The human somatosensory cortex contributes to the encoding of newly learned movements.

Recent studies have indicated somatosensory cortex involvement in motor learning and retention. However, the nature of its contribution is unknown. One possibility is that the somatosensory cortex is transiently engaged during movement. Alternatively, there may be durable learning-related changes which would indicate sensory participation in the encoding of learned movements. These possibilities are dissociated by disrupting the somatosensory cortex following learning, thus targeting learning-related changes which may have occurred. If changes to the somatosensory cortex contribute to retention, which, in effect, means aspects of newly learned movements are encoded there, disruption of this area once learning is complete should lead to an impairment. Participants were trained to make movements while receiving rotated visual feedback. The primary motor cortex (M1) and the primary somatosensory cortex (S1) were targeted for continuous theta-burst stimulation, while stimulation over the occipital cortex served as a control. Retention was assessed using active movement reproduction, or recognition testing, which involved passive movements produced by a robot. Disruption of the somatosensory cortex resulted in impaired motor memory in both tests. Suppression of the motor cortex had no impact on retention as indicated by comparable retention levels in control and motor cortex conditions. The effects were learning specific. When stimulation was applied to S1 following training with unrotated feedback, movement direction, the main dependent variable, was unaltered. Thus, the somatosensory cortex is part of a circuit that contributes to retention, consistent with the idea that aspects of newly learned movements, possibly learning-updated sensory states (new sensory targets) which serve to guide movement, may be encoded there.

Distinct parallel activation and interaction between dorsal and ventral pathways during phonological and semantic processing: A cTBS-fMRI study.

Successful visual word recognition requires the integration of phonological and semantic information, which is supported by the dorsal and ventral pathways in the brain. However, the functional specialization or interaction of these pathways during phonological and semantic processing remains unclear. Previous research has been limited by its dependence on correlational functional magnetic resonance imaging (fMRI) results or causal validation using patient populations, which are susceptible to confounds such as plasticity and lesion characteristics. To address this, the present study employed continuous theta-burst stimulation combined with fMRI in a within-subject design to assess rapid adaptation in regional activity and functional connectivity of the dorsal and ventral pathways during phonological and semantic tasks. This assessment followed the precise inhibition of the left inferior parietal lobule and anterior temporal lobe in the dorsal and ventral pathways, respectively. Our results reveal that both the dorsal and ventral pathways were activated during phonological and semantic processing, while the adaptation activation and interactive network were modulated by the task type and inhibited region. The two pathways exhibited interconnectivity in phonological processing, and disruption of either pathway led to rapid adaptation across both pathways. In contrast, only the ventral pathway exhibited connectivity in semantic processing, and disruption of this pathway alone resulted in adaptive effects primarily in the ventral pathway. These findings provide essential evidence supporting the interactive theory, phonological information processing in particular, potentially providing meaningful implications for clinical populations.

cTBS to Right DLPFC Modulates Physiological Correlates of Conflict Processing: Evidence from a Stroop task.

Conflict typically occurs when goal-directed processing competes with more automatic responses. Though previous studies have highlighted the importance of the right dorsolateral prefrontal cortex (rDLPFC) in conflict processing, its causal role remains unclear. In the current study, the behavioral experiment, the continuous theta burst stimulation (cTBS), and the electroencephalography (EEG) were combined to explore the effects of behavioral performance and physiological correlates during conflict processing, after the cTBS over the rDLPFC and vertex (the control condition). Twenty-six healthy participants performed the Stroop task which included congruent and incongruent trials. Although the cTBS did not induce significant changes in the behavioral performance, the cTBS over the rDLPFC reduced the Stroop effects of conflict monitoring-related frontal-central N2 component and theta oscillation, and conflict resolution-related parieto-occipital alpha oscillation, compared to the vertex stimulation. Moreover, a significant hemispheric difference in alpha oscillation was exploratively observed after the cTBS over the rDLPFC. Interestingly, we found the rDLPFC stimulation resulted in significantly reduced Stroop effects of theta and gamma oscillation after response, which may reflect the adjustment of cognitive control for the next trial. In conclusion, our study not only demonstrated the critical involvement of the rDLPFC in conflict monitoring, conflict resolution processing, and conflict adaptation but also revealed the electrophysiological mechanism of conflict processing mediated by the rDLPFC.

