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

Abstract

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. 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). 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. 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. 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.