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Does language shape human cognition? One aspect of this debate concerns whether the combinatorial operations of natural language also serve, supramodally, as a basis for the combinatorial operations of other domains of human thought such as mathematics, music, cognition, and theory of mind, among others. In the context of human reasoning, a growing body of research has generated two opposing views concerning the role of language in enabling deductive inference-making. Under the first, the structure-dependent operations required for deductive reasoning are linguistic in nature and thus based on the neural mechanisms of natural language. Under the second, deductive reasoning is supported by language independent processes principally implemented in frontomedial and left frontopolar cortices (in Brodmann areas [BA] 8 and 10, respectively). We tested the two competing views using continuous Theta Burst Stimulation (cTBS), an inhibitory neuromodulation approach. Here, we report a neural dissociation between the structure-dependent operations of natural language and those of deductive reasoning. Specifically, we found that transient cTBS inhibition of Brocas area, in the left inferior frontal gyrus (IFG), a region often associated with processing the hierarchical dependencies of natural language, impairs accuracy for linguistic problems but not for logic ones. Conversely, cTBS to frontomedial cortices produces the opposite pattern. Our results demonstrate that, in the adult brain, the structure-dependent operations of reasoning are not parasitic to the neural substrate of natural language.

The occipital face area (OFA) is hierarchically one of the first stages of the face processing network. It has originally been thought to be involved in early, structural processing steps, but currently more and more studies challenge this view and propose that it also takes part in higher level face processing, such as identification and recognition. Here we tested whether the OFA is involved in the initial steps of recognition memory and plays a causal role in the differential processing of familiar and unfamiliar faces. We used an offline, inhibitory continuous theta-burst stimulation (cTBS) protocol over the right OFA and the vertex as control site. Electroencephalographic (EEG) recording of event-related potentials (ERPs), elicited by visually presented familiar (famous) and unfamiliar faces was performed before and after stimulation. We observed a difference in ERPs for famous and unfamiliar faces in a time-window corresponding to the N250 component. Importantly, this difference was significantly increased by cTBS of the right OFA, suggesting its causal role in the differential processing of familiar and unfamiliar faces. The enhancement occurred focally, at electrodes close to the right hemispheric cTBS site, as well as over similar occipito-temporal sites of the contralateral hemisphere. To the best of our knowledge, this is the first study showing the causal role of the rOFA in the differential processing of familiar and unfamiliar faces, using combined cTBS and EEG recording methods. These results are discussed with respect to the nature of familiar face representations, supported by an extensive, bilateral network.

Mind wandering is a mental state that is typically characterized as attention drifting away from external tasks to internal thoughts (i.e., task-unrelated thought). The goal of this project is to reduce the propensity to mind wandering using continuous theta burst stimulation (cTBS) over the left angular gyrus (AG). cTBS is an repetitive transcranial magnetic stimulation (rTMS) technique developed to create long-lasting inhibitory effects in the stimulated brain regions (Rounis & Huang, 2020). In an accelerated protocol participants will be stimulated three times in a single session. The target region is the left angular gyrus (AG), an area that is part of the default mode network. By using inhibitory cTBS over the AG, we aim to reduce the propensity to mind wander by reducing the activity of the DMN. The rationale for this approach is that the DMN is commonly shown to be more active during mind wandering (Christoff et al., 2009; Mason et al., 2007), and a reduction of its activity and/or functional connectivity can therefore be hypothesized to result in a decrease of MW. If this approach is effective, it should make the participants able to stay more on task and to direct their attention better to the primary task, and therefore reduce mind wandering frequency. The outcome variables for this study will be self-reported mind wandering, and two behavioral features related to mind wandering (behavioral variability and randomness in sequence response). These behavioral features will be captured using a finger-tapping random-sequence generation task developed in our group (FT-RSGT; Boayue, et al., 2020). We expect that self-reported mind wandering and the behavioral measures will differ depending on whether the person received a real or fake stimulation.

The dorsolateral prefrontal cortex (DLPFC) is activated when bilinguals switch between languages. Language switching can also elicit the N2 event-related potential (ERP). This ERP component appears to capture the cognitive control processes related to conflict monitoring, response selection and response inhibition. In the present study, continuous theta-burst stimulation (cTBS) was used to examine the role of the left DLPFC in bilingual language switching, using a picture-naming task. Participants in the study were 17 Afrikaans-English bilinguals. The picture-naming task consisted of non-switch and switch trials. On non-switch trials, participants named two consecutive pictures in the same language. On switch trials, participants named consecutive pictures in different languages (e.g., Afrikaans and then English). The participants completed three testing sessions. In each session, participants received either cTBS to the left DLPFC or the vertex, or sham stimulation, and then completed the picture-naming task. The results showed that following DLPFC stimulation, the N2 ERP was attenuated on switch trials compared to non-switch trials. Vertex or sham stimulation did not modulate the N2 ERP. cTBS did not affect language switching at the behavioural level. These results provide support for the role of the left DLPFC in the cognitive control processes underlying bilingual language switching. Furthermore, the study demonstrates that these processes can be modulated via non-invasive brain stimulation and the effects detected at the neural level.

In everyday life, risky decision-making relies on multiple cognitive processes including sensitivity to reinforcers, exploration, learning, and forgetting. Neuroimaging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in exploration and risky decision-making, but the nature of its computations and its causal role remain uncertain. We provide evidence for the role of the DLPFC in value-independent, directed exploration on the Iowa Gambling Task (IGT) and we describe a new computational model to account for the competition of directed exploration and exploitation in guiding decisions. Forty-two healthy human participants were included in a right DLPFC, left DLPFC or sham stimulation groups using continuous theta-burst stimulation (cTBS). Immediately after cTBS, the IGT was completed. Computational modelling was used to account for exploration and exploitation with different combinations with value-based and sensitivity to reinforcers for each group. Applying cTBS to the left and right DLPFC selectively decreased directed exploration on the IGT compared to sham stimulation. Model-based analyses further indicated that the right (but not the left) DLPFC stimulation increased sensitivity to reinforcers, leading to avoidance of risky choices and promoting advantageous choices during the task. Although these findings are based on small sample sizes per group, they nevertheless elucidate the causal role of the right DLPFC in governing the exploration-exploitation tradeoff during decision-making in uncertain and ambiguous contexts.

Motor memories become resistant to interference by the process of consolidation, which leads to long-term retention. Studies have shown involvement of the somatosensory cortex in motor learning-related plasticity, but not directly in motor memory consolidation. This Neuro Forum article reviews evidence from a continuous theta-burst transcranial magnetic stimulation (cTBS) study by Kumar and colleagues (Kumar N, Manning TF, Ostry DJ. PLoS Biol 17: e3000469, 2019) that demonstrates the role of somatosensory, rather than motor, cortex in human motor memory consolidation during implicit motor learning.

