Physical Activity Enhances Physical Activity Enhances Brain FunctionBrain Function

Cognitive PhysiologyCognitive Physiology

In science, cognition refers to mental In science, cognition refers to mental processes. These processes include processes. These processes include attention, remembering, producing and attention, remembering, producing and understanding language, solving understanding language, solving problems, and making decisionsproblems, and making decisions

Cognitive physiology is the study of the Cognitive physiology is the study of the underlying mechanisms of human thoughtunderlying mechanisms of human thought

Physical Activity and CognitionPhysical Activity and Cognition

Numerous studies have shown that Numerous studies have shown that adequate physical activities improve adequate physical activities improve cognition in mice (Cotman CW, Berchtold cognition in mice (Cotman CW, Berchtold NC, Christie LA., 2007) and human NC, Christie LA., 2007) and human ((Benjamin A. Sibley, Jennifer L. 2010; Benjamin A. Sibley, Jennifer L. 2010; EtnierLautenschlager, Nicola T; Almeida, EtnierLautenschlager, Nicola T; Almeida, Osvaldo, p, 2006Osvaldo, p, 2006) )

Hippocampus of BrainHippocampus of Brain

The hippocampus is located in the medial The hippocampus is located in the medial temporal lobe of the brain. temporal lobe of the brain.

Lateral view of the human brain, the frontal Lateral view of the human brain, the frontal lobe is at left, the occipital lobe at right, lobe is at left, the occipital lobe at right, and the temporal and parietal lobes have and the temporal and parietal lobes have largely been removed to reveal the largely been removed to reveal the hippocampus underneathhippocampus underneath

Anatomy of human brainAnatomy of human brain

Structure of HippocampusStructure of Hippocampus

Structure of HippocampusStructure of Hippocampus

The hippocampus is a major component of The hippocampus is a major component of the brains of humans and other the brains of humans and other vertebrates.vertebrates.

The hippocampus is closely associated The hippocampus is closely associated with the cerebral cortex, and in primates is with the cerebral cortex, and in primates is located in the medial temporal lobe, located in the medial temporal lobe, underneath the cortical surface. It contains underneath the cortical surface. It contains two main interlocking parts: two main interlocking parts: Ammon's Ammon's hornhorn and the and the dentate gyrusdentate gyrus..

Structure of HippocampusStructure of Hippocampus

Function of HippocampusFunction of Hippocampus

It belongs to the It belongs to the limbic systemlimbic system and plays and plays important roles in the consolidation of important roles in the consolidation of information from information from short-term memory to short-term memory to long-term memorylong-term memory and and spatial spatial navigationnavigation. .

Humans and other mammals have two Humans and other mammals have two hippocampi, one in each side of the brain.hippocampi, one in each side of the brain.

Nerve cellsNerve cells

Basic Structure of a Chemical Basic Structure of a Chemical SynapseSynapse

Neurotransmitters and Synaptic Neurotransmitters and Synaptic TransmissionTransmission

Excitatory postsynaptic potentials (EPSP)Excitatory postsynaptic potentials (EPSP)– Causes depolarization Causes depolarization

Inhibitory postsynaptic potentials (IPSP)Inhibitory postsynaptic potentials (IPSP)– Causes hyperpolarizationCauses hyperpolarization

NeurogenesisNeurogenesisNew neurons are continually born throughout New neurons are continually born throughout adulthood in predominantly two regions of the adulthood in predominantly two regions of the brain:brain:– The subventricular zone (SVZ) lining the lateral The subventricular zone (SVZ) lining the lateral

ventricles, where neural stem cells and progenitor ventricles, where neural stem cells and progenitor generate new neurons (Neuroblast) that migrate to generate new neurons (Neuroblast) that migrate to the olfactory bulb via the rostral migratory streamthe olfactory bulb via the rostral migratory stream

– The subgranular zone (SGZ), part of the dentate The subgranular zone (SGZ), part of the dentate gyrus of hippocampus.gyrus of hippocampus.

