Cerebellum function: The chronometry of social perception.

The posterior cerebellum is emerging as a key structure for social cognition. A new study causally demonstrates its early involvement during emotion perception and functional connectivity with the posterior superior temporal sulcus, a cortical hub of the social brain.

Driving Hebbian plasticity over ventral premotor-motor projections transiently enhances motor resonance.

BACKGROUND: Making sense of others' actions relies on the activation of an action observation network (AON), which maps visual information about observed actions onto the observer's motor system. This motor resonance process manifests in the primary motor cortex (M1) as increased corticospinal excitability finely tuned to the muscles engaged in the observed action. Motor resonance in M1 is facilitated by projections from higher-order AON regions. However, whether manipulating the strength of AON-to-M1 connectivity affects motor resonance remains unclear. METHODS: We used transcranial magnetic stimulation (TMS) in 48 healthy humans. Cortico-cortical paired associative stimulation (ccPAS) was administered over M1 and the ventral premotor cortex (PMv), a key AON node, to induce spike-timing-dependent plasticity (STDP) in the pathway connecting them. Single-pulse TMS assessed motor resonance during action observation. RESULTS: Before ccPAS, action observation increased corticospinal excitability in the muscles corresponding to the observed movements, reflecting motor resonance in M1. Notably, ccPAS aimed at strengthening projections from PMv to M1 (PMv→M1) induced short-term enhancement of motor resonance. The enhancement specifically occurred with the ccPAS configuration consistent with forward PMv→M1 projections and dissipated 20 min post-stimulation; ccPAS administered in the reverse order (M1→PMv) and sham stimulation did not affect motor resonance. CONCLUSIONS: These findings provide the first evidence that inducing STDP to strengthen PMv input to M1 neurons causally enhances muscle-specific motor resonance in M1. Our study sheds light on the plastic mechanisms that shape AON functionality and demonstrates that exogenous manipulation of AON connectivity can influence basic mirror mechanisms that underlie social perception.

Neurophysiological Markers of Premotor-Motor Network Plasticity Predict Motor Performance in Young and Older Adults.

Aging is commonly associated with a decline in motor control and neural plasticity. Tuning cortico-cortical interactions between premotor and motor areas is essential for controlling fine manual movements. However, whether plasticity in premotor-motor circuits predicts hand motor abilities in young and elderly humans remains unclear. Here, we administered transcranial magnetic stimulation (TMS) over the ventral premotor cortex (PMv) and primary motor cortex (M1) using the cortico-cortical paired-associative stimulation (ccPAS) protocol to manipulate the strength of PMv-to-M1 connectivity in 14 young and 14 elderly healthy adults. We assessed changes in motor-evoked potentials (MEPs) during ccPAS as an index of PMv-M1 network plasticity. We tested whether the magnitude of MEP changes might predict interindividual differences in performance in two motor tasks that rely on premotor-motor circuits, i.e., the nine-hole pegboard test and a choice reaction task. Results show lower motor performance and decreased PMv-M1 network plasticity in elderly adults. Critically, the slope of MEP changes during ccPAS accurately predicted performance at the two tasks across age groups, with larger slopes (i.e., MEP increase) predicting better motor performance at baseline in both young and elderly participants. These findings suggest that physiological indices of PMv-M1 plasticity could provide a neurophysiological marker of fine motor control across age-groups.

The multifactorial nature of healthy brain ageing: Brain changes, functional decline and protective factors.

As the global population faces a progressive shift towards a higher median age, understanding the mechanisms underlying healthy brain ageing has become of paramount importance for the preservation of cognitive abilities. The first part of the present review aims to provide a comprehensive look at the anatomical changes the healthy brain endures with advanced age, while also summarizing up to date findings on modifiable risk factors to support a healthy ageing process. Subsequently, we describe the typical cognitive profile displayed by healthy older adults, conceptualizing the well-established age-related decline as an impairment of four main cognitive factors and relating them to their neural substrate previously described; different cognitive trajectories displayed by typical Alzheimer's Disease patients and successful agers with a high cognitive reserve are discussed. Finally, potential effective interventions and protective strategies to promote cognitive reserve and defer cognitive decline are reviewed and proposed.

Transcranial cortico-cortical paired associative stimulation (ccPAS) over ventral premotor-motor pathways enhances action performance and corticomotor excitability in young adults more than in elderly adults.

