Exercise-induced Neuroplasticity Research Articles

Exercise-induced neuroplasticity: a new perspective on rehabilitation for chronic low back pain.

Chronic low back pain patients often experience recurrent episodes due to various peripheral and central factors, leading to physical and mental impairments, affecting their daily life and work, and increasing the healthcare burden. With the continuous advancement of neuropathological research, changes in brain structure and function in chronic low back pain patients have been revealed. Neuroplasticity is an important mechanism of self-regulation in the brain and plays a key role in neural injury repair. Targeting neuroplasticity and regulating the central nervous system to improve functional impairments has become a research focus in rehabilitation medicine. Recent studies have shown that exercise can have beneficial effects on the body, such as improving cognition, combating depression, and enhancing athletic performance. Exercise-induced neuroplasticity may be a potential mechanism through which exercise affects the brain. This article systematically introduces the theory of exercise-induced neuroplasticity, explores the central effects mechanism of exercise on patients with chronic low back pain, and further looks forward to new directions in targeted neuroplasticity-based rehabilitation treatment for chronic low back pain.

Tongue exercise-induced plasticity in upper airway EMG activity in a model of hypoglossal motor neuron loss

Motor neuron diseases (MNDs) are a group of neuromuscular disorders in which motor neurons (MNs) required for activities of daily living are lost. Patients with MNDs often develop swallowing and breathing dysfunction due to pathology of the hypoglossal (XII) axis ( e.g., XII lower motor neurons, LMNs). These co-dependent, vital functions require reciprocal roles of the tongue during swallowing, and impaired control and coordination of these opposing behaviors can lead to aspiration pneumonia and respiratory failure. Due to a lack of research, available treatments for patients with MNDs are largely palliative, and there is a critical need for therapies targeting the preservation of upper airway function and coordination. The extensive tongue muscle weakness in patients with MNDs suggests a potential role for therapeutic exercise, but suffcient evidence is lacking to conclude if tongue exercise is beneficial or harmful. A barrier in studying the impact of XII LMN degeneration and developing therapies to improve swallowing and breathing function/coordination has been the lack of an appropriate model. We therefore developed a novel rodent model of XII LMN loss using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP), which has tongue motility and swallowing deficits that are mitigated by a high-repetition/low resistance tongue exercise paradigm for muscle growth. Here, we simultaneously studied upper airway (geniohyoid) and diaphragm EMG activity with swallowing ( via videofluoroscopy swallow studies; VFSS) and breathing ( via plethysmography) to discern whether CTB-SAP induced XII LMN loss results in upper airway deficits and discoordination of swallowing and breathing functions. We hypothesized that geniohyoid (not diaphragm) EMG activity would be decreased and swallow-breathing coordination would be altered in unanesthetized and spontaneously breathing CTB-SAP rats vs. controls, and that tongue exercise would mitigate these deficits. Using custom-made headcap implants, we embedded EMG electrodes into the geniohyoid and diaphragm muscles in adult male rats prior to intralingual injection of CTB-SAP or control (CTB unconjugated to SAP) and studied chronic EMG activity during VFSS or during plethysmography studies +/- tongue exercise (N=4-6/group). Our preliminary findings show decreased geniohyoid (but not diaphragm) EMG activity as well as swallow/breathing discoordination that appears to be reversed with tongue exercise in CTB-SAP rats vs. controls. In conclusion, tongue exercise appears to enhance XII axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration. Studies are now underway to understand the underlying mechanism of tongue exercise-induced neuroplasticity, which may help guide future translational studies in patients with MNDs. R01 HL153612 and Phi Zeta. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Changes in EEG Activity and Cognition Related to Physical Activity in Older Adults: A Systematic Review.

Aging is generally associated with a decline in important cognitive functions that can be observed in EEG. Physical activity in older adults should be considered one of the main strategies to promote health and prevent disease in the elderly. The present study aimed to systematically review studies of EEG activity and cognitive function changes associated with physical activity in older adults. Records from PubMed, Scopus, and EBSCO databases were searched and, following the PRISMA guidelines, nine studies were included in the present systematic review. A risk of bias assessment was performed using the National Institute of Health Quality Assessment Tool for Case-control Studies instrument. The studies analyzed used two main strategies to determine the effects of physical activity on cognition and EEG: (1) multiscale entropy and power frequencies; and (2) event-related potentials. In terms of EEG activity, it can be concluded that exercise-induced neuroplasticity underlies improvements in cognitive function in healthy older adults.