Many of the newborn cells die shortly after they Many of the newborn cells die shortly after they are born, but a number of them become are born, but a number of them become functionally integrated into the surrounding brain functionally integrated into the surrounding brain tissue.tissue.

BrdU (dyed in BrdU (dyed in redred), a ), a marker of DNA marker of DNA replication, highlights replication, highlights neurogenesis in the neurogenesis in the subgranular zone of subgranular zone of hippocampal dentate hippocampal dentate gyrus. gyrus. Fragment of an illustration from Fragment of an illustration from

Faiz et al., 2005.Faiz et al., 2005.

Neurogenesis and CognitionNeurogenesis and Cognition

Recent experimental evidence supports the Recent experimental evidence supports the role of role of Brain-Derived Neurotrophic FactorBrain-Derived Neurotrophic Factor (BDNF) in memory processes(BDNF) in memory processes

Memory acquisition and consolidation are Memory acquisition and consolidation are associated with an increase in BDNF mRNA associated with an increase in BDNF mRNA expression and the activation of its receptor: expression and the activation of its receptor: neurotrophic tyrosine kinase, receptor, type neurotrophic tyrosine kinase, receptor, type 2 (TrkB; 2 (TrkB; a protein that is encoded by neurotrophic tyrosine kinase a protein that is encoded by neurotrophic tyrosine kinase

receptor 2 ( NTRK2) gene has been localized to a region on chromosome receptor 2 ( NTRK2) gene has been localized to a region on chromosome

9q22-q23 in humans 9q22-q23 in humans ))

Yamada K, Nabeshima T. J. Pharmacol. Sci. (2003)

Brain-Derived Neurotrophic FactorBrain-Derived Neurotrophic Factor

Known as BDNF, is a protein Known as BDNF, is a protein that, in humans, is encoded that, in humans, is encoded by the BDNF gene.by the BDNF gene.

BDNF is a member of the BDNF is a member of the "neurotrophin" family "neurotrophin" family

In the brain, it is active in the In the brain, it is active in the hippocampus, cortex, and hippocampus, cortex, and basal forebrain—areas vital to basal forebrain—areas vital to learning, memory, and higher learning, memory, and higher thinking.thinking.

BDNF is important for long-BDNF is important for long-term memory.term memory.

Physical Activity and Brain Structure Physical Activity and Brain Structure and Functionand Function

Scientists have shown that physical Scientists have shown that physical activity in the form of voluntary exercise activity in the form of voluntary exercise results in an increase in the number of results in an increase in the number of newborn neurons in the hippocampus of newborn neurons in the hippocampus of aging mice. The same study demonstrates aging mice. The same study demonstrates an enhancement in learning of the an enhancement in learning of the "runner" (physically active) mice "runner" (physically active) mice

Animal model Animal model

Results of the studyResults of the studyThe results show that cell proliferation was onlyThe results show that cell proliferation was only

increased in mice housed with increased in mice housed with unrestricted access to a unrestricted access to a running wheel (runners).running wheel (runners).

voluntary physical activity and enrichmentvoluntary physical activity and enrichment roughly roughly doubled doubled the total number of surviving new-born cells in the dentate the total number of surviving new-born cells in the dentate gyrus.gyrus.

In contrast, In contrast, mice trained in the water maze and yoked-mice trained in the water maze and yoked-swim controls showed no changeswim controls showed no change the cell number, the cell number, suggesting that this type of learning or activity alone is suggesting that this type of learning or activity alone is not an adequate stimulus for adult hippocampal not an adequate stimulus for adult hippocampal neurogenesisneurogenesis

What is the implication of this study to you !!What is the implication of this study to you !!

Animal Model (II)Animal Model (II)

Results of the studyResults of the study

SummarySummary

Mice who exercised performed better on a spatial Mice who exercised performed better on a spatial learning task (finding their way through a water maze). learning task (finding their way through a water maze).

