Neuronavigated Transcranial Magnetic Stimulation Research Articles

Transformation but not generation of motor images is disrupted following stimulation over the left inferior parietal lobe

Motor imagery (MI) involves the generation, maintenance, and transformation of motor images; yet, the neural underpinnings of each stage are not well understood. Here, we investigated the role of the left inferior parietal lobe (IPL) in the stages of MI. Healthy participants (N=20) engaged in a MI task (making judgments about hands presented on a screen; hand laterality judgment task) over two days. Past literature demonstrates the mental rotation of hands in this task involves implicit MI (i.e., where MI occurs spontaneously in the absence of explicit instructions). During the task, active (Day A; 120% resting motor threshold) or sham (Day B; placebo) neuronavigated transcranial magnetic stimulation (TMS) was applied to the left IPL (location determined from past neuroimaging work) on 50% of trials at 250, 500, or 750ms post-stimulus onset, corresponding to different stages of MI. A/B days were randomized across participants. Linear mixed effects (LME) modelling conducted on reaction time and accuracy revealed that longer reaction times were observed when TMS was delivered at 750ms after trial onset, and more greatly for active vs. sham stimulation. This effect was exacerbated for palm- vs. back-view stimuli and for left vs. right hands. Accuracy overall was decreased for active vs. sham stimulation, and to a greater extent for palm- vs. back-view stimuli. Findings suggest that the left IPL is involved in image transformation. Overall this work informs on the neural underpinnings of the stages of MI.

Differences in the organization of the primary motor cortex in people with and without low back pain and associations with motor control and sensory tests

Differences in organization of the primary motor cortex and altered trunk motor control (sensing, processing and motor output) have been reported in people with low back pain (LBP). Little is known to what extent these differences are related. We investigated differences in 1) organization of the primary motor cortex and 2) motor and sensory tests between people with and without LBP, and 3) investigated associations between the organization of the primary motor cortex and motor and sensory tests. We conducted a case-control study in people with (N=25) and without (N=25) LBP. The organization of the primary motor cortex (Center of Gravity (CoG) and Area of the cortical representation of trunk muscles) was assessed using neuronavigated transcranial magnetic stimulation, based on individual MRIs. Sensory tests (quantitative sensory testing, graphaesthesia, two-point discrimination threshold) and a motor test (spiral-tracking test) were assessed. Participants with LBP had a more lateral and lower location of the CoG and a higher temporal summation of pain. For all participants combined, better vibration test scores were associated with a more anterior, lateral, and lower CoG and a better two-point discrimination threshold was associated with a lower CoG. A small subset of variables showed significance. Although this aligns with the concept of altered organization of the primary motor cortex in LBP, there is no strong evidence of the association between altered organization of the primary motor cortex and motor and sensory test performance in LBP. Focusing on subgroup analyses regarding pain duration can be a topic for future research.

Verification of neuronavigated TMS accuracy using structured-light 3D scans

Objective. To investigate the reliability and accuracy of the manual three-point co-registration in neuronavigated transcranial magnetic stimulation (TMS). The effect of the error in landmark pointing on the coil placement and on the induced electric and magnetic fields was examined. Approach. The position of the TMS coil on the head was recorded by the neuronavigation system and by 3D scanning for ten healthy participants. The differences in the coil locations and orientations and the theoretical error values for electric and magnetic fields between the neuronavigated and 3D scanned coil positions were calculated. In addition, the sensitivity of the coil location on landmark accuracy was calculated. Main results. The measured distances between the neuronavigated and 3D scanned coil locations were on average 10.2 mm, ranging from 3.1 to 18.7 mm. The error in angles were on average from two to three degrees. The coil misplacement caused on average a 29% relative error in the electric field with a range from 9% to 51%. In the magnetic field, the same error was on average 33%, ranging from 10% to 58%. The misplacement of landmark points could cause a 1.8-fold error for the coil location. Significance. TMS neuronavigation with three landmark points can cause a significant error in the coil position, hampering research using highly accurate electric field calculations. Including 3D scanning to the process provides an efficient method to achieve a more accurate coil position.