Background Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. Objective/Hypothesis This study brought together over 60 TMS researchers to form the ‘Big TMS Data Collaboration’, and create the largest known sample of individual participant TBS data to date. The goal was to enable a more comprehensive evaluation of factors driving TBS response variability. Methods 118 corresponding authors of TMS studies were emailed and asked to provide deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to iTBS and cTBS response variability. Results 430 healthy participants’ TBS data was pooled across 22 studies (mean age = 41.9; range = 17–82; females = 217). Baseline MEP amplitude, age, target muscle, and time of day significantly predicted iTBS-induced plasticity. Baseline MEP amplitude and timepoint after TBS significantly predicted cTBS-induced plasticity. Conclusions This is the largest known study of interindividual variability in TBS. Our findings indicate that a significant portion of variability can be attributed to the methods used to measure the modulatory effects of TBS. We provide specific methodological recommendations in order to control and mitigate these sources of variability.

We recently proposed a neurocognitive model of distancing-an emotion regulation tactic-with a focus on the lateral parietal cortex. Although this brain area has been implicated in both cognitive control and self-projection processes during distancing, fMRI work suggests that these processes may be dissociable here. This preregistered (NCT03698591) study tested the contribution of left temporoparietal junction (TPJ) to distancing using repetitive transcranial magnetic stimulation. We hypothesized that inhibiting left TPJ would decrease the efficiency of distancing but not distraction, another regulation tactic with similar cognitive control requirements, thus implicating this region in the self-projection processes unique to distancing. Active and sham continuous theta burst stimulation (cTBS) were applied to 30 healthy adults in a single-session crossover design. Tactic efficiency was measured using online reports of valence and effort. The stimulation target was established from the group TPJ fMRI activation peak in an independent sample using the same distancing task, and anatomical MRI scans were used for individual targeting. Analyses employed both repeated-measures ANOVA and analytic procedures tailored to crossover designs. Irrespective of cTBS, distancing led to greater decreases in negative valence over time relative to distraction, and distancing effort decreased over time while distraction effort remained stable. Exploratory analyses also revealed that active cTBS made distancing more effortful, but not distraction. Thus, left TPJ seems to support self-projection processes in distancing, and these processes may be facilitated by repeated use. These findings help to clarify the role of lateral parietal cortex in distancing and inform applications of distancing and distraction.

Prior functional magnetic resonance imaging (fMRI) studies indicate that a core network of brain regions, including the hippocampus, is jointly recruited during episodic memory, episodic simulation, and divergent creative thinking. Because fMRI data are correlational, it is unknown whether activity increases in the hippocampus, and the core network more broadly, play a causal role in episodic simulation and divergent thinking. Here we employed fMRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of hippocampal brain networks impairs both episodic simulation and divergent thinking. For each of two TMS sessions, continuous θ-burst stimulation (cTBS) was applied to either a control site (vertex) or to a left angular gyrus target region. The target region was identified on the basis of a participant-specific resting-state functional connectivity analysis with a hippocampal seed region previously associated with memory, simulation, and divergent thinking. Following cTBS, participants underwent fMRI and performed a simulation, divergent thinking, and nonepisodic control task. cTBS to the target region reduced the number of episodic details produced for the simulation task and reduced idea production on divergent thinking. Performance in the control task did not statistically differ as a function of cTBS site. fMRI analyses revealed a selective and simultaneous reduction in hippocampal activity during episodic simulation and divergent thinking following cTBS to the angular gyrus versus vertex but not during the nonepisodic control task. Our findings provide evidence that hippocampal-targeted TMS can specifically modulate episodic simulation and divergent thinking, and suggest that the hippocampus is critical for these cognitive functions.

More than a decade of neuroimaging and brain stimulation studies point to a crucial role for the right dorsolateral prefrontal cortex (rDLPFC) in prosocial behavior. The intuitive prosociality model postulates that the rDLPFC controls intuitive prosocial behavior, whereas the reflective model assumes that the rDLPFC controls selfish impulses during prosocial behavior. The intuitive prosociality model implies that the transient disruption of the rDLPFC should increase voluntary transfers in both dictator and generosity games. In contrast, the reflective model suggests that the transient disruption of the rDLPFC should decrease transfers in the dictator game, without affecting voluntary transfers in the generosity game, in which selfish motives are minimized. The aim of this paper was to compare predictions of the intuitive and reflective models using the classic dictator game and generosity game and continuous theta burst stimulation (cTBS). In this study, two groups of healthy participants (dictators) received either cTBS over the rDLPFC or right extrastriate visual areas. As shown by the results, the transient disruption of the rDLPFC significantly promoted prosocial motives in the dictator game only, particularly in the trials with the lowest dictator’s costs. These findings partially support the notion that the rDLPFC controls intuitive prosocial behavior.

When direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit partially distinct brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience. In humans, OFC activity is also correlated with inferred outcomes, but it is unclear whether OFC activity is required for inference-based behavior. To test this, we used noninvasive network-based continuous theta burst stimulation (cTBS) in human subjects (male and female) to target lateral OFC networks in the context of a sensory preconditioning task that was designed to isolate inference-based behavior from responding that can be based on direct experience alone. We show that, relative to sham, cTBS targeting this network impairs reward-related behavior in conditions in which outcome expectations have to be mentally inferred. In contrast, OFC-targeted stimulation does not impair behavior that can be based on previously experienced stimulus–outcome associations. These findings suggest that activity in the targeted OFC network supports decision-making when outcomes have to be mentally simulated, providing converging cross-species evidence for a critical role of OFC in model-based but not model-free control of behavior.SIGNIFICANCE STATEMENTIt is widely accepted that the orbitofrontal cortex (OFC) is important for decision-making. However, it is less clear how exactly this region contributes to behavior. Here we test the hypothesis that the human OFC is only required for decision-making when future outcomes have to be mentally simulated, but not when direct experience with stimulus–outcome associations is available. We show that targeting OFC network activity in humans using network-based continuous theta burst stimulation selectively impairs behavior that requires inference but does not affect responding that can be based solely on direct experience. These results are in line with previous findings in animals and suggest a critical role for human OFC in model-based but not model-free behavior.

Contains fulltext : 216048pub.pdf (Publisher’s version ) (Open Access) 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. 11 p.

