BACKGROUND
Concussion sets into motion a complex cascade of metabolic and neurochemical events in the brain that can last for weeks to months.1,2 Over the past decade, novel imaging approaches have been applied to evaluate the state of the brain during recovery after concussion.3 Results from functional imaging (eg, electroencephalography [EEG] and functional magnetic resonance imaging [fMRI]), structural imaging (eg, diffusion tensor imaging [DTI]), and noninvasive brain stimulation assessments (eg, transcranial magnetic stimulation [TMS]) provide a complex picture of the diffuse and multifocal changes in the brain following concussion and during recovery.
Youth (individuals aged 14-25 years) are disproportionally affected by concussion,4,5 and once injured, take longer to recover compared with adults.6 Symptoms of concussion, including physical symptoms and cognitive deficits,7 persist in a clinically significant proportion of individuals (ie, ∼20%) years after even one concussion.8,9 Importantly, persistent cognitive deficits affect learning, and academic and vocational success.10 Adolescence is a unique period of development with distinct immaturities in white matter11,12 that may increase vulnerability to brain injury and disrupt normal brain development. For example, youth have increased unmyelinated axonal tracts, which are more vulnerable to injury.13,14
Given the unique developmental changes in both brain and behavior in youth, age-specific guidelines for concussion management, in particular return to activity, are warranted. The current guidelines for return to activity after concussion include a brief period of physical and cognitive rest (eg, a few days), with a gradual progression to activity when symptom-free.7 However, the guidelines are quite general and do not provide recommendations on the type or amount of physical activity at different stages of recovery.
The overall objective of this article is to provide a topical review of recent neuroimaging results to inform physical activity participation guidelines for the management of concussed youth. Our specific aims are (1) to review findings of concussion-related brain changes (indexed through neuroimaging data including functional and structural brain imaging, and brain stimulation), (2) to review recent research evidence on the effects, generally of exercise and physical activity, in promoting positive brain changes (eg, in healthy individuals as well as other common neurological disorders), and (3) to discuss the potential benefit of exercise and physical activity in promoting recovery after concussion. Studies that fulfilled the aims of this topical review were identified through reference lists and citations of key literature2,15–22 and systematic reviews in this topic area.3,23–26
REVIEW OF BRAIN PHYSIOLOGY EVIDENCE
Neuroimaging results combined with symptomatology and neurobehavioral function provide fundamental understanding of the mechanisms involved in brain injury and recovery.27 These “brain biomarkers” of injury provide key information at a group level regarding the range of pathophysiological changes that may occur as a result of impact. While this information cannot directly be linked to an individual's diagnosis or recovery, collectively, these studies help characterize the complex and dynamic changes in brain structure and function at the time of injury and the pattern(s) of brain recovery that may be expected over time. By constructing a general neurobiological framework of these complex changes, our aim is to provide the first step for translating research findings into clinical practice.
FUNCTIONAL BRAIN IMAGING
In this section, we briefly review neuroimaging studies on concussion and recovery. Appendix 1 (see Supplemental Digital Content 2, available at: https://links.lww.com/JNPT/A206) provides a more detailed description of the imaging methods described in this review.
Functional Magnetic Resonance Imaging
fMRI is an indirect measure of neuronal activity. Changes in the concentration of oxygen-rich and oxygen-low hemoglobin in the blood reflect different metabolic demands of the neurons during brain activity. Two main methodologies are used in fMRI studies in the context of concussion: task-based or resting-state.15,28
Task-Based fMRI
Results from task-based fMRI studies in youth with concussion are quite variable due to the use of different methodologies and inconsistent time frames postinjury and recovery. Nevertheless, there are a few consistent patterns that emerge from these studies. During the acute (<1 week) and sub-acute phases (1 week to 6 months), 2 distinct patterns are observed. The first is a general pattern of higher brain activation (ie, hyperactivation) in specific brain regions compared with healthy controls.28–32 Hyperactivation, particularly in prefrontal and frontal-parietal regions, may reflect engagement of additional cognitive and attention resources required to accomplish the task in a compromised neural system or may be due to brain reorganization following injury.33 Alternatively, task-related hypoactivation (ie, reduced activation in brain regions involved in the cognitive task) has also been observed following concussion.17,34–36 The underlying neurophysiological basis of hypoactivation is less understood but may be related to several processes including difficulty in allocating appropriate cognitive and attention-related resources to the task or impaired neural functioning.36
Resting-State fMRI
Studies investigating default mode network (DMN) function in concussed youth also show mixed results with dynamic changes over the course of recovery.37 In the acute and subacute phases after concussion, specific regions within the DMN show increased connectivity (ie, increased coordination of activation within the network), while others show decreased connectivity.15,38–42 In later stages of recovery, specific regions within the DMN show decreased connectivity.31,43 The increases and decreases in activation within DMN may indicate a distributed activation, rather than the expected “normal” focused pattern of activation.
