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Time-Dependent Effects of Cardiovascular Exercise on Memory

Roig, Marc; Thomas, Richard; Mang, Cameron S.; Snow, Nicholas J.; Ostadan, Fatemeh; Boyd, Lara A.; Lundbye-Jensen, Jesper

Exercise and Sport Sciences Reviews: April 2016 - Volume 44 - Issue 2 - p 81–88
doi: 10.1249/JES.0000000000000078
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We present new evidence supporting the hypothesis that the effects of cardiovascular exercise on memory can be regulated in a time-dependent manner. When the exercise stimulus is coupled temporally with specific phases of the memory formation process, a single bout of cardiovascular exercise may be sufficient to improve memory.

The timing of exercise in relation to the information to be remembered is critical to maximize the effects of acute cardiovascular exercise on memory.

1School of Physical and Occupational Therapy, Faculty of Medicine, McGill University, Montreal; 2Memory and Motor Rehabilitation Laboratory (MEMORY-LAB), Feil and Oberfeld Research Centre, Jewish Rehabilitation Hospital, Montreal Center for Interdisciplinary Research in Rehabilitation (CRIR), Laval, Quebec, Canada; 3Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; 4Graduate Program in Rehabilitation Sciences, Faculty of Medicine, University of British Columbia; 5Graduate Program in Neuroscience, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; and 6Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark

Address for correspondence: Marc Roig, School of Physical & Occupational Therapy, Faculty of Medicine, McGill University, 3654 Promenade Sir-William-Osler, Davis House Room 30 Montreal, Quebec H3G 1Y5, Canada (E-mail: marc.roigpull@mcgill.ca).

Accepted for publication: February 2, 2016

Associate Editor: Demetra D. Christou, Ph.D.

Key Points

  • The relationship between cardiovascular exercise and memory in humans is extremely complex.
  • Studies showing positive but also nonsignificant effects on memory after several months of exercise are common in the literature.
  • Parameters of exercise such as intensity, frequency, and duration are thought to modulate the effects of this intervention on memory.
  • The timing of exercise in relation to the exposure of the information to be remembered also is critical to modulate the effectiveness of this intervention.
  • When exercise is performed in close temporal proximity to the exposure of the information to be remembered, the effects on memory are maximized.
  • Exercise triggers transient changes in brain function that might facilitate memory processing in a time-dependent fashion.
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INTRODUCTION

Studies investigating the effects of cardiovascular exercise on memory traditionally have used either acute or long-term exercise interventions. Acute interventions consist of performing a single bout of exercise in close temporal proximity to the exposure to the information to be remembered, whereas long-term interventions involve multiple exercise bouts performed at different time points during a period of several weeks or months. Improvements in memory in acute exercise studies usually are inferred from retention tests assessing recall of the specific information (e.g., procedural, visual) previously presented, which are performed at one or various time points (e.g., minutes to days) after the exercise bout (23) (Fig. 1A). In contrast, comparing the performance of memory tests administered at the beginning and the end of the training period assesses memory improvements in long-term exercise studies (8) (Fig. 1B).

Figure 1

Figure 1

Physiologically, these two interventions differ in that acute exercise provides a single exercise stimulus whereas long-term exercise provides multiple exposures for a period of time. However, with regard to memory processing, these two interventions also can be distinguished by the temporal relationship established between the exercise stimulus and the memory formation processes. We argue that the effects of acute exercise on memory are time-dependent, with specific phases of the formation of a memory being facilitated depending on whether the exercise bout is performed before, during, or after encoding a memory engram (22) (Fig. 1A). The effects of long-term exercise, in contrast, depend less on the temporal coupling between the exercise stimulus and the memory formation process but on the cumulative effects that regular bouts of exercise have on the brain structures responsible for memory processing (8) (Fig. 1B).

