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Neurobiological effects of physical exercise
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<h2 id="long-term-effects">Long-term effects</h2> <h3>Neuroplasticity</h3> <p><a href="/facts/Neuroplasticity/c0o0fvVm">Neuroplasticity</a> is the process by which <a href="/facts/Neuron/G7CyTVdH">neurons</a> adapt to a disturbance over time, and most often occurs in response to repeated exposure to stimuli.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> Aerobic exercise increases the production of <a href="/facts/Neurotrophic_factors/bJNG05TQ">neurotrophic factors</a><a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> (e.g., <a href="/facts/Brain-derived_neurotrophic_factor/1v80e05e">BDNF</a>, <a href="/facts/Insulin-like_growth_factor_1/2n0nPvtD">IGF-1</a>, <a href="/facts/Vascular_endothelial_growth_factor/kNDc0Xj0">VEGF</a>) which mediate improvements in cognitive functions and various forms of memory by promoting <a href="/facts/Angiogenesis/h0HF9IUd">blood vessel formation</a> in the brain, <a href="/facts/Adult_neurogenesis/U2VuCgKu">adult neurogenesis</a>,<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> and other forms of neuroplasticity.[2]<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a><a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a><a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> Consistent aerobic exercise over a period of several months induces <a href="/facts/Clinically_significant/74qRJnKD">clinically significant</a> improvements in <a href="/facts/Executive_function/QtflLj55">executive functions</a> and increased <a href="/facts/Gray_matter/rqRM0qYY">gray matter</a> volume in nearly all regions of the brain,<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> with the most marked increases occurring in brain regions that give rise to executive functions.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a><a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> The brain structures that show the greatest improvements in gray matter volume in response to aerobic exercise are the <a href="/facts/Prefrontal_cortex/dypYIrwx">prefrontal cortex</a>, <a href="/facts/Caudate_nucleus/tAkRY4c0">caudate nucleus</a>, and <a href="/facts/Hippocampus/X7CqbP8X">hippocampus</a>;<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a><a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> less significant increases in gray matter volume occur in the <a href="/facts/Anterior_cingulate_cortex/gMBsA5EJ">anterior cingulate cortex</a>, <a href="/facts/Parietal_cortex/T74NKNTN">parietal cortex</a>, <a href="/facts/Cerebellum/kBRS2Lou">cerebellum</a>, and <a href="/facts/Nucleus_accumbens/2M43u5X4">nucleus accumbens</a>.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> The prefrontal cortex, caudate nucleus, and anterior cingulate cortex are among the most significant brain structures in the <a href="/facts/Neurotransmitter/LlpYFSU3">dopamine and norepinephrine systems</a> that give rise to cognitive control.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> Exercise-induced neurogenesis (i.e., the increases in gray matter volume) in the hippocampus is associated with measurable improvements in <a href="/facts/Spatial_memory/K5GuDYW3">spatial memory</a>.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a><a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> Higher <a href="/facts/Physical_fitness/eSnf5IJ1">physical fitness</a> scores, as measured by <a href="/facts/VO2_max/5eCkeysG">VO2 max</a>, are associated with better executive function, faster information processing speed, and greater <a href="/facts/Gray_matter/rqRM0qYY">gray matter</a> volume of the hippocampus, caudate nucleus, and nucleus accumbens.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a> </p> <h4>Structural growth</h4> <p>Reviews of neuroimaging studies indicate that consistent aerobic exercise increases <a href="/facts/Gray_matter/rqRM0qYY">gray matter</a> volume in nearly all regions of the brain,<a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> with more pronounced increases occurring in brain regions associated with memory processing, cognitive control, <a href="/facts/Motor_function/IwK2rqNW">motor function</a>, and <a href="/facts/Reward_system/fotI0rcM">reward</a>;<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a><a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a><a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> 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.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a><a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> Moreover, the left and right halves of the prefrontal cortex, the hippocampus, and the <a href="/facts/Cingulate_cortex/Eerbtdvr">cingulate cortex</a> appear to become more <a href="/facts/Functional_connectivity/yq9Qk2Yg">functionally interconnected</a> in response to consistent aerobic exercise.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> 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.<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a><a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> Other regions of the brain that demonstrate moderate or less significant gains in gray matter volume during neuroimaging include the <a href="/facts/Anterior_cingulate_cortex/gMBsA5EJ">anterior cingulate cortex</a>, <a href="/facts/Parietal_cortex/T74NKNTN">parietal cortex</a>, <a href="/facts/Cerebellum/kBRS2Lou">cerebellum</a>, and <a href="/facts/Nucleus_accumbens/2M43u5X4">nucleus accumbens</a>.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a><a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> </p><p>Regular exercise has been shown to counter the shrinking of the hippocampus and memory impairment that naturally occurs in late adulthood.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> Sedentary adults over age 55 show a 1–2% decline in hippocampal volume annually.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a> A neuroimaging study with a sample of 120 adults revealed that participating in regular aerobic exercise increased the volume of the left hippocampus by 2.12% and the right hippocampus by 1.97% over a one-year period.<a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> 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.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a> In general, individuals that exercise more over a given period have greater hippocampal volumes and better memory function.<a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a> Aerobic exercise has also been shown to induce growth in the <a href="/facts/White_matter/mvHqXJYk">white matter</a> tracts in the anterior <a href="/facts/Corpus_callosum/jL54tgHn">corpus callosum</a>, which normally shrink with age.