Psychoneuroendocrinology (2014) 41, 121—131

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Impact of acute aerobic exercise and cardiorespiratory fitness on visuospatial attention performance and serum BDNF levels Chia-Liang Tsai a,*, Fu-Chen Chen b, Chien-Yu Pan c, Chun-Hao Wang a, Tsang-Hai Huang a, Tzu-Chi Chen a a

Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Taiwan Department of Recreational Sport and Health Promotion, National Pingtung University of Science and Technology, Taiwan c Department of Physical Education, National Kaohsiung Normal University, Taiwan b

Received 28 October 2013; received in revised form 10 December 2013; accepted 19 December 2013

KEYWORDS BDNF; Cognition; Acute exercise; Cardiorespiratory fitness; Behavior; Neuroelectric

Summary The purpose of the current study was to explore various behavioral and neuroelectric indices after acute aerobic exercise in young adults with different cardiorespiratory fitness levels when performing a cognitive task, and also to gain a mechanistic understanding of the effects of such exercise using the brain-derived neurotrophic factor (BDNF) biochemical index. Sixty young adults were separated into one non-exercise-intervention and two exercise intervention (EI) (i.e., EIH: higher-fit and EIL: lower-fit) groupsaccordingto their maximal oxygenconsumption.The participants’ cognitive performances (i.e., behavioral and neuroelectric indices via an endogenous visuospatial attentiontasktest) and serumBDNF levelsweremeasuredatbaselineand aftereither anacute boutof 30 min ofmoderateintensityaerobic exercise ora controlperiod. Analysesoftheresults revealed that although acute aerobic exercise decreased reaction times (RTs) and increased the central Contingent Negative Variation (CNV) area in both EI groups, only the EIH group showed larger P3 amplitude and increasedfrontalCNVareaafteracuteexercise.ElevatedBDNFlevelswereshownafteracuteexercise for both EI groups, but this was not significantly correlated with changes in behavioral and neuroelectric performances for either group. These results suggest that both EI groups could gain responserelated (i.e., RT and central CNV) benefits following a bout of moderate acute aerobic exercise. However, only higher-fit individuals could obtain particular cognition-process-related efficiency with regard to attentional resource allocation (i.e., P3 amplitude) and cognitive preparation processes (i.e., frontal CNV) after acute exercise, implying that the mechanisms underlying the effects of such exercise on neural functioning may be fitness dependent. However, the facilitating effects found in this work could not be attributed to the transient change in BDNF levels after acute exercise. # 2013 Elsevier Ltd. All rights reserved.

* Corresponding author at: Lab of Cognitive Neurophysiology, Institute of Physical Education, Health & Leisure Studies, No. 1, University Road, Tainan City 701, Taiwan. Tel.: +886 933306059/6 2757575x81809; fax: +886 6 2766427. E-mail address: [email protected] (C.-L. Tsai). 0306-4530/$ — see front matter # 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psyneuen.2013.12.014

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1. Introduction Over the past decade, there has been an accumulating literature which finds that both chronic and acute exercise are beneficial to the brain with regard to neural functioning and cognitive performance (Hillman et al., 2003; Tomporowski et al., 2011). This may be attributed to the development of a more efficient, plastic, and adaptive brain, as well as improved processes of neural adaptation, owing to an increase in regional blood flow and the promotion of brain vascularization (Endres et al., 2003; Pereira et al., 2007), stimulation of neurogenesis (Van Praag et al., 1999), and increases in the levels of some nerve growth factors, such as brain-derived neurotrophic factor (BDNF) (Neeper et al., 1995). Acute exercise refers to the practice of a single bout of exercise lasting from a few seconds to perhaps several hours (Dietrich and Audiffren, 2011). While a previous study suggested that the benefits on cognitive performance could be specific to acute aerobic exercise, and not acute resistance exercise (Pontifex et al., 2009), most researchers have demonstrated that acute exercise in general appears to aid the performance of a variety of cognitive tasks involving attention and memory (Colcombe and Kramer, 2003; Etnier et al., 1997). More specifically, it can enhance certain aspects of cognitive processing, such as response speed and accuracy, and cognitive tasks requiring extensive executive control demands, such as working memory or response inhibition (Tomporowski, 2003). However, it is worth pointing out that the performance of central executive tasks appears to improve only with moderate and not low or high intensity exercise (Tomporowski, 2003). BDNF, a member of the neurotrophic factors family, is an important molecular mediator of structural and functional plasticity in the brain (Jung et al., 2011), and plays a key role in improving neuronal transmission, modulation, and plasticity, as well as promoting neuronal proliferation, differentiation, and survival in the human brain (McAllister et al., 1999). Unlike other neurotrophins, this biomarker can transit the blood—brain barrier in both directions (Pan et al., 1998), and seems to be especially susceptible to regulation by physical activity with regard to both its release and expression (Schinder and Poo, 2000). Therefore, BDNF levels have been found to have a positive association with aerobic exercise, with higher levels being significantly related to improved cognitive performance and growth of brain tissues (Van Praag et al., 1999; Vaynman and Gomez-Pinilla, 2005). Although Bus et al. (2011) reported that lower serum BDNF levels were found in individuals aged 18 through 65 that engaged in more physical activity, Zoladz et al. (2008) reported that a five-week program of endurance exercise induced an increase in basal BDNF levels in young adults, while Ruscheweyh et al. (2009) reported that a six-month aerobic exercise intervention raised the serum BDNF levels in healthy adults, with such rises being significantly correlated with improved cognitive performance and local gray matter volume in the prefrontal and cingulate cortexes. A previous study also demonstrated that serum BDNF levels can be increased after an acute bout of aerobic exercise (Ferris et al., 2007). However, since the magnitude by which BDNF levels rise in response to acute aerobic exercise is exercise intensity independent, previous studies have