The positive adaptations that regular bouts of cardiovascular exercise exert on the brain structures that support various memory processes are indisputable (8). However, the effectiveness of long-term exercise interventions to improve memory in humans remains somewhat controversial (22). Examples of studies showing positive but also nonsignificant effects on memory after several months of regular cardiovascular exercise are common in the scientific literature (22). Inconsistencies in outcomes are believed to stem, in part (Fig. 2), from differences in the parameters of exercise. Consequently, there is emerging interest in what constitutes the most appropriate duration, intensity, and frequency to maximize the benefits of regular cardiovascular exercise on memory. Surprisingly, an additional aspect of exercise that has received much less attention refers to when the exercise is performed, relative to the exposure to the information to be remembered. Although memory formation processes are time-dependent by definition (15), to what extent the timing of exercise modulates the effects of cardiovascular exercise on memory has not been well established (2). Acute exercise experimental paradigms represent an excellent opportunity to explore potential time-dependent effects of cardiovascular exercise on memory. Here, we summarize data from acute exercise studies supporting the hypothesis that the effects of cardiovascular exercise on memory can be regulated in a time-dependent manner. The results of such studies suggest that the positive effects of cardiovascular exercise on memory can be maximized substantially when the exercise stimulus is placed in close temporal proximity to the different stages of the memory formation process.

Figure 2

Figure 2

We start this review by presenting several investigations that have used acute cardiovascular exercise experimental paradigms to demonstrate that, when performed immediately after or before the exposure to the information to be remembered, a single bout of exercise is sufficient to facilitate memory processing. The capacity for processing and storing information about facts and events depends on the declarative memory system, which mainly involves structures of the medial temporal lobe and, in particular, the hippocampus (32). In contrast, the formation of memories, such as those that store the sensorimotor information acquired during motor skill learning (i.e., procedural memories), depends mainly on the nondeclarative memory system, which primarily involves deep regions of the brain such as the striatum and cerebellum in addition to motor and premotor cortical areas (32). In this review, we primarily focus on the effects of acute exercise on procedural memory. Nevertheless, we also discuss the results of several other studies that have explored the effects of acute exercise on other, more declarative, types of memory such as visual and verbal memory.

We also present recent data revealing that increasing the time between exercise and exposure to the information to be remembered tend to reduce the benefits of exercise on memory. We then analyze how specific parameters of exercise, such as intensity and the delay of the retention tests used to assess improvements in memory, interact with the timing of exercise to mediate the effects of this intervention on different types of memory. We emphasize the importance of considering those aspects to clarify some conflicting results found in the literature (22) and also to design future experiments properly using acute exercise interventions to improve memory. In the last part of the review, we discuss the results of the very few studies that have explored potential mechanisms underlying the time-dependent effects of acute exercise on different types of memory. Finally, we show recent evidence in support of the hypothesis that the combination of acute and long-term interventions might maximize the effects of cardiovascular exercise on human memory.

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A Single Bout of Cardiovascular Exercise Can Improve Different Types of Learning and Memory

We recently conducted a meta-analysis, including data from 29 studies that demonstrated that acute cardiovascular exercise has positive effects on memory (22). Pooled standardized mean differences (SMD) revealed that this intervention induces small-to-moderate (SMD = 0.26; 95% confidence interval (CI) = 0.03–0.49; P = 0.03) and moderate-to-large (SMD = 0.52; 95% CI = 0.28–0.75; P < 0.0001) improvements in short- and long-term memory, respectively (22). More importantly, the results of such studies demonstrate that these memory improvements can be obtained in multiple age groups and in a wide variety of tasks involving different types of learning and memory. For example, Pesce et al. (20) showed better verbal memory scores in 11–12-year-old preadolescents when a free-recall word test was preceded by a single class of physical education consisting of either aerobic circuit training or group games. In contrast, when the recall tests were administered after a period of rest, improvements in verbal memory were negligible. In healthy young adults, Winter et al. (38) showed that 6 min of intense running performed immediately before a vocabulary task accelerated the acquisition of novel words and improved word recall 7 d after exercise. In another study, Coles and Tomporowski (6) showed that 40 min of moderate-intensity cycle ergometry also improved free-recall verbal memory in young healthy subjects. Similarly, 30 min of moderate-to-vigorous–intensity cycling performed immediately before listening to two paragraphs improved word recall 35 min after exposure in a group of young participants (12). Other studies have demonstrated similar memory enhancements after acute exercise but only in specific memory domains and in subjects with low-baseline memory scores (22).