Since the late 1990s, research (Cotman and Berchtold Since the late 1990s, research (Cotman and Berchtold 2002 and von Pragg 2008) has revealed that aerobic 2002 and von Pragg 2008) has revealed that aerobic exercise boosts levels of brain-derived neurotrophic exercise boosts levels of brain-derived neurotrophic factor (BDNF), a substance essential for the growth of factor (BDNF), a substance essential for the growth of brain cells brain cells

Mobilizes the expression of genes that are believed to Mobilizes the expression of genes that are believed to enhance brain plasticity—i.e., the ability of the brain to enhance brain plasticity—i.e., the ability of the brain to change its neural pathways change its neural pathways

Prevents brain tissue loss in older adultsPrevents brain tissue loss in older adults

Compared sedentary mice with mice that ran an Compared sedentary mice with mice that ran an average of 3 miles each night on a running average of 3 miles each night on a running wheel (van Pragg et al. 1999) the aerobically-wheel (van Pragg et al. 1999) the aerobically-challenged mice showed dramatic brain growth.challenged mice showed dramatic brain growth.

And the hippocampus—-a brain region And the hippocampus—-a brain region associated with learning and memory--was twice associated with learning and memory--was twice as large (van Pragg et al. 1999) as large (van Pragg et al. 1999)

the brain cells of the aerobic mouse could the brain cells of the aerobic mouse could sustain longer bouts of “long-term potentiation,” sustain longer bouts of “long-term potentiation,” the increased efficiency of communication the increased efficiency of communication between neurons that occurs after neurons fire. between neurons that occurs after neurons fire.

Long-term potentiation (LTP)Long-term potentiation (LTP)

Is a long-lasting enhancement in signal Is a long-lasting enhancement in signal transmission between two neurons that results transmission between two neurons that results from stimulating them synchronously. from stimulating them synchronously.

It is one of several phenomena underlying It is one of several phenomena underlying synaptic plasticity, the ability of chemical synaptic plasticity, the ability of chemical synapses to change their strength. synapses to change their strength.

As memories are thought to be encoded by As memories are thought to be encoded by modification of synaptic strength, LTP is widely modification of synaptic strength, LTP is widely considered one of the major cellular considered one of the major cellular mechanisms that underlies learning and memorymechanisms that underlies learning and memory

Long-term potentiation (LTP)Long-term potentiation (LTP)

Recordings are made intracellularly from Recordings are made intracellularly from CA1 neurons of the hippocampus while CA1 neurons of the hippocampus while stimulation is applied to the Schaffer stimulation is applied to the Schaffer collaterals of CA3 neurons. collaterals of CA3 neurons.

The amplitudes of the EPSPs in the CA1 The amplitudes of the EPSPs in the CA1 neurons are shown in B. For a single neurons are shown in B. For a single stimulus, the amplitude of the EPSPs is stimulus, the amplitude of the EPSPs is plotted at 100%. When a train of stimuli is plotted at 100%. When a train of stimuli is applied instead, the amplitude of the EPSPs applied instead, the amplitude of the EPSPs augment to about 150%, whereas with 4 augment to about 150%, whereas with 4 such trains the amplitude increases to 250%. such trains the amplitude increases to 250%.

Many people think that long-term Many people think that long-term potentiation is an example of Hebb’s rule at potentiation is an example of Hebb’s rule at work and that it is the physiological basis of work and that it is the physiological basis of memory.memory.

Mechanism of LTPMechanism of LTPGlutamine induces N-methyl-Glutamine induces N-methyl-D-aspartate (NMDA) D-aspartate (NMDA) receptor to depolarize and receptor to depolarize and remove Mgremove Mg++++ (inhibits Ca (inhibits Ca++++ binding)CaCa++ ++ then binds to NMDA receptor which increase a-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor number

AMPA increases potentiated nerve impulse and generates LTP in CA1 of hippocampusBeing suggests in associates with learning and memory

AMPA receptorsAMPA receptorsAMPA receptors can AMPA receptors can move between an move between an intracellular pool and the intracellular pool and the neuronal surface, by the neuronal surface, by the processes of exocytosis processes of exocytosis and endocytosis and endocytosis