Transcranial magnetic stimulation (TMS) methods such as cortico-cortical paired associative stimulation (ccPAS) can increase the strength of functional connectivity between ventral premotor cortex (PMv) and primary motor cortex (M1) via spike timing-dependent plasticity (STDP), leading to enhanced motor functions in young adults. However, whether this STDP-inducing protocol is effective in the aging brain remains unclear. In two groups of young and elderly healthy adults, we evaluated manual dexterity with the 9-hole peg task before and after ccPAS of the left PMv-M1 circuit. We observed that ccPAS enhanced dexterity in young adults, and this effect was anticipated by a progressive increase in motor-evoked potentials (MEPs) during ccPAS administration. No similar effects were observed in elderly individuals or in a control task. Across age groups, we observed that the magnitude of MEP changes predicted larger behavioral improvements. These findings demonstrate that left PMv-to-M1 ccPAS induces functionally specific improvements in young adults' manual dexterity and an increase in corticomotor excitability, but altered plasticity prevents the effectiveness of ccPAS in the elderly.

Cortico-cortical paired associative stimulation (ccPAS) over premotor-motor areas affects local circuitries in the human motor cortex via Hebbian plasticity.

Transcranial magnetic stimulation (TMS) studies have shown that cortico-cortical paired associative stimulation (ccPAS) can strengthen connectivity between the ventral premotor cortex (PMv) and the primary motor cortex (M1) by modulating convergent input over M1 via Hebbian spike-timing-dependent plasticity (STDP). However, whether ccPAS locally affects M1 activity remains unclear. We tested 60 right-handed young healthy humans in two studies, using a combination of dual coil TMS and ccPAS over the left PMv and M1 to probe and manipulate PMv-to-M1 connectivity, and single- and paired-pulse TMS to assess neural activity within M1. We provide convergent evidence that ccPAS, relying on repeated activations of excitatory PMv-to-M1 connections, acts locally over M1. During ccPAS, motor-evoked potentials (MEPs) induced by paired PMv-M1 stimulation gradually increased. Following ccPAS, the threshold for inducing MEPs of different amplitudes decreased, and the input-output curve (IO) slope increased, highlighting increased M1 corticospinal excitability. Moreover, ccPAS reduced the magnitude of short-interval intracortical inhibition (SICI), reflecting suppression of GABA-ergic interneuronal mechanisms within M1, without affecting intracortical facilitation (ICF). These changes were specific to ccPAS Hebbian strengthening of PMv-to-M1 connectivity, as no modulations were observed when reversing the order of the PMv-M1 stimulation during a control ccPAS protocol. These findings expand prior ccPAS research that focused on the malleability of cortico-cortical connectivity at the network-level, and highlight local changes in the area of convergent activation (i.e., M1) during plasticity induction. These findings provide new mechanistic insights into the physiological basis of ccPAS that are relevant for protocol optimization.

Gradual enhancement of corticomotor excitability during cortico-cortical paired associative stimulation.

Cortico-cortical paired associative stimulation (ccPAS) is an effective transcranial magnetic stimulation (TMS) method for inducing associative plasticity between interconnected brain areas in humans. Prior ccPAS studies have focused on protocol's aftereffects. Here, we investigated physiological changes induced "online" during ccPAS administration. We tested 109 participants receiving ccPAS over left ventral premotor cortex (PMv) and primary motor cortex (M1) using a standard procedure (90 paired-pulses with 8-ms interstimulus interval, repeated at 0.1 Hz frequency). On each paired-pulse, we recorded a motor-evoked potential (MEP) to continuously trace the emergence of corticomotor changes. Participant receiving forward-ccPAS (on each pair, a first TMS pulse was administered over PMv, second over M1, i.e., PMv-to-M1) showed a gradual and linear increase in MEP size that did not reach a plateau at the end of the protocol and was greater in participants with low motor threshold. Participants receiving reverse-ccPAS (i.e., M1-to-PMv) showed a trend toward inhibition. Our study highlights the facilitatory and inhibitory modulations that occur during ccPAS administration and suggest that online MEP monitoring could provide insights into the malleability of the motor system and protocol's effectiveness. Our findings open interesting prospects about ccPAS potential optimization in experimental and clinical settings.