It is noteworthy that the benefits that acute cardiovascular exercise has on memory can be obtained also in older adults, a group highly susceptible to experience a progressive decline in this important cognitive function. For example, Stones and Dawe (34) found improvements in semantic cued memory in healthy nursing home residents immediately after 15 min of cardiovascular exercise performed at a moderate intensity. Furthermore, 6 min of cycling at 70% of peak oxygen uptake (VO2 peak) performed immediately after watching a set of positive images improved visual recall, tested 1 h after the intervention, in elderly subjects with and without mild cognitive impairment (24).

Of importance for sports practice and physical rehabilitation, acute cardiovascular exercise also has been shown to improve procedural memory. For example, we showed that 15 min of high-intensity intervallic cycling performed either before or after practicing a visuo-motor-tracking task improved the retention of the skill 1 and 7 d after exercise in young healthy adults (23,29). More recently, we demonstrated that the benefits of this exercise intervention might be specific to certain domains of motor skill learning such as the temporal precision of movement (13,31). In summary, the results of all these studies confirm that, when strategically scheduled, a single bout of cardiovascular exercise has the potential to improve different aspects of procedural memory and learning.

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The Timing of Exercise Modulates the Effects of Acute Cardiovascular Exercise on Memory

The results from recent animal studies using acute exercise interventions reinforce the hypothesis that the effects of cardiovascular exercise on memory can be regulated in a time-dependent fashion. A paradigmatic example of such investigations is the study conducted by Siette et al. (25) who, in three elegant experiments performed on rats, demonstrated that a single bout of voluntary exercise can modulate memory formation processes by enhancing the consolidation (experiment 1), extinction (experiment 2), and reconsolidation (experiment 3) of a memory associated with context-conditioned fear induced with electrical shocks. Experiment 1 revealed that animals provided with access to a running wheel immediately before or after being exposed to electrical shocks froze more in a 24-h retention test than rats provided with access to the wheel only 6 h after. In contrast, in experiment 2, rats provided with access to the wheel immediately before or after being exposed to a nonshock condition froze less in the 24-h retention test. Experiment 3 showed that rats that exercised immediately after an extended nonshocked exposure to the conditioned context froze less, whereas the animals that exercised after a brief nonshocked exposure froze more than sedentary controls. Memories created through fear-conditioning tasks differ from memories created through emotionally neutral tasks in that they are encoded during high levels of emotional arousal that involve the activation of the amygdala (17). Nevertheless, the results of Siette et al. support the hypothesis that the effects of acute cardiovascular exercise on memory are time-dependent and, thus, maximized when the exercise is performed with increasingly close temporal proximity to the exposure to the information to be remembered (consolidation), forgotten (extinction), or even modified (reconsolidation). In contrast, when the exercise stimulus is performed 6 h after exposure, and not temporally coupled with the memory formation process, the positive effects that acute exercise has on memory lessen significantly (25).

Preliminary results obtained in experiments involving human subjects also reinforce the hypothesis that a time-dependent relationship modulates the effects of cardiovascular exercise on memory. For example, we recently exposed a group of young healthy participants to 15 min of high-intensity (90% VO2 peak) cycling either immediately, 1 h, or 2 h after practicing a motor skill, and only the group that exercised immediately after motor practice showed significant improvements in a skill retention test performed 7 d after the exercise bout (36). In another study, Statton et al. (33) reported that the performance of a single bout of moderate-intensity exercise immediately before motor practice improved skill acquisition in healthy young subjects. In contrast, when the exercise bout was performed 1 h before motor practice, the effects of exercise on the rate of skill acquisition were not significant. The results of these two studies (33,36) confirm that improvements in memory arising from acute cardiovascular exercise interventions depend, to a large extent, on the temporal coupling of the exercise stimulus with the different stages of the memory formation process. Taken together, the data from the three studies that specifically have explored the effects of timing of exercise on memory (25,33,36) suggest that the closer the exercise stimulus is to the exposure to the information to be remembered, the larger the effects of acute exercise on memory. However, as we discuss later in this review, this relationship may vary slightly depending on the intensity of exercise in relation to the delay of the retention test used to assess improvements in memory. Furthermore, because the effects of cardiovascular exercise on memory may manifest in a complex time-dependent fashion (2,3), more research will be needed until we can delineate accurately the specific temporal patterns that underlie the impact of a single bout of exercise on different phases of the memory formation process.

