The Role of Physical Exercise in Neuroplasticity


Article topic: The Role of Physical Exercise in Neuroplasticity
Author: Rahaf Al-Awawdeh, Etaf Alajjouri
Editor: Lubna AL-Rawabdeh
Reviewer: ُEthar Hazaimeh

Keywords:  Mental health, neuroplasticity, Neurorehabilitation, physical exercise, electrical stimulation.


The purpose of this review is to discuss various interventions for improving motor function and physical performance in individuals with health conditions such as aging, neurological conditions, and mobility impairments. The research discusses various interventions for improving motor function and physical performance, including resistance training, virtual reality, physiotherapy, physical exercises, balance training, electrical stimulation, and the combination of central and peripheral stimulation. The research also highlights the benefits of each intervention and their effects on cortical plasticity, brain activity, and functional recovery. Additionally, the review emphasizes the importance of exercise, a healthy diet, and cognitive engagement in promoting positive brain health. 


Neuroplasticity is the nervous system’s ability to adjust to intrinsic or external stimuli by readjusting structure, connections, and function [1].​ Neuroplasticity refers to the brain’s ability to reorganize itself by forming new neural connections throughout life in response to experiences, learning, and environmental factors [2].​ It’s the brain’s ability to modify its shape and make a new neuronal connection via a new stimulus [3].​The principles of neuroplasticity include the importance of feedback and feed-forward connections, the role of neuromodulatory processes in controlling plasticity, and the importance of small learning steps and repetition [2].​The brain has a special self-organization character, which is the development of an organized system without external factors [3].​The neuroplasticity process involves the formation and strengthening of neural connections as well as the pruning of unused connections. This is a fundamental process underlying learning, memory, and recovery from injury or disease. It is driven by the brain’s ability to modify the strength of existing connections between neurons and to create new connections in response to new experiences [2].​ The brain may learn and adapt to new experiences due to this dynamic process [4].​ Studies have shown that the processes in the brain that control fast learning can themselves be upregulated by specific forms of training [2]. Any change in the nervous system can cause changes in the neural network for motor, sensory, and cognitive functions [1].​​ There are various aspects of biochemical mechanisms supporting neuroplasticity, including the involvement of specific proteins such as protein kinases, proteases, and cytokines in synaptic plasticity.​ Therefore, biochemical mechanisms are essential for the brain’s ability to change and adapt throughout life, which is the essence of neuroplasticity.​ These therapeutic tools are designed to harness the brain’s ability to change and adapt in response to experiences and learning to address specific neurological and psychiatric disorders [2].​

Prevention methods

Maintaining a healthier brain can be achieved through modifiable lifestyle factors such as physical activity, cognitive engagement, and diet.​​ Regular physical activity has been shown to reduce the risk of cognitive decline in aging adults [5].​​ Exercise has the main role of improving physical performance and decreasing a wide range of pathologies, including cardiovascular, metabolic, and neurodegenerative disorders.​ Endurance exercise is a physical exercise that causes increases in the respiratory rate and heart rate, and it’s called aerobic exercise.​​ Endurance exercise is inexpensive and accessible and has a lot of benefits not only in the physical domain but also in the mental domain. It helps maintain memory and cognition, delay brain aging, and enhance neurodegenerative pathologies symptoms like Parkinson’s disease, ALS, and Alzheimer’s disease [6].​​ Endurance exercises are anti-aging therapies that improve neuronal survival, promote synaptic plasticity, and decrease the disease progression of neurodegeneration [6].​​

The neuroprotective impact of endurance exercise: decreases stress, anxiety, neuro-inflammation, and insulin resistance [6].​ Cognitive training and rehabilitation can be used to facilitate the reorganization and proper function of cognitive circuits, enhancing brain reserve and cognitive reserve [5].​ Preventive approaches to promote positive health habits such as reading, discussion groups, computer usage, participation in card and board games, solving puzzles, playing musical instruments, and learning a second language can also be beneficial for brain health [5].​ Also, the diet plays a significant role in protecting against cognitive decline [5].​Diet can affect our brain negatively or positively based on the type of food that we eat. It is one of the modifiable factors that can delay the aging process, such as decreased fat and sugar intake and opioid and alcohol addiction [3]. A review of the literature suggests that a Mediterranean-style diet, which is rich in fruits, vegetables, whole grains, fish, and healthy fats, may be particularly beneficial for brain health [5].​ Acute caffeine intake can improve performance on memory tasks, and regular, moderate consumption of coffee, tea, and cacao can enhance brain health. The neurological effects of caffeine are well-established, and it has been shown to improve cognitive performance for at least 10 hours [7].​