<a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a><a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a> </p><p>The various functions of the brain structures that show exercise-induced increases in gray matter volume include: </p> <ul><li><a href="/facts/Caudate_nucleus/tAkRY4c0">Caudate nucleus</a> – responsible for <a href="/facts/Classical_conditioning/ddtohoz3">stimulus-response learning</a> and inhibitory control; implicated in <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a> and ADHD<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a><a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a></li> <li><a href="/facts/Cerebellum/kBRS2Lou">Cerebellum</a> – responsible for <a href="/facts/Motor_coordination/rVJbx4mX">motor coordination</a> and <a href="/facts/Motor_learning/jnm0vf1k">motor learning</a><a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a></li> <li><a href="/facts/Hippocampus/X7CqbP8X">Hippocampus</a> – responsible for storage and consolidation of <a href="/facts/Declarative_memory/vrjuSCDG">declarative memory</a> and <a href="/facts/Spatial_memory/K5GuDYW3">spatial memory</a><a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a></li> <li><a href="/facts/Nucleus_accumbens/2M43u5X4">Nucleus accumbens</a> – responsible for <a href="/facts/Incentive_salience/zCVbavjh">incentive salience</a> ("wanting" or desire, the form of <a href="/facts/Motivation/uqLMfLKq">motivation</a> associated with <a href="/facts/Reward_system/fotI0rcM">reward</a>) and <a href="/facts/Positive_reinforcement/bn271VLa">positive reinforcement</a>; implicated in addiction<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a></li> <li><a href="/facts/Parietal_cortex/T74NKNTN">Parietal cortex</a> – responsible for <a href="/facts/Sensory_perception/xLK0n2q4">sensory perception</a>, working memory, and attention<a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a><a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a></li> <li><a href="/facts/Prefrontal_cortex/dypYIrwx">Prefrontal</a> and <a href="/facts/Anterior_cingulate/gMBsA5EJ">anterior cingulate</a> cortices – required for the cognitive control of behavior, particularly: <a href="/facts/Working_memory/kzeDD3KQ">working memory</a>, <a href="/facts/Attentional_control/gPbUhqSq">attentional control</a>, <a href="/facts/Decision-making/NbJYprSw">decision-making</a>, <a href="/facts/Cognitive_flexibility/5MCcwX16">cognitive flexibility</a>, <a href="/facts/Social_cognition/Vhd8AdyG">social cognition</a>, and <a href="/facts/Inhibitory_control/XD74uhFc">inhibitory control</a> of behavior;<a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a><a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a> implicated in <a href="/facts/Attention_deficit_hyperactivity_disorder/uSqjIyhd">attention deficit hyperactivity disorder</a> (ADHD) and addiction<a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a></li></ul> <h4>Persistent effects on cognition </h4> <p class="note">See also: <a href="/facts/Executive_functions/QtflLj55">Executive functions</a></p> <p>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.<a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a><a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a><a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a><a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a> In particular, consistent aerobic exercise has been shown to improve <a href="/facts/Attentional_control/gPbUhqSq">attentional control</a>,<a class="footnote-ref" id="fnref:82" href="#fn:82"><sup>82</sup></a> <a href="/facts/Mental_chronometry/K1SBWJ81">information processing speed</a>, <a href="/facts/Cognitive_flexibility/5MCcwX16">cognitive flexibility</a> (e.g., <a href="/facts/Task_switching_(psychology)/R4YrmweI">task switching</a>), <a href="/facts/Inhibitory_control/XD74uhFc">inhibitory control</a>,<a class="footnote-ref" id="fnref:83" href="#fn:83"><sup>83</sup></a> <a href="/facts/Working_memory/kzeDD3KQ">working memory</a> updating and capacity,<a class="footnote-ref" id="fnref:84" href="#fn:84"><sup>84</sup></a> <a href="/facts/Declarative_memory/vrjuSCDG">declarative memory</a>,<a class="footnote-ref" id="fnref:85" href="#fn:85"><sup>85</sup></a> and <a href="/facts/Spatial_memory/K5GuDYW3">spatial memory</a>.<a class="footnote-ref" id="fnref:86" href="#fn:86"><sup>86</sup></a><a class="footnote-ref" id="fnref:87" href="#fn:87"><sup>87</sup></a><a class="footnote-ref" id="fnref:88" href="#fn:88"><sup>88</sup></a><a class="footnote-ref" id="fnref:89" href="#fn:89"><sup>89</sup></a> In healthy young and middle-aged adults, the <a href="/facts/Effect_size/mIpNrPte">effect sizes</a> of improvements in cognitive function are largest for indices of executive functions and small to moderate for aspects of memory and information processing speed.<a class="footnote-ref" id="fnref:90" href="#fn:90"><sup>90</sup></a><a class="footnote-ref" id="fnref:91" href="#fn:91"><sup>91</sup></a> 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.<a class="footnote-ref" id="fnref:92" href="#fn:92"><sup>92</sup></a> Individuals who have a sedentary lifestyle tend to have impaired executive functions relative to other more physically active non-exercisers.<a class="footnote-ref" id="fnref:93" href="#fn:93"><sup>93</sup></a> 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.<a class="footnote-ref" id="fnref:94" href="#fn:94"><sup>94</sup></a> </p> <h3>Mechanism of effects</h3> <p class="note">Further information: <a href="/facts/Myokine/4ytmFxnK">Myokine</a></p> <h4>BDNF signaling</h4> <p class="note">Further information: <a href="/facts/Brain-derived_neurotrophic_factor/1v80e05e">Brain-derived neurotrophic factor</a></p> <p>One of the most significant effects of exercise on the brain is increased synthesis and expression of <a href="/facts/Brain-derived_neurotrophic_factor/1v80e05e">BDNF</a>, a <a href="/facts/Neuropeptide/YdycoGuR">neuropeptide</a> and <a href="/facts/Peptide_hormone/8AdC52vt">hormone</a>, resulting in increased signaling through its <a href="/facts/Receptor_tyrosine_kinase/1oNWIdV8">receptor tyrosine kinase</a>, <a href="/facts/Tropomyosin_receptor_kinase_B/rgnDhymj">tropomyosin receptor kinase B</a> (TrkB).<a class="footnote-ref" id="fnref:95" href="#fn:95"><sup>95</sup></a><a class="footnote-ref" id="fnref:96" href="#fn:96"><sup>96</sup></a><a class="footnote-ref" id="fnref:97" href="#fn:97"><sup>97</sup></a> Since BDNF is capable of crossing the <a href="/facts/Blood%25E2%2580%2593brain_barrier/xYzvVwdu">blood–brain barrier</a>, higher peripheral BDNF synthesis also increases BDNF signaling in the brain.<a class="footnote-ref" id="fnref:98" href="#fn:98"><sup>98</sup></a> Exercise-induced increases in BDNF signaling are associated with improved cognitive function, improved mood, and improved memory.<a class="footnote-ref" id="fnref:99" href="#fn:99"><sup>99</sup></a><a class="footnote-ref" id="fnref:100" href="#fn:100"><sup>100</sup></a> Furthermore, research has provided a great deal of support for the role of BDNF in hippocampal neurogenesis, synaptic plasticity, and neural repair.<a class="footnote-ref" id="fnref:101" href="#fn:101"><sup>101</sup></a><a class="footnote-ref" id="fnref:102" href="#fn:102"><sup>102</sup></a> Engaging in moderate-high intensity aerobic exercise such as running, swimming, and cycling increases BDNF <a href="/facts/Protein_biosynthesis/P4IcGjPd">biosynthesis</a> through <a href="/facts/Myokine/4ytmFxnK">myokine</a> signaling, resulting in up to a threefold increase in <a href="/facts/Blood_plasma/oHuwwugG">blood plasma</a> and BDNF levels;<a class="footnote-ref" id="fnref:103" href="#fn:103"><sup>103</sup></a><a class="footnote-ref" id="fnref:104" href="#fn:104"><sup>104</sup></a><a class="footnote-ref" id="fnref:105" href="#fn:105"><sup>105</sup></a> exercise intensity is positively correlated with the magnitude of increased BDNF biosynthesis and expression.<a class="footnote-ref" id="fnref:106" href="#fn:106"><sup>106</sup></a><a class="footnote-ref" id="fnref:107" href="#fn:107"><sup>107</sup></a><a class="footnote-ref" id="fnref:108" href="#fn:108"><sup>108</sup></a> A meta-analysis of studies involving the effect of exercise on BDNF levels found that consistent exercise modestly increases resting BDNF levels as well.<a class="footnote-ref" id="fnref:109" href="#fn:109"><sup>109</sup></a> 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.