ArticlePDF AvailableLiterature Review

Abstract

An emerging body of multidisciplinary literature has documented the beneficial influence of physical activity engendered through aerobic exercise on selective aspects of brain function. Human and non-human animal studies have shown that aerobic exercise can improve a number of aspects of cognition and performance. Lack of physical activity, particularly among children in the developed world, is one of the major causes of obesity. Exercise might not only help to improve their physical health, but might also improve their academic performance. This article examines the positive effects of aerobic physical activity on cognition and brain function, at the molecular, cellular, systems and behavioural levels. A growing number of studies support the idea that physical exercise is a lifestyle factor that might lead to increased physical and mental health throughout life.
Participation in physical activity has been
associated with the reduction of a number
of physical (for example, cardiovascular
disease, colon and breast cancer, and obes-
ity) and mental (for example, depression
and anxiety) disorders across the adult
lifespan
1
. Despite mounting evidence for
the importance of physical activity, 74% of
adults in the United States do not meet the
recommended guideline of at least 30 min-
utes of moderate-intensity physical activity
on most days of the week
1,2
. Recent evidence
further indicates that children are growing
increasingly sedentary and unfit, and that
these lifestyle factors are related to an earlier
onset of several chronic diseases (such as
type II diabetes and obesity), which typically
do not emerge before adulthood
3
. As a result,
recent estimates have indicated that younger
generations, for the first time in United States
history, might live less healthy lives than their
parents
4–5
. The economic cost of this seden-
tary lifestyle is enormous in both developed
and developing countries, with estimates
indicating that inactivity was associated with
2.4% of healthcare expenditures in 1995
(REF. 6) and ~US$76 billion in medical costs
in the year 2000 (REF. 7). Canadian estimates
concur, as 2.5% (or $2.1 billion) of the total
direct healthcare costs for the year 1999 were
related to physical inactivity
8
.
In addition to the physical and economic
impact of physical inactivity, a growing body
of literature has linked physical activity with
improvements in brain function and cogni-
tion. Animal research has long shown that
enriched environments, including access to
exercise equipment (such as running wheels),
has a positive effect on neuronal growth and
on the neural systems that are involved in
learning and memory, indicating that physi-
cally active behaviours influence cognitive
function and the supporting brain struc-
tures
9
. A similar perspective has emerged
in human research
10
; with recent advances in
neuroimaging techniques showing that
exercise leads to evident changes in brain
structure and function. These findings
allow for a better understanding of the
implications of specific lifestyle factors for
cognitive health.
Although the roots of a mind–body
connection can be traced back to at least
the ancient Greek civilization, the scientific
investigation of the relation between
physical activity and cognition began in
the 1930s. Evidence for a relationship
between physical conditioning and faster
reaction time was observed during the next
several decades
11–13
(although some studies
indicated no such relationship
14
). The first
systematic examination of this relation-
ship began in the 1970s, with findings
indicating that older adults who regularly
participated in physical activity had faster
psychomotor speed, relative to their sed-
entary counterparts, on simple and choice
reaction-time tests. Interestingly, no such
relationship was observed in comparable
groups of younger adults
15–18
, suggesting
that the benefits of physical activity on
cognition were specific to older adults (see
REF. 19 for a review). With recent technical
advancements, contemporary research
has sought to understand the mechanisms
that underlie the influence of exercise
participation on cognition.
Here we describe the latest research,
in both humans and non-human animals,
on the relationship between physical
activity (primarily aerobic exercise) and
cognition. The research with humans has
mostly focused on the effects of exercise
on cognitive processes, as assessed with
paper-and-pencil and computer-based tests.
However, neuroimaging techniques, such as
event-related brain potentials (ERP) and struc-
tural and functional MRI, are also being
used to examine the link between exercise
and cognition. Non-human animal research
takes this investigation one step further,
revealing some of the molecular and cellular
changes that occur in the brain following
exercise training. The findings we describe
could have important implications for future
healthcare and education policies.
Human research
Physical activity effects on cognition during
childhood and young adulthood. Despite
the fact that children in industrialized
countries are growing increasingly unfit and
unhealthy owing, in part, to the comforts of
technological advancements, the investiga-
tion of the effects of physical activity on
cognitive health during development has
received surprisingly little attention. In
S C I E N C E A N D S O C I E T Y
Be smart, exercise your heart:
exercise effects on brain and
cognition
Charles H. Hillman, Kirk I. Erickson and Arthur F. Kramer
Abstract | An emerging body of multidisciplinary literature has documented the
beneficial influence of physical activity engendered through aerobic exercise on
selective aspects of brain function. Human and non-human animal studies have
shown that aerobic exercise can improve a number of aspects of cognition and
performance. Lack of physical activity, particularly among children in the developed
world, is one of the major causes of obesity. Exercise might not only help to improve
their physical health, but might also improve their academic performance. This
article examines the positive effects of aerobic physical activity on cognition and
brain function, at the molecular, cellular, systems and behavioural levels. A growing
number of studies support the idea that physical exercise is a lifestyle factor that
might lead to increased physical and mental health throughout life.
58
|
JANUARY 2008
|
VOLUME 9 www.nature.com/reviews/neuro
PERSPECTIVES
© 2008 Nature Publishing Group
Mathematics achievement
Reading achievement
Aerobic capacity
Aerobic capacity
y = 150.44 + 0.68906x R
2
= 0.232
y = 150.64 + 0.57422x R
2
= 0.160
0
10 20 30 40 50 60 70 80
100
120
140
160
180
200
0
10 20 30 40 50 60 70 80
100
120
140
160
180
200
Nature Reviews | Neuroscience
PFC
Intraparietal
sulcus
PCC
fact, only a handful of studies using true
experimental designs exist in the literature
and, arguably, these studies have done
little to advance our understanding of the
mechanisms by which exercise influences
brain function and cognition. A recent
meta-analysis determined a positive relation
between physical activity and cognitive
performance in school-age children (aged
4–18 years) in eight measurement categories
(perceptual skills, intelligence quotient,
achievement, verbal tests, mathematic tests,
memory, developmental level/academic
readiness and other). A beneficial relation-
ship was found for all categories, with the
exception of memory, which was unrelated
to physical activity behaviour
20
, and for
all age groups (although it was stronger
for children in the age ranges of 4–7 and
11–13 years, compared with the age ranges
of 8–10 and 14–18 years)
20
. The effect size
(ES) observed by Sibley and Etnier
20
in their
meta-analysis was 0.32 (standard deviation
= 0.27), which is similar to that which was
observed in a meta-analysis of the effects of
physical activity on cognition (ES = 0.25)
across the lifespan (6–90 years)
21
. These
findings suggest that although physical
activity might be beneficial at all stages of
life, early intervention might be important
for the improvement and/or maintenance of
cognitive health and function throughout
the adult lifespan.
Recently, research efforts have focused
on the relation between physical activity and
the academic performance of school-age
children (BOX 1). Several studies have sug-
gested that participation in physical activity
has either a positive relation or is unrelated
to academic performance, with differences
across studies probably reflecting the tech-
niques that were used to assess behaviour
and/or the aspects of scholastic aptitude
that were measured (achievement testing,
grade-point average and academic records,
for example)
22–24
. Regardless of the measure,
these studies indicated that an increase in
the amount of time dedicated towards physi-
cal health-based activities (such as physical
education) is not accompanied by a decline
in academic performance. The implications
of these findings are important for promot-
ing better physical health, without the loss
of other educational benefits, in school-age
children.
Similar to the situation with children,
there is a dearth of research on exercise–
cognition effects in young adults. Although
exceptions exist, especially with regards to
acute exercise effects on cognition
25–26
(see
REF. 27 for a review), most research has used
Box 1 | Physical activity and academic performance in school-age children
Recently, owing to the increasing importance placed on standardized testing, many schools in the
United States have reduced or eliminated physical education (PE) requirements, in an effort to
increase students’ academic performance. However, no empirical evidence exists to suggest that
the elimination of non-academic programmes (such as PE) is related to higher academic
achievement. In fact, empirical evidence suggests otherwise. Aerobic fitness has a small but
positive relation to academic achievement, whereas body mass index (BMI) has a negative
relation
23
. Recent studies have indicated that achievement in standardized tests of mathematics
(the left-hand graph in the figure) and reading (the right-hand graph in the figure) was positively
related to physical fitness scores, measured using the progressive aerobic cardiovascular
endurance run (PACER) test (a 20 metre shuttle run that increases in difficulty and is considered a
field test of aerobic capacity), in school-age children
88
. This relationship was selective to aerobic
fitness, as muscle strength and flexibility fitness were unrelated to academic achievement
23
.
Similarly, beneficial relationships have been observed between physical activity and other
measures of academic performance, such as academic grades in the classroom
24,89–90
.
Relevant neural networks have been identified for component processes that might be involved in
mathematics and reading performance (see the lower two panels of the figure). Research that
examined the functional neuroanatomy of reading comprehension revealed an activation of the
prefrontal cortex (PFC) and parietal/posterior cingulate cortex (PCC)
91
. Likewise, mathematical
calculations and numerical magnitude processing have been linked to bilateral regions of the
intraparietal sulcus in children and adults
92–94
. However, children also recruit the right dorsolateral
prefrontal cortex
92,94
. Given that both mathematics and reading elicit activation in the frontoparietal
network, there is a sound basis for examining these structures in relation to academic performance.