There are a lot of neurological diseases that affect brain function such as:

  1. Alzheimer Disease:   
    Alzheimer’s is one of the most dangerous forms of dementia. It is considered one of the most severe economic, social, and medical diseases. The drugs that are mostly prescribed for Alzheimer’s disease are acetylcholinesterase inhibitors (Ach Els) and memantine. These drugs improve some symptoms, but surprisingly, they don’t have any effect on decreasing the progression of ADLs, social behaviors, or communication [8].​
    Studies showed that physical exercises not only have a positive effect on general health but also have other effects on mental health and prevent or decrease the risk of neurodegenerative diseases. Physical exercise has a positive effect on some of the most characteristic signs of Alzheimer’s disease, generally through the regulation of oxidative stress-related mechanisms in the brain, increased blood flow and metabolism, and especially the decrease of cortical formation and accumulation of Aβ. Moreover, some of the mechanisms through which exercise has a positive impact on Alzheimer’s disease appear to involve improvements in mitochondrial function. Also, exercise decreases the risk of cognitive impairment, so exercises that induce alterations in cognitive status are necessary for Alzheimer’s patients to improve their quality of life [9].​
    Exercises improve brain structure and function. The adaptation that occurs because of exercise increases hippocampal neurogenesis and volume, increases brain blood flow, increases plasticity, and decreases the brain atrophy that occurs due to aging. Recently, research showed that physical exercise is the most effective strategy to counteract and prevent neurodegenerative diseases like Alzheimer’s.​ Exercise intensity, repetition, and duration are not clear and are still under discussion [9].​
  2. Depression  
    In cases of depression, brain structure changes are nearly always associated with certain areas of the nervous system, including the anterior lobe, cingulate gyrus, hippocampus, striatum, and white matter. Reductions in brain volume (including structural brain changes like neuronal loss and dropped neurotrophic factor) are related to depressive episodes. The hippocampus plays an important role in cognitive exertion as well as stress and mood regulation in cases of depression. Exercise can play a positive role in preventing and treating depression. Different types of exercise, such as aerobic exercise, resistance exercise, and mind-body exercise, can palliate depressive symptoms and lower depression levels. Exercise can reshape the brain structure of depression cases, spark the function of affiliated brain areas, and promote behavioral adaptation, which changes the brain’s neuroprocessing and delays cognitive decline in depression cases [10].
     Aerobic exercise has been shown to result in decreased anxiety and depression in animal models, even in stressful situations. Physical exercise has an action similar to selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression and anxiety [11]. Exercise has a better antidepressant effect than traditional drugs, and moderate-intensity aerobic exercise for at least 9 weeks, 3–4 days a week, can effectively reduce the threat of depression [10].
    Physical exercise is associated with improved psychological well-being and satisfaction with life in humans [11].
  • Stroke (CVA)  
    A stroke is a medical contingency that occurs when the blood flow to the brain is cut off or reduced, depriving brain tissue of oxygen and nutrients. This can cause brain cells to die, leading to permanent brain damage, disability, or death. Stroke has two types: ischemic stroke and hemorrhagic stroke.