<a class="footnote-ref" id="fnref:110" href="#fn:110"><sup>110</sup></a> </p> <h4>IGF-1 signaling</h4> <p class="note">Further information: <a href="/facts/Insulin-like_growth_factor_1/2n0nPvtD">Insulin-like growth factor 1</a></p> <p>IGF-1 is a <a href="/facts/Peptide/C4ltc7UG">peptide</a> and <a href="/facts/Neurotrophic_factor/bJNG05TQ">neurotrophic factor</a> that mediates some of the effects of <a href="/facts/Growth_hormone/SLEJ1fws">growth hormone</a>;<a class="footnote-ref" id="fnref:111" href="#fn:111"><sup>111</sup></a> IGF-1 elicits its physiological effects by binding to a specific <a href="/facts/Receptor_tyrosine_kinase/1oNWIdV8">receptor tyrosine kinase</a>, the <a href="/facts/IGF-1_receptor/R4c7MCqp">IGF-1 receptor</a>, to control tissue growth and remodeling.<a class="footnote-ref" id="fnref:112" href="#fn:112"><sup>112</sup></a> In the brain, IGF-1 functions as a neurotrophic factor that, like BDNF, plays a significant role in cognition, neurogenesis, and neuronal survival.<a class="footnote-ref" id="fnref:113" href="#fn:113"><sup>113</sup></a><a class="footnote-ref" id="fnref:114" href="#fn:114"><sup>114</sup></a><a class="footnote-ref" id="fnref:115" href="#fn:115"><sup>115</sup></a> Physical activity is associated with increased levels of IGF-1 in <a href="/facts/Blood_serum/a22tvug9">blood serum</a>, which is known to contribute to neuroplasticity in the brain due to its capacity to cross the <a href="/facts/Blood%25E2%2580%2593brain_barrier/xYzvVwdu">blood–brain barrier</a> and <a href="/facts/Blood%25E2%2580%2593cerebrospinal_fluid_barrier/glqWkmkG">blood–cerebrospinal fluid barrier</a>;<a class="footnote-ref" id="fnref:116" href="#fn:116"><sup>116</sup></a><a class="footnote-ref" id="fnref:117" href="#fn:117"><sup>117</sup></a><a class="footnote-ref" id="fnref:118" href="#fn:118"><sup>118</sup></a><a class="footnote-ref" id="fnref:119" href="#fn:119"><sup>119</sup></a> 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".<a class="footnote-ref" id="fnref:120" href="#fn:120"><sup>120</sup></a><a class="footnote-ref" id="fnref:121" href="#fn:121"><sup>121</sup></a> The amount of IGF-1 released into blood plasma during exercise is positively correlated with exercise intensity and duration.<a class="footnote-ref" id="fnref:122" href="#fn:122"><sup>122</sup></a> </p> <h4>VEGF signaling</h4> <p class="note">Further information: <a href="/facts/Vascular_endothelial_growth_factor/kNDc0Xj0">Vascular endothelial growth factor</a></p> <p>VEGF is a neurotrophic and <a href="/facts/Angiogenesis/h0HF9IUd">angiogenic</a> (i.e., blood vessel growth-promoting) <a href="/facts/Cell_signaling/6oYAVP9I">signaling protein</a> that binds to two receptor tyrosine kinases, <a href="/facts/VEGFR1/F73KHUpI">VEGFR1</a> and <a href="/facts/VEGFR2/m1Yd5IUY">VEGFR2</a>, which are expressed in <a href="/facts/Neurons/G7CyTVdH">neurons</a> and <a href="/facts/Glial_cell/F8BhPmaA">glial cells</a> in the brain.<a class="footnote-ref" id="fnref:123" href="#fn:123"><sup>123</sup></a> <a href="/facts/Hypoxia_(medical)/JWV04G89">Hypoxia</a>, or inadequate cellular oxygen supply, strongly upregulates VEGF expression and VEGF exerts a neuroprotective effect in hypoxic neurons.<a class="footnote-ref" id="fnref:124" href="#fn:124"><sup>124</sup></a> Like BDNF and IGF-1, aerobic exercise has been shown to increase VEGF biosynthesis in peripheral tissue which subsequently crosses the blood–brain barrier and promotes neurogenesis and <a href="/facts/Angiogenesis/h0HF9IUd">blood vessel formation</a> in the <a href="/facts/Central_nervous_system/k8I6To97">central nervous system</a>.<a class="footnote-ref" id="fnref:125" href="#fn:125"><sup>125</sup></a><a class="footnote-ref" id="fnref:126" href="#fn:126"><sup>126</sup></a> Exercise-induced increases in VEGF signaling have been shown to improve cerebral blood volume and contribute to exercise-induced neurogenesis in the hippocampus.<a class="footnote-ref" id="fnref:127" href="#fn:127"><sup>127</sup></a><a class="footnote-ref" id="fnref:128" href="#fn:128"><sup>128</sup></a> </p> <h2 id="short-term-effects">Short-term effects</h2> <h3>Transient effects on cognition</h3> <p class="note">See also: <a href="/facts/Executive_functions/QtflLj55">Executive functions</a></p> <p>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.<a class="footnote-ref" id="fnref:129" href="#fn:129"><sup>129</sup></a><a class="footnote-ref" id="fnref:130" href="#fn:130"><sup>130</sup></a><a class="footnote-ref" id="fnref:131" href="#fn:131"><sup>131</sup></a> Reviews and meta-analyses of research on the effects of acute exercise on cognition in healthy young and middle-aged adults have concluded that information processing speed and a number of executive functions – including attention, working memory, problem solving, cognitive flexibility, verbal fluency, decision making, and inhibitory control – all improve for a period of up to 2 hours post-exercise.<a class="footnote-ref" id="fnref:132" href="#fn:132"><sup>132</sup></a><a class="footnote-ref" id="fnref:133" href="#fn:133"><sup>133</sup></a><a class="footnote-ref" id="fnref:134" href="#fn:134"><sup>134</sup></a> 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.<a class="footnote-ref" id="fnref:135" href="#fn:135"><sup>135</sup></a> 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.<a class="footnote-ref" id="fnref:136" href="#fn:136"><sup>136</sup></a><a class="footnote-ref" id="fnref:137" href="#fn:137"><sup>137</sup></a> </p> <h3>Exercise-induced euphoria</h3> <p class="note">Main article: <a href="/facts/Runner%2527s_high/kVVntCLn">Runner's high</a></p> <p>Continuous exercise can produce a transient state of <a href="/facts/Euphoria/u4cnbWC4">euphoria</a> – an emotional state involving the experience of <a href="/facts/Pleasure/rkU6McmK">pleasure</a> and feelings of profound contentment, elation, and well-being – which is colloquially known as a "<a href="/facts/Runner%2527s_high/kVVntCLn">runner's high</a>" in <a href="/facts/Distance_running/jJSRjrDd">distance running</a> or a "rower's high" in <a href="/facts/Rowing_(sport)/vN9AnU2G">rowing</a>.<a class="footnote-ref" id="fnref:138" href="#fn:138"><sup>138</sup></a><a class="footnote-ref" id="fnref:139" href="#fn:139"><sup>139</sup></a><a class="footnote-ref" id="fnref:140" href="#fn:140"><sup>140</sup></a><a class="footnote-ref" id="fnref:141" href="#fn:141"><sup>141</sup></a> Not everyone experiences this.<a class="footnote-ref" id="fnref:142" href="#fn:142"><sup>142</sup></a> </p> <h2 id="effects-on-neurochemistry">Effects on neurochemistry</h2> <h3>β-Phenylethylamine</h3> <table><tbody><tr><td></td></tr></tbody></table> <p><a href="/facts/%25CE%2592-Phenylethylamine/XyjysSul">β-Phenylethylamine</a>, commonly referred to as <i>phenethylamine</i>, is a human <a href="/facts/Trace_amine/WXRDyUMH">trace amine</a> and potent <a href="/facts/Catecholamine/hHFrCMgM">catecholaminergic</a> and <a href="/facts/Glutamate_(neurotransmitter)/GRqBSJ1P">glutamatergic</a> <a href="/facts/Neuromodulator/mwjkrkHt">neuromodulator</a> that has similar <a href="/facts/Psychostimulant/nmBdAXM5">psychostimulant</a> and <a href="/facts/Euphoriant/u4cnbWC4">euphoriant</a> effects and a similar <a href="/facts/Chemical_structure/r5rT1Lj4">chemical structure</a> to <a href="/facts/Amphetamine/yKIpLJ9E">amphetamine</a>.<a class="footnote-ref" id="fnref:143" href="#fn:143"><sup>143</sup></a> Thirty minutes of moderate to high intensity physical exercise has been shown to induce an enormous increase in urinary <a href="/facts/%25CE%2592-phenylacetic_acid/cjfwIEs2">β-phenylacetic acid</a>, the primary metabolite of phenethylamine.