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Distinct Phases of the Memory Formation Process Can be Enhanced with Acute Cardiovascular Exercise

Memories need to go through at least two main phases before they are formed: encoding and consolidation (Fig. 1A). Encoding is a process through which our senses acquire the information to be remembered that is essential because it is precisely during this initial phase of the memory formation process that the nervous system forms the memory engram that will later be used for the elaboration of a specific memory. However, the brain does not stop processing information after encoding it. It is through consolidation, a multiphasic complex process that continues to evolve long after encoding, that a memory engram matures and is strengthened progressively. If consolidation is successful, the engram becomes more robust, less susceptible to disruption, and the memory becomes ready for retrieval. However, when the engram does not consolidate properly, the formation of the memory is compromised and the retention of information is not achieved fully. Depending if the exercise bout is performed before, during, or after encoding, acute exercise will impact on different phases of the memory formation process (22). In principle, a bout of exercise performed before or during encoding will facilitate mainly the acquisition of information and, thus, improve primarily memory encoding (12,38). However, because the effects of exercise may persist long after its termination (2), it is possible that an exercise bout performed before or during exposure (i.e., encoding) also could have effects on the initial stages of memory consolidation, especially if the intensity of exercise is high and the effects of the exercise bout persist long after its termination. A bout of exercise performed after encoding, in contrast, would prime exclusively consolidation mechanisms (24) by facilitating the effective transformation of the memory engram into a more robust long-term memory.

Determining how acute exercise impacts on each phase of the memory formation process, however, is extremely complex because these phases involve several overlapping mechanisms (7). Furthermore, it is unclear if preferentially priming encoding, consolidation, or even both memory phases at the same time by exercising both before and after encoding would maximize improvements in memory. For example, we showed that 15 min of high-intensity cycling performed immediately after practicing a motor skill, during the first stages of memory consolidation, was more effective to improve long-term procedural memory assessed 7 d after motor practice than when the exercise bout was performed immediately before practice (23). This finding suggests that priming memory consolidation might be the most effective strategy to improve memory. Another study, however, showed that 20 min of moderate-intensity cycling significantly improved paragraph recall, but only in the group exercising immediately before exposure and not in the group exercising immediately after (12). In contrast to our previous results (23), in this study (12), facilitating exclusively memory consolidation did not translate to larger improvements in memory. Discrepancies between both studies could be due to differences in the intensity of exercise and/or the memory tasks. Furthermore, it should be noted that in this latter study (12), the group that exercised after exposure performed the retention test immediately after exercise. It is therefore not unlikely that the temporal proximity of the retention test to the exercise bout could have increased neural noise, impairing the recall of words at this short-term retention test. The omission of a delayed retention test, in addition, also could have left undetected potential memory gains in the group exercising after exposure due to improvements during the memory consolidation process. In the following section, we discuss the importance of including delayed retention tests to capture the long-term effects of acute exercise on memory.

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The Effects of Acute Cardiovascular Exercise on Memory Must be Assessed With Short- and Long-Term Retention Tests

Some studies have shown either nonsignificant or even detrimental effects of acute exercise on memory (22). An exhaustive analysis of these studies provides important information to explain why improvements in memory probably were not achieved. Firstly, most of these studies used retention tests performed during or shortly after an exercise bout of moderate or high intensity. This approach is not appropriate because the proximity of the retention test to the exercise stimulus can mask gains in memory performance easily due to disproportionate exercise-induced fatigue and/or arousal, especially when exercise is performed at higher intensity. The detrimental effects of exercise-induced fatigue on cognition in general and memory in particular are well described, and although physiological arousal may facilitate memory processing, its effects can be detrimental if the level of arousal and the delay of the memory retention tests are not controlled properly (18). For example, low arousal levels during memory encoding may lead to the detection of larger memory improvements immediately as compared with delayed retention tests (18). In contrast, higher arousal levels may result in negligible or even detrimental effects on memory assessed through short-term retention tests but lead to positive effects in tests performed long after exposure (18). Thus, in acute exercise studies, the intensity of exercise and the delay of the retention tests should be selected carefully to capture all the potential effects of this intervention on memory. For example, if the intensity of exercise were to be high, it would be advisable to include long-term retention tests, which are less affected by the immediate effects of excessive fatigue and arousal on performance that could impact the memory assessment negatively (23,29). In contrast, short-term retention tests could be used to capture the effects of moderate-intensity exercise on memory.

