Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

Stroke is one of the main causes of long-term disability worldwide, placing a large burden on individuals and society. Rehabilitation after stroke consists of an iterative process involving assessments and specialized training, aspects often constrained by limited resources of healthcare centers. Wearable technology has the potential to objectively assess and monitor patients inside and outside clinical environments, enabling a more detailed evaluation of the impairment and allowing the individualization of rehabilitation therapies. The present review aims to provide an overview of wearable sensors used in stroke rehabilitation research, with a particular focus on the upper extremity. We summarize results obtained by current research using a variety of wearable sensors and use them to critically discuss challenges and opportunities in the ongoing effort towards reliable and accessible tools for stroke rehabilitation. Finally, suggestions concerning data acquisition and processing to guide future studies performed by clinicians and engineers alike are provided.

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here we show successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, functional magnetic resonance imaging studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as an exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional role. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.