Intergroup bias, which is the tendency to behave more positively toward an in‐group member than toward an out‐group member, is pervasive in real life. In particular, intergroup bias in trust decisions substantially influences multiple areas of life and thus better understanding of this tendency can provide significant insights into human social behavior. Although previous functional magnetic resonance imaging studies showed the involvement of the right temporoparietal junction (TPJ) in intergroup trust bias, a causal relationship between the two has rarely been explored. By combining repetitive transcranial magnetic stimulation and a newly developed trust game task, we investigated the causal role of the right TPJ in intergroup bias in trust decisions. In the trust game task, the counterpart's group membership (in‐group or out‐group) and reciprocity were manipulated. We applied either neuronavigated inhibitory continuous theta burst stimulation (cTBS) or sham stimulation over the right TPJ before performing the trust game task in healthy volunteers. After the sham stimulation, the participants' degrees of investments with in‐group members were significantly higher than those with out‐group members. However, after cTBS to the right TPJ, this difference was not observed. The current results extend previous findings by showing that the causal roles of the right TPJ can be observed in intergroup bias in trust decisions. Our findings add to our understanding of the mechanisms of human social behavior.

The period immediately after the offset of visual training is thought to be critical for memory consolidation. Nevertheless, we still lack direct evidence for the causal role of this period to perceptual learning of either previously or subsequently trained material. To address these issues, we had human subjects complete two consecutive trainings with different tasks (detecting different Gabor orientations). We applied continuous theta burst stimulation (cTBS) to either the visual cortex or a control site (vertex) immediately after the offset of the first training. In the vertex cTBS condition, subjects showed improvement on the first task but not on the second task, suggesting the presence of anterograde interference. Critically, cTBS to the visual cortex abolished the performance improvement on the first task and released the second training from the anterograde interference. These results provide causal evidence for a role of the immediate post-training period in the consolidation of perceptual learning., Ji Won Bang et al. test the importance of the immediate post-visual training period for memory consolidation in human subjects. They apply continuous theta burst stimulation (cTBS) directly following a learning task and show that this does affect memory consolidation, and that this effect relies on the visual cortex.

Hemispheric asymmetries play an important role in multiple cerebral functions. Asymmetries in prefrontal cortex (PFC) function have been suggested to regulate emotional processing in that right-hemispheric dominance biases towards negative affect, whereas left PFC dominance favors positive affect. This study used transcranial magnetic stimulation to test the causal role of prefrontal asymmetries in the processing of emotional stimuli. To experimentally induce hemispheric asymmetries, 21 healthy volunteers underwent two separate sessions of inhibitory continuous theta burst stimulation (cTBS) to the left versus right dorsolateral prefrontal cortex. Each stimulation was followed by magnetoencephalographic (MEG) recordings of event-related fields elicited by visually presented emotional words in a silent reading task and a subsequent behavioral emotion categorization task. The asymmetry manipulation influenced valence processing of words in early, mid-latency and late time intervals in right occipitotemporal and parietal brain regions. Left-sided cTBS (inducing right-hemispheric dominance) consistently resulted in enhanced brain responses to negative words, while right-sided cTBS (inducing left-hemispheric dominance) enhanced responses to positive words. On a behavioral level, right-hemispheric dominance resulted in more categorization matches of negative compared to positive words, while left-hemispheric dominance resulted in reverse effects. These results provide direct evidence that bottom-up valence processing is influenced by prefrontal hemispheric asymmetry.

Theories of emotion suggest a close relation of interoception and emotion. However, knowledge of underlying neuronal networks is still sparse. Repetitive transcranial magnetic stimulation (rTMS) is one neurostimulation method allowing causal conclusions between functions and brain regions via stimulation or inhibition of underlying brain structures. In this study, rTMS with a continuous theta burst stimulation (cTBS) protocol was used aiming for inhibition of important interoceptive network structures (frontotemporal insular network and right somatosensory cortices). Stimulation effects were investigated on interoceptive accuracy (IAc), emotional evaluation and neuronal correlates of emotional picture processing in 18 male participants. The main findings were an emotional flattening in subjective valences for affective stimuli after inhibition of the frontotemporal anterior insular network and of somatosensory cortices, being mirrored in visual evoked potentials as increased N2/decreased P3, indicating an initial orientation reaction followed by decreased attentional processing of positive stimuli. Moreover, cardiac and respiratory IAc were positively associated with P3 amplitudes and negatively related to positive valence ratings. Positive associations of decreases of cardiac/respiratory IAc with decreases of arousal ratings and decreases of P3 amplitudes for negative stimuli after inhibition of the frontotemporal insular network and after inhibition of somatosensory cortices allow the conclusion of a causal relationship between reduced activity in interoceptive network structures and blunted emotional processing of visual stimuli. Our results suggest that both arousal, and valence aspects of emotional processing are disturbed after inhibition of interoceptive network structures, confirming core assumptions of peripheral theories of emotions and models of interoceptive predictive coding.

Cooperation enhances interpersonal communication and nurtures society. However, efforts to socially cooperate may often evoke conflict. Individuals may selfishly pursue a greater reward or success by exploiting the efforts of other individuals or taking unnecessary risk to oneself. Such a cooperation dilemma is highly prevalent in real life; thus, it has been studied in various disciplines. Although published functional magnetic resonance imaging studies have shown the involvement of the right temporoparietal junction (TPJ) in resolving a dilemma through cooperation, a causal relationship between the two has rarely been explored. Hence, we investigated this issue by combining repetitive transcranial magnetic stimulation with a priority game task (modified snowdrift game). In this game task, participants and opponent players jointly faced a problem whereby their collaboration was anticipated to defuse the situation. This conflicted with a choice in the participant's self-interest that was more rewarding but risky. We further included conditions with and without explicit social cues using figures describing elderly/pregnant passengers in the game opponent's car, and measured participants' prosocial traits to examine any cue-induced effect as well as the personality-cooperation relationship, respectively. The cooperation ratio was not statistically different in both the no-cue and with-cue conditions between the sham stimulation and inhibitory continuous theta burst stimulation (cTBS). However, after cTBS, in the no-cue condition, the strength of the association between cooperation ratio and empathy traits decreased significantly. These results add to our knowledge about the right TPJ's role in social cognition, which may be extraordinarily complex. This topic is deserving of further examination.

