Studying Exercise

The Physiology of Exercise

Welcome to this week on

exercise and the brain. 
We'll look at the science supporting the effects of exercise on a healthy brain and 
on brains afflicted with disease. 
We'll also explore several types of exercise.

Let's first start by defining various levels of physical activity. 

Daily activity is defined in terms of total daily energy expenditure or 
the amount of energy in the form of calories burned each day. 
This is usually calculated from the average number of steps a person takes 
in a given day. 
A sedentary life style is defined as less than 5,000 steps a day. 
But lets say a person goes for a short run or a brisk walk and 
then spends the rest of the day sitting, therefore totaling under 5,000 steps. 
This is still considered sedentary. 
An active lifestyle is generally defined as equal to or 
more than 7,500 steps per day.

The World Health Organization defines physical inactivity as being less than 
150 minutes of moderate intensity physical activity per week.

Moderate intensity physical activity is defined as requiring a moderate amount of 

effort causing a moderate increase in heart rate. 
Examples are dancing, brisk walking, gardening, 
playing with kids, or walking domestic animals.

An epidemic of sedentary lifestyle is occurring across the globe and 

this affects adults and children. 
In the US, the amount of sedentary time has increased and 
is projected to continue increasing through 2030. 
This trend is not limited to the US, however. 
In China, a health and nutrition survey evaluated adults' physical activity and 
sedentary behavior, the results were similar. 
There has been a sharp drop in physical activities since the 1990s and 
it's projected to continue through to 2030. 
What happens in the body and particularly in the brain when you exercise?

One of the main functions performed by the body is homeostasis, meaning 

maintaining basic levels of physiological functions necessary for life.

Examples of this are body temperature, pH in the body, and glucose amounts.

At any given time, 

the body must ensure sufficient fuel levels, usually in the form of glucose.

Glucose is maintained by a highly sensitive control system. 

It's used by a variety of tissues to sustain metabolism and 
a big portion of it goes to the brain.

In a normal resting state, glucose is released by the liver 

from breakdown of glycogen at rates equivalent to the rate of glucose uptake.

Of course, during exercise, your muscles are working more, so 

they need more fuel in the form of glucose.

Glucose shifts from the blood into the muscle at a rate that helps 
satisfy the metabolic requirement of the working muscle. 
The liver is stimulated to produce more glucose, 
maintaining a stable blood glucose.

If glucose production by the liver did not increase and the muscle was consuming 
more, you would end up hypoglycemic or with low blood sugar.

The liver must also have efficient means of replenishing glucose following 
exercise. 
This is achieved by the effect of the brain on the liver. 
During exercise, your heart rate goes up as soar your levels of epinephrine and 
adrenaline and norepinephrine.

The brain acts through the autonomic nervous system to increase your levels of 
cortisol and epinephrine.

This influences the pancreas, which stimulates the liver to 

make more glucagon, which is the storage form of glucose. 
That way the liver stores are not depleted. 
So, during exercise, glucagon levels go up, insulin goes down. 
Let's focus on what happens at the level of the brain. 
During exercise, 
the muscles secrete various chemicals that act as messengers to the brain. 
These include cyclic AMP and irisin that swim up to the brain and 
induce the brain to start pumping out more serotonin and or 
epinephrine which act as neurotransmitters. 
In addition to neurotransmitters, 
the brain also starts making what are called growth factors. 
These include insulin-like growth factor or IGF, 
vascular endothelial growth factor or VEGF, and 
brain derived neurotrophic factor or BDMF. 
BDNF is a very important protein, it was relatively unknown until the 1990s but 
there are now thousands of studies on the subject.

We now know that BDNF causes growth and the formation of new neurons, or 
neurogenesis. 
It favors long-term potentiation in the hippocampus, 
which is the molecular mechanism behind learning. 
And it even acts on the DNA of neurons to cause more transcription of 
genes that favor brain growth.