Pro-Brain-Derived Neurotrophic Factor (BDNF), but Not Mature BDNF, Is Expressed in Human Skeletal Muscle: Implications for Exercise-Induced Neuroplasticity.

Exercise promotes brain plasticity partly by stimulating increases in mature brain-derived neurotrophic factor (mBDNF), but the role of the pro-BDNF isoform in the regulation of BDNF metabolism in humans is unknown. We quantified the expression of pro-BDNF and mBDNF in human skeletal muscle and plasma at rest, after acute exercise (+/- lactate infusion), and after fasting. Pro-BDNF and mBDNF were analyzed with immunoblotting, enzyme-linked immunosorbent assay, immunohistochemistry, and quantitative polymerase chain reaction. Pro-BDNF was consistently and clearly detected in skeletal muscle (40-250 pg mg-1 dry muscle), whereas mBDNF was not. All methods showed a 4-fold greater pro-BDNF expression in type I muscle fibers compared to type II fibers. Exercise resulted in elevated plasma levels of mBDNF (55%) and pro-BDNF (20%), as well as muscle levels of pro-BDNF (∼10%, all P<0.05). Lactate infusion during exercise induced a significantly greater increase in plasma mBDNF (115%, P<0.05) compared to control (saline infusion), with no effect on pro-BDNF levels in plasma or muscle. A 3-day fast resulted in a small increase in plasma pro-BDNF (∼10%, P<0.05), with no effect on mBDNF. Pro-BDNF is highly expressed in human skeletal muscle, particularly in type I fibers, and is increased after exercise. While exercising with higher lactate augmented levels of plasma mBDNF, exercise-mediated increases in circulating mBDNF likely derive partly from release and cleavage of pro-BDNF from skeletal muscle, and partly from neural and other tissues. These findings have implications for preclinical and clinical work related to a wide range of neurological disorders such as Alzheimer's, clinical depression, and amyotrophic lateral sclerosis.

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.

Goal-directed and habitual control: from circuits and functions to exercise-induced neuroplasticity targets for the treatment of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor and cognitive impairments. The progressive depletion of dopamine (DA) is the pathological basis of dysfunctional goal-directed and habitual control circuits in the basal ganglia. Exercise-induced neuroplasticity could delay disease progression by improving motor and cognitive performance in patients with PD. This paper reviews the research progress on the motor-cognitive basal ganglia circuit and summarizes the current hypotheses for explaining exercise intervention on rehabilitation in PD. Studies on exercise mediated mechanisms will contribute to the understanding of networks that regulate goal-directed and habitual behaviors and deficits in PD, facilitating the development of strategies for treatment of PD.

Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss

Motor neuron diseases (MNDs) are a group of neuromuscular disorders in which motor neurons (MNs) required for activities of daily living are lost. Patients with MNDs often develop swallowing and breathing dysfunction, leading to aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting the preservation of upper airway function. Upper airway dysfunction in MNDs is largely attributed to degeneration of XII lower MNs (LMNs) which innervate the genioglossus muscle of the tongue and often results in progressive tongue weakness. The extensive tongue muscle weakness in patients with MNDs suggests a potential role for therapeutic exercise, but sufficient evidence is lacking to conclude if tongue exercise is beneficial or harmful. A barrier in studying the impact of XII LMN degeneration and developing therapies to improve swallowing and breathing function/coordination has been the lack of an appropriate model. We developed a novel rodent model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to induce targeted loss of XII MNs and XII motor output. CTB-SAP rats have degenerative changes in the XII nerve and genioglossus, as well as decreased tongue motility and swallowing deficits that are mitigated by tongue exercise. We hypothesize that upper airway function/coordination can be improved in the face of XII LMN degeneration by tongue exercise-induced XII-tongue axis plasticity. Here, we intralingually injected adult male rats with CTB-SAP or control (CTB unconjugated to SAP), and studied the following parameters +/- tongue exercise: 1) XII motor output in anesthetized and ventilated rats via in vivo neurophysiology; and 2) structural changes via magnetic resonance imaging. Thus far, our data suggests that tongue exercise in CTB-SAP rats results in enhanced XII motor plasticity and mitigates structural airway changes (p&lt;0.05 vs. sham-treated CTB-SAP rats). We have also started collecting pilot data to determine if upper airway (geniohyoid) EMG activity is decreased in unanesthetized and spontaneously breathing CTB-SAP rats, and if tongue exercise mitigates these deficits while diaphragm EMG activity remains unaffected +/- tongue exercise. In conclusion, tongue exercise appears to cause XII-tongue axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration. Studies are now underway to understand the underlying mechanism of tongue exercise-induced neuroplasticity, which may help guide future translational studies in patients with MNDs. Funded by: R01 HL153612 and Phi Zeta This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Associations of Brain-Derived Neurotropic Factor rs6265 Gene Polymorphism with Personality Dimensions among Athletes.

