View source for Philosophy:Neurobiological effects of physical exercise

{{short description|Neural, cognitive, and behavioral effects of physical exercise}}
{{Infobox medical intervention
| Name         = Neurobiological effects of<br />physical exercise
| subheader    = Exercise therapy&nbsp;–&nbsp;medical intervention
| image        = Jogging Woman in Grass.jpg
| caption      = A woman engaging in aerobic exercise (jogging)
| alt          = Image of a woman running
| ICD9         = [http://www.icd9data.com/2015/Volume3/87-99/93/default.htm#93.1 93.19]
| MeshID       = D005081
| LOINC        = {{LOINC|73986-2}}
| other_codes  = 
| MedlinePlus  = 
| eMedicine    = 324583
}}

The '''neurobiological effects of physical exercise''' involve possible interrelated effects on brain structure, brain function, and [[Cognition|cognition]].<ref name="Summary as of August 2015">{{cite journal|vauthors=Erickson KI, Hillman CH, Kramer AF|title=Physical activity, brain, and cognition|journal=Current Opinion in Behavioral Sciences|date=August 2015|volume=4|pages=27–32|doi=10.1016/j.cobeha.2015.01.005 |s2cid=54301951}}</ref><ref name="Exercise – neurotrophic factors + basal ganglia">{{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}}</ref><ref name="Summary of effects">{{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}}</ref><ref name="epigenome">{{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 | s2cid = 30210091}}</ref> Research in humans has demonstrated that consistent [[Medicine:Aerobic exercise|aerobic exercise]] (e.g., 30&nbsp;minutes every day) may induce improvements in certain cognitive functions, [[Biology:Neuroplasticity|neuroplasticity]] and [[Biology:Behavioral plasticity|behavioral plasticity]]; some of these long-term effects may include  increased [[Biology:Adult neurogenesis|neuron growth]], increased neurological activity (e.g., [[Biology:C-Fos|c-Fos]] and [[Biology:Brain-derived neurotrophic factor|BDNF]] signaling), improved stress coping, enhanced cognitive control of behavior, improved declarative, [[Physics:Spatial memory|spatial]], and [[Working memory|working]] memory, and structural and functional improvements in brain structures and pathways associated with cognitive control and memory.<ref name="Comprehensive review">{{cite journal |vauthors=Gomez-Pinilla F, Hillman C | journal = Comprehensive Physiology |title = The influence of exercise on cognitive abilities | volume = 3 | issue = 1 | pages = 403–428 | date = January 2013 | pmid = 23720292 | pmc = 3951958 | doi = 10.1002/cphy.c110063 | isbn = 9780470650714 }}</ref><ref name="cognitive control of exercise">{{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 | page = 747 | year = 2014 | pmid = 25324754 | pmc = 4179677 | doi = 10.3389/fnhum.2014.00747| doi-access = free }}</ref><ref name="Exercise healthy young adult 2016 SystRev">{{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}}</ref> The effects of exercise on cognition may affect academic performance in children and college students, improve adult productivity, preserve cognitive function in old age, preventing or treating certain [[Medicine:Neurological disorder|neurological disorder]]s, and improving overall [[Philosophy:Quality of life|quality of life]].<ref>{{Cite web |last=CDC |date=2023-08-01 |title=Benefits of Physical Activity |url=https://www.cdc.gov/physicalactivity/basics/pa-health/index.htm |access-date=2023-12-07 |website=Centers for Disease Control and Prevention |language=en-us}}</ref><ref name="Depression QoL meta-analysis">{{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 | pages = 47–54 | date = July 2016 | pmid = 27155287 | doi = 10.1016/j.psychres.2016.04.054 | s2cid = 4787287| url = https://kclpure.kcl.ac.uk/portal/en/publications/9d2c5d0c-a5a9-4e46-a763-6b1398bce0f6 }}</ref><ref name="Aging QoL review">{{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 =  International Scholarly Research Notices| volume = 2014 | pages = 257248 | date = November 2014 | pmid = 27351018 | doi = 10.1155/2014/257248 | pmc=4897547| doi-access = free }}</ref><ref>{{cite journal | vauthors = Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, Sorrentino G | title = Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits | journal = Frontiers in Psychology | volume = 9 | pages = 509 | date = 27 April 2018 | pmid = 29755380 | pmc = 5934999 | doi = 10.3389/fpsyg.2018.00509 | doi-access = free }}</ref>

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 consistent exercise over the course of several months.<ref name="Summary as of August 2015" /><ref name="Exercise healthy young adult 2016 SystRev" /><ref name="Neurobiological effects of acute exercise – 2017 review">{{cite journal | vauthors = Basso JC, Suzuki WA | title = The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review | journal = Brain Plasticity | volume = 2 | issue = 2 | pages = 127–152 | date = March 2017 | pmid = 29765853 | pmc = 5928534 | doi = 10.3233/BPL-160040| doi-access = free }}</ref> People who regularly perform an aerobic exercise (e.g., running, jogging, brisk walking, swimming, and cycling) have greater scores on [[Medicine:Neuropsychological test|neuropsychological function and performance tests]] that measure certain cognitive functions, such as [[Biology:Attentional control|attentional control]], [[Philosophy:Inhibitory control|inhibitory control]], [[Philosophy:Cognitive flexibility|cognitive flexibility]], [[Working memory|working memory]] updating and capacity, declarative memory, [[Physics:Spatial memory|spatial memory]], and [[Physics:Mental chronometry|information processing speed]].<ref name="Comprehensive review" /><ref name="Exercise healthy young adult 2016 SystRev" /><ref name="Neurobiological effects of acute exercise – 2017 review" /><ref>{{Cite web |publisher=Department of Health & Human Services|title=Exercise and mental health |url=http://www.betterhealth.vic.gov.au/health/healthyliving/exercise-and-mental-health |access-date=19 November 2022 |website=betterhealth.vic.gov.au |language=en}}</ref><ref>{{Cite journal |year=2013 |title=Exercise and Mental Health |url=http://dx.doi.org/10.5040/9781492595502.part-002 |journal=Exercise Psychology |pages=93–94 |doi=10.5040/9781492595502.part-002|isbn=9781492595502 }}</ref>

Aerobic exercise has both short and long term effects on mood and emotional states by promoting positive affect, inhibiting negative affect, and decreasing the biological response to acute [[Medicine:Psychological stress|psychological stress]].<ref name="Neurobiological effects of acute exercise – 2017 review" />  Aerobic exercise may affect both self-esteem and overall well-being (including sleep patterns) with consistent, long term participation.<ref>{{Cite web |title=10 great reasons to love aerobic exercise |url=https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/aerobic-exercise/art-20045541 |access-date=2023-12-05 |website=Mayo Clinic |language=en}}</ref> Regular aerobic exercise may improve symptoms associated with central nervous system disorders and may be used as adjunct therapy for these disorders. There is some evidence of exercise treatment efficacy for major depressive disorder and [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]].<ref name="Depression QoL meta-analysis" /><ref name="Exercise depression intervention">{{cite journal |vauthors=Josefsson T, Lindwall M, Archer T |year=2014 |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 |doi=10.1111/sms.12050 |pmid=23362828 |s2cid=29351791|doi-access=free }}</ref><ref name="Exercise MDD antidepressant">{{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 | s2cid = 32304140}}</ref><ref name="ADHD exercise 2016 SystRev">{{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}}</ref> The American Academy of Neurology's clinical practice guideline for [[Medicine:Mild cognitive impairment|mild cognitive impairment]] indicates that clinicians should recommend regular exercise (two times per week) to individuals who have been diagnosed with this condition.<ref name="December 2017 AAN Clinical Practice Guideline for MCI">{{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&nbsp;– 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}}</ref> 

Some preclinical evidence and emerging clinical evidence supports the use of exercise as an adjunct therapy for the treatment and prevention of drug addictions.<ref name="Addiction review 2016">{{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 | pages = 175 | date = February 2016 | pmid = 26903885 | pmc = 4745113 | doi = 10.3389/fpsyt.2015.00175| doi-access = free }}</ref><ref name="Running vs addiction">{{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}}</ref><ref name="Natural and drug addictions">{{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}}</ref><ref name="Exercise Rev 3">{{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}}</ref>

Reviews of clinical evidence also support the use of exercise as an adjunct therapy for certain neurodegenerative disorders, particularly [[Medicine:Alzheimer's disease|Alzheimer's disease]] and [[Medicine:Parkinson's disease|Parkinson's disease]].<ref name="Alz 1">{{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 | s2cid = 24936334}}</ref><ref name="Parkinson physiotherapy Cochrane">{{cite 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 = 9| pages = CD002817 | date = September 2013 | pmid = 24018704 | doi = 10.1002/14651858.CD002817.pub4 | pmc = 7120224 }}</ref> Regular exercise may be associated with a lower risk of developing neurodegenerative disorders.<ref name="Longitudinal SystRev dementia">{{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 | pages = 510 | date = May 2014 | pmid = 24885250 | pmc = 4064273 | doi = 10.1186/1471-2458-14-510 | doi-access = free }}</ref> 
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==Long-term effects==