If you were to sprinkle BDNF on neurons in a petri dish, 

it would cause growth of those neurons. 
Doctor John Ratey, a psychiatrist at Harvard and 
the Massachusetts General Hospital, 
became interested in the effects of exercise on mental illness. 
And calls BDNF Miracle-Gro for the brain. 
I couldn't think of a more fitting term. 
BDNF has actually been one of the most important molecules looked at when 
observing the effects of exercise on the brain. 
In some studies, impaired BDNF signalling has been shown to be a factor 
in Alzheimer's disease, depression, and even in some eating disorders.

Animal Studies
As we discussed in our last lesson, one of the effects of exercise on the brain is 
the increase in production of BDNF, or brain-derived neurotrophic factor. 
Exercise in my studies revealed that the memory areas of the brain, 
the dentate gyrus and the hippocampus, had an increased level of BDNF, and 
hence, new neurons.

The sedentary rodents on the other hand had low levels of new neurons.

In a landmark study on exercise and learning, mice were placed in two cages. 
One with a running wheel and one without. 
Mice love running wheels and 
can run on them for hours breaking up distances in kilometers overnight.

Then the two groups of mice were placed in a water maze, 

where they were supposed to learn to swim to a safe platform. 
When comparing the runner group to the non-exercising group, 
the running mice were found to have more new cells. 
They also made it to the safe platform, and 
hence, learned much faster compared to the control group. 
This was significant, even compared to mice that were put in enriched cages, 
meaning cages with toys and 
colored things, which causes brain stimulation and brain growth.

So, how does that relate to levels of BDNF in the brain, and 
what is the relationship between BDNF levels and learning? 
And, how much exercise are we talking about here? 
Does it have to be daily, or is intermittent exercise enough?

In one experiment, rats we're exposed to daily voluntary exercise using the running 
wheel and another group only had intimate access to the wheel on alternating days.

The research showed that in the daily exercise group, 

there was a rise of BDNF protein in the brain to 174% of it's original level.

And in the intermittent group it rose to 160% of its original level. 

This increasing median continued through 90 days of the daily group.

What happens to BDNF levels after you stop exercising? 

In similar experiments, rats were exposed to voluntary running daily or 
on alternating days. 
Then the wheels were locked and 
the animals were analyzed at varying days post-exercise. 
This experiment shows that levels gradually decline. 
It takes about 14 days for the daily running group and three days for 
the intermittent group to go back to non-significant levels.

In another study one group of sedentary animals we subjected to daily running 

which significantly increased BDNF levels. 
Even after just one week of rest BDNF amounts went back to almost 
baseline levels. 
If the animal begins running again, BDNF levels increase back 
to levels almost similar to as if they had never stopped running.

This effect is also seen even if the animals were allowed to rest for 
two weeks versus one. 
This has proved that there is almost a BDNF memory. 
Taking that hiatus will not be as detrimental as you might think.

How does BDNF act on the brain?

In experiments looking at the hippocampus, or learning area of the brain. 

Exercising animals had increase in new neurons and 
the more exercise the higher number of new neurons. 
Not only does BDNF cause the creation of new neurons, 
it also causes existing neurons to become bushier and 
have more dendritic branches which means they're more efficient. 
They become better at learning and clearing waste products. 
Like toxic proteins that can accumulate in the brain and 
cause diseases such as Alzheimer's.
Studies looking specifically at A Beta protein in the brain showed benefit. 
A Beta protein is a protein that gets cleared by the brain when it's normally 
functioning. 
It is found to accumulate in the brain of people with Alzheimer's and 
becomes toxic and kills brain cells. 
This effect was seen in both the frontal cortex and 
the hippocampus, which is the seat of memory and executive function.

The same results were found for animal models of Parkinson's disease.

Physical Inactivity, Mice, BDNF

Here are a few helpful resources based on information from the previous lectures.
 WHO Global Map of Physical Inactivity
 All You Need to Know About BDNF (Brain-Derived Neurotrophic Factor)
 Exercising Mice, BDNF, and Improvements in Learning

Human Studies on Exercise

Healthy Brains
Lets now take a look at the effects of exercise on human subjects. 
In a very large study following more than 18,000 women aged 70 to 81 for 
8 to 15 years, it was found that higher levels of long term regular 
physical exercise was strongly associated with higher levels of cognitive function.

