Proprioception in aging: A comprehensive characterization of peripheral alterations, network dynamics and neuroplasticity

The aim of this PhD project is to investigate age-related alterations in proprioception, with a specific focus on the peripheral and central mechanisms. The thesis is structured into six chapters. The first chapter provides a general introduction to proprioceptive function and outlines age-related changes affecting both peripheral receptors and central sensorimotor networks. The subsequent chapters present the experimental contributions conducted during the PhD, each addressing different aspects of proprioceptive processing and plasticity in aging. Chapter 2 characterizes behavioral changes in proprioception by comparing young and older adults in tasks assessing position sense and movement perception. While position matching performance was preserved in older adults, results revealed a pronounced age-related alteration in movement perception, characterized by a hyper-illusory experience and reduced discrimination ability for proprioceptive-induced sensations. These findings suggest that aging affects the processing of dynamic proprioceptive signals, potentially reflecting changes in muscle spindles sensitivity and central integration mechanisms. Chapter 3 investigates age-related changes in parieto-motor functional connectivity using a dual-site transcranial magnetic stimulation (TMS) approach. Results demonstrate that proprioceptive stimulation reveals the presence of facilitatory inputs from the posterior parietal cortex to the primary motor cortex in older adults, although these were delayed compared to Young adults and were absent at rest. Moreover, the strength of this connectivity seems associated with proprioceptive accuracy, suggesting a functional link between network dynamics and perceptual performance. Chapter 4 examines whether cortical plasticity induced by cortico-cortical paired associative stimulation (cPAS) can be enhanced by a state-dependent approach in older adults. Delivering cPAS during active task engagement leads to greater increases in cortical excitability and improved behavioral performance compared to stimulation at rest, highlighting the importance of brain state in modulating neuroplastic outcomes in aging. Chapter 5 explores the effects of a combined action observation and kinesthetic illusion (AO-KI) protocol on primary motor cortex excitability. Results show that AO-KI induces robust and long-lasting increases in corticospinal excitability in older adults, suggesting that multisensory stimulation can effectively engage preserved plasticity mechanisms even in aging populations. The sixth chapter outlines future directions and final conclusions of the knowledge provided by the studies presented in the thesis.