| 词条 | Neurobiological effects of physical exercise |
| 释义 |
| Name = Neurobiological effects of physical exercise | subheader = Exercise therapy – medical intervention | image = Jogging Woman in Grass.jpg | caption = A woman engaging in aerobic exercise | alt = Image of a woman running | ICD9 = 93.19 | MeshID = D005081 | LOINC = {{LOINC|73986-2}} | other_codes = | MedlinePlus = | eMedicine = 324583 }} The In healthy adults, aerobic exercise has been shown to induce transient effects on cognition after a single exercise session and persistent effects on cognition following regular exercise over the course of several months.[1][10][13] People who regularly perform aerobic exercise (e.g., running, jogging, brisk walking, swimming, and cycling) have greater scores on neuropsychological function and performance tests that measure certain cognitive functions, such as attentional control, inhibitory control, cognitive flexibility, working memory updating and capacity, declarative memory, spatial memory, and information processing speed.[1][5][7][9][10][13] The transient effects of exercise on cognition include improvements in most executive functions (e.g., attention, working memory, cognitive flexibility, inhibitory control, problem solving, and decision making) and information processing speed for a period of up to 2 hours after exercising.[13] Aerobic exercise induces short- and long-term effects on mood and emotional states by promoting positive affect, inhibiting negative affect, and decreasing the biological response to acute psychological stress.[13] Over the short-term, aerobic exercise functions as both an antidepressant and euphoriant,[14][15][16][17] whereas consistent exercise produces general improvements in mood and self-esteem.[18][19] Regular aerobic exercise improves symptoms associated with a variety of central nervous system disorders and may be used as an adjunct therapy for these disorders. There is clear evidence of exercise treatment efficacy for major depressive disorder and attention deficit hyperactivity disorder.[11][16][20][21][22][23] The American Academy of Neurology's clinical practice guideline for mild cognitive impairment indicates that clinicians should recommend regular exercise (two times per week) to individuals who have been diagnosed with this condition.[24] Reviews of clinical evidence also support the use of exercise as an adjunct therapy for certain neurodegenerative disorders, particularly Alzheimer’s disease and Parkinson's disease.[25][26][27][28][29][30] Regular exercise is also associated with a lower risk of developing neurodegenerative disorders.[28][31] A large body of preclinical evidence and emerging clinical evidence supports the use of exercise therapy for treating and preventing the development of drug addictions.[32][33][34][35][36] Regular exercise has also been proposed as an adjunct therapy for brain cancers.[37] Long-term effectsNeuroplasticityNeuroplasticity is the process by which neurons adapt to a disturbance over time, and most often occurs in response to repeated exposure to stimuli.[38] Aerobic exercise increases the production of neurotrophic factors{{#tag:ref|Neurotrophic factors are peptides or other small proteins that promote the growth, survival, and differentiation of neurons by binding to and activating their associated tyrosine kinases.[39]|group="note"}} (e.g., BDNF, IGF-1, VEGF) which mediate improvements in cognitive functions and various forms of memory by promoting blood vessel formation in the brain, adult neurogenesis,{{#tag:ref|Adult neurogenesis is the postnatal (after-birth) growth of new neurons, a beneficial form of neuroplasticity.[38]|group="note"}} and other forms of neuroplasticity.[2][5][18][62][63] Consistent aerobic exercise over a period of several months induces clinically significant improvements in executive functions and increased gray matter volume in nearly all regions of the brain,[40] with the most marked increases occurring in brain regions that give rise to executive functions.[1][5][6][7][9] The brain structures that show the greatest improvements in gray matter volume in response to aerobic exercise are the prefrontal cortex, caudate nucleus, and hippocampus;[1][5][6][8] less significant increases in gray matter volume occur in the anterior cingulate cortex, parietal cortex, cerebellum, and nucleus accumbens.[5][6][8] The prefrontal cortex, caudate nucleus, and anterior cingulate cortex are among the most significant brain structures in the dopamine and norepinephrine systems that give rise to cognitive control.[6][41] Exercise-induced neurogenesis (i.e., the increases in gray matter volume) in the hippocampus is associated with measurable improvements in spatial memory.[6][8][19][42] Higher physical fitness scores, as measured by VO2 max, are associated with better executive function, faster information processing speed, and greater gray matter volume of the hippocampus, caudate nucleus, and nucleus accumbens.[1][6] Long-term aerobic exercise is also associated with persistent beneficial epigenetic changes that result in improved stress coping, improved cognitive function, and increased neuronal activity ({{nowrap|c-Fos}} and BDNF signaling).[4][43]Structural growth{{anchor|Memory|Growth}}Reviews of neuroimaging studies indicate that consistent aerobic exercise increases gray matter volume in nearly all regions of the brain,[40] with more pronounced increases occurring in brain regions associated with memory processing, cognitive control, motor function, and reward;[1][5][6][8][40] the most prominent gains in gray matter volume are seen in the prefrontal cortex, caudate nucleus, and hippocampus, which support cognitive control and memory processing, among other cognitive functions.[1][6][8][9] Moreover, the left and right halves of the prefrontal cortex, the hippocampus, and the cingulate cortex appear to become more functionally interconnected in response to consistent aerobic exercise.[1][7] Three reviews indicate that marked improvements in prefrontal and hippocampal gray matter volume occur in healthy adults that regularly engage in medium intensity exercise for several months.[1][6][44] Other regions of the brain that demonstrate moderate or less significant gains in gray matter volume during neuroimaging include the anterior cingulate cortex, parietal cortex, cerebellum, and nucleus accumbens.[5][6][8][45] Regular exercise has been shown to counter the shrinking of the hippocampus and memory impairment that naturally occurs in late adulthood.[5][6][8] Sedentary adults over age 55 show a 1–2% decline in hippocampal volume annually.[8][111] A neuroimaging study with a sample of 120 adults revealed that participating in regular aerobic exercise increased the volume of the left hippocampus by 2.12% and the right hippocampus by 1.97% over a one-year period.[8][111] Subjects in the low intensity stretching group who had higher fitness levels at baseline showed less hippocampal volume loss, providing evidence for exercise being protective against age-related cognitive decline.[46] In general, individuals that exercise more over a given period have greater hippocampal volumes and better memory function.[5][8] Aerobic exercise has also been shown to induce growth in the white matter tracts in the anterior corpus callosum, which normally shrink with age.[5][44] The various functions of the brain structures that show exercise-induced increases in gray matter volume include:
Persistent effects on cognition {{anchor|Cognitive control and memory}}{{see also|Executive functions}}Concordant with the functional roles of the brain structures that exhibit increased gray matter volumes, regular exercise over a period of several months has been shown to persistently improve numerous executive functions and several forms of memory.[5][7][9][134][135][53] In particular, consistent aerobic exercise has been shown to improve attentional control,{{#tag:ref|Attentional control allows an individual to focus their attention on a specific source and ignore other stimuli that compete for one's attention,[41] such as in the cocktail party effect. |group="note"}} information processing speed, cognitive flexibility (e.g., task switching), inhibitory control,{{#tag:ref| Inhibitory control is the process of altering one's learned behavioral responses, sometimes called "prepotent responses", in a way that makes it easier to complete a particular goal.[51][54] Inhibitory control allows individuals to control their impulses and habits when necessary or desired,[51][134][54] e.g., to overcome procrastination. |group="note"}} working memory updating and capacity,{{#tag:ref|Working memory is the form of memory used by an individual at any given moment for active information processing,[41] such as when reading or writing an encyclopedia article. Working memory has a limited capacity and functions as an information buffer, analogous to a computer's data buffer, that permits the manipulation of information for comprehension, decision-making, and guidance of behavior.[51]|group="note"}} declarative memory,{{#tag:ref|Declarative memory, also known as explicit memory, is the form of memory that pertains to facts and events.[50]|group="note"}} and spatial memory.[5][6][7][9][10][55][56] In healthy young and middle-aged adults, the effect sizes of improvements in cognitive function are largest for indices of executive functions and small to moderate for aspects of memory and information processing speed.[1][10] It may be that in older adults, individuals benefit cognitively by taking part in both aerobic and resistance type exercise of at least moderate intensity.[57] Individuals who have a sedentary lifestyle tend to have impaired executive functions relative to other more physically active non-exercisers.[9][55] A reciprocal relationship between exercise and executive functions has also been noted: improvements in executive control processes, such as attentional control and inhibitory control, increase an individual's tendency to exercise.[9] Mechanism of effects{{Further|Myokine}}{{expand section|with=an introduction about myokines and how this concept relates to BDNF, IGF-1, VEGF, and other neuroactive biomolecules that penetrate the blood–brain or blood–CSF barriers. General references:[58][https://www.ncbi.nlm.nih.gov/pubmed/30627775]|date=March 2019|small=no}}BDNF signaling{{See also|Brain-derived neurotrophic factor}} One of the most significant effects of exercise on the brain is the increased synthesis and expression of BDNF, a neuropeptide and hormone, in the brain and periphery, resulting in increased signaling through its receptor tyrosine kinase, tropomyosin receptor kinase B (TrkB).[4][59][60] Since BDNF is capable of crossing the blood–brain barrier, higher peripheral BDNF synthesis also increases BDNF signaling in the brain.[62] Exercise-induced increases in brain BDNF signaling are associated with beneficial epigenetic changes, improved cognitive function, improved mood, and improved memory.[4][8][18][59] Furthermore, research has provided a great deal of support for the role of BDNF in hippocampal neurogenesis, synaptic plasticity, and neural repair.[5][59] Engaging in moderate-high intensity aerobic exercise such as running, swimming, and cycling increases BDNF biosynthesis through myokine signaling, resulting in up to a threefold increase in blood plasma and brain BDNF levels;[4][59][60] exercise intensity is positively correlated with the magnitude of increased BDNF biosynthesis and expression.