Figure 1 shows the DMN in healthy youth compared with youth with a clinical diagnosis of subacute (<2 months) concussion. Qualitatively, the concussed group shows a more dispersed pattern compared with healthy controls. Statistically, the concussed group showed significant increases in connectivity in the posterior cingulate cortex and significant decreases in connectivity in the frontal and parietal cortices.15
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Figure 1.: The default mode network in a group of healthy youth (n = 12) compared with youth with a clinical diagnosis of subacute (<2 months) concussion (n = 12). Qualitatively, the concussed group shows a more dispersed pattern compared with the healthy control group. Increased connectivity is shown in the posterior cingulate cortex and decreased connectivity in the frontal and parietal cortices.
The previous results highlight that changes in functional networks are not static or homogenous even within specific networks; they are continually changing even months after the initial concussion and often after the resolution of physical symptoms.16,20,44,45 Many questions still remain about the underlying nature of these changes and how these relate to behavior.
Electroencephalogram
EEG reflects the electrical activity of the brain and has been used to index the resting-state neural activity after concussion.46,47 After moderate to severe traumatic brain injury (TBI) in the chronic stage (eg, over 1-year postinjury), individuals show increased functional connectivity within the frontal lobe, which may compensate for lost structural connectivity.48 Alternately, this may reflect increased effort in recruiting the appropriate neural networks.49 It is not clear whether disruption in the overall organization in the frontal regions reflects an ongoing dynamic process related to the response to initial injury or to recovery mechanisms.
Following concussion in youth, increased connectivity indexed through EEG has been shown in a region of the frontal cortex (ie, right dorsolateral prefrontal cortex, DLPFC) known to be involved in high-level cognitive processes, suggesting that this region becomes a key hub region after concussion, with increased connectivity with neighboring regions.47 Changes in attentional network connectivity, such as the DLPFC, may relate to postconcussive symptoms such as increased cognitive fatigue, headache, and increased distractibility.47
STRUCTURAL BRAIN IMAGING
It is now well-known that the structure of the brain changes in response to aging,50 injury,51 and learning.52 The brain's structure can be indexed through a variety of MRI approaches. This review focuses on DTI, as other standard clinical methods of MRI analysis (eg, volumetric T1 MRI) do not show differences after concussion.7
Diffusion Tensor Imaging
There are many measures derived from DTI, with the most commonly reported in youth concussion being fractional anisotropy (FA). FA reflects the integrity of the white matter tracts. After concussion in youth, FA values increase acutely (<2 weeks) in regional white matter tracts53–55 and across the whole brain21,56 compared with healthy controls. Regional and whole-brain FA values continue to be high 1 month postconcussion21 and can remain elevated for 6 months.53 These changes likely reflect subtle tissue damage associated with concussion.
In contrast, studies in adult populations show decreased regional and whole-brain FA values at the acute and postacute phases.3 Notably, there are far fewer studies using DTI with a youth population compared with the adult population.24Figure 2 shows the differences in whole-brain FA for 1 healthy adolescent (left) and 1 adolescent after concussion (right). Darker colors reflect higher FA values while lighter colors show lower FA values. In summary, these increases in white matter tract FA are present after injury and months after injury in adolescents with concussion, compared with adolescents with no concussion.
Figure 2.: Whole brain diffusion tensor imaging tractography for 1 healthy adolescent (left) and 1 adolescent after concussion (right). Darker colors reflect higher FA values, whereas lighter colors reflect lower FA values. Note that diffuse increases in white matter tract FA are present after injury compared with an uninjured brain likely reflecting subtle tissue damage associated with concussion. FA, fractional anisotropy.
BRAIN STIMULATION
Transcranial Magnetic Stimulation
The subtle damage from concussive brain injuries can be investigated through brain stimulation techniques such as TMS.57 There are a growing number of studies using TMS to study youth with concussion in the short- and long-term periods after injury.19 In one study, youth with symptomatic concussion within a week postinjury demonstrate lower threshold of stimulation indicating increased cortical excitability.58 Other work showed longer silent period duration during active motor thresholds,59 suggesting an increase in γ-aminobutyric acid type B (GABA-B)-mediated inhibition. Although this initially may seem counterintuitive, these measures provide information on unique interneuronal pools that may be differentially impacted by concussion.