Semi-automated motor hotspot search (SAMHS): a framework toward an optimised approach for motor hotspot identification.

Motor hotspot identification represents the first step in the determination of the motor threshold and is the basis for the specification of stimulation intensity used for various Transcranial Magnetic Stimulation (TMS) applications. The level of experimenters' experience and the methodology of motor hotspot identification differ between laboratories. The need for an optimized and time-efficient technique for motor hotspot identification is therefore substantial. With the current work, we present a framework for an optimized and time-efficient semi-automated motor hotspot search (SAMHS) technique utilizing a neuronavigated robot-assisted TMS system (TMS-cobot). Furthermore, we aim to test its practicality and accuracy by a comparison with a manual motor hotspot identification method. A total of 32 participants took part in this dual-center study. At both study centers, participants underwent manual hotspot search (MHS) with an experienced TMS researcher, and the novel SAMHS procedure with a TMS-cobot (hereafter, called cobot hotspot search, CHS) in a randomized order. Resting motor threshold (RMT), and stimulus intensity to produce 1 mV (SI1mV) peak-to-peak of motor-evoked potential (MEP), as well as MEPs with 120% RMT and SI1mV were recorded as outcome measures for comparison. Compared to the MHS method, the CHS produced lower RMT, lower SI1mV and a trend-wise higher peak-to-peak MEP amplitude in stimulations with SI1mV. The duration of the CHS procedure was longer than that of the MHS (15.60 vs. 2.43 min on average). However, accuracy of the hotspot was higher for the CHS compared to the MHS. The SAMHS procedure introduces an optimized motor hotspot determination system that is easy to use, and strikes a fairly good balance between accuracy and speed. This new procedure can thus be deplored by experienced as well as beginner-level TMS researchers.

Shortened Motor Evoked Potential Latency in the Epileptic Hemisphere of Children With Focal Epilepsy.

Motor evoked potential (MEP) amplitude and latency are acquired routinely during neuronavigated transcranial magnetic stimulation, a method of functional mapping of the motor cortex before epilepsy surgery. Although MEP amplitude is routinely used to generate a motor map, MEP latency in patients with focal epilepsy has not been studied systematically. Given that epilepsy may alter myelination, we tested whether intrinsic hand muscle MEPs obtained from the hemisphere containing a seizure focus differ in latency from MEPs collected from the opposite hemisphere. Latencies of abductor pollicis brevis MEPs were obtained during routine motor mapping by neuronavigated transcranial magnetic stimulation in children with intractable, unihemispheric focal epilepsy. The primary motor cortex was stimulated bilaterally in all cases. Only data from patients without a lesion involving the corticospinal tract were included. We tested whether abductor pollicis brevis MEP latency varied as a function of seizure focus lateralization. In the 17 patients who met the inclusion criteria, the mean latency of MEPs with amplitudes in the top and bottom quartiles was shorter in the epileptic hemisphere. Interhemispheric latency difference was greater in patients with lesional epilepsy than in those with nonlesional epilepsy (0.7 ± 0.4 vs. 0.1 ± 0.6 milliseconds, P = 0.02). Motor evoked potential latency was shortened in the epileptic hemisphere of children with focal epilepsy.

Reliability of active robotic neuro-navigated transcranial magnetic stimulation motor maps.

