Cortical hyperexcitability and plasticity in Alzheimer’s disease: developments in understanding and management

INTRODUCTION: Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that provides important insights into Alzheimer's Disease (AD). A significant body of work utilizing TMS techniques has explored the pathophysiological relevance of cortical hyperexcitability and plasticity in AD and their modulation in novel therapies. AREAS COVERED: This review examines the technique of TMS, the use of TMS to examine specific features of cortical excitability and the use of TMS techniques to modulate cortical function. A search was performed utilizing the PubMed database to identify key studies utilizing TMS to examine cortical hyperexcitability and plasticity in Alzheimer's dementia. We then translate this understanding to the study of Alzheimer's disease pathophysiology, examining the underlying neurophysiologic links contributing to these twin signatures, cortical hyperexcitability and abnormal plasticity, in the cortical dysfunction characterizing AD. Finally, we examine utilization of TMS excitability to guide targeted therapies and, through the use of repetitive TMS (rTMS), modulate cortical plasticity. EXPERT OPINION: The examination of cortical hyperexcitability and plasticity with TMS has potential to optimize and expand the window of therapeutic interventions in AD, though remains at relatively early stage of development.