In the chronic phases of injury (ie, 1-5 years postinjury), youth with a history of multiple concussions show more motor cortical inhibition as indexed by lengthened silent period compared with youth with only one concussion and youth with no concussion history.60 Other work demonstrated that youth with a history of a single concussion showed longer silent period and increased GABA-B-mediated inhibition compared with youth with no concussion history.61,62
Children (ie, younger than 17 year), with symptomatic concussion 1 month postinjury, show reductions in inhibition associated with GABA-B receptor-mediated interneurons, compared with healthy controls and participants with asymptomatic concussion.63 However, there was no difference in other measures investigated (eg, threshold of stimulation to evoke a muscle response, length of silent period in muscle activity while sustaining a contraction) among symptomatic, asymptomatic, and healthy control groups.63 This suggests that children may have a different response to injury and recovery from concussion.
Taken together, this body of work shows that after concussion youth show disrupted GABA-B receptor-mediated intercortical circuitry; greater inhibition is noted in older youth after concussion (ie, average age >20 years), and reduced inhibition in the younger youth after concussion (ie, average age 14 years). Importantly, in all long-term studies reported previously, individuals with concussion were asymptomatic, suggesting that there are residual effects on neurophysiology that far outlast physical or cognitive symptoms. In this way, TMS may be useful in documenting not only the lasting impact of injury-induced brain changes but also an index of rehabilitation effectiveness. There is also potential to combine TMS with EEG, as has been done in other neurologically impaired clinical populations.64
SUMMARY OF BRAIN PHYSIOLOGY EVIDENCE
The results of the earlier-mentioned neuroimaging and brain stimulation investigations highlight that the neurophysiological and neurobiological changes due to concussion are still not well understood. The diffuse and continually evolving secondary changes combined with the heterogeneity of external factors, such as location of injury, severity of injury, history, and individual response to brain injury, can result in unique and dramatic changes in brain structure and brain function. This can occur at many levels ranging from microscopic tears in white matter to global changes in functional brain networks. The dynamic and complex nature of concussion injury and recovery is of particular concern in children and youth due to the complexity and heterogeneity of neurodevelopment. Given these factors, there is a need for highly individualized interventions following mild TBI.
Physical therapists are in an ideal position to evaluate the impact of injury and to determine the trajectory of recovery in individuals with concussion. Using knowledge of neurodevelopmental processes with the new information provided by neuroimaging studies, therapists can develop frameworks that facilitate recovery through physical activity. In the next section of the review, we review the impact of exercise on neurological health and recovery from impairment, with a specific emphasis on exercise after concussion in youth.
EXERCISE AS MEDICINE
In this review, we distinguish between physical activity (ie, movement with minimal exertion) and exercise (ie, movement with moderate to vigorous exertion). Both acute exercise and regular engagement in exercise have well-established positive effects on brain function in healthy individuals.65 Single bouts of moderate- to high-intensity aerobic exercise can alter brain neurophysiology,66 and regular aerobic exercise can benefit cognitive functioning.67–70
Numerous studies also show the benefits of exercise to promote recovery of function following neurological impairments. Behaviorally, aerobic exercise improves motor function and cardiovascular health after neurological damage or disease.68,71 After stroke, a prescribed program of intensive aerobic exercise followed by task practice training is associated with greater improvements in upper limb functional outcomes compared with voluntary exercise followed by task practice training, or task practice training alone.18 In addition, high-intensity locomotor training is associated with greater gains in walking outcomes in persons with stroke, compared with conventional training.72 Physical activity has a positive impact on motor learning (ie, physical skill acquisition and consolidation) in neurologically impaired adults.66,71 Importantly, after moderate to severe brain injuries, general fitness training can influence a number of outcomes beyond the direct physical benefits.73 For example, individuals who engaged in exercise after a severe TBI reported less depression, fewer symptoms, and improved self-reported health status than individuals who did not engage in exercise programs.74
Exercise-induced benefits on brain health have also been reported in multiple neuroimaging studies. EEG connectivity is enhanced both during and immediately following exercise in healthy individuals.75
Changes in EEG during a graded cycling task are shown in Figure 3.76 The EEG signal is composed of frequencies between less than 1 and 50 Hz. These frequencies can be grouped into different bands, ranging from slow (delta) to fast (gamma) with each band associated with specific levels of arousal and cognitive function.77 In this study, EEG was recorded during exercise, as the exercise load increased in a healthy young adult population (ie, ages 18 to 25 years, average age of 22.5 years). Note that there is an increase in heart rate and an associated increase in theta power in both left and right frontal regions. The theta band is associated with working memory and inhibitory control.76 Interestingly, absolute theta power decreased in the last 2 stages of the graded exercise test, suggesting that at the highest intensity levels, there may be a shift to alternate strategies (ie, distribution of activity to other cortical regions) to optimize neural efficiency. A recent TMS study showed that a single session of exercise leads to a reduction in inhibitory interneuronal circuitry in healthy individuals, providing an optimal environment for neuroplasticity.78
Figure 3.: Change in heart rate and theta power with increased exercise load. Testing setup, EEG during a graded cycling task A as exercise load increases from the baseline resting-state, there is an increase in heart rate and an associated increase in theta power in both left and right frontal regions.