===Neuroplasticity===
[[Biology:Neuroplasticity|Neuroplasticity]] is the process by which [[Biology:Neuron|neuron]]s adapt to a disturbance over time, and most often occurs in response to repeated exposure to stimuli.<ref name="NHM-Plasticity">{{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}}</ref> Aerobic exercise increases the production of [[Biology:Neurotrophic factors|neurotrophic factors]]{{#tag:ref|Neurotrophic factors are [[Chemistry:Peptide|peptide]]s or other small proteins that promote the growth, survival, and [[Biology:Cellular differentiation|differentiation]] of neurons by binding to and activating their associated [[Biology:Tyrosine kinase|tyrosine kinase]]s.<ref name="NHM-Neurotrophic factors">{{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}}</ref>|group="note"}} (e.g., [[Biology:Brain-derived neurotrophic factor|BDNF]], [[Biology:Insulin-like growth factor 1|IGF-1]], [[Biology:Vascular endothelial growth factor|VEGF]]) which mediate improvements in cognitive functions and various forms of memory by promoting [[Biology:Angiogenesis|blood vessel formation]] in the brain, [[Biology:Adult neurogenesis|adult neurogenesis]],{{#tag:ref|Adult neurogenesis is the postnatal (after-birth) growth of new neurons, a beneficial form of neuroplasticity.<ref name="NHM-Plasticity" />|group="note"}} and other forms of neuroplasticity.<ref name="Exercise – neurotrophic factors + basal ganglia" /><ref name="Comprehensive review" /><ref name="BDNF meta analysis">{{cite journal |vauthors=Szuhany KL, Bugatti M, Otto MW |date=October 2014 |title=A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor |journal=J Psychiatr Res |volume=60C |pages=56–64 |doi=10.1016/j.jpsychires.2014.10.003 |pmc=4314337 |pmid=25455510}}</ref><ref name="Cerebral hemodynamics and AD" /> 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,<ref name="Eighty percent of grey matter volume">{{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 | pages = 204–217 | date = June 2017 | pmid = 28600001 | doi = 10.1016/j.bbr.2017.06.002 | s2cid = 205895178}}</ref> with the most marked increases occurring in brain regions that give rise to executive functions.<ref name="Summary as of August 2015" /><ref name="Comprehensive review" /><ref name="cognitive control of exercise" /> The brain structures that show the greatest improvements in gray matter volume in response to aerobic exercise are the [[Biology:Prefrontal cortex|prefrontal cortex]], [[Biology:Caudate nucleus|caudate nucleus]], and [[Biology:Hippocampus|hippocampus]];<ref name="Summary as of August 2015" /><ref name="Comprehensive review" /> less significant increases in gray matter volume occur in the [[Biology:Anterior cingulate cortex|anterior cingulate cortex]], parietal cortex, [[Biology:Cerebellum|cerebellum]], and [[Biology:Nucleus accumbens|nucleus accumbens]].<ref name="Comprehensive review" /> The prefrontal cortex, caudate nucleus, and anterior cingulate cortex are among the most significant brain structures in the [[Biology:Neurotransmitter#Brain neurotransmitter systems|dopamine and norepinephrine systems]] that give rise to cognitive control.<ref name="Malenka pathways">{{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}}</ref> Exercise-induced neurogenesis (i.e., the increases in gray matter volume) in the hippocampus is associated with measurable improvements in [[Physics:Spatial memory|spatial memory]].<ref name="Exercise children">{{cite journal |vauthors=Lees C, Hopkins J |year=2013 |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 |pages=E174 |doi=10.5888/pcd10.130010 |pmc=3809922 |pmid=24157077}}</ref><ref name="Associated review">{{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 | pages = 661–682 | year = 2014 | pmid = 24748784 | pmc = 3990369 | doi = 10.2147/CIA.S55520 | doi-access = free }}</ref> Higher physical fitness scores, as measured by [[Medicine:VO2 max|VO<sub>2</sub> max]], are associated with better executive function, faster information processing speed, and greater gray matter volume of the hippocampus, caudate nucleus, and nucleus accumbens.<ref name="Summary as of August 2015" />

====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,<ref name="Eighty percent of grey matter volume" /> with more pronounced increases occurring in brain regions associated with memory processing, cognitive control, motor function, and [[Philosophy:Reward system|reward]];<ref name="Summary as of August 2015" /><ref name="Comprehensive review" /><ref name="Eighty percent of grey matter volume" /> 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.<ref name="Summary as of August 2015" /><ref name="cognitive control of exercise" /> Moreover, the left and right halves of the prefrontal cortex, the hippocampus, and the [[Biology:Cingulate cortex|cingulate cortex]] appear to become more functionally interconnected in response to consistent aerobic exercise.<ref name="Summary as of August 2015" /> 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.<ref name="Summary as of August 2015" /><ref name="Mind over matter">{{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 | s2cid = 20765865}}</ref> Other regions of the brain that demonstrate moderate or less significant gains in gray matter volume during neuroimaging include the [[Biology:Anterior cingulate cortex|anterior cingulate cortex]], parietal cortex, [[Biology:Cerebellum|cerebellum]], and [[Biology:Nucleus accumbens|nucleus accumbens]].<ref name="Comprehensive review" /><ref name="Ruscheweyh">{{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 | s2cid = 22238883 }}</ref>
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Regular exercise has been shown to counter the shrinking of the hippocampus and memory impairment that naturally occurs in late adulthood.<ref name="Comprehensive review" /> Sedentary adults over age&nbsp;55 show a 1–2%&nbsp;decline in hippocampal volume annually.<ref name="Hippocampus" /> A neuroimaging study with a sample of 120&nbsp;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.<ref name="Hippocampus" /> 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.<ref name="Hippocampus">{{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 | bibcode = 2011PNAS..108.3017E | doi-access = free }}</ref> In general, individuals that exercise more over a given period have greater hippocampal volumes and better memory function.<ref name="Comprehensive review" /> Aerobic exercise has also been shown to induce growth in the [[Biology:White matter|white matter]] tracts in the anterior [[Biology:Corpus callosum|corpus callosum]], which normally shrink with age.<ref name="Comprehensive review" /><ref name="Mind over matter" />

The various functions of the brain structures that show exercise-induced increases in gray matter volume include:
* [[Biology:Caudate nucleus|Caudate nucleus]]&nbsp;– responsible for [[Philosophy:Classical conditioning|stimulus-response learning]] and inhibitory control; implicated in [[Medicine:Parkinson's disease|Parkinson's disease]] and ADHD<ref name="NHM-Cognitive Control" /><ref name="NHM-Caudate Hippocampus">{{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}}</ref>
* [[Biology:Cerebellum|Cerebellum]]&nbsp;– responsible for [[Engineering:Motor coordination|motor coordination]] and [[Philosophy:Motor learning|motor learning]]<ref name="Cerebellum">{{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}}</ref>
* [[Biology:Hippocampus|Hippocampus]]&nbsp;– responsible for storage and consolidation of declarative memory and [[Physics:Spatial memory|spatial memory]]<ref name="NHM-Caudate Hippocampus" />
* [[Biology:Nucleus accumbens|Nucleus accumbens]]&nbsp;– responsible for incentive salience ("wanting" or desire, the form of [[Philosophy:Motivation|motivation]] associated with [[Philosophy:Reward system|reward]]) and positive reinforcement; implicated in addiction<ref name="NAcc function">{{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}}</ref>
* Parietal cortex&nbsp;– responsible for sensory perception, working memory, and attention<ref name="NHM-Cognitive Control">{{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 }}</ref><ref name="parietal ">{{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 }}</ref>
* [[Biology:Prefrontal cortex|Prefrontal]] and anterior cingulate cortices&nbsp;– required for the cognitive control of behavior, particularly: [[Working memory|working memory]], [[Biology:Attentional control|attentional control]], [[Decision-making|decision-making]], [[Philosophy:Cognitive flexibility|cognitive flexibility]], [[Philosophy:Social cognition|social cognition]], and [[Philosophy:Inhibitory control|inhibitory control]] of behavior;<ref name="NHM-Cognitive Control" /><ref name="NHM-PFC cognitive processes">{{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}}</ref> implicated in [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]] (ADHD) and addiction<ref name="NHM-Cognitive Control" />