Human cognition is often biased. It is a fundamental question in psychology how cognitive bias is modulated in the human brain. Automatic action tendency is a typical cognitive bias. The dorsolateral prefrontal cortex (DLPFC) is a crucial area for processing various behavioral tasks. We investigated the functional role of DLPFC in the modulation of cognitive bias by testing the automatic action tendency during automatic and regulated behavioral tasks. Unilateral intermittent or continuous theta burst stimulation (excitatory iTBS or inhibitory cTBS) was used to manipulate the left or right DLPFC excitability and assess the changes in automatic action tendency during a manikin task. An approaching behavior with positive stimulus and avoiding behavior with negative stimulus were performed in an automatic task. An approaching behavior with negative stimulus and avoiding behavior with positive stimulus were performed in a regulated task. Reaction time was measured. We confirmed the automatic action tendency that reaction time for performing an automatic task was shorter than that for performing a regulated task. The automatic action tendency was enhanced after left DLPFC excitatory iTBS and was abolished after left DLPFC inhibitory cTBS stimulation. On the other hand, right DLPFC excitatory iTBS accelerated the avoiding behaviors and right DLPFC inhibitory cTBS accelerated approaching behaviors. The results suggest that left DLPFC modulates the automatic action tendency while the right DLPFC modulates the direction of behavioral tasks. We conclude that left DLPFC and right DLPFC are key nodes in modulating the cognitive bias while their functional roles are different.

Disruption of resting-state functional connectivity (RSFC) between core regions of the dorsal attention network (DAN), including the bilateral superior parietal lobule (SPL), and structural damage of the right-lateralized ventral attention network (VAN), including the temporo-parietal junction (TPJ), have been described as neural basis for hemispatial neglect. Pursuing a virtual lesion model, we aimed to perturbate the attention networks of 22 healthy subjects by applying continuous theta burst stimulation (cTBS) to the right SPL or TPJ. We first created network masks of the DAN and VAN based on RSFC analyses from a RS-fMRI baseline session and determined the SPL and TPJ stimulation site within the respective mask. We then performed RS-fMRI immediately after cTBS of the SPL, TPJ (active sites) or vertex (control site). RSFC between SPL/TPJ and whole brain as well as between predefined regions of interest (ROI) in the attention networks was analyzed in a within-subject design. Contrary to our hypothesis, seed-based RSFC did not differ between the four experimental conditions. The individual change in ROI-to-ROI RSFC from baseline to post-stimulation did also not differ between active (SPL, TPJ) and control (vertex) cTBS. In our study, a single session offline cTBS over the right SPL or TPJ could not alter RSFC in the attention networks as compared to a control stimulation, maybe because effects wore off too early. Future studies should consider a modified cTBS protocol, concurrent TMS-fMRI or transcranial direct current stimulation.

Previous studies have shown that visuospatial working memory (VSWM) plays a key role in the encoding and processing of visuospatial information. More importantly, there is evidence suggesting the role of frontal and parietal cortical areas in VSWM and especially, the influence of the frontal cortex in regulating goal-directed behavior. However, the functional role of the right dorsolateral prefrontal cortex (rDLPFC) in visuospatial working memory is still unclear. Here, we noninvasively modulated the rDLPFC activity using continuous theta-burst stimulation (cTBS), with the vertex as the control site. Our study aimed to investigate the effects of cTBS over rDLPFC on working memory task (2- and 4-back) performance. Working memory performance was assessed at the baseline and after stimulation. We observed that the working memory performance as measured by discriminability index was impaired after cTBS over rDLPFC in 2-back task, whereas 4-back task performance was not significantly affected. More so, there was no effect on performance after cTBS over the vertex, suggesting a functional role of rDLPFC in VSWM. Our findings demonstrate the involvement of the rDLPFC in VSWM as well as the load-dependent effect of working memory performance. Taken together, our work constitutes a useful addition to the literature and underscores the effectiveness and efficiency of noninvasive brain stimulation in modulating neuro-cognitive activity.

The neural mechanisms underlying the effects of continuous Theta-Burst Stimulation (cTBS) in humans are poorly understood. Animal studies can clarify the effects of cTBS on individual neurons, but behavioral evidence is necessary to demonstrate the validity of the animal model. We investigated the behavioral effect of cTBS applied over parietal cortex in rhesus monkeys performing a visually-guided grasping task with two differently sized objects, which required either a power grip or a pad-to-side grip. We used Fitts' law, predicting shorter grasping times (GT) for large compared to small objects, to investigate cTBS effects on two different grip types. cTBS induced long-lasting object-specific and dose-dependent changes in GT that remained present for up to two hours. High-intensity cTBS increased GTs for a power grip, but shortened GTs for a pad-to-side grip. Thus, high-intensity stimulation strongly reduced the natural GT difference between objects (i.e. the Fitts' law effect). In contrast, low-intensity cTBS induced the opposite effects on GT. Modifying the coil orientation from the standard 45-degree to a 30-degree angle induced opposite cTBS effects on GT. These findings represent behavioral evidence for the validity of the nonhuman primate model to study the neural underpinnings of non-invasive brain stimulation. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Continuous theta burst stimulation (cTBS) is a powerful form of repetitive transcranial magnetic stimulation capable of suppressing cortical excitability for up to 50 min. A growing number of studies have applied cTBS to the visual cortex in human subjects to investigate the neural dynamics of visual processing, but few have specifically examined its effects on central vision, which has crucial implications for safety and inference on downstream cognitive effects. The present study assessed the safety of offline, neuronavigated cTBS to V2 by examining its effects on central vision performance. In this single-blind, randomized sham-controlled, crossover study, 17 healthy adults received cTBS (at 80% active motor threshold) and sham to V2 1–2 weeks apart. Their central vision (≤8°) was tested at 1-min (T1) and again at 50-min (T50) post-stimulation. Effects of condition (cTBS vs. sham) and time (T1 vs. T50) on accuracy and reaction time were examined using Bayes factor. Bayes factor results suggested that cTBS did not impair stimulus detection over the entire central visual field nor subfields at T1 or T50. Our results offer the first explicit evidence supporting that cTBS applied to V2 does not create blind spots in the central visual field in humans during a simple detection task. Any subtler changes to vision and downstream visual perception should be investigated in future studies.

The left dorsolateral prefrontal cortex (dlPFC) has been implicated in the regulation of stress-related cognitive processes and physiological responses and is the principal target of noninvasive brain stimulation techniques applied to psychiatric conditions. However, existing studies are mostly correlational and causal evidence on the role of this region in mediating specific psychophysiological mechanisms underpinning stress-related responses are needed to make the application of such techniques more efficient. To fill this gap, this study used inhibitory continuous theta burst stimulation (cTBS) in healthy individuals to examine the extent to which activity of the left dlPFC is associated with cognitive (subjective focus on a tracking task), behavioral (reaction times and variability), and physiological responses (heart rate and its variability and cortisol level) following induction of perseverative cognition. Compared to sham and left ventral PreMotor area stimulation (as active control area), inhibition of left dlPFC determined sustained autonomic and neuroendocrine activation and increased the subjective perception of being task-focused, while not changing the behavioral and self-reported stress-related responses. Adopting a causative approach, we describe a role of left dlPFC in inhibitory control of the physiological stress-response associated to perseverative thinking.

