The Neuroscience of Running

Just over a year ago I began running as form of regular exercise. I was looking for an outdoor activity that I could do year-round in New Hampshire and found running to be enjoyable in both warm and cold weather. It took a few weeks to (literally) get up to speed, but I have been running an average of twice a week ever since. Over the last year I have begun to collect all of the fitness-related neuroscience articles that occasionally arrive at my inbox. I have been saving a few of them for a short review on the anniversary of my first run. That time has arrived, and so has the post – click to read more.

I. The impact on mood

Endurance training has been shown to have a positive impact on affective state. Runners have known anecdotally about this effect for quite some time, but it is only in the last few decades that the neural underpinnings of this effect have been investigated. One mechanism that seems to be associated with increased positive mood is neurogenesis, or the creation of new neurons.

In a review of 14 studies examining the relationship between exercise and major depression Lawlor and Hopkor (2001) found that the magnitude of the antidepressant effect of exercise is generally equal to that of cognitive therapy. Strawbridge et al. (2002) further found that those who engage in exercise are less likely to develop a depressive disorder to begin with. These antidepressant effects have been shown to persist for over 21 months after exercise has stopped (Singh, Clements, and Singh, 2001). What causes this antidepressant effect?

The common belief used to be that the human brain did not form new neurons after early childhood, but recent evidence has accumulated that certain structures, such as the hippocampus, do create neurons as an adult (Lledo, Alonso and Grubb, 2006). The hippocampus is a structure in the brain known to be involved in memory and learning. In mice voluntary running has been shown to increase neurogenesis in the hippocampus (Naylor et al., 2008; van Praag, Kempermann, and Gage, 1999). The increase in neurogenesis has then been associated with reductions in depressive mood and depressive severity in rats (Bjørnebekk, Mathe, and Stefan Brene, 2005).

Running has also been associated with a reduced response to stress and anxiety. It can not only reduce the effects of a current stressful situation, but acts to guard against future stress (Greenwood and Fleshner, 2008). One source of this effect is a change of activity in the dorsal raphe nucleus (DRN), a center for serotonin in the brain. Hyperactivity in the DRN during stress has been shown to alter the behavior of an animal, often leading to a state of learned helplessness and avoidance (Maier and Watkins, 2005). In rats six weeks of wheel running was shown to significantly reduce DRN activity during uncontrollable stress (Greenwood and Fleshner, 2008). It also reduced the helpless behavior of the rats.

As a society the United States shells out over 25 billion dollars a year on antidepressants. The efficacy of these drugs is generally not as substantial as effects seen after exercise. Exercise also seems to impact a wider array of neural systems, positively affecting everything from single neurons to whole neural systems. Putting all of the above information into perspective, if I could create a pill that would increase positive mood in the same way that running does I would be a billionaire – seriously.

II. The impact on cognition

Exercise has been shown to provide cognitive improvements to both humans and animals. Researchers have observed benefits to long-term memory, learning, attention, executive control, and a host of other cognitive abilities. The brain as a whole seems to thrive on exercise.

One source of cognitive benefit is purely cardiovascular. Exercise increases cerebral blood flow and provides for more efficient glucose utilization (McCloskey et al., 2001). Let’s be clear, the brain lives on glucose. Over 25% of the energy you take in is going to fuel that little three-pound mass in your skull. When you are really working on a tough problem that percentage only goes up as energy usage increases. If you can more efficiently get energy where it needs to go that would represent a major benefit to cognitive processing.

Another source of cognitive benefit has to do with neurons and the environment they inhabit. The same mechanisms of neurogenesis described in section I are known to contribute to cognitive benefits as well (van Praag et al., 1999). Enhancement also is due to an increased level of brain-derived neurotrophic factor (BDNF) present after exercise. BDNF is a protein that helps existing neurons to survive and grow. Elevated corticosterone levels caused by acute stress tend to reduce levels of BDNF in the cortex and hippocampus, while exercise can raise levels significantly above baseline (Adlard and Cotman, 2004; Neeper et al., 1996).

Changes in the regional anatomy of the brain have also been observed after exercise. Grey matter differences in the frontal and temporal lobes were observed in association with individuals who exercise more frequently (Kemppainen et al., 2005). This may be related to the results of Colcombe et al (2004), who found that older adults with better fitness showed significantly higher activity in lateral frontal and superior parietal regions when engaged in an attention task.

Individuals suffering from cognitive deficits show benefits after beginning a new fitness regime. Exercise has been shown to improve the condition of Alzheimer’s patients (Teri et al., 2003) and stroke victims (Shepherd, 2001). While the effects are not gigantic, any improvement in the cognitive outcome of these disorders can greatly help a patient. Further, exercise reduces the risk of cognitive impariment, Alzheimer’s disease, and dementia to begin with (Lautenschlager, 2008; Friedland et al., 2001). This seems to be especially true if you have a genetic predisposition to these disorders.

As an aside, the PsyBlog has a great mini-review of typical cognitive enhancers and finds that between brain training, nutritional supplements, drugs, meditation and exercise that exercise is currently the best-bet for improving your cognitive ability. I tend to agree.

Much like the effect on mood, exercise affects a wide array of neural functions critical to cognition. Not only is there a boost in energy efficiency, but overall there is more energy available to burn. Further, the impact of events that seem to cause the most harm to our brain, such as acute stress, are marginalized and protected against. Together these factors help create a positive neural environment that supports cognitive improvement.