As fitness has also been related to the frontoparietal network
48,53,55
, it would follow that children
might derive benefits in school performance from increased participation in physical activity.
Finally, a few studies have indicated that physical activity is unrelated to academic performance.
For example, a study that relied on the self-reported teacher perception of studentsphysical activity
did not find a relation with academic performance
22
. However, another study
95
reported that pupils
who engaged in vigorous physical activity performed better in school than those that performed
moderate or no physical activity. Sallis et al.
96
observed a trend for improved achievement test scores
following physical activity, but the relationship might have been blunted because the school district
examined was one with historically high test scores. Collectively these data indicate that, at the very
least, time spent in physical activity programmes does not hinder academic performance, and it
might indeed improve performance. Given the positive health benefits that are derived from
physical activity, these studies support PE as an important component of childrens health and
wellbeing. Bottom panels adapted from REF. 97 (1996) Appleton & Lange.
P E R S P E C T I V E S
NATURE REVIEWS
|
NEUROSCIENCE VOLUME 9
|
JANUARY 2008
|
59
© 2008 Nature Publishing Group
Nature Reviews | Neuroscience
Effect size
Task type
Control
Exercise
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Executive Controlled Spatial Speed
younger adults merely for the purpose of
comparison with older adults, to provide
a basis for age-related deficits in cognitive
function and to better understand the pro-
phylactic or ameliorative effects of chronic
physical activity participation on cognitive
ageing. One obvious reason for this paucity
of literature is that cognitive health peaks
during young adulthood
28
, suggesting that
there is little room for exercise-related
improvement to cognitive function dur-
ing this period of the lifespan. However,
recent trends indicating a declining health
status among children
3
suggests that future
research should extend to periods of the
lifespan that are characterized by peak
cognitive health.
There is a small body of literature that
examines neurophysiological indices of
the benefits of chronic physical activity
participation on cognitive function in
young adults; however, the vast majority
of this research is focused on cognitive
ageing (see below). Future research in
this area needs to continue to build the
physical activity–cognition literature base,
similar to that for older adults and, if it
is to have societal implications, it should
also focus on bridging the gap between
the basic mechanisms that underlie the
effects of exercise on the brain and applied
aspects of cognition related to classroom
and job performance.
Physical-activity effects on cognition
during older adulthood. The study of
exercise and cognition with older adults
dates back several decades. Recently the
exercise–cognition relation in older adults
has been strengthened by the observation,
in prospective epidemiological studies,
that there are a number of lifestyle factors
— including intellectual engagement, social
interaction, diet and physical activity — that
are associated with the maintenance of
cognitive function and a reduction in risk for
age-associated neurodegenerative disorders,
such as Alzheimer’s disease and vascular
dementia
9,29–30
.
A small but growing number of rand-
omized intervention studies have examined
whether fitness training has a positive effect
on different aspects of perception and cogni-
tion in older adults. These studies generally
enrol healthy but sedentary adults between
the ages of 60 and 85 years and ask them
to participate in an exercise regime several
times per week over the course of several
months to several years. Cognition and
fitness is assessed before and after the inter-
vention. The central question is whether
individuals who participate in an aerobic
training regime show larger gains in cogni-
tion than wait-list control subjects or control
subjects who participate in non-aerobic
regimes, such as toning and stretching. In
one example
31
, older adults were randomized
into a pool-based aerobic exercise group or a
wait-list control. All participants were tested
with a series of single and dual auditory and
visual discrimination tasks both before and
after the 10-week intervention. Participants
in the aerobic training programme, but not
those in the control group, showed signifi-
cant improvement in dual-task performance
over the 10-week period. Improvements in
single-task performance were equivalent for
the two groups.
Although a number of intervention
studies have found improvements in
performance on cognitive tasks for aerobi-
cally trained but not control subjects, other
studies have found equivalent performance
improvements for both aerobic and control
subjects across cognitive tests. Given that the
number of randomized intervention trials
that have examined fitness training effects
on cognition is relatively small, and that
the particulars of these studies were varied,
there are a number of factors that might be
responsible for the mixed pattern of results.
Some of these factors include: the cognitive
processes examined; the length, intensity
and type of exercise programme; the age
range, health and education of participants;
and the manner in which fitness improve-
ments were measured. Fortunately, a few
meta-analyses have been conducted in
recent years to determine first whether the
fitness–cognition effect is robust across
the literature and second which factors
might moderate this relation
32–34
. Several
important results have been obtained from
these meta-analyses, which examined par-
tially overlapping sets of studies. First, and
perhaps most importantly, the effect size in
each meta-analysis was significant. That is,
in all studies, physical activity had a positive
effect on cognition. Second, a significant
relationship between physical activity train-
ing and improved cognition was obtained
for both normal adults and patients with
early signs of Alzheimers disease, in which
memory or cognitive ability was mildly
impaired
32–34
. Thus, it appears that physical
activity can have a positive effect on a wide
range of cognitive functions. Several other
moderator variables were also revealed
32
. As
indicated in FIG. 1, physical-activity training
appears to have both broad and specific
cognitive effects: broad in the sense that
various different cognitive processes benefit
from exercise participation, and specific in
the sense that the effects on some cognitive
processes, especially executive control proc-
esses (which include scheduling, planning,
working memory, multi-tasking and dealing
with ambiguity), are disproportionately
Figure 1 | Meta-analytic findings of exercise-training effects on cognition in older adults. The
results of a meta-analysis of the effects of fitness training on cognition showed that the benefits of
fitness training on four different cognitive tasks were significant. As illustrated in the figure, fitness
training has both broad and specific effects. The effects are broad in the sense that individuals in
aerobic fitness training groups (represented by the red bars) showed larger fitness training effects
across the different categories of cognitive processes illustrated on the x-axis. They are specific in the
sense that fitness training effects were larger for some cognitive processes, in particular executive
control processes, than for other cognitive processes. Figure reproduced, with permission, from REF. 32
(2003) Blackwell Publishers.
P E R S P E C T I V E S
60
|
JANUARY 2008
|
VOLUME 9 www.nature.com/reviews/neuro
© 2008 Nature Publishing Group
larger. This is particularly interesting as
executive control processes, and the brain
regions that support them (chiefly the
prefrontal cortex), show substantial age-
related deterioration the findings suggest
that even processes that display substantial
age-related change are amenable to interven-
tion. Additionally, the relationship between
physical activity training and cognition was
also influenced by programme duration, age,
gender
35
and type
32
.
In summary, although there are a mul-
titude of unanswered questions regarding
physical activity and cognition in older
adults, there is evidence of a relationship
between fitness training and improvements
in various aspects of cognition across a
broad range of ages. Collectively, the find-
ings suggest that physical activity is benefi-
cial across the human lifespan. However, the
mechanisms that underlie this relationship
are unclear and might differ during develop-
ment and ageing, as the brains of children
are still developing and undergoing organi-
zation whereas the brains of adults are not.
Physical activity during childhood might
encourage optimal cortical development,
promoting lasting changes in brain structure
and function. Future research should address
whether the mechanisms that support the
physical activity–cognition relationship are
different in children and adults.
Neuroimaging studies of physical activity
in humans. Neurophysiological studies
have revealed differences in cognitive
function that are related to physical activity
behaviour. Examination of baseline spectral
frequency distributions of electroencephalo-
grams (EEGs) has revealed increased activa-
tion in the theta (4–8 Hz), alpha (8–13 Hz)
and beta (13–20 Hz) spectral bands, and
higher mean frequency in the delta (0.25–4
Hz), theta and beta bands in more active or
aerobically fit individuals
36–39
. These findings
suggest that physical activity influences
baseline electrocortical function and, thus,
that it might affect cognitive operations.
Support for this influence is garnered from
the finding that inter-individual variability
in spectral frequency activation is related to
individual variations in the P3 component
of the ERP
40–41
, which has been found to be
especially sensitive to changes in physical
activity participation and aerobic fitness.
Research conducted over the past two
decades has described both aerobic fitness-
and physical activity-related differences
in the amplitude and latency of the P3
component in pre-adolescent children
42
,
young adults
43–44
and older adults
37,45–46
. This
component appears to be generated by a
network of neural structures, including the
frontal lobe, the anterior cingulate cortex
(ACC), the infero-temporal lobe and the
parietal cortex, that are involved in cognitive
operations, including stimulus processing
and memory updating
47
. Consistent and
robust findings have emerged: larger ampli-
tude and shorter latency P3s are observed
across a variety of cognitive tasks in indi-
viduals with high aerobic fitness compared
with unfit individuals. These results indicate
that greater amounts of physical activity
or aerobic fitness are generally beneficial
to cognitive processes that are related to
the allocation of attentional resources and
faster cognitive processing during stimulus
encoding. In agreement with these findings,
functional MRI (fMRI)
48
and behavioural
49–50
data show a physical activity-related modu-
lation that is disproportionately larger for
task components that necessitate greater
amounts of executive control
49
.
More recently, neurophysiological
research has focused on response-monitoring
processes elicited by the evaluation of con-
flict during instances of erroneous action.