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) that can be used to increase (intermittent TBS) or reduce (continuous TBS) cortical excitability. The current study provides a preliminary report of the effects of iTBS and cTBS in healthy young adults, to investigate the causal role of the posterior parietal cortex (PPC) during the performance of four cognitive functions: attention, inhibition, sequence learning and working memory. A 2 × 2 repeated measures design was incorporated using hemisphere (left/right) and TBS type (iTBS/cTBS) as the independent variables. 20 participants performed the cognitive tasks both before and after TBS stimulation in 4 counterbalanced experimental sessions (left cTBS, right cTBS, left iTBS and right iTBS) spaced 1 week apart. No change in performance was identified for the attentional cueing task after TBS stimulation, however TBS applied to the left PPC decreased reaction time when inhibiting a reflexive response. The sequence learning task revealed differential effects for encoding of the sequence versus the learnt items. cTBS on the right hemisphere resulted in faster responses to learnt sequences, and iTBS on the right hemisphere reduced reaction times during the initial encoding of the sequence. The reaction times in the 2-back working memory task were increased when TBS stimulation was applied to the right hemisphere. Results reveal clear differential effects for tasks explored, and more specifically where TBS stimulation on right PPC could provide a potential for further investigation into improving oculomotor learning by inducing plasticity-like mechanisms in the brain.

Neuromodulation of the primary visual cortex using anodal transcranial direct current stimulation (a-tDCS) can alter visual perception and enhance neuroplasticity. However, the mechanisms that underpin these effects are currently unknown. When applied to the motor cortex, a-tDCS reduces the concentration of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), an effect that has been linked to increased neuroplasticity. The aim of this study was to assess whether a-tDCS also reduces GABA-mediated inhibition when applied to the human visual cortex. Changes in visual cortex inhibition were measured using the mixed percept duration in binocular rivalry. Binocular rivalry mixed percept duration has recently been advocated as a direct and sensitive measure of visual cortex inhibition whereby GABA agonists decrease mixed percept durations and agonists of the excitatory neurotransmitter acetylcholine increase them. Our hypothesis was that visual cortex a-tDCS would increase mixed percept duration by reducing GABA-mediated inhibition and increasing cortical excitation. In addition, we measured the effect of continuous theta-burst transcranial magnetic stimulation (cTBS) of the visual cortex on binocular rivalry dynamics. When applied to the motor or visual cortex, cTBS increases GABA concentration and we therefore hypothesized that visual cortex cTBS would decrease the mixed percept duration. Binocular rivalry dynamics were recorded before and after active and sham a-tDCS (N=15) or cTBS (N=15). Contrary to our hypotheses, a-tDCS had no effect, whereas cTBS significantly increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.

BackgroundIt is well established that proprioception (position sense) is important for motor control, yet its role in motor learning and associated plasticity is not well understood. We previously demonstrated that motor skill learning is associated with enhanced proprioception and changes in sensorimotor neurophysiology. However, the neural substrates mediating these effects are unclear.ObjectiveTo determine whether suppressing activity in the cerebellum and somatosensory cortex (S1) affects proprioceptive changes associated with motor skill learning.Methods54 healthy young adults practiced a skill involving visually-guided 2D reaching movements through an irregular-shaped track using a robotic manipulandum with their right hand. Proprioception was measured using a passive two-alternative choice task before and after motor practice. Continuous theta burst stimulation (cTBS), was delivered over S1 or the cerebellum (CB) at the end of training for two consecutive days. We compared group differences (S1, CB, Sham) in proprioception and motor skill, quantified by a speed-accuracy function, measured on a third consecutive day (retention).ResultsAs shown previously, the Sham group demonstrated enhanced proprioceptive sensitivity after training and at retention. The S1 group had impaired proprioceptive function at retention through online changes during practice, whereas the CB group demonstrated offline decrements in proprioceptive function. All groups demonstrated motor skill learning, however, the magnitude of learning differed between the CB and Sham groups, consistent with a role for the cerebellum in motor learning.ConclusionOverall, these findings suggest that the cerebellum and S1 are important for distinct aspects of proprioceptive changes during skill learning.

Self-other distinction is crucial for empathy, since it prevents the confusion of self-experienced emotions with those of others. We aimed to extend our understanding of the neurocognitive mechanisms of self-other distinction. Thirty-one female participants underwent continuous theta burst transcranial magnetic stimulation (cTBS) targeting the right supramarginal gyrus (rSMG), a sub-region of the temporoparietal junction previously shown to be involved in self-other distinction, and the vertex, a cortical control site. Right after stimulation they completed a visuo-tactile empathy task in an MRI scanner. Self-other distinction was assessed by differences in emotion judgments, and brain activity between conditions differing in the requirement for self-other distinction. Effects of brain stimulation on self-other distinction depended on individual differences in dispositional empathic understanding: cTBS of rSMG, compared to vertex, enhanced self-other distinction in participants with lower dispositional empathic understanding, but diminished it in participants with higher empathic understanding. On the neural level, this inverse relationship between empathic disposition and self-other distinction performance was linked to a reduction of cTBS-induced rSMG activity in persons with lower dispositional empathy, and an increase in those with lower dispositional empathy. These opposite cTBS impacts were also associated with two anatomically and functionally distinct networks. These findings open up novel perspectives on the causal role of rSMG in self-other distinction and empathy. They also suggest that considering individual differences may yield novel insights into how brain stimulation affects higher-level affect and cognition, and its neural correlates.

Although an enhancing effect of reward on cognitive performance has been observed consistently, its neural underpinnings remain elusive. Recent evidence suggests that the inferior frontal junction (IFJ) may be a key player underlying such an enhancement by integrating motivational processes and cognitive control. However, its exact role and in particular a potential causality of IFJ activation is still unclear. In the present study, we therefore investigated the causal contributions of the left IFJ in motivated task switching by temporarily disrupting its activity using continuous theta burst stimulation (cTBS, Exp.1) or 1 Hz repetitive transcranial magnetic stimulation (rTMS, Exp.2). After TMS application over the left IFJ or a control site (vertex), participants performed a switch task in which numbers had to be judged by magnitude or parity. Different amounts of monetary rewards (high vs low) were used to manipulate the participants’ motivational states. We measured reaction times and error rates. Irrespective of TMS stimulation, participants exhibited slower responses following task switches compared to task repeats. This effect was reduced in high reward trials. Importantly, we found that disrupting the IFJ improved participants’ behavioral performance in the high reward condition. For high reward trials exclusively, error rates decreased when the IFJ was modulated with cTBS or 1 Hz rTMS but not after vertex stimulation. Our results suggest that the left IFJ is causally related to the increase in cognitive performance through reward.