The women who exercised regularly, 

behaved as if they were three years younger on average. 
And they had a 20% lower risk of having cognitive impairment. 
The benefits derived from physical exercise were not limited to women 
who did heavy, vigorous exercise. 
Women who walked more than or equal to an hour and a half per week, 
the equivalent of walking two times around a standard track in ten minutes per day. 
Also saw protective benefits against cognitive decline.

In another study, a hypothesis was tested, that aerobic fitness training enhances 
the cognitive vitality of healthy but sedentary older adults. 
18 studies published between 1966 and 2001, were entered into the analysis. 
Several theoretic and practically important results were obtained. 
Fitness training was found to have robust, but selective benefits for cognition, 
with the largest fitness induced benefits occurring for executive functions. 
Such as planning, decision making and multitasking. 
Exercise also showed positive effects on spatial recognition and speed. 
These studies showed a larger effect in women and 
the effect was the same on healthy and cognitively impaired adults.

Let's explore specific studies looking at the effects of aerobic 

exercise on cognition, brain function and brain structure in older adults. 
In a six-month study, one group was randomized to walk three times a week, and 
the other to stretch and perform relaxation techniques. 
All subjects then had their cognitive and executive functions measured. 
The walking group had, on average, 
a higher brain volume compared to the stretching group. 
This increase was seen more in the anterior cingulate area, which is the seat 
of emotional control, as well as the weight matter connecting both hemispheres. 
Possibly showing a more efficient communication between the hemispheres. 
From a neuropsychological standpoint, the walking group showed better attention and 
better memory. 
And this was thought to be correlated to those areas in the brain 
that increased in volume.

The same study was done, but the observation time was increased to a year. 
Subjects were randomized two or 
three times a week, walking program versus relaxation. 
Their cognition was measured and their brain volume evaluated.

Results showed that the hippocampus volume increased by 2%. 

You may think that this increase is not significant, but actually that increase 
corresponds to a reversal in age-related loss in volume by two years.

What about strength and resistance training? 

How does that affect the brain?

We know it has a lot of non-brain benefits, such as promoting bone health 

and reversing osteoporosis and sarcopenia, or loss of bone tissue. 
We also know its effects on muscles, but does it affect the brain?

In a study comparing the effect of moderate versus high intensity resistance 

training in two groups of subjects aged between the ages of 65 and 75. 
The group performing high intensity resistance training showed improvement in 
verbal and spatial memory compared to the group with moderate intensity training. 
In another study, resistance training versus balance exercises, 
three groups of subjects were randomized to once a week versus twice a week of 
resistance training. 
Versus twice a week of balanced exercises.

This group of subjects were all women between the ages of 65 and 
75 who had not partaken in resistance training before. 
These participates were all community dwelling women with no 
history of brain disease like stroke or a neurodegenerative disease. 
The resistance training group did 60 minutes of classes, 
including 40 minutes of resistance training with sets of eight reps, 
versus the group of balance, which also exercised for 60 minutes. 
More details on the exercises done can be found in the supplemental 
reading provided. 
The resistance training group showed significant improvements 
in executive functions at 12 months of training. 
And this was the case for both the once and twice a week groups.

And in a most recent study published just in 2018, 

a Swedish group published findings that moderate to high physical fitness in women 
was associated with a 90% decrease in risk of dementia. 
And even when dementia did occur, 
it happened on average 11 years later than expected. 
How about yoga? 
We know yoga is a great exercise for 
the mind body connection because it's itself a sort of moving meditation, and 
because it often includes a portion of meditation as well. 
It's well known that yoga decreases hypertension, 
stress, depression, and anxiety.

In a study, first-time yoga participants were enrolled in a 12 week program. 

Their brain physiology was measured through EEG measurements. 
And the subjects who went through the yoga training showed a higher activity of 
the left hemisphere, compared to the control group. 
That is typically associated with good and positive moods. 
The study also showed an increase in blood flow in the prefrontal cortex, 
which is the seat of executive function, including judgment, planning and such. 
The yoga practitioners also had changes in their amygdala and sensory motor cortex, 
which is where sensory phenomena and emotions get processed.

