COVID-19 pandemic – Exercise enhance motor skill learning via changes in brain’s transmitters

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Doctors have relentlessly impressed upon us the many benefits of exercise. Energy, mood, sleep and motor skills all improve with a regular fitness regimen that includes activities such as running.

This has become of particular interest in the time of the COVID-19 pandemic.

But what happens in the brain during these improved states of health?

The underlying neurological changes that open the door to these benefits have been unclear.

Now, Assistant Project Scientist Hui-quan Li and Distinguished Professor Nick Spitzer of the University of California San Diego have identified key neurological modifications following sustained exercise.

Comparing the brains of mice that exercised with those that did not, Li and Spitzer found that specific neurons switched their chemical signals, called neurotransmitters, following exercise, leading to improved learning for motor-skill acquisition.

“This study provides new insight into how we get good at things that require motor skills and provides information about how these skills are actually learned,” said Spitzer, the Atkinson Family Chair in the Biological Sciences Section of Neurobiology and a director of the Kavli Institute for Brain and Mind.

The study’s results are published May 4 in Nature Communications.

Spitzer’s laboratory discovered neurotransmitter switching in the adult mammalian brain and has led groundbreaking research on the ability of neurons to change their transmitter identity in response to sustained stimuli, typically leading to changes in behavior.

After carrying out research that described neurotransmitter switching in depression, Spitzer and his colleagues began to turn their attention to how such switching might be involved in healthy conditions.

Li says the results underscore the importance of exercise, even at home during the current pandemic quarantine situation.

“This study shows that it’s good for the brain to add more plasticity,” said Li. “For people who would like to enhance their motor skill learning, it may be useful to do some exercise to promote this form of plasticity to benefit the brain.

For example, if you hope to learn and enjoy challenging sports such as surfing or rock climbing when we’re no longer sheltering at home, it can be good to routinely run on a treadmill or maintain a yoga practice at home now.”

During the new study, Li and Spitzer compared mice that completed a week’s worth of exercise on running wheels with mice that had no access to running wheels. They found that the exercised group acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than the non-exercised group.

When the brains of the running mice were examined, a group of neurons in the brain region known as the caudal pedunculopontine nucleus (cPPN) that regulates motor coordination was discovered to have switched neurotransmitters from acetylcholine to GABA.

To confirm their findings, the researchers used molecular tools to block the newly identified transmitter switch resulting from exercise. They found that the enhancement of motor skill learning in these mice was prevented.

Based on their findings, the researchers propose a new model in which conversion of cPPN excitatory cholinergic neurons to inhibitory GABAergic neurons provides feedback control regulating motor coordination and skill learning.

The researchers say the discovery could lead to further findings where neurotransmitter switching leads to key motor skill changes. The researchers say they’d like to test ideas such as whether neurotransmitters could be deliberately switched to benefit motor skills, even without exercise.

They also plan to conduct research on whether exercise similarly triggers benefits of motor skill learning in those with neurological disorders.

“We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders,” the authors conclude in the paper.

Says Spitzer: “With an understanding of this mechanism comes the opportunity to manipulate and to harness it for further beneficial purposes. In the injured or diseased individual, it could be a way of turning things around… to give the nervous system a further boost.”

Funding: The research was funded by grants from the Ellison Medical Foundation, the W. M. Keck Foundation, the National Institutes of Health (NS047101) and the Overland Foundation.


Cognition is composed of several distinct processes including executive functioning, long-term memory, and motor learning. Research has demonstrated that all facets of cognition can be altered by both acute (4, 8, 13, 16, 21–23, 26) and chronic (12, 13, 16, 25) physical activity. Differences in cognition have been exhibited for various modes, intensities, and durations of exercise.

There are two leading factors theorized to influence the exercise-cognition relationship: attention and arousal. Attentional theories suggest that exercise itself demands attention and therefore only residual attention is dedicated to cognitive function. Different modes of exercise require varying levels of concentration for safe performance.

Hence, activities requiring high attention, such as treadmill running (which requires focus on balance, obstacles, and form), result in decreased cognitive capacity, whereas activities like stationary cycling result in no change in cognition (9, 15).

Arousal theories stem from research suggesting that there is an optimal level of arousal during exercise that can contribute to cognitive preservation or facilitation. This ideal level of arousal can be achieved by manipulating duration or intensity of an exercise bout (5, 6, 15–17).

Because there are several aspects of cognition that may be differentially influenced by exercise, it can be difficult to draw conclusions regarding the best way to maximize the cognitive benefits of exercise.

In general, ergometer cycling seems to be the best mode for cognitive enhancement (15, 22, 23), with only one study suggesting that intense treadmill running led to enhanced memorization speed (26). Regarding physiological arousal, moderate-intensity exercise is suggested to be favorable for cognition (6, 16, 17, 22).

For optimal cognitive outcomes, the duration of exercise also must be optimized. Chang et al. (5) reported that an aerobic training session consisting of a 5-min warm-up, 20-min work period, and 5-min cool down improved general cognition. Meta-analyses have reported that exercise must last at least 20 min for cognitive enhancement to be experienced during exercise (6, 15).

