Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

Background and purposeSmall vessel disease (mainly hypertensive arteriopathy and cerebral amyloid angiopathy (CAA)) is an important cause of spontaneous intracerebral haemorrhage (ICH), a devastating and still poorly understood stroke type. Enlarged perivascular spaces (EPVS) are a promising neuroimaging marker of small vessel disease. Based on the underlying arteriopathy distributions, we hypothesised that severe centrum semiovale EPVS are more common in lobar ICH attributed to CAA than other ICH. We evaluated EPVS prevalence, severity and distribution, and their clinical–radiological associations.MethodsRetrospective multicentre cohort study of 121 ICH patients. Clinical information was obtained using standardised forms. Basal ganglia and centrum semiovale EPVS on T2-weighted MRI (graded 0–4 (>40 EPVS)), white-matter changes, cerebral microbleeds (CMBs) and lacunes were rated using validated scales.ResultsPatients with probable or possible CAA (n=76) had a higher prevalence of severe (>40) centrum semiovale EPVS compared with other ICH patients (35.5% vs 17.8%; p=0.041). In logistic regression age (OR: 1.43; 95% CI 1.01 to 2.02; p=0.045), deep CMBs (OR: 3.27; 95% CI 1.27 to 8.45; p=0.014) and mean white-matter changes score (OR: 1.29; 95% CI 1.17 to 1.43; p<0.0001) were independently associated with increased basal ganglia EPVS severity; only age was associated with increased centrum semiovale EPVS severity (OR: 1.50; 95% CI 1.08 to 2.10; p=0.017).ConclusionsEPVS are common in ICH. Different mechanisms may account for EPVS according to their anatomical distribution. Severe centrum semiovale EPVS may be secondary to, and indicative of, CAA with value as a new neuroimaging marker. By contrast, basal ganglia EPVS severity is associated with markers of hypertensive arteriopathy.

Background and Purpose-Recent work demonstrated that application of peripheral nerve and cortical stimulation independently can induce modest improvements in motor performance in patients with stroke. The purpose of this study was to test the hypothesis that combining peripheral nerve stimulation (PNS) to the paretic hand with anodal direct current stimulation (tDCS) to the ipsilesional primary motor cortex (M1)