blood pressure (BP) variation. BP and cerebral blood velocity (CBV) in the middle cerebral artery were indexed non-invasively via finger photoplethysmography and transcranial Doppler ultrasound, respectively. Independent variables included sport (2) and concussion history (2). Outcomes Transfer function analysis point estimates at 0.05 and 0.10 Hz characterised the coherence (correlation), phase (synchronisation), and gain (amplitude buffer) between BP and CBV waveforms during the squat-stand manoeuvres. Results These findings suggest that, despite reductions in 0.10 Hz phase lead being reported acutely after concussion, multiple concussions do not appear to induce long-term impairments in dynamic cerebral autoregulation metrics. This is an important revelation as it indicates that the cerebrovasculature is able to adequately recover following the acutely diminished buffering capacity associated with a concussive injury Conclusions These findings suggest that, despite reductions in 0.10 Hz phase lead being reported acutely after concussion, multiple concussions do not appear to induce long-term impairments in dynamic cerebral autoregulation metrics. This is an important revelation as it indicates that the cerebrovasculature is able to adequately recover following the acutely diminished buffering capacity associated with a concussive injury Competing interests None.

Heart rate variability reductions following a season of sub-concussive head hits are related to the magnitude of impacts experienced

Objective To examine the effect of repetitive contact sport-related head trauma on indices ofheart rate variability (HRV). Design Prospective Cohort. Setting Laboratory. Participants Forty-ninemale contact-sport (hockey or football) and four non-contact control athletes (age range: 17–22). Intervention Prior to (T1) and upon completion of (T2) the competitive athletic season, a three-lead electrocardiogram and Kubios software (Kuopio, Finland) were used to assess heart rate variability during 5-minutes of quiet stance and while actively squatting at 0.10 Hz. Independent variables included condition (rest-vs-active) and time (T1-vs-T2). Outcome measures Time-Domain: square root of mean squared differences of successive R-R intervals (RMSSD), percentage of successive R-R intervals that differ by more than 50 milliseconds (pNN50); Non-Linear: approximateentropy (ApEn). In a subset of participants (n=29) biomechanical head-impact exposure data was estimated usingthe xPatch (X2 Biosystems), affixed to the right mastoid. Main results RM-ANOVA indicateda significant main effect of timein contact sport but not control athletes (all p>0.133). HRV metrics were decreased post-season relative to baseline (95% CI:s for differences: MeanRR4–48 ms, p=0.045; RMSSD 1–9 ms, p=0.018; pNN50 0.689–5.98, p=0.010; ApEn 0.022–0.163, p=0.044). Significant correlations were observed between the average peak linear acceleration per hit experienced and the change in MeanRR(R²=0.1382), and RMSSD (R²=0.1525). Conclusions Exposure to repetitive subconcussive impacts overone season of contact-sport leads to decreases in heart rate variability. The magnitude of HRV reduction is related to the average magnitude of the linear component of hits to the head experienced during play Competing interests None.

History of multiple sport-related concussions alters variability of heart rate response to activity

Objective To examine the effect of multiple previous concussions on heart rate variability (HRV) in contact-sport athletes. Design Retrospective Cohort. Setting Laboratory. Participants 136 male elite contact-sport (hockey and football) athletes were recruited for this study. Forty-one had no previous concussion history (Hx-), while nineteen had a history of three or more concussions (Hx+). All testing was preformed prior to the start of the competitive season Interventions HRV was assessed during 5-minutes of quiet stance, and while actively squatting at 0.10 Hz via a 3-lead electrocardiogram, using Kubios software. Independent variables included condition (rest vs active) and group (Hx+ vs Hx-) Outcome measures Time-Domain: square root of mean squared differences of successive R-R intervals (RMSSD), percentage of successive R-R intervals that differ by more than 50 milliseconds (pNN50). Frequency-Domain: total power. Main results Mixed ANOVA revealed repeated squat-stand manoeuvres challenged the autonomic system, increasing total power by 2477 milliseconds2 (95% CI: 1153–3801, p<0.001). A significant interaction effect was observed for RMSSD (p=0.031) and pNN50 (p=0.012), characterised by a greater increase in HRV in the Hx+ group than in Hx- from rest to squatting (95%CIs for group differences, RMSSD: 13.2–26.3 ms, p=0.006; pNN50: 3.6–15.1%, p=0.002) Conclusions A history of multiple sport-related concussions impairs the ability of the autonomic system to respond to an everyday stressor applied to the cardiovascular system (squatting and standing). This is an important finding, as it reveals that cumulative concussions may impart long-term impairments in the ability to accurately regulate the autonomic system. Competing interests None.

Effect of sub-concussive impacts sustained throughout a contact-sport season on quiet stance centre of pressure

Objective To examine how sub-concussive head trauma throughout a contact-sport season affects quiet stance centre of pressure (COP) sway Design Prospective cohort Setting Laboratory Participants: Twenty-four elite male football players (age range 18–22) were recruited for the study Intervention Quiet stance data was collected at the start and at the end of the competitive season. One-minute trials were performed with eyes-open and eyes-closed on a force plate (NDI True Impulse) with feet hip-width apart and hands-on-hips. Biomechanical head-impact exposure was indexed using the xPatch (X2 Biosystems) Outcome measures COP measures: Anterior/posterior (AP) and medial/lateral (ML) root-mean-square displacement (RMSd) and mean velocity. Biomechanical head-impact data: For hits above 20g, peak linear acceleration (PLA), and peak rotational acceleration (PRAwere estimated across the competitive season. Independent variables included time (2) and condition (2) Results RM-ANOVA reveal an effect of condition (eyes-open vs eyes-closed) in AP-RMSd (p=0.035, 95% CI: 0.006, 0.159), ML-RMSd (p<0.0001, CI: 0.083, 0.250), and ML mean velocity (p<0.0001, 95% CI: 0.111, 0.308). However, despite exposure to a cumulative 8147.2±6215.5 g in linear acceleration and 34.5 x 106 ± 59.0x106 rad/s2 in rotational acceleration, there were no significant differences between conditions for COP measures at post-season Conclusions In contrast to the prolonged COP alterations observed following acute concussions, there were no discernable effects of sub-concussive trauma on COP sway during quiet stance in the same population. This is an important finding as it reveals that participation in contract-sport does not impair quiet stance balance Competing interests None.