Another study compared age related gray matter decline in yoga practitioner and 
in a control group. 
In this study, they found that the control group displayed the well-documented 
age-related grey matter decline, while yogis did not, suggesting that 
yoga contributes to protecting the brain against age related decline. 
Also, the more time spent practicing yoga, the higher the effect on brain volumes. 
The number of years spent practicing yoga also correlated with gray matter volume 
differences in the left hemisphere, insula, frontal lobes, and 
orbitofrontal cortex. 
The results also suggested that yoga tunes the brain towards more positive states. 
Study analyses indicated that the combination of postures in meditation 
contributed the most to the size of the hippocampus and parietal lobe. 
While the combination of meditation and 
breathing exercises contributed the most to visual cortex volume. 
Yoga's potential neuro-protective effects may provide a neural basis for 
some of its beneficial effects.

Impaired Brains
 
We have discussed exercise on individuals with
relatively healthy brains and no history of cognitive impairment or disease. 
But what about people who have already had 
a stroke or even dementia or parkinson's disease. 
Is it too late for them to benefit? 
A six-month study looked at women diagnosed with mild cognitive impairment. 
After participating in a four times a week walking program, 
they were found to actually improve in 
their neuropsychological measures, looking executive function. 
Not only that, they had decreased levels of insulin, 
so better insulin sensitivity and reduced levels of cortisol which is involved in stress. 
In the excel study which stands for exercise for cognition and everyday living, 
86 women with objective cognitive deficits found on 
neuro-psychometric testing between the ages of 
70 and 80 years were randomized to three groups. 
One doing aerobic training twice a week, 
one doing resistance training twice a week 
and the third group doing balanced training twice a week. 
After just six months of training, 
subjects in the resistance training and aerobic training had 
significant improvement in their attention and 
decision-making compared to the balance training group. 
How about cognition in parkinson's disease? 
parkinson's disease is a neurodegenerative disease 
that affects neurons that produce dopamine in the brain. 
It results in a slow and steady loss of motor and cognition functions. 
There are multiple studies showing the efficacy of 
exercise namely tai chi in parkinson's disease. 
Almost all studies favor tai chi. 
Tai chi was shown to improve the unified parkinson's disease rating scale, 
which measures motor function. 
It also showed that parkinson's patients having trouble with initiating movements had 
better scores and that their speed which is 
typically slowed because of the disease was much improved. 
Nosera hitao showed that exercise not only improve the slow down of motor function, 
it also resulted in a less steep curve of cognitive decline. 
This has benefits on quality of life, 
decreasing falls from motor dysfunction, 
increasing independence in activities of daily living and slowing 
the progression of the dementia that can accompany parkinson's disease. 
What do we know about stroke and exercise? 
Most importantly, we know that exercise prevent stroke, 
exercise prevents or reverses high blood pressure and 
metabolic syndrome which is the combination of hypertension, 
diabetes, high cholesterol and obesity. 
It's not fully understood, 
but we do know that there is 
a dose-response relationship between physical activity and stroke, 
which has been proven in some analyses of 
the association between stroke and physical activity. 
So, the more you exercise the lower your risk of stroke. 
How about following a stroke? 
Where does exercise fit in there? 
Of course strokes cause physical disabilities that can 
make exercise difficult and even sometimes unsafe. 
It must be monitored and guided by a professional 
like a physical or occupational therapist. 
A very well-studied physical therapy exercise called constraint induced movement 
therapy has been shown effective in rehabilitating arm dysfunction. 
Their premise is that the good or unaffected arm is constrained often in a sling, 
so that the weak arm is forced to move and learn and get stronger. 
The specific therapy shows not only to increase 
arm strength which is achieved by other therapy modalities, 
but the strength also translates into independence in activities of daily living. 
A mental exercise important after a stroke is balance and mobility training. 
Stroke can cause serious handicaps when it affects your legs or sense of balance. 
Exercise helps to recover that lost balance and return a sense of independence. 
Exercise after stroke also helps from a cognitive standpoint. 
One of the most debilitating post stroke deficits is 
actually cognitive decline which affects up to 65 percent of patients. 
Post stroke fatigue also affects 40 to 77 percent of patients. 
Exercise helps in both those domains. 
Not only does exercise help with deficits caused by stroke, 
it helps increase quality of life and 
independence and it can also prevent another stroke. 
So, exercise is an important process that should be included in post stroke recovery. 
In summary, fitness training has clear and positive effects on 
cognition for both normal aging adults and those with early varieties of dementia.