Brain-Derived Neurotropic Factor (BDNF) is one of the essential mediating factors of exercise-induced neuroplasticity, but the underlying molecular mechanisms of exercise-induced neuroplasticity are still largely unknown. Personality dimensions differentiate individuals and depend on genes and environmental factors. The dimensions of openness to experience, emotional stability, extraversion and conscientiousness have been reported to be positively related to performance; considering agreeableness, a negative relation with sports performance was emphasized. However, not enough effort has been put into investigating the relationship between genetic polymorphisms affecting psychological abilities and competitive power sports. The aim of this study was to investigate the association of the rs6265 polymorphism of BDNF with personality dimensions in martial arts athletes. The study was conducted among martial arts athletes. The study group included 258 volunteers (martial arts athletes (n = 106) and controls (n = 152). BDNF polymorphism testing was performed using the real-time PCR method; personality dimensions were assessed using standardized NEO-FFI questionnaires. All analyses were performed using STATISTICA 13. We observed that martial arts athletes’ G/G genotypes compared to the control group G/G genotypes presented significantly higher severity of personality dimension “conscientiousness”. In comparison with the controls, the case group subjects had significantly higher scores in the dimension extraversion (M 6.89 vs. M 6.43, p = 0.0405) and conscientiousness/scale (M 7.23 vs. M 5.89, p < 0.0001). The results of 2 × 3 factorial ANOVA noticed a statistically significant effect of combined factor BDNF rs6265 genotype of martial arts/control (F2,252 = 3.11, p = 0.0465, η2 = 0.024). Additionally, we observed that the results of 2 × 3 factorial ANOVA showed a statistically significant influence of combined factor BDNF rs6265 of genotype martial arts/ control (F2,252 = 6.16, p = 0.0024, η2 = 0.047). The combination of the analysis of personality dimensions with genetics—as in the case of the polymorphism of the BDNF gene related to neuroplasticity—indicates that neurobiology cannot be ignored in educating sports champions. We already know that this is related to genetics. However, little is still known about the influence of personality traits on sports performance. We observed that martial arts athletes’ G/G genotypes, in comparison to the control group’s G/G genotypes, presented significantly higher severity of personality dimension “conscientiousness”. This is worthy of further analysis and probably longitudinal studies on a more numerous group of athletes.

Upper Airway Dysfunction and Discoordination are Reversed by Isometric Tongue Exercise in a Novel Rodent Model of Hypoglossal Motor Neuron Loss