Specifically, smaller error-related negativity
(ERN) amplitude following error com-
mission has been observed in more active
older adults
51
and fit young adults than in
unfit individuals of similar age
26
. Given that
source-localization techniques, such as dipole
modelling
52
, have localized the generation
of the ERN to the caudal portion of the
ACC, these findings corroborate previous
fMRI research that showed reduced activa-
tion of the ACC in fit older adults during
participation in tasks that required variable
amounts of executive control relative to unfit
individuals
48
(BOX 2). The implication of these
findings is that greater amounts of physical
activity and/or fitness might be associated
with a reduction in task-related response
conflict owing to increased top-down control
during task execution. Physical activity-
related influences on task performance are
further observed through the regulation
of top-down control, as more active and fit
individuals exhibit longer reaction times on
trials following erroneous action
26,51
.
MRI has also been used to examine the
effects of fitness on cognition. For example,
in cross-sectional comparisons between
individuals with high and low levels of
fitness and aerobic fitness training studies,
Colcombe and colleagues
48,53
found that
higher levels of fitness and fitness improve-
ments were related to larger volumes of
prefrontal and temporal grey matter, as
well as anterior white matter (see also
REFS 54,55). Such increases in brain volume
have previously been shown to be predictive
of performance in older adults
35,55
.
Aerobic fitness training has also been
found to induce changes in patterns of
functional activation using fMRI. For
example, older adults who participated
in a walking intervention over a 6-month
period showed increases in activation in the
middle frontal gyrus and superior parietal
cortex and decreases in activation in the
ACC, relative to a non-aerobic toning and
stretching control group
48
. These changes
in patterns of fMRI activation were related
to significant and substantial improvements
in the performance of a selective-attention
task. More recently, increases in measures
Glossary
Aerobic fitness
The maximal capacity of the cardiorespiratory system
to take up and use oxygen.
Behavioural conflict
The indecision that arises when multiple conflicting
responses can be elicited in response to a stimulus.
Dipole modelling
A method to determine the location of the sources that
underlie the responses measured in an electro-
encephalographic experiment. It provides an estimate of
the location, orientation and strength of the source as a
function of time after the stimulus was presented.
Error-related negativity
(ERN). A negative deflection in a response-locked ERP that
reflects neural correlates of action monitoring that is
associated with the evaluation of conflict.
Event-related brain potential
(ERP). A time-locked index of neuroelectrical activation
that is associated with specific cognitive processes.
Executive control
Computational processes involved in the selection,
scheduling and coordination of complex cognitive functions.
Exercise
Repetitive and planned physical activity with the goal of
maintaining or improving physical fitness.
P3
A positive deflection in a stimulus-locked ERP that reflects
changes in the neural representation of the stimulus
environment and is proportional to the amount of attention
that is required to encode a given stimulus (amplitude) as
well as the speed of stimulus evaluation (latency).
Physical activity
Bodily movement produced by skeletal muscles with the
expenditure of energy.
Top-down control
Refers to an individual’s ability to selectively process
information in the environment. Top-down control relies on
an observer’s expectancies about events in the
environment, knowledge of and experience with similar
environments, and the ability to develop and maintain an
attentional set for particular kinds of environmental events.
P E R S P E C T I V E S
NATURE REVIEWS
|
NEUROSCIENCE VOLUME 9
|
JANUARY 2008
|
61
© 2008 Nature Publishing Group
Nature Reviews | Neuroscience
ACC
SPLSPL
MFG
Z = 23 Z = 52 X = 4
10
8
6
4
2
0
–2
–4
–6
–200 –100 0 100 200 300 400 500 600
Time (ms)
Amplitude (µV)
Higher-fit error
Higher-fit correct
Lower-fit error
Lower-fit correct
of cerebral blood volume (CBV) in the
dentate gyrus of the hippocampus were
observed in a small group of middle aged
participants in a 3-month fitness training
study
56
. The increases in CBV were associ-
ated with improvements in verbal learning
and memory and cardiorespiratory fitness.
The regional specificity of the CBV changes
are particularly interesting, given previous
demonstrations of neurogenesis in the
dentate gyrus
57–59
as well as the association
between increased CBV and neurogenesis
in mice
56
. CBV changes in the hippocampus
might serve as a biomarker for neurogenesis
in humans.
Non-human animal research
Research on humans has demonstrated
improved cognitive performance as a result
of physical activity in both children and
older adults. However, there are clearly limi-
tations on the extent to which the human
brain can be examined with neuroimaging
techniques. Non-human animal research
can directly examine the cellular and
molecular cascades that are triggered by
exercise, which in humans can only be indi-
rectly examined and inferred. Additionally,
investigating the effect of exercise in non-
human animal populations has the benefit
of markedly reducing some of the inherent
confounding variables that are often
present in human studies (for example,
lack of adherence to treatment protocols,
and covariation with other lifestyle factors,
such as social interaction and diet with an
exercise intervention) while also providing
a translational and cross-species approach
to studying exercise-induced neural and
cognitive plasticity.
An increase in cell proliferation and cell
survival in the dentate gyrus of the hip-
pocampus is one of the most consistently
observed effects of exercise treatment
57–61
.
Exercise-induced hippocampal cell prolif-
eration and cell survival can occur at many
stages of development, including young
adulthood
58
, and in old age
62
. Even newborn
pups with mothers that had carried out aero-
bic exercise during the gestational period of
the pregnancy exhibited a greater number
of surviving cells in the hippocampus than
pups born from sedentary mothers
63–64
.
The functional significance of hippocampal
neurogenesis and the survival of the new neu-
rons is a source of great controversy, but the
behavioural performance improvements that
are associated with exercise treatments sug-
gest that these newborn cells might facilitate
learning and memory. Furthermore, demen-
tias such as Alzheimers disease are character-
ized by a marked reduction in the number of
neurons in the hippocampus, which might be
alleviated, in part, by increased neurogenesis
resulting from aerobic activity.
The proliferation of new cells in the
brain is accompanied by an increased
need for nutrients. This demand is met
by the stimulation of new blood vessel
growth in the cortex
65
, the cerebellum
66
,
the striatum
67
and the hippocampus
68
.
The growth of new vasculature might be
Box 2 | Physical activity and the anterior cingulate cortex
Physical activity has been found to enhance
cognition, with a selectively larger effect on
executive control functions compared with
other cognitive processes
32,50,98
. Accordingly,
brain structures that mediate executive
functions would be expected to show
disproportionate changes as a result of
participation in physical activity. One such
structure is the anterior cingulate cortex (ACC),
which is part of the brain’s limbic system and
has connections with multiple brain structures
that process sensory, motor, emotional and
cognitive information
99
. Two convergent lines
of research indicate that physical activity
exerts a substantial influence on the ACC and the concomitant executive processes that it mediates.
Neuroimaging research that examined the effects of changes in fitness on the ACC found that
aerobically trained older adults exhibited a reduction in activation (see figure, top panels), with a
concomitant decrease in behavioural conflict, during a task that required variable amounts of
executive control, relative to untrained individuals
48
. Furthermore, increased activation of the dorsal
prefrontal and parietal brain regions involved with task-related inhibitory functioning was
observed
48
, suggesting an increased ability of the frontal attentional network to bias task-relevant
activation in the posterior cortex
48
.
These findings are supported by neurophysiological and task-performance data
26,51
, which
demonstrated a reduction in error-related negativity (ERN) amplitude
52
; an event-related brain
potential (ERP) component with its primary neural generator in the caudal ACC (see figure, bottom
panel) . This reduction in the ERN amplitude was associated with greater regulation of behavioural
responses for physically active younger and older adults compared with inactive individuals. These
findings suggest an improvement in task performance in aerobically active individuals through a
reduction in conflict-related activation of action monitoring processes, resulting in a more efficient
neurophysiological profile. Collectively, convergent evidence supports the view that higher levels of
physical activity correlate with increased top-down control, which could be mediated through more
efficient activation of the ACC, resulting in better performance during tasks requiring executive
control. MFG, middle frontal gyrus; SPL, superior parietal lobule. Coordinates for the locations of
the clusters are given in Montreal Neurological Institute space. Top panel reproduced, with
permission, from REF. 48 (2004) National Academy of Sciences. Bottom panel reproduced,
with permission, from REF. 26 (2006) Elsevier Science.
P E R S P E C T I V E S
62
|
JANUARY 2008
|
VOLUME 9 www.nature.com/reviews/neuro
© 2008 Nature Publishing Group
dependent on the presence of molecules
such as vascular endothelial growth factor
(VEGF) and insulin-like growth factor 1
(IGF1). For example, systemic injection of
IGF1 effectively stimulates angiogenesis
in the brain, and inhibiting IGF1 reduces
angiogenesis. IGF1 might induce new blood
vessel formation through the regulation of
VEGF
68
, a growth factor that is prominently
involved in blood vessel formation and
development. Aerobic exercise increases
the production and release of both IGF1
and VEGF in young rodents, leading to the
formation of new blood vessels. It is likely
that angiogenic processes resulting from
aerobic activity occur both in childhood
and in old adulthood
67
(however, see REF. 62
for an exception).
Besides IGF1 and VEGF, brain-derived
neurotrophic factor (BDNF) is another
molecule that is consistently demonstrated
to be upregulated with exercise treatments
69
.
BDNF has been shown to be necessary for
long-term potentiation (LTP), a neural ana
-
logue of long-term memory formation, and
for the growth and survival of new neurons.