Transcranial magnetic stimulation (TMS) motor mapping is a safe, non-invasive method used to study corticomotor organization and intervention-induced plasticity. Reliability of resting maps is well established, but understudied for active maps and unestablished for active maps obtained using robotic TMS techniques. The objective of this study was to determine the reliability of robotic neuro-navigated TMS motor map measures during active muscle contraction. We hypothesized that map area and volume would show excellent short- and medium-term reliability. Twenty healthy adults were tested on 3 days. Active maps of the first dorsal interosseous muscle were created using a 12 × 12 grid (7mm spacing). Short- (24h) and medium-term (3-5weeks) relative (intra-class correlation coefficient) and absolute (minimal detectable change (MDC); standard error of measure) reliabilities were evaluated for map area, volume, center of gravity (CoG), and hotspot magnitude (peak-to-peak MEP amplitude at the hotspot), along with active motor threshold (AMT) and maximum voluntary contraction (MVC). This study found thatAMT and MVC had good-to-excellent short- and medium-term reliability. Map CoG (x and y) were the most reliable map measures across sessions with excellent short- and medium-term reliability (p < 0.001). Map area, hotspot magnitude, and map volume followed with better reliability medium-term than short-term, with a change of 28%, 62%, and 78% needed to detect a true medium-term change, respectively. Therefore,robot-guided neuro-navigated TMS active mapping is relatively reliable but varies across measures. This, and MDC, should be considered in interventional study designs.

Stability and test–retest reliability of neuronavigated TMS measures of corticospinal and intracortical excitability

The present study aimed at investigating the long-term stability and test–retest reliability of neuronavigated transcranial magnetic stimulation (nTMS) measures of cortical excitability, inhibition, and facilitation in the primary motor cortex. To fulfill these aims, thirty-one healthy adults underwent four nTMS sessions, over an average one-month period. Stability and test–retest reliability statistics were computed and analyzed to produce smallest real difference statistics, which indicate the absolute variation in a measurement that is likely to be the result of error (randomness). Excellent reliability was found for resting motor thresholds, which reflect baseline neuronal excitability. Good reliability statistics were found for input/output curve measurements, which reflect the excitability of a highly plastic neuronal population. Using the slope of mean amplitudes throughout the input/output curve or the stimulator intensity required to elicit motor evoked potentials of 1 mV presented good to excellent measurement reliability for global cortical excitability indexing, compared to mean MEP at a given intensity. Overall, this methodological study provides useful and novel information on transcranial magnetic stimulation interventions by providing smallest real difference statistics that inform on potential response thresholds across time, contributing to the validation of these measurements as clinical monitoring tools across time.

Differences in neurometabolites and transcranial magnetic stimulation motor maps in children with attention-deficit/hyperactivity disorder.

Background:Although much is known about cognitive dysfunction in attention-deficit/hyperactivity disorder (ADHD), few studies have examined the pathophysiology of disordered motor circuitry. We explored differences in neurometabolite levels and transcranial magnetic stimulation (TMS)–derived corticomotor representations among children with ADHD and typically developing children.Methods:We used magnetic resonance spectroscopy (MRS) protocols to measure excitatory (glutamate + glutamine [Glx]) and inhibitory (γ-aminobutyric acid [GABA]) neurometabolite levels in the dominant primary motor cortex (M1) and the supplementary motor area (SMA) in children with ADHD and typically developing children. We used robotic neuronavigated TMS to measure corticospinal excitability and create corticomotor maps.Results:We collected data from 26 medication-free children with ADHD (aged 7–16 years) and 25 typically developing children (11–16 years). Children with ADHD had lower M1 Glx (p = 0.044, d = 0.6); their mean resting motor threshold was lower (p = 0.029, d = 0.8); their map area was smaller (p = 0.044, d = 0.7); and their hotspot density was higher (p = 0.008, d = 0.9). M1 GABA levels were associated with motor map area (p = 0.036).Limitations: Some TMS data were lost because the threshold of some children exceeded 100% of the machine output. The relatively large MRS voxel required to obtain sufficient signal-to-noise ratio and reliably measure GABA levels encompassed tissue beyond the M1, making this measure less anatomically specific.Conclusion:The neurochemistry and neurophysiology of key nodes in the motor network may be altered in children with ADHD, and the differences appear to be related to each other. These findings suggest potentially novel neuropharmacological and neuromodulatory targets for ADHD.

Robotic mapping of motor cortex in children with perinatal stroke and hemiparesis.