An additional problem of using exclusively short-term retention tests to assess how acute exercise impacts memory is that performing these tests in close temporal proximity to the exercise bout does not allow for the detection of potential long-term effects of exercise on memory. As previously stated, the effects of exercise on cognition may endure well after exercise has finished (2,3), and we (23,29) and other research groups (38) have shown that, indeed, memory improvements after acute exercise may appear long after the performance of the exercise bout and not immediately after. Hence, performing retention tests too early after encoding, when the memory trace is still undergoing consolidation, and, thus, in a labile state, could limit the detection of potential long-term exercise-induced memory gains due to a premature disruption of the consolidation process (22). This hypothesis aligns well with the relatively larger effects that acute exercise tends to show on long-term memory (22) because this type of memory usually is assessed through delayed retention tests, which are not performed immediately after the exercise bout. Consequently, delaying the retention tests and allowing for memory consolidation to be completed could improve the detection of remote enhancing effects of acute exercise on memory taking place long after the exposure to the information to be remembered. This is especially important in studies, in which exercise is performed immediately after encoding, that rely entirely on the effects of exercise on memory consolidation. Because the inclusion of multiple retention tests introduces potential risks in the assessment of memory (e.g., reencoding), we recommend including one short- and long-term retention test to assess both the immediate and delayed effects of acute exercise on memory. This approach will ensure that we capture all the potential effects of cardiovascular exercise on different stages of the memory maturation process.

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Acute Cardiovascular Exercise Triggers Time-Dependent Mechanisms That May Facilitate Different Stages of the Memory Formation Process

We still know little about which specific time-dependent mechanisms lie behind the positive effects that a single bout of exercise has on memory. The successful stabilization of engrams later to become long-term memories depends, to a large extent, on the synaptic events occurring immediately before and after encoding (21). Thus, one potential mechanism through which acute exercise might improve memory is by facilitating transiently the synaptic transmission of the neural networks that will be tagged during encoding. Acute exercise could promote this facilitation by inducing long-term potentiation (LTP), a cellular mechanism that produces persistent increases in synaptic strength, which are needed for the formation of long-lasting memory. Certainly, animal studies have confirmed that cardiovascular exercise may enhance this form of synaptic plasticity although the exact amount of exercise to optimize LTP is not known currently (19).

Ensuring the temporal persistence of LTP during memory consolidation (9) could be an additional mechanism through which acute exercise might improve memory. LTP tends to decay back to baseline some hours after its induction with memory encoding. By transiently increasing the availability of catecholamines (e.g., norepinephrine, dopamine) and neurotrophic factors (brain-derived neurotrophic factor (BDNF)) (29) that maintain LTP activity during consolidation (1,21), acute exercise might facilitate the stabilization of the engram leading to a long-term memory. The fact that these two mechanisms need to occur in close temporal proximity to memory encoding to be effective (21) would be consistent with the studies showing that the effects of acute cardiovascular exercise on memory and learning are modulated in a time-dependent fashion (25,33,36). In the next two sections, we examine the very few human studies that have investigated these two mechanisms from different perspectives and discuss their potential role in the effects that acute cardiovascular exercise has on different types of memory.

