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

Article type: Research Article

Authors: Di Lorenzo, Francesco^a | Ponzo, Viviana^a | Motta, Caterina^a | Bonnì, Sonia^a | Picazio, Silvia^a | Caltagirone, Carlo^{a; b} | Bozzali, Marco^c | Martorana, Alessandro^{a; b} | Koch, Giacomo^{a; d; *}

Affiliations: [a] Department of Behavioural and Clinical Neurology, Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Rome, Italy | [b] Department of System Medicine, Tor Vergata University, Rome, Italy | [c] Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy | [d] Stroke Unit, Tor Vergata Hospital, Rome, Italy

Correspondence: [*] Correspondence to: Giacomo Koch, MD, PhD, Non Invasive Brain Stimulation Unit, Department of Behavioural and Clinical Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy. Tel.: +39 0651501181; E-mail: g.koch@hsantalucia.it.

Abstract: 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.

Keywords: Alzheimer’s disease, connectivity, long-term potentiation, motor cortex, parietal cortex, plasticity, spike-timing dependent plasticity

DOI: 10.3233/JAD-180503

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 983-991, 2018