The effect of mode, intensity, duration, or any other aspect of exercise on cognitive function is dependent upon the type of cognition tested. Researchers have identified benefits of acute and chronic exercise on attention and concentration (4, 16), executive function (12, 13, 22, 25), and motor learning (23).

However, most of these assessments, while perhaps correlated with ability to learn and perform well scholastically, do not directly contribute to learning. It can be challenging and time-demanding for researchers to develop an environment that would truly mimic the academic environment and level of rigor experienced at the university level.

However, it is possible to assess a simple type of learning, which is necessary for higher level cognitive processes. Bloom indicated that all learning is predicated by knowledge, further described as “the retention of specific, discrete pieces of information like facts and definitions (1).”

Hence, a simple but effective way to imitate basic academic study is to provide a memorization task with a delayed recall assessment.

Three pertinent studies were identified that assessed long-term memory with a delayed recall test. Winter et al. (26) required participants to undergo a moderate-intensity endurance run, high-intensity running intervals, or control activity prior to audiovisual vocabulary instruction in a foreign language, and it was determined there was no difference between the three conditions one week and at least eight months after initial material presentation.

Coles and Tomporowski (8) tested delayed recall before and after 40 min of moderate cycling on an ergometer, ergometer sitting, or watching an educational documentary. It was determined that moderate exercise preserved recall capacity whereas the two rest conditions resulted in declined recall ability after a 12-min delay.

In perhaps the most relevant study, Schmidt-Kassow et al. (24) assessed the ability to learn vocabulary in a foreign language during, after, or in the absence of 30 min of light-moderate intensity ergometer cycling.

Exercise condition was shown to significantly alter memory, with simultaneous exercise and learning resulting in improved vocabulary recall compared to the control condition 48 hrs later (28.4 ± 9.8 words after simultaneous exercise and study vs. 20.9 ± 7.9 words after relaxed study). Study after exercise did not differ from either of the other experimental conditions (26.6 ± 11.7 words).

While Schmidt-Kassow et al. did evaluate simultaneous study and exercise, the exercise bout was at a relatively low intensity, and all vocabulary was presented aurally as opposed to visually. However, students may be more apt to study visually from textbooks or notes. To better understand the efficacy of study during exercise, research is needed to assess the effect of an acute bout of concurrent moderate-intensity exercise and memorization using visual study materials on recall ability after an extended period.

Therefore, the purpose of this study was to determine if the timing of moderate-intensity cycling, an activity anticipated to be in agreement with both attentional and arousal theories of cognition, modulates memory and learning by assessing the ability of recreationally-active individuals to memorize words under three different conditions – simultaneous study and moderate-intensity exercise, study following moderate-intensity exercise, and study without exercise – and to recall these words 24 hrs later. Based upon prior research, it was anticipated that exercise would not inhibit learning and that one or both exercise conditions would result in augmented recall.

RESULTS

The number of words correctly recalled was assessed for each intervention and is presented in Table 2. The order in which the interventions were encountered did not affect the ability to recall words (F5,15 = 1.11, p = 0.396). The visit number when a participant encountered the intervention was also not significant (F2,38 = 1.53, p = 0.230), indicating a negligible learning effect.

The effect of participant nested within order was revealed to be statistically significant (F15,38 = 9.53, p = < 0.001), suggesting that individual memorization ability significantly impacted results. The effect of exercise intervention was not significant (F2,38 = 2.24, p = 0.121).

Researchers performed specific hypothesis testing following means analysis using Scheffé-corrected contrasts which demonstrated that when comparing memorization while exercising to the other two interventions, memorization during exercise resulted in significantly better word recall 24 hrs later (F1,38 = 4.40, p = 0.043) (see Table 2). Another contrast revealed that there was no difference between the control intervention and the combined effect of both exercise interventions (F1,38= 0.64, p = 0.4294).

Table 2

Summary of 24 hrs recall ability.

VariablesAverage Word Recall (95% CI)Cohen’s d
Study While Exercising51.5 ± 19.8* (42.5, 60.5)0.27
Study After Exercising45.1 ± 20.6 (35.7, 54.5)−0.03
Study Without Exercise45.7 ± 23.3 (35.1, 56.3)

Note: CI = confidence interval. Data is presented as mean ± SD. Cohen’s d calculated with Study Without Exercise as the control group.*p = 0.043, significantly different from combined average of other interventions using Scheffé Contrasts

DISCUSSION
The results of this research suggest that the proximity of a single exercise bout to studying does not inhibit the ability to recall information 24 hrs after exposure to the information, even if studying and exercise are pursued simultaneously.

Further, based on the results, the authors suggest that the effect of studying during exercise is beneficial compared to the combined effect of studying after or without exercise. These results imply that individuals who choose to participate in self-directed learning or studying during a moderate intensity cycling workout will not be limited cognitively.

By accounting for the visit number and the various orders, it was determined that there was not a significant learning effect, meaning that participants did not become significantly better at the recall task with repeated task performance.

As expected, the analysis demonstrated that the recall capacity after the memorization task was participant-dependent. Some participants found memorization to be an easy task, recalling nearly 90 words on each recall test, while others struggled to recall many words. This large variability in participants led to a range of 87 in the number of words correctly recalled.