Blocking the binding of BDNF to its tyrosine
kinase receptor (TRKB) abolishes LTP and
neurogenesis. Additionally, BDNF levels in
the hippocampus have been directly related
to the enhanced learning and memory proc-
esses that are observed with exercise treat-
ments in rodents
70
. Even in humans, serum
concentrations of BDNF are increased after
acute exercise regimens
71
in both young
adults and patients with multiple sclerosis
72
.
Increases in BDNF levels in response to an
exercise treatment could be an important
finding, as serum and cortical concentra-
tions of BDNF are reduced in Alzheimer’s
disease, Parkinsons disease, depression,
anorexia and many other diseases. Aerobic
activity might be neuroprotective, prevent-
ing the development of certain cognitive and
neural symptoms that are associated with
these diseases, through the regulation of
BDNF secretion
73
.
In summary, non-human research
strongly supports the positive effects of exer-
cise on cognition: aerobic activity improves
learning and task acquisition, increases the
secretion of key neurochemicals associated
with synaptic plasticity and promotes the
development of new neuronal architecture.
In addition, non-human animal research is
not only consistent with human literature
on aerobic activity, but also provides some
important mechanistic claims for how exer-
cise exerts its effects on the nervous system
in humans (see REF. 74 for an in-depth
review of the cellular and molecular effects
of exercise in non-human animals). Despite
having gained some mechanistic insights,
a large number of questions regarding the
generality of the effects of exercise on learn-
ing, the molecular and genetic transcription
cascades that result from exercise and the
durability of the effects, remain unresolved.
Although there are many missing links
between the human neuroimaging results
and non-human molecular and cellular
work, both bodies of research suggest that
aerobic exercise is an important lifestyle
factor that influences cognitive function
throughout the lifespan.
Conclusions and future directions
The human and non-human animal
research discussed above suggests that
physical activity, and aerobic fitness training
in particular, can have a positive effect on
multiple aspects of brain function and cog-
nition. Although the number of studies on
physical activity is certainly larger for older
adults than for other age groups, the data
suggest that physical activity can have ben-
eficial effects throughout the lifespan, even
for individuals with neurodegenerative dis-
eases
34,75
. Studies with non-human animals
have begun to shed light on the molecular
and cellular changes that are engendered
by exercise and that appear to underlie the
effects of fitness on cognition and perform-
ance. Fitness training has been observed to
selectively enhance angiogenesis, synap-
togenesis and neurogenesis (in the dentate
gyrus of the hippocampus), as well as to
upregulate a number of neurotrophic factors
in the mouse brain
9,74
.
Despite the wealth of knowledge that
has been obtained concerning the effects of
exercise and physical activity on brain and
cognition, there are a multitude of important
questions that remain to be answered. From
a practical perspective, at present we know
little about how to design exercise interven-
tions that optimize the effects on cognition
and brain health. Future research might be
able to answer questions such as: when is it
best to begin? What are the best varieties,
intensities, frequencies and durations of
exercise? Is it ever too late to start an exercise
programme? Can exercise be used to reduce
the deleterious effects of neurodegenerative
diseases
32,77
?
Some intriguing research has begun the
important task of exploring how exercise
interacts with other lifestyle factors in
influencing cognition and brain health. For
example, Molteni and colleagues
78
inves-
tigated the interaction of diet and exercise
at the behavioural and molecular levels
through their effects on learning and BDNF.
Exercise served to reverse the negative
effects of high-fat diets on BDNF levels and
learning. In another recent study, the effects
of exercise on hippocampal neurogenesis
were substantially delayed and reduced for a
group of socially isolated rodents compared
with animals that were housed in a group
setting
79
. Such results suggest the need to
further study the potential relationship
between social interaction (and social
isolation) and exercise on brain function
and cognition in humans. Finally, several
recent studies have described the benefits
of exercise training for the treatment of
depression
79–80
.
Although the prospective epidemiologi-
cal literature has examined the influence of
various lifestyle factors on cognition and
neurodegenerative disease, few studies have
explored the separate and interactive effects
of lifestyle factors. Karp et al.
29
recently
reported that cognitive, physical and social
engagement had served to decrease the risk
of dementia in a group of 778 adults over
a period of three years, with those adults
with high scores in all three factors showing
the greatest benefit. The results of these
studies are both intriguing and provocative;
however, they only scratch the surface in
terms of explaining the manner in which
different lifestyle factors interact to pro-
mote healthy brains and minds. Clearly,
additional observational and experimental
studies are needed to further explain the
effects of these interactions with regards to
cognition.
In recent years there has also been
increased acknowledgment of the role of
genetic polymorphisms on the heterogeneity
of treatment effects in drug trials, especially
with regards to the speed with which indi-
viduals metabolize different agents
81
. The
study of the potential moderating effect of
genetic variability has also begun to have a
role in the study of exercise effects on cogni-
tion. More specifically, a number of obser-
vational studies have examined whether the
presence of the e4 allele on the APOE gene
(which encodes apolipoprotein E) influences
the relationship between fitness and cogni-
tion in older adults
82–85
. The answer to this
question is, at present, unclear. However,
given that single nucleotide polymorphisms
exist on a number of genes that influence
proteins implicated in fitness-training
effects
86–87
(like BDNF and IGF1, for exam-
ple) future studies will certainly benefit from
the examination of the moderating influence
of genetic variability on relevant target
systems.
P E R S P E C T I V E S
NATURE REVIEWS
|
NEUROSCIENCE VOLUME 9
|
JANUARY 2008
|
63
© 2008 Nature Publishing Group
In conclusion, there is converging evi-
dence at the molecular, cellular, behavioural
and systems levels that physical activity
participation is beneficial to cognition. Such
evidence highlights the importance of pro-
moting physical activity across the lifespan
to reverse recent obesity and disease trends,
as well as to prevent or reverse cognitive and
neural decline. Accordingly, physical activity
can serve to promote health and function in
individuals, while also lessening the health
and economic burden placed on society.
Charles H. Hillman is at the Department of Kinesiology
and Community Health, 213 Louise Freer Hall, 906
South Goodwin Avenue, University of Illinois, Urbana,
Illinois 61801, USA.
Kirk I. Erickson and Arthur F. Kramer are at the
Beckman Institute for Advanced Science and
Technology, 405 North Mathews Avenue, University of
Illinois, Urbana, Illinois 61801, USA.
Correspondence to C.H.H.
e‑mail: chhillma@uiuc.edu
doi:10.1038/nrn2298
1. US Department of Health and Human Services.
Healthy People 2010 [online] http://www.
healthypeople.gov/Document (2000).
2.
Centers for Disease Control and Prevention.
Prevalence of physical activity, including lifestyle
activities among adults — United States, 2000–2001.
Morb. Mort. Weekly Report. 52, 764–769 (2003).
3.
Secretary of Health and Human Services and the
Secretary of Education. Promoting better health for
young people through physical activity and sports.
Centers for Disease Control and Prevention. [online]
http://www.cdc.gov/healthyyouth/physicalactivity/
promoting_health (2007).
4. Fontaine, K. R., Redden, D. T., Wang, C., Westfall,
A. O. & Allison, D. B. Years of life lost due to obesity.
J. Amer. Med. Assoc.
289, 187–193 (2003).
5. Olshansky, S. J. et al.
A potential decline in life
expectancy of the United States in the 21st Century.
N. Engl. J. Med. 352, 1138–1145 (2005).
6. Colditz, G. A. Economic costs of obesity and inactivity.
Med. Sci. Sport Exerc. 31, 663–667 (1999).
7. Pratt, M., Macera, M. A. & Wang, G. Higher direct
medical costs associated with physical inactivity.
Physician Sportsmed. 28, 63–70 (2000).
8. Katzmarzyk, P. T., Gledhill, N. & Shephard, R. J. The
economic burden of physical inactivity in Canada.
Can. Med. Assoc. J. 163, 1435–1440 (2000).
9.
Vaynman, S. & Gomez-Pinilla, F. Revenge of the “sit”:
how lifestyle impacts neuronal and cognitive health
though molecular systems that interface energy
metabolism with neuronal plasticity. J. Neurosci. Res.
84, 699–715 (2006).
10. Booth, F. W. & Lees, S. J. Physically active subjects
should be the control group. Med. Sci. Sport Exerc.
38, 405–406 (2006).
11. Burpee, R. H. & Stroll, W. Measuring reaction time of
athletes. Res. Quart. 7, 110–118 (1936).
12. Lawther, J. D. Psychology of coaching. (Prentice-Hall:
Englewood Cliffs, New Jersey, 1951).
13. Pierson, W. R. & Montoye, H. J. Movement time, reaction
time, and age. J. Gerontol. 13, 418–421 (1958).
14.
Beise, D. & Peaseley, V. The relationship of reaction
time, speed, and agility of big muscle groups and
certain sport skills. Res. Quart. 8, 133–142 (1937).
15. Baylor, A. M. & Spirduso, W. W. Systematic aerobic
exercise and components of reaction time in older
women. J. Gerontol. 43, 121–126 (1988).
16. Sherwood, D. E. & Selder, D. J. Cardiorespiratory
health, reaction time and aging. Med. Sci. Sports 11,
186–189 (1979).
17. Spirduso, W. W. Reaction and movement time as a
function of age and physical activity level. J. Gerontol.
30, 435–440 (1975).
18. Spirduso, W. W. & Clifford, P. Replication of age and
physical activity effects on reaction and movement
times. J. Gerontol. 33, 26–30 (1978).
