Category Archives: Memory

Departing the 2010’s, feelings of stress and worry among Americans were the highest they had been all decade and among the highest in the world [1]. I doubt that drops any jaws. We are a bit obsessed with stress – many trying to rid ourselves of the brute through everything from mindfulness and meditation to yoga retreats and medication. I love the work by Dr. Susan David, who has concluded that all of this energy expended to ‘rid ourselves of stress’ can actually make a person more stressed (dubbed type II stress). Oh, the irony!

Stress is an inescapable aspect of our lives, and it is undoubtedly useful in short-term fight-or-flight situations, helping us better mobilize resources like glucose and oxygen. It’s the prolonged and unrelenting variety of stress that comes at a cost to the brain. In particular, a robust field of research has found that chronic stress shrinks the hippocampus [2, 3]. This region has long been implicated in learning and memory (episodic & spatial) [2, 4]. As a powerful illustration, atrophy in the hippocampus is the hallmark of Alzheimer’s disease. It is one of the most susceptible brain regions to cell death, and it may be particularly vulnerable to the impact of long-term stress because it has a high concentration of cortisol receptors [5].

So, that’s the bad news. Here’s the good: because the hippocampus exhibits so much adaptive plasticity, the effects produced by chronic stress are largely reversible. Better still, there is a free and readily accessible intervention that can dampen and even reverse these effects. I’ll give you one guess.

Most people have an anecdotal appreciation for the benefits of exercise on stress and get a feel-good buzz after a bout of exercise. What is often underappreciated is that exercise reaps very tangible anatomical and physiological benefits to the brain.  Cue my favorite study [6].

One hundred and twenty older adults were recruited and randomly assigned to 3 days a week of either moderate-intensity aerobic exercise or stretching/toning (control).*  After one year of this intervention, MRI scans showed a 2% increase in hippocampal volume for the aerobic exercise group (see graph)[6]. Exercise grew brains. Unsurprisingly, but still remarkably – the  hippocampal growth corresponded to improved memory function.

Notice in the figure how the red line (stretching/control group) slopes down? These data support previous research showing a 1-2% decline in hippocampal volume each year in older adults, free of dementia [8]. That trajectory is inverted with the exercise group (blue line). Getting out the door for a walk 3 days a week effectively reversed age-related loss in the hippocampus by 1 to 2 years. Powerful stuff, exercise.

Now, back to stress. While there haven’t been any exercise interventions in people that look specifically at reversing the effects of stress, it doesn’t take a huge leap of fate to connect the dots here. We know chronic stress shrinks the hippocampus while exercise grows it.** Still, I like to be persuasive, and findings from a recent study in mice is just that.

Researchers at BYU had one group of mice run on wheels (covering ~5k day), while the other group remained sedentary [9]. Half of each group was also exposed to stressful situations – swimming in cold water or walking on an elevated platform. They then looked in the hippocampi of mice to assess a process called long-term potentiation (LTP). Memory formation and recall are most effective when connections between neurons are strengthened over time. LTP is a measure of this connectivity, and ultimately memory.  In the sedentary group, researchers found chronic stress weakened the synaptic connections between neurons, decreasing LTP. The mice allowed to run while exposed to stress had significantly higher LTP, and they performed better on a memory test (radial arm maze) [9]. The research team concluded, “exercise is a viable method to protect learning and memory mechanisms from the negative cognitive impact of chronic intermittent stress on the brain.”

In terms of how exercise supports the hippocampus – we believe it is a combination of increased blood flow to the brain and hippocampus [10] as well as through increased production of BDNF [6, 9, 11]. Brain derived neurotrophic factor (BDNF) is essentially a growth factor for neurons…miracle grow for brain cells.

Ridding ourselves of all the stressors in our lives is not a particularly practical option for most of us. Yet, the negative toll that stress can take is not a phenomenon beyond our control. I think that is downright empowering. So, transitioning into this next decade, resolve to move for your physical health, move for your mental health, and move for your brain health.

*Noteworthy – both groups in the study attended the same number of exercise sessions and therefore had an equal amount of social interactions. This is important because human interactions also have very real benefits on brain function [7] and may be less frequent in the older adult population.  In other words, exercise appears to protect our brains in a way that other interactions cannot. This appears to be true, even if you start moving in your 70s.

**Aerobic training grows brain regions other than the hippocampus. Another exercise intervention in older adults found increased gray and white matter volume in the prefrontal cortex after 6-months [12]. This region is instrumental to executive control functions.

References

[1] Chokshi, N. (2019, April 25). Americans Are Among the Most Stressed People in the World, Poll Finds. The New York Times.  Retrieved from https://www.nytimes.com/2019/04/25/us/americans-stressful.html

[2] Conrad, C. (2010). A critical review of chronic stress effects on spatial learning and memory. Prog Neuropsychopharmacol Biol Psychiatry 34(5): 742-755.

[3] Conrad, C. (2008). Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis. Reviews in Neurosciences 19(6): 395-411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746750/

[4] McEwen, B., Nasca, C., Gray, J. (2016) Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology Reviews, 41, 3-23.

[5] Kino, T. (2015). Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders. Frontiers in Physiology 19. https://www.frontiersin.org/articles/10.3389/fphys.2015.00230/full

[6] Erickson et al. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences, 108 (7): 3017-3022.   

[7] Hari, R. & Kujala, M. (2009). Brain basis of human social interactions: from concepts to brain imaging. Physiological Reviews, 89, 453-479.

[8] Raz N, et al. (2005) Regional brain changes in aging healthy adults: General trends, individual differences and modifiers. Cereb Cortex, 15, 1676–1689.

[9] Miller, R. et al. (2018). Running exercise mitigates the negative consequences of chronic stress on dorsal hippocampal long-term potentiation in male mice. Neurobiology of Learning and Memory, 149. DOI: 10.1016/j.nlm.2018.01.008

[10] Burdette J., et al. (2010) Using network science to evaluate exercise-associated brain changes in older adults. Front Aging Neurosci 2:23.

[11] Vaynman S., Ying Z., Gomez-Pinilla F. (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. European Journal of Neurosciences 20:2580–2590.

[12] Colcombe S., et al. (2006) Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci, 61, 1166–1170.