Exercise your way to a healthy brain



During the conference, over 300 abstracts demonstrated the powerful effects of exercise on the brain. Sadly, I couldn’t get to them all. Here I have highlighted several exciting new pieces of evidence showing that physical activity helps improve brain function and physiology.

Increased aerobic fitness is related to increased anterior dentate gyrus/CA3 volume in healthy young adults following exercise training (RK Nauer, MF Dunne, TW Storer, CE Stern, & K Schon)
In rodents, aerobic exercise is known to enhance rates of neurogenesis in the dentate gyrus of the hippocampus, which is an effect that has been linked to improvements in hippocampal-dependent cognitive functions such as pattern separation. In humans, aerobic exercise has been shown to increase the volume of the hippocampus. However, it is unknown whether the exercise-induced hippocampal size enhancements in humans are related to gains in cognition. Therefore, Rachel Nauer and colleagues from Boston University wanted to determine if a 12-week exercise intervention that included either resistance or endurance training in healthy young adults (ages 18 to 35) could lead to increases in the size of the hippocampus as well as changes in pattern separation or “disambiguation of similar stimuli”. Findings: The change in aerobic fitness predicted size changes in the left dentate gyrus/CA3 region (but not the subiculum or CA1), a finding that is consistent with the animal literature. In addition, lower fit individuals showed the largest gains in exercise-induced improvements in a hippocampal-dependent cognitive task. These results show that long-term exercise can enhance hippocampal size and that initially low-fit individuals may be the ones to show the largest improvements.

Acute mild exercise improves memory by enhancing hippocampal-neocortical connectivity (K Suwabe, K Byun, K Hyodo, Z Reagh, K Saotome, G Ochi, MA Yassa, & H Soya)
It is known that long-term exercise promotes plasticity in the hippocampus, especially the neurogenic dentate gyrus. This exercise-induced enhancement in plasticity leads to an increased capacity for pattern separation, or the ability to distinguish between similar sets of stimuli – an ability that is involved for proper episodic memory. However, it is unclear whether a single bout of exercise can enhance patterns separation and it is unknown what the neural correlates of this effect might be. Therefore, Kazuya Suwabe and colleagues from the University of Tsukuba had subjects engage in a mild bout of exercise (10 minutes of cycling at 30% of VO2 peak) and only five minutes after, engage in a hippocampal-dependent task called the mnemonic similarity task. Findings: A single exercise session enhanced pattern separation abilities and increased activity in the dentate gyrus/CA3, CA1, and subiculum. Further, the enhanced functional connectivity between the dentate gyrus/CA and regions of the cortex (angular gyurs, fusiform gyrus, and parahippocampal cortex) predicted performance on the task. These results indicate that acute exercise enhances pattern separation, a behavior that depends on the dentate gyrus subregion of the hippocampus, and that this effect may be driven by functional connectivity between the hippocampus and cortex.

Acute physical exercise improves memory consolidation in humans via BDNF and endocannabinoid signaling (K Igloi, B Martin Bosch, A Bringard, G Ferretti, S Schwartz)
Acute exercise is known to both enhance hippocampal-dependent memory as well as increase levels of brain derived neurotrophic factor (BDNF) and endocannabinoids (especially anandamide) in the hippocampus. However, it is unknown how increases in peripheral levels of these substances relate to exercise-induced improvements in learning and memory. Therefore, Kinga Igloi and her colleagues at the University of Geneva in Switzerland had subjects engage in an associative learning task in a magnetic resonance imaging scanner before and after a period of rest or moderate- (30 minutes at 60% of maximal cardiac frequency) or high-intensity (15 minutes at 80% of maximal cardiac frequency) exercise. Blood samples were also taken both before and after exercise. Findings: Enhanced performance on the associative learning task was seen after moderate- but not high-intensity exercise. In addition, higher anandamide levels after exercise predicted greater hippocampal activation during the task and greater BDNF levels after exercise predicted better decoding of correct trials in the hippocampus. Finally, memory improvements that were maintained 3 months later were dependent on the functional connection between the hippocampus and prefrontal cortex. This exercise-induced long-term memory enhancement was correlated to the increase in peripheral BDNF levels that occurred after the exercise session. These results show that a bout of moderate-intensity exercise may be best to enhance hippocampal-dependent learning and memory and that increases in anadamide and BDNF may underlie these effects.

The exercise hormone FNDC5/irisin is required for the exercise-induced improvements of spatial learning and memory (CD Wrann, MF Young, MR Islam, MP Jedrychowski, KK Gerber, BJ Caldarone, H Van Praag, BM Spiegelman)
This group previously demonstrated that exercise upregulates FNDC5 and its secreted form irisin. It is unknown, however, how these molecules support exercise-induced improvements in spatial learning and memory. To further investigate the involvement of these molecules, Wrann and colleagues at Massachusetts General Hospital and Harvard Medical School created a FNDC5 knockout mice. Though these mice ran similar distances as their wild type counterparts, they showed baseline cognitive impairments and were resistant to the exercise-induced improvements in spatial learning and memory (studied via the Morris Water Maze). In addition, FNDC5 knockout mice show impairments in running-induced increases in hippocampal expression of BDNF and other markers as well as neurogenesis and long-term potentiation. These results indicate that FND5/irisin is an important moderator of the beneficial effects of exercise on cognitive function.

Voluntary exercise restores adolescent binge ethanol-induced loss of basal forebrain cholinergic neurons in adulthood (RP Vetreno, FT Crews)
The adolescent brain is in a constant state of change and therefore has a heightened capacity for neural plasticity. Unfortunately, binge drinking is a common occurrence during this critical time of development. Using a rodent model of adolescent binge drinking, this group found that intermittent alcohol exposure during adolescence decreased levels of cholinergic neurons in the basal forebrain in adulthood. These mice also showed impairments in behavioral flexibility (as measured through a reversal learning paradigm) as adults. They then exposed the mice to voluntary wheel running throughout the adolescent period to see if this healthy behavior could restore the alcohol-induced cell loss. When mice received both exercise and periodic binge drinking, the cholinergic cells of the basal forebrain were preserved and they did not show the behavioral impairments associated with binge drinking. Further experiments indicated that both immune system and neurotropic factor mechanisms may be at play in this exercise-induced restoration effect. These results indicate that the adolescent brain is an especially plastic time of brain development, and that exercise may help to restore neuronal loss due to episodes of heavy drinking, which are common during this exploratory time period.

The effects of a semester of aerobic exercise on fitness, cognition, mood, and GPA in college students (Basso JC, Crosta C, Raskin M, Wang A, Kadakia D, Choi J, Milburn E, Trivedi R, Suzuki WA)
Long-term aerobic exercise enhances mood state and improves a range of cognitive functions including attention, information processing speed and both short- and long-term memory. Though a recent study found that first-year medical school students who regularly exercised attained higher grades than those who remained sedentary, little has been done to assess whether long-term exercise in undergraduate students positively influences cognitive function and academic performance. Therefore, we examined the effects of an aerobic exercise intervention on mood, cognitive function and academic performance in first-year college students. Previously sedentary students engaged in one typically sedentary semester and one semester where they exercised approximately 3 times per week. Before and after each semester, students were tested on cardiopulmonary fitness, cognitive functioning, mood state, and their learning and studies strategies. Compared to a sedentary experience, exercise enhanced the ability to recall information, increased information processing speed, and improved creative thinking. Exercise also increased the motivation to exercise and enhanced mood state (via a decrease in negative affect), with those individuals gaining the most in the their fitness, showing the largest behavioral improvements. These findings have important implications for academia and indicate that students should be exercising along with their studies to possibly enhance academic performance.

Julia C. Basso, PhD