Motor neuron diseases (e.g., amyotrophic lateral sclerosis, pseudobulbar palsy, and Kennedy’s disease) result in life‐threatening alterations in upper airway function (i.e., swallowing and breathing) primarily due to degeneration of hypoglossal (XII) motor neurons, which leads to ventilator and/or feeding‐tube dependence. Despite its critical importance, upper airway function has seldom been studied in motor neuron diseases; thus, effective treatments remain to be discovered. Since genetic rodent models of motor neuron loss develop global symptoms (e.g., limb dysfunction, etc.), we have developed an inducible model of only XII motor neuron death in order to study targeted therapeutic interventions to enhance the functional capacity of spared XII motor neurons to improve functional outcomes. We have previously found that adult male rats intralingually injected with cholera toxin B conjugated to saporin (CTB‐SAP) have XII motor neuron loss and decreased XII motor output, degenerative changes in the XII nerve and genioglossus, and decreased tongue motility and swallowing rate. We hypothesize that deficits in upper airway function and coordination are reversed by using a translational, non‐invasive therapeutic strategy of tongue resistance exercise training in CTB‐SAP rats. To test our hypothesis, we intralingually injected adult male rats with CTB‐SAP or control (CTB unconjugated to SAP), and then studied the following parameters +/‐ isometric tongue exercise (n=3‐7/group): 1) swallowing function via videofluoroscopic swallow studies and force lickometer testing; 2) breathing function via whole‐body plethysmography; 3) XII motor output at baseline and in response to a maximal ventilatory challenge in anesthetized and ventilated rats via in vivo neurophysiology; 4) coordination of swallowing and breathing in anesthetized rats via evoked swallowing electrophysiological recordings; and 5) structural changes via magnetic resonance imaging. Thus far, our data suggests that tongue exercise in CTB‐SAP treated rats remarkably preserves tongue strength and motility and swallowing and breathing patterns/coordination, and reduces structural degeneration in the brainstem and tongue (p&lt;0.05 vs. controls). In conclusion, tongue exercise appears to preserve upper airway function and coordination in the face of XII motor neuron degeneration. Studies are now underway to understand the underlying mechanism of tongue exercise‐induced neuroplasticity in spared XII motor neurons. If successful, this work will identify behavioral (tongue exercise) and molecular strategies for future translational studies to prolong and/or improve upper airway function and coordination in patients with motor neuron diseases to significantly improve their quality and duration of life.

Abstract TP13: Beneficial Effects Of Exercise On Functional Outcome After Ischemic Stroke: A New Insight On Astrocytes Activation And Cellular Crosstalk

Introduction: It has been recognized that astrocytes potentially affect the recruitment and function of neurons, and the interactions among astrocytes, microglia and neurons modulate neuroplasticity and neural circuit function. The present study attempted to explore whether astrocytes activation and cellular crosstalk were involved in neuroplasticity and neurorehabilitation. Methods: Sprague-Dawley adult rats were subjected to 2 h middle cerebral artery occlusion followed by reperfusion. Treadmill exercise (15m/min) was initiated 24 h after reperfusion for up to 21 days. Rats were assigned to groups entailing post-stroke rest or exercise for 30 min. Motor and cognitive functions were tracked. Western blotting was used to assess the proteins expression for neuroplasticity, including GAP-43, PSD-95 and BDNF. Immunofluorescence was used to assess astrocyte proliferation. Primary cells co-cultivation were used to determine the interaction of astrocyte and microglia by IL-33/ST2 interplays, and interaction of microglia and neuron by BDNF/TrkB interplays. The interactions affected by exercise were detected by Co-IP in ischemic rats. Besides, D-serine release by ELISA and NMDAR receptor expression were used to assess astrocyte-neuron direct communication. Results: Physical exercise significantly induce neuroplasticity and functional outcomes in ischemic rats, in association with astrocyte proliferation. Exercise induced IL-33/ST2 and BDNF/TrkB interplays in rats, suggesting the increasing astrocyte-microglia and microglia-neuron crosstalk. Exercise significantly increase astrocyte D-serine release and neural NMDAR expression, indicating the direct crosstalk in astrocyte and neuron. Primary cells co-cultivation further demonstrated the IL-33/ST2 interplays showing astrocyte-microglia crosstalk and BDNF/TrkB interplays showing microglia-neuron communication. Conclusion: These findings indicated beneficial effects of long-term treadmill exercise on neuroplasticity and functional outcome. Importantly, the results showed astrocyte activation and interaction with microglia and neuron in the biochemical processes underlying the exercise-induced post-stroke neuroplasticity and neurorehabilitation.

Abstract TP2: Rehabilitative Effects Of Exercise Pattens On Functional Outcome After Ischemic Stroke