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Acute Cardiovascular Exercise Promotes Neuroplasticity Changes in Cortical Areas Involved in Procedural Memory

Recent investigations have examined the effects of acute exercise on the neuroplasticity of discrete areas of the brain involved in the elaboration of procedural memory. Because mechanisms of synaptic plasticity cannot be assessed directly in humans, noninvasive brain stimulation protocols that provide indirect measures of activity between neuronal populations have been used. Arguably, exercise-induced changes in different forms of corticospinal excitability (CSE) assessed with transcranial magnetic stimulation (TMS), applied to the nonexercised upper limb muscle representations in the primary motor cortex (M1), has been the most commonly used measure (28). Changes in CSE from M1 after a single bout of cardiovascular exercise have been evaluated using both single- and paired-pulse stimulation protocols. Single-pulse protocols assess CSE by measuring changes in the following: (i) the amplitude of motor evoked potentials (MEP) induced at a fixed or variable TMS intensity; (ii) the motor threshold, defined as the minimum TMS intensity required to observe an MEP of a specific amplitude (e.g., 50 μV); and (iii) the lowest TMS intensity required to obtain an MEP of certain amplitude (e.g., 1 mV). Increases in the amplitude of MEP or reductions in the intensity of the stimulation are regarded commonly as indirect markers of enhanced LTP, a mechanism also necessary for the formation of procedural memory and motor skill learning. However, it should be noted that the physiological underpinnings of MEP still are not well understood, and changes in CSE also may be affected by other neural mechanisms (4). Paired-pulse stimulation protocols, in contrast, assess facilitative and inhibitory processes involving cortical interneurons by providing a conditioning stimulus followed by a test stimulus delivered several milliseconds after. The amplitude of the MEP elicited by the test stimulus normalized to the MEP amplitude obtained at baseline provides an estimate of facilitation and/or inhibition (26).

To date, the results of the studies that have explored the effects of a single bout of exercise on the CSE from M1 using single-pulse TMS protocols have been inconsistent. Some studies have shown increases in CSE (5), whereas some other studies have not detected any significant change after exercise (13,14). Inconsistencies among outcomes could be explained by the fact that studies differ in both the exercise (e.g., exercise intensity) and TMS protocols used. In any event, the results of these single-pulse studies should be interpreted with caution because most of these experiments failed to factorize changes in muscle contractility as a result of exercise that could affect the MEP amplitude obtained with TMS. This is critical, given the significant decline in muscle contractility (i.e., M-wave amplitude) shown after a single bout of exercise, even in muscles not actively involved in the exercise bout (14). Normalizing MEP to measures of maximal muscle activation (Mmax) is critical to factorize potential exercise-induced changes (e.g., fatigue) in muscle contractility that could affect CSE measurements.

The results of studies using paired-pulse protocols are consistent with the hypothesis that acute exercise may lead to increases in CSE. For example, acute exercise performed at moderate and moderate-to-high intensity has been shown to reduce short-interval intracortical inhibition and increase intracortical facilitation (26,30). It has been suggested that these increases in intracortical CSE reflect positive transient changes induced by acute cardiovascular exercise, which are required for more long-lasting changes in neuroplasticity (28). However, before determining if these changes in CSE preclude the synaptic plasticity changes that subserve the effects of acute exercise on procedural memory and skill learning, more research will be required. To date, all studies have assessed changes in CSE immediately or soon after exercise (e.g., 30 min after the exercise) (14,26,27,30). Thus, whether acute exercise triggers remote changes in CSE that become prominent long after the termination of exercise and that may contribute to the stabilization of the procedural memory engram after motor practice is not known (37). More importantly, neither study has investigated if the combination of acute exercise with motor practice modulates the CSE of M1 during consolidation.

Noninvasive brain stimulation protocols applied immediately after a single bout of acute exercise have been used recently to investigate the transient modulatory effect of a single bout of cardiovascular exercise on synaptic plasticity. For example, paired associative stimulation (PAS) protocols induce LTP-like synaptic plasticity on M1 by pairing electrical stimulation of a hand muscle with TMS applied several milliseconds after to the representational area of that muscle on the M1 (13). A single bout of cardiovascular exercise performed at moderate (27) or high intensity (13) has been shown to enhance the immediate response to a PAS protocol, increasing the CSE of the representational area of a nonexercised upper limb muscle on M1.

