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The development of novel strategies to augment motor training success is of great interest for healthy persons and neurological patients. A promising approach is the combination of training with transcranial electric stimulation. However, limited reproducibility and varying effect sizes make further protocol optimization necessary. We tested the effects of a novel cerebellar transcranial alternating current stimulation protocol (tACS) on motor skill learning. Furthermore, we studied underlying mechanisms by means of transcranial magnetic stimulation and analysis of fMRI-based resting-state connectivity. N = 15 young, healthy participants were recruited. 50 Hz tACS was applied to the left cerebellum in a double-blind, sham-controlled, cross-over design concurrently to the acquisition of a novel motor skill. Potential underlying mechanisms were assessed by studying short intracortical inhibition at rest (SICI rest ) and in the premovement phase (SICI move ), intracortical facilitation at rest (ICF rest ), and seed-based resting-state fMRI-based functional connectivity (FC) in a hypothesis-driven motor learning network. Active stimulation did not enhance skill acquisition or retention. Minor effects on striato-parietal FC were present. Linear mixed effects modelling identified SICI move modulation and baseline task performance as the most influential determining factors for predicting training success. Accounting for the identified factors may allow to stratify participants for future training-based interventions.

Abstract With the increase in life expectancy and the rapid evolution of daily life technologies, older adults must constantly learn new skills to adapt to society. Sleep reinforces skills acquired during the day and is associated with the occurrence of specific oscillations such as spindles. However, with age, spindles deteriorate and thus likely contribute to memory impairments observed in older adults. The application of electric currents by means of transcranial alternating current stimulation (tACS) with spindle-like waveform, applied during the night, was found to enhance spindles and motor memory consolidation in young adults. Here, we tested whether tACS bursts inspired by spindles applied during daytime naps may (i) increase spindle density and (ii) foster motor memory consolidation in older adults. Twenty-six healthy older participants performed a force modulation task at 10:00, were retested at 16:30, and the day after the initial training. They had 90-minute opportunity to take a nap while verum or placebo spindle-inspired tACS bursts were applied with similar temporal parameters to those observed in young adults and independently of natural spindles, which are reduced in the elderly. We show that the density of natural spindles correlates with the magnitude of memory consolidation, thus confirming that spindles are promising physiological targets for enhancing memory consolidation in older adults. However, spindle-inspired tACS, as used in the present study, did not enhance either spindles or memory consolidation. We therefore suggest that applying tACS time-locked to natural spindles might be required to entrain them and improve their related functions.

Spontaneous activity in the human cortex is organized along large-scale functional gradients, yet how these macroscale patterns relate to laminar functional architecture remains unclear. Here, we use sub-millimeter, layer-resolved 7T resting-state fMRI to map whole-brain functional connectivity gradients across cortical depth. We represent the cortex as a multilayer network with distinct connectivity profiles for deep, middle, and superficial layers, and derive laminar dissimilarity indices that quantify differences between layer-wise gradient embeddings within and across regions. These indices systematically distinguish canonical resting-state networks and vary along a histology-informed microstructural axis that captures a canonical sensory-to-limbic gradient of cytoarchitectural differentiation. Layer-specific analyses further show that the balance between deep- and superficial-layer dissimilarity tracks a functional hierarchy estimated from independent effective-connectivity modelling, consistent with feedback-like intrinsic connectivity at rest. Together, the results establish laminar gradient-derived indices as a bridge between cortical microstructure, large-scale network organization, and hierarchical information flow in the human cortex.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredSwiss National Science Foundation, https://ror.org/00yjd3n13, 212714

Peripersonal space (PPS) is the region of space surrounding the body. It has a dedicated multisensory-motor representation, whose purpose is to predict and plan interactions with the environment, and which can vary depending on environmental circumstances. Here, we investigated the effect on the PPS representation of an experimentally induced stress response. We assessed PPS representation in healthy humans, before and after a stressful manipulation, by quantifying visuotactile interactions as a function of the distance from the body, while monitoring salivary cortisol concentration. Participants, who showed a cortisol stress response, presented enhanced visuotactile integration for stimuli close to the body and reduced for far stimuli. Conversely, individuals, with a less pronounced cortisol response, showed a reduced difference in visuotactile integration between the near and the far space. In our interpretation, physiological stress resulted in a freezing-like response, where multisensory-motor resources are allocated only to the area immediately surrounding the body. Competing Interest Statement The authors have declared no competing interest.