Bridging Brain, Mind, and Behavior Research Award

James S. McDonnell Foundation

Brain Plasticity and Neuro-Rehabilitation

Our brains are constantly changing throughout our lives.  Connections between neurons are strengthened or weakened as we learn each new skill and acquire each new memory.  Such circuitry changes, called ‘brain plasticity’, serve to optimize the brain’s function to meet each individual’s needs.  If I decide one day I want to get better at tap dancing, wine tasting, or identifying bird calls, my brain is happy to oblige and rewire its circuits to make these skills possible.  Practice makes perfect because practice triggers plasticity.  


The observation that people can get ten times better at most simple tasks with a few weeks of practice has lead some to wrongly conclude that we use only ten percent of our brains.  In fact, the brain allocates its computational resources with great efficiency.   Brain plasticity allows neural networks to accomplish difficult tasks that evolution never selected for, including freeway driving, Braille reading, and calculus.  The nervous system, like the immune system, evolved to solve undefined problems and adapt to changing environments.  Even the brain’s remarkable ability to adapt does have limits, however. 


Brain damage can cause pain, paralysis, blindness, and loss of language depending on the regions of the brain that are affected.  Plasticity helps restore some function by rewiring damaged circuits, but is often insufficient for full recovery, even after months of rehabilitation. 


Despite advances in neurosurgery, there is presently no way to directly rewire the brain.  While physicians can treat many of the symptoms of brain damage, there is little they can do to stimulate recovery.  In this way treatment for neurological disease is very much like treatment for infection and cancer was a century ago.  Recent research offers new hope for millions of stroke patients struggling to regain lost independence.   It may one day be possible to rebuild damaged circuits and restore lost function by guiding plasticity in much the same way that doctors now routinely manipulate the immune system. 


We know from studies of normal learning that plasticity depends on repetition and attention.  If I intently practice bird call identification, for example, the part of my brain that responds to these sounds would increase, making it easier to distinguish the subtle differences between them.  However, if I simply heard the sounds over and over without focusing on them, there would be no change in my brain and I would learn nothing.  Focused attention stimulates release of neurotransmitters that encourage plasticity and learning.  Without this mechanism to regulate plasticity our neurons would try to learn every detail about common, but useless stimuli like air conditioner sounds and the textures of our clothes. 


During the period after brain damage decreases levels of neurotransmitters like acetylcholine, dopamine, and norepinephrine are decreased, limiting the brain’s rewiring potential.  Drugs that increase release of these transmitters don’t help much because they tend to stimulate non-specific plasticity.  However, if one could direct the form of plasticity stimulated by these drugs, it might be possible to control rewiring and restore lost function.


I have recently demonstrated that it is possible to precisely manipulate plasticity in animals by controlling neurotransmitter release and sensory experience.  Using electrical stimulation of one of the brain’s learning centers, I was able to alter both the brain’s wiring and processing speed.  My next goals are to develop a method to control plasticity by combining drug therapy with sensory stimulation and to test its effectiveness in restoring functions lost to brain damage.  


Preliminary evidence indicates that combining speech and physical therapy with pharmacological stimulation can significantly improve recovery from stroke.  As these techniques are refined, they may make complete recovery from stroke a realistic goal.  The potential to manipulate plasticity in humans would also be beneficial for patients suffering from other neurological disorders.  Many scientists believe that epilepsy, focal dystonia, tinnitus, and chronic pain result from pathological forms of plasticity.  While current treatments attempt to alleviate the symptoms of these conditions, neurorehabilitation could be used to reverse the bad wiring that causes them.    It may even be possible to use therapeutic plasticity as a treatment for psychiatric disorders, such as posttraumatic stress disorder, drug addiction, obsessive-compulsive disorder, and phobia. 


The proposed experiments will provide a solid experimental foundation for further development of neurorehabilitation to minimize side effects and optimize patient recovery.  Although far from proven, neurorehabilitation has the potential to transform the treatment of brain disease in the same way that antibiotics and chemotherapy have changed the treatment of infection and cancer. 


-         For preliminary findings see our Society for Neuroscience 2005 Poster