Introduction: Although physical exercise has been demonstrated to augment recovery of the post-stroke brain, how exercise patten optimizes neurological outcomes post-stroke remains to be determined. Forced exercise containing a stressful component is reported to be better than voluntary exercise on functional recovery. The present study attempted to explore a suitable exercise patten for better functional recovery and stronger neuroplasticity. Methods: Sprague-Dawley adult rats were subjected to 2 h middle cerebral artery occlusion followed by reperfusion. Treadmill exercise (15m/min) was initiated 24 hours after reperfusion for up to 21 days. Rats were assigned to a control group entailing post-stroke rest or three exercise groups: 1) exercise 5 min and rest 5 min for 6 cycles (E5), exercise 10 min and rest 10 min for 3 cycles (E10), and exercise for 30 min without rest for 1 cycle (E30). Infarct volume was determined by TTC after 48 h. Motor and cognitive functions were tracked. Western blotting was used to assess the proteins expression for neuroplasticity, including GAP-43, PSD-95, synapsin I, and BDNF. Levels of corticosterone were measured using ELISA. Changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR. Results: E30 but not E5 and E10 exercise models reduced brain infarct. All the exercise protocols significantly induced neuroplasticity and functional outcomes in ischemic rats, with E30 being most effective on the neuroplasticity and neurorehabilitation. A significant increase in corticosterone level in E30 were observed, indicating physical stress endurance may actually lead to a decrease in the resultant damage to the brain after an ischemic attack. mRNA expression of Hsp 27 and 70 were increased in E30, suggesting increasing response to physical stress in terms of the protection against cerebral ischemia. Conclusion: These findings contribute to the growing body of literature regarding the positive effects of long-term treadmill exercise on neuroplasticity and functional outcome. Additionally, the results suggested that physical stress played a role in the biochemical processes underlying exercise-induced post-stroke neuroplasticity.

Transcranial Magnetic Stimulation to Assess Exercise-Induced Neuroplasticity.

Aerobic exercise facilitates neuroplasticity and has been linked to improvements in cognitive and motor function. Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to quantify changes in neurophysiology induced by exercise. The present review summarizes the single- and paired-pulse TMS paradigms that can be used to probe exercise-induced neuroplasticity, the optimal stimulation parameters and the current understanding of the neurophysiology underlying each paradigm. Further, this review amalgamates previous research exploring the modulation of these paradigms with exercise-induced neuroplasticity in healthy and clinical populations and highlights important considerations for future TMS-exercise research.

Effects of physical exercise on the aging brain across imaging modalities: A meta-analysis of neuroimaging studies in randomized controlled trials.

Physical exercise is effective in protecting against age-related neurodegeneration and cognitive decline. Although there are many neuroimaging studies to evaluate the effect of physical exercise on aging brains, consistent conclusions are limited due to the wide variety of measuring techniques and small sample sizes. Identify brain regions that show exercise-induced neuroplasticity consistently across various imaging modalities and correlate regional neuroplasticity with cognitive changes in older adults. An electronic literature search for randomized controlled trials with magnetic resonance imaging measures was performed. We conducted a series of quantitative meta-analyses using activation likelihood estimation on included studies with voxel-based neuroimaging findings. Nonvoxelbased findings were summarized as a descriptive review. Out of 839 publications identified from the literature search, 30 experiments including 2670 participants from 22 papers met the criteria of meta-analyses. Overall, physical exercise consistently results in structural and functional changes in the hippocampus/parahippocampusl area and a cluster within the cerebellum. Although changes of medial/superior prefrontal cortex did not pass the stringent threshold, they were associated with cognitive changes. This study highlights the effectiveness of physical exercise in inducing hippocampus plasticity, which may be crucially relevant for maintaining memory function in older adults.

Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice.

Background:Despite considerable research on exercise-induced neuroplasticity in the brain, a major ongoing challenge in translating findings from animal studies to humans is that clinical and preclinical settings employ very different techniques.Objective:Here we aim to bridge this divide by using diffusion tensor imaging MRI (DTI), an advanced imaging technique commonly applied in human studies, in a longitudinal exercise study with mice.Methods:Wild-type mice were exercised using voluntary free-wheel running, and MRI scans were at baseline and after four weeks and nine weeks of running.Results:Both hippocampal volume and fractional anisotropy, a surrogate for microstructural directionality, significantly increased with exercise. In addition, exercise levels correlated with effect size. Histological analysis showed more PDGFRα+ oligodendrocyte precursor cells in the corpus callosum of running mice.Conclusions:These results provide compelling in vivo support for the concept that similar adaptive changes occur in the brains of mice and humans in response to exercise.