<a class="footnote-ref" id="fnref:144" href="#fn:144"><sup>144</sup></a><a class="footnote-ref" id="fnref:145" href="#fn:145"><sup>145</sup></a><a class="footnote-ref" id="fnref:146" href="#fn:146"><sup>146</sup></a> Two reviews noted a study where the average 24 hour urinary β-phenylacetic acid concentration among participants following just 30 minutes of intense exercise increased by 77% relative to baseline concentrations in resting control subjects;<a class="footnote-ref" id="fnref:147" href="#fn:147"><sup>147</sup></a><a class="footnote-ref" id="fnref:148" href="#fn:148"><sup>148</sup></a><a class="footnote-ref" id="fnref:149" href="#fn:149"><sup>149</sup></a> the reviews suggest that phenethylamine synthesis sharply increases while an individual is exercising, during which time it is rapidly metabolized due to its short half-life of roughly 30 seconds.<a class="footnote-ref" id="fnref:150" href="#fn:150"><sup>150</sup></a><a class="footnote-ref" id="fnref:151" href="#fn:151"><sup>151</sup></a><a class="footnote-ref" id="fnref:152" href="#fn:152"><sup>152</sup></a><a class="footnote-ref" id="fnref:153" href="#fn:153"><sup>153</sup></a> In a resting state, phenethylamine is synthesized in <a href="/facts/Catecholamine/hHFrCMgM">catecholamine</a> neurons from L-<a href="/facts/Phenylalanine/eyojfW7t">phenylalanine</a> by <a href="/facts/Aromatic_amino_acid_decarboxylase/EUQpb2Rr">aromatic amino acid decarboxylase</a> (AADC) at approximately the same rate at which <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a> is produced.<a class="footnote-ref" id="fnref:154" href="#fn:154"><sup>154</sup></a> </p><p>In light of this observation, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing <a href="/facts/Euphoria/u4cnbWC4">euphoric</a> effects of a runner's high, as both phenethylamine and amphetamine are potent euphoriants.<a class="footnote-ref" id="fnref:155" href="#fn:155"><sup>155</sup></a><a class="footnote-ref" id="fnref:156" href="#fn:156"><sup>156</sup></a><a class="footnote-ref" id="fnref:157" href="#fn:157"><sup>157</sup></a> </p> <h3>β-Endorphin</h3> <p><a href="/facts/%25CE%2592-Endorphin/FQVE1eY1">β-Endorphin</a> (contracted from "endogenous morphine") is an endogenous <a href="/facts/Opioid/EGnE2x99">opioid</a> <a href="/facts/Neuropeptide/YdycoGuR">neuropeptide</a> that binds to <a href="/facts/%25CE%259C-opioid_receptor/8a3wdeTc">μ-opioid receptors</a>, in turn producing <a href="/facts/Euphoria/u4cnbWC4">euphoria</a> and <a href="/facts/Analgesia/xLj4XBcq">pain relief</a>.<a class="footnote-ref" id="fnref:158" href="#fn:158"><sup>158</sup></a> A <a href="/facts/Meta-analytic/IcfChd8z">meta-analytic</a> review found that exercise significantly increases the secretion of β-endorphin and that this secretion is correlated with improved mood states.<a class="footnote-ref" id="fnref:159" href="#fn:159"><sup>159</sup></a> Moderate intensity exercise produces the greatest increase in β-endorphin synthesis, while higher and lower intensity forms of exercise are associated with smaller increases in β-endorphin synthesis.<a class="footnote-ref" id="fnref:160" href="#fn:160"><sup>160</sup></a> A review on 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.<a class="footnote-ref" id="fnref:161" href="#fn:161"><sup>161</sup></a> </p><p>However, human studies showed that pharmacological blockade of endogenous endorphins does not inhibit a runner's high, while blockade of endocannabinoids may have such an effect.<a class="footnote-ref" id="fnref:162" href="#fn:162"><sup>162</sup></a> </p> <h3>Anandamide</h3> <p><a href="/facts/Anandamide/dwkXv1fC">Anandamide</a> is an <a href="/facts/Endocannabinoid/MHcltwTn">endogenous cannabinoid</a> and <a href="/facts/Retrograde_neurotransmitter/tuSHb1Pj">retrograde neurotransmitter</a> that binds to <a href="/facts/Cannabinoid_receptor/o92UKAxQ">cannabinoid receptors</a> (primarily <a href="/facts/Cannabinoid_receptor_1/7b2tfePV">CB1</a>), in turn producing euphoria.<a class="footnote-ref" id="fnref:163" href="#fn:163"><sup>163</sup></a><a class="footnote-ref" id="fnref:164" href="#fn:164"><sup>164</sup></a> 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).<a class="footnote-ref" id="fnref:165" href="#fn:165"><sup>165</sup></a> Increases in plasma anandamide levels are associated with <a href="/facts/Psychoactive_drug/dNXrUmsx">psychoactive effects</a> because anandamide is able to cross the <a href="/facts/Blood%25E2%2580%2593brain_barrier/xYzvVwdu">blood–brain barrier</a> and act within the central nervous system.<a class="footnote-ref" id="fnref:166" href="#fn:166"><sup>166</sup></a> 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.<a class="footnote-ref" id="fnref:167" href="#fn:167"><sup>167</sup></a><a class="footnote-ref" id="fnref:168" href="#fn:168"><sup>168</sup></a> </p> <h3>Cortisol and the psychological stress response</h3> <p class="note">See also: <a href="/facts/Effects_of_stress_on_memory/U8v29F0S">Effects of stress on memory</a></p> <p>The "stress hormone", <a href="/facts/Cortisol/5IvRV0cm">cortisol</a>, is a <a href="/facts/Glucocorticoid/2P91Aj3S">glucocorticoid</a> that binds to <a href="/facts/Glucocorticoid_receptor/NUsGokjq">glucocorticoid receptors</a>.<a class="footnote-ref" id="fnref:169" href="#fn:169"><sup>169</sup></a><a class="footnote-ref" id="fnref:170" href="#fn:170"><sup>170</sup></a><a class="footnote-ref" id="fnref:171" href="#fn:171"><sup>171</sup></a> <a href="/facts/Psychological_stress/eqat8pq9">Psychological stress</a> induces the release of cortisol from the <a href="/facts/Adrenal_gland/3f8jV5aJ">adrenal gland</a> by activating the <a href="/facts/Hypothalamic%25E2%2580%2593pituitary%25E2%2580%2593adrenal_axis/062CevaI">hypothalamic–pituitary–adrenal axis</a> (HPA axis).<a class="footnote-ref" id="fnref:172" href="#fn:172"><sup>172</sup></a><a class="footnote-ref" id="fnref:173" href="#fn:173"><sup>173</sup></a><a class="footnote-ref" id="fnref:174" href="#fn:174"><sup>174</sup></a> Short-term increases in cortisol levels are associated with adaptive cognitive improvements, such as enhanced inhibitory control;<a class="footnote-ref" id="fnref:175" href="#fn:175"><sup>175</sup></a><a class="footnote-ref" id="fnref:176" href="#fn:176"><sup>176</sup></a> however, excessively high exposure or prolonged exposure to high levels of cortisol causes impairments in cognitive control and has <a href="/facts/Neurotoxic/FrgTICfX">neurotoxic</a> effects in the human brain.<a class="footnote-ref" id="fnref:177" href="#fn:177"><sup>177</sup></a> For example, chronic psychological stress decreases BDNF expression, which has detrimental effects on hippocampal volume and can lead to depression.<a class="footnote-ref" id="fnref:178" href="#fn:178"><sup>178</sup></a> </p><p>As a physical stressor, aerobic exercise stimulates cortisol secretion in an intensity-dependent manner;<a class="footnote-ref" id="fnref:179" href="#fn:179"><sup>179</sup></a> 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 <a href="/facts/Energy_homeostasis/0quwmrbc">energy balance</a>.<a class="footnote-ref" id="fnref:180" href="#fn:180"><sup>180</sup></a><a class="footnote-ref" id="fnref:181" href="#fn:181"><sup>181</sup></a> Aerobic exercise increases <a href="/facts/Physical_fitness/eSnf5IJ1">physical fitness</a> and lowers <a href="/facts/Neuroendocrinology/lVldJ7MB">neuroendocrine</a> (i.e., HPA axis) reactivity and therefore reduces the biological response to psychological stress in humans (e.g., reduced cortisol release and attenuated <a href="/facts/Heart_rate/YngB0bzg">heart rate</a> response).