====Persistent effects on cognition {{anchor|Cognitive control and memory}}====

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.<ref name="Comprehensive review" /><ref name="cognitive control of exercise" /><ref name="Attention-acute exercise" /><ref>{{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 | year = 2017 | pmid = 28825973 | pmc = 5566451| doi = 10.7554/eLife.25062 | doi-access = free }}</ref> In particular, consistent aerobic exercise has been shown to improve [[Biology:Attentional control|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,<ref name="Malenka pathways" /> such as in the [[Physics:Cocktail party effect|cocktail party effect]]. |group="note"}} [[Physics:Mental chronometry|information processing speed]], [[Philosophy:Cognitive flexibility|cognitive flexibility]] (e.g., task switching), [[Philosophy:Inhibitory control|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.<ref name="NHM-Cognitive Control" /><ref name="Cognitive and motivational effects">{{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| s2cid = 15788121 | url = https://repository.upenn.edu/neuroethics_pubs/130 }}</ref> Inhibitory control allows individuals to control their impulses and habits when necessary or desired,<ref name="NHM-Cognitive Control" /><ref name="Cognitive and motivational effects" /> e.g., to overcome [[Philosophy:Procrastination|procrastination]]. |group="note"}} [[Working memory|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,<ref name="Malenka pathways" /> 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|data buffer]], that permits the manipulation of information for comprehension, decision-making, and guidance of behavior.<ref name="NHM-Cognitive Control" />|group="note"}} declarative memory,{{#tag:ref|Declarative memory, also known as [[Biology:Explicit memory|explicit memory]], is the form of memory that pertains to facts and events.<ref name="NHM-Caudate Hippocampus" />|group="note"}} and [[Physics:Spatial memory|spatial memory]].<ref name="Comprehensive review" /><ref name="cognitive control of exercise" /><ref name="Exercise healthy young adult 2016 SystRev" /><ref name="Attention-acute exercise">{{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 | pages = 410 | year = 2014 | pmid = 25133092 | pmc = 4132441 | doi = 10.1186/2193-1801-3-410| doi-access = free }}</ref> In healthy young and middle-aged adults, the [[Effect size|effect size]]s of improvements in cognitive function are largest for indices of executive functions and small to moderate for aspects of memory and information processing speed.<ref name="Summary as of August 2015" /><ref name="Exercise healthy young adult 2016 SystRev" /> 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.<ref>{{cite journal | vauthors = Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Rattray B | title = Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis | journal = British Journal of Sports Medicine | volume = 52 | issue = 3 | pages = 154–160 | date = February 2018 | pmid = 28438770 | doi = 10.1136/bjsports-2016-096587 | s2cid = 13553374 | doi-access = free }}</ref> Individuals who have a sedentary lifestyle tend to have impaired executive functions relative to other more physically active non-exercisers.<ref name="cognitive control of exercise" /> 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.<ref name="cognitive control of exercise" />

=== Mechanism of effects ===
{{Further|Biology:Myokine}}

====BDNF signaling====
<!--The BDNF article links to the anchor/heading "BDNF signaling"-->{{Further|Brain-derived neurotrophic factor}}
One of the most significant effects of exercise on the brain is increased synthesis and expression of [[Biology:Brain-derived neurotrophic factor|BDNF]], a [[Biology:Neuropeptide|neuropeptide]] and [[Biology:Peptide hormone|hormone]], resulting in increased signaling through its [[Biology:Receptor tyrosine kinase|receptor tyrosine kinase]], [[Biology:Tropomyosin receptor kinase B|tropomyosin receptor kinase B]] (TrkB).<ref name="epigenome" /><ref name="trophic factor signaling">{{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 | pages = 170 | year = 2014 | pmid = 24999318 | pmc = 4064707 | doi = 10.3389/fncel.2014.00170| doi-access = free }}</ref><ref name="Organ response">{{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}}</ref> Since BDNF is capable of crossing the [[Biology:Blood–brain barrier|blood–brain barrier]], higher peripheral BDNF synthesis also increases BDNF signaling in the brain.<ref name="Cerebral hemodynamics and AD" /> Exercise-induced increases in BDNF signaling are associated with improved cognitive function, improved mood, and improved memory.<ref name="BDNF meta analysis" /><ref name="trophic factor signaling" /> Furthermore, research has provided a great deal of support for the role of BDNF in hippocampal neurogenesis, synaptic plasticity, and neural repair.<ref name="Comprehensive review" /><ref name="trophic factor signaling" /> Engaging in moderate-high intensity aerobic exercise such as running, swimming, and cycling increases BDNF [[Biology:Protein biosynthesis|biosynthesis]] through [[Biology:Myokine|myokine]] signaling, resulting in up to a threefold increase in [[Biology:Blood plasma|blood plasma]] and BDNF levels;<ref name="epigenome" /><ref name="trophic factor signaling" /><ref name="Organ response" /> exercise intensity is positively correlated with the magnitude of increased BDNF biosynthesis and expression.<ref name="epigenome" /><ref name="trophic factor signaling" /><ref name="Organ response" /> A meta-analysis of studies involving the effect of exercise on BDNF levels found that consistent exercise modestly increases resting BDNF levels as well.<ref name="BDNF meta analysis" /> This has important implications for exercise as a mechanism to reduce stress since stress is closely linked with decreased levels of BDNF in the hippocampus. In fact, studies suggest that BDNF contributes to the anxiety-reducing effects of antidepressants. The increase in BDNF levels caused by exercise helps reverse the stress-induced decrease in BDNF which mediates stress in the short term and buffers against stress-related diseases in the long term.<ref name=":0">{{cite journal | vauthors = Anderson E, Shivakumar G | title = Effects of exercise and physical activity on anxiety | journal = Frontiers in Psychiatry | volume = 4 | pages = 27 | year = 2013 | pmid = 23630504 | pmc = 3632802 | doi = 10.3389/fpsyt.2013.00027 | doi-access = free }}</ref>

====IGF-1 signaling====
{{Further|Biology:Insulin-like growth factor 1}}
{{abbr|IGF-1|Insulin-like growth factor 1}} is a [[Chemistry:Peptide|peptide]] and neurotrophic factor that mediates some of the effects of [[Biology:Growth hormone|growth hormone]];<ref name="Serum-brain IGF-1" /> IGF-1 elicits its physiological effects by binding to a specific [[Biology:Receptor tyrosine kinase|receptor tyrosine kinase]], the IGF-1 receptor, to control tissue growth and remodeling.<ref name="Serum-brain IGF-1" /> 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.<ref name="trophic factor signaling" /><ref name="IGF-1 neuroplasticity">{{cite journal | vauthors = Aberg D | title = Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis | journal = Endocr Dev | volume = 17 | pages = 63–76 | year = 2010 | pmid = 19955757 | doi = 10.1159/000262529| series = Endocrine Development | isbn = 978-3-8055-9302-1 }}</ref><ref name="NHM IGF-1 VEGF">{{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}}</ref> 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 [[Biology:Blood–brain barrier|blood–brain barrier]] and blood–cerebrospinal fluid barrier;<ref name="Comprehensive review" /><ref name="trophic factor signaling" /><ref name="Serum-brain IGF-1">{{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 | s2cid = 27947753| doi-access = free }}</ref><ref name="IGF-1 neuroplasticity" /> 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".<ref name="Serum-brain IGF-1" /><ref name="IGF-1 neuroplasticity" /> The amount of IGF-1 released into blood plasma during exercise is positively correlated with exercise intensity and duration.<ref name="pmid22714057">{{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 | s2cid = 22974661}}</ref>

====VEGF signaling====
{{Further|Biology:Vascular endothelial growth factor}}
{{abbr|VEGF|Vascular endothelial growth factor}} is a neurotrophic and [[Biology:Angiogenesis|angiogenic]] (i.e., blood vessel growth-promoting) [[Biology:Cell signaling|signaling protein]] that binds to two receptor tyrosine kinases, [[Biology:VEGFR1|VEGFR1]] and VEGFR2, which are expressed in neurons and glial cells in the brain.<ref name="NHM IGF-1 VEGF" /> [[Medicine:Hypoxia (medical)|Hypoxia]], or inadequate cellular oxygen supply, strongly upregulates VEGF expression and VEGF exerts a neuroprotective effect in hypoxic neurons.<ref name="NHM IGF-1 VEGF" /> 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 [[Biology:Angiogenesis|blood vessel formation]] in the [[Biology:Central nervous system|central nervous system]].<ref name="Cerebral hemodynamics and AD">{{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 | pages = 6 | date = January 2014 | pmid = 24478719 | pmc = 3896879 | doi = 10.3389/fphys.2014.00006| doi-access = free }}</ref><ref name="VEGF aging brain">{{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}}</ref> Exercise-induced increases in VEGF signaling have been shown to improve cerebral blood volume and contribute to exercise-induced neurogenesis in the hippocampus.<ref name="Comprehensive review" /><ref name="VEGF aging brain" />