Brain stimulation combined with intensive therapy may improve hand function in children with perinatal stroke‐induced unilateral cerebral palsy (UCP). However, response to therapy varies and underlying neuroplasticity mechanisms remain unclear. Here, we aimed to characterize robotic motor mapping outcomes in children with UCP. Twenty‐nine children with perinatal stroke and UCP (median age 11 ± 2 years) were compared to 24 typically developing controls (TDC). Robotic, neuronavigated transcranial magnetic stimulation was employed to define bilateral motor maps including area, volume, and peak motor evoked potential (MEP). Map outcomes were compared to the primary clinical outcome of the Jebsen–Taylor Test of Hand Function (JTT). Maps were reliably obtained in the contralesional motor cortex (24/29) but challenging in the lesioned hemisphere (5/29). Within the contralesional M1 of participants with UCP, area and peak MEP amplitude of the unaffected map were larger than the affected map. When comparing bilateral maps within the contralesional M1 in children with UCP to that of TDC, only peak MEP amplitudes were different, being smaller for the affected hand as compared to TDC. We observed correlations between the unaffected map when stimulating the contralesional M1 and function of the unaffected hand. Robotic motor mapping can characterize motor cortex neurophysiology in children with perinatal stroke. Map area and peak MEP amplitude may represent discrete biomarkers of developmental plasticity in the contralesional M1. Correlations between map metrics and hand function suggest clinical relevance and utility in studies of interventional plasticity.

An Automated Workflow for the Electric Field Modeling of High-definition Transcranial Direct Current Stimulation (HD-tDCS) in Chronic Stroke with Lesions.

Transcranial Direct Current Stimulation is a popular noninvasive brain stimulation (NIBS) technique that modulates brain excitability by means of low-amplitude electrical current (usually <4mA) delivered to the electrodes on the scalp. The NIBS research has gained significant momentum in the past decade, prompting tDCS as an adjunctive therapeutic tool for neuromuscular disorders like stroke. However, due to stroke lesions and the differences in individual neuroanatomy, the targeted brain region may not show the same response upon NIBS across stroke patients. To this end, we conducted a study to test the feasibility of targeted NIBS. The hand motor hotspot (HMH) for each chronic stroke participant was identified using Neuronavigated Transcranial Magnetic Stimulation (TMS). After identifying the HMH as the neural target site, we applied High-definition TDCS with the current delivered at 2mA for 20 minutes. To simulate the effects of HD-tDCS in the brain, especially with stroke lesions, we used the computational modeling tool (ROAST). The lesion mask was identified using an automated tool (LINDA). This paper demonstrates that the stroke lesions can be incorporated in the computational modeling of electric field distribution upon HD-tDCS without manual intervention.

The role of overlap and distribution of robotic TMS motor maps in children's hand function

Abstract Introduction: Robotic transcranial magnetic stimulation (TMS) can be used to map individual hand muscles in primary motor cortex (M1). Distribution and overlap of such cortical representations are unknown in children. We quantified Jaccard Overlap (JO) (map similarity/overlap) and Earth Mover’s Distance (EMD) (map dissimilarity/distribution) of hand muscle representations to explore motor map organization and associations with function. Methods: Typically developing, right-handed children received bilateral neuronavigated robotic TMS motor mapping. A 12x12 grid (7mm spacing) was placed over the hand knob of left and right M1. Four TMS pulses were delivered per grid-point. Motor evoked potentials from the primary muscle (first dorsal interosseous, FDI), created 2D/3D maps that were compared to abductor pollicus brevis (APB), abductor digiti minimi (ADM) and wrist extensor (WEX). JO and EMD for each were evaluated within and between hemispheres using Friedman ANOVAs and Wilcoxon Tests. Associations between map metrics and motor performance (Purdue Pegboard Task, PPT) were explored with Spearman correlations. Results: Maps were obtainable and well tolerated in all 24 participants (12-18 years old, 50% female). JO and EMD were comparable between hemispheres. EMD within each hemisphere differed with anatomically approximated muscles exhibiting higher map JO and lower EMD. Within each hemisphere, cortical representation JO differed between muscle pairs. Differences in JO and EMD were greater in the dominant hemisphere. Left hemisphere JO FDI-APB correlated with right hand PPT scores. EMD and JO in the right hemisphere did not correlate with left hand motor performance. Conclusion: JO and EMD of hand muscle cortical representations may be useful measures for investigating M1 physiology and plasticity. Comparable JO and EMD between right and left hands suggest symmetrical hemispheric motor organization in healthy children. Keywords: Robotic Transcranial Magnetic Stimulation (TMS), Motor Mapping, Motor Performance, Pediatrics

Abnormal changes in motor cortical maps in humans with spinal cord injury.

