69. Impaired spike timing dependent cortico-cortical plasticity in Alzheimer's Disease patients. Issue 12 (December 2016)

• Record Type: Journal Article
• Authors: Di Lorenzo, F.; Martorana, A.; Ponzo, V.; Bonní, S.; Koch, G.
• Is Part Of: Clinical neurophysiology. Volume 127:Issue 12(2016:Dec.)
• Page Start: e340
• Publication Date: 2016-12
• Subjects: Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2016.10.081
• Languages: English
• ISSNs: 1388-2457

Abstract

Abstract : Mechanisms of cortical plasticity have been widely investigated in Alzheimer's Disease (AD) patients with transcranial magnetic stimulation (TMS) protocols as Theta Burst Stimulation, 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. The aim of our study is to investigate mechanisms of spike-timing dependent plasticity in Alzheimer's disease patients and furthermore to investigate the effects of the modulation of PPC-M1 pathway on cholinergic transmission, greatly impaired in AD patients. Twelve AD patients and eight age-matched healthy subjects were evaluated. We used bifocal TMS to repeatedly activate the connection between the PPC and M1 of the left-dominant hemisphere. Left PPC TMS preceded or followed the M1 stimulation by 5 ms, respectively PAS +5 and PAS −5. To best activate the ipsilateral PPCâ€"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 â̂1/48.3 min. Motor evoked potentials and central cholinergic pathway, evaluated with Short-latency afferent inhibition (SAI) protocol, were evaluated before and after PAS (+5 or −5) protocol. 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 didn't show any significant 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. The data here presented confirm that in AD patients there is an altered cortical plasticity, elicited with a new TMS protocol able to investigate the connections between PPC-M1. The central cholinergic pathway as indexed by the amount of SAI, is altered in AD patients, but it is normalized after the application of PAS +5 protocol, suggesting a possible role of PPC-M1 pathway on the 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.