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Non-invasive brain stimulation is a useful tool to probe brain function and provide therapeutic treatments in disease. When applied to the right posterior parietal cortex (PPC) of healthy participants, it is possible to temporarily shift spatial attention and mimic symptoms of spatial neglect. However, the field of brain stimulation is plagued by issues of high response variability. The aim of this study was to investigate baseline functional connectivity as a predictor of response to an inhibitory brain stimulation paradigm applied to the right PPC. In fourteen healthy adults (9 female, aged 24.8 ± 4.0 years) we applied continuous theta burst stimulation (cTBS) to suppress activity in the right PPC. Resting state functional connectivity was quantified by recording electroencephalography and assessing phase consistency. Spatial attention was assessed before and after cTBS with the Landmark Task. Finally, known determinants of response to brain stimulation were controlled for to enable robust investigation of the influence of resting state connectivity on cTBS response. We observed significant inter-individual variability in the behavioral response to cTBS with 53.8% of participants demonstrating the expected rightward shift in spatial attention. Baseline high beta connectivity between the right PPC, dorsomedial pre-motor region and left temporal-parietal region was strongly associated with cTBS response (R2 = 0.51). Regression analysis combining known cTBS determinants (age, sex, motor threshold, physical activity, stress) found connectivity between the right PPC and left temporal-parietal region was the only significant variable (p = 0.011). These results suggest baseline resting state functional connectivity is a strong predictor of a shift in spatial attention following cTBS. Findings from this study help further understand the mechanism by which cTBS modifies cortical function and could be used to improve the reliability of brain stimulation protocols.

Background: The beneficial effects of both single-session bouts of aerobic exercise and therapeutic exercise interventions on the cortical regions associated with top-down attentional control [i.e., prefrontal cortex (PFC)] have been well documented. However, it remains unclear whether aerobic exercise can be used to buffer against suppressive influences on the dorsolateral PFC (dlPFC).Objective: The current study sought to determine whether a single session of moderate intensity aerobic exercise can offset the expected suppressive effects of continuous theta burst stimulation (cTBS) targeting the dorsolateral prefrontal cortex (dlPFC).Methods: Twenty-two right-handed participants (aged 19–30) completed a 20-minute movement-only control session [10% heart rate reserve (HRR)] and moderate intensity (50% HRR) exercise in a counterbalanced order. Following each exercise session, participants received active cTBS to the left dlPFC. Changes in executive functions were quantified using a Flanker paradigm employed at baseline, post-exercise and post-cTBS time points. Additionally, EEG was used to measure changes in event-related potential components related to inhibitory control (i.e., N2) and attentional control (i.e., P3) during the flanker task.Results: Behavioral results from the flanker task revealed a significant improvement in task performance following an acute bout of moderate intensity exercise. Furthermore, the effect of cTBS in both the movement-only control and moderate intensity conditions were non-significant. Similarly, EEG data from P3b and N2 ERP components revealed no changes to amplitude across time and condition. P3b latency data revealed a significant effect of time in both the moderate intensity and movement-only conditions, such that P3b latencies were significantly shorter across time points. Latency data within the N2 ERP component revealed no significant interactions or main effects.Conclusion: The findings of the current study provide tentative support for the hypothesis that both moderate and light intensity exercise promote cortical buffering against the suppressive effects of cTBS targeting the dlPFC. However, in the absence of a no-movement control, a lack of expected suppressive effects of cTBS cannot be ruled out.

The potential benefits of priming intermittent theta burst stimulation (iTBS) with continuous theta burst stimulation (cTBS) have not been examined in regard to sensorimotor oscillatory activities recorded in electroencephalography (EEG). The objective of this study was to investigate the modulatory effect of priming iTBS (cTBS followed by iTBS) delivered to the motor cortex on movement-related and mirror visual feedback (MVF)-induced sensorimotor event-related desynchronization (ERD), compared with iTBS alone, on healthy adults. Twenty participants were randomly allocated into Group 1: priming iTBS—cTBS followed by iTBS, and Group 2: non-priming iTBS—sham cTBS followed by iTBS. The stimulation was delivered to the right primary motor cortex daily for 4 consecutive days. EEG was measured before and after 4 sessions of stimulation. Movement-related ERD was evaluated during left-index finger tapping and MVF-induced sensorimotor ERD was evaluated by comparing the difference between right-index finger tapping with and without MVF. After stimulation, both protocols increased movement-related ERD and MVF-induced sensorimotor ERD in high mu and low beta bands, indicated by significant time effects. A significant interaction effect favoring Group 1 in enhancing movement-related ERD was observed in the high mu band [F(1,18) = 4.47, p = 0.049], compared with Group 2. Our experiment suggests that among healthy adults priming iTBS with cTBS delivered to the motor cortex yields similar effects with iTBS alone on enhancing ERD induced by MVF-based observation, while movement-related ERD was more enhanced in the priming iTBS condition, specifically in the high mu band.

Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity.Methods: Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI.Results: For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration.Conclusions: cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects.Significance: These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts.

Theta-burst stimulation (TBS), a variant of repetitive transcranial magnetic stimulation (rTMS), can potentially benefit the treatment of swallowing disorders. However, the after-effects of TBS on the swallowing motor cortex remain uncertain. The newly developed graph-based analysis of the centrality approach has been increasingly used to explore brain networks. The purpose of this study was to identify degree centrality (DC) alterations in the brain network after different TBS protocols were performed over the suprahyoid muscles motor cortex in healthy subjects. A total of 40 right-handed healthy subjects (mean age: 23.73 ± 2.57 years, range: 21–30, 20 females) were included in this study and randomly assigned to two groups, including the continuous TBS (cTBS) group and the intermittent TBS (iTBS) group. All of the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning before and after TBS implementation. Compared to the baseline, cTBS resulted in increased DC values in the left inferior frontal gyrus (P < 0.01). In the iTBS group, decreased DC was observed in the left cerebellum and left medial frontal gyrus; However, increased DC was observed in several brain areas including the right superior temporal gyrus, right superior frontal gyrus, right postcentral gyri and left paracentral lobule (P < 0.01). These results indicated that cTBS mainly results in increasing DC in the ipsilateral. However, iTBS is capable of facilitating the excitability of the swallowing motor cortex and increasing the connectivity of multiple brain regions, including the bilateral sensorimotor network, and might have therapeutic potential in the treatment of swallowing disorders.

Neural activity related to language can be modulated within widespread networks following learning or in response to disruption-including the experimental application of noninvasive brain stimulation. However, the spatiotemporal characteristics of such modulation remain insufficiently explored. The present study combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to explore the modulation of activity across the language network following continuous theta-burst stimulation (cTBS) of the left pars opercularis. In 10 healthy subjects (21 ± 2 years old, four females), neuronavigated cTBS was delivered over the left pars opercularis of the frontal operculum (part of the traditional Broca's area) at 80% of active motor threshold (AMT) stimulation intensity. Real cTBS and sham cTBS were performed in two different visits separated by at least 48 h. Before, immediately, and 10 min after cTBS, 30 single pulses of TMS were delivered to the left pars opercularis at 80% of the resting motor threshold (RMT), whereas EEG was simultaneously recorded. We examined the cTBS-induced modulation of phase locking values (PLVs) between the TMS-evoked potentials (TEPs) recorded over the pars opercularis and those recorded over its right-hemispheric homolog area, the left supramarginal area, and the left superior temporal area in different EEG frequency bands and different time windows following cTBS. cTBS to the left pars opercularis induced within the gamma band: (1) a significant increase in TEP phase synchronization between the left and right pars opercularis at an early time window (250-350 ms) following cTBS; and (2) significantly increased PLV with the left supramarginal area and the left superior temporal area at a later time window (600-700 ms). In the theta and delta band, cTBS to the left pars opercularis induced significantly increased phase synchronization of TEPs between the left pars opercularis and the posterior left hemispheric language areas at a late time window. In sham condition, there was a significant decrease in TEP phase synchronization of the high beta band between left pars opercularis and left superior temporal area at 200-300 ms. These results contribute to characterize the dynamics of the language network and may have implications in the development of noninvasive stimulation protocols to promote the language rehabilitation in aphasia patients.