Exercise-induced changes in brain activity during memory encoding and retrieval after long-term bed rest

Episodic memory depends decisively on the hippocampus and the parahippocampal gyrus, brain structures that are also prone to exercise-induced neuroplasticity and cognitive improvement. We conducted a randomized controlled trial to investigate the effects of a high-intensity exercise program in twenty-two men resting in bed for 60 days on episodic memory and its neuronal basis. All participants were exposed to 60 days of uninterrupted bed rest. Eleven participants were additionally assigned to a high-intensity interval training that was performed five to six times weekly for 60 days. Episodic memory and its neural basis were determined four days prior to and on the 58th day of bed rest using functional magnetic resonance imaging (fMRI). We found increased BOLD signal in the left hippocampus and parahippocampal gyrus in the non-exercising group compared to the exercising bed rest group whereas the mnemonic performance did not differ significantly. These findings indicate a higher neuronal efficiency in the training group during memory encoding and retrieval and may suggest a dysfunctional mechanism in the non-exercising bed rest group induced by two months of physical inactivity. Our results provide further support for the modulating effects of physical exercise and adverse implications of a sedentary lifestyle and bedridden patients.

A Review of Exercise-Induced Neuroplasticity in Ischemic Stroke: Pathology and Mechanisms.

After ischemic stroke, survivors experience motor dysfunction and deterioration of memory and cognition. These symptoms are associated with the disruption of normal neuronal function, i.e., the secretion of neurotrophic factors, interhemispheric connections, and synaptic activity, and hence the disruption of the normal neural circuit. Exercise is considered an effective and feasible rehabilitation strategy for improving cognitive and motor recovery following ischemic stroke through the facilitation of neuroplasticity. In this review, our aim was to discuss the mechanisms by which exercise-induced neuroplasticity improves motor function and cognitive ability after ischemic stroke. The associated mechanisms include increases in neurotrophins, improvements in synaptic structure and function, the enhancement of interhemispheric connections, the promotion of neural regeneration, the acceleration of neural function reorganization, and the facilitation of compensation beyond the infarcted tissue. We also discuss some common exercise strategies and a novel exercise therapy, robot-assisted movement, which might be widely applied in the clinic to help stroke patients in the future.

Medial temporal lobe cortical changes in response to exercise interventions in people with early psychosis: A randomized controlled trial

ObjectiveIndividuals with early psychosis may have prefrontal-limbic cortical deficits, which are associated with symptom severity and cognitive impairment. This study investigated the impact of an exercise intervention on fronto-temporal cortical plasticity in female participants with early psychosis. MethodsIn a cohort of 51 female participants with early psychosis from Hong Kong, we investigated the effects of a 12-week, moderate intensity aerobic or Hatha yoga exercise trial (yoga (N = 21), aerobic (N = 18) or waitlist group (N = 12)) on cortical grey matter. Clinical assessments and structural MRI were completed pre- and post- a 12-week exercise intervention. ResultsIncreases in cortical volume and thickness were observed in the medial temporal cortical regions, primarily in fusiform cortical thickness (F(2, 48) = 4.221, p = 0.020, η2 = 0.150) and volume (F(2, 48) = 3.521, p = 0.037, η2 = 0.128) for participants with early psychosis in the aerobic arm, but not in the yoga and waitlist arms. Increased fusiform cortical thickness (ß = 0.402, p = 0.003) was associated with increased hippocampal volume for all psychosis participants. For the aerobic group only, increases in the entorhinal and fusiform temporal gyri were associated with reduced symptom severity. ConclusionsThese findings suggest exercise-induced neuroplasticity in medial temporal cortical regions occurs with aerobic exercise. These changes may be associated with improvements in psychosis symptom severity. People with early psychosis may benefit from exercise interventions, particularly aerobic exercise, as an adjunct treatment to address clinical, physical health, and neuroanatomic concerns.NIH National Library of Medicine ClinicalTrials.gov Registration #: NCT01207219https://clinicaltrials.gov/ct2/show/NCT01207219

A Single Bout of High-intensity Interval Exercise Increases Corticospinal Excitability, Brain-derived Neurotrophic Factor, and Uncarboxylated Osteolcalcin in Sedentary, Healthy Males