Cognitive Training
I often get asked by patients, family and friends whether video games, Sudoku and 
other similar puzzle activities make the brain stronger and prevent dementia. 
Is there data supporting that?

Let me start with cognitive training.

Cognitive training is a set of validated exercises that healthcare professionals, 

such as physical therapists, occupational therapists and neuropsychologists use to 
improve an individual's cognitive function, typically after a brain injury. 
The goal of these exercises is to improve attention, memory, reasoning and judgment.
Reproduce el video desde ::35 y sigue la transcripción0:35
The Advanced Cognitive Training for Independent and Vital Elderly, or ACTIVE, 
study was the first large-scale randomized trial to show that cognitive training 
improves cognitive function in community-dwelling older adults, and 
to show evidence of transfer of that training to daily function.
Reproduce el video desde ::53 y sigue la transcripción0:53
The ACTIVE training study focused on memory, reasoning, and 
speed of processing, because prior research indicated that these abilities 
show early age-related decline and are related to activities of daily living.
Reproduce el video desde :1:7 y sigue la transcripción1:07
The training was conducted in small groups in 10 60 to 75-minute 
sessions over 5 to 6 weeks.
Reproduce el video desde :1:14 y sigue la transcripción1:14
Memory training focused on improving verbal, 
episodic memory through instruction and practicing strategy use. 
Reasoning training focused on improving the ability to solve 
problems that contained a serial pattern.
Reproduce el video desde :1:29 y sigue la transcripción1:29
Speed of processing training focused on visual search and 
ability to process increasingly more complex information 
presented in successively shorter inspection times.
Reproduce el video desde :1:39 y sigue la transcripción1:39
In summary, ACTIVE was the first multi-site clinical trial to test 
the effects of cognitive training interventions on cognitive abilities and 
daily function.
Reproduce el video desde :1:48 y sigue la transcripción1:48
Results at ten years demonstrate that cognitive training has 
beneficial effects on cognitive abilities. 
These results provide support for the development of other interventions, 
particularly those that target multiple cognitive abilities.
Reproduce el video desde :2:3 y sigue la transcripción2:03
Results from ACTIVE demonstrated that each of the three cognitive training 
interventions, memory, reasoning and visual speed of processing 
affected their targeted, proximal and primary outcomes over both short and 
long term, one to five years of follow up periods and even at ten years. 
These changes reflected the restoration of the equivalent of six years in memory, 
four years in reasoning, and eight years in visual speed-of-processing, 
the biggest effect.
Reproduce el video desde :2:32 y sigue la transcripción2:32
Only the visual speed-of-processing intervention had significant effects on 
a variety of health outcomes, including health-related quality of life, 
depressive symptoms and self-rated health that lasted up to five years. 
A study called the Iowa Healthy and 
Active Mind study compared cognitive training to crossword puzzles. 
Details about the cognitive training exercises can be found in the supplemental 
reading provided with the course. 
It addressed some of ACTIVE's limitations, such as allowing younger subjects to 
participate, so they started recruiting at the age of 55 and up. 
They divided the participants into four groups. 
One group that had five training sessions of two hours each on site. 
One group that had similar training, but got a booster session. 
One group that was given the software and instructions and asked to do the training 
at home, and a control group that only did crossword puzzles.

