Tuesday, July 10, 2012

Neural plasticity and rehab - Jeffrey Kleim

A member of SomaSimple, "Elanchaim", found and posted this three-year old video to SomaSimple: 

Enjoy! It's about 1 hr 17 minutes long. At the time, he was at U Florida. 

Highlights of the first 10 minutes: 

1. How neurobiology of the brain changes with damage and how it restores itself.
2. Why we don't have a breakthrough, a "polio vaccine" for stroke: There has been a disconnect between basic sciences and clinical sciences. At almost any university you find speech path, OT and PT departments are completely separate from medical facilities often from basic neurosciences, speak different languages, different journals - huge gap. Also, until just lately, basic sciences haven't really had a whole lot to tell clinical sciences about how they should be doing rehab. 

Definition of Neural Plasticity (minute 4:30)

3. The term "Neuroplasticity" was first coined in the 1800s by psychologist William James: about "habit" he said, "The phenomenon of habit in living beings are due to the plasticity of the organic materials of which their bodies are composed... nervous tissue seems endowed with a very extraordinary degree of plasticity." - William James 1887
4. Research into neural plasticity exploded after about 1995, because of new techniques for investigation.
5. Plasticity begins at level of genome, in genes that seem to be turned on by certain kinds of stimulation; transcriptional products of those gene expressions are proteins which go off in the neurons and impart some kind of change, form new synapses, change connections between neurons. The idea is that this can be manipulated across 100's of millions of neurons.
6. First we must adopt the idea of neural monism, that there is no mind/body problem, no dualism.  

  • "All behaviour, whether it is motor, or sensory, or cognitive, is a product of neural activity."
  • "Changes in behaviour can be observed as changes in neural circuits."

7. Working definition by Kleim, minute 7:50: "Any observable change in neuron structure or function", measurable in several ways; directly by observing individual neurons, or indirectly, inferred from measures across populations of neurons, either anatomically or physiologically.

  • Individual/anatomical: dendritic arborization, spine density, axonal arborization, bouton density, synapse number. 
  • Individual/physiological: unit activity, intrinsic excitability, synaptic currents, axonal bouton density.
  • Population/anatomical: structure weight, structural thickness, structure volume, neuron number, neuron density.
  • Population/physiological: regional blood flow, regional EEG, field EPSPs, sensory representations, motor representations.

Kleim, formerly at U Lethbridge, developed his neural plasticity work at the Greenough Lab in the Beckman Institue in Illinois
“All of my work in graduate school was about how motor learning in an intact nervous system is affected by the way that neurons were connected, looking at plasticity and neural connections,” he said. “I spent most of my graduate career looking at plasticity within motor brain areas and when I left I went on to try and apply that plasticity to a damaged brain, to find out how relearning might be accomplished by the same neuromechanisms that account for learning in a normal brain.”

He currently works as associate professor at the school of Biological and Health Systems Engineering at Arizona State U, in Tempe.
"Jeffrey Kleim studies how neural plasticity supports learning in the intact brain and “relearning” in the damaged or diseased brain. His research is directed at developing therapies that optimize plasticity in order to enhance recovery after stroke and Parkinson’s Disease.The brain is a highly dynamic organ that is capable of structural and functional reorganization in response to a variety of manipulations. This neural plasticity is the mechanism by which the brain encodes experience. My laboratory examines how plasticity within rat and human motor cortex supports learning in the intact brain and “relearning” after stroke. We use intracortical microstimulation in rats and transcranial magnetic stimulation in humans to examine how motor training alters the functional organization of motor cortex. This work has demonstrated that rehabilitation-dependent recovery of motor function after stroke is associated with a reorganization of movement representations in rodent motor cortex. Furthermore, there are specific behavioral and neural signals that drive both recovery and plasticity. These experiments are being used to test novel therapies for enhancing motor recovery in stroke patients."

Here is a list of his publications at PubMed, including these five free ones

1.  Tennant KA, Adkins DL, Donlan NA, Asay AL, Thomas N, Kleim JA, Jones TA. The Organization of the Forelimb Representation of the C57BL/6 Mouse Motor Cortex as Defined by Intracortical Microstimulation and CytoarchitectureCereb Cortex. 2011 April; 21(4): 865–876.
Published online 2010 August 25. doi:  10.1093/cercor/bhq159

2. Tennant KA, Asay AL, Allred RP, Ozburn AR, Kleim JA, Jones TA. The Vermicelli and Capellini Handling Tests: Simple quantitative measures of dexterous forepaw function in rats and miceJ Vis Exp. 2010; (41): 2076. Published online 2010 July 21. doi:  10.3791/2076

3. McHughen SA, Rodriguez PF, Kleim JA, Kleim ED, Marchal Crespo L, Procaccio V, Cramer SC. BDNF Val66Met Polymorphism Influences Motor System Function in the Human Brain. Cereb Cortex. 2010 May; 20(5): 1254–1262. Published online 2009 September 10. doi:  10.1093/cercor/bhp189

4. Kleim JA, Markham JA, Vij K, Freese JL, Ballard DH, Greenough WT. Motor learning induces astrocytic hypertrophy in the cerebellar cortex. Behav Brain Res. Author manuscript; available in PMC 2008 October 29. Published in final edited form as: Behav Brain Res. 2007 March 28; 178(2): 244–249. Published online 2007 January 25. doi:  10.1016/j.bbr.2006.12.022

5. Kleim JA, Freeman JH Jr, Bruneau R, Nolan BC, Cooper NR, Zook A, Walters D. Synapse formation is associated with memory storage in the cerebellumProc Natl Acad Sci U S A. 2002 October 1; 99(20): 13228–13231. Published online 2002 September 16. doi:  10.1073/pnas.202483399 PMCID: PMC130615 Neuroscience

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