[4][59][60] A meta-analysis of studies involving the effect of exercise on BDNF levels found that consistent exercise modestly increases resting BDNF levels as well.[18] IGF-1 signaling{{See also|Insulin-like growth factor 1}}{{abbr|IGF-1|Insulin-like growth factor 1}} is a peptide and neurotrophic factor that mediates some of the effects of growth hormone;[177] IGF-1 elicits its physiological effects by binding to a specific receptor tyrosine kinase, the IGF-1 receptor, to control tissue growth and remodeling.[177] In the brain, IGF-1 functions as a neurotrophic factor that, like {{abbr|BDNF|brain-derived neurotrophic factor}}, plays a significant role in cognition, neurogenesis, and neuronal survival.[59][61][62] Physical activity is associated with increased levels of IGF-1 in blood serum, which is known to contribute to neuroplasticity in the brain due to its capacity to cross the blood–brain barrier and blood–cerebrospinal fluid barrier;[5][59][63][61] consequently, one review noted that IGF-1 is a key mediator of exercise-induced adult neurogenesis, while a second review characterized it as a factor which links "body fitness" with "brain fitness".[63][61] The amount of IGF-1 released into blood plasma during exercise is positively correlated with exercise intensity and duration.[64]VEGF signaling{{See also|Vascular endothelial growth factor}}{{abbr|VEGF|Vascular endothelial growth factor}} is a neurotrophic and angiogenic (i.e., blood vessel growth-promoting) signaling protein that binds to two receptor tyrosine kinases, VEGFR1 and VEGFR2, which are expressed in neurons and glial cells in the brain.[62] Hypoxia, or inadequate cellular oxygen supply, strongly upregulates VEGF expression and VEGF exerts a neuroprotective effect in hypoxic neurons.[62] Like {{abbr|BDNF|brain-derived neurotrophic factor}} and {{abbr|IGF-1|Insulin-like growth factor 1}}, aerobic exercise has been shown to increase VEGF biosynthesis in peripheral tissue which subsequently crosses the blood–brain barrier and promotes neurogenesis and blood vessel formation in the central nervous system.[65][63][66] Exercise-induced increases in VEGF signaling have been shown to improve cerebral blood volume and contribute to exercise-induced neurogenesis in the hippocampus.[5][63][66]Short-term effectsTransient effects on cognition{{see also|Executive functions}}In addition to the persistent effects on cognition that result from several months of daily exercise, acute exercise (i.e., a single bout of exercise) has been shown to transiently improve a number of cognitive functions.[13][198][199] Reviews and meta-analyses of research on the effects of acute exercise on cognition in healthy young and middle-aged adults have concluded that information processing speed and a number of executive functions – including attention, working memory, problem solving, cognitive flexibility, verbal fluency, decision making, and inhibitory control – all improve for a period of up to 2 hours post-exercise.[13][67][68] A systematic review of studies conducted on children also suggested that some of the exercise-induced improvements in executive function are apparent after single bouts of exercise, while other aspects (e.g., attentional control) only improve following consistent exercise on a regular basis.[56] Other research has suggested performative enhancements during exercise, such as exercise-concurrent improvements in processing speed during visual working memory tasks.[69] Exercise-induced euphoria {{Anchor|Euphoria}}{{hatnote|For further information on the neural substrates of pleasure cognition, see Hedonic hotspots.}}Continuous exercise can produce a transient state of euphoria – a positively-valenced affective state involving the experience of pleasure and feelings of profound contentment, elation, and well-being – which is colloquially known as a "runner's high" in distance running or a "rower's high" in rowing.[14][15][70][71] Current medical reviews indicate that several endogenous euphoriants are responsible for producing exercise-related euphoria, specifically phenethylamine (an endogenous psychostimulant), {{nowrap|β-endorphin}} (an endogenous opioid), and anandamide (an endogenous cannabinoid).[209][210][211][212][213] Effects on neurochemistryβ-Phenylethylamine{{Catecholamine and trace amine biosynthesis|align=right}}β-Phenylethylamine, commonly referred to as phenethylamine, is a human trace amine and potent catecholaminergic and glutamatergic neuromodulator that has similar psychostimulant and euphoriant effects and a similar chemical structure to amphetamine.[72] Thirty minutes of moderate to high intensity physical exercise has been shown to induce an enormous increase in urinary {{nowrap|β-phenylacetic acid}}, the primary metabolite of phenethylamine.[73][74][75] Two reviews noted a study where the average 24 hour urinary {{nowrap|β-phenylacetic acid}} concentration among participants following just 30 minutes of intense exercise increased by 77% relative to baseline concentrations in resting control subjects;[73][74][75] the reviews suggest that phenethylamine synthesis sharply increases while an individual is exercising, during which time it is rapidly metabolized due to its short half-life of roughly 30 seconds.[73][74][75][224] In a resting state, phenethylamine is synthesized in catecholamine neurons from {{nowrap|{{smallcaps all|L}}-phenylalanine}} by aromatic amino acid decarboxylase (AADC) at approximately the same rate at which dopamine is produced.[76]In light of this observation, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing euphoric effects of a runner's high, as both phenethylamine and amphetamine are potent euphoriants.[73][74][75] β-Endorphinβ-Endorphin (contracted from "endogenous morphine") is an endogenous opioid neuropeptide that binds to μ-opioid receptors, in turn producing euphoria and pain relief.[77] A meta-analytic review found that exercise significantly increases the secretion of {{nowrap|β-endorphin}} and that this secretion is correlated with improved mood states.[77] Moderate intensity exercise produces the greatest increase in {{nowrap|β-endorphin}} synthesis, while higher and lower intensity forms of exercise are associated with smaller increases in {{nowrap|β-endorphin}} synthesis.[77] A review on {{nowrap|β-endorphin}} and exercise noted that an individual's mood improves for the remainder of the day following physical exercise and that one's mood is positively correlated with overall daily physical activity level.[77]AnandamideAnandamide is an endogenous cannabinoid and retrograde neurotransmitter that binds to cannabinoid receptors (primarily CB1), in turn producing euphoria.[70][78] It has been shown that aerobic exercise causes an increase in plasma anandamide levels, where the magnitude of this increase is highest at moderate exercise intensity (i.e., exercising at ~70–80% maximum heart rate).[78] Increases in plasma anandamide levels are associated with psychoactive effects because anandamide is able to cross the blood–brain barrier and act within the central nervous system.[78] Thus, because anandamide is a euphoriant and aerobic exercise is associated with euphoric effects, it has been proposed that anandamide partly mediates the short-term mood-lifting effects of exercise (e.g., the euphoria of a runner's high) via exercise-induced increases in its synthesis.[70][78]In mice it was demonstrated that certain features of a runner's high depend on cannabinoid receptors. Pharmacological or genetic disruption of cannabinoid signaling via cannabinoid receptors prevents the analgesic and anxiety-reducing effects of running.[79]{{npsn|date=April 2016}} Cortisol and the psychological stress response{{See also|Effects of stress on memory}}The "stress hormone", cortisol, is a glucocorticoid that binds to glucocorticoid receptors.[240][241][242] Psychological stress induces the release of cortisol from the adrenal gland by activating the hypothalamic–pituitary–adrenal axis (HPA axis).[80][81][242] Short-term increases in cortisol levels are associated with adaptive cognitive improvements, such as enhanced inhibitory control;[63][81][242] however, excessively high exposure or prolonged exposure to high levels of cortisol causes impairments in cognitive control and has neurotoxic effects in the human brain.[63][55][82] For example, chronic psychological stress decreases {{abbr|BDNF|brain-derived neurotrophic factor}} expression which has detrimental effects on hippocampal volume and can lead to depression.[63][80] As a physical stressor, aerobic exercise stimulates cortisol secretion in an intensity-dependent manner;[81] however, it does not result in long-term increases in cortisol production since this exercise-induced effect on cortisol is a response to transient negative energy balance.{{#tag:ref|In healthy individuals, this energy deficit resolves simply from eating and drinking a sufficient amount of food and beverage after exercising.|group="note"}}[81] Individuals who have recently exercised exhibit improvements in stress coping behaviors.[4][83][43] Aerobic exercise increases physical fitness and lowers neuroendocrine (i.e., {{abbr|HPA axis|hypothalamic–pituitary–adrenal axis}}) reactivity and therefore reduces the biological response to psychological stress in humans (e.g., reduced cortisol release and attenuated heart rate response).[13][83][84] Exercise also reverses stress-induced decreases in {{abbr|BDNF|brain-derived neurotrophic factor}} expression and signaling in the brain, thereby acting as a buffer against stress-related diseases like depression.[83][80][84] Glutamate and GABA{{expand section|[13]|date=June 2017}}Glutamate, one of the most common neurochemicals in the brain, is an excitatory neurotransmitter involved in many aspects of brain function, including learning and memory.[85] Based upon animal models, exercise appears to normalize the excessive levels of glutamate neurotransmission into the nucleus accumbens that occurs in drug addiction.[33] A review of the effects of exercise on neurocardiac function in preclinical models noted that exercise-induced neuroplasticity of the rostral ventrolateral medulla (RVLM) has an inhibitory effect on glutamatergic neurotransmission in this region, in turn reducing sympathetic activity;[86] the review hypothesized that this neuroplasticity in the RVLM is a mechanism by which regular exercise prevents inactivity-related cardiovascular disease.[86]Monoamine neurotransmitters{{further|Central nervous system fatigue}}{{expand section|[13]|date=March 2015}}Acetylcholine{{expand section|[13]|date=June 2017}}Effects in children{{medical citations needed|section|date=February 2015}}Sibley and Etnier (2003) performed a meta-analysis that looked at the relationship between physical activity and cognitive performance in children.[273] They reported a beneficial relationship in the categories of perceptual skills, intelligence quotient, achievement, verbal tests, mathematic tests, developmental level/academic readiness and other, with the exception of memory, that was found to be unrelated to physical activity.[87] The correlation was strongest for the age ranges of 4–7 and 11–13 years.