Exercise-Induced Neuroplasticity: A Mechanistic Model and Prospects for Promoting Plasticity

Aerobic exercise improves cognitive and motor function by inducing neural changes detected using molecular, cellular, and systems level neuroscience techniques. This review unifies the knowledge gained across various neuroscience techniques to provide a comprehensive profile of the neural mechanisms that mediate exercise-induced neuroplasticity. Using a model of exercise-induced neuroplasticity, this review emphasizes the sequence of neural events that accompany exercise, and ultimately promote changes in human performance. This is achieved by differentiating between neuroplasticity induced by acute versus chronic aerobic exercise. Furthermore, this review emphasizes experimental considerations that influence the opportunity to observe exercise-induced neuroplasticity in humans. These include modifiable factors associated with the exercise intervention and nonmodifiable factors such as biological sex, ovarian hormones, genetic variations, and fitness level. To maximize the beneficial effects of exercise in health, disease, and following injury, future research should continue to explore the mechanisms that mediate exercise-induced neuroplasticity. This review identifies some fundamental gaps in knowledge that may serve to guide future research in this area.

[1]  L. Nifong,et al.  Angiogenic growth factor response to acute systemic exercise in human skeletal muscle. , 2004, Journal of applied physiology.

[2]  L. Boyd,et al.  The Effect of an Acute Bout of Moderate-Intensity Aerobic Exercise on Motor Learning of a Continuous Tracking Task , 2016, PloS one.

[3]  Raymond M. Kraus,et al.  Circulating plasma VEGF response to exercise in sedentary and endurance-trained men. , 2004, Journal of applied physiology.

[4]  Tao Huang,et al.  The effects of physical activity and exercise on brain‐derived neurotrophic factor in healthy humans: A review , 2014, Scandinavian journal of medicine & science in sports.

[5]  J. Krieger,et al.  Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism. , 2016, Physiological genomics.

[6]  D. Voskuil,et al.  Determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1–3 in premenopausal women: physical activity and anthropometry (Netherlands) , 2001, Cancer Causes & Control.

[7]  A. Nevill,et al.  Cardio-respiratory fitness, habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women , 2009, Neuroscience Letters.

[8]  Scott M. Hayes,et al.  A review of cardiorespiratory fitness-related neuroplasticity in the aging brain , 2013, Front. Aging Neurosci..

[9]  Chun-Hao Wang,et al.  Effects of acute aerobic exercise on a task‐switching protocol and brain‐derived neurotrophic factor concentrations in young adults with different levels of cardiorespiratory fitness , 2016, Experimental physiology.

[10]  Jinsoo Uh,et al.  Masters athletes exhibit larger regional brain volume and better cognitive performance than sedentary older adults , 2013, Journal of magnetic resonance imaging : JMRI.

[11]  A. Swartz,et al.  A positive association between active lifestyle and hemispheric lateralization for motor control and learning in older adults , 2016, Behavioural Brain Research.

[12]  Edward McAuley,et al.  The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one‐year exercise intervention , 2013, Human brain mapping.

[13]  I. Torres-Aleman,et al.  Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus , 2001, The Journal of Neuroscience.

[14]  E. McAuley,et al.  Exercise training increases size of hippocampus and improves memory , 2011, Proceedings of the National Academy of Sciences.

[15]  Helgi B. Schiöth,et al.  Association between physical activity and brain health in older adults , 2013, Neurobiology of Aging.

[16]  James P. Coxon,et al.  High-intensity Interval Exercise Promotes Motor Cortex Disinhibition and Early Motor Skill Consolidation , 2017, Journal of Cognitive Neuroscience.

[17]  G. Yancopoulos,et al.  A BDNF autocrine loop in adult sensory neurons prevents cell death , 1995, Nature.

[18]  F. Gage,et al.  IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes , 2004, The Journal of cell biology.

[19]  A. Kramer,et al.  Fitness Effects on the Cognitive Function of Older Adults , 2003, Psychological science.

[20]  Walter Paulus,et al.  Sex differences in cortical neuroplasticity in humans , 2006, Neuroreport.

[21]  K. Rockwood,et al.  Prevention of CIND by physical activity: Different impact on VCI-ND compared with MCI , 2008, Journal of the Neurological Sciences.

