Neuroplasticity After Brain Injury: Principles and Methods for Postinjury Improvement

Brain injury survivors experience a wide range of secondary physical, cognitive, and behavioral consequences that may significantly impact daily life. Ranging from seizures, paralysis, and pain to learning and memory impairment, disorientation, aggression, impulsivity, and noncompliance. Cognitive function postinjury is considered the most impacted and is also cited as the most important predictor for returning to work or prior living status. Improving these symptoms/functions is a primary goal of brain injury rehabilitation and is made possible through the process of neuroplasticity.

What Is Neuroplasticity?

Neuroplasticity is the science of how the brain changes its structure and function in response to input. These changes include creation of new blood vessels, creation of new synapses, dendritic arborization, and creation of new neurons. These changes may occur in response to positive, as well as negative stimuli (maladaptive vs adaptive plasticity). Examples of maladaptive plasticity include neuronal structure/function changes in response to addictive substances, as well as the strengthening of connections and reinforcement of compensatory mechanisms that impede recovery. Neuroplasticity can occur at multiple levels, from the molecular and synaptic level to higher order levels of cortical maps and large-scale neuronal networks. Data indicates that the brain continuously restructures neural circuitry, in fact, this is the foundation for encoding new experiences and enabling changes in behavior. Channeling this innate ability of the brain to change is essential to maximizing the benefits of rehabilitation.¹ Change requires structure, repetition, and consistency by trained and experienced staff. This need for structure, repetition, and consistency is illustrated in a set of principles of neuroplasticity.

Principles of Neuroplasticity²

1. Use it or lose it: This principle describes the degradation of neural circuits not actively engaged in task performance for long periods of time. For example, individuals with left side strokes may lose some function on the right side of their bodies. Since tasks with the right side become more difficult, they default to use of the unaffected (left) side. The brain reorganizes and dedicates more “space” to the left motor area, thus limiting recovery potential of the right side.
2. Use it and improve it: Plasticity can be induced through extended training. In other words, training that drives a specific brain function can lead to enhancement of that function. For example, under the guidance of trained staff, a technique known as constraint-induced movement therapy can be used to restrain the arm on the nonaffected side, so that the patient is compelled to use their affected limb as much as possible, thereby improving its function.
3. Specificity: From a treatment standpoint, specificity highlights the importance of tailoring an activity or exercise to produce a result in specific circuitry. Research in this area has shown that specific skill acquisition produces greater changes in the brain than unskilled repetitive movements. While physical exercises aimed at strengthening leg muscles will ultimately help patients improve their sit-to-stand from a chair or bed, more significant changes will occur when that specific sit-to-stand skill is practiced.
4. Repetition matters: Patients may often ask, “how long is this going to take?” While it is difficult to give a precise answer, research shows that thousands and even tens of thousands of repetitions are required to generate change. Utilization of combination therapies can be particularly beneficial for increasing repetitions without necessarily increasing time. For example, physical therapists may increase a patient’s steps outside of their therapy session by having them walk between therapy sessions or stand during their other therapy sessions. Likewise, speech therapists could have patients working on memory or pathfinding activities during their PT session.
5. Intensity matters: This principle can be thought of as the dosage required to induce change. The intensity, or dosage, is highly dependent upon the therapy goals; however, data shows that the more intense a therapy program, the more likely it is that the program will result in substantial change and the more sustainable those changes will be.
6. Time matters: “Plasticity occurs at different times during recovery.” This is particularly relevant in the context of brain injury recovery, as in the acute phase especially, the brain is actively looking for new ways to rewire to regain function (making the training much easier). Without access to the appropriate training during this phase, the brain will instead develop less desirable compensatory mechanisms (like a stroke patient not using their affected limb to do daily tasks). Early access to treatment helps avoid development of maladaptive behaviors.
7. Salience matters: Research suggests that emotions play a role in neuroplasticity. It is easier for us to learn things that we are interested in or that excite us. It is important for therapists to know what really matters to their patients in order to improve skill acquisition by targeting relevant and salient tasks.
8. Age matters: Our brains are much more adaptable when we are younger, which makes change in structure and function easier to achieve. An aging brain is very capable of neuroplasticity, it simply may take more time and be more difficult, requiring more repetitions and higher intensity.
9. Transference or generalization: “Plasticity in response to one training experience can enhance acquisition of similar behaviors.” This principle is best explained in the context of rehabilitation. During therapy, the goal is to get the patient to a level where they can function as independently as possible, meaning that it is important to utilize techniques that can be applied outside of the therapy environment. For example, having a patient reach out to grab an object during PT or OT knowing that they will be able to utilize that same technique to reach for objects at home.
10. Interference: This principle is referencing the development of maladaptive behaviors. When therapy is delayed and maladaptive behaviors surface, therapy is made more challenging by needing to unlearn the maladaptive compensatory mechanisms before real positive change can occur.

