A new index of cortical plasticity induced by paired associative stimulation to describe cognitive status in aged healthy subjects

Nicola Loi¹Francesca Ginatempo^2*Mohammed Zeroual²Lucia Ventura¹Antonella Cano¹Carmen Oneto²Paola Ortu³Maria Rita Piras³Franca Deriu^2,4*

• ¹Azienda Ospedaliero Universitaria Sassari, Sassari, Italy
• ²Department of Biomedical Sciences, University of Sassari, Sassari, Italy
• ³Institute of Genetic and Biomedical Research, Department of Biomedical Sciences, National Research Council (CNR), Monserrato, Calabria, Italy
• ⁴Unit of Endocrinology, Nutritional and Metabolic Disorders, AOU Sassari, Sassari, Italy

Cortical plasticity is a key factor for cognitive skills and, in humans, paired associative stimulation (PAS) is a useful tool to study it. Currently, due to the number of non-responders to PAS and to discrepancies in the post-PAS time points assessed, a plasticity index describing PAS effects and correlating it to cognitive status is lacking. Therefore, this study investigated which PAS index better discriminates between responders (RRs) and non-responders (NRs) and correlates with cognitive status. Seventy-six healthy aged subjects (67.0±7.2 y.o., 35 males) were enrolled. The Montreal cognitive assessment (MoCA), the mini mental state examination (MMSE) and the Addenbrooke's cognitive assessment (ACE-R) were used to assess cognitive status. Motor-evoked potentials (MEP) were recorded from the first dorsal interosseous muscle at baseline and after 0, 10, 20 and 30 minutes from PAS, pairing a peripheral median nerve stimulation with a transcranial magnetic stimulation stimulus over the left primary motor cortex. MEP amplitude was used to calculate the grand average (GrA), which is the most used PAS plasticity index, and two newly introduced indexes: the curve concavity (CC) and the pre-vs post-PAS difference (PPPD). CC described the curve shape of the PAS effects while PPPD calculated the significant differences between baseline and post-PAS MEP amplitude. CC demonstrated good consistency as PAS-plasticity index with high odds ratios and sensibility in discrimination of responsiveness to PAS; PPPD had higher specificity in the identification of RRs. Only MoCA score was significantly higher (p=0.006) in RRs than NRs when the two groups were discriminated according to CC and it significantly correlated with CC (p=0.013). In conclusion, CC may represent a potential PAS-plasticity index to describe cortical plasticity and cognitive status in humans, with a possible practical application in patients with cognitive impairment.