Suppressing visual hallucinations in an adolescent by occipital transcranial magnetic stimulation: A single-case experimental research design.

Visual hallucinations after central or peripheral impairment, commonly called Charles Bonnet syndrome, are often highly distressing and with few available treatment options. Here we report a case where an adolescent developed severely distressing visual hallucinations after hypoxic damage to the occipital cortex following a suicide attempt. The patient received active and sham occipital continuous theta-burst stimulation (cTBS) in a single-case experimental research design and a subsequent open phase, to evaluate cTBS as a Charles Bonnet treatment. The visual hallucinations seemed to decrease more during active than sham cTBS in the blind phase, and in the following week of repeated five daily treatments they almost disappeared. A normalization of increased activity in the lateral visual network after cTBS was observed on a functional magnetic resonance imaging resting-state analysis compared with 42 healthy controls. Visual evoked potentials stayed largely unchanged both in the sham-controlled blind phase and the subsequent open phase. During the two weeks after the open phase with repeated cTBS sessions, the visual hallucinations gradually reappeared and almost returned to the baseline level. Our findings suggest that active cTBS over the primary visual cortex can reduce visual hallucinations through modulation of downstream visual regions, though the effect is temporally limited.

The immediate impact of transcranial magnetic stimulation on brain structure: Short-term neuroplasticity following one session of cTBS.

Recent evidence demonstrates that activation-dependent neuroplasticity on a structural level can occur in a short time (2 hour or less) in the human brain. However, the exact time scale of structural plasticity in the human brain remains unclear. Using voxel-based morphometry (VBM), we investigated changes in grey matter (GM) after one session of continuous theta-burst stimulation (cTBS) delivered to the anterior temporal lobe (ATL). Twenty-five participants received cTBS over the left ATL or the occipital pole as a control site outside of the scanner, followed by structural and functional imaging. During functional imaging, participants performed a semantic association task and a number judgment task as a control task. VBM results revealed decreased GM in the left ATL and right cerebellum after the ATL stimulation compared to the control stimulation. In addition, cTBS over the left ATL induced slower semantic reaction times, reduced regional activity at the target site, and altered functional connectivity between the left and right ATL during semantic processing. Furthermore, the decreased ATL GM density was associated with the interhemispheric ATL-connectivity changes after the ATL stimulation. These results demonstrate that structural alterations caused by one session of cTBS are mirrored in the functional reorganizations in the semantic representation system, showing the rapid dynamics of cortical plasticity. Our findings support fast adapting neuronal plasticity such as synaptic morphology changes. Our results suggest that TBS is able to produce powerful changes in regional synaptic activity in the adult human brain.

Role of the frontal eye field in human pupil and saccade orienting responses.

The appearance of a salient stimulus evokes a series of orienting responses including saccades and pupil size to prepare the body for appropriate action. The midbrain superior colliculus (SC) that receives critical control signals from the frontal eye field (FEF) is hypothesized to coordinate all components of orienting. It has shown recently that the FEF, together with the SC, is also importantly involved in the control of pupil size, in addition to its well-documented role in eye movements. Although the role of the FEF in pupil size is demonstrated in monkeys, its role in human pupil responses and the coordination between pupil size and saccades remains to be established. Through applying continuous theta-burst stimulation over the right FEF and vertex, we investigated the role of the FEF in human pupil and saccade responses evoked by a salient stimulus, and the coordination between pupil size and saccades. Our results showed that neither saccade reaction times (SRT) nor pupil responses evoked by salient stimuli were modulated by FEF stimulation. In contrast, the correlation between pupil size and SRTs in the contralateral stimulus condition was diminished with FEF stimulation, but intact with vertex stimulation. Moreover, FEF stimulation effects between saccade and pupil responses associated with salient stimuli correlated across participants. This is the first transcranial magnetic stimulation (TMS) study on the pupil orienting response, and our findings suggest that human FEF was involved in coordinating pupil size and saccades, but not involved in the control of pupil orienting responses.