[87] On the other hand, Chaddock and colleagues (2011) found results that contrasted Sibley and Etnier's meta-analysis. In their study, the hypothesis was that lower-fit children would perform poorly in executive control of memory and have smaller hippocampal volumes compared to higher-fit children.[276] Instead of physical activity being unrelated to memory in children between 4 and 18 years of age, it may be that preadolescents of higher fitness have larger hippocampal volumes, than preadolescents of lower fitness. According to a previous study done by Chaddock and colleagues (Chaddock et al. 2010), a larger hippocampal volume would result in better executive control of memory.[88] They concluded that hippocampal volume was positively associated with performance on relational memory tasks.[88] Their findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain.[88] In Best’s (2010) meta-analysis of the effect of activity on children’s executive function, there are two distinct experimental designs used to assess aerobic exercise on cognition. The first is chronic exercise, in which children are randomly assigned to a schedule of aerobic exercise over several weeks and later assessed at the end.[89] The second is acute exercise, which examines the immediate changes in cognitive functioning after each session.[89] The results of both suggest that aerobic exercise may briefly aid children’s executive function and also influence more lasting improvements to executive function.[89] Other studies have suggested that exercise is unrelated to academic performance, perhaps due to the parameters used to determine exactly what academic achievement is.[90] This area of study has been a focus for education boards that make decisions on whether physical education should be implemented in the school curriculum, how much time should be dedicated to physical education, and its impact on other academic subjects.[87] Another study found that sixth-graders who participated in vigorous physical activity at least three times a week had the highest scores compared to those who participated in moderate or no physical activity at all. The kids who participated in vigorous physical activity scored three points higher, on average, on their academic test, which consisted of math, science, English, and world studies.[91] Animal studies have also shown that exercise can impact brain development early on in life. Mice that had access to running wheels and other such exercise equipment had better neuronal growth in the neural systems involved in learning and memory.[90] Neuroimaging of the human brain has yielded similar results, where exercise leads to changes in brain structure and function.[90] Some investigations have linked low levels of aerobic fitness in children with impaired executive function in older adults, but there is mounting evidence it may also be associated with a lack of selective attention, response inhibition, and interference control.[92] Effects on central nervous system disorders{{anchor|Effects on neural disorders}}{{See also|Central nervous system disorders}}}}2. ^1 2 {{cite journal | vauthors = Paillard T, Rolland Y, de Souto Barreto P | title = Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review | journal = J Clin Neurol | volume = 11 | issue = 3 | pages = 212–219 | date = July 2015 | pmid = 26174783 | pmc = 4507374 | doi = 10.3988/jcn.2015.11.3.212 | quote = Aerobic physical exercise (PE) activates the release of neurotrophic factors and promotes angiogenesis, thereby facilitating neurogenesis and synaptogenesis, which in turn improve memory and cognitive functions. ... Exercise limits the alteration in dopaminergic neurons in the substantia nigra and contributes to optimal functioning of the basal ganglia involved in motor commands and control by adaptive mechanisms involving dopamine and glutamate neurotransmission.}} 3. ^1 {{cite journal | vauthors = McKee AC, Daneshvar DH, Alvarez VE, Stein TD | title = The neuropathology of sport | journal = Acta Neuropathol. | volume = 127 | issue = 1 | pages = 29–51 | date = January 2014 | pmid = 24366527 | pmc = 4255282 | doi = 10.1007/s00401-013-1230-6 | quote = The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable ... Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration.}} 4. ^1 2 3 4 5 6 7 {{cite journal |vauthors=Denham J, Marques FZ, O'Brien BJ, Charchar FJ | title = Exercise: putting action into our epigenome | journal = Sports Med | volume = 44 | issue = 2 | pages = 189–209 | date = February 2014 | pmid = 24163284 | doi = 10.1007/s40279-013-0114-1 | quote = Aerobic physical exercise produces numerous health benefits in the brain. Regular engagement in physical exercise enhances cognitive functioning, increases brain neurotrophic proteins, such as brain-derived neurotrophic factor (BDNF), and prevents cognitive diseases [76–78]. Recent findings highlight a role for aerobic exercise in modulating chromatin remodelers [21, 79–82]. ... These results were the first to demonstrate that acute and relatively short aerobic exercise modulates epigenetic modifications. The transient epigenetic modifications observed due to chronic running training have also been associated with improved learning and stress-coping strategies, epigenetic changes and increased c-Fos-positive neurons ... Nonetheless, these studies demonstrate the existence of epigenetic changes after acute and chronic exercise and show they are associated with improved cognitive function and elevated markers of neurotrophic factors and neuronal activity (BDNF and c-Fos). ... The aerobic exercise training-induced changes to miRNA profile in the brain seem to be intensity-dependent [164]. These few studies provide a basis for further exploration into potential miRNAs involved in brain and neuronal development and recovery via aerobic exercise.}} 5. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 {{cite book |vauthors=Gomez-Pinilla F, Hillman C | title = The influence of exercise on cognitive abilities | journal = Compr. Physiol. | volume = 3 | issue = 1 | pages = 403–428 | date = January 2013 | pmid = 23720292 | pmc = 3951958 | doi = 10.1002/cphy.c110063 | quote = | isbn = 9780470650714 }} 6. ^1 2 3 4 5 6 7 8 9 10 11 12 13 {{cite journal |vauthors=Erickson KI, Leckie RL, Weinstein AM | title = Physical activity, fitness, and gray matter volume | journal = Neurobiol. Aging | volume = 35 Suppl 2 | issue = | pages = S20–528 | date = September 2014 | pmid = 24952993 | pmc = 4094356 | doi = 10.1016/j.neurobiolaging.2014.03.034 | quote = }} 7. ^1 2 3 4 5 {{cite journal |vauthors=Guiney H, Machado L | title = Benefits of regular aerobic exercise for executive functioning in healthy populations | journal = Psychon Bull Rev | volume = 20 | issue = 1 | pages = 73–86 | date = February 2013 | pmid = 23229442 | doi = 10.3758/s13423-012-0345-4 | quote = }} 8. ^1 2 3 4 5 6 7 8 9 10 11 12 13 {{cite journal | vauthors = Erickson KI, Miller DL, Roecklein KA | title = The aging hippocampus: interactions between exercise, depression, and BDNF | journal = Neuroscientist | volume = 18 | issue = 1 | pages = 82–97 | year = 2012 | pmid = 21531985 | pmc = 3575139 | doi=10.1177/1073858410397054 | quote = }} 9. ^1 2 3 4 5 6 7 {{cite journal |vauthors=Buckley J, Cohen JD, Kramer AF, McAuley E, Mullen SP | title = Cognitive control in the self-regulation of physical activity and sedentary behavior | journal = Front Hum Neurosci | volume = 8 | issue = | page = 747 | year = 2014 | pmid = 25324754 | pmc = 4179677 | doi = 10.3389/fnhum.2014.00747 | quote = }} 10. ^1 2 3 4 {{cite journal | vauthors = Cox EP, O'Dwyer N, Cook R, Vetter M, Cheng HL, Rooney K, O'Connor H | title = Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review | journal = J. Sci. Med. Sport | volume = 19 | issue = 8 | pages = 616–628 | date = August 2016 | pmid = 26552574 | doi = 10.1016/j.jsams.2015.09.003 | quote = A range of validated platforms assessed CF across three domains: executive function (12 studies), memory (four studies) and processing speed (seven studies). ... In studies of executive function, five found a significant ES in favour of higher PA, ranging from small to large. Although three of four studies in the memory domain reported a significant benefit of higher PA, there was only one significant ES, which favoured low PA. Only one study examining processing speed had a significant ES, favouring higher PA. CONCLUSIONS: A limited body of evidence supports a positive effect of PA on CF in young to middle-aged adults. Further research into this relationship at this age stage is warranted. ... Significant positive effects of PA on cognitive function were found in 12 of the 14 included manuscripts, the relationship being most consistent for executive function, intermediate for memory and weak for processing speed.}} 11. ^1 2 {{cite journal | vauthors = Schuch FB, Vancampfort D, Rosenbaum S, Richards J, Ward PB, Stubbs B | title = Exercise improves physical and psychological quality of life in people with depression: A meta-analysis including the evaluation of control group response | journal = Psychiatry Res. | volume = 241 | issue = | pages = 47–54 | date = July 2016 | pmid = 27155287 | doi = 10.1016/j.psychres.2016.04.054 | quote = Exercise has established efficacy as an antidepressant in people with depression. ... Exercise significantly improved physical and psychological domains and overall QoL. ... The lack of improvement among control groups reinforces the role of exercise as a treatment for depression with benefits to QoL.}} 12. ^{{cite journal | vauthors = Pratali L, Mastorci F, Vitiello N, Sironi A, Gastaldelli A, Gemignani A | title = Motor Activity in Aging: An Integrated Approach for Better Quality of Life | journal = Int. Sch. Res. Notices | volume = 2014 | issue = | pages = 257248 | date = November 2014 | pmid = 27351018 | doi = 10.1155/2014/257248 | pmc=4897547 | quote = Research investigating the effects of exercise on older adults has primarily focused on brain structural and functional changes with relation to cognitive improvement. In particular, several cross-sectional and intervention studies have shown a positive association between physical activity and cognition in older persons [86] and an inverse correlation with cognitive decline and dementia [87]. Older adults enrolled in a 6-month aerobic fitness intervention increased brain volume in both gray matter (anterior cingulate cortex, supplementary motor area, posterior middle frontal gyrus, and left superior temporal lobe) and white matter (anterior third of corpus callosum) [88]. In addition, Colcombe and colleagues showed that older adults with higher cardiovascular fitness levels are better at activating attentional resources, including decreased activation of the anterior cingulated cortex. One of the possible mechanisms by which physical activity may benefit cognition is that physical activity maintains brain plasticity, increases brain volume, stimulates neurogenesis and synaptogenesis, and increases neurotrophic factors in different areas of the brain, possibly providing reserve against later cognitive decline and dementia [89, 90].}} 13. ^1 2 3 4 5 6 7 8 9 {{cite journal|author1=Basso JC, Suzuki WA|title=The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review|journal=Brain Plasticity|date=March 2017|volume=2|issue=2|pages=127–152|doi=10.3233/BPL-160040|pmid=29765853|pmc=5928534|doi-access=free|url=http://content.iospress.com/articles/brain-plasticity/bpl160040|lay-source=Can A Single Exercise Session Benefit Your Brain?