The functional role of motor cortical reorganization following spinal cord injury (SCI) remains largely unknown. Here, we tested motor maps in a hand muscle at rest and during voluntary contraction of the hand with and without voluntary contraction of a proximal arm muscle. Motor map area in participants with SCI decreased during hand voluntary contraction and further decreased during additional contraction of a proximal arm muscle compared with rest. In contrast, motor map area in controls increased during the same motor tasks. Participants with SCI with more severe sensory deficits in the hand showed larger decreases in motor map area. Ten minutes of hand muscle-tendon vibration increased the motor map area during voluntary contraction in SCI participants. These novel findings suggest that abnormal changes in motor cortical maps during voluntary contraction after SCI can be reshaped by sensory input, knowledge that can have implications for rehabilitation. Motor cortical representations reorganize following cervical spinal cord injury (SCI). The functional role of this reorganization remains largely unknown. Using neuronavigated transcranial magnetic stimulation, we examined motor cortical maps during voluntary contraction in humans with chronic cervical SCI and age-matched controls. We constructed motor maps in the first dorsal interosseous (FDI) muscle at rest and during voluntary contraction of the FDI with and without voluntary contraction of the biceps brachi (BB). The role of sensory input into this reorganization was examined by muscle-tendon vibration. We found that, at rest, motor maps were larger in SCI (22.3cm2 ) compared with control (12.6cm2 , P<0.001) participants. Motor map area increased during voluntary contraction of the FDI (120.7%) and further increased during contraction of the BB (143.9%) compared with rest in control subjects; however, motor map area decreased during voluntary contraction of the FDI (69.5%) and further decreased during contraction of the BB (55.5%) in individuals with SCI. SCI participants with larger decreases in map area during voluntary contraction of the FDI were those with larger sensory deficits in the hand and 10min of hand muscle-tendon vibration increased motor map area. These results provide the first evidence of abnormal changes in motor cortical maps in humans with chronic SCI during voluntary contraction, suggesting that sensory input can help to reshape this reorganization.

State-dependent TMS effects in the visual cortex after visual adaptation: A combined TMS–EEG study

ObjectiveThe impact of transcranial magnetic stimulation (TMS) has been shown to depend on the initial brain state of the stimulated cortical region. This observation has led to the development of paradigms that aim to enhance the specificity of TMS effects by using visual/luminance adaptation to modulate brain state prior to the application of TMS. However, the neural basis of interactions between TMS and adaptation is unknown. Here, we examined these interactions by using electroencephalography (EEG) to measure the impact of TMS over the visual cortex after luminance adaptation. MethodsSingle-pulses of neuronavigated TMS (nTMS) were applied at two different intensities over the left visual cortex after adaptation to either high or low luminance. We then analyzed the effects of adaptation on the global and local cortical excitability. ResultsThe analysis revealed a significant interaction between the TMS-evoked responses and the adaptation condition. In particular, when nTMS was applied with high intensity, the evoked responses were larger after adaptation to high than low luminance. ConclusionThis result provides the first neural evidence on the interaction between TMS with visual adaptation. SignificanceTMS can activate neurons differentially as a function of their adaptation state.

Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia.

Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study. Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials. There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI. Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.