====Irisin====
{{Further|Biology:FNDC5}}
A study using FNDC5 knock-out mice as well as artificial elevation of circulating irisin levels showed that irisin confers beneficial cognitive effects of physical exercise and that it can serve an exercise mimetic in mice in which it could "improve both the cognitive deficit and neuropathology in [[Medicine:Alzheimer's disease|Alzheimer's disease]] mouse models". The mediator and its regulatory system is therefore being investigated for potential interventions to improve – or further improve – cognitive function or alleviate Alzheimer's disease in humans.<ref>{{cite news |title=The hormone irisin is found to confer benefits of exercise on cognitive function |url=https://medicalxpress.com/news/2021-08-hormone-irisin-confer-benefits-cognitive.html |access-date=21 September 2021 |work=medicalxpress.com |language=en}}</ref><ref>{{cite news | vauthors = Reynolds G |title=How Exercise May Help Keep Our Memory Sharp |url=https://www.nytimes.com/2021/08/25/well/move/exercise-brain-memory-benefits.html |access-date=21 September 2021 |work=The New York Times |date=25 August 2021}}</ref><ref name="10.1038/s42255-021-00438-z">{{cite journal | vauthors = Islam MR, Valaris S, Young MF, Haley EB, Luo R, Bond SF, Mazuera S, Kitchen RR, Caldarone BJ, Bettio LE, Christie BR, Schmider AB, Soberman RJ, Besnard A, Jedrychowski MP, Kim H, Tu H, Kim E, Choi SH, Tanzi RE, Spiegelman BM, Wrann CD | display-authors = 6 | title = Exercise hormone irisin is a critical regulator of cognitive function | journal = Nature Metabolism | volume = 3 | issue = 8 | pages = 1058–1070 | date = August 2021 | pmid = 34417591 | doi = 10.1038/s42255-021-00438-z | pmc = 10317538 | s2cid = 237254736 }}</ref> Experiments indicate irisin may be linked to regulation of BDNF and neurogenesis in mice.<ref name="10.1210/endrev/bnab003">{{cite journal | vauthors = Maak S, Norheim F, Drevon CA, Erickson HP | title = Progress and Challenges in the Biology of FNDC5 and Irisin | journal = Endocrine Reviews | volume = 42 | issue = 4 | pages = 436–456 | date = July 2021 | pmid = 33493316 | pmc = 8284618 | doi = 10.1210/endrev/bnab003 }}</ref>

==Short-term effects==

===Transient effects on cognition===

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.<ref name="Neurobiological effects of acute exercise – 2017 review" /><ref name="pmid26581791" /><ref name="pmid23064033" /> 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&nbsp;hours post-exercise.<ref name="Neurobiological effects of acute exercise – 2017 review" /><ref name="pmid26581791">{{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 | volume = 21 | issue = 10 | pages = 791–801 | date = November 2015 | pmid = 26581791 | doi = 10.1017/S135561771500106X | doi-access = free }}</ref><ref name="pmid23064033">{{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 | s2cid = 8320775 }}</ref> 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.<ref name="Attention-acute exercise" /> Other research has suggested immediate performative enhancements during exercise, such as exercise-concurrent improvements in processing speed and accuracy during both visual attention and working memory tasks.<ref>{{cite journal | vauthors = Dodwell G, Müller HJ, Töllner T | title = Electroencephalographic evidence for improved visual working memory performance during standing and exercise | journal = British Journal of Psychology | volume = 110 | issue = 2 | pages = 400–427 | date = May 2019 | pmid = 30311188 | doi = 10.1111/bjop.12352 | s2cid = 52960179 | doi-access = free }}</ref><ref>{{Cite journal |last1=Dodwell |first1=Gordon |last2=Liesefeld |first2=Heinrich R. |last3=Conci |first3=Markus |last4=Müller |first4=Hermann J. |last5=Töllner |first5=Thomas |date=December 2021 |title=EEG evidence for enhanced attentional performance during moderate-intensity exercise |url=https://onlinelibrary.wiley.com/doi/10.1111/psyp.13923 |journal=Psychophysiology |language=en |volume=58 |issue=12 |pages=e13923 |doi=10.1111/psyp.13923 |pmid=34370887 |s2cid=236969156 |issn=0048-5772}}</ref>

{{Anchor|Euphoria}}

===Exercise-induced euphoria===
<!--Runner's high and Rower's high redirect here.  These terms are bolded per MOS:BOLD-->
{{hatnote|For further information on the [[Biology:Neural substrate|neural substrate]]s of pleasure cognition, see Hedonic hotspots.}}
{{split section|Runner's high|discuss=Talk:Neurobiological effects of physical exercise#Split Runner's high|date=April 2021}}
[[File:LairigGhru-8246.jpg|thumb|250px|Runners can experience a euphoric state often called a "runner's high".]]

Continuous exercise can produce a transient state of [[Chemistry:Euphoria|euphoria]]&nbsp;– a positively-valenced [[Philosophy:Affect (psychology)|affective state]] involving the experience of [[Philosophy:Pleasure|pleasure]] and feelings of profound contentment, elation, and well-being&nbsp;– which is colloquially known as a "'''runner's high'''" in distance running or a "'''rower's high'''" in rowing.<ref name="Euphoria review">{{cite journal |vauthors=Cunha GS, Ribeiro JL, Oliveira AR |date=June 2008 |title=[Levels of beta-endorphin in response to exercise and overtraining] |journal=Arq Bras Endocrinol Metabol |language=pt |volume=52 |issue=4 |pages=589–598 |doi=10.1590/S0004-27302008000400004 |pmid=18604371 |doi-access=free|hdl=10183/40053 |hdl-access=free }}</ref><ref name="Runner's high euphoria primary">{{cite journal |vauthors=Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR |year=2008 |title=The runner's high: opioidergic mechanisms in the human brain |journal=Cereb. Cortex |volume=18 |issue=11 |pages=2523–2531 |doi=10.1093/cercor/bhn013 |pmid=18296435 |quote=The runner's high describes an euphoric state resulting from long-distance running. |doi-access=free}}</ref><ref name="Primary-Runner's high definition">{{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 | s2cid = 5129200| doi-access = free }}</ref><ref name="Primary-Rower's high definition">{{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 }}</ref> Current medical reviews indicate that several endogenous [[Chemistry:Euphoriant|euphoriant]]s are responsible for producing exercise-related euphoria, specifically [[Biology:Phenethylamine|phenethylamine]] (an endogenous psychostimulant), {{nowrap|β-endorphin}} (an endogenous opioid), and [[Chemistry:Anandamide|anandamide]] (an endogenous cannabinoid).<ref name="PEA exercise primary" /><ref name="Renaissance" /><ref name="Neuropsychiatric" /><ref name="Endorphin" /><ref name="endocannabinoids" />

==Effects on neurochemistry==

===β-Phenylethylamine===
{{Catecholamine and trace amine biosynthesis|align=right}}
β-Phenylethylamine, commonly referred to as ''phenethylamine'', is a human [[Biology:Trace amine|trace amine]] and potent [[Biology:Catecholamine|catecholamine]]rgic and glutamatergic neuromodulator that has similar psychostimulant and [[Chemistry:Euphoriant|euphoriant]] effects and a similar [[Chemistry:Chemical structure|chemical structure]] to [[Chemistry:Amphetamine|amphetamine]].<ref name="Berry hTAAR pharmacology December 2017 review">{{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 | pages = 161–180 | date = December 2017 | pmid = 28723415 | doi = 10.1016/j.pharmthera.2017.07.002 | s2cid = 207366162| doi-access = free }}</ref> 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.<ref name="PEA exercise primary">{{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}}</ref><ref name="Renaissance">{{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}}</ref><ref name="Neuropsychiatric">{{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| citeseerx = 10.1.1.329.563 }}</ref> Two reviews noted a study where the average 24&nbsp;hour urinary {{nowrap|β-phenylacetic acid}} concentration among participants following just 30&nbsp;minutes of intense exercise increased by 77% relative to baseline concentrations in resting control subjects;<ref name="PEA exercise primary" /><ref name="Renaissance" /><ref name="Neuropsychiatric" /> 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&nbsp;seconds.<ref name="PEA exercise primary" /><ref name="Renaissance" /><ref name="Neuropsychiatric" /><ref name="Vascular" /> In a resting state, phenethylamine is synthesized in [[Biology:Catecholamine|catecholamine]] neurons from {{nowrap|{{smallcaps all|L}}-[[Chemistry:Phenylalanine|phenylalanine]]}} by aromatic amino acid decarboxylase (AADC) at approximately the same rate at which [[Biology:Dopamine|dopamine]] is produced.<ref name="Vascular">{{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}}</ref>

In light of this observation, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing [[Chemistry:Euphoria|euphoric]] effects of a runner's high, as both phenethylamine and amphetamine are potent euphoriants.<ref name="PEA exercise primary" /><ref name="Renaissance" /><ref name="Neuropsychiatric" />

===β-Endorphin===

[[Chemistry:Β-Endorphin|β-Endorphin]] (contracted from "endogenous morphine") is an endogenous [[Chemistry:Opioid|opioid]] [[Biology:Neuropeptide|neuropeptide]] that binds to [[Biology:Μ-opioid receptor|μ-opioid receptor]]s, in turn producing [[Chemistry:Euphoria|euphoria]] and pain relief.<ref name="Endorphin">{{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 | s2cid = 40951545}}</ref> 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.<ref name="Endorphin" /> 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.<ref name="Endorphin" /> 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.<ref name="Endorphin" />

However, humans studies showed that pharmacological blockade of endogenous endorphins does not inhibit a runner's high, while blockade of endocannabinoids may have such an effect.<ref>{{cite journal | vauthors = Siebers M, Biedermann SV, Bindila L, Lutz B, Fuss J | title = Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans | journal = Psychoneuroendocrinology | volume = 126 | pages = 105173 | date = April 2021 | pmid = 33582575 | doi = 10.1016/j.psyneuen.2021.105173| s2cid = 231858251 }}</ref>