The effects of 30 Hz, 50 Hz AND 100 Hz continuous theta burst stimulation via transcranial magnetic stimulation on the electrophysiological parameters in healthy individuals.

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation is a non-invasive procedure that uses robust magnetic fields to create an electrical current in the cerebral cortex. Dual stimulation consists of administering subthre-shold conditioning stimulation (CS), then suprathreshold test stimulation (TS). When the interstimulus interval (ISI) is 1-6 msec, the motor evoked potential (MEP) decreases in amplitude; this decrease is termed "short interval intracortical inhibition" (SICI); when the ISI is 7-30 msec, an increase in MEP amplitude occurs, termed "short interval intracortical facilitation" (SICF). Continuous theta burst stimulation (cTBS), often applied at a frequency of 50 Hz, has been shown to decrease cortical excitability. The primary objective is to determine which duration of cTBS achieves better inhibition or excitation. The secondary objective is to compare 50 Hz cTBS to 30 Hz and 100 Hz cTBS. METHODS: The resting motor threshold (rMT), MEP, SICI, and SICF were studied in 30 healthy volunteers. CS and TS were administered at 80%-120% and 70%-140% of rMT at 2 and 3-millisecond (msec) intervals for SICI, and 10- and 12-msec intervals for SICF. Ten individuals in each group received 30, 50, or 100 Hz, followed by administration of rMT, MT-MEP, SICI, SICF immediately and at 30 minutes. RESULTS: Greater inhibition was achieved with 3 msec than 2 msec in SICI, whereas better facilitation occurred at 12 msec than 10 msec in SICF. At 30 Hz, cTBS augmented inhibition and suppressed facilitation, while 50 Hz yielded less inhibition and greater inter-individual variability. At 100 Hz, cTBS provided slight facilitation in MEP amplitudes with less interindividual variability. SICI and SICF did not differ significantly between 50 Hz and 100 Hz cTBS. CONCLUSION: Our results suggest that performing SICI and SICF for 3 and 12 msec, respectively, and CS and TS at 80%-120% of rMT, demonstrate safer inhibition and facilitation. Recently, TBS has been used in the treatment of various neurological diseases, and we recommend preferentially 30 Hz over 50 Hz cTBS for better inhibition with greater safety and less inter-individual variability.

Transient perturbation of the left temporal cortex evokes plasticity-related reconfiguration of the lexical network.

While much progress has been made in how brain organization supports language function, the language network's ability to adapt to immediate disturbances by means of reorganization remains unclear. The aim of this study was to examine acute reorganizational changes in brain activity related to conceptual and lexical retrieval in unimpaired language production following transient disruption of the left middle temporal gyrus (MTG). In a randomized single-blind within-subject experiment, we recorded the electroencephalogram from 16 healthy participants during a context-driven picture-naming task. Prior to the task, the left MTG was perturbed with real continuous theta-burst stimulation (cTBS) or sham stimulation. During the task, participants read lead-in sentences creating a constraining (e.g., "The farmer milks the") or nonconstraining context (e.g., "The farmer buys the"). The last word was shown as a picture that participants had to name (e.g., "cow"). Replicating behavioral studies, participants were overall faster in naming pictures following a constraining relative to a nonconstraining context, but this effect did not differ between real and sham cTBS. In contrast, real cTBS increased overall error rates compared to sham cTBS. In line with previous studies, we observed a decrease in alpha-beta (8-24 Hz) oscillatory power for constraining relative to nonconstraining contexts over left temporal-parietal cortex after participants received sham cTBS. However, following real cTBS, this decrease extended toward left prefrontal regions associated with both domain-general and domain-specific control mechanisms. Our findings provide evidence that immediately after perturbing the left MTG, the lexical-semantic network is able to quickly reconfigure, also recruiting domain-general regions.

Both 50 and 30 Hz continuous theta burst transcranial magnetic stimulation depresses the cerebellum.