[22]  I. Torres-Aleman,et al.  Insulin-like growth factor I is required for vessel remodeling in the adult brain. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  S. Schulte,et al.  Effects of strength and endurance training on brain-derived neurotrophic factor and insulin-like growth factor 1 in humans. , 2009, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[24]  James S. Williams,et al.  The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. , 2007, Medicine and science in sports and exercise.

[25]  H. Koistinen,et al.  Effect of marathon run on serum IGF-I and IGF-binding protein 1 and 3 levels. , 1996, Journal of applied physiology.

[26]  Arthur F. Kramer,et al.  Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults , 2012, Journal of aging research.

[27]  L. Galea,et al.  Personalising exercise recommendations for brain health: considerations and future directions , 2016, British Journal of Sports Medicine.

[28]  H. Kyröläinen,et al.  Physical Fitness and Hormonal Profile During an 11-Week Paratroop Training Period , 2015, Journal of Strength and Conditioning Research.

[29]  Keith M. McGregor,et al.  Physical activity and neural correlates of aging: A combined TMS/fMRI study , 2011, Behavioural Brain Research.

[30]  O. Güntürkün,et al.  Transcallosal inhibition across the menstrual cycle: A TMS study , 2006, Clinical Neurophysiology.

[31]  J. García-Verdugo,et al.  IGF‐I stimulates neurogenesis in the hypothalamus of adult rats , 2010, The European journal of neuroscience.

[32]  H. Scharfman,et al.  Brain-derived neurotrophic factor. , 2004, Growth factors.

[33]  Tad T. Brunyé,et al.  Acute exercise increases oxygenated and deoxygenated hemoglobin in the prefrontal cortex , 2014, Neuroreport.

[34]  W. Freeman,et al.  Insulin-like growth factor-1 in CNS and cerebrovascular aging , 2013, Front. Aging Neurosci..

[35]  Feliberto de la Cruz,et al.  Changes in fMRI activation in anterior hippocampus and motor cortex during memory retrieval after an intense exercise intervention , 2017, Biological Psychology.

[36]  Agnieszka Z. Burzynska,et al.  Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults , 2015, Front. Aging Neurosci..

[37]  Steven A. Goldman,et al.  Coordinated Interaction of Neurogenesis and Angiogenesis in the Adult Songbird Brain , 2002, Neuron.

[38]  A. Kramer,et al.  Exercise, brain, and cognition across the life span. , 2011, Journal of applied physiology.

[39]  J. Shoemaker,et al.  Impact of Long-Term Endurance Training vs. Guideline-Based Physical Activity on Brain Structure in Healthy Aging , 2016, Front. Aging Neurosci..

[40]  Christopher J. Marley,et al.  Acute Exercise Stress Reveals Cerebrovascular Benefits Associated with Moderate Gains in Cardiorespiratory Fitness , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  E. McAuley,et al.  Aerobic fitness is associated with hippocampal volume in elderly humans , 2009, Hippocampus.

[42]  Thomas E. Nichols,et al.  An Ultra-High Field Magnetic Resonance Spectroscopy Study of Post Exercise Lactate, Glutamate and Glutamine Change in the Human Brain , 2015, Front. Physiol..

[43]  V. Brümmer,et al.  Changes in brain cortical activity measured by EEG are related to individual exercise preferences , 2009, Physiology & Behavior.

[44]  Kirk I. Erickson,et al.  Physical activity, fitness, and gray matter volume , 2014, Neurobiology of Aging.

[45]  J. Morys,et al.  BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity , 2017, Cellular and Molecular Neurobiology.

[46]  W. McIlroy,et al.  Impact of a Single Bout of Aerobic Exercise on Regional Brain Perfusion and Activation Responses in Healthy Young Adults , 2014, PloS one.

[47]  B Villiger,et al.  Increase in immune activation, vascular endothelial growth factor and erythropoietin after an ultramarathon run at moderate altitude. , 2000, Immunobiology.

[48]  Kathy A. Low,et al.  Cardiorespiratory fitness mediates the effects of aging on cerebral blood flow , 2014, Front. Aging Neurosci..

[49]  S. Cramer,et al.  BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex , 2006, Nature Neuroscience.

[50]  Nick S. Ward,et al.  Beta oscillations reflect changes in motor cortex inhibition in healthy ageing , 2014, NeuroImage.