74 Participants began cycling at 30% (A) of their target heart rate for 5 minutes. Intensity was gradually increased to 40% (B), 50% (C), 60% (D), and 70% (E) of target heart rate. Panel A = testing setup. Panel B = theta absolute power. EEG, electroencephalography.
EXERCISE AS MEDICINE: YOUTH CONCUSSION
Although there is a large body of evidence on the benefits of physical activity and exercise in healthy individuals and in adults following acquired brain injury or neurological disease, few studies have systematically studied the effect of exercise on concussion recovery. This is in part influenced by previous consensus opinion that cognitive and physical rest should be the primary treatment in the acute phase of concussion.79 It is now recognized that prolonged rest (eg, >3 days) and activity restriction is not beneficial for recovery.80 For instance, withdrawal from physical activity participation and regular school activity can lead to rapid physically deconditioning, changes in mood, anxiety, and even depression in some youth.80 In addition, the fear of exacerbating symptoms often underlies inactivity, as seen in chronic fatigue syndrome81 and chronic pain.82 Individuals who avoid activities may in turn strengthen a negative self-perpetuating cycle.83
In a retrospective study, youth athletes with concussion who engaged in low to moderate physical activities (eg, light jogging) and cognitive tasks (eg, light school work) experienced fewer symptoms and better neurocognitive test performance compared with youth athletes with concussion who engaged in no physical activity (eg, complete rest from exercise and cognitive tasks), and compared with youth athletes with concussion who engaged in high levels of activity (eg, full school work and sports games).84 Similarly, in a prospective study of children and youth with concussion, individuals who engaged in moderate physical activities early after concussion (eg, within 7 days) had significantly fewer symptoms than individuals who followed physical activity restrictions.85
There are a small number of studies investigating the effects of physical activity or exercise on brain activity in youth measured using neuroimaging techniques. Only 2 studies used resting-state fMRI to consider this question in youth.22,86 In 1 study, both asymptomatic youth with concussion and healthy controls showed similar patterns of connectivity in the DMN at rest. Yet, after a highly intensive exercise paradigm (eg, a stress test), there are significant reductions in the connectivity and activation in asymptomatic youth with concussion compared with individuals without concussion, indicating a negative change in brain-related outcomes with vigorous exercise.22 Furthermore, youth with asymptomatic concussion demonstrated a disrupted functional network (eg, reduced interhemispheric connectivity in the primary visual cortex, hippocampal and dorsolateral prefrontal cortex networks) at rest as well as in response to physical stress compared with healthy controls.86 It is possible that vigorous exercise in the acute phase of recovery after concussion may be associated with disrupted brain dynamics and increased symptoms. However, more research is needed to understand both the immediate and long-term neurophysiological responses to this type of exercise.
A recent small pilot study (n = 4 per group, comparing exercise vs rest) found that moderate exercise led to an improvement in symptom severity and normalization in brain activation patterns, indexed by task-based fMRI.87 These findings are promising but should be interpreted cautiously, as the groups differed with respect to time post-injury and there was a small sample size. Further research is needed to outline the precise effects of exercise on the recovery of the brain after concussion.
IMPLICATIONS FOR PRACTICE
Based on this review, and in line with multiple consensus guidelines,88–90 exercise and physical activity are important components in concussion management to promote recovery in youth. Although adolescents do take longer to recover, there is no evidence that they require more time to rest.91 Guidelines have been published for return to sports-related physical activity, following a stepwise approach with checkpoints required to progress to later stages of recovery (eg, symptom-free for 24 hours and medical clearance prior to game-play).89
A suggested progression of engagement in physical activity and exercise after concussion consistent with published guidelines are provided in the Table.25,88–90 Although the activity levels and progression listed in this table have yet to be experimentally tested, these guidelines may serve as a framework for clinicians who wish to employ exercise during rehabilitation for mild TBI. Future work is required to experimentally test these guidelines and subsequently refine their clinical use.