Methods for Improving Neuroplasticity After Brain Injury

Structured Rehabilitation

Structured rehabilitation is the most direct way to improve neuroplasticity postinjury, especially multidisciplinary programs. Multidisciplinary programs including all therapeutic disciplines (cognitive, physical, occupational, educational, and counseling) allow for the most efficient use of time and the highest amount of carry over by creating well-balanced and coordinated treatment plans that are supported by each department. Progress can then be reassessed across time, and therapy goals redirected as appropriate.

Physical Exercise and Cognitive Activity

A large body of evidence tells us that exercise is neuroprotective. Its mechanisms include anti-inflammatory effects, neuro- and angiogenesis, decreasing oxidative stress, promoting long-term strengthening of synapses [long-term potentiation (LTP)], and increasing transcription of genes associated with plasticity.³ Functionally, this leads to improvements in depressive symptoms, cognitive function, balance, and sleep. By combining the effects of exercise with cognitive training, we are likely to see a substantial impact on neural structure and function.

Noninvasive Neurostimulation and Rehabilitation

There are a number of different methods of noninvasive neurostimulation (ie, tDCS, TMS, tACS). While these methods of stimulation are not enough to generate action potentials on their own, they produce sub-threshold changes in the firing patterns of already active neurons. By producing these small subthreshold changes, the stimulation may be able to prime the neural circuits so that the brain is more responsive to rehabilitation.⁴

Addressing Underrecognized Comorbidities

Sleep

Sleep-wake disturbances are common after brain injury, impacting up to 80% of brain injury survivors. These disturbances are often multiple and multifaceted ranging from sleep disordered breathing (sleep apnea) to REM sleep behavior disorders, circadian rhythm disorders, and disruptions in sleep architecture. Sleep has long been established as critical for learning and memory and is now also associated with the ability to suppress memories and unlearn, as well as decrease depressive symptoms. Sleep also impacts various aspects of synaptic strength and structure, including stabilization of dendritic spines and spine pruning, and decreases inflammation.⁵ By objectively addressing any sleep disturbances, we can weed out the impact of sleep on cognitive and behavioral function, as well as directly improve the capacity for neuroplastic change.

Neuroendocrine Function

Neuroendocrine dysfunction is not uncommon postinjury and may or may not be associated with sleep disturbances, since sleep impacts hormone function and vice versa. In general, the pituitary gland, which directs neuroendocrine function, is very susceptible to injury due to its size and location. Our neuroendocrine system relies on tightly regulated negative feedback loops to function properly. When the hypothalamus and/or pituitary is injured, these feedback loops breakdown and lead to widespread functional damage. One specific example is the impact of prolonged stress on neuroplasticity. If the brain is not receiving and sending stress signals appropriately, leading to a prolonged response, we can see atrophy and remodeling of neurons, impacts on gene expression, decreases in LTP, and increases in depression and anxiety.⁶

Concluding Thoughts

Understanding and utilizing neuroplasticity principles is crucial in neurorehabilitation. Early access to multidisciplinary therapy programs with experienced and trained staff will aid in improving a patient’s ability to engage in daily activities and participate in meaningful social roles. In fact, substantial recovery or restoration of function is unlikely in the absence of targeted intervention. In addition to targeted rehabilitation, we can bolster neuroplasticity by using combination therapies, noninvasive neurostimulation, and addressing underrecognized comorbidities such as sleep and neuroendocrine function.

Dr Howell is a senior neuroscientist and Director of Research Integration at the Centre for Neuro Skills. She is a specialist in brain injury rehabilitation, neurodegenerative disease, and clinical research.

References

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2. Kleim JA, Jones TA. Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J Speech Lang Hear Res. 2008;51(1):S225-239.

3. Xing Y, Bai Y. A review of exercise-induced neuroplasticity in ischemic stroke: pathology and mechanisms. Mol Neurobiol. 2020;57(10):4218-4231.

4. Zaninotto AL, El-Hagrassy MM, Green JR, et al. Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: a systematic review. Dement Neuropsychol. 2019;13(2):172-179.

5. Sun L, Zhou H, Cichon J, Yang G. Experience and sleep-dependent synaptic plasticity: from structure to activity. Philos Trans R Soc Lond B Biol Sci. 2020;375(1799):20190234.

6. Radley J, Morilak D, Viau V, Campeau S. Chronic stress and brain plasticity: mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders. Neurosci Biobehav Rev. 2015;58:79-91.