19. Spirduso, W. W. Physical fitness, aging, and
psychomotor speed: a review. J. Gerontol. 6,
850–865 (1980).
20. Sibley, B. A. & Etnier, J. L. The relationship between
physical activity and cognition in children: a meta-
analysis. Ped. Exerc. Sci. 15, 243–256 (2003).
21. Etnier, J. L. et al.
The influence of physical fitness and
exercise upon cognitive functioning: a meta-analysis.
J. Sport Exerc. Psychol.
19, 249–274 (1997).
22.
Ahamed, Y. et al. School-based physical activity does
not compromise children’s academic performance.
Med. Sci. Sport Exerc. 39, 371–376 (2007).
23. Castelli, D. M., Hillman, C. H., Buck, S. M. & Erwin, H.
Physical fitness and academic achievement in 3rd &
5th Grade Students. J. Sport Exerc. Psychol. 29,
239–252 (2007).
24. Kim, H.-Y. P. et al.
Academic performance of Korean
children is associated with dietary behaviours and
physical status. Asian Pac. J. Clin. Nutr. 12, 186–192
(2003).
25. Hillman, C. H., Snook, E. M., Jerome, G. J. Acute
cardiovascular exercise and executive control function.
Int. J. Psychophysiol. 48, 307–314 (2003).
26. Themanson, J. R. & Hillman, C. H. Cardiorespiratory
fitness and acute aerobic exercise effects on
neuroelectric and behavioral measures of action
monitoring. Neurosci. 141, 757–767 (2006).
27. Tomporowski, P. D. Effects of acute bouts of exercise
on cognition. Acta Psychol. 112, 297–324 (2003).
28. Salthouse, T. A. & Davis, H. P. Organization of
cognitive abilities and neuropsychological variables
across the lifespan. Develop. Rev. 26, 31–54 (2006).
29.
Karp, A. et al. Mental, physical, and social
components in leisure activities equally contribute to
decrease dementia risk. Dement. Geriat. Cogn. Disord.
21, 65–73 (2006).
30. Wilson, R. S. et al.
Participation in cognitively
stimulating activities and risk of incident Alzheimer
disease. J. Amer. Med. Assoc. 287, 742–748 (2002).
31. Hawkins, H. L., Kramer, A. F. & Capaldi, D. Aging,
exercise, and attention. Psychol. Aging 7, 643–653
(1992).
32. Colcombe, S. & Kramer, A. F. Fitness effects on the
cognitive function of older adults: a meta-analytic
study. Psychol. Sci. 14, 125–130 (2003).
33. Etnier, J. L., Nowell, P. M., Landers, D. M. & Sibley,
B. A. A meta-regression to examine the relationship
between aerobic fitness and cognitive performance.
Brain Res. Rev. 52, 119–130 (2006).
34. Heyn, P., Abreu, B. C. & Ottenbacher, K. J. The effects
of exercise training on elderly persons with cognitive
impairment and dementia: a meta-analysis. Arch.
Phys. med. Rehab. 84, 1694–1704 (2004).
35. Erickson, K. I. et al.
Interactive effects of fitness and
hormone treatment on brain health in elderly women.
Neurobiol. Aging 28, 179–185 (2007).
36. Bashore, T. R. Age, physical fitness, and mental
processing speed. Ann. Rev. Gerontol. Geriat. 9,
120–144 (1989).
37. Dustman, R. E. et al.
Age and fitness effects on EEG,
ERPs, visual sensitivity, and cognition. Neurobiol.
Aging 11, 193–200 (1990).
38. Dustman, R. E., LaMarsh, J. A., Cohn, N. B., Shearer,
D. E. & Talone, J. M. Power spectral analysis and
cortical coupling of EEG for young and old normal
adults. Neurobiol. Aging 6, 193–198 (1985).
39. Lardon, M. T. & Polich, J. EEG changes from long-
term physical exercise. Biol. Psychol. 44, 19–30
(1996).
40. Mecklinger, A., Kramer, A. F. & Strayer, D. L. Event-
related potentials and EEG components in a semantic
memory search task. Psychophysiol. 29, 104–119
(1992).
41.
Polich, J. & Lardon, M. P300 and long term physical
exercise. Electroencephalogr. Clin. Neurophysiol. 103,
493–498 (1997).
42. Hillman, C. H., Castelli, D. & Buck, S. M. Aerobic
fitness and cognitive function in healthy preadolescent
children. Med. Sci. Sport Exerc. 37, 1967–1974
(2005).
43. Hillman, C. H., Kramer, A. F., Belopolsky, A. V. &
Smith, D. P. Physical activity, aging, and executive
control: implications for increased cognitive health.
Int. J. Psychophysiol. 59, 30–39 (2006).
44.
Polich, J. & Lardon, M. P300 and long term physical
exercise. Electroencephalogr. Clin. Neurophysiol. 103,
493–498 (1997).
45. Hillman, C. H.,
Weiss, E. P., Hagberg, J. M. & Hatfield,
B. D. The relationship to age and cardiovascular
fitness to cognitive and motor processes.
Psychophysiol. 39, 303–312 (2002).
46. Hillman, C. H., Belopolsky, A., Snook, E. M., Kramer,
A. F. & McAuley, E. Physical activity and executive
control: implications for increased cognitive health
during older adulthood. Res. Q. Exerc. Sport 75,
176–185 (2004).
47.
Polich, J. Clinical applications of the P300 event-
related brain potential. Phys. Med. Rehabil. Clin. N.
Am. 15, 133–161 (2004).
48. Colcombe, S. J. et al.
Cardiovascular fitness, cortical
plasticity, and aging. Proc. Natl Acad. Sci. USA 101,
3316–3321 (2004).
49. Hillman, C. H. et al.
Physical activity and cognitive
function in a cross-section of younger and older
community-dwelling individuals. Health Psychol. 25,
678–687 (2006).
50. Kramer, A. F. et al.
Aging, fitness, and neurocognitive
function. Nature 400, 418–419 (1999).
51. Themanson, J. R., Hillman, C. H. & Curtin, J. J. Age
and physical activity influences on neuroelectric
indices of action monitoring during task switching.
Neurobiol. Aging 27, 1335–1345 (2006).
52. van Veen, V. & Carter, C. S. The timing of action-
monitoring processes in the anterior cingulated
cortex. J. Cogn. Neurosci. 14, 593–602 (2002).
53. Colcombe, S. J. et al.
Aerobic exercise training
increases brain volume in aging humans. J. Gerontol.
A Biol. Sci. Med. Sci. 61, 1166–1170 (2006).
54. Gordon, B. A. et al.
Neuroanatomical correlates of
aging, cardiopulmonary fitness level, and education.
Psychophysiol. (in the press).
55. Marks, B. L. et al.
Role of aerobic fitness and aging in
cerebral white matter integrity. Ann. NY Acad. Sci.
1097, 171–174 (2007).
56. Pereira, A. C. et al.
An in vivo correlate of exercise-
induced neurogenesis in the adult dentate gyrus.
Proc. Natl Acad. Sci. 104, 5638–5643 (2007).
57.
Brown, J. et al. Enriched environment and physical
activity stimulate hippocampal but not olfactory bulb
neurogenesis. Eur. J. Neurosci. 17, 2042–2046
(2003).
58. Van Praag, H., Christie, B. R., Sejnowski, T. J. & Gage,
F. H. Running enhances neurogenesis, learning, and
long-term potentiation in mice. Proc. Natl Acad. Sci.
USA
96, 13427–13431 (1999).
59. Van Praag, H., Kempermann, G. & Gage, F. H. Running
increases cell proliferation and neurogenesis in the
adult mouse dentate gyrus. Nature Neurosci. 2,
266–270 (1999).
60. Trejo, J. L., Carro, E. & Torres-Aleman, I. Circulating
insulin-like growth factor mediates exercise-induced
increases in the number of new neurons in the adult
hippocampus. J. Neurosci. 21, 1628–1634 (2001).
61. Eadie, B. D., Redilla, V. A. & Christie, B. R. Voluntary
exercise alters the cytoarchitecture of the adult
dentate gyrus by increasing cellular proliferation,
dendritic complexity, and spine density. J. Compar.
Neurol. 486, 39–47 (2005).
62. Van Praag, H, Shubert, T., Zhao, C. & Gage, F. H.
Exercise enhances learning and hippocampal
neurogenesis in aged mice. J. Neurosci. 25,
8680–8685 (2005).
63. Kim, H., Lee, S. H., Kim, S. S., Yoo, J. H. & Kim, C. J.
The influence of maternal treadmill running during
pregnancy on short-term memory and hippocampal
cell survival in rat pups. Int. J. Devel. Neurosci. 25,
243–249 (2007).
64. Lee, H. H. et al.
Maternal swimming during pregnancy
enhances short-term memory and neurogenesis in the
hippocampus of rat pups. Brain Devel. 28, 147–154
(2006).
65. Kleim, J. A., Cooper, N. R. & Vandenberg, P. M.
Exercise induces angiogenesis but does not alter
movement representations within rat motor cortex.
Brain Res. 934, 1–6 (2002).
66. Black, J. E., Isaacs, K. R., Anderson, B. J., Alcantara,
A. A. & Greenough, W. T. Learning causes
synaptogenesis, whereas motor activity causes
angiogenesis, in cerebellar cortex of adult rats. Proc.
Natl Acad. Sci. 87, 5568–5572 (1990).
