Transcranial magnetic stimulation in Alzheimer's disease: A neurophysiological marker of cortical hyperexcitability

Giovanni Pennisi, Raffaele Ferri, Giuseppe Lanza, Mariagiovanna Cantone, Manuela Pennisi, Valentina Puglisi, Giulia Malaguarnera, Rita Bella

Research output: Contribution to journalArticle


Recently, neuropathological studies have shown an important motor cortex involvement in Alzheimer's disease (AD), even in its early stages, despite the lack of clinically evident motor deficit. Transcranial magnetic stimulation (TMS) studies have demonstrated that cortical excitability is enhanced in AD patients. This cortical hyperexcitability is believed to be a compensatory mechanism to execute voluntary movements, despite the progressive impairment of associative cortical areas. At present, it is not clear if these motor cortex excitability changes might be the expression of an involvement of intracortical excitatory glutamatergic circuits or an impairment of inhibitory cholinergic and, to a lesser extent, gabaergic activity. Although the main hypothesis for the pathogenesis of AD remains the degeneration of the basal forebrain cholinergic neurons, the development of specific TMS protocols, such as the paired-pulse TMS and the study of the short-latency afferent inhibition, points out the role of other neurotransmitters, such as gamma-amino-butyric acid, glutamate and dopamine. The potential therapeutic effect of repetitive TMS in restoring or compensating damaged cognitive functions, might become a possible rehabilitation tool in AD patients. Based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological brain aging, mild cognitive impairment, AD and other dementing disorders. The present review provides a perspective of these TMS techniques by further understanding the role of different neurotransmission pathways and plastic remodelling of neuronal networks in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)587-598
Number of pages12
JournalJournal of Neural Transmission
Issue number4
Publication statusPublished - Apr 2011



  • Aging
  • Alzheimer's disease
  • Cortical excitability
  • Neuroplasticity
  • Neurotransmission
  • Transcranial magnetic stimulation

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

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