[51]  Jeffrey S. Spence,et al.  Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging , 2013, Front. Aging Neurosci..

[52]  P. Ye,et al.  In vivo actions of insulin-like growth factor-I (IGF-I) on brain myelination: studies of IGF-I and IGF binding protein-1 (IGFBP-1) transgenic mice , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  Shane M. O'Mara,et al.  Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males , 2011, Physiology & Behavior.

[54]  C. Zinner,et al.  Effects of acid–base balance and high or low intensity exercise on VEGF and bFGF , 2011, European Journal of Applied Physiology.

[55]  Caterina Pesce,et al.  Antecedent acute cycling exercise affects attention control: an ERP study using attention network test , 2015, Front. Hum. Neurosci..

[56]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. , 1993, Neuron.

[57]  I. Torres-Aleman,et al.  Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects , 2007, Molecular Psychiatry.

[58]  L. Boyd,et al.  Exploring genetic influences underlying acute aerobic exercise effects on motor learning , 2017, Scientific Reports.

[59]  Kirk I. Erickson,et al.  Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis , 2016, Front. Hum. Neurosci..

[60]  Steven C Cramer,et al.  Genetic Influences on Neural Plasticity , 2010, PM & R : the journal of injury, function, and rehabilitation.

[61]  E. McAuley,et al.  Functional connectivity: A source of variance in the association between cardiorespiratory fitness and cognition? , 2010, Neuropsychologia.

[62]  A. Rouzi,et al.  Physical activity in relation to serum sclerostin, insulin-like growth factor-1, and bone turnover markers in healthy premenopausal women: a cross-sectional and a longitudinal study. , 2012, The Journal of clinical endocrinology and metabolism.

[63]  Bijli Nanda,et al.  The Acute Effects of a Single Bout of Moderate-intensity Aerobic Exercise on Cognitive Functions in Healthy Adult Males. , 2013, Journal of clinical and diagnostic research : JCDR.

[64]  M. Falkenstein,et al.  Lifelong physical activity and executive functions in older age assessed by memory based task switching , 2015, Neuropsychologia.

[65]  A Berardelli,et al.  Ovarian hormones and cortical excitability. An rTMS study in humans , 2004, Clinical Neurophysiology.

[66]  D. Rubinow,et al.  Effects of ovarian hormones on human cortical excitability , 2002, Annals of neurology.

[67]  H. Fukuyama,et al.  Brain functional activity during gait in normal subjects: a SPECT study , 1997, Neuroscience Letters.

[68]  J. Polich,et al.  P300 topography and modality effects from a single-stimulus paradigm. , 1996, Psychophysiology.

[69]  Heather Carnahan,et al.  EEG activity and mood in health orientated runners after different exercise intensities , 2009, Physiology & Behavior.

[70]  M. Higuchi,et al.  18F-FDG PET mapping of regional brain activity in runners. , 2001, The Journal of sports medicine and physical fitness.

[71]  Henriette van Praag,et al.  Neurogenesis and Exercise: Past and Future Directions , 2008, NeuroMolecular Medicine.

[72]  Kathy A. Low,et al.  Comparing Aging and Fitness Effects on Brain Anatomy , 2016, Front. Hum. Neurosci..

[73]  I. Torres-Aleman,et al.  Trophic effects of basic fibroblast growth factor on fetal rat hypothalamic cells: interactions with insulin-like growth factor I. , 1990, Brain research. Developmental brain research.

[74]  J. Bülow,et al.  Growth hormone enhances effects of endurance training on oxidative muscle metabolism in elderly women. , 2000, American journal of physiology. Endocrinology and metabolism.

[75]  Jie Li,et al.  Cerebral angiogenesis and expression of angiogenic factors in aging rats after exercise. , 2006, Current neurovascular research.

[76]  Heidi Johansen-Berg,et al.  A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain , 2016, NeuroImage.

[77]  Paige E. Scalf,et al.  Aerobic exercise training increases brain volume in aging humans. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[78]  L. Middleton,et al.  Multiple sclerosis in Cyprus , 1991, Journal of the Neurological Sciences.

[79]  Chobok Kim,et al.  Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors , 2012, NeuroImage.

