Although the brain’s ability to change constantly in response to external and internal inputs is now well recognized
the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding,
transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical
neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether
repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer’s
and Parkinson’s disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably
coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological
variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about
TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures
with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal
brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology
and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements
of cortical excitability and plasticity in physiological aging, Alzheimer’s, Parkinson’s, and Huntington’s, disease.
The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic
aging from neurodegeneration and its potential as a method of therapeutic intervention.
Keywords: Transcranial magnetic stimulation, normal aging, neurodegeneration, Alzheimer's disease, Parkinson's disease,
Huntington's disease, cortical reactivity, cortical plasticity.
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