The cerebellum is implicated in the pathophysiology of numerous movement disorders, which makes it an attractive target for noninvasive neurostimulation. Continuous theta burst stimulation (cTBS) can induce long lasting plastic changes in human brain; however, the efficacy of different simulation protocols has not been investigated at the cerebellum. Here, we compare a traditional 50-Hz and a modified 30-Hz cTBS protocols at modulating cerebellar activity in healthy subjects. Seventeen healthy adults participated in two testing sessions where they received either 50-Hz (cTBS50) or 30-Hz (cTBS30) cerebellar cTBS. Cerebellar brain inhibition (CBI), a measure of cerebello-thalamocortical pathway strength, and motor evoked potentials (MEP) were measured in the dominant first dorsal interosseous muscle before and after (up to ~ 40 min) cerebellar cTBS. Both cTBS protocols induced cerebellar depression, indicated by significant reductions in CBI (P < 0.001). No differences were found between protocols (cTBS50 and cTBS30) at any time point (P = 0.983). MEP amplitudes were not significantly different following either cTBS protocol (P = 0.130). The findings show cerebellar excitability to be equally depressed by 50-Hz and 30-Hz cTBS in heathy adults and support future work to explore the efficacy of different cerebellar cTBS protocols in movement disorder patients where cerebellar depression could provide therapeutic benefits.

The neurocognitive mechanisms underlying food cravings and snack food consumption. A combined continuous theta burst stimulation (cTBS) and EEG study.

Regulation of food cravings is thought to be critical for modulating eating behavior, yet we do not fully understand the mechanisms by which cognitive control operates in the eating context. The current study combined rTMS and EEG paradigms to examine the causal role of the left dorsolateral prefrontal cortex (dlPFC) in modulating visceral and behavioral responses to high calorie foods, and the mediational mechanisms underlying this relation. 28 right-handed female participants received both active and sham continuous theta burst stimulation (cTBS; a rTMS variant used to decrease cortical activity) targeting the left dlPFC in a counterbalanced order. Prior to and following each stimulation session participants completed a flanker and food-cue presentation (high and low calorie food) task. Following cTBS participants had the opportunity to consume both high and low calorie foods during a taste test. Findings revealed a reliable effect of cTBS on food consumption, such that participants selectively ingested significantly more calories from appetitive calorie dense snack foods following active relative to sham cTBS; this effect did not translate to control (low calorie) food consumption. In addition, attenuation of dlPFC activity resulted in the significant increase in N2 amplitude and P3b latency to incongruent flanker trials, and the selective significant increase in the P3a amplitude to and P3a amplitude bias for high calorie food stimuli. Results from the parallel mediation analysis revealed that only the indirect effect of flanker task performance was significant; the indirect effects of stimulation induced changes in the P3 bias for high calorie foods, the urge to consume high calorie foods, and the general liking ratings for high calorie foods were not significant. These findings confirm the causal role of the left dlPFC in the modulation of calorie dense food consumption via inhibitory control capacity.

Theta-burst modulation of mid-ventrolateral prefrontal cortex affects salience coding in the human ventral tegmental area.

In the context of hedonic (over-)eating the ventral tegmental area (VTA) as a core part of the dopaminergic reward system plays a central role in coding incentive salience of high-caloric food. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate whether transcranial magnetic theta-burst stimulation (TBS) over the right mid-ventrolateral prefrontal cortex (mid-VLPFC) can induce modulation of calorie-sensitive brain activation in the VTA. The prefrontal location for TBS had been predetermined by seed-based resting-state fMRI with a functionally defined portion of the VTA serving as seed region obtained from an independent second fMRI experiment. In a sample of 15 healthy male participants, modulation of calorie-sensitive VTA activation did not significantly differ between the two TBS protocols. Comparisons with baseline revealed that both TBS protocols significantly affected calorie-sensitive neural processing of the mid-VLPFC in a rather similar way. In the VTA significant modulation of calorie-sensitive activation was observed after continuous TBS, whereas the modulatory effect of intermittent TBS was less reliable but also associated with a decrease of activation for high-caloric food images. Neurostimulation of right mid-VLPFC is suggestive as a main entry point of downstream signal changes for high- and low-caloric food cues that could enforce a shift in valuating stimuli of initially different incentive salience.

Stimulation of PPC Affects the Mapping between Motion and Force Signals for Stiffness Perception But Not Motion Control.