[80]  M. Hampson,et al.  A single session of exercise increases connectivity in sensorimotor-related brain networks: a resting-state fMRI study in young healthy adults , 2014, Front. Hum. Neurosci..

[81]  S. Mohan,et al.  Effect of brief exercise on circulating insulin-like growth factor I. , 1994, Journal of applied physiology.

[82]  Carl W. Cotman,et al.  Exercise builds brain health: key roles of growth factor cascades and inflammation , 2007, Trends in Neurosciences.

[83]  A. Benraiss,et al.  Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain , 2001, The Journal of Neuroscience.

[84]  Arthur F. Kramer,et al.  Physical Activity and Cardiorespiratory Fitness Are Beneficial for White Matter in Low-Fit Older Adults , 2014, PloS one.

[85]  Arthur F. Kramer,et al.  White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults , 2016, NeuroImage.

[86]  W. Klimesch.  Alpha-band oscillations, attention, and controlled access to stored information , 2012, Trends in Cognitive Sciences.

[87]  M. Ridding,et al.  Determinants of the induction of cortical plasticity by non‐invasive brain stimulation in healthy subjects , 2010, The Journal of physiology.

[88]  M. Schmolesky,et al.  The effects of aerobic exercise intensity and duration on levels of brain-derived neurotrophic factor in healthy men. , 2013, Journal of sports science & medicine.

[89]  Arthur F. Kramer,et al.  BDNF mediates improvements in executive function following a 1-year exercise intervention , 2014, Front. Hum. Neurosci..

[90]  H. Langberg,et al.  Physical capacity influences the response of insulin-like growth factor and its binding proteins to training. , 2002, Journal of applied physiology.

[91]  Wildor Hollmann,et al.  Effects of Physical Exercise on Individual Resting State EEG Alpha Peak Frequency , 2015, Neural plasticity.

[92]  D. Landers,et al.  Motor performance and motor learning as a function of age and fitness. , 1998, Research quarterly for exercise and sport.

[93]  Peiying Liu,et al.  Life‐long aerobic exercise preserved baseline cerebral blood flow but reduced vascular reactivity to CO2 , 2013, Journal of magnetic resonance imaging : JMRI.

[94]  A. McTiernan,et al.  Effect of a 12-Month Exercise Intervention on Serum Biomarkers of Angiogenesis in Postmenopausal Women: A Randomized Controlled Trial , 2014, Cancer Epidemiology, Biomarkers & Prevention.

[95]  K. Jin,et al.  Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[96]  Katherine Reiter,et al.  Exercise Training and Functional Connectivity Changes in Mild Cognitive Impairment and Healthy Elders. , 2017, Journal of Alzheimer's disease : JAD.

[97]  C. Ritz,et al.  Acute Exercise and Motor Memory Consolidation: The Role of Exercise Timing , 2016, Neural plasticity.

[98]  J. Kaiser,et al.  Kinetics of serum brain-derived neurotrophic factor following low-intensity versus high-intensity exercise in men and women , 2012, Neuroreport.

[99]  T. Liu-Ambrose,et al.  Sex differences in exercise efficacy to improve cognition: A systematic review and meta-analysis of randomized controlled trials in older humans , 2017, Frontiers in Neuroendocrinology.

[100]  R. Maddock,et al.  Acute Modulation of Cortical Glutamate and GABA Content by Physical Activity , 2016, The Journal of Neuroscience.

[101]  J. Zoladz,et al.  Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[102]  K. Cosgrove,et al.  Evolving Knowledge of Sex Differences in Brain Structure, Function, and Chemistry , 2007, Biological Psychiatry.

[103]  G. Sorrentino,et al.  Biological Mechanisms of Physical Activity in Preventing Cognitive Decline , 2010, Cellular and Molecular Neurobiology.

[104]  M. Otto,et al.  A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. , 2015, Journal of psychiatric research.

[105]  J. Mitchell,et al.  Activation of the insular cortex is affected by the intensity of exercise. , 1999, Journal of applied physiology.

[106]  B. McEwen,et al.  Ovarian steroids and the brain , 1997, Neurology.

[107]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in tTransgenic mice , 1993, Neuron.

[108]  L. J. Peacock,et al.  Does body temperature mediate anxiolytic effects of acute exercise? , 1993, Journal of applied physiology.