===Anandamide===

[[Chemistry:Anandamide|Anandamide]] is an endogenous cannabinoid and retrograde neurotransmitter that binds to [[Biology:Cannabinoid receptor|cannabinoid receptor]]s (primarily [[Biology:Cannabinoid receptor 1|CB<sub>1</sub>]]), in turn producing euphoria.<ref name="Primary-Runner's high definition" /><ref name="endocannabinoids">{{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 | s2cid = 14531019}}</ref> 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).<ref name="endocannabinoids" /> Increases in plasma anandamide levels are associated with psychoactive effects because anandamide is able to cross the [[Biology:Blood–brain barrier|blood–brain barrier]] and act within the central nervous system.<ref name="endocannabinoids" /> 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.<ref name="Primary-Runner's high definition" /><ref name="endocannabinoids" />

===Cortisol and the psychological stress response===
[[Image:HPA Axis Diagram (Brian M Sweis 2012).svg|right|325px|thumb|Diagram of the hypothalamic–pituitary–adrenal axis|alt=Diagram of the HPA axis]]
The "stress hormone", [[Chemistry:Cortisol|cortisol]], is a [[Chemistry:Glucocorticoid|glucocorticoid]] that binds to [[Biology:Glucocorticoid receptor|glucocorticoid receptor]]s.<ref name="NHM-Stress" /><ref name="Exercise neuroendocrine effects" /><ref name="Endocrine cognition" /> [[Medicine:Psychological stress|Psychological stress]] induces the release of cortisol from the adrenal gland by activating the [[Medicine:Hypothalamic–pituitary–adrenal axis|hypothalamic–pituitary–adrenal axis]] (HPA axis).<ref name="NHM-Stress">{{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}}</ref><ref name="Exercise neuroendocrine effects">{{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}}</ref><ref name="Endocrine cognition" /> Short-term increases in cortisol levels are associated with adaptive cognitive improvements, such as enhanced inhibitory control;<ref name="Exercise neuroendocrine effects" /><ref name="Endocrine cognition" /> 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.<ref name="Endocrine cognition">{{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 | pages = 1595 | date = January 2015 | pmid = 25657633 | pmc = 4302708 | doi = 10.3389/fpsyg.2014.01595| doi-access = free }}</ref> 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.<ref name="NHM-Stress" />

As a physical stressor, aerobic exercise stimulates cortisol secretion in an intensity-dependent manner;<ref name="Exercise neuroendocrine effects" /> 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 [[Biology:Energy homeostasis|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"}}<ref name="Exercise neuroendocrine effects" /> 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|heart rate]] response).<ref name="Neurobiological effects of acute exercise – 2017 review" /><ref name="Exercise mental disorders">{{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  | pages = S12–521 | date = January 2013 | issue = Suppl 1 | pmid = 23412549 | pmc = 3567313 | doi = 10.3961/jpmph.2013.46.S.S12}}</ref> 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.<ref name="NHM-Stress" /><ref name="Exercise mental disorders" />

===Glutamate and GABA===

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.<ref name="NHM-glutamate">{{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}}</ref> Based upon animal models, exercise appears to normalize the excessive levels of glutamate neurotransmission into the [[Biology:Nucleus accumbens|nucleus accumbens]] that occurs in drug addiction.<ref name="Running vs addiction" /> A review of the effects of exercise on neurocardiac function in preclinical models noted that exercise-induced neuroplasticity of the [[Biology:Rostral ventrolateral medulla|rostral ventrolateral medulla]] (RVLM) has an inhibitory effect on glutamatergic neurotransmission in this region, in turn reducing sympathetic activity;<ref name="Neurocardiology">{{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}}</ref> the review hypothesized that this neuroplasticity in the RVLM is a mechanism by which regular exercise prevents inactivity-related [[Medicine:Cardiovascular disease|cardiovascular disease]].<ref name="Neurocardiology" />

===Exerkines and other circulating compounds===
[[Biology:Exerkine|Exerkine]]s are putative "signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways".<ref>{{cite journal | vauthors = Chow LS, Gerszten RE, Taylor JM, Pedersen BK, van Praag H, Trappe S, Febbraio MA, Galis ZS, Gao Y, Haus JM, Lanza IR, Lavie CJ, Lee CH, Lucia A, Moro C, Pandey A, Robbins JM, Stanford KI, Thackray AE, Villeda S, Watt MJ, Xia A, Zierath JR, Goodpaster BH, Snyder MP | display-authors = 3 | title = Exerkines in health, resilience and disease | journal = Nature Reviews. Endocrinology | volume = 18 | issue = 5 | pages = 273–289 | date = May 2022 | pmid = 35304603 | pmc = 9554896 | doi = 10.1038/s41574-022-00641-2 }}</ref>

==Effects in children==

Engaging in active physical pursuits has demonstrated positive effects on the mental health of children and adolescents,<ref>{{Cite journal|display-authors=3 |last1=Strong |first1=William B. |last2=Malina |first2=Robert M. |last3=Blimkie |first3=Cameron J.R. |last4=Daniels |first4=Stephen R. |last5=Dishman |first5=Rodney K. |last6=Gutin |first6=Bernard |last7=Hergenroeder |first7=Albert C. |last8=Must |first8=Aviva |last9=Nixon |first9=Patricia A. |last10=Pivarnik |first10=James M. |last11=Rowland |first11=Thomas |last12=Trost |first12=Stewart |last13=Trudeau |first13=François |date=June 2005 |title=Evidence Based Physical Activity for School-age Youth |url=http://dx.doi.org/10.1016/j.jpeds.2005.01.055 |journal=The Journal of Pediatrics |volume=146 |issue=6 |pages=732–737 |doi=10.1016/j.jpeds.2005.01.055 |pmid=15973308 |issn=0022-3476}}</ref> enhances their academic performance,<ref>{{Cite journal |date=2002 |title=Physical activity levels among children aged 9-13 years: United States, 2002. |url=http://dx.doi.org/10.1037/e303072004-001 |access-date=2023-12-08 |website=PsycEXTRA Dataset|doi=10.1037/e303072004-001 }}</ref> boosts cognitive function,<ref>{{Cite journal |last1=Ebbeling |first1=Cara B |last2=Pawlak |first2=Dorota B |last3=Ludwig |first3=David S |date=August 2002 |title=Childhood obesity: public-health crisis, common sense cure |url=http://dx.doi.org/10.1016/s0140-6736(02)09678-2 |journal=The Lancet |volume=360 |issue=9331 |pages=473–482 |doi=10.1016/s0140-6736(02)09678-2 |pmid=12241736 |s2cid=6374501 |issn=0140-6736}}</ref> and diminishes the likelihood of obesity and cardiovascular diseases among this demographic.<ref>{{Cite book |last1=Ward |first1=Dianne Stanton |last2=Saunders |first2=Ruth P. |last3=Pate |first3=Russell R. |date=2007 |title=Physical Activity Interventions in Children and Adolescents |url=http://dx.doi.org/10.5040/9781492596868 |doi=10.5040/9781492596868|isbn=9781492596868 }}</ref> Establishing consistent exercise routines with regular frequency and duration is pivotal.<ref>{{Cite journal |last1=van Sluijs |first1=Esther M F |last2=McMinn |first2=Alison M |last3=Griffin |first3=Simon J |date=2007-09-20 |title=Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials |journal=BMJ |volume=335 |issue=7622 |pages=703 |doi=10.1136/bmj.39320.843947.be |pmid=17884863 |s2cid=5659723 |issn=0959-8138|doi-access=free |pmc=2001088 }}</ref><ref>{{Cite journal |last1=Pate |first1=Russell R. |last2=Trost |first2=Stewart G. |last3=Mullis |first3=Rebecca |last4=Sallis |first4=James F. |last5=Wechsler |first5=Howell |last6=Brown |first6=David R. |date=August 2000 |title=Community Interventions to Promote Proper Nutrition and Physical Activity among Youth |url=http://dx.doi.org/10.1006/pmed.2000.0632 |journal=Preventive Medicine |volume=31 |issue=2 |pages=S138–S149 |doi=10.1006/pmed.2000.0632 |issn=0091-7435}}</ref><ref>{{Cite journal |last1=Stone |first1=Elaine J |last2=McKenzie |first2=Thomas L |last3=Welk |first3=Gregory J |last4=Booth |first4=Michael L |date=November 1998 |title=Effects of physical activity interventions in youth |url=http://dx.doi.org/10.1016/s0749-3797(98)00082-8 |journal=American Journal of Preventive Medicine |volume=15 |issue=4 |pages=298–315 |doi=10.1016/s0749-3797(98)00082-8 |pmid=9838974 |issn=0749-3797}}</ref> Cultivating beneficial exercise habits and sustaining adequate physical activity may support the overall physical and mental well-being of young individuals. Therefore, identifying factors that either impede or encourage exercise behaviors could be a significant strategy in promoting the development of healthy exercise habits among children and adolescents.