<a class="footnote-ref" id="fnref:182" href="#fn:182"><sup>182</sup></a><a class="footnote-ref" id="fnref:183" href="#fn:183"><sup>183</sup></a> Exercise also reverses stress-induced decreases in BDNF expression and signaling in the brain, thereby acting as a buffer against stress-related diseases like depression.<a class="footnote-ref" id="fnref:184" href="#fn:184"><sup>184</sup></a><a class="footnote-ref" id="fnref:185" href="#fn:185"><sup>185</sup></a> </p> <h3>Glutamate and GABA</h3> <p><a href="/facts/Glutamate/7oXbNcvu">Glutamate</a>, one of the most common neurochemicals in the brain, is an <a href="/facts/Excitatory_neurotransmitter/LlpYFSU3">excitatory neurotransmitter</a> involved in many aspects of brain function, including learning and memory.<a class="footnote-ref" id="fnref:186" href="#fn:186"><sup>186</sup></a> Based upon animal models, exercise appears to normalize the excessive levels of glutamate neurotransmission into the <a href="/facts/Nucleus_accumbens/2M43u5X4">nucleus accumbens</a> that occurs in drug addiction.<a class="footnote-ref" id="fnref:187" href="#fn:187"><sup>187</sup></a> A review of the effects of exercise on neurocardiac function in preclinical models noted that exercise-induced neuroplasticity of the <a href="/facts/Rostral_ventrolateral_medulla/tTG8EIgx">rostral ventrolateral medulla</a> (RVLM) has an inhibitory effect on glutamatergic neurotransmission in this region, in turn reducing <a href="/facts/Sympathetic_nervous_system/hs8psNRd">sympathetic activity</a>;<a class="footnote-ref" id="fnref:188" href="#fn:188"><sup>188</sup></a> the review hypothesized that this neuroplasticity in the RVLM is a mechanism by which regular exercise prevents inactivity-related <a href="/facts/Cardiovascular_disease/HD420nMv">cardiovascular disease</a>.<a class="footnote-ref" id="fnref:189" href="#fn:189"><sup>189</sup></a> </p> <h3>Exerkines and other circulating compounds</h3> <p>Exerkines are putative "signalling moieties released in response to acute and/or chronic exercise, which exert their effects through <a href="/facts/Endocrine/PDvN5cpj">endocrine</a>, <a href="/facts/Paracrine/V8eVwG9z">paracrine</a> and/or <a href="/facts/Autocrine/EwfQEYzG">autocrine</a> pathways".<a class="footnote-ref" id="fnref:190" href="#fn:190"><sup>190</sup></a> </p> <h2 id="effects-in-children">Effects in children</h2> <p>Engaging in active physical pursuits has demonstrated positive effects on the mental health of children and adolescents,<a class="footnote-ref" id="fnref:191" href="#fn:191"><sup>191</sup></a> enhances their academic performance,<a class="footnote-ref" id="fnref:192" href="#fn:192"><sup>192</sup></a> boosts cognitive function,<a class="footnote-ref" id="fnref:193" href="#fn:193"><sup>193</sup></a> and diminishes the likelihood of obesity and cardiovascular diseases among this demographic.<a class="footnote-ref" id="fnref:194" href="#fn:194"><sup>194</sup></a> Establishing consistent exercise routines with regular frequency and duration is pivotal.<a class="footnote-ref" id="fnref:195" href="#fn:195"><sup>195</sup></a><a class="footnote-ref" id="fnref:196" href="#fn:196"><sup>196</sup></a><a class="footnote-ref" id="fnref:197" href="#fn:197"><sup>197</sup></a> 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. </p><p>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.<a class="footnote-ref" id="fnref:198" href="#fn:198"><sup>198</sup></a> The correlation was strongest for the age ranges of 4–7 and 11–13 years.<a class="footnote-ref" id="fnref:199" href="#fn:199"><sup>199</sup></a> </p><p>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.<a class="footnote-ref" id="fnref:200" href="#fn:200"><sup>200</sup></a> Other studies suggested that exercise is unrelated to academic performance, perhaps due to the parameters used to determine exactly what academic achievement is.<a class="footnote-ref" id="fnref:201" href="#fn:201"><sup>201</sup></a> 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.<a class="footnote-ref" id="fnref:202" href="#fn:202"><sup>202</sup></a> </p><p>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.<a class="footnote-ref" id="fnref:203" href="#fn:203"><sup>203</sup></a> </p><p>Neuroimaging studies indicate that exercise may influence changes in brain structure and function.<a class="footnote-ref" id="fnref:204" href="#fn:204"><sup>204</sup></a> 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.<a class="footnote-ref" id="fnref:205" href="#fn:205"><sup>205</sup></a> </p> <h2 id="effects-on-central-nervous-system-disorders">Effects on central nervous system disorders</h2> <p class="note">See also: <a href="/facts/Central_nervous_system_disorders/EGlB2D4w">Central nervous system disorders</a></p> <h3>Exercise as prevention and treatment of drug addictions</h3> <p>Clinical and preclinical evidence indicate that consistent aerobic exercise, especially endurance exercise (e.g., <a href="/facts/Marathon_running/IP3eBrhS">marathon running</a>), actually prevents the development of certain <a href="/facts/Drug_addiction/76UrWQuT">drug addictions</a> and is an effective adjunct treatment for drug addiction, and psychostimulant addiction in particular.<a class="footnote-ref" id="fnref:206" href="#fn:206"><sup>206</sup></a><a class="footnote-ref" id="fnref:207" href="#fn:207"><sup>207</sup></a><a class="footnote-ref" id="fnref:208" href="#fn:208"><sup>208</sup></a><a class="footnote-ref" id="fnref:209" href="#fn:209"><sup>209</sup></a> 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.<a class="footnote-ref" id="fnref:210" href="#fn:210"><sup>210</sup></a><a class="footnote-ref" id="fnref:211" href="#fn:211"><sup>211</sup></a> Moreover, aerobic exercise decreases psychostimulant self-administration, reduces the <a href="/facts/Reinstatement/XskgIodS">reinstatement</a> (i.e., relapse) of drug-seeking, and induces opposite effects on <a href="/facts/Striatum/MjNnTjSd">striatal</a> <a href="/facts/Dopamine_receptor_D2/SmmP3QyU">dopamine receptor D2</a> (DRD2) signaling (increased DRD2 density) to those induced by pathological stimulant use (decreased DRD2 density).<a class="footnote-ref" id="fnref:212" href="#fn:212"><sup>212</sup></a><a class="footnote-ref" id="fnref:213" href="#fn:213"><sup>213</sup></a> Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.<a class="footnote-ref" id="fnref:214" href="#fn:214"><sup>214</sup></a><a class="footnote-ref" id="fnref:215" href="#fn:215"><sup>215</sup></a> As of 2016<a href="https://en.wikipedia.org/w/index.php?title=Neurobiological_effects_of_physical_exercise&action=edit">[update]</a>, more clinical research is still needed to understand the mechanisms and confirm the efficacy of exercise in drug addiction treatment and prevention.