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

ABSTRACT

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.

KEYWORDS:

• Alzheimer’s dementia
• neurodegeneration
• transcranial magnetic stimulation
• cortical plasticity
• cortical hyperexcitability
• SAI
• SICI
• rTMS

Article highlights

• The examination of cortical excitability and plasticity can be reliably undertaken by the non-invasive technique of Transcranial Magnetic Stimulation (TMS)

• Cortical dysfunction in Alzheimer’s disease (AD) is defined by twin signatures of cortical hyperexcitability and abnormal plasticity which are readily demonstrable TMS findings. Cholinergic, GABAergic and Glutamatergic circuits each contribute to cortical hyperexcitability seen with AD.

• Utilization of specific signatures of cortical hyperexcitability has promise in developing targeted therapies for patients with AD though these endeavors remain within the realms of clinical research.

• Repetitive TMS (rTMS) protocols which combine multi-site stimulation with cognitive therapies show promise in the treatment of Alzheimer’s dementia at an early stage, though further refinements of protocols and patient selection criteria are needed.

• Novel techniques such as TMS-EEG will enable the identification of cortical abnormalities within non-motor areas at an earlier point in the clinical disease spectrum, and with further advancements potentially also enable the tailored delivery of rTMS techniques.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.