You Are as Old as the Connectivity You Keep: Distinct Neurophysiological Mechanisms Underlying Age-Related Changes in Hand Dexterity and Strength

Background: Aging can lead to a decline in motor control. While age-related motor impairments have been documented, the underlying changes in cortico-cortical interactions remain poorly understood. Methods: We took advantage of the high temporal resolution of dual-site transcranial magnetic stimulation (dsTMS) to investigate how communication between higher-order rostral premotor regions and the primary motor cortex (M1) influences motor control in young and elderly adults. We assessed the dynamics of connectivity from the inferior frontal gyrus (IFG) or pre-supplementary motor area (preSMA) to M1, by testing how conditioning of the IFG/preSMA affected the amplitude of motor evoked potentials (MEPs) induced by M1 stimulation at different temporal intervals. Moreover, we explored how age-related changes in premotor-M1 interactions relate to motor performance. Results: Our results show that both young and elderly adults had excitatory IFG-M1 and preSMA-M1 interactions, but the two groups’ timing and strength differed. In young adults, IFG-M1 interactions were early and time-specific (8 ms), whereas in older individuals, they were delayed and more prolonged (12-16 ms). PreSMA-M1 interactions emerged early (6 ms) and peaked at 10-12 ms in young individuals but were attenuated in older individuals. Critically, a connectivity profile of the IFG-M1 circuit like that of the young cohort predicted better dexterity in older individuals, while preserved preSMA-M1 interactions predicted greater strength, suggesting that age-related motor decline is associated with specific changes in premotor-motor networks. Conclusions: Preserving youthful motor network connectivity in older individuals is related to maintaining motor performance and providing information for interventions targeting aging effects on behavior.