<a class="footnote-ref" id="fnref:216" href="#fn:216"><sup>216</sup></a> </p> Summary of addiction-related plasticity<table><tbody><tr><th scope="col" rowspan="2">Form of <a href="/facts/Neuroplasticity/c0o0fvVm">neuroplasticity</a> or <a href="/facts/Behavioral_plasticity/Bezn2xm1">behavioral plasticity</a></th><th scope="col" colspan="6">Type of <a href="/facts/Reinforcement/bn271VLa">reinforcer</a></th><th scope="col" rowspan="2">Sources</th></tr><tr><th scope="col">Opiates</th><th scope="col">Psychostimulants</th><th scope="col">High fat or sugar food</th><th scope="col"><a href="/facts/Sexual_intercourse/okjwpVnB">Sexual intercourse</a></th><th scope="col">Physical exercise(aerobic)</th><th scope="col"><a href="/facts/Environmental_enrichment/UDueI4mS">Environmentalenrichment</a></th></tr><tr><td scope="row"><a href="/facts/%25CE%2594FosB/KHElvauK">ΔFosB</a> expression in<a href="/facts/Nucleus_accumbens/2M43u5X4">nucleus accumbens</a> <a href="/facts/D1-type/yu13N9ky">D1-type</a> <a href="/facts/Medium_spiny_neurons/pgzI2WKw">MSNs</a>Tooltip medium spiny neurons</td><td>↑</td><td>↑</td><td>↑</td><td>↑</td><td>↑</td><td>↑</td><td><a class="footnote-ref" id="fnref:217" href="#fn:217"><sup>217</sup></a></td></tr><tr><th scope="col" colspan="8">Behavioral plasticity</th></tr><tr><td scope="row">Escalation of intake</td><td>Yes</td><td>Yes</td><td>Yes</td><td></td><td></td><td></td><td><a class="footnote-ref" id="fnref:218" href="#fn:218"><sup>218</sup></a></td></tr><tr><td scope="row">Psychostimulant<a href="/facts/Addiction/76UrWQuT">cross-sensitization</a></td><td>Yes</td><td>Not applicable</td><td>Yes</td><td>Yes</td><td>Attenuated</td><td>Attenuated</td><td><a class="footnote-ref" id="fnref:219" href="#fn:219"><sup>219</sup></a></td></tr><tr><td scope="row">Psychostimulant<a href="/facts/Self-administration/QpVQv4xS">self-administration</a></td><td>↑</td><td>↑</td><td>↓</td><td></td><td>↓</td><td>↓</td><td><a class="footnote-ref" id="fnref:220" href="#fn:220"><sup>220</sup></a></td></tr><tr><td scope="row">Psychostimulant<a href="/facts/Conditioned_place_preference/C69ShbqG">conditioned place preference</a></td><td>↑</td><td>↑</td><td>↓</td><td>↑</td><td>↓</td><td>↑</td><td><a class="footnote-ref" id="fnref:221" href="#fn:221"><sup>221</sup></a></td></tr><tr><td scope="row"><a href="/facts/Reinstatement_of_drug-seeking_behavior/XskgIodS">Reinstatement of drug-seeking behavior</a></td><td>↑</td><td>↑</td><td></td><td></td><td>↓</td><td>↓</td><td><a class="footnote-ref" id="fnref:222" href="#fn:222"><sup>222</sup></a></td></tr><tr><th scope="col" colspan="8">Neurochemical plasticity</th></tr><tr><td scope="row"><a href="/facts/CAMP_response_element-binding_protein/ug1kE9j0">CREB</a>Tooltip cAMP response element-binding protein <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a>in the nucleus accumbens</td><td>↓</td><td>↓</td><td>↓</td><td></td><td>↓</td><td>↓</td><td><a class="footnote-ref" id="fnref:223" href="#fn:223"><sup>223</sup></a></td></tr><tr><td scope="row">Sensitized <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a> responsein the nucleus accumbens</td><td>No</td><td>Yes</td><td>No</td><td>Yes</td><td></td><td></td><td><a class="footnote-ref" id="fnref:224" href="#fn:224"><sup>224</sup></a></td></tr><tr><td scope="row">Altered <a href="/facts/Striatum/MjNnTjSd">striatal</a> <a href="/facts/Dopamine_receptor/fgsjJwkL">dopamine signaling</a></td><td>↓<a href="/facts/DRD2/SmmP3QyU">DRD2</a>, ↑<a href="/facts/DRD3/e1L1KnJq">DRD3</a></td><td>↑<a href="/facts/DRD1/fkWRTblS">DRD1</a>, ↓<a href="/facts/DRD2/SmmP3QyU">DRD2</a>, ↑<a href="/facts/DRD3/e1L1KnJq">DRD3</a></td><td>↑<a href="/facts/DRD1/fkWRTblS">DRD1</a>, ↓<a href="/facts/DRD2/SmmP3QyU">DRD2</a>, ↑<a href="/facts/DRD3/e1L1KnJq">DRD3</a></td><td></td><td>↑<a href="/facts/DRD2/SmmP3QyU">DRD2</a></td><td>↑<a href="/facts/DRD2/SmmP3QyU">DRD2</a></td><td><a class="footnote-ref" id="fnref:225" href="#fn:225"><sup>225</sup></a></td></tr><tr><td scope="row">Altered striatal <a href="/facts/Opioid_receptor/eDIAqgV3">opioid signaling</a></td><td>No change or↑<a href="/facts/%25CE%259C-opioid_receptor/8a3wdeTc">μ-opioid receptors</a></td><td>↑<a href="/facts/%25CE%259C-opioid_receptor/8a3wdeTc">μ-opioid receptors</a>↑<a href="/facts/%25CE%259A-opioid_receptor/zJRo3NoF">κ-opioid receptors</a></td><td>↑<a href="/facts/%25CE%259C-opioid_receptor/8a3wdeTc">μ-opioid receptors</a></td><td>↑<a href="/facts/%25CE%259C-opioid_receptor/8a3wdeTc">μ-opioid receptors</a></td><td>No change</td><td>No change</td><td><a class="footnote-ref" id="fnref:226" href="#fn:226"><sup>226</sup></a></td></tr><tr><td scope="row">Changes in striatal <a href="/facts/Opioid_peptide/FhQc0ntm">opioid peptides</a></td><td>↑<a href="/facts/Dynorphin/ent2QkXk">dynorphin</a>No change: <a href="/facts/Enkephalin/lVvearbQ">enkephalin</a></td><td>↑<a href="/facts/Dynorphin/ent2QkXk">dynorphin</a></td><td>↓<a href="/facts/Enkephalin/lVvearbQ">enkephalin</a></td><td></td><td>↑<a href="/facts/Dynorphin/ent2QkXk">dynorphin</a></td><td>↑<a href="/facts/Dynorphin/ent2QkXk">dynorphin</a></td><td><a class="footnote-ref" id="fnref:227" href="#fn:227"><sup>227</sup></a></td></tr><tr><th scope="col" colspan="8"><a href="/facts/Dopaminergic_pathways/EFooas5U">Mesocorticolimbic</a> <a href="/facts/Synaptic_plasticity/rdVFxItN">synaptic plasticity</a></th></tr><tr><td scope="row">Number of <a href="/facts/Dendrite/bwv8MABY">dendrites</a> in the nucleus accumbens</td><td>↓</td><td>↑</td><td></td><td>↑</td><td></td><td></td><td><a class="footnote-ref" id="fnref:228" href="#fn:228"><sup>228</sup></a></td></tr><tr><td scope="row"><a href="/facts/Dendritic_spine/wg54o3YT">Dendritic spine</a> density inthe nucleus accumbens</td><td>↓</td><td>↑</td><td></td><td>↑</td><td></td><td></td><td><a class="footnote-ref" id="fnref:229" href="#fn:229"><sup>229</sup></a></td></tr></tbody></table> <h3>Attention deficit hyperactivity disorder</h3> <p>Regular physical exercise, particularly aerobic exercise, is an effective <a href="/facts/Adjunct_therapy/WrmcN4nU">add-on treatment</a> for <a href="/facts/Attention_deficit_hyperactivity_disorder/uSqjIyhd">ADHD</a> in children and adults, particularly when combined with stimulant medication (i.e., <a href="/facts/Amphetamine/yKIpLJ9E">amphetamine</a> or <a href="/facts/Methylphenidate/PHmG2R5p">methylphenidate</a>), although the best intensity and type of aerobic exercise for improving symptoms are not currently known.<a class="footnote-ref" id="fnref:230" href="#fn:230"><sup>230</sup></a><a class="footnote-ref" id="fnref:231" href="#fn:231"><sup>231</sup></a> In particular, the long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved <a href="/facts/Executive_functions/QtflLj55">executive functions</a> (including attention, <a href="/facts/Inhibitory_control/XD74uhFc">inhibitory control</a>, and <a href="/facts/Planning/ckzCp5tv">planning</a>, among other cognitive domains), faster information processing speed, and better memory.<a class="footnote-ref" id="fnref:232" href="#fn:232"><sup>232</sup></a> 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.<a class="footnote-ref" id="fnref:233" href="#fn:233"><sup>233</sup></a> Exercising while on stimulant medication augments the effect of stimulant medication on executive function.<a class="footnote-ref" id="fnref:234" href="#fn:234"><sup>234</sup></a> It is believed that these short-term effects of exercise are mediated by an increased abundance of <a href="/facts/Synapse/vdMRJCUn">synaptic</a> dopamine and norepinephrine in the brain.<a class="footnote-ref" id="fnref:235" href="#fn:235"><sup>235</sup></a> </p> <h3>Major depressive disorder</h3> <p>Numerous <a href="/facts/Systematic_review/dGvq3BGx">systematic reviews</a> and <a href="/facts/Meta-analysis/IcfChd8z">meta-analyses</a> have indicated that exercise has a marked and persistent <a href="/facts/Antidepressant/N62ND3Fa">antidepressant</a> effect in humans,<a class="footnote-ref" id="fnref:236" href="#fn:236"><sup>236</sup></a><a class="footnote-ref" id="fnref:237" href="#fn:237"><sup>237</sup></a><a class="footnote-ref" id="fnref:238" href="#fn:238"><sup>238</sup></a><a class="footnote-ref" id="fnref:239" href="#fn:239"><sup>239</sup></a><a class="footnote-ref" id="fnref:240" href="#fn:240"><sup>240</sup></a> an effect believed to be mediated through enhanced BDNF signaling in the brain.