Another noninvasive brain stimulation protocol that has been used to study the transient effects of acute cardiovascular exercise on synaptic plasticity is continuous theta burst stimulation (cTBS). This high-frequency TMS protocol, which consists of bursts of three stimuli applied on M1 at 50 Hz for 40 s, produces a transient suppression (20–25 min) of CSE assessed from M1 with TMS (11). McDonnell et al. (14) showed that 30 min of moderate-intensity cycling performed immediately before cTBS prevented the decline in CSE commonly observed after this stimulation paradigm (11). In contrast, the cTBS protocol lowered CSE when preceded by either an acute bout of exercise of the same duration (30 min) but performed at low intensity or no exercise. Thus, it is possible that only the exercise performed at moderate intensity was effective in maintaining CSE, counteracting the suppression of excitability normally observed after cTBS (11).

Taken together, the studies that have used noninvasive brain stimulation protocols to investigate the transient modulatory effect of a single bout of cardiovascular exercise on synaptic plasticity reinforce the hypothesis that this intervention promotes changes in CSE. However, acute exercise may either increase (13,27) or prevent a decrease (14) of CSE, depending on the nature (i.e., excitatory or inhibitory) of the protocol used. It is important to reiterate that these studies (13,14,27) used lower limb exercise interventions whereas CSE was measured from a nonexercised upper limb muscle. Thus, the effects of acute exercise on the neuroplasticity of the corticospinal pathway may extend to other motor areas of the brain not intrinsically involved in the execution of movements during exercise. This might be relevant for the rehabilitation of patients with upper limb limitations because lower body exercise may still promote neuroplasticity in areas of the brain involved in the motor recovery of these patients.

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The Peripheral Concentration of Neurochemicals After Acute Cardiovascular Exercise Is Associated With Memory Improvements

Recent investigations have explored associations between transient increases in the concentration of peripheral biomarkers released during acute exercise and improvements in memory. As previously stated, the increased availability of some neurochemicals during memory encoding and consolidation might facilitate the persistence of LTP-like mechanisms during consolidation and, thus, the formation of long-term memory (21). For example, improvements in visual memory after 6 min of moderate-intensity cycling have been associated with increases in norepinephrine assessed from saliva immediately after exercise both in healthy elderly subjects and subjects with mild cognitive impairment (24). Winter et al. (38) showed that more sustained BDNF levels during a novel vocabulary learning task after 6 min of high-intensity treadmill running were related to better short-term learning success. In the same study, the concentration of blood catecholamines assessed immediately after exercise was associated to better intermediate- (dopamine) and long-term (epinephrine) retention of words. We have reported similar associations between procedural memory and the peripheral concentrations of lactate, BDNF, and norepinephrine after 15 min of high-intensity cycling. The associations found in all these studies are not entirely surprising given the importance of these neurochemicals in memory formation processes. The role of catecholamines in the regulation of arousal-mediated memory is well established (16), and BDNF is an essential neurotrophin, influencing synaptic plasticity and orchestrating mechanisms underlying memory formation (1). Similarly, brain lactate has been shown to be essential in ensuring energy availability in astrocyte-regulated long-term memory formation processes, at least in animal experiments using in vitro techniques (35).

It would be tempting to overstate the importance of the associations found between the increase of these neurochemicals and different types of memory. However, these associations should be interpreted with much caution. The studies described previously (24,29,38) used a correlational approach that does not prove a direct implication of these neurochemicals in the effects of acute exercise on memory. Furthermore, because some of those biomarkers (i.e., catecholamines) show an inverted-U dose-response effect, with large concentrations even having detrimental effects on memory (16), it is unlikely that these correlations follow a simple linear pattern. It is also unclear to what extent the systemic levels of these neurochemicals are indicative of concentrations in the brain. Although some of these substances (i.e., epinephrine) can act peripherally to modulate memory processing (16), the aforementioned neurochemicals (with the exception of lactate) do not cross the blood-brain barrier in large amounts. Even in the event that the availability of these substances in the brain is increased with acute exercise, this does not imply that they are being used to optimize memory processes specifically in the synaptic networks tagged during encoding. More importantly, the concentration of these neurochemicals returns to baseline level some minutes after exercise, and we know little about the time course of the molecular pathways modulating the effects that these substances have on different stages of the memory formation process (2). Hence, although establishing correlations between the increase of these biomarkers and memory improvements offers preliminary insights into the potential molecular pathways modulating the time-dependent effects of cardiovascular exercise on memory, the complex temporal pattern of their action should be considered carefully.