    A stroke can cause abrupt paralysis or numbness in the face, arm, or leg, particularly on one side of the body; unexpected confusion; difficulty speaking or understanding speech; loss of balance or coordination; and a sudden severe headache with no known cause [12].
    After a stroke, the brain undergoes neuroplastic changes that can lead to motor impairment. There are various approaches and techniques for stroke rehabilitation that aim to enhance neuroplasticity and improve motor function after stroke, such as:
    ​ 1. Physical therapy: This involves exercises and activities that help improve strength, flexibility, and coordination.
    2. Pharmacological interventions: Medications such as antidepressants, anti-spasticity agents, and neuroprotective agents may be used to improve motor function after stroke.
    3. Stem cells: Stem cells may be used to promote neural repair and regeneration after stroke.
    4. Neural growth factors: These are proteins that promote the growth and survival of neurons and may be used to enhance neuroplasticity after stroke.
    5. Exogenous biomaterials: These are materials that can be implanted or injected into the body to promote neural repair and regeneration.
    6. Robot-assisted therapy: This involves the use of robotic devices to assist with movement and improve motor function.
    7. Orthotics: These are devices such as braces or splints that can be worn to support and stabilize the affected limb.
    8. Peripheral nerve/muscle stimulation: Electrical stimulation of the nerves or muscles may be used to improve motor function after stroke.
    9. Transcranial magnetic stimulation: This involves the use of magnetic fields to stimulate the brain and improve motor function.
    10. Occupational therapy and speech [12].
    The effect of physical exercises after stroke is described as the first-line intervention strategy to decrease the chronic impairment of sensory and motor function.

    Physical exercise can be used as a diagnostic, rehabilitation, and preventive tool for stroke patients. For starters, acute exercise could be used as a diagnostic tool to uncover new neural mechanisms underlying stroke pathology. Furthermore, physical exercise training is recommended as a useful rehabilitation tool, it inhibits inflammatory processes and the expression of apoptotic markers in the brain, promotes angiogenesis and the expression of some growth factors in the brain, and improves the activation of affected muscles during exercise. Its depending on the exercise parameters used, exercise training may aggravate sensorimotor deficits and brain injuries. Therefore, it is important to design individualized exercise programs that consider the patient’s specific needs and limitations. Regular physical activity before a stroke may decrease the severity of motor outcomes after having a stroke and help reduce the severity of the motor result.
    Therefore, to prevent stroke using physical exercise, it is recommended to engage in regular physical activity, such as walking, jogging, cycling, or swimming, for at least 30 minutes a day, five days a week. Additionally, it is important to maintain a healthy diet, control blood pressure, quit smoking, limit alcohol consumption, and manage diabetes to reduce the risk of developing stroke [13].​
    Physiotherapy can help patients return to their daily living activities and professional activities, reducing the burden on their caregivers and the healthcare system. Physiotherapy approaches may include exercises to improve strength, balance, and coordination, as well as gait training and functional activities to improve mobility and independence.
    Overall, physiotherapy is an essential component of stroke recovery and can significantly improve outcomes for stroke patients [14].​
  1. Spinal cord injuries (SCI) 
    The impact of a spinal cord injury is the sudden loss of movement and function, which can be life-changing. Spinal cord injury can affect motor, sensory, and autonomic functions, and result in local and global inflammatory reactions. Motor function loss following SCI, as well as plastic changes in the spinal cord because of the injury, can result in hyperreflexia, spasticity, and spasms. Spinal cord injury can also trigger a loss of downstream activity-dependent processes, producing spinal interneuron degeneration and several activity-dependent maladaptive changes [15].​
    Activity-dependent neuroplasticity can be used to promote motor recovery after spinal cord injury by promoting the formation of new functional connections and strengthening spared connections in the spinal cord. Motor rehabilitation can also be used to promote motor recovery by training circuits and promoting adaptive plasticity [15].​
  2. Parkinson’s disease (PD) 
    Parkinson’s Disease (PD) is a progressive neurodegenerative movement disorder that is characterized by motor symptoms such as resting tremor, rigidity, bradykinesia or akinesia, and postural instability.
    It is caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to motor and cognitive dysfunction as well as mood disorders. Age is the most important risk factor for developing PD, but environmental factors like pesticide exposure, β-adrenergic antagonist use, and male gender also increase PD risk. Exercise has been shown to modify dopaminergic signaling and sensitivity, increase neurotrophic factors and angiogenesis, and reduce inflammatory pathways, making it an attractive therapeutic target for PD [6].
    Combining prefrontal and motor cortex stimulation could reduce the freezing of gait and improve mobility in patients with Parkinson’s disease. In summary, the prefrontal cortex can be used to enhance cognitive performance, attention, and executive functions, as well as motor recovery [16].
    There are several benefits of exercise for people with Parkinson’s disease (PD), including: 