Table. -
Progression of physical activity and exercise after concussion
|
Summary |
Description |
Measured Intensity |
Examples of Activities |
Activities to Avoid |
| Stage 1 |
Rest |
Physical rest until symptoms begin to improve OR after resting for a maximum of 2-3 days |
Not applicable |
Not applicable |
All forms of exertion, exercise, or physical activity |
| Stage 2 |
Light exertion |
Low intensity exercise |
<3 metabolic equivalent |
Slow-paced walking (4km/hour), slow-paced stationary cycling (<50 watts) |
Resistance training, activities that have increased risk of head impact |
| Stage 3 |
Moderate exertion |
Moderate intensity exercise |
3-6 metabolic equivalent |
Swimming, fast walking (4-5.5km/hour), stationary cycling (50-100 watts), core stability training |
Resistance training, activities that have increased risk of head impact |
| Stage 4 |
Moderate exertion with cognitive demands |
Moderate intensity exercise with occasional cognitively challenging task |
3-6 metabolic equivalent |
Moderate intensity sporting drills (e.g., throwing and catching), cycling (16km/hour) |
Activities that have increased risk of head impact |
| Stage 5a |
High exertion |
High intensity exercise |
>6 metabolic equivalent |
Running, calisthenics (push-ups, jumping jacks), jump rope |
Not applicable |
| Stage 6 |
High exertion with cognitive demands |
High intensity exercise with occasional cognitively challenging tasks |
>6 metabolic equivalent |
Running in a sporting drill (e.g., running to catch a ball) |
Not applicable |
aMedical clearance required prior to progressing to stage 5.Each stage should last a minimum of one day, with the overall length depending on exacerbation of symptoms.
It is important that physical therapists encourage youth with concussion to engage in physical activity after a short period of rest (eg, 2-3 days). Using clinical judgment and in consultation with the youth, family, and interdisciplinary team, physical therapists should recommend a stepwise progression of exertion activities, commencing with light-intensity exercise, followed by moderate- and then high-intensity exercise as long as symptoms do not get worse. Youth should continually monitor symptoms during each stage of the physical activity progression. Importantly, the experience of mild symptoms during exercise should not limit engagement in other activities (eg, socialization), nor should it necessarily stop progression to the next stage of physical activity.
Physical therapists can encourage adherence to these physical activity and exercise recommendations in accordance with an exercise capacity and tolerance assessment following concussion. Implementation of exercise as daily therapy should ideally involve a scheduled routine and incorporate peer networks to improve compliance, which is particularly relevant in youth concussion. Importantly, as stated in multiple guidelines, physical activity after concussion should be limited to activities that do not have a risk of sustaining another concussion (eg, not returning to high-impact sport) until receiving medical clearance.92 Notably, encouraging social activities (eg, group physical activities) and allowing moderate use of social media (eg, mobile phone use) can promote recovery and minimize the risk of postconcussive symptoms.83 In this way, youth should be encouraged to continue to participate in normal physical activity, albeit with reduced intensity, as this can foster socialization and sense of belonging. In addition, activities that promote mindfulness (eg, yoga and meditation) can promote symptom resolution.93
SUMMARY
Results from neuroimaging studies provide key information about the changing dynamics of brain structure and function following concussion. From the survey of the literature, there does not appear to be any major risk or negative impact from short bouts of moderate-intensity supervised exercise following the initial injury. In fact, there are clear benefits for brain healthy (eg, neuroplasticity and recovery) after physical activity. Engagement in structured physical activity is a key element in concussion intervention. Physical therapists are in an ideal position to manage concussion from providing education about prevention, guiding the recovery process through progression of supervised exercise. The understanding of concussion management is at an early stage, but research in this area is expanding rapidly. Clinicians should be aware that information from a single brain imaging tool will only provide a limited and constrained view of this complex injury. New approaches are now being developed that combine information from a range of neuroimaging tools, and this will, in the future, develop brain-based classifications of severity and index change over time. These composite biomarkers will provide a powerful approach to understand the pathology of concussion, the evolving nature of the injury, and ultimately to evaluate the impact of neurorehabilitation.
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