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Combining Acute and Long-Term Cardiovascular Exercise Maximizes Improvements in Memory

The effects of long-term cardiovascular exercise on short (SMD = 0.15; 95% CI = 0.02–0.27; P = 0.02) and long-term (SMD = 0.07; 95% CI = −0.13–0.26; P = 0.51) memory are small (22). However, repeated bouts of exercise are shown to be necessary to maintain the positive adaptations that cardiovascular exercise exerts on some of the structures and functions of the brain that are involved in memory formation processes (8). More importantly, recent investigations have shown that by maintaining these adaptations, long-term cardiovascular exercise may increase the responsiveness to acute exercise interventions by priming some of the mechanisms that facilitate memory processing. For example, Berchtold et al. (3) demonstrated that after several days of daily cardiovascular training, mice exposed to a short period of exercise 14 d after the termination of training showed a quick return to BDNF hippocampal protein expression levels similar to those observed at the end of the training period. This rapid recovery of BDNF levels is important because the availability of this neurotrophin is associated strongly with better memory performance in spatial memory tasks such as the maze radial water task (2). Another study in humans showed that the effectiveness of acute exercise to improve memory was increased in subjects previously exposed to 4 wk of regular (four times a week) cardiovascular training (10). Taken together, the results of these two studies emphasize the importance of combining both acute and long-term interventions to maximize the cumulative effects of cardiovascular exercise on human memory (33).

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SUMMARY

This review revisits the complex relationship between cardiovascular exercise and memory focusing on the timing of exercise as an important factor modulating memory formation. The temporal relationship between the exercise stimulus and the exposure to the information to be remembered is overlooked commonly in studies investigating the impact of this type of exercise on memory. However, the data presented here support the hypothesis that the effects of cardiovascular exercise on memory are regulated in a time-dependent manner. When performed in close temporal proximity to memory encoding, a single bout of exercise may facilitate the long-term retention of information. By focusing on the timing of exercise, however, we are not denying the importance of parameters of exercise that may influence the effects of exercise on memory (Fig. 2). Similarly, we are not underestimating the value of regular bouts of exercise to maintain the molecular machinery responsible for memory processing (Fig. 1B). We simply argue that, when cardiovascular exercise is prescribed with the goal of improving memory, the timing of exercise is an important parameter to consider. Strategically scheduled, single bouts of cardiovascular exercise performed in close temporal proximity to the exposure of the information to be remembered may maximize the effects of this intervention on memory. These effects may be particularly beneficial when the relationship between exercise timing, intensity, and the targeted memory formation stage are considered together. The findings presented here have important implications for the prescription of cardiovascular exercise to improve memory in different populations. For example, this intervention could maximize the retention of information provided in school settings, improve cognitive function or reduce cognitive decline in elderly individuals, or enhance the retention of motor skills during rehabilitation in turn serving to accelerate the motor recovery of patients with mobility deficits.

M.R. was supported with funds from the Natural Sciences and Engineering Research Council of Canada (Discovery Grant), Canada Foundation for Innovation (John R. Evans Leaders Fund), Réseau Provincial de Recherche en Adaptation-Réadaptation (Recherche Clinique), and the Montréal Centre for Interdisciplinary Research in Rehabilitation (New Investigator). C.S.M. and N.J.S. were supported by the Natural Sciences and Engineering Research Council of Canada and the University of British Columbia. L.A.B. received salary support from the Canada Research Chairs and the Michael Smith Foundation for Health Research. R.T. and J.L.J. were supported with funds from Nordea-fonden via the Copenhagen Centre for Team Sports and Health at the University of Copenhagen.

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Keywords:

cardiovascular exercise; memory; encoding; consolidation; biomarkers; cortical excitability

© 2016 American College of Sports Medicine