P271 Impaired spike timing dependent cortico-cortical plasticity in Alzheimer's disease patients. Issue 3 (March 2017)

• Record Type: Journal Article
• Authors: Di Lorenzo, F.; Ponzo, V.; Caltagirone, C.; Martorana, A.; Koch, G.
• Is Part Of: Clinical neurophysiology. Volume 128:Issue 3(2017:Mar.)
• Page Start: e143
• Publication Date: 2017-03
• Subjects: Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2016.10.381
• Languages: English
• ISSNs: 1388-2457

Abstract

Abstract : Introduction: Mechanisms of cortical plasticity have been widely investigated in Alzheimer's disease (AD) patients with TMS protocols, showing a clear impairment of Long-Term Potentiation (LTP) cortical-like plasticity and a relative sparing of Long Term Depression (LTD) mechanisms. Recently a new TMS protocol, investigating the connections between posterior parietal cortex (PPC) and primary motor cortex (M1), elicited in a bidirectional way LTP and LTD effects. Objective: We investigated mechanisms of spike-timing dependent plasticity in AD patients and the effects of the modulation of PPC-M1 pathway on cholinergic transmission, greatly impaired in AD patients. Material and methods: Twelve AD patients and eight age-matched healthy subjects (HS) were evaluated. We used bifocal TMS to repeatedly activate the connections between the PPC and M1 of the left-dominant hemisphere. PPC TMS preceded or followed the M1 stimulation by 5 ms, respectively PAS +5 and PAS −5. To best activate the ipsilateral PPC-M1 connection, the conditioning stimulus was applied over the left PPC at an intensity of 90% of the ipsilateral resting motor threshold. For the PAS protocol, 100 pairs of stimuli were continuously delivered at a rate of 0.2 Hz for ∼8.3 min. Motor evoked potentials and central cholinergic way, evaluated with Short-latency afferent inhibition (SAI) protocol, were evaluated before and after PAS (+5 or −5) protocol. Results: as expected HS showed an LTP-like cortical plasticity following PAS −5 protocol and an LTD-like cortical plasticity after PAS +5 protocol, while AD patients did not show any modification of the amplitude of MEP after repeated activation of PPC-M1 connections. As compared to HS, AD patients showed worst SAI values. Interestingly, after PAS +5 protocol, in AD patients SAI levels were restored. Conclusions: The data here presented confirm that in AD patients there is an altered cortical plasticity. The central cholinergic way is altered in AD patients, but after the application of PAS +5 protocol his levels are restored, suggesting a possible role of PPC-M1 pathway on modulation of this inhibitory intracortical circuit. PAS protocol is able to investigate the mechanisms of altered cortical plasticity in AD patients. Central cholinergic transmission can be modulated by stimulation of PPC-M1 connections.