Adaptation of a semantic picture-word interference paradigm for future language mapping with transcranial magnetic stimulation: A behavioural study

Neuro-navigated transcranial magnetic stimulation (TMS) helps to identify language-related cortical regions prior to brain tumour surgery. We adapted a semantic picture-word interference (PWI) paradigm from psycholinguistics to high-resolution TMS language mapping which prospectively can be used to specifically address the level of semantic processing. In PWI, pictures are presented along with distractor words which facilitate or inhibit the lexical access to the picture name. These modulatory effects of distractors can be annihilated in language-sensitive areas by the inhibitory effects of TMS on language processing. The rationale here is to observe the distractor effect without active stimulation and then to observe presumably its elimination by interference of the TMS stimulation. The special requirements to use PWI in this setting are (1) identifying word material for accelerating reliably naming latencies, choosing (2) the ideal presentation modality, and (3) the appropriate timing of distractor presentation. These are then controlled in real TMS language mapping. To adapt a semantic PWI naming paradigm for TMS application we employed 30 object-pictures in spoken German language. Part-whole associative semantic related or unrelated distractors were presented in two experiments including 15 healthy volunteers each, once auditorily and once visually. Data analysis across the entire stimulus set revealed a trend for facilitation in the visual condition, whereas no effects were observed for auditory distractors. In a sub-set, we found a significant facilitation effect for visual semantic distractors. Thus, with this study we provide a well-controlled item set for future studies implementing effective TMS language mapping applying visual semantic PWI.

Perturbation of resting-state network nodes preferentially propagates to structurally rather than functionally connected regions

Combining Transcranial Magnetic Stimulation (TMS) with electroencephalography (EEG) offers the opportunity to study signal propagation dynamics at high temporal resolution in the human brain. TMS pulse induces a local effect which propagates across cortical networks engaging distant cortical and subcortical sites. However, the degree of propagation supported by the structural compared to functional connectome remains unclear. Clarifying this issue would help tailor TMS interventions to maximize target engagement. The goal of this study was to establish the contribution of functional and structural connectivity in predicting TMSinducedsignal propagation after perturbation of two distinct brain networks. For this purpose,24 healthy individuals underwent two identical TMS-EEG visits where neuronavigated TMS pulses were delivered to nodes of the default mode network (DMN) and the dorsal attention network (DAN). The functional and structural connectivity derived from each individual stimulation spot were characterized via functional magnetic resonance imaging (fMRI) and Diffusion Weighted Imaging (DWI), and signal propagation across these two metrics was compared. Direct comparison between the signal extracted from brain regions either functionally or structurally connected to the stimulation sites, shows a stronger activation overcortical areas connected via white matter pathways, with a minor contribution of functional projections. This pattern was not observed when analyzing spontaneous resting state EEG activity. Overall, results suggest that structural links can predict network-level response to perturbation more accurately than functional connectivity. Additionally, DWI-based estimation of propagation patterns can be used to estimate off-target engagement of other networks and possibly guide target selection to maximize specificity.

Robotic transcranial magnetic stimulation motor maps and hand function in adolescents.

IntroductionTranscranial magnetic stimulation (TMS) motor mapping can characterize the neurophysiology of the motor system. Limitations including human error and the challenges of pediatric populations may be overcome by emerging robotic systems. We aimed to show that neuronavigated robotic motor mapping in adolescents could efficiently produce discrete maps of individual upper extremity muscles, the characteristics of which would correlate with motor behavior.MethodsTypically developing adolescents (TDA) underwent neuronavigated robotic TMS mapping of bilateral motor cortex. Representative maps of first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles in each hand were created. Map features including area (primary), volume, and center of gravity were analyzed across different excitability regions (R100%, R75%, R50%, R25%). Correlations between map metrics and validated tests of hand motor function (Purdue Pegboard Test as primary) were explored.ResultsTwenty‐four right‐handed participants (range 12–18 years, median 15.5 years, 52% female) completed bilateral mapping and motor assessments with no serious adverse events or dropouts. Gender and age were associated with hand function and motor map characteristics. Full motor maps (R100%) for FDI did not correlate with motor function in either hand. Smaller excitability subset regions demonstrated reduced variance and dose‐dependent correlations between primary map variables and motor function in the dominant hemisphere.ConclusionsHand function in TDA correlates with smaller subset excitability regions of robotic TMS motor map outcomes. Refined motor maps may have less variance and greater potential to quantify interventional neuroplasticity. Robotic TMS mapping is safe and feasible in adolescents.