AMPA receptors are also AMPA receptors are also immobilized by increases immobilized by increases in intracellular calcium in intracellular calcium levels, perhaps after levels, perhaps after calcium influx through calcium influx through postsynaptic calcium postsynaptic calcium channelschannels

Running animal and LTPRunning animal and LTP

GlutamateGlutamate

Neurovascular adaptations to exercise in the dentate Neurovascular adaptations to exercise in the dentate gyrus of young adult mice associated with cognitive gyrus of young adult mice associated with cognitive gain gain

Clark PJ, Brzezinska WJ, Puchalski EK, Krone DA, Rhodes JS.2009

Neurovascular AdaptationsNeurovascular Adaptations

Image shows the high Image shows the high density of blood density of blood vessels in the brain vessels in the brain and the close and the close proximity of brain proximity of brain cells to those vessels. cells to those vessels. A cut-away of one A cut-away of one blood vessel shows blood vessel shows vessel lining cells vessel lining cells (endothelia-red). (endothelia-red).

Physical activity for Body and BrainPhysical activity for Body and Brain

Cotman CW, Berchtold NC, Christie LA. (2007) Cotman CW, Berchtold NC, Christie LA. (2007) advocated that exercise increases synaptic advocated that exercise increases synaptic plasticity by directly affecting synaptic structure plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by and potentiating synaptic strength, and by strengthening the underlying systems that strengthening the underlying systems that support plasticity including neurogenesis, support plasticity including neurogenesis, metabolism and vascular functionmetabolism and vascular function

In addition, exercise reduces peripheral risk In addition, exercise reduces peripheral risk factors such as diabetes, hypertension and factors such as diabetes, hypertension and cardiovascular disease, which converge to cardiovascular disease, which converge to cause brain dysfunction and neurodegeneration.cause brain dysfunction and neurodegeneration.

Human studies (I)Human studies (I)Davis, C. L. (2011a) used sedentary, overweight Davis, C. L. (2011a) used sedentary, overweight 7- to 11-year-old children (N = 171, 56% girls, 7- to 11-year-old children (N = 171, 56% girls, 61% Black, M ± SD age = 9.3 ± 1.0 years, body 61% Black, M ± SD age = 9.3 ± 1.0 years, body mass index [BMI] = 26 ± 4.6 kg/m², BMI z-score mass index [BMI] = 26 ± 4.6 kg/m², BMI z-score = 2.1 ± 0.4) whom were randomized to 13 ± 1.6 = 2.1 ± 0.4) whom were randomized to 13 ± 1.6 weeks of an weeks of an exercise program (20 or 40 exercise program (20 or 40 min/daymin/day), or a control condition. ), or a control condition.

Dose-response benefits of exercise on Dose-response benefits of exercise on executive function and mathematics executive function and mathematics achievementachievement. .

Physical activity may prove to be a simple, Physical activity may prove to be a simple, important method of enhancing aspects of important method of enhancing aspects of children's mental functioning that are central to children's mental functioning that are central to cognitive developmentcognitive development

Human study (II)Human study (II)Davis, C. L. (2011b) examined effects of Davis, C. L. (2011b) examined effects of aerobic exercise on overweight children's aerobic exercise on overweight children's cognitive functioningcognitive functioningNinety-four sedentary, overweight but Ninety-four sedentary, overweight but otherwise healthy children (mean age = 9.2 otherwise healthy children (mean age = 9.2 years, body mass index 85th percentile) were years, body mass index 85th percentile) were randomized to a randomized to a low-dose (20 min/day low-dose (20 min/day exercise), high-dose (40 min/day exercise), exercise), high-dose (40 min/day exercise), or control conditionor control condition.. Exercise sessions met 5 days/week for 15 Exercise sessions met 5 days/week for 15 weeksweeks. The Cognitive Assessment System . The Cognitive Assessment System (CAS), a standardized test of cognitive (CAS), a standardized test of cognitive processes, was administered individually processes, was administered individually before and following interventionbefore and following intervention

Cont.Cont.