The individual nature of memorization documented in this research is likely due to factors modifying memorization capacity (e.g., motivation, environment, previous exposure and experience, etc.) as well as memorization techniques. Participants who previously had more need to memorize material outside of this research had likely developed useful skills (i.e., imagery or creation of pneumonic devices) that aided their performance in this protocol.

Less experienced memorizers may have relied primarily on rote memorization. This discrepancy in memorization techniques and abilities, coupled with the sample size, could limit the statistical power of this investigation.

Based upon prior research, it was expected that (1) exercise timing would not inhibit recall and (2) that one or both exercise conditions would result in higher recall than memorization without exercise.

These hypotheses were built upon the work of other researchers who revealed exercise in proximity to cognitive testing or memory tasks led to better performance (6, 13, 26). While the effect of memorization during exercise was small and did not necessarily indicate improvement, exercise did not hinder recall ability, as there was no statistical difference between any of the conditions.

This finding, in and of itself, is promising, as it suggests that multi-tasking may not be detrimental at this exercise intensity and mode. However, further hypothesis testing demonstrated that simultaneous exercise and study resulted in a positive increase in recall ability compared to the combined effects of the other two conditions, suggesting that the attentional demands and physiological arousal caused by this work bout created a promising setting for memorization.

This discovery is similar to that of Schmidt-Kassow et al. (24) who noted that light-moderate exercise during memorization of aurally presented novel vocabulary words resulted in better recall capacity 48 hrs later. However, the present study uses a higher intensity suggesting that moderately-intense cycling may also create a beneficial environment for encoding of memories.

This result strengthens the implications for students who desire to multitask by reviewing course materials during a workout. Also, the present research provides evidence that the encoding of facts from visual information (e.g., the word list) without aural presentation of information is not inhibited during exercise. This aspect of this study is important, as students may only have access to visual study aides as opposed to audio recordings.

This study produces evidence that would support the concept of an “active classroom” in which students would cycle on an ergometer during educational encounters. Based on the results of this study, we would expect to see courses utilizing the “active classroom” model to score as well or better than a standard classroom.

Several researchers have found that active workstations (50 min of low-intensity treadmill walking) do not detrimentally affect cognitive ability and concentration, while simultaneously combatting sedentary behavior (2, 10). Children have been shown to have increased scores in several subjects when they participate in 20–30 min of moderate-vigorous intensity physical activity during instructional periods (18, 19).

Concentration has also been shown to be improved in children who perform 15 min of moderate-vigorous physical activity during school lessons (11). Given the propensity toward sedentariness in our culture, active classrooms may be a good way to introduce greater physical activity into student lives, without compromising the purposes of the classroom. The present study supports the use of moderate-intensity exercise during learning periods, which may result in greater aerobic fitness and preserved education.

Our investigation is not without limitations. First, the study is likely moderately underpowered and would have been strengthened with a larger sample, as the noted effect size is not as large as was anticipated during sample size planning.

Second, it is likely that the relationship between cognitive capacity and exercise is influenced by aerobic fitness and this study could have been strengthened by assessing maximal aerobic capacity or utilizing more restrictive physical activity requirements. Individuals with lower aerobic fitness likely experienced higher heart rates, respiration rates, and attentional demands than those who were more fit.

This would have potentially conflicted with both the attentional and arousal theories of exercise and cognition. Third, it would have been beneficial to assess long-term memory using a standardized and validated test at the beginning of the study, to allow research to account for individual memorization capacity.

Because memorization can be influenced by a multitude of factors (i.e., motivation, concentration, previous experience with the task, etc.), beginning the study with a validated assessment of memory would have enabled researchers to present a better picture of the relative influence of the exercise intervention, as opposed to the absolute effect of exercise.

Fourth, participants did not complete a standardized warm-up, which while more similar to what each individual would do outside of the research, adds an element of variability. Future studies should utilize a brief but standardized warm up and cool down protocol as opposed to those which are self-guided.

While this research attempted to quantify the effect of exercise on studying, it would be interesting to know the effect of studying on exercise quality. Future researchers may aim to understand if multi-tasking leads to diminished workout quality, intensity, or duration. While a variety of procedures have been employed to assess the impact of multi-tasking on learning with contradictory results (7), no identified research has investigated the effect on exercise output when participants perform an additional unrelated task during an exercise bout.

Additionally, future research may want to evaluate if other modes of exercise, for instance ellipticals or graded treadmill walking, have a similar relationship with regard to memory and recall. It would likewise be worthwhile to research the influence of the presence of music and musical selection on recall when exercise and study occur concurrently.

This is the first study of its kind to provide a visual memorization task during moderate-intensity exercise and to test for delayed recall after a night of sleep. Despite the previously mentioned limitations, it is important to note that this research indicates that studying may safely be combined with moderate intensity cycling exercise without any compromise in ability to recall memorized information.

Future research should test higher levels of cognitive learning such as comprehension, application, or analysis (1) using a traditional college course. In addition to further exploration into the active classroom design, research should also focus on the efficacy of studying during exercise when higher-order cognitive processes are requisite for success.

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