|lay-url=http://neurosciencenews.com/brain-exercise-6892/|lay-date=12 June 2017 | quote = A large collection of research in humans has shown that a single bout of exercise alters behavior at the level of affective state and cognitive functioning in several key ways. In terms of affective state, acute exercise decreases negative affect, increases positive affect, and decreases the psychological and physiological response to acute stress [28]. These effects have been reported to persist for up to 24 hours after exercise cessation [28, 29, 53]. In terms of cognitive functioning, acute exercise primarily enhances executive functions dependent on the prefrontal cortex including attention, working memory, problem solving, cognitive flexibility, verbal fluency, decision making, and inhibitory control [9]. These positive changes have been demonstrated to occur with very low to very high exercise intensities [9], with effects lasting for up to two hours after the end of the exercise bout (Fig. 1A) [27]. Moreover, many of these neuropsychological assessments measure several aspects of behavior including both accuracy of performance and speed of processing. McMorris and Hale performed a meta-analysis examining the effects of acute exercise on both accuracy and speed of processing, revealing that speed significantly improved post-exercise, with minimal or no effect on accuracy [17]. These authors concluded that increasing task difficulty or complexity may help to augment the effect of acute exercise on accuracy. ... However, in a comprehensive meta-analysis, Chang and colleagues found that exercise intensities ranging from very light (<50% MHR) to very hard (>93% MHR) have all been reported to improve cognitive functioning [9].}} 14. ^1 {{cite journal | vauthors = Cunha GS, Ribeiro JL, Oliveira AR | title = [Levels of beta-endorphin in response to exercise and overtraining] | language = Portuguese | journal = Arq Bras Endocrinol Metabol | volume = 52 | issue = 4 | pages = 589–598 | date = June 2008 | pmid = 18604371 | doi = 10.1590/S0004-27302008000400004| quote = Interestingly, some symptoms of OT are related to beta-endorphin (beta-end(1-31)) effects. Some of its effects, such as analgesia, increasing lactate tolerance, and exercise-induced euphoria, are important for training.}} 15. ^1 {{cite journal | vauthors = Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR | title = The runner's high: opioidergic mechanisms in the human brain | journal = Cereb. Cortex | volume = 18 | issue = 11 | pages = 2523–2531 | year = 2008 | pmid = 18296435 | doi = 10.1093/cercor/bhn013 | quote = The runner's high describes a euphoric state resulting from long-distance running.}} 16. ^1 2 3 {{cite journal | vauthors = Josefsson T, Lindwall M, Archer T | title = Physical exercise intervention in depressive disorders: meta-analysis and systematic review | journal = Scand J Med Sci Sports | volume = 24 | issue = 2 | pages = 259–272 | year = 2014 | pmid = 23362828 | doi = 10.1111/sms.12050 | quote = }} 17. ^1 2 {{cite journal | vauthors = Rosenbaum S, Tiedemann A, Sherrington C, Curtis J, Ward PB | title = Physical activity interventions for people with mental illness: a systematic review and meta-analysis | journal = J Clin Psychiatry | volume = 75 | issue = 9 | pages = 964–974 | year = 2014 | pmid = 24813261 | doi = 10.4088/JCP.13r08765 | quote = This systematic review and meta-analysis found that physical activity reduced depressive symptoms among people with a psychiatric illness. The current meta-analysis differs from previous studies, as it included participants with depressive symptoms with a variety of psychiatric diagnoses (except dysthymia and eating disorders). ... This review provides strong evidence for the antidepressant effect of physical activity; however, the optimal exercise modality, volume, and intensity remain to be determined. ... Conclusion Few interventions exist whereby patients can hope to achieve improvements in both psychiatric symptoms and physical health simultaneously without significant risks of adverse effects. Physical activity offers substantial promise for improving outcomes for people living with mental illness, and the inclusion of physical activity and exercise programs within treatment facilities is warranted given the results of this review.}} 18. ^1 2 3 {{cite journal |vauthors=Szuhany KL, Bugatti M, Otto MW | title = A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor | journal = J Psychiatr Res | volume = 60C | issue = | pages = 56–64 | date = October 2014 | pmid = 25455510 | pmc = 4314337 | doi = 10.1016/j.jpsychires.2014.10.003 | quote = Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1111 participants) examining the effect of exercise on BDNF levels in three exercise paradigms: (1) a single session of exercise, (2) a session of exercise following a program of regular exercise, and (3) resting BDNF levels following a program of regular exercise. Moderators of this effect were also examined. Results demonstrated a moderate effect size for increases in BDNF following a single session of exercise (Hedges' g = 0.46, p < 0.001). Further, regular exercise intensified the effect of a session of exercise on BDNF levels (Hedges' g = 0.59, p = 0.02). Finally, results indicated a small effect of regular exercise on resting BDNF levels (Hedges' g = 0.27, p = 0.005). ... Effect size analysis supports the role of exercise as a strategy for enhancing BDNF activity in humans.}} 19. ^1 {{cite journal |vauthors=Lees C, Hopkins J | title = Effect of aerobic exercise on cognition, academic achievement, and psychosocial function in children: a systematic review of randomized control trials | journal = Prev Chronic Dis | volume = 10 | issue = | pages = E174 | year = 2013 | pmid = 24157077 | pmc = 3809922 | doi = 10.5888/pcd10.130010 | quote = This omission is relevant, given the evidence that aerobic-based physical activity generates structural changes in the brain, such as neurogenesis, angiogenesis, increased hippocampal volume, and connectivity (12,13). In children, a positive relationship between aerobic fitness, hippocampal volume, and memory has been found (12,13). ... Mental health outcomes included reduced depression and increased self-esteem, although no change was found in anxiety levels (18). ... This systematic review of the literature found that [aerobic physical activity (APA)] is positively associated with cognition, academic achievement, behavior, and psychosocial functioning outcomes. Importantly, Shephard also showed that curriculum time reassigned to APA still results in a measurable, albeit small, improvement in academic performance (24). ... The actual aerobic-based activity does not appear to be a major factor; interventions used many different types of APA and found similar associations. In positive association studies, intensity of the aerobic activity was moderate to vigorous. The amount of time spent in APA varied significantly between studies; however, even as little as 45 minutes per week appeared to have a benefit.}} 20. ^1 2 3 {{cite journal | vauthors = Mura G, Moro MF, Patten SB, Carta MG | title = Exercise as an add-on strategy for the treatment of major depressive disorder: a systematic review | journal = CNS Spectr | volume = 19 | issue = 6 | pages = 496–508 | year = 2014 | pmid = 24589012 | doi = 10.1017/S1092852913000953 | quote = Considered overall, the studies included in the present review showed a strong effectiveness of exercise combined with antidepressants. ... Conclusions This is the first review to have focused on exercise as an add-on strategy in the treatment of MDD. Our findings corroborate some previous observations that were based on few studies and which were difficult to generalize.41,51,73,92,93 Given the results of the present article, it seems that exercise might be an effective strategy to enhance the antidepressant effect of medication treatments. Moreover, we hypothesize that the main role of exercise on treatment-resistant depression is in inducing neurogenesis by increasing BDNF expression, as was demonstrated by several recent studies.}} 21. ^1 2 3 {{cite journal | vauthors = Ranjbar E, Memari AH, Hafizi S, Shayestehfar M, Mirfazeli FS, Eshghi MA | title = Depression and Exercise: A Clinical Review and Management Guideline | journal = Asian J. Sports Med. | volume = 6 | issue = 2 | pages = e24055 | date = June 2015 | pmid = 26448838 | pmc = 4592762 | doi = 10.5812/asjsm.6(2)2015.24055 | quote = Keeping in mind that exercise shows no medication side effects such as withdrawal symptoms (20), weight gain, dry mouth or insomnia (21), but shows potential health benefits such as weight reduction, it is highly recommended to use exercise as an adjunctive treatment for depression (22). New findings confirm that exercise can be recommended as a first-line treatment for mild to moderate depression; as an adjunct to medications (23); as an alternative to cognitive behavioral therapy (11); and in preventing depression in clinical as well as healthy populations (24–26). ... Although recent findings have shown that exercise can decrease depressive symptoms, there are still many questions and limitations to wider application of exercise in depression. For instance, there are deficiencies in methodological planning such as uncontrolled nonrandomized trials, small sample sizes, inadequate allocation concealment, lack of intention-to-treat analyses, non-blinded outcome assessments, and inclusion of subjects without clinical diagnosis that limit the interpretability of research outcomes (53).}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592762/table/tbl26409/ Box 1: Patients with Depression Who May Particularly Benefit From Exercise Programs] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592762/table/tbl26410/ Box 2: Depressive Disorders Other Than Major Depression That May Benefit From Exercise Programs] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592762/table/tbl26411/ Box 3: The Characteristics of an Exercise Program that will Maximize the Anti-depressive Properties] 22. ^1 2 3 4 {{cite journal | vauthors = Den Heijer AE, Groen Y, Tucha L, Fuermaier AB, Koerts J, Lange KW, Thome J, Tucha O | title = Sweat it out? The effects of physical exercise on cognition and behavior in children and adults with ADHD: a systematic literature review | journal = J. Neural Transm. (Vienna) | volume = 124| issue = Suppl 1| pages = 3–26| date = July 2016 | pmid = 27400928 | pmc = 5281644 | doi = 10.1007/s00702-016-1593-7 | quote = }} 23. ^1 {{cite journal | vauthors = Kamp CF, Sperlich B, Holmberg HC | title = Exercise reduces the symptoms of attention-deficit/hyperactivity disorder and improves social behaviour, motor skills, strength and neuropsychological parameters | journal = Acta Paediatr. | volume = 103 | issue = 7 | pages = 709–14 | date = July 2014 | pmid = 24612421 | doi = 10.1111/apa.12628 | quote = The present review summarises the impact of exercise interventions (1–10 weeks in duration with at least two sessions each week) on parameters related to ADHD in 7-to 13-year-old children. We may conclude that all different types of exercise (here yoga, active games with and without the involvement of balls, walking and athletic training) attenuate the characteristic symptoms of ADHD and improve social behaviour, motor skills, strength and neuropsychological parameters without any undesirable side effects. Available reports do not reveal which type, intensity, duration and frequency of exercise is most effective in this respect and future research focusing on this question with randomised and controlled long-term interventions is warranted.}} 24. ^1 2 {{cite journal | vauthors=Petersen RC, Lopez O, Armstrong MJ, Getchius T, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M, Stevens J, Rae-Grant A | title=Practice guideline update summary: Mild cognitive impairment – Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology | journal=Neurology | date=January 2018 | volume=90 | issue=3 | pages=126–135 | pmid=29282327 | pmc=5772157 | doi=10.1212/WNL.0000000000004826 | series=Special article | lay-source=Exercise may improve thinking ability and memory | lay-url=https://www.aan.com/AAN-Resources/Details/press-room/current-press-release/december-27-2017/ | lay-date=27 December 2017 | quote=In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures. ... Clinicians should recommend regular exercise (Level B). ... Recommendation For patients diagnosed with MCI, clinicians should recommend regular exercise (twice/week) as part of an overall approach to management (Level B).}} 25. ^1 2 3 4 {{cite journal | vauthors = Farina N, Rusted J, Tabet N | title = The effect of exercise interventions on cognitive outcome in Alzheimer's disease: a systematic review | journal = Int Psychogeriatr | volume = 26 | issue = 1 | pages = 9–18 | date = January 2014 | pmid = 23962667 | doi = 10.1017/S1041610213001385 | quote = Six RCTs were identified that exclusively considered the effect of exercise in AD patients. Exercise generally had a positive effect on rate of cognitive decline in AD. A meta-analysis found that exercise interventions have a positive effect on global cognitive function, 0.75 (95% CI = 0.32–1.17). ... The most prevalent subtype of dementia is Alzheimer’s disease (AD), accounting for up to 65.0% of all dementia cases ... Cognitive decline in AD is attributable at least in part to the buildup of amyloid and tau proteins, which promote neuronal dysfunction and death (Hardy and Selkoe, 2002; Karran et al., 2011). Evidence in transgenic mouse models of AD, in which the mice have artificially elevated amyloid load, suggests that exercise programs are able to improve cognitive function (Adlard et al., 2005; Nichol et al., 2007). Adlard and colleagues also determined that the improvement in cognitive performance occurred in conjunction with a reduced amyloid load. Research that includes direct indices of change in such biomarkers will help to determine the mechanisms by which exercise may act on cognition in AD.}} 26. ^1 2 3 {{cite journal | vauthors = Rao AK, Chou A, Bursley B, Smulofsky J, Jezequel J | title = Systematic review of the effects of exercise on activities of daily living in people with Alzheimer's disease | journal = Am J Occup Ther | volume = 68 | issue = 1 | pages = 50–56 | date = January 2014 | pmid = 24367955 | doi = 10.5014/ajot.2014.009035 | quote = Alzheimer’s disease (AD) is a progressive neurological disorder characterized by loss in cognitive function, abnormal behavior, and decreased ability to perform basic activities of daily living [(ADLs)] ... All studies included people with AD who completed an exercise program consisting of aerobic, strength, or balance training or any combination of the three. The length of the exercise programs varied from 12 weeks to 12 months. ... Six studies involving 446 participants tested the effect of exercise on ADL performance ... exercise had a large and significant effect on ADL performance (z = 4.07, p < .0001; average effect size = 0.80). ... These positive effects were apparent with programs ranging in length from 12 wk (Santana-Sosa et al., 2008; Teri et al., 2003) and intermediate length of 16 wk (Roach et al., 2011; Vreugdenhil et al., 2012) to 6 mo (Venturelli et al., 2011) and 12 mo (Rolland et al., 2007). Furthermore, the positive effects of a 3-mo intervention lasted 24 mo (Teri et al., 2003). ... No adverse effects of exercise on ADL performance were noted. ... The study with the largest effect size implemented a walking and aerobic program of only 30 min four times a week (Venturelli et al., 2011).| pmc = 5360200 }} 27. ^1 {{vcite2 journal | vauthors = Mattson MP | title = Interventions that improve body and brain bioenergetics for Parkinson's disease risk reduction and therapy | journal = J Parkinsons Dis | volume = 4 | issue = 1 | pages = 1–13 | year = 2014 | pmid = 24473219 | doi = 10.3233/JPD-130335 }} 28. ^1 2 {{vcite2 journal | vauthors = Grazina R, Massano J | title = Physical exercise and Parkinson's disease: influence on symptoms, disease course and prevention | journal = Rev Neurosci | volume = 24 | issue = 2 | pages = 139–152 | year = 2013 | pmid = 23492553 | doi = 10.1515/revneuro-2012-0087 }} 29. ^1 {{vcite2 journal | vauthors = van der Kolk NM, King LA | title = Effects of exercise on mobility in people with Parkinson's disease | journal = Mov. Disord. | volume = 28 | issue = 11 | pages = 1587–1596 | date = September 2013 | pmid = 24132847 | doi = 10.1002/mds.25658 }} 30. ^1 {{vcite2 journal | vauthors = Tomlinson CL, Patel S, Meek C, Herd CP, Clarke CE, Stowe R, Shah L, Sackley CM, Deane KH, Wheatley K, Ives N | title = Physiotherapy versus placebo or no intervention in Parkinson's disease | journal = Cochrane Database Syst Rev | volume = 9 | issue = | pages = CD002817 | date = September 2013 | pmid = 24018704 | doi = 10.1002/14651858.CD002817.pub4 }} 31. ^1 2 {{cite journal | vauthors = Blondell SJ, Hammersley-Mather R, Veerman JL | title = Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies | journal = BMC Public Health | volume = 14 | issue = | pages = 510 | date = May 2014 | pmid = 24885250 | pmc = 4064273 | doi = 10.1186/1471-2458-14-510 | quote = Longitudinal observational studies show an association between higher levels of physical activity and a reduced risk of cognitive decline and dementia. A case can be made for a causal interpretation. Future research should use objective measures of physical activity, adjust for the full range of confounders and have adequate follow-up length. Ideally, randomised controlled trials will be conducted. ... On the whole the results do, however, lend support to the notion of a causal relationship between physical activity, cognitive decline and dementia, according to the established criteria for causal inference.}} 32. ^{{cite journal | vauthors = Carroll ME, Smethells JR | title = Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments | journal = Front. Psychiatry | volume = 6 | issue = | pages = 175 | date = February 2016 | pmid = 26903885 | pmc = 4745113 | doi = 10.3389/fpsyt.2015.00175 | quote = There is accelerating evidence that physical exercise is a useful treatment for preventing and reducing drug addiction ... In some individuals, exercise has its own rewarding effects, and a behavioral economic interaction may occur, such that physical and social rewards of exercise can substitute for the rewarding effects of drug abuse. ... The value of this form of treatment for drug addiction in laboratory animals and humans is that exercise, if it can substitute for the rewarding effects of drugs, could be self-maintained over an extended period of time. Work to date in [laboratory animals and humans] regarding exercise as a treatment for drug addiction supports this hypothesis. ... However, a RTC study was recently reported by Rawson et al. (226), whereby they used 8 weeks of exercise as a post-residential treatment for METH addiction, showed a significant reduction in use (confirmed by urine screens) in participants who had been using meth 18 days or less a month. ... Animal and human research on physical exercise as a treatment for stimulant addiction indicates that this is one of the most promising treatments on the horizon. [emphasis added]}} 33. ^1 {{cite journal |vauthors=Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA | title = Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis | journal = Neurosci Biobehav Rev | volume = 37 | issue = 8 | pages = 1622–1644 |date=September 2013 | pmid = 23806439 | pmc = 3788047 | doi = 10.1016/j.neubiorev.2013.06.011 | quote = }} 34. ^{{cite journal | vauthors= Olsen CM | title = Natural rewards, neuroplasticity, and non-drug addictions | journal = Neuropharmacology | volume = 61 | issue = 7 | pages = 1109–1122 |date=December 2011 | pmid = 21459101 | pmc = 3139704 | doi = 10.1016/j.neuropharm.2011.03.010 | quote = Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse (Cosgrove et al., 2002; Zlebnik et al., 2010). There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers (Daniel et al., 2006; Prochaska et al., 2008), and one drug recovery program has seen success in participants that train for and compete in a marathon as part of the program (Butler, 2005). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008).}} 35. ^{{cite journal | vauthors = Linke SE, Ussher M | title = Exercise-based treatments for substance use disorders: evidence, theory, and practicality | journal = Am J Drug Alcohol Abuse | volume = 41 | issue = 1 | pages = 7–15 | year = 2015 | pmid = 25397661 | doi = 10.3109/00952990.2014.976708 | pmc=4831948 | quote = The limited research conducted suggests that exercise may be an effective adjunctive treatment for SUDs. In contrast to the scarce intervention trials to date, a relative abundance of literature on the theoretical and practical reasons supporting the investigation of this topic has been published. ... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.}} 36. ^{{cite journal | vauthors = Zhou Y, Zhao M, Zhou C, Li R | title = Sex differences in drug addiction and response to exercise intervention: From human to animal studies | journal = Front. Neuroendocrinol. | volume = 40| issue = | pages = 24–41| date = July 2015 | pmid = 26182835 | doi = 10.1016/j.yfrne.2015.07.001 | quote = Collectively, these findings demonstrate that exercise may serve as a substitute or competition for drug abuse by changing ΔFosB or cFos immunoreactivity in the reward system to protect against later or previous drug use. ... As briefly reviewed above, a large number of human and rodent studies clearly show that there are sex differences in drug addiction and exercise. The sex differences are also found in the effectiveness of exercise on drug addiction prevention and treatment, as well as underlying neurobiological mechanisms. The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation. ... In particular, more studies on the neurobiological mechanism of exercise and its roles in preventing and treating drug addiction are needed. | pmc=4712120}} 37. ^1 {{cite journal | vauthors = Cormie P, Nowak AK, Chambers SK, Galvão DA, Newton RU | title = The potential role of exercise in neuro-oncology | journal = Front. Oncol. | volume = 5 | issue = | pages = 85 | date = April 2015 | pmid = 25905043 | pmc = 4389372 | doi = 10.3389/fonc.2015.00085 }} 38. ^1 {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 5, 351 | edition = 2nd | quote = The clinical actions of fluoxetine, like those of many neuropharmacologic agents, reflect drug-induced neural plasticity, which is the process by which neurons adapt over time in response to chronic disturbance. ... For example, evidence indicates that prolonged increases in cortisol may be damaging to hippocampal neurons and can suppress hippocampal neurogenesis (the generation of new neurons postnatally).