Planning scores for the high-dose group Planning scores for the high-dose group were significantly greater than those of the were significantly greater than those of the control group. control group. the effect of exercise seemed to depend the effect of exercise seemed to depend on the dose. Kids enrolled in the on the dose. Kids enrolled in the 40-40-minute-a-day program made the minute-a-day program made the biggest improvementsbiggest improvements – an average – an average increase of 3.8 points in IQ. Kids in the 20-increase of 3.8 points in IQ. Kids in the 20-minute-a-day program made smaller minute-a-day program made smaller gains.gains.

PAAC promoted 90min/week of moderate to vigorous physically active academic lessons(3.0 to 6.0METS,~10 min each) delivered intermittently throughout the school day. Lessons were usually delivered in the classroom, but were also delivered in alternate school sites such as hallways and outdoors. PAAC=physical activity across curriculum

Exercise may prove to be a simple, yet important, Exercise may prove to be a simple, yet important, method of enhancing aspects of children's mental method of enhancing aspects of children's mental functioning that are central to cognitive and social functioning that are central to cognitive and social developmentdevelopment

40 minutes a day of aerobic exercise improved 40 minutes a day of aerobic exercise improved executive function—-that aspect of intelligence that executive function—-that aspect of intelligence that helps us pay attention, plan, and resist distractions helps us pay attention, plan, and resist distractions (Davis et al 2007). (Davis et al 2007).

13 weeks of aerobic exercise was also linked with 13 weeks of aerobic exercise was also linked with improved math skills and increased activity in the improved math skills and increased activity in the bilateral prefrontal cortex, a brain region associated bilateral prefrontal cortex, a brain region associated with executive function (Davis et al 2011). with executive function (Davis et al 2011).

SummarySummary

Exercise for children is probably beneficial for Exercise for children is probably beneficial for the brain. Given that physical fitness is also the brain. Given that physical fitness is also good for the bodygood for the body

Exercise should be fun. The mouse experiments Exercise should be fun. The mouse experiments are based on voluntary wheel-running. When are based on voluntary wheel-running. When rodents are forced to exercise, they don’t always rodents are forced to exercise, they don’t always reap the benefitsreap the benefits

aerobic exercise that your child really enjoys. aerobic exercise that your child really enjoys. Structured activities—-like team sports or dance Structured activities—-like team sports or dance lessons—-may be fine options. But so are nature lessons—-may be fine options. But so are nature walks, tree-climbing, roller-skating, and playing walks, tree-climbing, roller-skating, and playing hide-and-seek. hide-and-seek.

Exercise improves brain function and reduces Exercise improves brain function and reduces the risk of cognitive impairment associated with the risk of cognitive impairment associated with agingaging

Regular exercise can protect the brain against:Regular exercise can protect the brain against:– Disease (Alzheimer’s) Disease (Alzheimer’s) – Certain types of brain injury (stroke)Certain types of brain injury (stroke)

How does exercise enhance brain health?How does exercise enhance brain health?– Enhances learning and memoryEnhances learning and memory– Stimulates formation of new neuronsStimulates formation of new neurons– Improves brain vascular function and blood flowImproves brain vascular function and blood flow– Attenuates mechanisms driving depressionAttenuates mechanisms driving depression– Reduces peripheral factors for cognitive declineReduces peripheral factors for cognitive decline

Inflammation, hypertension, and insulin resistanceInflammation, hypertension, and insulin resistance

Exercise Has Broad Positive Exercise Has Broad Positive Benefits on Brain HealthBenefits on Brain Health

DiscussionDiscussionIn your opinion, what is the most effective In your opinion, what is the most effective physical activity promote brain function for physical activity promote brain function for seniors.seniors.

Why the role of Brain-Derived Neurotrophic Why the role of Brain-Derived Neurotrophic Factor (BDNF) is important in memory Factor (BDNF) is important in memory processes.processes.

What do you do If you are going to What do you do If you are going to implement a PAAC program in a junior high implement a PAAC program in a junior high school class and may expect what kind of school class and may expect what kind of change as to brain function of the students.change as to brain function of the students.