In skilled object lifting, fingertip forces need to be carefully scaled to object weight, which can be inferred from object properties, such as size or material. This anticipatory force scaling ensures smooth and efficient lifting movements. However, even with accurate motor plans, weight perception can still be biased. In the size-weight illusion, objects of different size but equal weight are perceived to differ in heaviness, with the small object perceived to be heavier than the large object. The neural underpinnings of the size-weight illusion and anticipatory force scaling to object size are largely unknown. In this study, we hypothesized a possible role of the anterior intraparietal cortex (aIPS) in predictive force scaling and the size-weight illusion, which we investigated by applying continuous theta burst stimulation (cTBS) prior to participants lifting objects designed to induce the size-weight illusion. Participants received cTBS over aIPS, the primary motor cortex (control area), or sham stimulation. We found no evidence that aIPS stimulation affected the size-weight illusion. Small effects were, however, found on anticipatory force scaling, where grip force was less tuned to object size during initial lifts. These findings suggest that, while aIPS might be peripherally involved in sensorimotor prediction, other brain areas underpin the processes that mediate the size-weight illusion.

Primary motor (M1) areas for speech production activate during speech perception. It has been suggested that such activation may be dependent upon modulatory inputs from premotor cortex (PMv). If and how PMv differentially modulates M1 activity during perception of speech that is easy or challenging to understand, however, is unclear. This study aimed to test the link between PMv and M1 during challenging speech perception in two experiments. The first experiment investigated intra-hemispheric connectivity between left hemisphere PMv and left M1 lip area during comprehension of speech under clear and distorted listening conditions. Continuous theta burst stimulation (cTBS) was applied to left PMv in eighteen participants (aged 18–35). Post-cTBS, participants performed a sentence verification task on distorted (imprecisely articulated), and clear speech, whilst also undergoing stimulation of the lip representation in the left M1 to elicit motor evoked potentials (MEPs). In a second, separate experiment, we investigated the role of inter-hemispheric connectivity between right hemisphere PMv and left hemisphere M1 lip area. Dual-coil transcranial magnetic stimulation was applied to right PMv and left M1 lip in fifteen participants (aged 18–35). Results indicated that disruption of PMv during speech perception affects comprehension of distorted speech specifically. Furthermore, our data suggest that listening to distorted speech modulates the balance of intra- and inter-hemispheric interactions, with a larger sensorimotor network implicated during comprehension of distorted speech than when speech perception is optimal. The present results further understanding of PMv-M1 interactions during auditory-motor integration.

Previous research indicates that alcohol intoxication impairs inhibitory control and that the right dorsolateral prefrontal cortex (rDLPFC) is a functional brain region important for exercising control over thoughts and behaviour. At the same time, the extent to which changes in inhibitory control following initial intoxication mediate subsequent drinking behaviours has not been elucidated fully. Ascertaining the extent to which inhibitory control impairments drive alcohol consumption, we applied continuous theta burst transcranial magnetic stimulation (rDLPFC cTBS vs. control) to isolate how inhibitory control impairments (measured using the Stop-Signal task) shape ad libitum alcohol consumption in a pseudo taste test. Twenty participants (13 males) took part in a within-participants design; their age ranged between 18 and 27 years (M = 20.95, SD = 2.74). Results indicate that following rDLPFC cTBS participants’ inhibitory control was impaired, and ad libitum consumption increased. The relationship between stimulation and consumption did not appear to be mediated by inhibitory control in the present study. Overall, findings suggest that applying TMS to the rDLPFC may inhibit neural activity and increase alcohol consumption. Future research with greater power is recommended to determine the extent to which inhibitory control is the primary mechanism by which the rDLPFC exerts influence over alcohol consumption, and the degree to which other cognitive processes may play a role.

Background The dorsolateral prefrontal cortex (dlPFC) plays a central role in the inhibition of eating, but also the modulation of conscious thought processes that might precede, accompany or follow initial food tasting. The latter might be particularly important to the extent that post-tasting cognitions may drive prolonged eating beyond the satiety point. However, we know very little about the effect of the dlPFC on conation following initial food sampling. This investigation compared the effects of dlPFC attenuation using repetitive transcranial magnetic stimulation (rTMS) on social cognition following (Study 1) and prior to (Study 2) a food consumption opportunity. Methods In Study 1, participants (N = 21; Mage = 21 years) were randomized to active or sham continuous theta-burst stimulation (cTBS; an inhibitory variant of rTMS) targeting the left dlPFC followed by an interference task. Participants subsequently completed measures of attitudes, norms and perceived control following a mock taste test. In Study 2, a second sample of right handed participants (N = 37; Mage = 21 years) were assigned to active or sham cTBS, followed by an interference task and two measures of attitudes (implicit and explicit), both assessed prior to the same taste test paradigm. Results In Study 1, findings revealed a reliable effect of cTBS on post-tasting attitudes (t(1,19) = 3.055, p = .007; d = 1.34), such that attitudes towards calorie dense snack foods were significantly more positive following active stimulation than following sham stimulation. Similar effects were found for social norms (t(1,19) = 3.024, p = .007, d = 1.31) and perceived control (t(1,20) = 19.247, p Conclusions The left dlPFC may selectively modulate facilitative social cognition following initial food sampling (but not pre-consumption).