67.
Ding, Y. et al. Exercise pre-conditioning reduces
brain damage in ischemic rats that may be
associated with regional angiogenesis and cellular
overexpression of neurotrophin. Neurosci. 124,
583–591 (2004).
68.
Lopez-Lopez, C., LeRoith, D. & Torres-Aleman, I.
Insulin-like growth factor I is required for vessel
remodeling in the adult brain. Proc. Natl Acad. Sci.
USA 101, 9833–9838 (2004).
69. Cotman, C. W. & Berchtold, N. C. Exercise: a
behavioral intervention to enhance brain health and
plasticity. Trends Neurosci. 25, 295–301 (2002).
P E R S P E C T I V E S
64
|
JANUARY 2008
|
VOLUME 9 www.nature.com/reviews/neuro
© 2008 Nature Publishing Group
70. Vaynman, S., Ying, Z. & Gomez-Pinilla, F. Hippocampal
BDNF mediates the efficacy of exercise on synaptic
plasticity and cognition. Eur. J. Neurosci. 20,
1030–1034 (2004).
71. Ferris, L. T., Williams, J. S. & Shen, C. L. The effect of
acute exercise on serum brain-derived neurotrophic
factor levels and cognitive function. Med. Sci. Sport
Exerc. 39, 728–734 (2007).
72. Gold, S. M. et al.
Basal serum levels and reactivity of
nerve growth factor and brain-derived neurotrophic
factor to standardized acute exercise in multiple
sclerosis and controls. J. Neuroimmunol. 138,
99–105 (2003).
73. Adlard, P. A., Perreau, V. M., Pop, V. & Cotman, C. W.
Voluntary exercise decreases amyloid load in a
transgenic model of Alzheimer’s disease. J. Neurosci.
25, 4217–4221 (2005).
74. Cotman, C. W., Berchtold, N. C. & Christie, L.-A.
Exercise builds brain health: key roles of growth factor
cascades and inflammation. Trends Neurosci. 30,
464–472 (2007).
75.
Prakash, R. et al. Cardiorespiratory fitness: a predictor
of cortical plasticity in multiple sclerosis. Neuroimage
34, 1238–1244 (2007).
76. Berchtold, N. C., Chinn, G., Chou, M., Kesslak, J. P. &
Cotman, C. W. Exercise primes a molecular memory
for brain derived neurotrophic factor protein induction
in the rate hippocampus. Neurosci. 133, 853–861
(2005).
77.
Molteni, R. et al. Exercise reverses the harmful effects
of consumption of a high-fat diet on synaptic and
behavioral plasticity associated to the action of brain-
derived neurotrophic factor. Neurosci. 123, 429–440
(2004).
78. Stranahan, A. M. et al.
Social isolation delays the
positive effects of running on adult neurogenesis.
Nature Neurosci. 9, 526–533 (2006).
79. Barbour, K. A. & Blumenthal, J. A. Exercise training
and depression in older adults. Neurobiol. Aging 26
(Suppl. 1), 119–123 (2005).
80. Russo-Neustadt, A. A. & Chen, M. J. Brain-derived
neurotrophic factor and antidepressant activity.
Curr. Pharm. Des. 11, 1495–1510 (2005).
81. Goldstein, D. B., Need, A. C., Singh, R. & Sisodiya, S. M.
Potential genetic causes of heterogeneity of treatment
effects. Am. J. Med.120 (Suppl. 1), S21–S25 (2007).
82.
Etnier, J. et al. Cognitive performance in older women
relative to ApoeE-epsilon4 genotype and aerobic
fitness. Med. Sci. Sport Exerc. 39, 199–207 (2007).
83. Podewils, L. J. et al.
Physical activity, APOE genotype, and
dementia risk: findings from the cardiovascular health
cognition study. Am. J. Epi. 161, 639–651 (2005).
84.
Rovio, S. et al. Leisure time physical activity at midlife
and the risk of dementia and Alzheimer’s disease.
Lancet Neurol. 4, 705–711 (2005).
85. Schuit, A. J. et al.
Physical activity and cognitive
decline, the role of apoliprotein e4 allele. Med. Sci.
Sports Exerc. 26, 772–777 (2001).
86. Egan, M. F. et al.
The BDNF val66met polymorphism
affects activity dependent secretion of BDNF and
human memory and hippocampal function. Cell 112,
257–269 (2003).
87. Kleim, J. A. et al.
BDNF val66met polymorphism is
associated with modified experienced dependent
plasticity in human motor cortex. Nature Neurosci. 9,
735–737 (2006).
88.
California Department of Education. California
physical fitness test: Report to the governor and
legislature. Sacramento, California. Department of
Education Standards and Assessment Division (2001).
89. Fields, T., Diego, M. & Sanders, C. E. Exercise is
positively related to adolescents’ relationships and
academics. Adolescence 36, 105–110 (2001).
90. Lindner, K. J. The physical activity participation-
academic performance relationship revisited:
perceived and actual performance and the effect of
banding (academic tracking). Ped. Exerc. Sci. 14,
155–169 (2002).
91. Maguire, E. A., Frith, C. D. & Morris, R. G. M. The
functional neuroanatomy of comprehension and
memory: the importance of prior knowledge. Brain
122, 1839–1850 (1999).
92.
Ansari, D. & Dhital, B. Age-related changes in the
activation of the intraparietal sulcus during
nonsymbolic magnitude processing: an event-related
functional magnetic resonance imaging study. J. Cogn.
Neuro. 18, 1820–1828 (2006).
93. Gobel, S. M., Johansen-Berg, H., Behrens, T. &
Rushworth, M. F. Response-selection-related parietal
activation during number comparison. J. Cogn.
Neurosci. 16, 1536–1551 (2004).
94. Rivera, S. M., Reiss, A. L., Eckert, M. A. & Menon, V.
Developmental changes in mental arithmetic: evidence
for increased functional specialization in the left
inferior parietal cortex. Cereb. Cortex. 15,
1779–1790 (2005).
95. Coe, D. P., Pivarnik, J. M., Womack, C. J., Reeves,
M. J. & Malina, R. M. Effects of physical education
and activity levels on academic achievement in children.
Med. Sci. Sport Exerc. 38, 1515–1519 (2006).
96. Sallis, J. F.
et al. Effects of health-related physical
education on academic achievement: Project SPARK.
Res. Q. Exerc. Sport. 70, 127–138 (1999).
97. Martin, J. H.
Neuroanatomy Text and Atlas. 2nd edn
(Appleton and Lange, Stanford Connecticut, 1996).
98. Hall, C. D. Smith, A. L. & Keele, S. W. The impact of
aerobic activity on cognitive function in older adults: a
new synthesis based on the concept of executive
control. Eur. J. Cogn. Psychol. 13, 279–300 (2001).
99. Bush, G., Luu, P. & Posner, M. I. Cognitive and
emotional influences in anterior cingulate cortex.
Trends Cogn. Sci. 4, 215–222 (2000).
Acknowledgments
We would like to thank the National Institute on Aging (R01
AG25,667, R01 AG25,032, R01 AG021,188) for their sup-
port of our research and the preparation of this article. We
would also like to thank A. R. Kramer for her help in crafting
the article title.
DATABASES
Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.
fcgi?db=gene
APOE | BDNF | IGF1 | TRKB| VEGF
OMIM: http://www.ncbi.nlm.nih.gov/entrez/query.
fcgi?db=OMI
M
Alzheimers disease | Parkinsons disease
FURTHER INFORMATION
Charles H. Hillman’s homepage: http://www.kch.uiuc.edu/
labs/neurocognitive%2Dkinesiology/default.htm
ALL LINKS ARE ACTIVE IN THE ONLINE PDF
P E R S P E C T I V E S
NATURE REVIEWS
|
NEUROSCIENCE VOLUME 9
|
JANUARY 2008
|
65
© 2008 Nature Publishing Group
... Deficiencies of vitamins A, B, D, and K, as well as iron and calcium, in preschoolers are all included, and these deficiencies encounter detrimental effects on children's development worldwide. Many children in underdeveloped nations are malnourished chronically [13]. Children's growth is jeopardized by poor nutrition. ...
... Malnutrition has a variety of effects on development and not just growth. Children who are malnourished have cognitive difficulties, as well as problems with motivation, curiosity, and the capacity to engage with their surroundings [13]. During the drought in early childhood, malnutrition causes long-term deficiencies. ...
... A major development in early life is the refining of motor abilities that require hand-eye coordination and little movements and those that engage the body's primary muscles [13]. Children between three and six years of age make significant progress in running and jumping, which are examples of gross motor abilities. ...
Article
Full-text available
In human beings, the development of a child involves biological, emotional, and psychological changes that happen between birth and the conclusion of adolescence. Childhood is divided into three stages: early childhood, middle childhood, and late childhood (preadolescence). Early childhood is typically from infancy to six years of age. The methods for maintaining health and dealing with already-existing sicknesses and the social and economic settings in which children are born, grow up, live, and eventually work are referred to as the social determinants of health. Despite advances in health, child malnutrition remains a problem salutariness (severe) issue with massive human and economic resource implications. There is currently a growing corpus of research on how early development influences a child's success later in life. From conception to two years of age, the first 1,000 days of life are becoming more well-recognized as important for the development of brain circuits that lead to linguistic, cognitive, and socio-emotional abilities, all of which are predictors of later-life labor market outcomes. The social patterning of health, sickness, and illness can be influenced by the social determinants of a child's health. This can also influence a person's overall well-being and functioning throughout their lifetime factors of a child's health, early childhood care, and development from an ecological standpoint, and as planned, a participatory approach in early childhood care and development is implemented. The social determinants of health are the elements that cause positive or negative changes in health or alter disease risks. The social determinants of health, which are different from medical treatment, can be altered by social policy. Social gradients and health equality are ideas that are related to understanding how social factors impact health.
... Although observational results suggested that physical activity enhanced cognitive function [19][20][21], more recent studies showed that higher levels of cognitive function can increase the engagement in physical activity [22][23][24][25]. The effect of physical activity on cognitive function can be explained by the effects of physical activity on angiogenesis, neurogenesis, cortical thickness, and growth factor production [26][27][28]. The effect in the opposite direction (cognitive function → physical activity) can be explained by experimental and theoretical work related to the theory of effort minimization [29][30][31][32][33][34]. ...
... Altogether, though not directly assessed, the current findings fit well with TEMPA. It is worth noting that the aforementioned scenarios are not mutually exclusive, as several studies not only demonstrated the protective effect of physical activity on cognitive function [19][20][21], but also provided biological explanations for this effect [26][27][28]. Finally, the complementary analyses showed mixed, small, and non-significant within-person effects. This result suggests that within-person changes in cognitive function and physical activity did not predict within-person changes in depressive symptoms. ...
Article
Full-text available
Cognitive function, physical activity, and depressive symptoms are intertwined in later life. Yet, the nature of the relationship between these three variables is unclear. Here, we aimed to determine which of physical activity or cognitive function mediated this relationship. We used large-scale longitudinal data from 51,191 adults 50 years of age or older (mean: 64.8 years, 54.7% women) from the Survey of Health, Ageing and Retirement in Europe (SHARE). Results of the longitudinal mediation analyses combined with autoregressive cross-lagged panel models showed that the model with physical activity as a mediator better fitted the data than the model with cognitive function as a mediator. Moreover, the mediating effect of physical activity was 8–9% of the total effect of cognitive function on depressive symptoms. Our findings suggest that higher cognitive resources favor the engagement in physical activity, which contributes to reduced depressive symptoms.
... Spatial perception related to vision has a clinical significance since it affects not only the positional relationship of spatial structures and objects in three-dimensional spaces but also the synaptic plasticity and rescue in the brain, especially the hippocampus [17][18][19]. ...
... Post-treadmill spatial perception was improved compared to that of pre-treadmill spatial perception. In recent years, many kinds of research regarding fitness and cognition including spatial perception have been reported [17,38] and have revealed the effects of exercise on the hippocampus related to augmented spatial perception in older animals [38]. Cardiopulmonary fitness alters neuroplasticity, which means structural changes in the brain [38,39]. ...
Article
Background: This study aimed to identify the association between cardiopulmonary exercise and neurological activation by measuring dictation accuracy and the extent of spatial perception. Methods: First of all, the body composition of subjects was analyzed to verify their physical abnormality. The subjects were given treadmill exercise using modified Bruce protocol. Before and after the treadmill exercise, a spatial perception test and dictation task with auditory and visual stimulation were carried out to identify the changes in neurological activation. Results: The scores of spatial perception after treadmill exercise were higher than those before treadmill exercise (p < 0.05). In addition, the speed of the post-treadmill dictation task with visual stimulation was significantly increased compared to that of the pre-treadmill dictation task (p < 0.05). However, the accuracy of the post-treadmill dictation task with visual stimulation was significantly decreased compared to that of the pre-treadmill dictation task (p < 0.05). Conclusion: In this study, it was shown that spatial perception and speed of visual dictation were increased after treadmill exercise. These results suggest that cardiovascular fitness exercise increases spatial perception and typing speed by facilitating neurological activation.
... The cognitive benefit of physical activity has been indisputably recognized in old age; it is known that a physically active lifestyle contributes to optimizing brain function and avoiding age-related cognitive decline [5]. However, cognitive benefits in regular sport-practicing young adults have been poorly analyzed in comparison to children and older adults [56]. Less obvious benefices are expected in those in their 20s because the brain is at peak performance age [57]. ...
Article
Full-text available
Physically active lifestyle has huge implications for the health and well-being of people of all ages. However, excessive training can lead to severe cardiovascular events such as heart fibrosis and arrhythmia. In addition, strenuous exercise may impair brain plasticity. Here we investigate the presence of any deleterious effects induced by chronic high-intensity exercise, although not reaching exhaustion. We analyzed cardiovascular, cognitive, and cerebral molecular changes in young adult male mice submitted to treadmill running for eight weeks at moderate or high-intensity regimens compared to sedentary mice. Exercised mice showed decreased weight gain, which was significant for the high-intensity group. Exercised mice showed cardiac hypertrophy but with no signs of hemodynamic overload. No morphological changes in the descending aorta were observed, either. High-intensity training induced a decrease in heart rate and an increase in motor skills. However, it did not impair recognition or spatial memory, and, accordingly, the expression of hippocampal and cerebral cortical neuroplasticity markers was maintained. Interestingly, proteasome enzymatic activity increased in the cerebral cortex of all trained mice, and catalase expression was significantly increased in the high-intensity group; both first-line mechanisms contribute to maintaining redox homeostasis. Therefore, physical exercise at an intensity that induces adaptive cardiovascular changes parallels increases in antioxidant defenses to prevent brain damage.
... Neuroscientists have found evidence of a relationship between physical activity and cognitive development in children. It implies that physical activity actively allocates brain resources and promotes faster cognitive processing via stimulus encoding (Hillman et al., 2008). Furthermore, physical activity can improve cell stability and mitigate the negative effects of stress on the body (Puterman et al., 2010). ...
... ;https://doi.org/10.1101https://doi.org/10. /2022 demonstrated beneficial effects of exercise (Hillman et al., 2008;Kramer & Colcombe, 2018), higher cardiorespiratory fitness level (Sokołowski et al., 2021) and participation in everyday activities (Chan et al., 2018;Fratiglioni et al., 2004;Gow et al., 2017) on various cognitive functions in older adults. Importantly, the evidence of beneficial effects of high intensity exercise remains unclear, and a recent 5-year randomized controlled trial revealed no additional effects of exercise with higher intensity compared to following national physical activity guidelines on brain volume (Pani et al., 2021) or cognition (Sokołowski et al., 2021) after the age of 70. ...
Preprint
Background: Cerebral blood flow (CBF) is critical for brain metabolism and overall function. Age-related changes in CBF have been associated with cognitive deficits and increased risk of neurocognitive disorders and vascular events such as stroke. Exercise is considered among the protective factors for age-related brain and cognitive impairment, but how different lifestyle characteristics, such as low or moderate-to-vigorous physical activity or frequency of everyday activities, relate to cross-sectional and longitudinal measures of CBF has not been established. Objective: With the main aim of identifying potential targets for interventions, our objective was to examine associations between cortical and subcortical CBF and frequency of diverse everyday activities in healthy community-dwelling adults aged 65-89 years, and assess to which degree activity level at baseline is associated with longitudinal changes in CBF across a one-to-two years interval. Method: One hundred nineteen (N = 119) adults underwent brain magnetic resonance imaging (MRI), neurocognitive, physical, and activity assessment at baseline. CBF was obtained using pseudo-continuous arterial spin labelling (ASL) MRI. Frequency of everyday activities were measured using Frenchay Activities index, while minutes of low and moderate-to-vigorous intensity physical activity were measured using a StepWatch Activity Monitor. Eighty-six participants completed a follow-up ASL MRI, on average 506 (SD = 113) days after the baseline scan. Results: Bayesian multilevel modelling revealed positive associations between baseline cortical and subcortical CBF and various everyday activities. Higher baseline accumbens, putamen and pallidum CBF was associated with more time spent on low intensity (> 0 steps/minute to < 100 steps/minute) physical activity, higher accumbens and caudate CBF with more moderate to vigorous intensity (≥ 100 steps/minute) physical activity, higher cerebral cortical CBF with more participation in social activity, higher cortical and thalamic CBF with more reading, and higher baseline pallidum CBF with more actively pursuing hobbies. We did not find evidence for an association between baseline activity level and longitudinal changes in CBF. Conclusion: The identified associations between everyday activity measures and CBF provide new knowledge on malleable lifestyle factors that may indicate or contribute to healthy brain aging. In addition to the relevance for prioritizing targets for public health guidelines, our findings contribute to disclose parts of the intricate connection between brain metabolism and everyday activities in aging.
... The percentage change in reaction time was found to be linearly associated with respiratory quotient Figure 4 and could significantly predict the same Table 3, Figure 5. Conversely, when percentage change in reaction time was dichotomized to whether it improved or not after the physical activity of schoolbag carriage, the respiratory quotient served as good tool indicating this binary outcome as depicted by the ROC curve Figure 6. A myriad of beneficial neurological processes emanates from regular physical activity induced cardio-respiratory fitness [29]. Respiratory quotient is a respiratory parameter whose high values are indicative of gain in body weight, fat mass [30] connoting the tendency to being overweight or obese. ...