This study was novel, because it compared older and younger users. 
It also compared users in their own home with those in a supervised setting. 
And it looked at crosswords, 
which is an exercise most people think of when they think of brain training. 
The results of the study found that the group using the computerized exercise for 
just ten hours had significant gains in cognitive function, 
while the group doing crosswords on the computer for 
an equal period of time had no significant improvements. 
The group at home had no improvements in their cognitive function and speed, but 
the group with on-site training and a four-hour booster did the best. 
What about intellectual engagement for the elderly? 
What I mean by that is reading, doing handy crafts such as knitting, 
having political interests, meeting with friends in groups, gardening, 
playing cards, and so on? 
In a Swedish study by Carp et al, a total of 776 non-demented subjects aged 75 years 
and above were followed for more than 6 years to detect incident dementia cases.
Reproduce el video desde :4:27 y sigue la transcripción4:27
These subjects were asked what kinds of activities they engaged in, and 
a score of one to three was assigned to each activity. 
The study showed that the higher the score, meaning the more activities these 
elderly people engaged in, the less the risk of dementia developing down the road.
Reproduce el video desde :4:42 y sigue la transcripción4:42
These findings suggest that engaging in a broad spectrum of activities 
is more beneficial than being engaged in only one type of activity. 
Remember though that fitness training has both broad and 
specific effects on cognition. 
Meaning with just one exercise, you can target different domains, including 
executive function, spacial orientation and speed, whereas with cognitive training 
you should do a specific exercise to target each specific domain.
Physical & Cognitive
Exercise
Here are a few helpful resources based on information from the previous lectures.
Physical Exercise
 Exercise and Cognitive Function in Older Women
 Aerobic Exercise Increases Brain Size and Aerobic Exercise Improves Executive Function
 How Yoga Changes the Brain
 EXCEL: Exercise for Cognition and Everyday Living
 NOMAS Study: Exercise May Delay Cognitive Decline (access requires free registration)
 Exercise and Alzheimer's
 Exercise (Tai Chi) and Parkinson's
 Exercise and Stroke
Cognitive Exercise
 What Is Cognitive Training?
 Free Brain Training Games and Lumosity
 Ten-Year Effects of the ACTIVE Cognitive Training Trial

Completado(a)

1.
Pregunta 1
What is Brain-Derived Neurotrophic Factor (BDNF)?
1 punto
BDNF is a specialized sensory neuron that corresponds to all five of the senses.
BDNF is a neurotransmitter involved in social behavior and motor control.
BDNF is a protein that promotes neurogenesis and is vital to learning.
BDNF is a hormone important for appetite and digestion.

2.
Pregunta 2
Aerobic exercise increases levels of Brain-Derived Neurotrophic Factor (BDNF).
1 punto
True
False

3.
Pregunta 3
What is the minimal number of steps you should take daily to lead an active lifestyle?
1 punto
4000 steps per day
5500 steps per day
6000 steps per day
7500 steps per day

4.
Pregunta 4
Yoga training has been linked to higher activity in which area of the brain?
1 punto
Wernicke's area
Left hemisphere
Right hemisphere
Broca's area

5.
Pregunta 5
Which of the following occurred for animals after exercise interventions were introduced?
1 punto
Increased production of new neurons
Increased dendrites in neurons
Increased knowledge retention
All of the above

6.
Pregunta 6
Sedentary older adults experienced the greatest impact with which cognitive ability after aerobic fitness
training?
1 punto
Decision making
Writing
Empathy
All of the above

7.
Pregunta 7
Tai Chi can improve the slowdown of motor function in Parkinson's disease.
1 punto
True
False

8.
Pregunta 8
What is cognitive training?
1 punto
Specialized brain exercises that target breathing, heart rate, pupil dilation, etc.
Specialized brain exercises that target speech, empathy, writing, etc.
Specialized brain exercises that target movement, speed, balance, etc.
Specialized brain exercises that target memory, reasoning, judgement, attention, etc.

9.
Pregunta 9
Breathing exercises only alter brain function, not brain structure.
1 punto
True
False

10.
Pregunta 10
The Iowa Healthy and Active Minds Study proved that crossword puzzles significantly increased
cognitive function.
1 punto
True
False