Theta burst stimulation (TBS) is a highly efficient repetitive transcranial magnetic stimulation (rTMS) variant employed in experimental and clinical treatment paradigms. Despite widespread usage of TBS targeting the prefrontal cortex (PFC), there has been no systematic review of the evidence linking TBS protocols to changes in task performance on common measures of prefrontal function in general, and executive functions specifically. A systematic review of the literature was conducted using PsycINFO, PubMed, Web of Science and Scopus databases to identify articles examining the effects of TBS targeting the PFC on executive function task performance. Both the up-regulating (intermittent theta burst stimulation; iTBS) and down-regulating (continuous theta burst stimulation; cTBS) variants of TBS were considered. 32 (29 cTBS; 8 iTBS) studies met the inclusion criteria. Participants (n = 759; 51.41% female) were primarily young adults (Mage = 26), with one study examining the effects of cTBS and iTBS in older adults. Results from individual studies were converted to Hedge's g and random-effects models were used to estimate the overall effect size for each protocol. Age, biological sex, and control methodology were examined as potential moderators of the cTBS effect on executive function test performance. Findings indicated a- reliable attentuating effect of cTBS on executive function task performance (g = −.244, Z = −5.920, p

Prefrontal cortex (PFC) plays an important role in emotional processing and therefore is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) in clinical trials, especially in the treatment of emotional disorders. As an approach to enhance the effectiveness of rTMS, continuous theta burst stimulation (cTBS) has been demonstrated to be efficient and safe. However, it is unclear how cTBS affects brain processes related to emotion. In particular, psychophysiological studies on the underlying neural mechanisms are sparse. In the current study, we investigated how the cTBS influences emotional processing when applied over the right PFC. Participants performed an emotion recognition Go/NoGo task, which asked them to select a GO response to either happy or fearful faces after the cTBS or after sham stimulation, while 64-channel electroencephalogram (EEG) was recorded. EEG oscillation was examined using event-related spectral perturbation (ERSP) in a time-interval between 170 and 310ms after face stimuli onset. In the sham group, we found a significant difference in the alpha band between response to happy and fearful stimuli but that effect did not exist in the cTBS group. The alpha band activity at the scalp was reduced suggesting the excitatory effect at the brain level. The beta and gamma band activity was not sensitive to cTBS intervention. The results of the current study demonstrate that cTBS does affect emotion processing and the effect is reflected in changes in EEG oscillations in the alpha band specifically. The results confirm the role of prefrontal cortex in emotion processing. We also suggest that this pattern of cTBS results elucidates mechanisms by which mood improvement in depressive disorders is achieved using cTBS intervention.

Microsaccade is a type of fixational eye movements that is modulated by various sensory and cognitive processes, and impact our visual perception. Although studies in monkeys have demonstrated a functional role for the superior colliculus and frontal eye field (FEF) in controlling microsaccades, our understanding of the neural mechanisms underlying the generation of microsaccades is still limited. By applying continuous theta-burst stimulation (cTBS) over the right FEF and the vertex, we investigated the role of the FEF in generating human microsaccade responses evoked by salient stimuli or by changes in background luminance. We observed higher microsaccade rates prior to target appearance, and larger rebound in microsaccade occurrence following salient stimuli, when disruptive cTBS was applied over FEF compared to vertex stimulation. Moreover, the microsaccade direction modulation after changes in background luminance was disrupted with FEF stimulation. Together, our results constitute the first evidence of FEF modulation in human microsaccade responses.

Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n=30; female, n=30; mean age=23.5y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a novel evidence for the short-term effect of TBS on spontaneous brain activation.

We used complete-linkage cluster analysis to identify healthy subpopulations with distinct responses to continuous theta-burst stimulation (cTBS).21 healthy adults (age±SD, 36.9±15.2years) underwent cTBS of left motor cortex. Natural log-transformed motor evoked potentials (LnMEPs) at 5-50min post-cTBS (T5-T50) were calculated.Two clusters were found; Group 1 (n=12) that showed significant MEP facilitation at T15, T20, and T50 (p's0.006), and Group 2 (n=9) that showed significant suppression at T5-T15 (p's0.022). LnMEPs at T10 and T40 were best predictors of, and together accounted for 80% of, cluster assignment. In an exploratory analysis, we examined the roles of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms in the cTBS response. Val66Met participants showed greater facilitation at T10 than Val66Val participants (p=0.025). BDNF and cTBS intensity predicted 59% of interindividual variability in LnMEP at T10. APOE did not significantly affect LnMEPs at any time point (p's0.32).Data-driven cluster analysis can identify healthy subpopulations with distinct cTBS responses. T10 and T40 LnMEPs were best predictors of cluster assignment. T10 LnMEP was influenced by BDNF polymorphism and cTBS intensity.Healthy adults can be sorted into subpopulations with distinct cTBS responses that are influenced by genetics.

Network connectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has revealed the contribution of distinct cerebellar lobules to an array of brain wide networks sub-serving motor and cognitive processes. As distinct cerebellar lobules form relatively accessible nodes of different brain networks, this raises the possibility for site-specific modulation of network connectivity using non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). Continuous theta burst transcranial magnetic stimulation (cTBS) induces long-lasting inhibition of cortical areas. Although previous studies have shown that cTBS of the lateral cerebellum modulates motor cortical excitability and improves symptoms in several movement disorders, the effect on cognitive domains has not been examined. We explored the immediate effects of cTBS in a sham-controlled study on the strength of intrinsic functional connectivity between cerebellar and cortical motor and cognitive regions in 12 participants. Lateral cerebellar cTBS significantly decreased functional connectivity with frontal and parietal cognitive regions, while connectivity with motor regions remained unaltered. Sham stimulation had no effect on either motor or cognitive connectivity. These results show that inhibitory cerebellar stimulation reduces intrinsic functional connectivity between different cortical areas, in keeping with the known connectivity pattern of the cerebellum. The results highlight the plasticity of cerebello-cerebral networks and indicate for the first time that this functional connectivity can be downregulated using an inhibitory neurostimulation paradigm. This may shed light on the pathophysiology of network dysfunction and is a potential treatment for cognitive and movement disorders.

The presence of a network of areas in the parietal and premotor cortices, which are active both during action execution and observation, suggests that we might understand the actions of other people by activating those motor programs for making similar actions. Although neurophysiological and imaging studies show an involvement of the somatosensory cortex (SI) during action observation and execution, it is unclear whether SI is essential for understanding the somatosensory aspects of observed actions. To address this issue, we used off-line transcranial magnetic continuous theta-burst stimulation (cTBS) just before a weight judgment task. Participants observed the right hand of an actor lifting a box and estimated its relative weight. In counterbalanced sessions, we delivered sham and active cTBS over the hand region of the left SI and, to test anatomical specificity, over the left motor cortex (M1) and the left superior parietal lobule (SPL). Active cTBS over SI, but not over M1 or SPL, impaired task performance relative to sham cTBS. Moreover, active cTBS delivered over SI just before participants were asked to evaluate the weight of a bouncing ball did not alter performance compared to sham cTBS. These findings indicate that SI is critical for extracting somatosensory features (heavy/light) from observed action kinematics and suggest a prominent role of SI in action understanding., Highlights • TMS over the somatosensory cortex disrupts performance on a weight judgment task. • Disruption is specific for judgements based on observed human actions. • No TMS effect is found for judgements based on observed non-human motion. • No effect is found when TMS is administered over nearby frontal and parietal region.