A 2003 meta-analysis found a positive effect of exercise in children on perceptual skills, intelligence quotient, achievement, verbal tests, mathematic tests, and academic readiness.<ref name="sibley">{{cite journal | vauthors = Sibley BA, Etnier JL |title=The Relationship between Physical Activity and Cognition in Children: A Meta-Analysis |journal=Pediatric Exercise Science |date=August 2003 |volume=15 |issue=3 |pages=243–256 |doi=10.1123/pes.15.3.243 |s2cid=56815489 }}</ref> The correlation was strongest for the age ranges of 4–7 and 11–13 years.<ref name="sibley" />  

A 2010 meta-analysis of the effect of activity on children's executive function found that aerobic exercise may briefly aid children's executive function and also influence more lasting improvements to executive function.<ref name="best">{{cite journal | vauthors = Best JR | title = Effects of Physical Activity on Children's Executive Function: Contributions of Experimental Research on Aerobic Exercise | journal = Developmental Review | volume = 30 | issue = 4 | pages = 331–551 | date = December 2010 | pmid = 21818169 | pmc = 3147174 | doi = 10.1016/j.dr.2010.08.001 }}</ref> Other studies suggested that exercise is unrelated to academic performance, perhaps due to the parameters used to determine exactly what academic achievement is.<ref name="hillman">{{cite journal | vauthors = Hillman CH, Erickson KI, Kramer AF | title = Be smart, exercise your heart: exercise effects on brain and cognition | journal = Nature Reviews. Neuroscience | volume = 9 | issue = 1 | pages = 58–65 | date = January 2008 | pmid = 18094706 | doi = 10.1038/nrn2298 | s2cid = 1204039 }}</ref> 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.<ref name="sibley" />

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. Children 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.<ref>{{cite journal | vauthors = Coe DP, Pivarnik JM, Womack CJ, Reeves MJ, Malina RM | title = Effect of physical education and activity levels on academic achievement in children | journal = Medicine and Science in Sports and Exercise | volume = 38 | issue = 8 | pages = 1515–1519 | date = August 2006 | pmid = 16888468 | doi = 10.1249/01.mss.0000227537.13175.1b | s2cid = 9676116 | doi-access = free }}</ref>

Neuroimaging studies indicate that exercise may influence changes in brain structure and function.<ref name=hillman /> Some investigations have linked low levels of aerobic fitness in children with impaired executive function when older as adults, but lack of selective attention, response inhibition, and interference control may also explain this outcome.<ref name=chaddock>{{cite journal | vauthors = Chaddock L, Hillman CH, Buck SM, Cohen NJ | title = Aerobic fitness and executive control of relational memory in preadolescent children | journal = Medicine and Science in Sports and Exercise | volume = 43 | issue = 2 | pages = 344–349 | date = February 2011 | pmid = 20508533 | doi = 10.1249/MSS.0b013e3181e9af48 | s2cid = 400283 | doi-access = free }}</ref>

==Effects on central nervous system disorders{{anchor|Effects on neural disorders}}==
<!--Signs of cognitive decline become more evident with age. [[Social:Cross-sectional study|Cross-sectional studies]] have shown a positive link between exercise and general cognitive function in older individuals.<ref name=dik>{{cite journal | vauthors= Dik MG, Deeg DJH, Visser M, Jonker C | year = 2003 | title = Early Life Physical Activity and Cognition at Old Age | journal = Journal of Clinical and Experimental Neuropsychology | volume = 25 | issue = 5| pages = 643–653 | doi=10.1076/jcen.25.5.643.14583}}</ref> Fitness is associated with better cognitive performance in individuals with cardiovascular disease.<ref name=Swardfager2010>{{cite journal | vauthors = Swardfager W, Herrmann N, Marzolini S, Saleem M, Kiss A, Shammi P, Oh PI, Lanctôt KL | display-authors = 6 | title = Cardiopulmonary fitness is associated with cognitive performance in patients with coronary artery disease | journal = Journal of the American Geriatrics Society | volume = 58 | issue = 8 | pages = 1519–1525 | date = August 2010 | pmid = 20646102 | doi = 10.1111/j.1532-5415.2010.02966.x }}</ref>-->

===Exercise as prevention and treatment of drug addictions{{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.<ref name="Addiction review 2016" /><ref name="Running vs addiction" /><ref name="Natural and drug addictions" /><ref name="Exercise Rev 3" /> Consistent aerobic exercise magnitude-dependently (i.e., by duration and intensity) may reduce drug addiction risk, which appears to occur through the reversal of drug-induced, addiction-related neuroplasticity.<ref name="Running vs addiction" /><ref name="Natural and drug addictions" /> Moreover, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces opposite effects on [[Biology:Striatum|striatal]] [[Biology:Dopamine receptor D2|dopamine receptor D<sub>2</sub>]] (DRD2) signaling (increased DRD2 density) to those induced by pathological stimulant use (decreased DRD2 density).<ref name="Running vs addiction" /><ref name="Natural and drug addictions" /> Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.<ref name="Running vs addiction" /><ref name="Exercise Rev 3" /> {{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.<ref name="Addiction review 2016" />
{{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 [[Medicine:Attention deficit hyperactivity disorder|ADHD]] in children and adults, particularly when combined with stimulant medication (i.e., [[Chemistry:Amphetamine|amphetamine]] or [[Chemistry:Methylphenidate|methylphenidate]]), although the best intensity and type of aerobic exercise for improving symptoms are not currently known.<ref name="ADHD exercise 2016 SystRev" /><ref name="ADHD Exercise 2013">{{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}}</ref> In particular, the long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved [[Philosophy:Executive functions|executive functions]] (including attention, [[Philosophy:Inhibitory control|inhibitory control]], and [[Engineering:Planning|planning]], among other cognitive domains), faster information processing speed, and better memory.<ref name="ADHD exercise 2016 SystRev" /> Parent-teacher ratings of behavioral and socio-emotional outcomes in response to regular aerobic exercise include: better overall function, reduced ADHD symptoms, better self-esteem, reduced levels of anxiety and depression, fewer somatic complaints, better academic and classroom behavior, and improved social behavior.<ref name="ADHD exercise 2016 SystRev" /> Exercising while on stimulant medication augments the effect of stimulant medication on executive function.<ref name="ADHD exercise 2016 SystRev" /> It is believed that these short-term effects of exercise are mediated by an increased abundance of [[Biology:Synapse|synaptic]] dopamine and norepinephrine in the brain.<ref name="ADHD exercise 2016 SystRev" />

===Major depressive disorder===
A number of medical reviews have indicated that exercise has a marked and persistent [[Chemistry:Antidepressant|antidepressant]] effect in humans,<ref name="Comprehensive review" /><ref name="Exercise depression intervention" /><ref name="Physical activity intervention">{{cite journal |vauthors=Rosenbaum S, Tiedemann A, Sherrington C, Curtis J, Ward PB |year=2014 |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 |doi=10.4088/JCP.13r08765 |pmid=24813261}}</ref><ref name="Exercise MDD antidepressant" /><ref name="Cochrane exercise depression" /><ref name="Running antidepressant">{{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 }}</ref> an effect believed to be mediated through enhanced {{abbr|BDNF|brain-derived neurotrophic factor}} signaling in the brain.<ref name="Exercise MDD antidepressant" /> Several systematic reviews have analyzed the potential for physical exercise in the treatment of depressive disorders. The 2013 Cochrane Collaboration review on {{no selflink|physical exercise}} for depression noted that, based upon limited evidence, it is more effective than a control intervention and comparable to psychological or antidepressant drug therapies.<ref name="Cochrane exercise depression">{{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 = 2013 | issue = 9 | pages = CD004366 | date = September 2013 | pmid = 24026850 | doi = 10.1002/14651858.CD004366.pub6 | pmc = 9721454}}</ref> Three subsequent 2014 systematic reviews that included the Cochrane review in their analysis concluded with similar findings: one indicated that physical exercise is effective as an adjunct treatment (i.e., treatments that are used together) with antidepressant medication;<ref name="Exercise MDD antidepressant" /> the other two indicated that physical exercise has marked antidepressant effects and recommended the inclusion of physical activity as an adjunct treatment for mild–moderate depression and mental illness in general.<ref name="Exercise depression intervention" /><ref name="Physical activity intervention" /> One systematic review noted that yoga may be effective in alleviating symptoms of prenatal depression.<ref name="Yoga depression SystRev">{{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 | pages = 14 | date = February 2015 | pmid = 25652267 | pmc = 4323231 | doi = 10.1186/s12888-015-0393-1 | doi-access = free }}</ref> Another review asserted that evidence from clinical trials supports the efficacy of physical exercise as a treatment for depression over a 2–4&nbsp;month period.<ref name="Comprehensive review" /> These benefits have also been noted in [[Biology:Old age|old age]], with a review conducted in 2019 finding that exercise is an effective treatment for clinically diagnosed depression in older adults.<ref name=miller2020>{{cite journal | vauthors= Miller KJ, Gonçalves-Bradley DC, Areerob P, Hennessy D, Mesagno C, Grace F | year = 2020 | title = Comparative effectiveness of three exercise types to treat clinical depression in older adults: A systematic review and network meta-analysis of randomised controlled trials | url = http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/172086| journal = Ageing Research Reviews | volume = 58 | pages = 100999 | pmid = 31837462 | doi = 10.1016/j.arr.2019.100999 | hdl = 1959.17/172086 | s2cid = 209179889 }}</ref>