1. Improving physiologic, functional, clinical, and molecular outcomes.

2. Enhancing mobility and cognition in PD patients.

3. Preserving and restoring dopaminergic neurons in the midbrain.

4. In Parkinson’s disease patients who completed high-intensity exercise, there was a dose-dependent improvement in mobility as well as a normalization of corticomotor excitability.

5. Improving walking speed, stride, and step length in PD patients with mild-to-moderate disability.

6. Providing maximum benefit to PD patients when exercise is diffuse as opposed to training targeted to specific deficits.

7. Improving both forward and backward walking in PD patients who completed treadmill exercise.

8. Providing some benefit from increased activity in PD patients who completed low-intensity exercise.​

Physical exercises’ effects on brain plasticity

The positive effects of physical exercise on brain activity, specifically its effects on cognitive functions, spatial learning, and short-term and long-term memory [17].
Physical exercise induces an increase in the synthesis and release of neurotrophins and growth factors, which include brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (EGF). Modulation of these neuromediators appears to increase neuronal subtype survival and development [9].​
Neuroplasticity has been seen in humans by growing white and gray matter in various brain locations following various physical exercise programs. Physical exercise has a positive effect on mental health outcomes. The practice of physical exercise increases the plasticity of the hippocampus, promoting changes in serotonin metabolism and synaptic plasticity [11].
Gross motor performance is increased by resistive training, which increases the maximal voluntary force in specific tasks, An increase in motor performance occurs because of neuroplastic adaptations in the brain [18].​ 
Resistance training (RT) has been shown to induce neuroplasticity, which refers to the ability of the nervous system to adapt and reorganize in response to changes in the environment or behavior. RT can induce favorable changes in the nervous system, which may mediate improvements in physical and cognitive function [18].​
The functional relevance of resistance training-induced neuroplasticity in health and disease refers to the potential benefits of resistance training (RT) on improving motor function and physical performance in individuals with various health conditions, such as aging, neurological conditions (e.g., Parkinson’s disease, multiple sclerosis, and stroke), and mobility impairments [18].
Fit or aerobically trained older adults have greater functional connectivity between parts of the frontal, posterior, and temporal cortices involved in spatial selection and inhibitory function [19].
Several studies mentioned in the document suggested that resistance training can enhance motor cortical plasticity, increase gray matter density in elderly individuals, and lead to functional and/or structural brain changes that improve cognitive function [18].

