The effect of acute exercise and fitness level on the aging brain, an investigation with fMRI

A growing body of evidence suggests that multiple cognitive domains can be
improved by physical exercise, either by a single bout of exercise or exercise
training (Colcombe & Kramer, 2003), but little is known about the effect of
exercise on working memory and temporal attention. The aging brain shows
bilateral brain activity in the prefrontal cortex (PFC), which is suggested to
be a compensation mechanism, during a variety of tasks. Recent studies suggest
acute exercise enhances bilateral activity in the PFC in older adults, while a
high fitness level leads to activation patterns similar to young adults.
However, this hypothesis has not been investigated with a working memory task.
Li et al. (2014) is the only neuroimaging study investigating the effect of
acute exercise on working memory using the N-back task. They found no
difference in behavioral performance, but did observe differences in
task-induced increases in activation of prefrontal regions among others. We
will attempt to expand their results by investigating the effect of acute
exercise on the N-back task in young and older adults. In addition, as one of
the hypotheses explaining the beneficial effect of exercise on cognition is
that it increases cerebral blood flow (CBF), we will investigate the effect of
acute exercise on CBF in rest.
There is also little knowledge about the effect of exercise on temporal
attention. Wu & Hillman (2013) showed that fitness level is positively related
to visual temporal attention in pre-adolescent children, measured with an
Attentional Blink (AB) task. The authors propose that high fitness levels
increase the control over the distribution of attentional resources. In the
proposed study, we will attempt to replicate and extend these results in young
and older adults. As a measure of fitness level, participants will perform a
submaximal exercise test. Whereas Wu & Hillman used electroencephalography
(EEG) to measure brain responses, we will measure pupil dilation signal
instead. Task-evoked pupil dilation is thought to reflect changes in attention
and has shown to be a reliable and more sensitive measure than EEG (Wierda et
al., 2012), thus requiring fewer trials.
With the proposed study, we will expand the knowledge about the effect
of an acute bout of exercise on CBF and working memory performance and
underlying neural correlates. As life-span is increasing and cognitive decline
increases with age, acquiring knowledge about the effect of exercise on
cognition would be especially of importance for the older population, as it may
contribute to future interventions to maintain cognitive functioning and
improve quality of life.

The main objective of the study is to investigate (1) whether acute exercise
influences brain responses to a working memory task, (2) the effect of acute
exercise on CBF responses to acute aerobic exercise and (3) whether fitness
level is related to temporal attention.

Participants will be asked to fill in questionnaires measuring health, amount
of hours playing video games and MRI compatibility and will be screened for in-
and exclusion criteria. During the first site visit, participants will practice
on a bicycle ergometer with the Borg RPE (rating of perceived exertion) Scale.
Then, questionnaires will be taken measuring general intelligence (MMSE),
levels of anxiety and depression (HADS), to ensure participants do not have
memory complains or high levels of anxiety or depression, as these could
influence task-performance. Then, participants will perform a submaximal
exercise test. During the second and third site visit, participants will
perform two Magnetic Resonance Imaging (MRI) session that will be
counterbalanced across subjects: an exercise session and control session.
During the second site visit, participants will be presented with two versions
of the AB task while pupil dilation signal is measured, followed by one of the
MRI sessions. The third site visit consists of three tests: Digit Symbol
Substitution Task, Dutch National Adult Reading Test, and Trail Making Test A
and B. In addition, the third site visit consists of the second MRI session. In
the exercise session, CBF and resting state scans will be taken of
participants, followed by a 20-minute period of aerobic exercise outside the
MRI scanner on a stationary bicycle, of which 15 minutes will be at 70% of the
maximal heart rate (HR).
Participants are asked to cycle for two minutes at RPE level 13. RPE 13 has
been shown to be equal to *moderate intensity* and approximately 74% of the
maximal HR. Then, CBF and resting state scans will be taken again, followed by
an N-back task. In the control session, participants will rest instead of
performing exercise outside the MRI scanner.

The burden associated with participation consists of four questionnaires via
post or email (with a duration of 30 minutes) and three site visits. The first
site visit will have a duration of approximately 90 minutes. Participants will
perform a submaximal exercise test at the SportsFieldLab. As participants fill
in a health questionnaire before the submaximal test, we consider the risks to
be minimal. The second site visit will have a duration of 171 minutes and the
third site visit will have a duration of 105 minutes. Pupil dilation will be
measured with an eye tracker during the AB tasks. Participants will keep their
head in a chin rest during all blocks to optimize eye-tracking and viewing
conditions. Concerning the MRI scanner, participants will be exposed to a
field-strength of 3 Tesla and scanner noise. Thus far, there is no evidence to
suggest that exposing humans to a magnetic field of this strength has a
negative influence on their health. With regard to the noise, earplugs and
headphones will be provided. If evident abnormalities in the brain are noticed,
then the General Practitioner, who is indicated by the participant, will be
notified.

Subjects will not benefit directly from participating in the study, however the
data collected during this study will enhance understanding of the complex
relationship between physical fitness, acute exercise and cognition. As life
expectancy is increasing and cognitive decline increases with age, acquiring
knowledge about the effect of exercise on cognition would be especially of
importance for the older population, as it may contribute to future
interventions to maintain cognitive functioning and improve quality of life.