C.-L. Tsai et al. demonstrated that a moderate intensity of acute aerobic exercise can effectively elevate serum BDNF concentrations (Gold et al., 2003; Heyman et al., 2012; Tang et al., 2008; Vega et al., 2006), which may be due to the release of BDNF in the brain (Rasmussen et al., 2009). In terms of physical fitness and BDNF levels, the resting levels of serum BDNF are associated with the cardiorespiratory fitness level, with higher basal serum BDNF levels being reported in aerobicexercise-trained/higher VO2max compared to untrained/ lower VO2max young healthy adults (Zoladz et al., 2008). BDNF could thus be a potential modulator of the effects of acute aerobic exercise and cardiorespiratory fitness on cognitive performance in young adults. Previous studies have demonstrated that the eventrelated potentials (ERPs) components related to different aspects of cognitive processes that serve executive functions, such as the response preparation and evaluation (Contingent Negative Variation, CNV) and attentional stimulus evaluation (P3) processes, are positively modulated by both physical fitness and acute bouts of exercise (Hillman et al., 2002, 2005; Kamijo et al., 2004; Magnie et al., 2000; Stroth et al., 2009). For example, Hillman et al. (2002) and Stroth et al. (2009) found that CNV amplitudes were significantly greater for higher-fit individuals compared to lower-fit ones. In addition, Hillman et al. (2005) found that higher-fit adolescents exhibited larger P3 amplitudes than lower-fit ones, while and Kamijo et al. (2004) and Magnie et al. (2000) found that P3 amplitude increased following an acute bout of aerobic exercise. In covert orienting of a visuospatial attention task in the Posner paradigm, the endogenous attention network test involves alerting, orienting, and executive attention, and such a cognitive task can effectively evoke the two ERP components mentioned above, namely: (1) an expectancy wave (i.e., CNV) generated when the preparation for an upcoming stimulus is produced by a warning stimulus, and (2) a late potential activity, such as P3 for cognitive responses (i.e., motor processes) (Tsai et al., 2009). Since an acute bout of exercise can increase the arousal and activation statuses (Dietrich and Audiffren, 2011), which induce more resources being made available for stimulus-driven attention and motor readiness, it would be reasonable to predict that a greater P3 amplitude, as well as larger CNV area, will emerge after an acute bout of moderate aerobic exercise in young adults, especially among those with higher physical fitness, when performing the endogenous Posner paradigm. Notwithstanding previous studies have demonstrated that physical fitness (Aberg et al., 2009) and acute aerobic exercise (Pontifex et al., 2009) are positively related to cognitive performance in young adults, thus far, only two studies have tried to elucidate the mechanisms underlying this process by directly comparing the effects of physical fitness and acute exercise on cognitive performance among the same group of participants using behavioral and neuroelectric indices (Magnie et al., 2000; Stroth et al., 2009). However, the results of these work are equivocal due to conflicting data. Moreover, while it has been proposed that BDNF may mediate the beneficial effects of aerobic exercise on the brain (Lee et al., 2014; Neeper et al., 1995), no research has yet been conducted to examine relationship between changes in neurocognitive performance and serum BDNF levels after acute aerobic exercise in individuals with different levels of

BDNF, acute exercise, cardiorespiratory fitness, and cognition physical fitness. Therefore, the aims of the present study are as follows: (1) to examine and compare the effects of cardiorespiratory fitness and an acute bout of moderate intensity aerobic exercise on the behavioral and neuroelectric correlates using a visuospatial attention task, and (2) to examine how the biomarker BDNF is involved in the impact that moderately intense aerobic exercise has on cognitive functions in young adults with different levels of cardiorespiratory fitness. We hypothesize that (1) an acute bout of moderate intense aerobic exercise would produce beneficial effects with regard to behavioral and neuroelectric performance in the exercise-intervention group relative to those seen in the non-exercise-intervention group, and these facilitating effects would be more significant on the neurocognitive dimensions in the highercompared to lower-fit individuals, since young adults with higher cardiorespiratory fitness could have higher serum BDNF levels at baseline (Zoladz et al., 2008) and after acute exercise, and these would facilitate better neurocognitive performance (Van Praag et al., 1999; Vaynman and GomezPinilla, 2005); and that (2) BDNF levels would be elevated after acute exercise, and the changes in the BNDF levels would directly correlate with the changes in behavioral and neuroelectric performance in the young adults when performing the visuospatial attention task. We believe that the current study can provide additional insights into the relation between acute aerobic exercise and the potential mechanisms underlying changes in neurocognitive performance in the brain.

2. Methods 2.1. Participants Sixty male participants aged between 19 and 28 were recruited and completed a medical history and demographics questionnaire. They reported being free of any psychiatric or neurological disorders, cardiovascular or metabolic diseases, or medication intake that influenced central nervous system functioning. None of the participants showed any symptoms of cognitive impairment or depression, as separately measured by the Mini-Mental State Examination (all scored below 24) and Beck Depression Inventory II (DBI II, all scored below 13). All the participants were non-smokers, right-handed,

123 and had normal or corrected-to-normal vision. After the VO2max test to identify individual fitness levels, they were divided into two exercise-intervention (EI) groups [higherfit (EIH, n = 20, VO2max = 58.04  6.67 ml/kg/min) and lower-fit (EIL, n = 20, VO2max = 36.04  3.64 ml/kg/min)] and one non-exercise-intervention (NEI) group (n = 20, VO2max = 46.59  9.40 ml/kg/min, to examine whether the effects observed in this study simply reflect repeated measurements for two EI groups). The overall energy expenditure per week (MET-min/week), as assessed using International Physical Activity Questionnaire (IPAQ), and resting heart rate, showed significant differences between the EIH and EIL groups (both ps < .05). With regard to their ages and body mass indices, no significant differences existed among the groups (both ps > .05) (see Table 1). All the participants provided written informed consent to participate in the experiment, which was approved by the Institutional Ethics Committee of National Cheng Kung University, Taiwan.

2.2. Procedures The participants were required to make two visits to the cognitive neurophysiology laboratory. On the first visit the research assistant explained the experimental procedure, and asked the participants to complete an informed consent form, a medical history and demographic questionnaire, DBI II, and a handedness inventory (Chapman and Chapman, 1987). To provide sufficient preactivity screening to lower potential risk factors before the maximal cardiorespiratory endurance (VO2max) assessment, the participants also completed the IPAQ to ascertain that their overall energy expenditure achieved a minimum of at least 600 metabolic equivalents per week (MET-min/week). Their height and weight were also measured to calculate their BMI. They were then fitted with a Polar heart rate (HR) monitor (RX800CX, Finland) and took the continuous graded maximal exercise test, so that they could be divided into each of three groups. Before an acute bout of exercise, the participants were asked to refrain from strenuous exercise and alcohol intake for 24 h, and caffeine were also prohibited for 3 h before exercising. On the second visit in the same week, each participant was asked to sit in an adjustable chair in front

Table 1 Demographic characteristics (mean  SD) of the two exercise intervention groups (i.e., EIL and EIH for lower- and higherfit young adults, respectively) and one non-exercise-intervention (NEI) group. Group

EIL (n = 20)

EIH (n = 20)

NEI (n = 20)

Age (years) Body mass index (kg/m2) Education (years) VO2max (ml/kg/min)* MMSE BDI-II Resting HR (beats/min)* IPAQ (MET-min/week)*

23.10  2.20 24.50  4.50 17.10  2.20 36.04  3.64 29.30  0.86 4.15  3.77 68.00  10.91 2366.03  1017.66

22.20  2.17 22.20  2.29 16.20  2.17 58.04  6.67 29.35  0.75 3.95  3.33 60.55  6.86 5857.06  2768.87

22.20  1.70 22.25  1.89 16.20  1.70 46.59  9.40 28.95  0.76 4.65  4.09 63.80  6.81 4163.36  2904.40

MMSE, Mini-Mental State Examination; BDI, Beck Depression Inventory; HR: heart rate; IPAQ: International Physical Activity Questionnaire. (*p < .05: VO2max between three groups; resting HR and IPAQ values between EIL and EIH groups).

124 of a computer screen (with a width of 43 cm) in an acoustically shielded room with dimmed lights, and approximately 90 min after eating a meal, at about 9:00—10:00 am. An electrocap and electrooculographic (EOG) electrodes were attached to the participant’s scalp and face before the visuospatial-attention-task test. The viewing distance was approximately 75 cm. After 10 practice trials to help the participants became familiar with the experimental procedure, blood was withdrawn and then the formal cognitive test was immediately administered, during which the participants had to respond as quickly and accurately as possible, with their neuroelectric signals being recorded. Both EI groups then performed 30 min of moderate acute aerobic exercise on a motor-driven treadmill. After the acute aerobic exercise, body temperature was measured with tenth of a degree precision, and HR was assessed with a Polar HR monitor, with both measurements taken every 3 min. Since exerciseinduced hyperthermia and tachycardia are associated with P3 modifications (Geisler and Polich, 1990), once the participants’ body temperature and heart rate had returned to within 10% of pre-exercise levels (on average about 15— 20 min after a bout of acute exercise), blood was immediately withdrawn from them, and they then completed the cognitive task along with ERP recording again. With regard to the NEI group, after the first cognitive test they took a rest of about 47 min, during which they read magazines, and then they took the cognitive test again. All of the participants performed the cognitive test at the same time of day to control for circadian influences.

2.3. Cardiorespiratory endurance test Maximal cardiorespiratory endurance was measured using a modified Bruce Protocol treadmill test, which was carried out on a Medtrack ST55 Control Treadmill (Quinton Instrument Company, USA). This involved running on a treadmill, with both the speed and slope increasing every 3 min (Kalyani et al., 2008), until volitional exhaustion occurred or other criteria were met, as explained below. Each participant was first familiarized with the exercise equipment and then fitted with headgear and a mouthpiece to collect expired gases using semicomputerized open-circuit spirometry with the logic pathway on a Vmax system (Vmax Spectra Series Model 29, VIASYS Respiratory Care Inc., USA). This was needed to measure the following respiratory parameters, oxygen uptake (VO2), minute ventilation (VE), carbon dioxide output (VCO2), and respiratory exchange ratio (RER, VO2/VCO2), with a sampling interval of 20 s to determine the maximal oxygen uptake during the graded exercise test (GXT). Heart rate and rhythm were monitored during the GXT via electrocardiography (Yorba Linda, VIASYS Respiratory Care Inc., CA). A Polar HR monitor was also used to measure HR throughout the test. Each session included a 3-min warm-up period, followed by the period of exercise, and a 3-min cool down on a motor-driven treadmill. During the VO2max test, the participants were verbally encouraged to continue exercising until exhausted, and the test was terminated when three of the following four criteria were met (ACSM, 2000): (1) indication of maximal exhaustion; (2) peak HR reaching more than 90% of the theoretical age-predicted maximum (220 — age); (3) a plateau in oxygen consumption corresponding to

C.-L. Tsai et al. an increase of less than 150 mL in VO2 values, despite an increase in exercise workload; or (4) an RER greater than 1.15.

2.4. Moderate intensity aerobic exercise There was a minimal rest period of 48 h between the acute aerobic exercise and the GXT. Before the acute aerobic exercise, each participant was asked to wear a Polar HR monitor. After a 3-min warm-up on a motor-driven treadmill, the participant performed a 30-min bout of exercise at moderate intensity, corresponding to 60% of the individual VO2max value, as determined for each individual from the GXT, and then a 3-min cool down was performed.

2.5. The visuospatial attention paradigm A modified visuospatial attention task (Tsai et al., 2009) was used in the current study. All the stimuli were created and controlled using the Neuroscan Stim2 software (Neuroscan Ltd., EI Paso, USA) and presented on a black background. The central fixation point at the beginning of the process was designed to be a white fixation cross subtending a visual angle of 0.58  0.58, which was positioned midway between two empty white square boxes (each 2 cm  2 cm) on the same horizontal plane. The two empty boxes were arranged 1 cm from the fixation cross, and served as potential locations for target delivery. During each trial, the overall stimulus display remained the same, except for the white fixation cross, which was replaced by a yellow cue arrow. A trial commenced with a 3-s countdown followed 1000 ms later by the appearance of the two white stimulus square boxes and the white fixation cross which, in turn, were followed 1000 ms later by the replacement of the fixation cross by the yellow cue arrow. The cue was a single arrow (1.5 cm in length) which pointed to the right or left. After a further 350 ms interval between cue onset and the appearance of the target, a green circle target stimulus with a diameter of 1.6 cm appeared in the center of the right or left white stimulus box. After a response was made, the screen cleared and the next trial began 1500 ms later. If there was no response, the maximal inter-trial interval occurred 3 s after the target stimulus, and in such cases the computer program noted that there was a lack of response and started a new trial. Accordingly, the inter-trial interval was variable. Upon detection of the green circle target the participants were asked to press as quickly as possible the N or M button of the computer keyboard with the index or middle fingers of the dominant hand. Each participant completed 270 trials (90 trials  3 blocks), with a 3-min rest break after each block of trials, during which they remained at the workstation. Each block consisted of three conditions in a random order: (i) 54 valid conditions, where the target appeared in the stimulus box that had been indicated by the cue; (ii) 27 invalid conditions, where the target appeared in the stimulus box that was not the one indicated by the cue; and (iii) nine neutral conditions where the target appeared without any cue. The probability of the targets being presented in the right and left stimulus boxes was equal, and the direction of the arrow to the right or left was random and equally probable.

BDNF, acute exercise, cardiorespiratory fitness, and cognition

2.6. Psychophysiological recording methods Electroencephalographic (EEG) activity was measured at 18 electrode sites embedded in an electrocap (Quik-Cap, Compumedics Neuroscan Inc., El Paso, TX) according to the International 10—20 System, referenced to linked mastoid electrodes, with AFz placed on the forehead serving as the ground electrode, and skin impedance kept below 5 kV. To monitor possible artifacts due to eye movements, horizontal and vertical bipolar electrooculographic activity (HEOG and VEOG) was recorded using the adhesive electrodes placed on the supero-lateral right canthus and below and lateral to the left eye. The raw EEG signal was acquired with an A/D rate of 500 Hz/channel and a band-pass filter of 0.1—50 Hz, a 60-Hz notch filter, and written continuously to hard disk for offline analysis using Neuroscan Scan 4.3 software (Neuro Inc., EI Paso, TX, USA) (Tsai et al., 2009).

2.7. Blood sampling and analysis A 10-mL vein blood sample was withdrawn from the antecubital vein by a trained phlebotomist using an aseptic technique before two cognitive task tests, both before and after acute exercise, for the determination of serum BDNF levels. The blood was allowed to clot (BD Vacutainer Plus) and then centrifuged at 3000 rpm for 15 min at 4 8C (Hettich Mikro 22R, C1110). The supernatant was frozen and stored at 80 8C for further serum marker assays. The levels of serum BDNF were analyzed using a Chenikine BDNF sandwich (Cat. No. CYT306, Millipore, USA) with a detection range of 7.8—500 pg/ ml. The BDNF intra-assay and inter-assay variations were 3.7% (125 pg/ml) and 8.5% (125 pg/ml), respectively.

2.8. Data processing and analysis The behavioral performance [reaction times (RTs in milliseconds) and accuracy rate] was automatically calculated by Neuroscan Stim2 software. The RTs were discarded if an error was recorded [i.e., an orientation error (a button-pressing error, that is, the response was inconsistent with where the target actually appeared), and anticipatory or delay errors (responding sooner than 150 ms and later than 2000 ms after target onset, respectively)]. In terms of the ERP components, offline EOG correction was applied to the individual trials prior to averaging using a spatial filter. Trials with a behavioral error or artifacts (i.e., VEOG, HEOG, and electromyogram exceeding 100 mV) were rejected. The rest of the ERP data for correct trials were then separately averaged offline and constructed from the different conditions over a 1550 ms epoch, beginning 550 ms prior to target stimulus onset. The amplitude values for all ERP components relative to a 200 ms pre-cue baseline were calculated within latency windows centered on the peak latency of the grand mean ERP. Latencies were measured within the latency window for every participant. These windows were determined from inspection of the group grand average waveforms, and were equivalent for the ERP elicited by all conditions and participants. Since the endogenous Posner paradigm is more dependent on the activation of cortical attention areas, such as the parietal cortex and frontal lobes (Posner et al., 2007), the target-elicited P3 (defined as the major positive deflection

125 occurring 300—700 ms after the target) was distinguished and calculated over the Cz and Pz electrodes (Tsai et al., 2009). The CNV component (defined as a slow negative potential preceding the target) was calculated using the value of the mean area under this curve and given in mVms within a 160 ms latency window (from 110 ms before the target stimulus to 50 ms after the target stimulus, Tsai et al., 2009) at the Fz and Cz electrodes, since this component appears significantly at these two electrodes (Tsai et al., 2009). All independent variables (i.e., behavioral, ERPs, and biochemical index) from the acute bout of moderate aerobic exercise were analyzed with a repeated-measures ANOVA (RM ANOVA), with the main effects examined with time (pre- and post-exercise) as the within-subjects factor and group as the between-subjects factor, using mean RTs, separate ERP parameters (i.e., CNV and P3 amplitude) in the valid and invalid conditions (excluding the neutral condition, since the total number of trials was not sufficient to average the ERP components), and BDNF as the dependent variable. Where a significant difference occurred, Bonferroni post hoc analyses were performed. A value of p < .05 was considered to be significant. The significance levels of the F ratios were adjusted with the Greenhouse—Geisser correction if the assumption of sphericity was violated. Partial h2 (h2p ), a measure of effect size, was used for the group comparison to complement the significance testing, with the following standards used to determine the magnitude of the mean effect size: 0.01—0.059 representing a small effect, 0.06 to 0.139 a medium effect, and >0.14 a large effect size (Cohen, 1973). The changes in the biochemical marker (i.e., BDNF) and the behavioral and neuroelectric performances were examined with the Pearson product—moment correlation.

3. Results 3.1. Behavioral performance As seen in Fig. 1, the RM ANOVA on the RTs revealed significant main effects of group [F(2, 57) = 5.03, p = .010, h2p ¼ 0:15], time [F(1, 57) = 47.67, p < .001, h2p ¼ 0:46], and condition [F(1, 57) = 230.22, p < .001, h2p ¼ 0:80]. These main effects were superseded by the time  group [F(2, 57) = 15.83, p < .001, h2p ¼ 0:36] and time  condition [F(1, 57) = 10.20, p = .002, h2p ¼ 0:15] interactions. Post hoc analyses indicated that, before exercise, the EIH group only responded faster overall than the EIL one; the pre-exercise RTs were slower than the post-exercise ones only for the two EI groups; and the RTs for the valid condition were faster than those for the invalid one for all three groups. In terms of the mean accuracy rate, neither significant main effects of group and time, nor significant interactions between group and time ( ps > .20 in all cases), were obtained. There were also no other significant main effects or interactions.

3.2. ERPs performance 3.2.1. CNV There were significant main effects of group [F(2, 57) = 4.47, p = .016, h2p ¼ 0:14] on the CNV component, as well as time  group [F(2, 57) = 3.25, p = .046, h2p ¼ 0:10] and time  electrode  group [F(2, 57) = 5.94, p = .005, h2p ¼ 0:17]

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C.-L. Tsai et al.

Fig. 1 Behavioral performance (mean  SD) for the two exercise intervention groups (i.e., EIL and EIH for lower- and higher-fit young adults, respectively) before and after an acute bout of moderate aerobic exercise and one non-exercise-intervention (NEI) group before and after rest (*:p < .05).

interactions. Post hoc tests confirmed that the EIH group showed significantly larger negative-wave areas concerning the motor preparatory process after exercise compared to before exercise for the Fz (586.33  417.74 vs. 430.49  437.22 mVms, p = .005) and Cz (867.37  506.57 vs. 658.90  557.23 mVms, p = .001) electrodes, but the EIL group only showed significantly larger negative-wave values after exercise compared to before exercise for the Cz electrode (706.66  506.68 vs. 531.18  470.97 mVms, p = .011). In addition, electrode [F(1, 57) = 54.51, p < .001, partial h2 = 0.49] and the time  electrode [F(1, 57) = 8.59, p = .005, h2p ¼ 0:13] interaction also yielded a significant effect, with significantly larger values found only for the Cz electrode after exercise in comparison with before it (606.51  528.66 vs. 499.40  502.77 mVms, p = .021). 3.2.2. Target-evoked P3 amplitude The grand averaged ERP waveforms obtained for the three groups are shown in Fig. 2. There was a significant main effect of group [F(2, 57) = 8.43, p = .001, h2p ¼ 0:23] on the amplitude of the P3 component, reflecting the fact that the EIH (10.99 mV) group showed significantly larger P3 amplitudes than the EIL (6.84 mV) and NEI (7.06 mV) ones. Time [F(1, 57) = 6.70, p = .012, h2p ¼ 0:11] and time  group [F(2, 57) = 3.33, p = .043, h2p ¼ 0:11] also produced significant main effects, both indicating that the EIH group showed significantly greater P3 amplitudes than the EIL group before (EIH: 9.72 mV vs. EIL: 6.61 mV) and after (EIH: 12.27 mV vs. EIL: 7.08 mV) exercise, the EIH group only showed significantly greater P3 amplitudes than the NEI group after exercise (EIH: 12.27 mV vs. NEI: 7.14 mV), and only the EIH group showed significantly larger P3 amplitudes after exercise compared to before exercise ( p = .001). In addition, condition [F(1, 57) = 7.95, p = .007, h2p ¼ 0:12], electrode [F(1, 57) = 13.87, p < .001, h2p ¼ 0:20], and the condition  electrode [F(1, 57) = 21.63,

p < .001, h2p ¼ 0:28] interaction yielded a significant effect, with smaller values found in the valid condition (7.90 mV) in comparison with the invalid one (9.23 mV), and greater amplitudes at the Pz electrode (9.06 mV) as compared to the Cz one (8.07 mV).

3.3. BDNF response As seen in Fig. 3, time [F(1, 57) = 5.42, p = .023, h2p ¼ 0:09] and time  group [F(2, 57) = 3.70, p = .031, h2p ¼ 0:12] produced a significant interaction effect, reflecting the fact that the post-exercise BDNF levels were higher than the preexercise ones only for both EI groups. There were no significant correlations among the BDNF levels and behavioral (i.e., RTs and accuracy rate) and ERP (i.e., P3 amplitude and CNV) performances before and after acute exercise in any of the three groups. In addition, no significant correlations emerged among the changes in BDNF levels and changes in behavioral and ERP performances with acute exercise in any of the EI groups.

4. Discussion 4.1. Main findings The current study assessed the effects of acute aerobic exercise on a visuospatial attention task in individuals with different cardiorespiratory fitness levels, using a biochemical index to better characterize the relationship between such exercise and cognitive performance. The main findings were that shorter RTs and an increased central CNV area were shown following a bout of acute exercise for both EI groups. However, only the EIH group exhibited a larger P3 amplitude and increased frontal CNV area after the acute exercise. In

BDNF, acute exercise, cardiorespiratory fitness, and cognition

127

Fig. 2 Grand averaged ERP waveforms in the valid and invalid conditions for the two exercise intervention groups (i.e., EIL and EIH for lower- and higher-fit young adults, respectively) before and after an acute bout of moderate aerobic exercise and one non-exerciseintervention (NEI) group before and after rest.

addition, increased BDNF levels were also found after acute exercise for both EI groups. However, there was no significant correlation between the changes in BDNF levels and behavioral and neuroelectric performances. This study extends the findings of previous works and provides evidence for the

beneficial effects of acute aerobic exercise of moderate intensity on the performance of a visuospatial attention task, especially in young adults with high cardiorespiratory fitness. However, changes in circulating BDNF levels could not be a molecular mediator in the beneficial effects on behavioral

Fig. 3 Changes in BDNF levels (mean  SD) for the two exercise intervention groups (i.e., EIL and EIH for lower- and higher-fit young adults, respectively) before and after an acute bout of moderate aerobic exercise and one non-exercise-intervention (NEI) group before and after rest (*: p < .05).

128 and neuroelectric performances seen in young adults after acute aerobic exercise.

4.2. Behavioral index The EIH group showed shorter RTs before and after moderate acute aerobic exercise compared to the EIL group, providing support for the view that young adults with lower cardiorespiratory fitness suffer from a generalized reduction in the time efficiency of the central processing of cognitive functions, or greater difficulty in processing the precues and preparing intricate motor responses in real time. In addition, the difference between these RTresults may be due to the fact that using the endogenous Posner paradigm to assess the visuospatial information processing of the participants was appropriate, because the attention network test involves alerting, orienting, and executive attention components (Posner et al., 2007), which could be performed better in individuals with higher physical activity levels (Tsai et al., 2009). Therefore, physical fitness is related to shorter RTs for a cognitive task requiring greater amounts of top-down attention control, as seen in the current work. Moreover, as expected, the current findings indicated a shorter RT latency after an acute bout of moderate aerobic exercise, relative to before exercise, for task conditions across both EI groups. Indeed, since an inverted U-shaped relationship was found between exercise intensity and cognitive performance in previous studies (Kamijo et al., 2004, 2007), it was not surprising that the 30-min acute bout of moderate aerobic exercise used in this work did enhance the reaction processes (i.e., stimulus evaluation, response selection, and response execution) in both groups of young adults that underwent the acute exercise intervention. This is compatible with Pontifex et al.’s (2009) finding that acute aerobic exercise has beneficial effects on cognitive tasks requiring executive control, both immediately and 30 min after the exercise. This finding may be explained by the action of the intermediary factors, such as arousal, nervous system activation, or modification of humoral functioning (Joyce et al., 2009). Another explanation could be that the reticular-activating process leads to greater efficiency of the sensory and motor processes of the peripheral system on bottom-up processing after acute moderate intensity exercise (i.e., better synchronization of the motor units discharge), which results in faster RTs (Dietrich and Audiffren, 2011).

4.3. Neuroelectric index The CNV, a negative slow-wave cortical potential of an ERP that serves as a preparatory motor activity/readiness potential, reflects the processes of response preparation and evaluation in response to an imperative stimulus (Brunia and van Boxtel, 2001; Tsai et al., 2009). More specifically, frontal CNV is related to ‘‘cognitive’’ preparation processes, while central CNV is associated with ‘‘response’’ preparation ones (Kamijo et al., 2010). CNV can thus be used to examine whether physical fitness and/or an acute bout of moderate aerobic exercise enhance task preparation, which was assessed in this work in the interval between cue stimulus and onset of the following target stimulus requiring a motor response. In the current study, significantly larger CNV areas emerged post-exercise relative to pre-exercise at the central

C.-L. Tsai et al. lobe for both EI groups, indicating that the ‘‘response’’ preparation processes were more efficient after acute moderate aerobic exercise. However, only the EIH group exhibited larger CNV areas after acute exercise at the frontal lobe, suggesting that the function of ‘‘cognitive’’ preparation processes could be enhanced via acute moderate aerobic exercise for these individuals. Taken together, the finding that the post-exercise RTs were faster than the pre-exercise RTs for both EI groups could be explained by the differences among the CNV areas, since faster RTs might result from more efficient ‘‘motor’’ preparation process (Ishihara and Imanaka, 2007). As the central CNV is associated with ‘‘response’’ preparation processes (Kamijo et al., 2010), the greater CNV areas at the Cz electrodes for both EI groups after acute aerobic exercise support the positive effects of exercise on RT performance, casting aside the beneficial relation of aerobic fitness to ‘‘response’’ preparation processes. P3 is an ERP component typically associated with attentional stimulus evaluations, that is, the P3 amplitude is proportional to the amount of attentional resources allocated to a task (Tsai et al., 2009). In the present study, a trend for greater P3 amplitude was observed for higher- compared to lower-fit individuals, indicating that the former exhibited more efficient allocation of attentional resources when performing the cognitive task. In addition, the enhanced P3 amplitudes were only found for the EIH group after compared to before acute aerobic exercise in the current study, suggesting that such individuals might maintain a higher reactivity to acute exercise, which could induce increases in neural activation and physiological arousal, and thus enable them to allocate more attentional resources (Pesce et al., 2011). However, this difference in P3 amplitude is especially significant given the lack of fitness-related differences in behavioral performance (i.e., RTs) that were found in the current study, supporting the notion that selectively greater effects emerge for cognitive relative to motor processes as a function of fitness (Kamijo et al., 2010), as supported by the above-mentioned CNV findings. Interestingly, these findings were inconsistent with those of some previous studies, which indicted that physical fitness and acute exercise had no such effects on the P3 component (Magnie et al., 2000; Dustman et al., 1990). Three plausible reasons for the different effect of acute exercise on the P3 amplitude in the EIH and EIL groups are as follows. First, since young adults with higher cardiorespiratory fitness (i.e., the EIH group) showed higher physical activity levels (as seen from IPAQ data) and lower resting heart rates in the current study, they could spend less energy finishing the 30-min acute bout of aerobic exercise, as demonstrated in the previous study (Seiler et al., 2007), and thus could reserve more energy and allocate more attentional resources to perform the subsequent cognitive task. Second, the EIH group might be more sensitive to this kind of acute stress, and their brain nerves more adaptive and responsive to exercise induced stimulus. Third, higher serum BDNF levels in the EIH group could contribute to the neural efficiency, since BDNF is a molecular mediator of neural functioning (McAllister et al., 1999).

4.4. Brain-derived neutrophic factor Previous studies have demonstrated that acute endurance exercise leads to increases in BDNF in various brain regions

BDNF, acute exercise, cardiorespiratory fitness, and cognition and serum (Ferris et al., 2007). In the present study, BDNF levels rose after a bout of acute moderate aerobic exercise for both EI groups, in line with the findings of previous works which found that serum BDND concentrations were augmented after 25—30 min of moderate acute aerobic exercise (Gold et al., 2003). A previous study suggested that the activity dependence of BDNF may mean that it is particularly capable of mediating the beneficial effects of exercise on cognitive functioning (Vaynman and Gomez-Pinilla, 2005). However, although the BDNF levels rose for both EI groups after acute aerobic exercise, the increased levels were not significantly related to any changes in the behavioral or neuroelectric indices. These results are partially in accordance with those obtained in Ferris et al. (2007), which demonstrated that changes in BDNF concentrations after acute aerobic exercise did not correlate with changes in the performance of different cognitive tasks. It is likely that the elevated serum BDNF levels found during the recovery phase are transient after moderate acute aerobic exercise, based on the results of many previous studies, with a rapid decrease to basal concentration by the 10-min time point after 10-min acute exercise (Vega et al., 2006), 50-min time point after 15-min acute exercise (Tang et al., 2008), and the 60-min time point after 30-min acute exercise (Gold et al., 2003). Therefore, the beneficial effects of moderate acute aerobic exercise on cognition could thus be due to a temporary enhancement, rather than any long-term improvement in cognitive functioning. Indeed, as demonstrated in previous studies, only regular chronic aerobic exercise can effectively and stably elevate the basal BDNF levels in healthy young adults (Zoladz et al., 2008), and the long-term effects of regular exercise on neurocognitive performance should be more robust than the short-term ones after a single bout of exercise (Stroth et al., 2009). Additionally, since the enhanced cognitive and motor processes that have been found after an acute bout of aerobic exercise suggest an increase in arousal of the central nervous system (Magnie et al., 2000; Polich and Lardon, 1997), the beneficial effects found in the present study suggest that the biochemical markers regarding the general arousal effects derived from such exercise should be further investigated, especially among higher-fit individuals.

129

4.6. Final conclusions The finding of the present study that young adults with higher cardiorespiratory fitness exhibited better behavioral and ERP performances before acute exercise shows support for the cardiovascular fitness hypothesis, which states that physical fitness is a physiological mediator that benefits various aspects of cognitive functioning, possibly due to more oxygen being delivered to and utilized by the brain neurons (Etnier et al., 1997). Indeed, over the past few years there has been growing evidence of a positive relationship between aerobic fitness and cognitive functioning (Hillman et al., 2008). In terms of the effect of moderate acute aerobic exercise, the results of this study show that it enhanced response-related performance (i.e., RTs and central CNV) in both EI groups. However, cardiorespiratory fitness positively modulated the relation between acute exercise and cognition-process-related performance (i.e., P3 amplitude and frontal CNV) in younger adults with higher VO2max when performing the visuospatial attention task. That is, higher-fit individuals showed particular neural efficiency with regard to attentional resource allocation and cognitive preparation processes after moderate acute aerobic exercise, which means that the mechanisms underlying the effects of such exercise on cognitive functioning may be fitness dependent. In addition, although the BDNF levels were elevated after acute aerobic exercise in both EI groups, the changes in behavioral and neuroelectric performances after acute exercise could not be attributed to the change in BDNF levels. However, it is worth pointing out that BDNF is an important molecular mediator of neural efficiency in human brain (McAllister et al., 1999). We can thus not negate the possible role of BDNF in the beneficial effects of regular longterm aerobic exercise on neurocognitive functioning (Neeper et al., 1995).

Role of the funding source This research was supported by a grant from the National Science Council in Taiwan (NSC 100-2410-H-006-074-MY2).

Conflict of interest

4.5. Strengths and weaknesses

None declared.

Whether peripheral BDNF levels reflect the effects of brain BDNF levels on cognitive performance remains unclear in the literature (Elfving et al., 2010; Karege et al., 2002; Sartorius et al., 2009). In animal studies, although the correlation between peripheral and brain BDNF levels could not be observed in mature rats, Karege et al. (2002) found that the serum BDNF levels in newborn rats positively correlated with cortical levels, and thus peripheral BDNF levels could reflect brain BDNF levels (Karege et al., 2002; Sartorius et al., 2009). Additionally, we could not explain the relationship of each form of BDNF with the behavioral and neuroelectric indices, since the systemic BDNF levels measured in this study likely represent a mixture of the proBDNF and mature BDNF forms (Michalski & Fahnestock, 2003). More research is thus needed to clarify how accurately peripheral BDNF reflects brain BDNF in humans, and which form of BDNF is associated with behavioral and neuroelectric performance.

Acknowledgements This research was supported by a grant from the National Science Council in Taiwan (NSC 100-2410-H-006-074-MY2). The authors are also grateful to the participants who gave their precious time to facilitate the work reported here.

References Aberg, M.A., Pedersen, N.L., Toren, K., Svartengren, M., Backstrand, B., Johnsson, T., Cooper-Kuhn, C.M., Aberg, N.D., Nilsson, M., Kuhn, H.G., 2009. Cardiovascular fitness is associated with cognition in young adulthood. Proc. Natl. Acad. Sci. U. S. A. 106, 20906—20911. American College of Sports Medicine, 2000. ACSM’s Guidelines for Exercise Testing and Prescriptions, 6th ed. Lippincott, Williams, and Wilkins, Philadelphia.

130 Brunia, C.H., van Boxtel, G.J., 2001. Wait and see. Int. J. Psychophysiol. 43, 59—75. Bus, B.A., Molendijk, M.L., Penninx, B.J., Buitelaar, J.K., Kenis, G., Prickaerts, J., Elzinga, B.M., Voshaar, R.C., 2011. Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology 36, 228—239. Chapman, L.J., Chapman, J.P., 1987. The measurement of handedness. Brain Cogn. 6, 175—183. Cohen, J., 1973. Eta-squared and partial eta-squared in fixed factor ANOVA designs. Educ. Psychol. Meas. 33, 107—112. Colcombe, S., Kramer, A.F., 2003. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol. Sci. 14, 125—130. Dietrich, A., Audiffren, M., 2011. The reticular-activating hypofrontality (RAH) model of acute exercise. Neurosci. Biobehav. Rev. 35, 1305—1325. Dustman, R.E., Emmerson, R.Y., Ruhling, R.O., Shearer, D.E., Steinhaus, L.A., Johnson, S.C., Bonekat, H.W., Shigeoka, J.W., 1990. Age and fitness effects on EEG, ERPs, visual sensitivity, and cognition. Neurobiol. Aging 11, 193—200. Elfving, B., Plougmann, P.H., Muller, H.K., Mathe, A.A., Rosenberg, R., Wegener, G., 2010. Inverse correlation of brain and blood BDNF levels in a genetic rat model of depression. Int. J. Neuropsychopharmacol. 13, 563—572. Endres, M., Gertz, K., Lindauer, U., Katchanov, J., Schultze, J., Schro ¨ck, H., Nickenig, G., Kuschinsky, W., Dirnagl, U., Laufs, U., 2003. Mechanisms of stroke protection by physical activity. Ann. Neurol. 54, 582—590. Etnier, J.L., Salazar, W., Landers, D.M., Petruzello, S.J., Han, M., Nowell, P., 1997. The influence of physical fitness and exercise upon cognitive functioning: a meta-analysis. J. Sport Exerc. Psychol. 19, 249—277. Ferris, L.T., Williams, J.S., Shen, C.L., 2007. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med. Sci. Sports Exerc. 39, 728—734. Gold, S.M., Schulz, K.H., Hartmann, S., Mladek, M., Lang, U.E., Hellweg, R., Reer, R., Braumann, K.M., Heesen, C., 2003. Basal serum levels and reactivity of nerve growth factor and brainderived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J. Neuroimmunol. 138, 99—105. Geisler, M.W., Polich, J., 1990. P300 and time of day: circadian rhythms, food intake, and body temperature. Biol. Psychol. 31, 117—136. Heyman, E., Gamelin, F.X., Goekint, M., Piscitelli, F., Roelands, B., Leclair, E., Di Marzo, V., Meeusen, R., 2012. Intense exercise increases circulating endocannabinoid and BDNF levels in humans–—possible implications for reward and depression. Psychoneuroendocrinology 37, 844—851. Hillman, C.H., Castelli, D.M., Buck, S.M., 2005. Aerobic fitness and neurocognitive function in healthy preadolescent children. Med. Sci. Sports Exerc. 37, 1967—1974. Hillman, C.H., Erickson, K.I., Kramer, A.F., 2008. Be smart, exercise your heart: exercise effects on brain and cognition. Nat. Rev. Neurosci. 9, 58—65. Hillman, C.H., Snook, E.M., Jerome, G.J., 2003. Acute cardiovascular exercise and executive control function. Int. J. Psychophysiol. 48, 307—314. Hillman, C.H., Weiss, E.P., Hagberg, J.N., Hatfield, B.D., 2002. The relationship of age and cardiovascular fitness to cognitive and motor processes. Psychophysiology 39, 3030—3312. Ishihara, M., Imanaka, K., 2007. Motor preparation of manual aiming at a visual target manipulated in size, luminance contrast, and location. Perception 36, 1375—1390. Joyce, J., Graydon, J., McMorris, T., Davranche, K., 2009. The time course effect of moderate intensity exercise on response execution and response inhibition. Brain Cogn. 71, 14—19. Jung, S.H., Kim, J., Davis, J.M., Blair, S.N., Cho, H.C., 2011. Association among basal serum BDNF, cardiorespiratory fitness and

C.-L. Tsai et al. cardiovascular disease risk factors in untrained healthy Korean men. Eur. J. Appl. Physiol. 111, 303—311. Kalyani, M.N., Ebadi, A., Mehri, S.N., Jamshidi, N., 2008. Comparing the effect of fire-fighting protective clothes and usual work clothes on aerobic capacity (VO2max). Pak. J. Med. Sci. 24, 678—683. Kamijo, K., Nishihira, Y., Hatta, A., Kaneda, T., Wasaka, T., Kida, T., Kuroiwa, K., 2004. Differential influences of exercise intensity on information processing in the central nervous system. Eur. J. Appl. Physiol. 92, 305—311. Kamijo, K., Nishihira, Y., Higashiura, T., Kuroiwa, K., 2007. The interactive effect of exercise intensity and task difficulty on human cognitive processing. Int. J. Psychophysiol. 65, 114—121. Kamijo, K., O’Leary, K.C., Pontifex, M.B., Themanson, J.R., Hillman, C.H., 2010. The relation of aerobic fitness to neuroelectric indices of cognitive and motor task preparation. Psychophysiology 47, 814—821. Karege, F., Schwald, M., Cisse, M., 2002. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci. Lett. 328, 261—264. Lee, T.M., Wong, M.L., Lau, B.W., Lee, J.C., Yau, S.Y., So, K.F., 2014. Aerobic exercise interacts with neurotrophic factors to predict cognitive functioning in adolescents. Psychoneuroendocrinology 39, 214—224. Magnie, M.N., Bermon, S., Martin, F., Madany-Lounis, M., Suisse, G., Muhammad, W., Dolisi, C., 2000. P300, N400, aerobic fitness, and maximal aerobic exercise. Psychophysiology 37, 369—377. McAllister, A.K., Katz, L.C., Lo, D.C., 1999. Neurotrophins and synaptic plasticity. Annu. Rev. Neurosci. 22, 295—318. Michalski, B., Fahnestock, M., 2003. Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer’s disease. Brain Res. Mol. Brain Res. 111, 148—154. Neeper, S.A., Gomez-Pinilla, F., Choi, J., Cotman, C., 1995. Exercise and brain neurotrophins. Nature 373, 109. Pan, W., Banks, W.A., Fasold, M.B., Bluth, J., Kastin, A.J., 1998. Transport of brain-derived neurotrophic factor across the blood— brain barrier. Neuropharmacology 37, 1553—1561. Pereira, A.C., Huddleston, D.E., Brickman, A.M., Sosunov, A.A., Hen, R., McKhann, G.M., Sloan, R., Gage, F.H., Brown, T.R., Small, S.A., 2007. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc. Natl. Acad. Sci. U. S. A. 104, 5638—5643. Pesce, C., Cereatti, L., Forte, R., Crova, C., Casella, R., 2011. Acute and chronic exercise effects on attentional control in older road cyclist. Gerontology 57, 121—128. Polich, J., Lardon, M.T., 1997. P300 and long-term physical exercise. Electroencephalogr. Clin. Neurophysiol. 103, 493—498. Pontifex, M.B., Hillman, C.H., Fernhall, B., Thompson, K.M., Valentini, T.A., 2009. The effect of acute aerobic and resistance exercise on working memory. Med. Sci. Sports Exerc. 41, 927— 934. Posner, M.I., Rothbart, M.K., Sheese, B.E., 2007. Attention genes. Dev. Sci. 10, 24—29. Rasmussen, P., Brassard, P., Adser, H., Pedersen, M.V., Leick, L., Hart, E., Secher, N.H., Pedersen, B.K., Pilegaard, H., 2009. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp. Physiol. 94, 1062—1069. Ruscheweyh, R., Willemer, C., Kruger, K., Duning, T., Warnecke, T., Sommer, J., Volker, K., Ho, H.V., Mooren, F., Knecht, S., Floel, A., 2009. Physical activity and memory functions: an interventional study. Neurobiol. Aging 30, 1114—1124. Sartorius, A., Hellweg, R., Litzke, J., Vogt, M., Dormann, C., Vollmayr, B., Danker-Hopfe, H., Gass, P., 2009. Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry 42, 270—276. Schinder, A.F., Poo, M., 2000. The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci. 23, 639—645.

BDNF, acute exercise, cardiorespiratory fitness, and cognition Seiler, S., Haugen, O., Kuffel, E., 2007. Autonomic recovery after exercise in trained athletes: intensity and duration effects. Med. Sci. Sports Exerc. 39, 1366—1373. Stroth, S., Kubesch, S., Dieterle, K., Ruchsow, M., Heim, R., Kiefer, M., 2009. Physical fitness, but not acute exercise modulates event-related potential indices for executive control in healthy adolescents. Brain Res. 1269, 114—124. Tang, S.W., Chu, E., Hui, T., Helmeste, D., Law, C., 2008. Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects. Neurosci. Lett. 431, 62—65. Tomporowski, P.D., 2003. Effects of acute bouts of exercise on cognition. Acta Psychol. 112, 297—324. Tomporowski, P.D., Lambourne, K., Okumura, M.S., 2011. Physical activity interventions and children’s mental function: an introduction and overview. Prev. Med. 52 (Suppl. 1) S3—S9. Tsai, C.L., Pan, C.Y., Cherng, R.J., Hsu, Y.W., Chiu, H.H., 2009. Mechanisms of deficit of visuospatial attention shift in children

131 with developmental coordination disorder: a neurophysiological measures of the endogenous Posner paradigm. Brain Cogn. 71, 246—258. Van Praag, H., Kempermann, G., Gage, F.H., 1999. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266—270. Vaynman, S., Gomez-Pinilla, F., 2005. License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil. Neural. Repair 19, 283—295. Vega, S.R., Struder, H.K., Wahrmann, B.V., Schmidt, A., Bloch, W., Hollmann, W., 2006. Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res. 1121, 59—65. Zoladz, J.A., Pilc, A., Majerczak, J., Grandys, M., Zapart-Bukowska, J., Duda, K., 2008. Endurance training increases plasma brain derived neurotrophic factor concentration in young healthy men. J. Physiol. Pharmacol. 59 (Suppl. 7) 119—132.