Background The potential of non-invasive brain stimulation (NIBS) for both probing human neuroplasticity and the induction of functionally relevant neuroplastic change has received significant interest. However, at present the utility of NIBS is limited due to high response variability. One reason for this response variability is that NIBS targets a diffuse cortical population and the net outcome to stimulation depends on the relative levels of excitability in each population. There is evidence that the relative excitability of complex oligosynaptic circuits (late I-wave circuits) as assessed by transcranial magnetic stimulation (TMS) is useful in predicting NIBS response. Objective Here we examined whether an additional marker of cortical excitability, MEP amplitude variability, could provide additional insights into response variability following application of the continuous theta burst stimulation (cTBS) NIBS protocol. Additionally we investigated whether I-wave recruitment was associated with MEP variability. Methods Thirty-four healthy subjects (15 male, aged 18–35 years) participated in two experiments. Experiment 1 investigated baseline MEP variability and cTBS response. Experiment 2 determined if I-wave recruitment was associated with MEP variability. Results Data show that both baseline MEP variability and late I-wave recruitment are associated with cTBS response, but were independent of each other; together, these variables predict 31% of the variability in cTBS response. Conclusions This study provides insight into the physiological mechanisms underpinning NIBS plasticity responses and may facilitate development of more reliable NIBS protocols.

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies.

Although it is well established that fronto-parietal regions are active during action observation, whether they play a causal role in the ability to infer others’ intentions from visual kinematics remains undetermined. In experiments reported here, we combined offline continuous theta-burst stimulation (cTBS) with computational modeling to reveal and causally probe single-trial computations in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Participants received cTBS over the left anterior IPL and the left IFG pars orbitalis, in separate sessions, before completing an intention discrimination task (discriminate intention of observed reach-to-grasp acts) or a kinematic discrimination task unrelated to intention (discriminate peak wrist height of the same acts). We targeted intention-sensitive regions whose fMRI activity, recorded when observing the same reach-to-grasp acts, could accurately discriminate intention. We found that transient disruption of activity of the left IPL, but not the IFG, impaired the observer’s ability to attribute intention to action. Kinematic discrimination unrelated to intention, in contrast, was largely unaffected. Computational analyses of how encoding – the mapping of intention to movement kinematics – and readout – the mapping of kinematics to intention choices – intersect at the single-trial level revealed that IPL cTBS did not diminish the overall sensitivity of intention readout to movement kinematics. Rather, it selectively misaligned intention readout with respect to encoding, thereby deteriorating the mapping from informative kinematic features to intention choices. These results provide causal evidence of how left anterior IPL computes the mapping from kinematics to intentions.

Although it is well established that fronto-parietal regions are active during action observation, whether they play a causal role in the ability to “mindread” others’ actions remains controversial. In experiments reported here, we combined offline continuous theta-burst stimulation (cTBS) with computational modeling to reveal single-trial computations in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Participants received cTBS over the left IPL and IFG, in separate sessions, before completing an intention discrimination task or a kinematic discrimination task unrelated to intention. We found that transient disruption of activity of the IPL, but not the IFG, specifically impaired the observer’s ability to judge intention from movement kinematics. Kinematic discrimination unrelated to intention, in contrast, was largely unaffected. Computational analyses revealed that IPL cTBS did not impair the ability to ‘see’ changes in movement kinematics, nor did it alter the weight given to informative versus non-informative kinematic features. Rather, it selectively impaired the ability to link variations in informative features to the correct intention. These results provide the first causal evidence that IPL maps kinematics to intentions.

Patients with cerebellar lesions have shown altered responses to unpredictable stimuli. This finding has led to the belief that the cerebellum is involved in comparing incoming stimuli with previously experienced stimuli in order to predict and coordinate responses. The role of the cerebellum is thought to extend beyond motor control to higher-order executive functions, which allow for the evaluation of stimuli that influence our personal reactions, emotions, and thoughts. This current study tested the role of the cerebellum on cognitive function by examining incoming sensory stimuli being unattended by the participant. Median and ulnar nerve somatosensory evoked potentials (SEPs) were elicited by electrical stimulation via surface electrodes. Nerve stimulation was presented in an oddball fashion where median and ulnar stimulation were presented as frequent and deviant stimuli, respectively. Electroencephalography (EEG) was used to measure participants’ cortical responses both before and after either continuous theta burst stimulation (cTBS) used to transiently inhibit cerebellar activity, or a sham condition. The N140 was shown to be modulated in response to deviant stimuli, resulting in a large negativity pre-cTBS, referred to as the mismatch-negativity (MMN). Following cTBS, the MMN was reduced, resulting in similar waveform patterns in response to both the frequent and deviant stimuli. The mechanisms that are thought to modulate this change within the N140 in response to deviant stimuli are believed to be different from those that govern its response to frequent stimuli. The cerebellum may be involved in attentive change-detection processes that are critical for a wide-range of everyday processes.

Previous studies suggest an inhibitory top-down control of the amygdala by the prefrontal cortex (PFC). Both brain regions play a role in the modulation of prepulse modification (PPM) of the acoustic startle response by a pre-stimulus. Repetitive transcranial magnetic stimulation (rTMS) can modulate the activity of the PFC and might thus affect PPM. This study tested the effect of inhibitory rTMS on PPM accounting for a genetic variant of the dopamine transporter gene (DAT1). Healthy participants (N = 102) were stimulated with continuous theta burst stimulation (cTBS, an intense form of inhibitory rTMS) or sham treatment over the right PFC. Afterwards, during continuous presentation of a background white noise a louder noise burst was presented either alone (control startle) or preceded by a prepulse. Participants were genotyped for a DAT1 variable number tandem repeat (VNTR) polymorphism. Two succeeding sessions of cTBS over the right PFC (2 × 600 stimuli with a time lag of 15 min) attenuated averaged prepulse inhibition (PPI) in participants with a high resting motor threshold. An attenuation of PPI induced by prepulses with great distances to the pulse (480, 2000 ms) was observed following active cTBS in participants that were homozygous carriers of the 10-repeat-allele of the DAT1 genotype and had a high resting motor threshold. Our results confirm the importance of the prefrontal cortex for the modulation of PPM. The effects were observed in participants with a high resting motor threshold only, probably because they received a higher dose of cTBS. The effects in homozygous carriers of the DAT1 10-repeat allele confirm the relevance of dopamine for PPM. Conducting an exploratory study we decided against the use of a correction for multiple testing.

Background: Primary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults. Objective: To investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects. Methods: In 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude. Results: In young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04). Conclusions: Priming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly.