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CIMIT Summer Education Series 2007
Neurotechnology: Translating Basic Discoveries into Clinical Promise



7.24.2007

Neural Control of Movement and Applications for Stroke Intervention

SPEAKER: Emilio Bizzi, MD, PhD: MIT


Cortical Stimulation to Promote Stroke Recovery

SPEAKER: Alvaro Pascual-Leone, MD, PhD:
HMS, BIDMC

 

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Experts discuss stroke-recovery research

The third segment of the CIMIT Summer Education Series 2007 produced thoughtful and penetrating presentations of the brain’s response to a stroke.

Presenting were Emilio Bizzi, MD, PhD, Institute Professor, McGovern Institute of Brain Research, at MIT; and Alvaro Pascual-Leone, MD, PhD, professor of neurology, Harvard Medical School; director of the Berenson-Allen Center for Noninvasive Brain Stimulation; and attending neurologist and director of research, Behavioral Neurology Unit, Beth Israel Deaconess Medical Center.

The session was part of the summer series titled, “Neurotechnology: Translating Basic Discoveries into Clinical Promise.”

Close to 1 million Americans suffer strokes each year, and it is the leading cause of disability in the developing world.

Dr. Pascual-Leone spoke on the topic of “Cortical Stimulation to Promote Recovery after Stroke.” He said that both noninvasive and invasive brain stimulation techniques have been recently tested in proof-of-principle studies with stroke patients aimed at enhancing functional recovering.

He cited techniques such as repetitive transcranial magnetic stimulation, transcranial director current stimulation and direct cortical stimulation with epidural electrodes.

Dr. Pascual-Leone said that ongoing clinical trials confirm promising results. He showed tape of a stroke patient before and after stimulation of specific parts of the brain, and the patient showed improved mobility in the hand and arm following stimulation.

Dr. Bizzi spoke on the topic of “Neural Control of Movement and Applications for Stroke Intervention.”

He said neuronal recordings from awake monkeys have revealed plasticity at the single-cell level, and some of the neurons of the cortical motor areas exhibit learning-dependent activity changes.

Whether the adapted cells represent simple command signals or the formation of internal models designed to handle a new dynamic environment is still open to question, he said, but studies continue.

Neural Control of Movement and Applications for Stroke Intervention

When one thinks of learning, one rarely thinks of simple motor tasks such as picking up an object or taking a step.  The brain seems to learn these actions effortlessly.  Unfortunately, a stroke can undermine even the most basic movements and can make it impossible for a person to lead an independent life.  Hoping to help stroke patients, researchers are attempting to deconstruct the neurological processes that underlie motor function.

To understand how motor learning is accomplished at a cellular level, the lab of Dr. Emilio Bizzi has studied cells in the motor cortices of monkeys.  In one experiment, as monkeys reached for objects, members of the lab measured the activity of individual cortical neurons.  The experimenters manipulated the task by applying perpendicular forces to the monkeys’ arms, and over time, the monkeys began to compensate for these forces.  Single-cell recordings showed that certain cells in the monkeys’ cortices responded to the perpendicular forces by gaining directional sensitivity that they had previously lacked or by losing directional sensitivity that they had once possessed.  These “memory cells” retained their new directional sensitivities (or lack thereof) even when the perpendicular forces were no longer applied, suggesting that motor learning occurs, at least to some extent, in the cortex. 

On the musculoskeletal level, the Bizzi lab attempted to determine how the activity of thousands of motor neurons is coordinated, a process that takes place every time one does so much as move a hand.  They hypothesized that motor units, each composed of a single motor neuron and its associated muscle cells, are organized in a hierarchical and modular fashion.  Measuring muscle stimulation in frogs’ legs and using an extraction algorithm to identify correlated activity, they found that “muscle synergies” – groups of motor units whose activity is correlated – do indeed exist.

These results suggest that strokes should be considered by analyzing how they affect synergies in the cortex.  Perhaps brain lesions caused by strokes eliminate synergies or alter the balance of muscles within them.  Hopefully, learning about the brain’s modularity will further the rehabilitation of stroke patients.  

Cortical Stimulation to Promote Stroke Recovery

Stroke is the leading cause of disability in developed societies.  A stroke’s severity depends on its size and on the ability of the brain to relearn various functions with restricted resources.  Because of the human brain’s plasticity, some stroke survivors don’t even realize that they have had a stroke.  In many cases, however, the brain’s ability to compensate for stroke damage is limited.  Seeking to promote this process of compensation, researchers are attempting to use electromagnetic brain stimulation to help stroke victims recover lost motor abilities.

Using functional magnetic resonance imaging (fMRI), researchers can localize areas of the brain involved in the execution of a given task.  In stroke patients, one hemisphere of the brain is damaged, and tasks governed by this side of the brain can be impaired.  When a stroke patient attempts to perform a task governed the damaged portion of the brain, fMRI usually shows activity in both hemispheres of the brain.  The activity in the healthy hemisphere does not control the motor circuitry involved in the task; in fact, the activity in the healthy hemisphere seems to prevent the damaged hemisphere from functioning effectively.  A team of researchers led by Dr. Pascual-Leone is working on a variety of techniques to reduce this “excessive interhemispheric interference,” hoping that these techniques will promote the rehabilitation of stroke patients.

Transcranial magnetic stimulation (TMS) provides one means of controlling interhemispheric interference.  When a patient undergoes TMS, an electromagnet is positioned on the surface of his or her scalp.  Depending on the frequency of the current applied to the magnet, activity in the nearby region of the brain can be increased or decreased.  By using TMS to decrease activity in areas of the stroke patient’s healthy hemisphere, doctors have been able to enhance the ability of stroke patients to perform tasks such as picking up a telephone. 

Transcranial direct current stimulation (tDCS) also allows doctors to suppress inhibitory activity in the healthy hemisphere of the brain.  The technique involves running current between two electrodes placed on the scalp.  It has not proven extremely effective for stroke patients because fluid and scar tissue leftover after a stroke can shunt current away from the target location. 

Dr. Pascual-Leone’s team has conducted a proof-of-principle study that has shown that ten days of TMS can help stroke patients perform previously difficult tasks and that these improvements can last for at least eight months after the therapy has ended.  In the future, engineers may be able to design epidural or subdural TMS devices that patients could wear continuously.  TMS could also be combined with therapies involving motor training.   

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