Online and offline effects of transcranial alternating current stimulation of the primary motor cortex

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms by means of external sinusoidal potentials. The physiological mechanisms underlying tACS effects are still under debate. Whereas online (e.g., ongoing) tACS over the motor cortex induces robust state-, phase- and frequency-dependent effects on cortical excitability, the offline effects (i.e. after-effects) of tACS are less clear. Here, we explored online and offline effects of tACS in two single-blind, sham-controlled experiments. In both experiments we used neuronavigated transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) as a probe to index changes of cortical excitability and delivered M1 tACS at 10 Hz (alpha), 20 Hz (beta) and sham (30 s of low-frequency transcranial random noise stimulation; tRNS). Corticospinal excitability was measured by single pulse TMS-induced motor evoked potentials (MEPs). tACS was delivered online in Experiment 1 and offline in Experiment 2. In Experiment 1, the increase of MEPs size was maximal with the 20 Hz stimulation, however in Experiment 2 neither the 10 Hz nor the 20 Hz stimulation induced tACS offline effects. These findings support the idea that tACS affects cortical excitability only during online application, at least when delivered on the scalp overlying M1, thereby contributing to the development of effective protocols that can be applied to clinical populations.

Visual Sensory Cortices Causally Contribute to Auditory Word Recognition Following Sensorimotor-Enriched Vocabulary Training.

Despite a rise in the use of “learning by doing” pedagogical methods in praxis, little is known as to how the brain benefits from these methods. Learning by doing strategies that utilize complementary information (“enrichment”) such as gestures have been shown to optimize learning outcomes in several domains including foreign language (L2) training. Here we tested the hypothesis that behavioral benefits of gesture-based enrichment are critically supported by integrity of the biological motion visual cortices (bmSTS). Prior functional neuroimaging work has implicated the visual motion cortices in L2 translation following sensorimotor-enriched training; the current study is the first to investigate the causal relevance of these structures in learning by doing contexts. Using neuronavigated transcranial magnetic stimulation and a gesture-enriched L2 vocabulary learning paradigm, we found that the bmSTS causally contributed to behavioral benefits of gesture-enriched learning. Visual motion cortex integrity benefitted both short- and long-term learning outcomes, as well as the learning of concrete and abstract words. These results adjudicate between opposing predictions of two neuroscientific learning theories: While reactivation-based theories predict no functional role of specialized sensory cortices in vocabulary learning outcomes, the current study supports the predictive coding theory view that these cortices precipitate sensorimotor-based learning benefits.

A Causal Role of Area hMST for Self-Motion Perception in Humans.

Previous studies in the macaque monkey have provided clear causal evidence for an involvement of the medial-superior-temporal area (MST) in the perception of self-motion. These studies also revealed an overrepresentation of contraversive heading. Human imaging studies have identified a functional equivalent (hMST) of macaque area MST. Yet, causal evidence of hMST in heading perception is lacking. We employed neuronavigated transcranial magnetic stimulation (TMS) to test for such a causal relationship. We expected TMS over hMST to induce increased perceptual variance (i.e., impaired precision), while leaving mean heading perception (accuracy) unaffected. We presented 8 human participants with an optic flow stimulus simulating forward self-motion across a ground plane in one of 3 directions. Participants indicated perceived heading. In 57% of the trials, TMS pulses were applied, temporally centered on self-motion onset. TMS stimulation site was either right-hemisphere hMST, identified by a functional magnetic resonance imaging (fMRI) localizer, or a control-area, just outside the fMRI localizer activation. As predicted, TMS over area hMST, but not over the control-area, increased response variance of perceived heading as compared with noTMS stimulation trials. As hypothesized, this effect was strongest for contraversive self-motion. These data provide a first causal evidence for a critical role of hMST in visually guided navigation.