[109]  Arthur F. Kramer,et al.  Physical Activity and Executive Control: Implications for Increased Cognitive Health during Older Adulthood , 2004, Research quarterly for exercise and sport.

[110]  B. Greenberg,et al.  Menstrual cycle effects on cortical excitability , 1999, Neurology.

[111]  Anne B. Newman,et al.  Cardiorespiratory fitness and brain diffusion tensor imaging in adults over 80 years of age , 2014, Brain Research.

[112]  J. Benson,et al.  BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABAA receptor surface expression , 2001, The European journal of neuroscience.

[113]  P. Rodríguez,et al.  BDNF val66met polymorphism influences motor system function in the human brain. , 2010, Cerebral cortex.

[114]  Arthur F. Kramer,et al.  Human Neuroscience , 2022 .

[115]  Marc Roig,et al.  A Single Bout of Exercise Improves Motor Memory , 2012, PloS one.

[116]  R. Ophoff,et al.  The association of sleep and physical activity with integrity of white matter microstructure in bipolar disorder patients and healthy controls , 2017, Psychiatry Research: Neuroimaging.

[117]  A. Baiker,et al.  VEGF is necessary for exercise‐induced adult hippocampal neurogenesis , 2003, The European journal of neuroscience.

[118]  D. Cook,et al.  Detecting changes in human cerebral blood flow after acute exercise using arterial spin labeling: Implications for fMRI , 2010, Journal of Neuroscience Methods.

[119]  Vanesa Nieto-Estévez,et al.  IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain , 2016, Front. Neurosci..

[120]  L. Boyd,et al.  Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits , 2016, Neural plasticity.

[121]  A. Pearce,et al.  What has transcranial magnetic stimulation taught us about neural adaptations to strength training? A brief review. , 2011, Journal of strength and conditioning research.

[122]  Ben Godde,et al.  Human Neuroscience , 2009 .

[123]  Xia Shen,et al.  Long-term effects of exercise and physical therapy in people with Parkinson disease , 2017, Nature Reviews Neurology.

[124]  Arthur F. Kramer,et al.  Neurobiological markers of exercise-related brain plasticity in older adults , 2013, Brain, Behavior, and Immunity.

[125]  G. Jahreis,et al.  Effect of endurance exercise on somatomedin-C/insulin-like growth factor I concentration in male and female runners. , 2009, Experimental and clinical endocrinology.

[126]  Stanley J. Wiegand,et al.  Intraventricular Administration of BDNF Increases the Number of Newly Generated Neurons in the Adult Olfactory Bulb , 1998, Molecular and Cellular Neuroscience.

[127]  J. Przybylski,et al.  The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise. , 2006, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[128]  Richard J. Maddock,et al.  Vigorous exercise increases brain lactate and Glx (glutamate+glutamine): A dynamic 1H-MRS study , 2011, NeuroImage.

[129]  Meigen Liu,et al.  Effects of pedaling exercise on the intracortical inhibition of cortical leg area , 2012, Experimental Brain Research.

[130]  B. Johannes,et al.  Vascular endothelial growth factor in exercising humans under different environmental conditions , 1999, European Journal of Applied Physiology and Occupational Physiology.

[131]  L. Banks,et al.  The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events. , 2016, The Canadian journal of cardiology.

[132]  P. Celnik,et al.  A Single Bout of Moderate Aerobic Exercise Improves Motor Skill Acquisition , 2015, PloS one.

[133]  N. Cohen,et al.  Aerobic fitness reduces brain tissue loss in aging humans. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[134]  H. Johansen-Berg,et al.  The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity , 2015, Brain Stimulation.

[135]  A. Genazzani,et al.  Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. , 2007, Human reproduction.

[136]  J. Flory,et al.  Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults. , 2000, American journal of medical genetics.

[137]  Y. Tzeng,et al.  Post-stroke recovery: the role of activity-dependent release of brain-derived neurotrophic factor , 2014, Expert review of neurotherapeutics.

[138]  F. Lee,et al.  Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice , 2016, Neuropsychopharmacology.

[139]  M. Beyazova,et al.  The effect of a single session submaximal aerobic exercise on premotor fraction of reaction time: an electromyographic study. , 2008, Clinical biomechanics.

[140]  D. Bucci,et al.  Differential effects of acute and regular physical exercise on cognition and affect , 2012, Neuroscience.

[141]  Paul J. Laurienti,et al.  Frontiers in Aging Neuroscience Aging Neuroscience , 2022 .

[142]  E. Acevedo,et al.  Rigorous Running Increases Growth Hormone and Insulin-Like Growth Factor-I Without Altering Ghrelin , 2004, Experimental biology and medicine.

[143]  Marc Roig,et al.  Acute exercise improves motor memory: Exploring potential biomarkers , 2014, Neurobiology of Learning and Memory.

[144]  B. Nindl,et al.  IGF-I, IGFBPs, and Inflammatory Cytokine Responses During Gender-Integrated Israeli Army Basic Combat Training , 2012, Journal of strength and conditioning research.

[145]  A. J. Schwarz,et al.  Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men. , 1996, The Journal of clinical endocrinology and metabolism.

[146]  Chih-Hsin Tang,et al.  Brain-derived neurotrophic factor increases vascular endothelial growth factor expression and enhances angiogenesis in human chondrosarcoma cells. , 2014, Biochemical pharmacology.

[147]  Keiichi Oda,et al.  Gait adaptability and brain activity during unaccustomed treadmill walking in healthy elderly females. , 2013, Gait & posture.

[148]  Simone Kühn,et al.  Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults , 2016, NeuroImage.

[149]  Thomas E. Nichols,et al.  Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise , 2016, NeuroImage.

[150]  D. Rudman,et al.  Serum Insulin‐Like Growth Factor I in Healthy Older Men in Relation to Physical Activity , 1994, Journal of the American Geriatrics Society.

[151]  Lars Nyberg,et al.  Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default-mode network—A multimodal approach , 2016, NeuroImage.

[152]  N. Secher,et al.  Endurance training enhances BDNF release from the human brain. , 2010, American journal of physiology. Regulatory, integrative and comparative physiology.

[153]  Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness. , 2001 .

[154]  Michael Falkenstein,et al.  Long-term habitual physical activity is associated with lower distractibility in a Stroop interference task in aging: Behavioral and ERP evidence , 2015, Brain and Cognition.

[155]  A. Strafella,et al.  TMS and drugs revisited 2014 , 2015, Clinical Neurophysiology.

[156]  H. Heinze,et al.  Vascular hippocampal plasticity after aerobic exercise in older adults , 2014, Molecular Psychiatry.

[157]  Lars S. Jonasson,et al.  Aerobic Exercise Intervention, Cognitive Performance, and Brain Structure: Results from the Physical Influences on Brain in Aging (PHIBRA) Study , 2017, Front. Aging Neurosci..

[158]  T. Scheewe,et al.  Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls. , 2015, Schizophrenia bulletin.

[159]  Mu-ming Poo,et al.  Neurotrophins as synaptic modulators , 2001, Nature Reviews Neuroscience.

[160]  K Ide,et al.  Cerebral metabolic response to submaximal exercise. , 1999, Journal of applied physiology.

[161]  M. Ridding,et al.  The influence of a single bout of aerobic exercise on short-interval intracortical excitability , 2014, Experimental Brain Research.

[162]  J. Nielsen,et al.  Cerebral activation during bicycle movements in man , 2000, Experimental Brain Research.

[163]  J. Haines,et al.  Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis , 1997 .

[164]  Timothy B. Weng,et al.  Differential Effects of Acute Exercise on Distinct Aspects of Executive Function. , 2015, Medicine and science in sports and exercise.

[165]  W. Byblow,et al.  Acute aerobic exercise modulates primary motor cortex inhibition , 2016, Experimental Brain Research.

[166]  C. White,et al.  Effect of hypoxia on cerebrovascular and cognitive function during moderate intensity exercise , 2016, Physiology & Behavior.

[167]  M. Barrot,et al.  Essential role of brain-derived neurotrophic factor in adult hippocampal function. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[168]  Masako Okamoto,et al.  Acute moderate exercise elicits increased dorsolateral prefrontal activation and improves cognitive performance with Stroop test , 2010, NeuroImage.

[169]  Chia-Liang Tsai,et al.  Effect of resistance-exercise training on cognitive function in healthy older adults: a review. , 2012, Journal of aging and physical activity.