Exercise induces neuroplasticity in descending motor pathways facilitating motor learning, and as such it could be utilized as an intervention in neurorehabilitation, for example when re-learning motor skills after stroke. To date, however, the neurophysiological and molecular mechanisms underlying exercise-induced neuroplasticity remain largely unknown impeding the potential utilization of exercise protocols as ‘motor learning boosters’ in clinical and non-clinical settings. Here, we assessed corticospinal excitability, intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS) and serum biochemical markers including brain-derived neurotrophic factor (BDNF), total and precursor cathepsin B (tCTSB, proCTSB), uncarboxylated and carboxylated osteocalcin (unOCN, cOCN) and irisin using ELISA. Measurements were carried out in sedentary, healthy males before and after a single session of high-intensity interval exercise (HIIE) or in individuals who rested and did not perform exercise (No Exercise). We found that HIIE increased corticospinal excitability, BDNF and unOCN, and decreased cOCN. We also determined that greater increases in BDNF were associated with increases in unOCN and irisin and decreases in cOCN only in participants who underwent HIIE, suggesting that unOCN and irisin may contribute to exercise-induced BDNF increases. Conversely, no changes other than a decrease in serum unOCN/tOCN were found in No Exercise participants. The present findings show that a single session of HIIE is sufficient to modulate corticospinal excitability and to increase BDNF and unOCN in sedentary, healthy males.

Exercise-Induced Brain Excitability Changes in Progressive Multiple Sclerosis: A Pilot Study.

Even a single bout of aerobic exercise (AE) enhances corticospinal excitability (CSE), a biomarker of neuroplasticity. Because neurodegeneration limits capacity for neuroplasticity, it is not clear whether AE would induce CSE changes in people with progressive multiple sclerosis (MS). People with progressive MS (n = 10) requiring ambulatory assistive devices completed a graded maximal exercise test. Dual-energy x-ray absorptiometry was used to quantify body fat and lean mass. Before and following one 40-minute AE session using body weight-supported (<10% support) treadmill at moderate intensity, CSE was measured using transcranial magnetic stimulation. Variables included resting and active motor thresholds, motor evoked potential (MEP) amplitudes, recruitment curves, and length of the cortical silent period (CSP). Aerobic exercise reduced inhibition (shorter CSP) and increased excitation (increased MEP amplitude) only in the hemisphere corresponding to the stronger hand. Controlling for age, higher fitness and lower body fat significantly predicted exercise-induced reduction in resting motor threshold (ΔR = +0.458, P = 0.046) and CSP (ΔR = +0.568, P = 0.030), respectively. Despite high levels of disability, capacity for exercise-induced neuroplasticity was retained among people with progressive MS. The hemisphere contralateral to the weaker hand was resistant to exercise-induced CSE changes, suggesting less neuroplastic potential. Lower fitness and higher body fat were associated with diminished exercise-induced CSE benefits, suggesting that therapists should consider interventions aimed at improving fitness and combating sedentarism to ultimately enhance the benefits of exercise on the brain.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A302).

Feasibility Aspects of Exploring Exercise-Induced Neuroplasticity in Parkinson's Disease: A Pilot Randomized Controlled Trial.

Background Recent studies indicate that exercise can induce neuroplastic changes in people with Parkinson's disease (PwPD). Reports of feasibility outcomes from existing pilot trials however are, of date, insufficient to enable replication by others in larger definitive trials. Objective To evaluate trial design for a definitive trial by exploring process and scientific feasibility. Methods The trial design was a parallel-group RCT pilot with a 1 : 1 allocation ratio to either HiBalance or an active control group (HiCommunication). Both groups received one-hour sessions twice weekly, plus home exercises weekly, for 10 weeks. Participants with mild-to-moderate Parkinson's disease (PD) were recruited via advertisement. Assessment included physical performance, structural and functional MRI, blood sampling, neuropsychological assessment, and speech/voice assessment. Process and scientific feasibility were monitored throughout the study. Process feasibility involved recruitment, participant acceptability of assessments and interventions, assessment procedures (focus on imaging, blood sampling, and dual-task gait analysis), and blinding procedures. Scientific feasibility involved trends in outcome response and safety during group training and home exercises. Data are presented in median, minimum, and maximum values. Changes from pre- to postintervention are reported descriptively. Results Thirteen participants were included (4 women, mean age 69.7 years), with a recruitment rate of 31%. Attendance rates and follow-up questionnaires indicated that both groups were acceptable to participate. Image quality was acceptable; however, diplopia and/or sleepiness were observed in several participants during MRI. With regard to dual-task gait performance, there appeared to be a ceiling effect of the cognitive tasks with seven participants scoring all correct answers at pretest. Blinding of group allocation was successful for one assessor but was broken for half of participants for the other. Conclusions The overall trial design proved feasible to perform, but further strengthening ahead of the definitive RCT is recommended, specifically with respect to MRI setup, cognitive dual-tasks during gait, and blinding procedures. This trial is registered with NCT03213873.