A [[Meta-analysis|meta-analysis]] from July 2016 concluded that physical exercise improves overall quality of life in individuals with depression relative to controls.<ref name="Depression QoL meta-analysis" /><ref>{{cite journal | vauthors = Chaturvedi SK, Chandra PS, Issac MK, Sudarshan CY | title = Somatization misattributed to non-pathological vaginal discharge | journal = Journal of Psychosomatic Research | volume = 37 | issue = 6 | pages = 575–579 | date = September 1993 | pmid = 8410743 | doi = 10.1016/0022-3999(93)90051-G }}</ref>

===Cerebrovascular disease===
Physical exercise plays a significant role in the prevention and management of [[Medicine:Stroke|stroke]]. It is well established that physical activity decrease the risk of ischemic stroke and intracerebral haemorrhage.<ref>{{cite journal | vauthors = O'Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, Rangarajan S, Islam S, Pais P, McQueen MJ, Mondo C, Damasceno A, Lopez-Jaramillo P, Hankey GJ, Dans AL, Yusoff K, Truelsen T, Diener HC, Sacco RL, Ryglewicz D, Czlonkowska A, Weimar C, Wang X, Yusuf S | display-authors = 6 | title = Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study | journal = Lancet | volume = 376 | issue = 9735 | pages = 112–123 | date = July 2010 | pmid = 20561675 | doi = 10.1016/s0140-6736(10)60834-3 | s2cid = 2753073 }}</ref><ref>{{cite journal | vauthors = Lee CD, Folsom AR, Blair SN | title = Physical activity and stroke risk: a meta-analysis | journal = Stroke | volume = 34 | issue = 10 | pages = 2475–2481 | date = October 2003 | pmid = 14500932 | doi = 10.1161/01.STR.0000091843.02517.9D | s2cid = 2332015 | doi-access = free }}</ref> Engaging in physical activity before experiencing a stroke has been found to have a positive impact on the severity and outcomes of stroke.<ref>{{cite journal | vauthors = Viktorisson A, Reinholdsson M, Danielsson A, Palstam A, Sunnerhagen KS | title = Pre-stroke physical activity in relation to post-stroke outcomes - linked to the International Classification of Functioning, Disability and Health (ICF): A scoping review | journal = Journal of Rehabilitation Medicine | volume = 54 | pages = jrm00251 | date = January 2022 | pmid = 34904691 | pmc = 8862654 | doi = 10.2340/jrm.v53.51 }}</ref> Exercise has the potential to increase the expression of VEGF, [[Biology:Caveolin|caveolin]], and [[Biology:Angiopoietin|angiopoietin]] in the brain. These changes may promote [[Biology:Angiogenesis|angiogenesis]] and [[Biology:Neovascularization|neovascularization]] that contribute to improved blood supply to the stroke affected areas of the brain.<ref>{{cite journal | vauthors = Ding YH, Luan XD, Li J, Rafols JA, Guthinkonda M, Diaz FG, Ding Y | title = Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke | journal = Current Neurovascular Research | volume = 1 | issue = 5 | pages = 411–420 | date = December 2004 | pmid = 16181089 | doi = 10.2174/1567202043361875 | s2cid = 22015361 }}</ref><ref>{{cite journal | vauthors = Rezaei R, Nasoohi S, Haghparast A, Khodagholi F, Bigdeli MR, Nourshahi M | title = High intensity exercise preconditioning provides differential protection against brain injury following experimental stroke | journal = Life Sciences | volume = 207 | pages = 30–35 | date = August 2018 | pmid = 29522768 | doi = 10.1016/j.lfs.2018.03.007 | s2cid = 3812671 }}</ref><ref>{{cite journal | vauthors = Gao Y, Zhao Y, Pan J, Yang L, Huang T, Feng X, Li C, Liang S, Zhou D, Liu C, Tu F, Tao C, Chen X | display-authors = 6 | title = Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat brains through caveolin-1/VEGF signaling pathways | journal = Brain Research | volume = 1585 | pages = 83–90 | date = October 2014 | pmid = 25148708 | doi = 10.1016/j.brainres.2014.08.032 | s2cid = 25507984 }}</ref> Exercise may affect the activation of [[Biology:Endothelial NOS|endothelial nitric oxide synthase]] (eNOS) and subsequent production of [[Chemistry:Nitric oxide|nitric oxide]] (NO).<ref>{{cite journal | vauthors = Endres M, Gertz K, Lindauer U, Katchanov J, Schultze J, Schröck H, Nickenig G, Kuschinsky W, Dirnagl U, Laufs U | display-authors = 6 | title = Mechanisms of stroke protection by physical activity | journal = Annals of Neurology | volume = 54 | issue = 5 | pages = 582–590 | date = November 2003 | pmid = 14595647 | doi = 10.1002/ana.10722 | s2cid = 28445967 }}</ref><ref>{{cite journal | vauthors = Gertz K, Priller J, Kronenberg G, Fink KB, Winter B, Schröck H, Ji S, Milosevic M, Harms C, Böhm M, Dirnagl U, Laufs U, Endres M | display-authors = 6 | title = Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow | journal = Circulation Research | volume = 99 | issue = 10 | pages = 1132–1140 | date = November 2006 | pmid = 17038638 | doi = 10.1161/01.RES.0000250175.14861.77 | s2cid = 9063866 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hafez S, Khan MB, Awad ME, Wagner JD, Hess DC | title = Short-Term Acute Exercise Preconditioning Reduces Neurovascular Injury After Stroke Through Induced eNOS Activation | journal = Translational Stroke Research | volume = 11 | issue = 4 | pages = 851–860 | date = August 2020 | pmid = 31858409 | doi = 10.1007/s12975-019-00767-y | s2cid = 255954922 }}</ref> The increase in NO production may lead to improved post-stroke cerebral blood flow, ensuring a sufficient oxygen and nutrient supply to the brain. Physical activity has been associated with increased expression and activation of [[Biology:HIF1A|hypoxia-inducible factor 1 alpha]] (HIF-1α), heat shock proteins, and [[Biology:Brain-derived neurotrophic factor|brain-derived neurotrophic factor]] (BDNF).<ref>{{cite journal | vauthors = Sharp FR, Bernaudin M | title = HIF1 and oxygen sensing in the brain | journal = Nature Reviews. Neuroscience | volume = 5 | issue = 6 | pages = 437–448 | date = June 2004 | pmid = 15152194 | doi = 10.1038/nrn1408 | s2cid = 318020 }}</ref><ref>{{cite journal | vauthors = Dornbos D, Ding Y | title = Mechanisms of neuronal damage and neuroprotection underlying ischemia/reperfusion injury after physical exercise | journal = Current Drug Targets | volume = 13 | issue = 2 | pages = 247–262 | date = February 2012 | pmid = 22204323 | doi = 10.2174/138945012799201658 }}</ref><ref>{{cite journal | vauthors = Wang L, Deng W, Yuan Q, Yang H | title = Exercise preconditioning reduces ischemia reperfusion-induced focal cerebral infarct volume through up-regulating the expression of HIF-1α | journal = Pakistan Journal of Pharmaceutical Sciences | volume = 28 | issue = 2 Suppl | pages = 791–798 | date = March 2015 | pmid = 25796156 | url = https://pubmed.ncbi.nlm.nih.gov/25796156 }}</ref> These factors play crucial roles in promoting cellular survival, neuroprotection, and repair processes in the brain following a stroke. Exercise also inhibit [[Chemistry:Glutamic acid|glutamate]] and [[Biology:Caspase|caspase]] activities, which are involved in neuronal death pathways.<ref>{{cite journal | vauthors = Jia J, Hu YS, Wu Y, Liu G, Yu HX, Zheng QP, Zhu DN, Xia CM, Cao ZJ | display-authors = 6 | title = Pre-ischemic treadmill training affects glutamate and gamma aminobutyric acid levels in the striatal dialysate of a rat model of cerebral ischemia | journal = Life Sciences | volume = 84 | issue = 15–16 | pages = 505–511 | date = April 2009 | pmid = 19302809 | doi = 10.1016/j.lfs.2009.01.015 }}</ref><ref>{{cite journal | vauthors = Zhang F, Wu Y, Jia J, Hu YS | title = Pre-ischemic treadmill training induces tolerance to brain ischemia: involvement of glutamate and ERK1/2 | journal = Molecules | volume = 15 | issue = 8 | pages = 5246–5257 | date = August 2010 | pmid = 20714296 | pmc = 6257775 | doi = 10.3390/molecules15085246 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yang X, He Z, Zhang Q, Wu Y, Hu Y, Wang X, Li M, Wu Z, Guo Z, Guo J, Jia J | display-authors = 6 | title = Pre-ischemic treadmill training for prevention of ischemic brain injury via regulation of glutamate and its transporter GLT-1 | journal = International Journal of Molecular Sciences | volume = 13 | issue = 8 | pages = 9447–9459 | date = 2012-07-26 | pmid = 22949807 | pmc = 3431805 | doi = 10.3390/ijms13089447 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Aboutaleb N, Shamsaei N, Khaksari M, Erfani S, Rajabi H, Nikbakht F | title = Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation | journal = The Journal of Physiological Sciences | volume = 65 | issue = 5 | pages = 435–443 | date = September 2015 | pmid = 26012958 | doi = 10.1007/s12576-015-0382-7 | s2cid = 255606303 | doi-access = free | pmc = 10717499 }}</ref> Additionally, it may promote [[Biology:Neurogenesis|neurogenesis]] in the brain. These effects collectively contribute to the reduction of brain infarction and edema, leading to potential improvements in neurological and functional outcomes. The neuroprotective properties of physical activity in relation to haemorrhagic strokes are less studied. Pre-stroke physical activity has been associated with improved outcomes after intracerebral haemorrhages.<ref>{{cite journal | vauthors = Viktorisson A, Buvarp D, Reinholdsson M, Danielsson A, Palstam A, Stibrant Sunnerhagen K | title = Associations of Prestroke Physical Activity With Stroke Severity and Mortality After Intracerebral Hemorrhage Compared With Ischemic Stroke | journal = Neurology | volume = 99 | issue = 19 | pages = e2137–e2148 | date = November 2022 | pmid = 36344278 | pmc = 9651453 | doi = 10.1212/WNL.0000000000201097 }}</ref> Furthermore, physical activity may reduce the volume of intracerebral haemorrhages.<ref>{{cite journal | vauthors = Viktorisson A, Buvarp D, Danielsson A, Skoglund T, Sunnerhagen KS | title = Prestroke physical activity is associated with admission haematoma volume and the clinical outcome of intracerebral haemorrhage | journal = Stroke and Vascular Neurology | pages = 511–520 | date = May 2023 | volume = 8 | issue = 6 | pmid = 37137521 | doi = 10.1136/svn-2023-002316 | s2cid = 258464205 | doi-access = free | pmc = 10800276 }}</ref><ref>{{cite journal | vauthors = Kinoshita K, Hamanaka G, Ohtomo R, Takase H, Chung KK, Lok J, Lo EH, Katsuki H, Arai K | display-authors = 6 | title = Mature Adult Mice With Exercise-Preconditioning Show Better Recovery After Intracerebral Hemorrhage | journal = Stroke | volume = 52 | issue = 5 | pages = 1861–1865 | date = May 2021 | pmid = 33840224 | pmc = 8085050 | doi = 10.1161/STROKEAHA.120.032201 }}</ref>  Being physically active after stroke also enhance the functional recovery.<ref>{{cite journal | vauthors = McKevitt C, Fudge N, Redfern J, Sheldenkar A, Crichton S, Rudd AR, Forster A, Young J, Nazareth I, Silver LE, Rothwell PM, Wolfe CD | display-authors = 6 | title = Self-reported long-term needs after stroke | journal = Stroke | volume = 42 | issue = 5 | pages = 1398–1403 | date = May 2011 | pmid = 21441153 | doi = 10.1161/STROKEAHA.110.598839 | s2cid = 33967186 }}</ref><ref>{{cite journal | vauthors = Buvarp D, Viktorisson A, Axelsson F, Lehto E, Lindgren L, Lundström E, Sunnerhagen KS | title = Physical Activity Trajectories and Functional Recovery After Acute Stroke Among Adults in Sweden | journal = JAMA Network Open | volume = 6 | issue = 5 | pages = e2310919 | date = May 2023 | pmid = 37126346 | pmc = 10152305 | doi = 10.1001/jamanetworkopen.2023.10919 }}</ref><ref>{{cite journal | vauthors = Gunnes M, Indredavik B, Langhammer B, Lydersen S, Ihle-Hansen H, Dahl AE, Askim T | title = Associations Between Adherence to the Physical Activity and Exercise Program Applied in the LAST Study and Functional Recovery After Stroke | journal = Archives of Physical Medicine and Rehabilitation | volume = 100 | issue = 12 | pages = 2251–2259 | date = December 2019 | pmid = 31374191 | doi = 10.1016/j.apmr.2019.04.023 | hdl = 10642/8488 | s2cid = 199388335 | hdl-access = free }}</ref>