<a class="footnote-ref" id="fnref:241" href="#fn:241"><sup>241</sup></a> Several systematic reviews have analyzed the potential for physical exercise in the treatment of <a href="/facts/Major_depressive_disorder/l2lQeWqr">depressive disorders</a>. The 2013 <a href="/facts/Cochrane_Collaboration/UlmdJ1H8">Cochrane Collaboration</a> review on <a href="/facts/Physical_exercise/egYQjt8A">physical exercise</a> for depression noted that, based upon limited evidence, it is more effective than a control intervention and comparable to psychological or antidepressant drug therapies.<a class="footnote-ref" id="fnref:242" href="#fn:242"><sup>242</sup></a> 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;<a class="footnote-ref" id="fnref:243" href="#fn:243"><sup>243</sup></a> 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.<a class="footnote-ref" id="fnref:244" href="#fn:244"><sup>244</sup></a><a class="footnote-ref" id="fnref:245" href="#fn:245"><sup>245</sup></a> A 2016 meta-analysis concluded that physical exercise improves overall quality of life in individuals with depression relative to controls. One systematic review noted that <a href="/facts/Yoga_as_exercise/9g7DfeWz">yoga</a> may be effective in alleviating symptoms of <a href="/facts/Prenatal_depression/PdBYgMwm">prenatal depression</a>.<a class="footnote-ref" id="fnref:246" href="#fn:246"><sup>246</sup></a> Another review asserted that evidence from <a href="/facts/Clinical_trials/q8LMr832">clinical trials</a> supports the efficacy of physical exercise as a treatment for depression over a 2–4 month period.<a class="footnote-ref" id="fnref:247" href="#fn:247"><sup>247</sup></a> These benefits have also been noted in <a href="/facts/Old_age/nEpQmo9g">old age</a>, with a review conducted in 2019 finding that exercise is an effective treatment for clinically diagnosed depression in older adults.<a class="footnote-ref" id="fnref:248" href="#fn:248"><sup>248</sup></a> </p><p>A 2024 systematic review and network meta-analysis of 218 <a href="/facts/Randomized_controlled_trial/LG9lkyVx">randomized controlled trials</a> involving over 14,000 participants found that various forms of exercise, including walking or <a href="/facts/Jogging/XQeTpmTt">jogging</a>, yoga, <a href="/facts/Strength_training/G5u5cBH0">resistance training</a>, and mixed <a href="/facts/Aerobic_exercise/T5E59k2L">aerobic activities</a>, were associated with reductions in depressive symptoms. The review observed that the effects of exercise were comparable to those of <a href="/facts/Psychotherapy/n2hDjaop">psychotherapy</a> and <a href="/facts/Pharmacotherapy/bEX4Xo3y">pharmacotherapy</a>, with more intensive exercise yielding greater benefits. Resistance training was identified as particularly effective for younger individuals, while yoga appeared to be more beneficial for older adults. While confidence in the findings was limited by methodological concerns in the included studies, the review noted that exercise produced significant improvements in symptoms across a wide range of participants and treatment contexts.<a class="footnote-ref" id="fnref:249" href="#fn:249"><sup>249</sup></a> </p> <h3>Cerebrovascular disease</h3> <p>Physical exercise plays a significant role in the prevention and management of <a href="/facts/Stroke/DwpjdzY0">stroke</a>. It is well established that physical activity decrease the risk of ischemic stroke and <a href="/facts/Intracerebral_haemorrhage/LEmd3czW">intracerebral haemorrhage</a>.<a class="footnote-ref" id="fnref:250" href="#fn:250"><sup>250</sup></a><a class="footnote-ref" id="fnref:251" href="#fn:251"><sup>251</sup></a><a class="footnote-ref" id="fnref:252" href="#fn:252"><sup>252</sup></a> Engaging in physical activity before experiencing a stroke has been found to have a positive impact on the severity and outcomes of stroke.<a class="footnote-ref" id="fnref:253" href="#fn:253"><sup>253</sup></a> Exercise has the potential to increase the expression of VEGF, <a href="/facts/Caveolin/WqTV8bgh">caveolin</a>, and <a href="/facts/Angiopoietin/eK3rqdHE">angiopoietin</a> in the brain. These changes may promote <a href="/facts/Angiogenesis/h0HF9IUd">angiogenesis</a> and <a href="/facts/Neovascularization/fHWnN6dw">neovascularization</a> that contribute to improved blood supply to the stroke affected areas of the brain.<a class="footnote-ref" id="fnref:254" href="#fn:254"><sup>254</sup></a><a class="footnote-ref" id="fnref:255" href="#fn:255"><sup>255</sup></a><a class="footnote-ref" id="fnref:256" href="#fn:256"><sup>256</sup></a> Exercise may affect the activation of <a href="/facts/Endothelial_NOS/jxYpbqWD">endothelial nitric oxide synthase</a> (eNOS) and subsequent production of <a href="/facts/Nitric_oxide/UvhdvDzp">nitric oxide</a> (NO).<a class="footnote-ref" id="fnref:257" href="#fn:257"><sup>257</sup></a><a class="footnote-ref" id="fnref:258" href="#fn:258"><sup>258</sup></a><a class="footnote-ref" id="fnref:259" href="#fn:259"><sup>259</sup></a> 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 <a href="/facts/HIF1A/C2A2AXkH">hypoxia-inducible factor 1 alpha</a> (HIF-1α), <a href="/facts/Heat_shock_protein/PxDzSx0g">heat shock proteins</a>, and <a href="/facts/Brain-derived_neurotrophic_factor/1v80e05e">brain-derived neurotrophic factor</a> (BDNF).<a class="footnote-ref" id="fnref:260" href="#fn:260"><sup>260</sup></a><a class="footnote-ref" id="fnref:261" href="#fn:261"><sup>261</sup></a><a class="footnote-ref" id="fnref:262" href="#fn:262"><sup>262</sup></a> These factors play crucial roles in promoting cellular survival, neuroprotection, and repair processes in the brain following a stroke. Exercise also inhibit <a href="/facts/Glutamic_acid/7oXbNcvu">glutamate</a> and <a href="/facts/Caspase/YPl75Q9B">caspase</a> activities, which are involved in neuronal death pathways.<a class="footnote-ref" id="fnref:263" href="#fn:263"><sup>263</sup></a><a class="footnote-ref" id="fnref:264" href="#fn:264"><sup>264</sup></a><a class="footnote-ref" id="fnref:265" href="#fn:265"><sup>265</sup></a><a class="footnote-ref" id="fnref:266" href="#fn:266"><sup>266</sup></a> Additionally, it may promote <a href="/facts/Neurogenesis/XSteTv8s">neurogenesis</a> 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.<a class="footnote-ref" id="fnref:267" href="#fn:267"><sup>267</sup></a> Furthermore, physical activity may reduce the volume of intracerebral haemorrhages.<a class="footnote-ref" id="fnref:268" href="#fn:268"><sup>268</sup></a><a class="footnote-ref" id="fnref:269" href="#fn:269"><sup>269</sup></a> Being physically active after stroke also enhance the functional recovery.<a class="footnote-ref" id="fnref:270" href="#fn:270"><sup>270</sup></a><a class="footnote-ref" id="fnref:271" href="#fn:271"><sup>271</sup></a><a class="footnote-ref" id="fnref:272" href="#fn:272"><sup>272</sup></a> </p> <h3>Mild cognitive impairment</h3> <p>The <a href="/facts/American_Academy_of_Neurology/crE3fa6T">American Academy of Neurology</a>'s January 2018 update of their <a href="/facts/Clinical_practice_guideline/l4EfFfa2">clinical practice guideline</a> for <a href="/facts/Mild_cognitive_impairment/exP4LUyC">mild cognitive impairment</a> states that clinicians should recommend regular exercise (two times per week) to individuals who have been diagnosed with this condition.<a class="footnote-ref" id="fnref:273" href="#fn:273"><sup>273</sup></a> 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.<a class="footnote-ref" id="fnref:274" href="#fn:274"><sup>274</sup></a> </p> <h3>Neurodegenerative disorders</h3> <h4>Alzheimer's disease</h4> <p><a href="/facts/Alzheimer%2527s_disease/w7Ad6tdg">Alzheimer's disease</a> is a cortical neurodegenerative disorder and the most prevalent form of <a href="/facts/Dementia/T0MRDE9I">dementia</a>, representing approximately 65% of all cases of dementia; it is characterized by impaired cognitive function, behavioral abnormalities, and a reduced capacity to perform <a href="/facts/Activities_of_daily_living/0AYDmmSA">basic activities of daily life</a>.