III. High as a kite

I would be remiss not to comment on the “runner’s high” that many people experience after extended exertion. This is often described as a state of euphoria or pleasure that occurs late into a long run. Recent evidence suggests that this state of euphoria is the direct result of engaging the brain’s endogenous opiate system. Boecker et al. (2008) found that strenuous running induced significant opiate binding in orbitofrontal, anterior cingulate, insula, and temporoparietal cortex in addition to multiple limbic and paralimbic subcortical areas. These are brain areas involved in the mapping of body state to emotional state. Their results are bolstered by other studies showing that naloxone, an opiate binding inhibitor, blocks the runner’s high from taking place (Janal et al, 1984).

It makes sense that our brain is providing this opiate system to us, otherwise running would be a pretty miserable experience. Still, opiates can be very addictive. Most of us might have already encountered opiates as medication in the form of morphine or codeine. Heroin is an illegal drug that is chemically similar to morphine and every bit as addictive. I have to wonder what role the opiate system plays in people getting addicted to running. We know that there are varying levels of susceptibility to drug addiction – two people can take the same amount of drug and only one will go on to become an addict. Is the same true of highly trained runners?

IV. Conclusions

This is perhaps less of a blog post and more a collection of interesting tidbits related to running that I have come across. Still, it helps that there is a big-picture view that goes along with all of the above. The view is this: exercise is nothing short of magic when it comes to your brain. The cognitive and emotional benefits you get from strenuous exercise are virtually unmatched when compared to prescription drugs or therapy. While this post has focused primarily on the neuroscience of exercise and running, you cannot ignore the other health benefits of exercise. Heart disease is the #1 killer of men and women in America. If you don’t get up and run for your brain, then (really) do it for your heart.


Adlard PA, Cotman CW. (2004). Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression. Neuroscience. 124(4):985-92.

Bjørnebekk A, Mathé AA, Brené S. (2005). The antidepressant effect of running is associated with increased hippocampal cell proliferation. Int J Neuropsychopharmacol. 8(3):357-68.

Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR. (2008). The Runner’s High: Opioidergic Mechanisms in the Human Brain. Cereb Cortex. Feb 21.

Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, Cohen NJ, Webb A, Jerome GJ, Marquez DX, Elavsky S. (2004). Cardiovascular fitness, cortical plasticity, and aging. PNAS. 101(9):3316-21.

Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, Petot GJ, Debanne SM. (2001). Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control-group members. PNAS. 98(6):3440-5. Epub 2001 Mar 6.

Greenwood BN, Fleshner M. (2008). Exercise, learned helplessness, and the stress-resistant brain. Neuromolecular Med. 10(2):81-98.

Janal MN, Colt EW, Clark WC, Glusman M. (1984). Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone. Pain. 19(1), 13-25.

Kemppainen J, Aalto S, Fujimoto T, Kalliokoski KK, Långsjö J, Oikonen V, Rinne J, Nuutila P, Knuuti J. (2005). High intensity exercise decreases global brain glucose uptake in humans. J Physiol. 568(Pt 1):323-32.

Lautenschlager NT, Cox KL, Flicker L; et al. (2008). Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 300(9):1027-1037.

Lawlor DA, Hopker SW. (2001). The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ. 322(7289):763-7.

Lledo PM, Alonso M, Grubb MS. (2006). Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 7(3):179-93.

Maier SF, Watkins LR. (2005). Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci Biobehav Rev 29(4-5):829-41.

McCloskey DP, Adamo DS, Anderson BJ. (2001). Exercise increases metabolic capacity in the motor cortex and striatum, but not in the hippocampus. Brain Res. 891(1-2):168-75.

Naylor AS, Bull C, Nilsson MK, Zhu C, Björk-Eriksson T, Eriksson PS, Blomgren K, Kuhn HG. (2008). Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. PNAS. 2008 Sep 2.

Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW. (1996). Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 726(1-2):49-56.

Shepherd RB. (2001). Exercise and training to optimize functional motor performance in stroke: driving neural reorganization? Neural Plast. 8(1-2):121-9.

Singh NA, Clements KM, Singh MA. (2001). The efficacy of exercise as a long-term antidepressant in elderly subjects: a randomized, controlled trial. J Gerontol A Biol Sci Med Sci. 56(8):M497-504.

Strawbridge WJ, Deleger S, Roberts RE, Kaplan GA. (2003). Physical activity reduces the risk of subsequent depression for older adults. Am J Epidemiol. 156(4):328-34.

Teri L, Gibbons LE, McCurry SM; et al. (2003). Exercise plus behavioral management in patients with Alzheimer’s disease: a randomized controlled trial. JAMA. 290(15):2015-2022.

van Praag H, Kempermann G, Gage FH. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 2(3):203-5.

5 Responses to “The Neuroscience of Running”

  1. Rich Elliott - July 31st, 2010

    I am interested in the situation whereby a long-distance runner (26 mile marathons) for many years, stops running. He is now 67 and witnessing reduction in size (first measurement) of hippocampus, with warnings of impending Alzheimer’s or other cognitive (orientation) problems. Any ideas? Richard

  2. Alexis Shea - July 26th, 2012

    Thanks for this – it all seems so obvious, when I’m doing a lot running I feel calmer, happier, more focused on any work/fun task I’m undertaking; it’s good to be able to understand why that is in terms if what’s going on in the body/brain.

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