AEROBIC EXERCISE &

BRAIN-DERIVED NEUROTROPHIC
FACTOR:
IMPLICATIONS FOR NEURAL PLASTICITY AND MOTOR
LEARNING
GREGORY A. BRUSOLA, SPT
TEXAS WOMANS UNIVERSITY HOUSTON
DOCTOR OF PHYSICAL THERAPY PROGRAM
OCTOBER 04, 2013
NEXUS TOUCHSTONE NEURORECOVERY CENTER

 Develop a current understanding of neural plasticity.

Recognize the value of aerobic exercise, its general
effects, and specific effects on the neurological
system.

OBJECTIVES

Develop a general understanding of brain-derived

neurotrophic factor (BDNF) and its role in neural
plasticity and motor learning.
Appreciate the role aerobic exercise has on BDNF, and
accordingly on neural plasticity and motor learning.
Relate the clinical implications of aerobic exercise to
the science of neurorehabilition.

NEURAL
PLASTICITY
The abridged version

 Neural Plasticity

NEURAL
PLASTICITY

Any change in neuron structure or function that is

observed directly from measures of individual
neurons or inferred from measures taken across
populations of neurons.
Measures of behavior are not themselves direct
measures of NP, according to this definition.
Reflects changes in neural circuitry.

Functional improvement after CNS injury

CNS relies on the same fundamental
neurobiological processes initially used to acquire
behaviors.
How neural circuits adapt to encode new
behaviors do not change even after injury.

NEURAL
PLASTICITY

Learning skilled movements requires

numerous brain areas: primary motor
cortex, supplementary motor cortex,
premotor cortex, cerebellum, somatosensory
cortex, and other subcortical areas.
Experience-dependent plasticity is dynamic;
comprised of complex cascades of
molecular, cellular, structural, and
physiological events changing over time.

NEURAL
PLASTICITY:
EXPERIENC
EDEPENDENT

Skilled task and motor training effects on

neural structure

Denditric growth
Synaptogenesis
Enhanced synaptic response
Expansion of motor and sensory maps

FUNDAMENTA
L PROPERTIES
OF BRAIN
ORGANIZATIO
N:
REDUNDANC
Y

Internal Redundancy independent clusters of

neurons responding to similar information
Somatosensory representations repeated multiple
times within primary somatosensory cortex
Enhances neural integration
Serves to enhance brains ability for motor function
improvement after brain injury (BI)

External Redundancy same functions represented

across distinct brain areas (parallel processing)
Occurs across brain regions that work in one general
modality or across regions working in different
modalities

Enhances ability of the brain to adapt to injury

 Issues

RECOVERY VS.
COMPENSATION
:
A (VERY) QUICK
REVIEW

Differing terminologies barrier to interdisciplinary

communication.
Neuroscientists: true recovery is impossible; once
neural tissue is gone, it does not return. So, any
functional improvement is compensatory in nature
Therapists: functional improvements represent
recovery because patients are able to perform tasks
they were unable to immediately after injury.

Solution?
Levin et al. and definitions of each according to the
WHO ICF framework
Recovery and compensation can be observed at both
behavioral and neural levels, delineating movement
ability and task performance.

Restoration, Recruitment, & Retraining

BRAIN-DERIVED
NEUROTROPHIC
FACTOR (BDNF)
And its role in neuroplasticity

 Member of neurotrophin family.

BRAIN-DERIVED
NEUROTROPHI
C FACTOR

Activity-dependent
Neuroprotection
Neurogenesis
Neuroplasticity

Formed by vascular endothelial cells

(CNS) and peripheral blood mononuclear
cells.
Role in central and peripheral cellular energy
metabolism.

Reduces food intake.

Increases C6H12O6 oxidation.
Lowers blood C6H12O6 levels.
Increases insulin sensitivity.

 High expressions of BDNF mRNA found in

hippocampus, frontal & prefrontal cortex,
hypothalamus, cerebellum.

BDNF
&
MOTOR
LEARNING

BDNF expression during complex vs. simple tasks

in different brain areas.
Facilitates long-term potentiation.
Formation, retention, recall of memory
Mediator of motor learning and rehabilitation
post-stroke and those with neurodegenerative
disease.
Influences learning at the cortical, sub-cortical, and
spinal cord levels.

WHAT
ABOUT
MOTOR
LEARNING?

Two forms of long-term memory

Explicit
(declarativ
e)

MOTOR
LEARNING:
Fact and
events

MEMORY
Medial temporal lobe
Sensory association
cortex
Hippocampus

Implicit (non-declarative)
Nonassociative
learning
Reflex pathways

Associative learning

Emotional
responses

Skeletal
musculature

Amygdala

Cerebellum
Deep cerebellar
nuclei
Premotor cortex

Procedural

Striatum
Cerebellum
Other motor areas

Types of Memory
Emotiona
l

Declarati
ve

Procedu
ral

Feelings

Facts, events,
concepts,
locations

Skilled
movements and
habits

Amygdala

Cerebral cortex
Hippocampus

Frontal cortex
Thalamus
Basal ganglia

BDNF
&
MOTOR
LEARNING

Low levels correlated with depression, increased

hippocampal atrophy, decreased memory
retention and spatial memory performance,
dementia, T2DM.
Multiple animal studies where endogenous BDNF was
blocked using antisense oligonucleotide have found
rehabilitation-induced skilled reaching recovery
to be prevented.
Reduced BDNF and cortical map reorganization.
Additionally, intracortical injections have been shown to
restore cortical M1 map functionality partially.

Circulating BDNF scores significantly associated with

cognitive test scores.