<a class="footnote-ref" id="fnref:275" href="#fn:275"><sup>275</sup></a> 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.<a class="footnote-ref" id="fnref:276" href="#fn:276"><sup>276</sup></a> A subsequent review found higher levels of physical activity may be associated with reduced risk of dementia and cognitive decline.<a class="footnote-ref" id="fnref:277" href="#fn:277"><sup>277</sup></a> </p> <h4>Parkinson's disease</h4> <p><a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a> symptoms reflect various functional impairments and limitations, such as <a href="/facts/Postural_instability/bNx5197G">postural instability</a>, <a href="/facts/Gait_disturbance/g41Fl77p">gait disturbance</a>, immobility, and frequent falls. Some evidence suggests that physical exercise may lower the risk of Parkinson's disease.<a class="footnote-ref" id="fnref:278" href="#fn:278"><sup>278</sup></a> A 2017 study found that strength and endurance training in people with Parkinson's disease had positive effects lasting for several weeks.<a class="footnote-ref" id="fnref:279" href="#fn:279"><sup>279</sup></a> A 2023 Cochrane review on the effects of physical exercise in people with Parkinson's disease indicated that <a href="/facts/Water_aerobics/2zhLGsMc">aquatic exercise</a> might reduce severity of motor symptoms and improve quality of life.<a class="footnote-ref" id="fnref:280" href="#fn:280"><sup>280</sup></a> Furthermore, <a href="/facts/Endurance_training/e7tRhK8T">endurance training</a>, <a href="/facts/Functional_training/cuNGl7RK">functional training</a>, and multi-domain training (i.e., engaging in several types of exercise) may provide improvements.<a class="footnote-ref" id="fnref:281" href="#fn:281"><sup>281</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Brain_fitness/j5z9LJG6">Brain fitness</a></li> <li><a href="/facts/Exercise_is_Medicine/2kcEjRXH">Exercise is Medicine</a></li> <li><a href="/facts/Exercise_prescription/Cv42a11B">Exercise prescription</a></li> <li><a href="/facts/Exercise_therapy/q24XDqHF">Exercise therapy</a></li> <li><a href="/facts/Memory_improvement/SRzaNKJL">Memory improvement</a></li> <li><a href="/facts/Neuroinflammation/4D4PjYz2">Neuroinflammation#Exercise</a></li> <li><a href="/facts/Nootropic/XRMFvK7L">Nootropic</a></li></ul> <h2 id="notes">Notes</h2> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Erickson KI, Hillman CH, Kramer AF (August 2015). "Physical activity, brain, and cognition". Current Opinion in Behavioral Sciences. 4: 27–32. doi:10.1016/j.cobeha.2015.01.005. S2CID 54301951. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>McKee AC, Daneshvar DH, Alvarez VE, Stein TD (January 2014). "The neuropathology of sport". Acta Neuropathol. 127 (1): 29–51. doi:10.1007/s00401-013-1230-6. PMC 4255282. PMID 24366527. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255282" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255282</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Denham J, Marques FZ, O'Brien BJ, Charchar FJ (February 2014). "Exercise: putting action into our epigenome". Sports Med. 44 (2): 189–209. doi:10.1007/s40279-013-0114-1. PMID 24163284. S2CID 30210091. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Gomez-Pinilla F, Hillman C (January 2013). "The influence of exercise on cognitive abilities". Comprehensive Physiology. 3 (1): 403–428. doi:10.1002/cphy.c110063. ISBN 9780470650714. PMC 3951958. PMID 23720292. <a href="9780470650714" target="_blank">9780470650714</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Buckley J, Cohen JD, Kramer AF, McAuley E, Mullen SP (2014). "Cognitive control in the self-regulation of physical activity and sedentary behavior". Front Hum Neurosci. 8: 747. doi:10.3389/fnhum.2014.00747. PMC 4179677. PMID 25324754. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179677" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179677</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Cox EP, O'Dwyer N, Cook R, Vetter M, Cheng HL, Rooney K, O'Connor H (August 2016). "Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review". J. Sci. Med. Sport. 19 (8): 616–628. doi:10.1016/j.jsams.2015.09.003. PMID 26552574. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>CDC (1 August 2023). "Benefits of Physical Activity". Centers for Disease Control and Prevention. Retrieved 7 December 2023. <a href="https://www.cdc.gov/physicalactivity/basics/pa-health/index.htm" target="_blank">https://www.cdc.gov/physicalactivity/basics/pa-health/index.htm</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Schuch FB, Vancampfort D, Rosenbaum S, Richards J, Ward PB, Stubbs B (July 2016). "Exercise improves physical and psychological quality of life in people with depression: A meta-analysis including the evaluation of control group response". Psychiatry Res. 241: 47–54. doi:10.1016/j.psychres.2016.04.054. PMID 27155287. S2CID 4787287. <a href="https://kclpure.kcl.ac.uk/portal/en/publications/9d2c5d0c-a5a9-4e46-a763-6b1398bce0f6" target="_blank">https://kclpure.kcl.ac.uk/portal/en/publications/9d2c5d0c-a5a9-4e46-a763-6b1398bce0f6</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Pratali L, Mastorci F, Vitiello N, Sironi A, Gastaldelli A, Gemignani A (November 2014). "Motor Activity in Aging: An Integrated Approach for Better Quality of Life". International Scholarly Research Notices. 2014: 257248. doi:10.1155/2014/257248. PMC 4897547. PMID 27351018. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897547" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897547</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, Sorrentino G (27 April 2018). "Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits". Frontiers in Psychology. 9: 509. doi:10.3389/fpsyg.2018.00509. PMC 5934999. PMID 29755380. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934999" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934999</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Erickson KI, Hillman CH, Kramer AF (August 2015). "Physical activity, brain, and cognition". Current Opinion in Behavioral Sciences. 4: 27–32. doi:10.1016/j.cobeha.2015.01.005. S2CID 54301951. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Cox EP, O'Dwyer N, Cook R, Vetter M, Cheng HL, Rooney K, O'Connor H (August 2016). "Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review". J. Sci. Med. Sport. 19 (8): 616–628. doi:10.1016/j.jsams.2015.09.003. PMID 26552574. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Basso JC, Suzuki WA (March 2017). "The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review". Brain Plasticity. 2 (2): 127–152. doi:10.3233/BPL-160040. PMC 5928534. PMID 29765853. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928534" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928534</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Gomez-Pinilla F, Hillman C (January 2013). "The influence of exercise on cognitive abilities". Comprehensive Physiology. 3 (1): 403–428. doi:10.1002/cphy.c110063. ISBN 9780470650714. PMC 3951958. PMID 23720292. <a href="9780470650714" target="_blank">9780470650714</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Cox EP, O'Dwyer N, Cook R, Vetter M, Cheng HL, Rooney K, O'Connor H (August 2016). "Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review". J. Sci. Med. Sport. 19 (8): 616–628. doi:10.1016/j.jsams.2015.09.003. 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