Article
While structured physical activity improves cardio-pulmonary parameters and Reaction Time (RT), heavy weight schoolbag carriage is detrimental. Schoolbag carriage may have either consequence. The purpose of this study is to explore the consequences of heavy and light weighing schoolbags on cardio-pulmonary parameters and RT. Healthy male participants (10-15 years) carrying schoolbags- 0%, 4%, 8%, 12%, 16% load of bodyweight walked (20-minutes) for 5 times each. For each of the 30 participants, during walks, COSMED k4b2 measured heart rate (HR), respiratory quotient (R), total energy expenditure (EEtot) and number of steps taken. Ruler-drop-test marked RT before and after each walk. RT improved after walking with schoolbags weighing 0%, 4% of bodyweight. RT didn’t improve for 8%, 12% carriage, worsened for 16% load carriage. HR and EEtot showed proportionality (r=0.24, p<0.05), R correlated positively to percentage change in RT (r=0.24, p<0.05) and inversely to number of steps taken (r=-0.40, p<0.01). Percentage change in RT could significantly predict R (R=1.223+0.028(Percentage RT change)). Respiratory quotient can predict whether or not reaction time worsens for 20-minutes schoolbag carriage as per Receiver Operating Characteristic (ROC) curve (Area Under Curve (AUC)=0.668, 95% confidence interval: 0.558-0.779, p<0.01). Carrying light-weight schoolbags (4% of bodyweight) for 20-minutes is beneficial, but heavy-backpack carriage effectuates adverse cardio-pulmonary response and higher RT.
... where x = # of genes in common between two groups; n = # of genes in group 1; D = # of genes in group 2; N = total genes, in this case 20,203 genes (RefSeq, a database run by the US National Center for Biotechnology Information (NCBI)); C (a,b) is the number of combinations of a thing taken 'b' at 'a' time [51,52]. ...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motoneurons (MNs) with a fatal outcome. The typical degeneration of cortico-spinal, spinal, and bulbar MNs, observed in post-mortem biopsies, is associated with the activation of neuroimmune cells. GJA1, a member of the connexins (Cxs) gene family, encodes for connexin 43 (Cx43), a core gap junctions (GJs)- and hemichannels (HCs)-forming protein, involved in cell death, proliferation, and differentiation. Recently, Cx43 expression was found to play a role in ALS pathogenesis. Here, we used microarray and RNA-seq datasets from the NCBI of the spinal cord of control (NDC) and ALS patients, which were stratified according to the GJA1 gene expression. Genes that positively or negatively correlated to GJA1 expression were used to perform a genomic deconvolution analysis (GDA) using neuroimmune signatures. Expression analysis revealed a significantly higher GJA1 expression in the MNs of ALS patients as compared to NDC. Gene deconvolution analysis revealed that positively correlated genes were associated with microglia activation, whereas negatively correlated genes were associated with neuronal activation profiles. Moreover, gene ontology analysis, performed on genes characterizing either microglia or neuronal signature, indicated immune activation or neurogenesis as main biological processes. Finally, using a synthetic analysis of drugs able to revert the GJA1 transcriptomic signatures, we found a specific drug profile for ALS patients with high GJA1 expression levels, composed of amlodipine, sertraline, and prednisolone. In conclusion, our exploratory study suggests GJA1 as a new neuro-immunological gene correlated to microglial cellular profile in the spinal cord of ALS patients. Further studies are warranted to confirm these results and to evaluate the therapeutic potential of drugs able to revert typical GJA1/CX43 signature in ALS patients
Article
Full-text available
This project deals with preparing, implementing, and analyzing the Learning-HITT program. For this purpose, an intervention will be developed for two months in CLIL classrooms (classrooms where bilingual education is taught), which will yield results in four areas: physiological-health, cognitive, motivational, and learning. The implementation of this program involved performing a high-intensity physical activity following the instructions presented on a projector during the first 10 minutes of a regular class. Students subsequently conducted a CLIL self-assessment task. In the first phase of the project, the design of the didactic material and the experimental design was carried out. After the second phase (the intervention itself), we proceeded to analyze the results to provide scientific evidence for future programs or didactic approaches that propose integrating physical activity with learning content or acquiring skills.
Article
Rationale and Hypothesis Advancements in technology, human adaptability, and funding have increased space exploration and in turn commercial spaceflight. Corporations such as Space X and Blue Origin are exploring methods to make space tourism possible. This could lead to an increase in the number of patients presenting with neurological diseases associated with spaceflight. Therefore, a comprehensive understanding of the spaceflight stressors is required to manage neurological disease in high-risk individuals. Objectives This review aims to describe the neurological effects of spaceflight. Pre-flight prophylaxis, training, and potential medication to reduce spaceflight symptoms and long-term effects. Methodology A literature search was performed for available studies conducted in astronauts and those that obtained data in models that simulated the space environment. Many studies, however, only discussed these with scientific reasoning and did not include any experimental methods. Relevant studies were identified through searching research databases such as PubMed and Google Scholar. No inclusion or exclusion criteria were used. Findings Analysis of these studies provided a holistic understanding of the acute and chronic neurological changes that occur during space flight. Astronauts are exposed to hazards that include microgravity, cosmic radiation, hypercapnia, isolation, confinement and disrupted circadian rhythms. Microgravity, the absence of a gravitational force, is linked to disturbances in the vestibular system, intracranial and intraocular pressures. Furthermore, microgravity affects near field vision as part of the spaceflight-associated neuro-ocular syndrome. Exposure to cosmic radiation can increase the risk of neurodegenerative conditions and malignancies. It is estimated that cosmic radiation may have significantly higher ionising capabilities than the ionising radiation used in medicine. Space travel also has potential benefits to the nervous system, including psychological development and effects on learning and memory. Future work needs to focus on how we can compare a current astronaut to a future space tourist. Potentially the physiological and psychological stresses of space flight might lead to neurological complications in future space travellers that do not have the physiological reserve of current astronauts .
Article
Full-text available
Extensive research on humans suggests that exercise could have benefits for overall health and cognitive function, particularly in later life. Recent studies using animal models have been directed towards understanding the neurobiological bases of these benefits. It is now clear that voluntary exercise can increase levels of brain-derived neurotrophic factor (BDNF) and other growth factors, stimulate neurogenesis, increase resistance to brain insult and improve learning and mental performance. Recently, high-density oligonucleotide microarray analysis has demonstrated that, in addition to increasing levels of BDNF, exercise mobilizes gene expression profiles that would be predicted to benefit brain plasticity processes. Thus, exercise could provide a simple means to maintain brain function and promote brain plasticity.
Article
Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.
Article
Background: About two-thirds of Canadians are physically inactive. As a risk factor for several chronic diseases, physical inactivity can potentially be a substantial public health burden. We estimated the direct health care costs attributable to physical inactivity in Canada, the number of lives lost prematurely each year that are attributable to a sedentary lifestyle and the effect that a reduction of 10% in inactivity levels (a Canadian objective for 2003) could have on reducing direct health care costs. Methods: We calculated summary relative risk (RR) estimates from prospective longitudinal studies of the effects of physical inactivity on coronary artery disease, stroke, colon cancer, breast cancer, type 2 diabetes mellitus and osteoporosis. We then computed the population-attributable fraction (PAF) for each illness from the summary RR and the prevalence of physical inactivity (i.e., 62%) and applied the PAF to the total direct health care expenditures for 1999 and to the number of deaths in 1995 associated with each disease to determine the health care costs and lives lost prematurely that were directly attributable to physical inactivity. Results: About $2.1 billion, or 2.5% of the total direct health care costs in Canada, were attributable to physical inactivity in 1999. A sensitivity analysis (simultaneously varying each of the health care costs and PAF by +/- 20%) indicated that the costs could be as low as $1.4 billion and as high as $3.1 billion. About 21,000 lives were lost prematurely in 1995 because of inactivity. A 10% reduction in the prevalence of physical inactivity has the potential to reduce direct health care expenditures by $150 million a year. Interpretation: Physical inactivity represents an important public health burden in Canada. Even modest reductions in inactivity levels could result in substantial cost savings.
Article
This study examined the relationship between academic performance and physical activity participation using objective measures of scholastic achievement, and the effect of banding (academic tracking). The sample comprised 1,447 students (aged 13-17 years) in secondary grades 2, 4, and 6 (736 boys; 711 girls). Academic records were collected from the schools, and a participation questionnaire was administered to the students. School banding was found to be a significant predictor of participation time, and students from higher-banded schools had generally greater participation time than lower-band students. Conversely, perceived academic performance and potential tended to be higher for students with more participation time in physical activity, particularly so for the males. However, for actual academic grades this positive association was not found when banding was taken into consideration. No relationship was found for the middle- and high-band students, while a slight negative relationship was observed for the low-band students.
Article
Nearly 200 studies have examined the impact that either acute or long-term exercise has upon cognition. Subsets of these studies have been reviewed using the traditional narrative method, and the common conclusion has been that the results are mixed. Therefore, a more comprehensive review is needed that includes all available studies and that provides a more objective and reproducible review process. Thus, a meta-analytic review was conducted that included all relevant studies with sufficient information for the calculation of effect size (W = 134). The overall effect size was 0.25, suggesting that exercise has a small positive effect on cognition. Examination of the moderator variables indicated that characteristics related to the exercise paradigm, the participants, the cognitive tests, and the quality of the study influence effect size. However, the most important finding was that as experimental rigor decreased, effect size increased. Therefore, more studies need to be conducted that emphasize experimental rigor.