}} 39. ^{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 199, 215 | chapter=Chapter 8:Atypical Neurotransmitters | edition = 2nd | quote = Neurotrophic factors are polypeptides or small proteins that support the growth, differentiation, and survival of neurons. They produce their effects by activation of tyrosine kinases.}} 40. ^1 2 {{cite journal | vauthors = Batouli SH, Saba V | title = At least eighty percent of brain grey matter is modifiable by physical activity: A review study | journal = Behavioural Brain Research | volume = 332 | issue = | pages = 204–217 | date = June 2017 | pmid = 28600001 | doi = 10.1016/j.bbr.2017.06.002 | quote = The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with PA. This finding has important implications in utilizing PA as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations. ... There is a significant association between the volume of the brain areas and their corresponding functions. Examples include the association of total and regional brain volumes (BV) with executive function and speed of processing, intelligence, working, verbal and spatial memory, and skill acquisition performance [27–29]. The connections between brain function and structure is due to the neural information processing being dependent on the size, arrangement, and configuration of the neurons, the number and type of the synaptic connections of the neurons, on the quality of their connection with distant neurons, and on the properties of non-neuronal cells such as glia [30]. ... This study showed that PA is positively associating with nearly all brain regions.}} 41. ^1 2 {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 147–148, 154–157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = }} 42. ^{{cite journal | vauthors = Carvalho A, Rea IM, Parimon T, Cusack BJ | title = Physical activity and cognitive function in individuals over 60 years of age: a systematic review | journal = Clin Interv Aging | volume = 9 | issue = | pages = 661–682 | year = 2014 | pmid = 24748784 | pmc = 3990369 | doi = 10.2147/CIA.S55520 }} 43. ^1 {{cite journal |vauthors=Ehlert T, Simon P, Moser DA | title = Epigenetics in sports | journal = Sports Med | volume = 43 | issue = 2 | pages = 93–110 | date = February 2013 | pmid = 23329609 | doi = 10.1007/s40279-012-0012-y | quote = Alterations in epigenetic modification patterns have been demonstrated to be dependent on exercise and growth hormone (GH), insulin-like growth factor 1 (IGF-1), and steroid administration. ... the authors observed improved stress coping in exercised subjects. Investigating the dentate gyrus, a brain region which is involved in learning and coping with stressful and traumatic events, they could show that this effect is mediated by increased phosphorylation of serine 10 combined with H3K14 acetylation, which is associated with local opening of condensed chromatin. Consequently, they found increased immediate early gene expression as shown for c-FOS (FBJ murine osteosarcoma viral oncogene homologue).}} 44. ^1 {{cite journal | vauthors = Valkanova V, Eguia Rodriguez R, Ebmeier KP | title = Mind over matter—what do we know about neuroplasticity in adults? | journal = Int Psychogeriatr | volume = 26 | issue = 6 | pages = 891–909 | date = June 2014 | pmid = 24382194 | doi = 10.1017/S1041610213002482 | quote = Control group: Active Intervention: Aerobic exercise [Increased GMV in:] Lobes (dorsal anterior cingulate cortex, supplementary motor area, middle frontal gyrus bilaterally); R inferior frontal gyrus, middle frontal gyrus and L superior temporal lobe; increase in the volume of anterior white matter tracts ... ↑GMV anterior hippocampus}} 45. ^{{cite journal |vauthors=Ruscheweyh R, Willemer C, Krüger K, Duning T, Warnecke T, Sommer J, Völker K, Ho HV, Mooren F, Knecht S, Flöel A | title = Physical activity and memory functions: an interventional study | journal = Neurobiol. Aging | volume = 32 | issue = 7 | pages = 1304–19 |date=July 2011 | pmid = 19716631 | doi = 10.1016/j.neurobiolaging.2009.08.001 |url=}} 46. ^1 2 {{cite journal |vauthors=Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF | title = Exercise training increases size of hippocampus and improves memory | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 108 | issue = 7 | pages = 3017–3022 |date=February 2011 | pmid = 21282661 | pmc = 3041121 | doi = 10.1073/pnas.1015950108 |url=| bibcode = 2011PNAS..108.3017E }} 47. ^{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | page = 315 | edition = 2nd | chapter = Chapter 13: Higher Cognitive Function and Behavioral Control | quote = The anterior cingulate cortex is involved in processes that require correct decision-making, as seen in conflict resolution (eg, the Stroop test, see in Chapter 16), or cortical inhibition (eg, stopping one task and switching to another). The medial prefrontal cortex is involved in supervisory attentional functions (eg, action-outcome rules) and behavioral flexibility (the ability to switch strategies). The dorsolateral prefrontal cortex, the last brain area to undergo myelination during development in late adolescence, is implicated in matching sensory inputs with planned motor responses. The ventromedial prefrontal cortex seems to regulate social cognition, including empathy. The orbitofrontal cortex is involved in social decision making and in representing the valuations assigned to different experiences. }} 48. ^{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 147, 266, 376 | edition = 2nd | quote = }} 49. ^{{cite journal | vauthors = Grimaldi G, Argyropoulos GP, Bastian A, Cortes M, Davis NJ, Edwards DJ, Ferrucci R, Fregni F, Galea JM, Hamada M, Manto M, Miall RC, Morales-Quezada L, Pope PA, Priori A, Rothwell J, Tomlinson SP, Celnik P | title = Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease | journal = Neuroscientist | volume = 22 | issue = 1| pages = 83–97 | year = 2014 | pmid = 25406224 | doi = 10.1177/1073858414559409 | pmc=4712385}} 50. ^1 2 {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 148, 324–328, 438 | edition = 2nd | quote = }} 51. ^1 2 3 4 5 6 {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 313–321 | edition = 2nd | chapter = Chapter 13: Higher Cognitive Function and Behavioral Control | quote =}} 52. ^{{cite journal | vauthors = Sereno MI, Huang RS | title = Multisensory maps in parietal cortex | journal = Curr. Opin. Neurobiol. | volume = 24 | issue = 1 | pages = 39–46 | year = 2014 | pmid = 24492077 | pmc = 3969294 | doi = 10.1016/j.conb.2013.08.014 |url=}} 53. ^{{cite journal |vauthors=Moreau D, Kirk IJ, Waldie, KE | title = High-intensity training enhances executive function in children in a randomized, placebo-controlled trial | journal = eLife | volume = 6:e25062 | issue = | page = | year = 2017 | pmid = 28825973 | pmc = 5566451| doi = 10.7554/eLife.25062 }} 54. ^1 {{cite journal | vauthors = Ilieva IP, Hook CJ, Farah MJ | title = Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis | journal = J Cogn Neurosci | volume = 27 | issue = 6| pages = 1–21 | year = 2015 | pmid = 25591060 | doi = 10.1162/jocn_a_00776| url = https://repository.upenn.edu/neuroethics_pubs/130 }} 55. ^1 2 3 4 {{cite journal | vauthors= Diamond A | title = Executive functions | journal = Annu Rev Psychol | volume = 64 | issue = | pages = 135–168 | year = 2013 | pmid = 23020641 | pmc = 4084861 | doi = 10.1146/annurev-psych-113011-143750 | quote = }} 56. ^1 2 {{cite journal | vauthors = Janssen M, Toussaint HM, van Mechelen W, Verhagen EA | title = Effects of acute bouts of physical activity on children's attention: a systematic review of the literature | journal = SpringerPlus | volume = 3 | issue = | pages = 410 | year = 2014 | pmid = 25133092 | pmc = 4132441 | doi = 10.1186/2193-1801-3-410 | quote = There is weak evidence for the effect of acute bouts of physical activity on attention. ... Fortunately, the literature-base on the acute effect of PA on the underlying cognitive processes of academic performance is growing. Hillman et al. (2011) found in their review a positive effect of acute PA on brain health and cognition in children, but concluded it was complicated to compare the different studies due to the different outcome measures (e.g. memory, response time and accuracy, attention, and comprehension). Therefore, this review focuses on the sole outcome measure ‘attention’ as a mediator for cognition and achievement.}} 57. ^{{Cite journal|last=Northey|first=Joseph Michael|last2=Cherbuin|first2=Nicolas|last3=Pumpa|first3=Kate Louise|last4=Smee|first4=Disa Jane|last5=Rattray|first5=Ben|date=30 March 2017|title=Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis|url=http://bjsm.bmj.com/content/early/2017/03/30/bjsports-2016-096587|journal=Br J Sports Med|volume=52|issue=3|language=en|pages=bjsports–2016–096587|doi=10.1136/bjsports-2016-096587|issn=0306-3674|pmid=28438770}} 58. ^{{cite journal|last1=Delezie|first1=Julien|last2=Handschin|first2=Christoph|title=Endocrine Crosstalk Between Skeletal Muscle and the Brain|journal=Frontiers in Neurology|volume=9|year=2018|issn=1664-2295|pmid=30197620|doi=10.3389/fneur.2018.00698}} 59. ^1 2 3 4 5 6 {{cite journal |vauthors=Phillips C, Baktir MA, Srivatsan M, Salehi A | title = Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling | journal = Front Cell Neurosci | volume = 8 | issue = | pages = 170 | year = 2014 | pmid = 24999318 | pmc = 4064707 | doi = 10.3389/fncel.2014.00170 | quote = }} 60. ^1 2 {{cite journal |vauthors=Heinonen I, Kalliokoski KK, Hannukainen JC, Duncker DJ, Nuutila P, Knuuti J | title = Organ-Specific Physiological Responses to Acute Physical Exercise and Long-Term Training in Humans | journal = Physiology | volume = 29 | issue = 6 | pages = 421–436 | date = November 2014 | pmid = 25362636 | doi = 10.1152/physiol.00067.2013 | quote = }} 61. ^1 2 {{cite book | vauthors = Aberg D | title = Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis | journal = Endocr Dev | volume = 17 | issue = | pages = 63–76 | year = 2010 | pmid = 19955757 | doi = 10.1159/000262529 | quote = | series = Endocrine Development | isbn = 978-3-8055-9302-1 }} 62. ^1 2 {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 221, 412 | edition = 2nd | quote = }} 63. ^1 2 3 {{cite journal | vauthors = Torres-Aleman I | title = Toward a comprehensive neurobiology of IGF-I | journal = Dev Neurobiol | volume = 70 | issue = 5 | pages = 384–96 | year = 2010 | pmid = 20186710 | doi = 10.1002/dneu.20778 | quote = }} 64. ^{{cite journal | vauthors = Gatti R, De Palo EF, Antonelli G, Spinella P | title = IGF-I/IGFBP system: metabolism outline and physical exercise | journal = J. Endocrinol. Invest. | volume = 35 | issue = 7 | pages = 699–707 | date = July 2012 | pmid = 22714057 | doi = 10.3275/8456 |quote =Copeland et al. (90) studied the effect of a moderate-intensity exercise and a high-intensity equal duration intervalled exercise in healthy males. IGF-I and IGFBP-3 increased during both exercise trials, but only the IGFBP-3 area under curve was significantly greater during high-intensity exercise than resting control session. ... Decreased IGF-I and increased IGFBP-1 levels, observed by Rarick et al. (100) after mild aerobic training, might be an adaptive physiological response to prevent hypoglycemia following insulin-sensitizing training. In fact the decrease of circulating IGF-I during short-term training seems to be reflective of favorable neuromuscular anabolic adaptation and is a normal adaptive response to increased physical activity. The potential for exercise-induced increases in circulating IGF-I seems to require longer training duration (100).}} 65. ^1 2 {{cite journal | vauthors = Tarumi T, Zhang R | title = Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise | journal = Front Physiol | volume = 5 | issue = | pages = 6 | date = January 2014 | pmid = 24478719 | pmc = 3896879 | doi = 10.3389/fphys.2014.00006 | quote = Exercise-related improvements in brain function and structure may be conferred by the concurrent adaptations in vascular function and structure. Aerobic exercise increases the peripheral levels of growth factors (e.g., BDNF, IFG-1, and VEGF) which cross the blood-brain barrier (BBB) and stimulate neurogenesis and angiogenesis (Trejo et al., 2001; Lee et al., 2002; Fabel et al., 2003; Lopez-Lopez et al., 2004).}} 66. ^1 {{cite journal | vauthors = Bouchard J, Villeda SA | title = Aging and brain rejuvenation as systemic events | journal = J. Neurochem. | volume = 132 | issue = 1 | pages = 5–19 | year = 2015 | pmid = 25327899 | pmc = 4301186 | doi = 10.1111/jnc.12969 | quote = }} 67. ^1 {{cite journal | vauthors = Basso JC, Shang A, Elman M, Karmouta R, Suzuki WA | title = Acute Exercise Improves Prefrontal Cortex but not Hippocampal Function in Healthy Adults | journal = Journal of the International Neuropsychological Society : JINS | volume = 21 | issue = 10 | pages = 791–801 | date = November 2015 | pmid = 26581791 | doi = 10.1017/S135561771500106X | url = }} 68. ^1 {{cite journal | vauthors = McMorris T, Hale BJ | title = Differential effects of differing intensities of acute exercise on speed and accuracy of cognition: a meta-analytical investigation | journal = Brain and Cognition | volume = 80 | issue = 3 | pages = 338–351 | date = December 2012 | pmid = 23064033 | doi = 10.1016/j.bandc.2012.09.001 | url = }} 69. ^{{Cite journal|last=Dodwell|first=Gordon|last2=Müller|first2=Hermann J.|last3=Töllner|first3=Thomas|date=12 October 2018|title=Electroencephalographic evidence for improved visual working memory performance during standing and exercise|journal=British Journal of Psychology|language=en|doi=10.1111/bjop.12352|pmid=30311188|issn=0007-1269}} 70. ^1 2 {{cite journal | vauthors = Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A | title = Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high' | journal = J. Exp. Biol. | volume = 215 | issue = Pt 8 | pages = 1331–1336 | year = 2012 | pmid = 22442371 | doi = 10.1242/jeb.063677 | quote = Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. ... Thus, a neurobiological reward for endurance exercise may explain why humans and other cursorial mammals habitually engage in aerobic exercise despite the higher associated energy costs and injury risks}} 71. ^{{cite journal | vauthors = Cohen EE, Ejsmond-Frey R, Knight N, Dunbar RI | title = Rowers' high: behavioural synchrony is correlated with elevated pain thresholds | journal = Biol. Lett. | volume = 6 | issue = 1 | pages = 106–108 | year = 2010 | pmid = 19755532 | pmc = 2817271 | doi = 10.1098/rsbl.2009.0670 |url=}} 72. ^{{cite journal | vauthors = Berry MD, Gainetdinov RR, Hoener MC, Shahid M | title = Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges | journal = Pharmacology & Therapeutics | volume = 180 | issue = | pages = 161–180 | date = December 2017 | pmid = 28723415 | doi = 10.1016/j.pharmthera.2017.07.002 | quote = As initial trace amine research focussed largely on p-tyramine, 2-phenylethylamine, and to a lesser extent tryptamine and p-octopamine, the term subsequently became synonymous with these compounds. These initial research efforts stalled, however, through a combination of a focus on the “false neurotransmitter”, amphetamine-like, indirect sympathomimetic action of p-tyramine and 2-phenylethylamine at plasma membrane monoamine transporters, and the lack of a receptor target for other effects.}} 73. ^1 2 3 4 {{cite journal | vauthors = Szabo A, Billett E, Turner J | title = Phenylethylamine, a possible link to the antidepressant effects of exercise? | journal = Br J Sports Med | volume = 35 | issue = 5 | pages = 342–343 | year = 2001 | pmid = 11579070 | pmc = 1724404 | doi = 10.1136/bjsm.35.5.342| quote = The 24 hour mean urinary concentration of phenylacetic acid was increased by 77% after exercise. ... As phenylacetic acid reflects phenylethylamine levels3, and the latter has antidepressant effects, the antidepressant effects of exercise appear to be linked to increased phenylethylamine concentrations. Furthermore, considering the structural and pharmacological analogy between amphetamines and phenylethylamine, it is conceivable that phenylethylamine plays a role in the commonly reported "runners high" thought to be linked to cerebral β-endorphin activity. The substantial increase in phenylacetic acid excretion in this study implies that phenylethylamine levels are affected by exercise. ... A 30 minute bout of moderate to high intensity aerobic exercise increases phenylacetic acid levels in healthy regularly exercising men.}} 74. ^1 2 3 4 {{cite journal | vauthors = Lindemann L, Hoener MC | title = A renaissance in trace amines inspired by a novel GPCR family | journal = Trends Pharmacol. Sci. | volume = 26 | issue = 5 | pages = 274–281 | year = 2005 | pmid = 15860375 | doi = 10.1016/j.tips.2005.03.007 | quote = The pharmacology of TAs might also contribute to a molecular understanding of the well-recognized antidepressant effect of physical exercise [51]. In addition to the various beneficial effects for brain function mainly attributed to an upregulation of peptide growth factors [52,53], exercise induces a rapidly enhanced excretion of the main β-PEA metabolite β-phenylacetic acid (b-PAA) by on average 77%, compared with resting control subjects [54], which mirrors increased β-PEA synthesis in view of its limited endogenous pool half-life of ~30 s [18,55].}} 75. ^1 2 3 4 {{cite journal | vauthors = Berry MD | title = The potential of trace amines and their receptors for treating neurological and psychiatric diseases | journal = Rev Recent Clin Trials | volume = 2 | issue = 1 | pages = 3–19 | year = 2007 | pmid = 18473983 | doi = 10.2174/157488707779318107| quote = It has also been suggested that the antidepressant effects of exercise are due to an exercise-induced elevation of PE [151].| citeseerx = 10.1.1.329.563 }} 76. ^1 {{cite journal | vauthors= Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacol. Ther. | volume = 125 | issue = 3 | pages = 363–375 |date=March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005 | quote = Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ... Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ... Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ...}} 77. ^1 2 3 4 {{cite journal | vauthors = Dinas PC, Koutedakis Y, Flouris AD | title = Effects of exercise and physical activity on depression | journal = Ir J Med Sci | volume = 180 | issue = 2 | pages = 319–325 | year = 2011 | pmid = 21076975 | doi = 10.1007/s11845-010-0633-9 | quote = }} 78. ^1 2 3 4 {{cite journal | vauthors = Tantimonaco M, Ceci R, Sabatini S, Catani MV, Rossi A, Gasperi V, Maccarrone M | title = Physical activity and the endocannabinoid system: an overview | journal = Cell. Mol. Life Sci. | volume = 71 | issue = 14 | pages = 2681–2698 | year = 2014 | pmid = 24526057 | doi = 10.1007/s00018-014-1575-6 | quote = }} 79. ^{{cite journal | vauthors = Fuss J, Steinle J, Bindila L, Auer MK, Kirchherr H, Lutz B, and Gass P | title = A runner's high depends on cannabinoid receptors in mice | journal = PNAS | volume = 112 | issue = 42 | pages = 13105–13108| year = 2015 | pmid = 26438875 | doi = 10.1073/pnas.1514996112 | pmc=4620874 | quote = | bibcode = 2015PNAS..11213105F }} 80. ^1 2 3 {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 350–359 | chapter = Chapter 14: Mood and Emotion | edition = 2nd | quote = The excessive release of stress hormones, such as cortisol, which occurs in many individuals with mood disorders, may result from hyperfunctioning of the PVN of the hypothalamus, hyperfunctioning of the amygdala (which activates the PVN), or hypofunctioning of the hippocampus (which exerts a potent inhibitory influence on the PVN). ... Chronic stress decreases the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, which in turn may contribute to the atrophy of CA3 neurons and their increased vulnerability to a variety of neuronal insults. Chronic elevation of glucocorticoid levels is also known to decrease the survival of these neurons. Such activity may increase the dendritic arborizations and survival of the neurons, or help repair or protect the neurons from further damage. ... Stress and glucocorticoids inhibit, and a wide variety of antidepressant drugs, exercise, and enriched environments activate hippocampal neurogenesis.}} 81. ^1 2 3 4 {{cite journal | vauthors = Fuqua JS, Rogol AD | title = Neuroendocrine alterations in the exercising human: implications for energy homeostasis | journal = Metab. Clin. Exp. | volume = 62 | issue = 7 | pages = 911–921 | date = July 2013 | pmid = 23415825 | doi = 10.1016/j.metabol.2013.01.016 | quote = }} 82. ^1 2 3 {{cite journal | vauthors = Ebner NC, Kamin H, Diaz V, Cohen RA, MacDonald K | title = Hormones as "difference makers" in cognitive and socioemotional aging processes | journal = Front Psychol | volume = 5 | issue = | pages = 1595 | date = January 2015 | pmid = 25657633 | pmc = 4302708 | doi = 10.3389/fpsyg.2014.01595 | quote = }} 83. ^1 2 3 4 5 6 7 8 {{cite journal |vauthors=Silverman MN, Deuster PA | title = Biological mechanisms underlying the role of physical fitness in health and resilience | journal = Interface Focus | volume = 4 | issue = 5 | pages = 20140040 | date = October 2014 | pmid = 25285199 | doi = 10.1098/rsfs.2014.0040 | pmc=4142018 | quote = }} 84. ^1 {{cite journal |vauthors=Zschucke E, Gaudlitz K, Ströhle A | title = Exercise and physical activity in mental disorders: clinical and experimental evidence | journal = J Prev Med Public Health | volume = 46 Suppl 1 | issue = | pages = S12–521 | date = January 2013 | pmid = 23412549 | pmc = 3567313 | doi = 10.3961/jpmph.2013.46.S.S12 | quote = In psychiatric patients, different mechanisms of action for PA and EX have been discussed: On a neurochemical and physiological level, a number of acute changes occur during and following bouts of EX, and several long-term adaptations are related to regular EX training. For instance, EX has been found to normalize reduced levels of brain-derived neurotrophic factor (BDNF) and therefore has neuroprotective or even neurotrophic effects [7–9]. Animal studies found EX-induced changes in different neurotransmitters such as serotonin and endorphins [10,11], which relate to mood, and positive effects of EX on stress reactivity (e.g., the hypothalamus-pituitary-adrenal axis [12,13]). Finally, anxiolytic effects of EX mediated by atrial natriuretic peptide have been reported [14]. Potential psychological mechanisms of action include learning and extinction, changes in body scheme and health attitudes/behaviors, social reinforcement, experience of mastery, shift of external to more internal locus of control, improved coping strategies, or simple distraction [15,16]. }} 85. ^{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 117–130 | edition = 2nd | chapter = Chapter 5: Excitatory and Inhibitory Amino Acids | quote = {{bull}} The major excitatory neurotransmitter in the brain is glutamate; the major inhibitory neurotransmitter is GABA. ... {{bull}} The most extensively studied form of synaptic plasticity is long-term potentiation (LTP) in the hippocampus, which is triggered by strong activation of NMDA receptors and the consequent large rise in postsynaptic calcium concentration. {{bull}} Long-term depression (LTD), a long-lasting decrease in synaptic strength, also occurs at most excitatory and some inhibitory synapses in the brain. ... The bidirectional control of synaptic strength by LTP and LTD is believed to underlie some forms of learning and memory in the mammalian brain.}} 86. ^1 {{cite journal | vauthors = Mischel NA, Subramanian M, Dombrowski MD, Llewellyn-Smith IJ, Mueller PJ | title = (In)activity-related neuroplasticity in brainstem control of sympathetic outflow: unraveling underlying molecular, cellular, and anatomical mechanisms | journal = Am. J. Physiol. Heart Circ. Physiol. | volume = 309 | issue = 2 | pages = H235–43 | date = May 2015 | pmid = 25957223 | doi = 10.1152/ajpheart.00929.2014 | pmc=4504968}} 87. ^1 2 3 {{cite journal | vauthors= Sibley BA, Etnier JL | year = 2003 | title = The Relationship Between Physical Activity and Cognition in Children: A Meta-Analysis | url = | journal = Pediatric Exercise Science | volume = 15 | issue = 3| pages = 243–256 | doi = 10.1123/pes.15.3.243 }} 88. ^1 2 {{cite journal | vauthors= Chaddock I, Erickson KI, Prakash RS, Kim JS, Voss MA, VanPatter M, etal | year = 2010 | title = A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children | journal = Brain Research | volume = 1358 | issue = | pages = 172–183 | doi=10.1016/j.brainres.2010.08.049 | pmid=20735996 | pmc=3953557 }} 89. ^1 2 {{cite journal | vauthors= Best JR | year = 2010 | title = Effects of physical activity on children's executive function: Contributions of experimental research on aerobic exercise | url = | journal = Developmental Review | volume = 30 | issue = 4| pages = 331–351 | doi = 10.1016/j.dr.2010.08.001 | pmid = 21818169 | pmc = 3147174 }} 90. ^1 2 {{cite journal | vauthors= Hillman CH, Erickson KI, Kramer AF | year = 2008 | title = Be smart, exercise your heart: exercise effects on brain and cognition | url = | journal = Nature Reviews Neuroscience | volume = 9 | issue = 1| pages = 58–65 | doi=10.1038/nrn2298 | pmid=18094706}} 91. ^{{Cite journal|last=COE|first=DAWN PODULKA|last2=PIVARNIK|first2=JAMES M.|last3=WOMACK|first3=CHRISTOPHER J.|last4=REEVES|first4=MATHEW J.|last5=MALINA|first5=ROBERT M.|date=1 August 2006|title=Effect of Physical Education and Activity Levels on Academic Achievement in Children|journal=Medicine & Science in Sports & Exercise|language=ENGLISH|volume=38|issue=8|pages=1515–1519|doi=10.1249/01.mss.0000227537.13175.1b|pmid=16888468|issn=0195-9131}} 92. ^1 {{cite journal | vauthors= Chaddock L, Hillman CH, Buck SM, Cohen NJ | year = 2011 | title = Aerobic Fitness and Executive Control of Relational Memory in Preadolescent Children | url = | journal = Medicine & Science in Sports & Exercise | volume = 43 | issue = 2| pages = 344–349 | doi=10.1249/mss.0b013e3181e9af48| pmid = 20508533 }} 93. ^{{cite journal | vauthors= Dik MG, Deeg DJH, Visser M, Jonker C | year = 2003 | title = Early Life Physical Activity and Cognition at Old Age | url = | journal = Journal of Clinical and Experimental Neuropsychology | volume = 25 | issue = 5| pages = 643–653 | doi=10.1076/jcen.25.5.643.14583}} 94. ^Swardfager W, Herrmann N, Marzolini S, Saleem M, Kiss A, Shammi P, Oh PI and Lanctôt KL, 2010. Cardiopulmonary fitness is associated with cognitive performance in patients with coronary artery disease. J. Amer. Geriatrics. Soc. 58(8):1519–25.===Addiction{{anchor|ΔFosB|ΔFosB and addiction}}===Clinical and preclinical evidence indicate that consistent aerobic exercise, especially endurance exercise (e.g., marathon running), actually prevents the development of certain drug addictions and is an effective adjunct treatment for drug addiction, and psychostimulant addiction in particular. Consistent aerobic exercise magnitude-dependently (i.e., by duration and intensity) reduces drug addiction risk, which appears to occur through the reversal of drug-induced, addiction-related neuroplasticity. One review noted that exercise may prevent the development of drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of the reward system. Moreover, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces opposite effects on striatal dopamine receptor D2 (DRD2) signaling (increased DRD2 density) to those induced by pathological stimulant use (decreased DRD2 density). Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction. {{As of|2016}}, more clinical research is still needed to understand the mechanisms and confirm the efficacy of exercise in drug addiction treatment and prevention.{{FOSB addiction table|Table title=Summary of addiction-related plasticity}}===Attention deficit hyperactivity disorder===Regular physical exercise, particularly aerobic exercise, is an effective add-on treatment for ADHD in children and adults, particularly when combined with stimulant medication (i.e., amphetamine or methylphenidate), although the best intensity and type of aerobic exercise for improving symptoms are not currently known.{{cite journal | vauthors = Rommel AS, Halperin JM, Mill J, Asherson P, Kuntsi J | title = Protection from genetic diathesis in attention-deficit/hyperactivity disorder: possible complementary roles of exercise | journal = J. Am. Acad. Child Adolesc. Psychiatry | volume = 52 | issue = 9 | pages = 900–910 | date = September 2013 | pmid = 23972692 | pmc = 4257065 | doi = 10.1016/j.jaac.2013.05.018 | quote = As exercise has been found to enhance neural growth and development, and improve cognitive and behavioural functioning in [healthy] individuals and animal studies, we reviewed the literature on the effects of exercise in children and adolescents with ADHD and animal models of ADHD behaviours. A limited number of undersized non-randomized, retrospective and cross-sectional studies have investigated the impact of exercise on ADHD and the emotional, behavioural and neuropsychological problems associated with the disorder. The findings from these studies provide some support for the notion that exercise has the potential to act as a protective factor for ADHD. ... Although it remains unclear which role, if any, BDNF plays in the pathophysiology of ADHD, enhanced neural functioning has been suggested to be associated with the reduction of remission of ADHD symptoms.49,50,72 As exercise can elicit gene expression changes mediated by alterations in DNA methylation38, the possibility emerges that some of the positive effects of exercise could be caused by epigenetic mechanisms, which may set off a cascade of processes instigated by altered gene expression that could ultimately link to a change in brain function.}} 95. ^{{cite journal | vauthors = Brené S, Bjørnebekk A, Aberg E, Mathé AA, Olson L, Werme M | title = Running is rewarding and antidepressive | journal = Physiol. Behav. | volume = 92 | issue = 1–2 | pages = 136–140 | year = 2007 | pmid = 17561174 | pmc = 2040025 | doi = 10.1016/j.physbeh.2007.05.015 }} 96. ^1 {{cite journal | vauthors = Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, McMurdo M, Mead GE | title = Exercise for depression | journal = Cochrane Database Syst. Rev. | volume = 9 | issue = 9 | pages = CD004366 | date = September 2013 | pmid = 24026850 | doi = 10.1002/14651858.CD004366.pub6 | quote = Exercise is moderately more effective than a control intervention for reducing symptoms of depression, but analysis of methodologically robust trials only shows a smaller effect in favour of exercise. When compared to psychological or pharmacological therapies, exercise appears to be no more effective, though this conclusion is based on a few small trials.}} 97. ^{{cite journal | vauthors = Gong H, Ni C, Shen X, Wu T, Jiang C | title = Yoga for prenatal depression: a systematic review and meta-analysis | journal = BMC Psychiatry | volume = 15 | issue = | pages = 14 | date = February 2015 | pmid = 25652267 | pmc = 4323231 | doi = 10.1186/s12888-015-0393-1 }} 98. ^{{cite journal | vauthors = Adlard PA, Perreau VM, Pop V, Cotman CW | title = Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease | journal = J. Neurosci. | volume = 25 | issue = 17 | pages = 4217–21 | year = 2005 | pmid = 15858047 | doi = 10.1523/JNEUROSCI.0496-05.2005 }} 99. ^1 {{cite journal | vauthors = Elwood P, Galante J, Pickering J, Palmer S, Bayer A, Ben-Shlomo Y, Longley M, Gallacher J | title = Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the Caerphilly cohort study | journal = PLoS ONE | volume = 8 | issue = 12 | pages = e81877 | date = December 2013 | pmid = 24349147 | pmc = 3857242 | doi = 10.1371/journal.pone.0081877 | url = | bibcode = 2013PLoSO...881877E }} 100. ^{{cite journal | vauthors = Morgan GS, Gallacher J, Bayer A, Fish M, Ebrahim S, Ben-Shlomo Y | title = Physical activity in middle-age and dementia in later life: findings from a prospective cohort of men in Caerphilly, South Wales and a meta-analysis | journal = J. Alzheimers Dis. | volume = 31 | issue = 3 | pages = 569–80 | year = 2012 | pmid = 22647258 | doi = 10.3233/JAD-2012-112171 | url = }} 101. ^{{cite journal | vauthors= Baatile J, Langbein WE, Weaver F, Maloney C, Jost MB | year = 2000 | title = Effect of exercise on perceived quality of life of individuals with Parkinson's Disease | url = | journal = Journal of Rehabilitation Research and Development | volume = 37 | issue = 5| pages = 529–534 }} 102. ^1 {{cite journal | vauthors= Kramer AF, Erickson KI, Colcombe SJ | year = 2006 | title = Exercise, cognition, and the aging brain | url = | journal = Journal of Applied Physiology | volume = 101 | issue = 4| pages = 1237–1242 | doi=10.1152/japplphysiol.00500.2006 | pmid=16778001}} 103. ^{{cite journal | vauthors = Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, Chason J, Vakil E, Bardell L, Boileau RA, Colcombe A | title = Ageing, fitness and neurocognitive function | journal = Nature | volume = 400 | issue = 6743 | pages = 418–419 | date = July 1999 | pmid = 10440369 | doi = 10.1038/22682 | url = | bibcode = 1999Natur.400..418K }} 104. ^1 {{cite journal | vauthors= Nocera JR, Altman LJ, Sapienza C, Okun MS, Hass CJ | year = 2010 | title = Can exercise improve language and cognition in Parkinson's disease? A case report | url = | journal = Neurocase: The Neural Basis of Cognition | volume = 16 | issue = 4| pages = 301–306 | doi=10.1080/13554790903559663| pmid = 20391181 }} References 17 : Addiction|Addiction medicine|Aerobic exercise|Antidepressants|Attention|Cognition|Cognitive neuroscience|Epigenetics|Euphoriants|Exercise physiology|Memory|Neuropsychology|Physical exercise|Physical psychiatric treatments|Treatment and management of attention deficit hyperactivity disorder|Treatment of depression|Sports science |
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