How motion and sensory inputs are combined to assess an object's stiffness is still unknown. Here, we provide evidence for the existence of a stiffness estimator in the human posterior parietal cortex (PPC). We showed previously that delaying force feedback with respect to motion when interacting with an object caused participants to underestimate its stiffness. We found that applying theta-burst transcranial magnetic stimulation (TMS) over the PPC, but not the dorsal premotor cortex, enhances this effect without affecting movement control. We explain this enhancement as an additional lag in force signals. This is the first causal evidence that the PPC is not only involved in motion control, but also has an important role in perception that is disassociated from action. We provide a computational model suggesting that the PPC integrates position and force signals for perception of stiffness and that TMS alters the synchronization between the two signals causing lasting consequences on perceptual behavior. SIGNIFICANCE STATEMENT: When selecting an object such as a ripe fruit or sofa, we need to assess the object's stiffness. Because we lack dedicated stiffness sensors, we rely on an as yet unknown mechanism that generates stiffness percepts by combining position and force signals. Here, we found that the posterior parietal cortex (PPC) contributes to combining position and force signals for stiffness estimation. This finding challenges the classical view about the role of the PPC in regulating position signals only for motion control because we highlight a key role of the PPC in perception that is disassociated from action. Altogether this sheds light on brain mechanisms underlying the interaction between action and perception and may help in the development of better teleoperation systems and rehabilitation of patients with sensory impairments.

Primary motor cortex contributes to the implementation of implicit value-based rules during motor decisions.

In the present study, we investigated the functional contribution of the human primary motor cortex (M1) to motor decisions. Continuous theta burst stimulation (cTBS) was used to alter M1 activity while participants performed a decision-making task in which the reward associated with the subjects' responses (right hand finger movements) depended on explicit and implicit value-based rules. Subjects performed the task over two consecutive days and cTBS occurred in the middle of Day 2, once the subjects were just about to implement implicit rules, in addition to the explicit instructions, to choose their responses, as evident in the control group (cTBS over the right somatosensory cortex). Interestingly, cTBS over the left M1 prevented subjects from implementing the implicit value-based rule while its implementation was enhanced in the group receiving cTBS over the right M1. Hence, cTBS had opposite effects depending on whether it was applied on the contralateral or ipsilateral M1. The use of the explicit value-based rule was unaffected by cTBS in the three groups of subject. Overall, the present study provides evidence for a functional contribution of M1 to the implementation of freshly acquired implicit rules, possibly through its involvement in a cortico-subcortical network controlling value-based motor decisions.

Selective TMS-induced modulation of functional connectivity correlates with changes in behavior.

Despite the increasing use of functional connectivity (FC) studies in fundamental and clinical research, the link between FC and behavior is still poorly understood. To test the hypothesis that artificial modulation of FC correlates with changes in behavior in a quantitative manner, we performed behavioral and resting state fMRI experiments in monkeys while perturbing, offline, the frontal eye fields (FEF) using unilateral continuous theta burst transcranial magnetic stimulation (FEF-cTBS). Stimulation of left and right FEF caused remarkably specific decreases in FC, which were symmetric for intra-hemispheric and asymmetric for inter-hemispheric FC. Surprisingly, FEF-cTBS improved the performance and compensated intrinsic choice biases in saccadic behavior of four monkeys, independent of the initial bias direction. Moreover, the direction of the stimulation-induced effects on both behavior (i.e. bias compensation) and FC (i.e. decrease) were independent of the stimulated hemisphere, while their magnitude depended on the side of stimulation, choice bias and monkey. Overall, the naturally-occurring saccade biases determined the FC changes following FEF-cTBS. Finally, we showed that the average decreases in FC in the FEF network induced by cTBS can be used to predict, with high specificity, both the direction (opposite to the saccadic biases) and the magnitude of the shift in saccadic choice preference relative to the unperturbed state. To reconcile the apparent contradiction between improved performance and bias compensation vs. decrease in functional connectivity, we propose that the main functional consequences of FEF-cTBS relate to adjusting inter-hemispheric imbalances.

Disruption of right posterior parietal cortex by continuous Theta Burst Stimulation alters the control of body balance in quiet stance.

