Transcranial magnetic stimulation of the brain: What is stimulated? - A consensus and critical position paper.

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.

Dynamics of cortical and corticomuscular connectivity during planning and execution of visually guided steps in humans.

The cortical mechanisms underlying the act of taking a step-including planning, execution, and modification-are not well understood. We hypothesized that oscillatory communication in a parieto-frontal and corticomuscular network is involved in the neural control of visually guided steps. We addressed this hypothesis using source reconstruction and lagged coherence analysis of electroencephalographic and electromyographic recordings during visually guided stepping and 2 control tasks that aimed to investigate processes involved in (i) preparing and taking a step and (ii) adjusting a step based on visual information. Steps were divided into planning, initiation, and execution phases. Taking a step was characterized by an upregulation of beta/gamma coherence within the parieto-frontal network during planning followed by a downregulation of alpha and beta/gamma coherence during initiation and execution. Step modification was characterized by bidirectional modulations of alpha and beta/gamma coherence in the parieto-frontal network during the phases leading up to step execution. Corticomuscular coherence did not exhibit task-related effects. We suggest that these task-related modulations indicate that the brain makes use of communication through coherence in the context of large-scale, whole-body movements, reflecting a process of flexibly fine-tuning inter-regional communication to achieve precision control during human stepping.

Transcutaneous spinal direct current stimulation increases corticospinal transmission and enhances voluntary motor output in humans.

Optimization of motor performance is of importance in daily life, in relation to recovery following injury as well as for elite sports performance. The present study investigated whether transcutaneous spinal direct current stimulation (tsDCS) may enhance voluntary ballistic activation of ankle muscles and descending activation of spinal motor neurons in able-bodied adults. Forty-one adults (21 men; 24.0 ± 3.2 years) participated in the study. The effect of tsDCS on ballistic motor performance and plantar flexor muscle activation was assessed in a double-blinded sham-controlled cross-over experiment. In separate experiments, the underlying changes in excitability of corticospinal and spinal pathways were probed by evaluating soleus (SOL) motor evoked potentials (MEPs) following single-pulse transcranial magnetic stimulation (TMS) over the primary motor cortex, SOL H-reflexes elicited by tibial nerve stimulation and TMS-conditioning of SOL H-reflexes. Measures were obtained before and after cathodal tsDCS over the thoracic spine (T11-T12) for 10 min at 2.5 mA. We found that cathodal tsDCS transiently facilitated peak acceleration in the ballistic motor task compared to sham tsDCS. Following tsDCS, SOL MEPs were increased without changes in H-reflex amplitudes. The short-latency facilitation of the H-reflex by subthreshold TMS, which is assumed to be mediated by the fast conducting monosynaptic corticomotoneuronal pathway, was also enhanced by tsDCS. We argue that tsDCS briefly facilitates voluntary motor output by increasing descending drive from corticospinal neurones to spinal plantar flexor motor neurons. tsDCS can thus transiently promote within-session CNS function and voluntary motor output and holds potential as a technique in the rehabilitation of motor function following central nervous lesions.

Effects of Exercise on Cognitive Performance in Children and Adolescents with ADHD: Potential Mechanisms and Evidence-based Recommendations.

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a complex symptomatology, and core symptoms as well as functional impairment often persist into adulthood. Recent investigations estimate the worldwide prevalence of ADHD in children and adolescents to be ~7%, which is a substantial increase compared to a decade ago. Conventional treatment most often includes pharmacotherapy with central nervous stimulants, but the number of non-responders and adverse effects call for treatment alternatives. Exercise has been suggested as a safe and low-cost adjunctive therapy for ADHD and is reported to be accompanied by positive effects on several aspects of cognitive functions in the general child population. Here we review existing evidence that exercise affects cognitive functions in children with and without ADHD and present likely neurophysiological mechanisms of action. We find well-described associations between physical activity and ADHD, as well as causal evidence in the form of small to moderate beneficial effects following acute aerobic exercise on executive functions in children with ADHD. Despite large heterogeneity, meta-analyses find small positive effects of exercise in population-based control (PBC) children, and our extracted effect sizes from long-term interventions suggest consistent positive effects in children and adolescents with ADHD. Paucity of studies probing the effect of different exercise parameters impedes finite conclusions in this regard. Large-scale clinical trials with appropriately timed exercise are needed. In summary, the existing preliminary evidence suggests that exercise can improve cognitive performance intimately linked to ADHD presentations in children with and without an ADHD diagnosis. Based on the findings from both PBC and ADHD children, we cautiously provide recommendations for parameters of exercise.

The Beneficial Effect of Acute Exercise on Motor Memory Consolidation is Modulated by Dopaminergic Gene Profile.

When aerobic exercise is performed following skilled motor practice, it can enhance motor memory consolidation. Previous studies have suggested that dopamine may play a role in motor memory consolidation, but whether it is involved in the exercise effects on consolidation is unknown. Hence, we aimed to investigate the influence of dopaminergic pathways on the exercise-induced modulation of motor memory consolidation. We compared the effect of acute exercise on motor memory consolidation between the genotypes that are known to affect dopaminergic transmission and learning. By combining cluster analyses and fitting linear models with and without included polymorphisms, we provide preliminary evidence that exercise benefits the carriers of alleles that are associated with low synaptic dopamine content. In line with previous reports, our findings implicate dopamine as a modulator of the exercise-induced effects on motor memory consolidation, and suggest exercise as a potential clinical tool to counteract low endogenous dopamine bioavailability. Further experiments are needed to establish causal relations.

Motor-Enriched Learning Activities Can Improve Mathematical Performance in Preadolescent Children.

Objective: An emerging field of research indicates that physical activity can benefit cognitive functions and academic achievements in children. However, less is known about how academic achievements can benefit from specific types of motor activities (e.g., fine and gross) integrated into learning activities. Thus, the aim of this study was to investigate whether fine or gross motor activity integrated into math lessons (i.e., motor-enrichment) could improve children's mathematical performance. Methods: A 6-week within school cluster-randomized intervention study investigated the effects of motor-enriched mathematical teaching in Danish preadolescent children (n = 165, age = 7.5 ± 0.02 years). Three groups were included: a control group (CON), which received non-motor enriched conventional mathematical teaching, a fine motor math group (FMM) and a gross motor math group (GMM), which received mathematical teaching enriched with fine and gross motor activity, respectively. The children were tested before (T0), immediately after (T1) and 8 weeks after the intervention (T2). A standardized mathematical test (50 tasks) was used to evaluate mathematical performance. Furthermore, it was investigated whether motor-enriched math was accompanied by different effects in low and normal math performers. Additionally, the study investigated the potential contribution of cognitive functions and motor skills on mathematical performance. Results: All groups improved their mathematical performance from T0 to T1. However, from T0 to T1, the improvement was significantly greater in GMM compared to FMM (1.87 ± 0.71 correct answers) (p = 0.02). At T2 no significant differences in mathematical performance were observed. A subgroup analysis revealed that normal math-performers benefitted from GMM compared to both CON 1.78 ± 0.73 correct answers (p = 0.04) and FMM 2.14 ± 0.72 correct answers (p = 0.008). These effects were not observed in low math-performers. The effects were partly accounted for by visuo-spatial short-term memory and gross motor skills. Conclusion: The study demonstrates that motor enriched learning activities can improve mathematical performance. In normal math performers GMM led to larger improvements than FMM and CON. This was not the case for the low math performers. Future studies should further elucidate the neurophysiological mechanisms underlying the observed behavioral effects.