Physiotherapy interventions

Physiotherapy interventions can assist patients to enhance their performance and abilities. Both Conventional physiotherapy interventions and a standard protocol called neurorestoration are effective in improving balance and functional ability in acute stroke survivors. The neurorestoration protocol, which combined several established interventions, was found to be more effective. The Physiotherapy interventions, including the neurorestoration protocol, should be considered as a core intervention in treatment alongside medical and pharmaceutical interventions [21].​
Physical exercises are described as a non-pharmacological method that has a positive effect on memory, spatial learning, and cognitive function. Also, it helps in treating neurodegenerative diseases and improving brain health. 
 The recommendation of the American College of Sports and Exercise is to train most of the week with aerobic and resistance exercises.  
The different types of physical exercises are non-forced, such as activity wheels, and forced, such as the treadmill, which causes hippocampal plasticity, cell proliferation, and branching of the dendrites.  
A study of the effect of running on the dentate gyrus for long-term potential showed that running decreases the age associated with long-term potential. Another study showed that neuroreceptors can improve the capacity of cells in the long term. A study using radiant as an animal model showed that the radiant subjected to aerobic exercises on treadmills for 12 weeks had better outcomes in hippocampal plasticity, memory, and spatial learning after training than other groups [17].​
Based on the randomized control trial that reviewed the relation between balance training exercises in cortical thickness in visual and vestibular cortical regions, Participants had 12 weeks of continuous training; they took 2 sessions/week, and the duration of each session was 50 mins. They were categorized into 2 groups: the balance group and the relaxation group. Each group had from 10-12 participants [22].
1) Balance training: This section was directed as a circuit training with 8 stations, the duration of each station lasted 5 mins. 
 The participants trained on different surfaces, such as a firm foam surface, and in different conditions such as dynamic or static balance, eyes open or closed, a wide base of support, and a narrow base of support. 
 The exercise station was replaced with a new one after six weeks of training to make it more challenging.​22​ 
2) Relaxation training: This group practiced progressive muscle relaxation and autogenic exercises. The short form of progressive muscle relaxation was instructed in the first 6 weeks.  
The single muscle group tensed 5-7sec, then 45-sec relaxation, and repeated 2 times per session [22].
The autogenic training was introduced after 6 weeks; this training included breathing exercises, and the participants were trained on how to concentrate on the breathing rhythm as well as on heartbeats. The enhancements in balance performance have a relationship with the change in cortical thickness in both the left and right pre-central gyrus. 
 The improvement in balance performance is associated with a huge increase in pre-central cortical thickness, there is no significant difference for relaxation groups [22].​
Another study showed that Aerobic, resistance, and balance activities may be beneficial in improving physical function and increasing brain activity. The exercise intervention increased step length but decreased cadence in the intervention group. The changes in gait are associated with age-related brain changes, including global brain atrophy, cerebral white matter lesions, and micro-bleeds. In older persons, exercise and gait training can enhance both physical and mental performance [19].
Recent studies of animals and humans showed that acute exercises could make changes in muscle activation after having cerebral ischemia and the early treadmill exercises make neuroplasticity by working on the angiogenesis and vasomotor activity of the brain. 
 Preischemic exercises like treadmill workouts for 30 mins. for 5 days/week for 3 weeks decrease infarct volume and edema [13].​

Virtual reality (VR) can have a positive impact on neural plasticity.
VR-based interventions can provide enriched environments for rehabilitation, which can promote experience-dependent plasticity in stroke patients.​20​ 
The mirror neuron system is a neural network that is involved in motor observation, imitation, and imagery and can be activated by VR-based interventions, the mirror neuron system can be encompassed in VR interventions, and it reveals the possible specific neural mechanisms of VR. The core mirror neuron system in humans includes the inferior parietal lobule, ventral premotor cortex, and inferior frontal gyrus, and it is more like a functionally distributed network involving the primary and secondary motor areas than specific separate regions [20].
VR systems should be designed to provide a high level of immersion and engagement, as this can enhance the effectiveness of VR-based interventions. Additionally, the development of VR systems that can be used in a variety of settings, including inpatient and outpatient rehabilitation, and that can be adapted to the changing needs of stroke patients over time [20].