Control of body balance relies on the integration of multiple sensory modalities. Lightly touching an earth-fixed reference augments the control of body sway. We aimed to advance the understanding of cortical integration of an afferent signal from light fingertip contact (LT) for the stabilisation of standing body balance. Assuming that right-hemisphere Posterior Parietal Cortex (rPPC) is involved in the integration and processing of touch for postural control, we expected that disrupting rPPC would attenuate any effects of light touch. Eleven healthy right-handed young adults received continuous Theta Burst Stimulation over the left- and right-hemisphere PPC with sham stimulation as an additional control. Before and after stimulation, sway of the blindfolded participants was assessed in Tandem-Romberg stance with and without haptic contact. We analysed sway in terms of the variability of Centre-of-Pressure (CoP) rate of change as well as Detrended Fluctuation Analysis of CoP position. Light touch decreased sway variability in both directions but showed direction-specific changes in its dynamic complexity: a positive increase in complexity in the mediolateral direction coincided with a reduction in the anteroposterior direction. rPPC disruption affected the control of body sway in two ways: first, it led to an overall decrease in sway variability irrespective of the presence of LT; second, it reduced the complexity of sway with LT at the contralateral, non-dominant hand. We speculate that rPPC is involved in the active exploration of the postural stability state, with utilisation of LT for this purpose if available, by normally inhibiting mechanisms of postural stiffness regulation.

After Effects of Cerebellar Continuous Theta Burst Stimulation on Reflexive Saccades and Smooth Pursuit in Humans.

The use of cerebellar repetitive transcranial magnetic stimulation has been attempted for perturbing reflexive and voluntary eye movements, but discrepancies are seen between the results of distinct studies possibly due to the different stimulation sites, intensities, and paradigms. We describe the after effects of 20 and 40 s continuous Theta Burst Stimulation (cTBS) as compared to sham stimulation, applied over the lateral cerebellar vermis and paravermis on Reflexive Saccades (RS) and Smooth Pursuit (SP) eye movements, recorded in the 30 min following stimulation. The experiments were carried out in eight healthy volunteers, and eye movements were recorded monocularly with video-oculography. The 40 s cTBS significantly increased the amplitude of ipsilateral RS and the acceleration of the ipsilateral SP, and this effect was detectable all over the 30-min recording period; 40 s cTBS did not modify the other parameters, namely the peak velocity, the duration and the latency of RS, and the latency and the velocity of SP. The 20 s cTBS was ineffective on all RS and SP parameters. Finally, we detected a significant quite-linear reduction of RS peak velocity over time, but this was independent from cTBS and was probably caused by fatigue. The effects of 40 s cTBS in our experiments mimic the disorder of ocular motility in Wallenberg's syndrome and could result from functional impairment of cerebellopontine pathways. This effect lasts 30 min at least, and can provide a useful framework for adaptive ocular motor studies.

Theta Burst Stimulation of the Precuneus Modulates Resting State Connectivity in the Left Temporal Pole.

It has been shown that continuous theta burst stimulation (cTBS) over the precuneus acts on specific memory retrieval abilities. In order to study the neural mechanisms beyond these findings, we combined cTBS and resting-state functional magnetic resonance imaging. Our experimental protocol involved stimulation and sham conditions on a group of healthy subjects, and each condition included a baseline and two follow-up acquisitions (5 and 15 min after baseline) after cTBS. We analysed brain functional connectivity by means of graph theoretical measures, with a specific focus on the network modular structure. Our results showed that cTBS of the precuneus selectively affects the left temporal pole, decreasing its functional connectivity in the first follow-up. Moreover, we observed a significant increase in the size of the module of the precuneus in the second follow-up. Such effects were absent in the sham condition. We observed here a modulation of functional connectivity as a result of inhibitory stimulation over the precuneus. Such a modulation first acts indirectly on the temporal area and then extends the connectivity of the precuneus itself by a feed-back mechanism. Our current findings extend our previous behavioural observations and increase our understanding of the mechanisms underlying the stimulation of the precuneus.

Mapping the Dynamic Network Interactions Underpinning Cognition: A cTBS-fMRI Study of the Flexible Adaptive Neural System for Semantics.

Higher cognitive function reflects the interaction of a network of multiple brain regions. Previous investigations have plotted out these networks using functional or structural connectivity approaches. While these map the topography of the regions involved, they do not explore the key aspect of this neuroscience principle-namely that the regions interact in a dynamic fashion. Here, we achieved this aim with respect to semantic memory. Although converging evidence implicates the anterior temporal lobes (ATLs), bilaterally, as a crucial component in semantic representation, the underlying neural interplay between the ATLs remains unclear. By combining continuous theta-burst stimulation (cTBS) with functional magnetic resonance imaging (fMRI), we perturbed the left ventrolateral ATL (vATL) and investigated acute changes in neural activity and effective connectivity of the semantic system. cTBS resulted in decreased activity at the target region and compensatory, increased activity at the contralateral vATL. In addition, there were task-specific increases in effective connectivity between the vATLs, reflecting an increased facilitatory intrinsic connectivity from the right to left vATL. Our results suggest that semantic representation is founded on a flexible, adaptive bilateral neural system and reveals an adaptive plasticity-based mechanism that might support functional recovery after unilateral damage in neurological patients.

Disrupting the supplementary motor area makes physical effort appear less effortful.

The perception of physical effort is relatively unaffected by the suppression of sensory afferences, indicating that this function relies mostly on the processing of the central motor command. Neural signals in the supplementary motor area (SMA) correlate with the intensity of effort, suggesting that the motor signal involved in effort perception could originate from this area, but experimental evidence supporting this view is still lacking. Here, we tested this hypothesis by disrupting neural activity in SMA, in primary motor cortex (M1), or in a control site by means of continuous theta-burst transcranial magnetic stimulation, while measuring effort perception during grip forces of different intensities. After each grip force exertion, participants had the opportunity to either accept or refuse to replicate the same effort for varying amounts of reward. In addition to the subjective rating of perceived exertion, effort perception was estimated on the basis of the acceptance rate, the effort replication accuracy, the influence of the effort exerted in trial t on trial t+1, and pupil dilation. We found that disruption of SMA activity, but not of M1, led to a consistent decrease in effort perception, whatever the measure used to assess it. Accordingly, we modeled effort perception in a structural equation model and found that only SMA disruption led to a significant alteration of effort perception. These findings indicate that effort perception relies on the processing of a signal originating from motor-related neural circuits upstream of M1 and that SMA is a key node of this network.

Differential effects of continuous theta burst stimulation over left premotor cortex and right prefrontal cortex on modulating upper limb somatosensory input.

Somatosensory evoked potentials (SEPs) represent somatosensory processing in non-primary motor areas (i.e. frontal N30 and N60) and somatosensory cortices (i.e. parietal P50). It is well-known that the premotor cortex (PMC) and prefrontal cortex (PFC) are involved in the preparation and planning of upper limb movements but it is currently unclear how they modulate somatosensory processing for upper limb motor control. In the current study, two experiments examined SEP modulations after continuous theta burst stimulation (cTBS) was used to transiently disrupt the left PMC (Experiment 1) and right PFC (Experiment 2). Both Experiment 1 (n=15) and Experiment 2 (n=16) used pre-post experimental designs. In both experiments participants performed a task requiring detection of varying amplitudes of attended vibrotactile (VibT) stimuli to the left index finger (D2) and execution of a pre-matched finger sequence with the right (contralateral) hand to specific VibT targets. During the task, SEPs were measured to median nerve (MN) stimulations time-locked during pre-stimulus (250 ms before VibT), early response selection (250 ms after VibT), late preparatory (750 ms after VibT) and execution (1250 ms VibT) phases. The key findings of Experiment 1 revealed significant decreases in N30 and N60 peak amplitudes after cTBS to PMC. In contrast, the results of Experiment 2, also found significant decreased N60 peak amplitudes as well as trends for increased N30 and P50 peak amplitudes. A direct comparison of Experiment 1 and Experiment 2 confirmed differential modulation of N30 peak amplitudes after PMC (gated) compared to PFC (enhanced) cTBS. Collectively, these results support that both the left PMC and right PFC have modulatory roles on early somatosensory input into non-primary motor areas, such as PMC and supplementary motor area (SMA), represented by frontal N30 and N60 SEPs. These results confirm that PMC and PFC are both part of a network that regulates somatosensory input for upper limb motor control.