===Mild cognitive impairment===

The American Academy of Neurology's January 2018 update of their clinical practice guideline for [[Medicine:Mild cognitive impairment|mild cognitive impairment]] states that clinicians should recommend regular exercise (two times per week) to individuals who have been diagnosed with this condition.<ref name="December 2017 AAN Clinical Practice Guideline for MCI" /> This guidance is based upon a moderate amount of high-quality evidence which supports the efficacy of regular physical exercise (twice weekly over a 6-month period) for improving cognitive symptoms in individuals with mild cognitive impairment.<ref name="December 2017 AAN Clinical Practice Guideline for MCI" />

===Neurodegenerative disorders===

====Alzheimer's disease====
[[Medicine:Alzheimer's disease|Alzheimer's disease]] is a cortical neurodegenerative disorder and the most prevalent form of [[Medicine:Dementia|dementia]], representing approximately 65% of all cases of dementia; it is characterized by impaired cognitive function, behavioral abnormalities, and a reduced capacity to perform [[Medicine:Activities of daily living|basic activities of daily life]].<ref name="Alz 1" /> Two reviews found evidence for possible positive effects of physical exercise on cognitive function, the rate of cognitive decline, and the ability to perform activities of daily living in individuals with Alzheimer's disease.<ref name="Alz 1" /> A subsequent review found higher levels of physical activity may be associated with reduced risk of dementia and cognitive decline.<ref name="Longitudinal SystRev dementia" />

==== Parkinson's disease ====
[[Medicine:Parkinson's disease|Parkinson's disease]] symptoms reflect various functional impairments and limitations, such as postural instability, gait disturbance, immobility, and frequent falls. Some evidence suggests that physical exercise may lower the risk of Parkinson's disease.<ref>{{cite journal |vauthors=Fang X, Han D, Cheng Q, Zhang P, Zhao C, Min J, Wang F |date=September 2018 |title=Association of Levels of Physical Activity With Risk of Parkinson Disease: A Systematic Review and Meta-analysis |journal=JAMA Network Open |volume=1 |issue=5 |pages=e182421 |doi=10.1001/jamanetworkopen.2018.2421 |pmc=6324511 |pmid=30646166}}</ref> A 2017 study found that strength and endurance training in people with Parkinson's disease had positive effects lasting for several weeks.<ref name=":1">{{Cite journal |last1=Mak |first1=Margaret K. |last2=Wong-Yu |first2=Irene S. |last3=Shen |first3=Xia |last4=Chung |first4=Chloe L. |date=November 2017 |title=Long-term effects of exercise and physical therapy in people with Parkinson disease |url=https://www.nature.com/articles/nrneurol.2017.128 |journal=Nature Reviews Neurology |language=en |volume=13 |issue=11 |pages=689–703 |doi=10.1038/nrneurol.2017.128 |pmid=29027544 |s2cid=29666456 |issn=1759-4766}}</ref> A 2023 Cochrane review on the effects of physical exercise in people with Parkinson's disease indicated that aquatic exercise might reduce severity of motor symptoms and improve quality of life.<ref name=":2">{{Cite journal|display-authors=3 |last=Ernst |first=Moritz |last2=Folkerts |first2=Ann-Kristin |last3=Gollan |first3=Romina |last4=Lieker |first4=Emma |last5=Caro-Valenzuela |first5=Julia |last6=Adams |first6=Anne |last7=Cryns |first7=Nora |last8=Monsef |first8=Ina |last9=Dresen |first9=Antje |last10=Roheger |first10=Mandy |last11=Eggers |first11=Carsten |last12=Skoetz |first12=Nicole |last13=Kalbe |first13=Elke |date=2023-01-05 |title=Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis|journal=The Cochrane Database of Systematic Reviews |volume=1 |issue=1 |pages=CD013856 |doi=10.1002/14651858.CD013856.pub2 |issn=1469-493X |pmc=9815433 |pmid=36602886}}</ref> Furthermore, endurance training, functional training, and multi-domain training (i.e., engaging in several types of exercise) may provide improvements.<ref name=":2" />

==See also==
{{col div|colwidth=30em}}
*Brain fitness
*Exercise is Medicine
*[[Medicine:Exercise prescription|Exercise prescription]]
*Exercise therapy
*[[Biology:Memory improvement|Memory improvement]]
*[[Biology:Neuroinflammation#Exercise|Neuroinflammation]]
*[[Chemistry:Nootropic|Nootropic]]
{{colend}}

==Notes==
<references group="note" />

==References==
{{reflist}}

{{Memory}}

[[Category:Antidepressants]]
[[Category:Cognition]]
[[Category:Cognitive neuroscience]]
[[Category:Epigenetics]]
[[Category:Euphoriants]]
[[Category:Exercise physiology]]
[[Category:Neuropsychology]]

{{Sourceattribution|Neurobiological effects of physical exercise}}