VR makes neural plasticity changes in stroke survivors, and there is a positive relationship between neural plasticity changes and functional recovery [20].
The neurophysiological effects are enhancing inter-hemispheric balance; improving cortical connectivity, raising the cortical mapping of the affected muscles, and increasing the activation in the frontal cortex regions, involving the mirror neuron system, and all the improvements of the behavioral outcomes related to the improvement in neural plasticity [20].
Balance performance can be improved by specific exercise programs for blind adults. A blind adult showed an improvement in static, dynamic, and functional balance after 12 weeks of balance exercises [23].​
Electrical stimulation  
Electrical stimulation is used in neuromuscular electrical stimulation (NMES) to activate muscles that have become weak or paralyzed as a result of stroke. The electrical stimulation is delivered through electrodes placed on the skin over the targeted muscles. The purpose of NMES is to improve muscle strength, reduce muscle atrophy, and promote motor relearning. NMES can be used as a standalone therapy or in combination with other rehabilitation therapies. The peripheral and central effects of NMES include an increase in contractile force and fatigue resistance, as well as changes in cortical excitability and functional cortical reorganization. There are various NMES modalities used for upper and lower limb rehabilitation, such as cyclic, EMG-triggered, and contralaterally controlled NMES, and they have been evaluated for therapeutic effects [24].​
The purposes of NMES for upper and lower limb rehabilitation after stroke. One of the most common manifestations of stroke is paresis, which is the inability or decreased ability to volitionally activate motor units. Paresis manifests as muscle weakness and decreased activation speed, as well as the inability to generate functionally effective movement of the afflicted limb. The combination of paresis, loss of fractionated motions, flexor hypertonia, and somatosensory anomalies frequently appear as trouble functionally extending the elbow and opening the hand, significantly limiting the functional workspace. There are several NMES modes available for upper limb rehabilitation. Cyclic NMES is a technique that employs a one- or two-channel stimulator to repeatedly stimulate (cyclically) via surface electrodes implanted on specific areas of the body above the motor sites of those muscles [24].​
The peripheral effects of NMES include an increase in contractile force and fatigue resistance, as well as a reduction in muscle atrophy. NMES can also promote motor relearning by providing an artificial way of ensuring synchronized presynaptic and postsynaptic activity. This is especially true if the electrical stimulation is combined with a concurrent voluntary effort that activates the remaining upper motor neurons. Cortical excitability alterations and functional cortical reconfiguration are two of the main impacts of NMES. By causing long-term potentiation in the sensorimotor cortex brought on by proprioceptive and cutaneous afferent input occurring concurrently with attempted movements, NMES may improve cortical excitability​ [24].

The combination of central and peripheral stimulation, specifically the use of transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) together [16].​
Studies have shown positive results regarding the combination of central and peripheral stimulation, including pain relief in patients with chronic pain and substantial functional improvements in patients with motor deficits. The benefits of peripheral stimulation, specifically the use of (TENS), which is a safe and non-invasive device that aims to stimulate nerves for therapeutic purposes, have been proven. The gate control theory, which says that physical pain is not a direct outcome of the activation of pain receptor neurons, has been suggested to explain how TENS functions; its perception is influenced by the interaction of distinct neurons [16].​
The benefits of central stimulation, specifically the use of (tDCS), which is a non-invasive technique that aims to modulate cortical excitability by applying a weak electrical current to the scalp, have been investigated for different conditions, such as stroke, Parkinson’s disease, and depression.. tDCS can alter a response and facilitate cortical remodeling when it is applied across a specific motor cortex region. By combining central stimulation with peripheral stimulation, it would be possible to enhance the effects of each intervention individually and achieve faster and long-lasting results. The utilization of prefrontal montage to improve motor, cognitive, and attentional functions. Specifically, the document mentions the use of anodal tDCS over the dorsolateral prefrontal cortex (DLPFC) for enhancing cognitive performance, including attention and executive functions [16].​ The use of cerebellar stimulation, specifically transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), for motor and cognitive functions. Cerebellar stimulation has been investigated for different conditions, such as stroke, Parkinson’s disease, and balance disorders. The cerebellum is known to play a crucial role in motor coordination, balance, and cognitive functions. Cerebellar stimulation can modulate cortical excitability using cerebello-cortical connectivity, which can lead to improvements in motor learning, cognitive functions, and balance. Furthermore, cerebellar stimulation can be used to augment language treatment post-stroke as well as modulate the acquisition of conditioned eyeblink responses. In conclusion, cerebellar stimulation can help with balance, emotional perception, and motor and cognitive abilities [16].


The findings of this literature review are that physical exercise has a positive effect on brain activity, specifically its effects on cognitive functions, spatial learning, and short-term and long-term memory. 
Resistance training exercises affect neuroplasticity in the brain by improving motor function and physical performance in individuals with various health conditions. 
A study of Aerobic exercises showed that running decreases the age associated with long-term potential. 
Virtual reality (VR) has a positive impact on neural plasticity because it provides enriched environments for rehabilitation, which can promote experience-dependent plasticity. 
Studies showed positive effects regarding the combination of central and peripheral stimulation, including pain relief in patients with chronic pain and substantial functional improvements in patients with motor deficits.


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