[170]  Lara A Boyd,et al.  Promoting Neuroplasticity for Motor Rehabilitation After Stroke: Considering the Effects of Aerobic Exercise and Genetic Variation on Brain-Derived Neurotrophic Factor , 2013, Physical Therapy.

[171]  M. Berchicci,et al.  From cognitive motor preparation to visual processing: The benefits of childhood fitness to brain health , 2015, Neuroscience.

[172]  C. Ritz,et al.  Acute Exercise and Motor Memory Consolidation: The Role of Exercise Intensity , 2016, PloS one.

[173]  Paige E. Scalf,et al.  Cardiovascular fitness, cortical plasticity, and aging. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[174]  Brigitte Röder,et al.  Cardiovascular fitness modulates brain activation associated with spatial learning , 2012, NeuroImage.

[175]  Joe R. Nocera,et al.  Effects of Aerobic Fitness on Aging-Related Changes of Interhemispheric Inhibition and Motor Performance , 2013, Front. Aging Neurosci..

[176]  Tea Lulic,et al.  Physical activity levels determine exercise-induced changes in brain excitability , 2017, PloS one.

[177]  Gao-Xia Wei,et al.  Acute Aerobic Exercise Increases Cortical Activity during Working Memory: A Functional MRI Study in Female College Students , 2014, PloS one.

[178]  M. Suwa,et al.  Different circulating brain-derived neurotrophic factor responses to acute exercise between physically active and sedentary subjects. , 2012, Journal of sports science & medicine.

[179]  Pedro Ribeiro,et al.  Beta and alpha electroencephalographic activity changes after acute exercise. , 2007, Arquivos de neuro-psiquiatria.

[180]  F. Sohrabji,et al.  Estrogen–BDNF interactions: Implications for neurodegenerative diseases , 2006, Frontiers in Neuroendocrinology.

[181]  Nancy W Glynn,et al.  Physical activity predicts microstructural integrity in memory-related networks in very old adults. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[182]  S. Knecht,et al.  Physical activity and memory functions: An interventional study , 2011, Neurobiology of Aging.

[183]  Stanley J. Wiegand,et al.  Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus , 2001, The Journal of Neuroscience.

[184]  Notger G. Müller,et al.  Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults , 2016, NeuroImage.

[185]  Gene E. Alexander,et al.  Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls , 2016, Front. Hum. Neurosci..

[186]  C. Ritz,et al.  Acute exercise and motor memory consolidation: Does exercise type play a role? , 2017, Scandinavian journal of medicine & science in sports.

[187]  Sidong Yang,et al.  The beneficial role of early exercise training following stroke and possible mechanisms. , 2018, Life sciences.

[188]  V. Tillmann,et al.  Body composition, maximal aerobic performance and inflammatory biomarkers in endurance‐trained athletes , 2017, Clinical physiology and functional imaging.

[189]  W. Staines,et al.  Aerobic exercise modulates intracortical inhibition and facilitation in a nonexercised upper limb muscle , 2014, BMC Sports Science, Medicine and Rehabilitation.

[190]  C. Voelcker-Rehage,et al.  Does physical activity benefit motor performance and learning of upper extremity tasks in older adults? – A systematic review , 2017, European Review of Aging and Physical Activity.

[191]  Stefan Knecht,et al.  Physical activity and memory functions: Are neurotrophins and cerebral gray matter volume the missing link? , 2010, NeuroImage.

[192]  H. Strüder,et al.  pH Buffering Does not Influence BDNF Responses to Exercise , 2011, International Journal of Sports Medicine.

[193]  Vijay K. Venkatraman,et al.  Psychomotor speed and functional brain MRI 2 years after completing a physical activity treatment. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[194]  G. Koob,et al.  Methamphetamine Self-Administration and Voluntary Exercise Have Opposing Effects on Medial Prefrontal Cortex Gliogenesis , 2007, The Journal of Neuroscience.

[195]  D. Holtzman,et al.  Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[196]  J. Brun,et al.  The effects of intensive training on insulin-like growth factor I (IGF-I) and IGF binding proteins 1 and 3 in competitive cyclists: relationships with glucose disposal , 2003, Journal of sports sciences.

[197]  E. Franz,et al.  Effect of age on exercise-induced alterations in cognitive executive function: Relationship to cerebral perfusion , 2012, Experimental Gerontology.