Impaired Spike Timing Dependent Cortico-Cortical Plasticity in Alzheimer's Disease Patients

Francesco Di Lorenzo, Viviana Ponzo, Caterina Motta, Sonia Bonnì, Silvia Picazio, Carlo Caltagirone, Marco Bozzali, Alessandro Martorana, Giacomo Koch

Research output: Contribution to journalArticlepeer-review


Background: Mechanisms of cortical plasticity have been recently investigated in Alzheimer's disease (AD) patients with transcranial magnetic stimulation protocols showing a clear impairment of long-Term potentiation (LTP) cortical-like plasticity mechanisms. Objective: We aimed to investigate mechanisms of cortico-cortical spike-Timing dependent plasticity (STDP) in AD patients investigating the connections between posterior parietal cortex (PPC) and primary motor cortex (M1). Methods: We used a cortico-cortical paired associative stimulation (cc-PAS) protocol to repeatedly activate the connection between PPC and M1 of the left-dominant hemisphere in a sample of fifteen AD patients and ten age-matched healthy subjects. PPC transcranial magnetic stimulation preceded (ccPAS +5) or followed M1 stimulation (ccPAS-5) by 5 ms. Motor-evoked potentials (MEPs) were collected to assess the time course of the after effects of cc-PAS protocol measuring MEP amplitude as index of cortico-cortical associative plasticity. Results: In healthy subjects, ccPAS-5 protocol induced the expected long-lasting increase of MEP amplitude compatible with LTP-like cortical plasticity while PAS +5 protocol induced the opposite effect. AD patients did not show any significant modification of the amplitude of MEP after both ccPAS protocols. Conclusions: Our study shows that in AD patients the time-locked activation of human cortico-cortical connections is not able to form STDP, reflecting an impairment of a multi-factor plasticity process.

Original languageEnglish
Pages (from-to)983-991
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - Jan 1 2018


  • Alzheimer's disease
  • connectivity
  • long-Term potentiation
  • motor cortex
  • parietal cortex
  • plasticity
  • spike-Timing dependent plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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