AEROBIC EXERCISE
How we as neurorehabilitation specialists may
effect endogenous changes in BDNF

 Strengthening muscles of respiration.

Strengthening and improving heart efficiency.
Improving circulation and tissue & organ perfusion.

AEROBIC
EXERCISE:
GENERAL
EFFECTS

Reducing blood pressure.

Increasing circulating erythrocytes.
Improving mental health
Reducing risks for sedentary lifestyle diseases.
Improved metabolic efficiency.
Neovascularization of myogenic tissues.
Aerobic capacity improvement.
Improving healing rates.
Attenuates effects of atherosclerotic cerebrovascular
diseases.
Neuroprotective.

 Improves cognition on variety of tasks.

Increased mental arousal.

AEROBIC
EXERCISE:
COGNITION

Strongest benefit for executive-control processes

as opposed to other cognitive measures, e.g. speed,
visuospatial, controlled-processing).
Planning, scheduling, working memory, multi-tasking.

Improvements in information processing, motor

learning, and mobility.
Exhibits prophylactic and disease-attenuating effects
of dementia, Alzheimers Disease, and other
neurodegenerative conditions.

AEROBIC
EXERCISE:
MOTOR
LEARNING

Improved within-session performance of motor

sequence task (8-wk aerobic program vs. stretching
program) in pts with CVA.
Improved information processing and memory in
healthy adults with aerobic exercise.
Alters memory processing, impacting learning and
changes in motor behavior.
Experience-dependent
Aerobic exercise not responsible for inducing
neuroplastic changes alone.
For most meaningful effects: Paired closely, temporally,
with sufficient and meaningful practice.

 Multiple neurotrophins are released during exercise, singlebout and training period.
BDNF
Synapsin-1
Insulin-like growth factor 1

AEROBIC
EXERCISE
&
BDNF

BDNF most responsive to exercise.

Activity-dependent.
Aerobic exercise upregulates BDNF in periphery and CNS.
Upregulation is transientelevated BDNF post-exercise
levels do not persist long-term when training is stopped.
BDNF response an epiphenomenon of what happens
centrally, even though basal BDNF, peripherally, remains
unchanged.
Resistance Training?
Limited evidence showing significant effects on BDNF levels
and motor learning.

 Small, but growing evidence in CVA, TBI, MS, SCI,

dementia, AD
Pathologic animal studies have demonstrated:

EVIDENCE

Improved motor learning at cortical and spinal cord

levels.
Improved skilled reaching after aerobic exercise +
motor retraining intervention (focal ischemia).
Improved staircase task negotiation.
Improved memory in spatial tasks.

Pathologic human studies have demonstrated:

Improved sequential motor skill acquisition.
Improved STM and LTM.
Improved cognition in executive-control domain.

Aerobic
Exercis
e (&
RT)

IF YOU STILL
HAVENT
GOTTEN
IT

BDNF

Taskoriente
d
trainin
g

Improve
d motor
learning

 Prime the CNS for the neuroplastic changes

underlying the desired change in behavior.

PRIMING
MOTOR
LEARNING
&
MOTOR
REHABILITATIO
N

When should aerobic exercise be performed?

Before or after motor task practice?
Before
Facilitates detection and encoding of information
relevant to task.

After
Facilitates processes involved in motor memory
consolidation.

When EXACTLY???
1-2 hours post-exercise demonstrated increased
BDNF levels, in which motor learning will also be most
likely enhanced.

 Based on the currently available literature

PRIMING
MOTOR
LEARNING
&
MOTOR
REHABILITATIO
N

Aerobic exercise sessions of 30 minutes.

Training intensities ~60-70% Hrmax.
At least 4 days per week.
Combination of aerobic and resistance exercise.

Alternatives?
Cycling and high intensity intervals (3x3 minutes
above ventilatory threshold) immediately before or
after practice enhanced motor performance on
retention tests 1 and 7 days post-practice (in healthy
individuals).

IN SUMMARY
Three sentences + 2 charts

IN
SUMMARY

Aerobic exercise can be utilized more effectively by

neurorehabilitation specialists to enhance the CNSs
capacity for neural plasticity by up-regulation of BDNF
and other neurotrophins.
Aerobic exercise alone does not induce neural
plasticityit merely provides an enriched
environment that supports it.
Temporal proximity is integral to effectively capitalize
on aerobic exercises effects on BDNF.

Aerobic
Exercise
Indirect
Effects

Direct
Effects

Physical
Fitness
(cardiorespiratory
& muscular)
Systemic &
CNS
Inflammation

Neurotrophic
Growth Factors
(BDNF, NT-3, etc.)

Neuroplasticit
Cerebral
y
Blood Flow

Neurogenesis

Neuroprotecti
Brain health
on
cognitive function (learning,
memory, attention.
mood, arousal
neurodegeneration

Neurotransmitte
rs (dopamine,
serotonin, etc.)

Aerobic exercise
bout

Primed for
neuroplasticity

BDNF in
cerebral
cortex,
hippocampu
s,
cerebellum,
and spinal
cord

Motor
training

Response to
rehabilitation

LTP and
dentritic
branching in
neural
circuits
supporting
movement
and
learning

THANKS
TO

Likes Apple
, REI, la
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own jokes,
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and not sig
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k later, lea
ding to con
Gregs and
fused
6 inch pile
s of paper
desk. At le
on his
ast hes a
doctor.

DR. COBY,
JULIE, &
ANU!

Evidence
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REFERENCES
Wheres the evidence? On the next two slides.
WHY DIDNT YOU CITE EACH ONE ON EVERY SLIDE?!
Easy. Im a slacker, and I would have cited every one on each
slide.

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