Impaired neural plasticity may be an important mechanism in the pathophysiology of major depressive disorder (MDD). Coupled with electromyography (EMG), repetitive transcranial magnetic stimulation (rTMS) is a useful tool to evaluate corticospinal excitability and cortical neuroplasticity in living humans. The goal of this study was to compare rTMS-induced cortical plasticity changes in patients with MDD and in healthy volunteers. In this single-blind controlled study, 11 drug-free patients with MDD and 11 matched healthy controls were analyzed. Cortical excitability, measured by the amplitude of motor evoked potentials (MEPs) evoked by single-pulse TMS, was assessed before and repeatedly after (for 30 min) participants received a single session of intermittent theta-burst stimulation (iTBS) and continuous TBS (cTBS). rTMS was applied over the left motor cortex using a neuronavigation system. Intensity was set at 80% of the active motor threshold (AMT). A large interindividual variability was observed after both iTBS and cTBS in the two groups. At the group level, we observed impaired iTBS-induced neuroplasticity in patients with MDD compared to that in controls. No differences were observed between the groups regarding cTBS-induced neuroplasticity. Our results suggest impaired long-term potentiation (LTP)-like mechanisms in MDD. Clinical Trial Registration: www.Clinicaltrials.gov, identifier #NCT02438163.

The dorsolateral prefrontal cortex (DLPFC) plays a key role in the modulation of affective processing. However, its specific role in the regulation of neurocognitive processes underlying the interplay of affective perception and visual awareness has remained largely unclear. Using a mixed factorial design, this study investigated effects of inhibitory continuous theta-burst stimulation (cTBS) of the right DLPFC (rDLPFC) compared to an Active Control condition on behavioral (N = 48) and electroencephalographic (N = 38) correlates of affective processing in healthy Chinese participants. Event-related potentials (ERPs) in response to passively viewed subliminal and supraliminal negative and neutral natural scenes were recorded before and after cTBS application. We applied minimum-norm approaches to estimate the corresponding neuronal sources. On a behavioral level, we found evidence for reduced emotional interference by, and less negative and aroused ratings of negative supraliminal stimuli following rDLPFC inhibition. We found no evidence for stimulation effects on self-reported mood or the behavioral discrimination of subliminal stimuli. On a neurophysiological level, rDLPFC inhibition relatively enhanced occipito-parietal brain activity for both subliminal and supraliminal negative compared to neutral images (112–268 ms; 320–380 ms). The early onset and localization of these effects suggests that rDLPFC inhibition boosts automatic processes of “emotional attention” independently of visual awareness. Further, our study reveals the first available evidence for a differential influence of rDLPFC inhibition on subliminal versus supraliminal neural emotion processing. Explicitly, our findings indicate that rDLPFC inhibition selectively enhances late (292–360 ms) activity in response to supraliminal negative images. We tentatively suggest that this differential frontal activity likely reflects enhanced awareness-dependent down-regulation of negative scene processing, eventually leading to facilitated disengagement from and less negative and aroused evaluations of negative supraliminal stimuli.

Although previous studies have shown that the rostral prefrontal cortex (rPFC) plays a crucial role in executive tasks, the various functions of the rPFC in the human are still understudied. Here we used transcranial magnetic stimulation (TMS) with continuous theta burst stimulation (cTBS) to interfere with the executive control functions of the right rostrolateral PFC (RLPFC) or the right rostromedial PFC (RMPFC). Subjects performed a task-switching paradigm, which included spatial detection (SD), prospective memory (PM), and working memory (WM) tasks, after cTBS. The performance of eighteen healthy volunteers was evaluated on different days after cTBS over the right RLPFC, the right RMPFC, and the vertex (serving as a control site). The application of cTBS over the RLPFC significantly increased the switching costs (SCs) of the error rates (ERs) when switching to the PM task, while RMPFC-cTBS decreased SCs of ERs when switching to the WM task, compared with the control vertex site. These findings provide evidence for a differential role of the RLPFC and the RMPFC in executive functions, with a specific involvement of the RLPFC and the RMPFC in PM, and WM, respectively.

Previous studies have established a role for premotor cortex in the processing of auditory emotional vocalizations. Inhibitory continuous theta burst transcranial magnetic stimulation (cTBS) applied to right premotor cortex selectively increases the reaction time to a same-different task, implying a causal role for right ventral premotor cortex (PMv) in the processing of emotional sounds. However, little is known about the functional networks to which PMv contribute across the cortical hemispheres. In light of these data, the present study aimed to investigate how and where in the brain cTBS affects activity during the processing of auditory emotional vocalizations. Using functional neuroimaging, we report that inhibitory cTBS applied to the right premotor cortex (compared to vertex control site) results in three distinct response profiles: following stimulation of PMv, widespread frontoparietal cortices, including a site close to the target site, and parahippocampal gyrus displayed an increase in activity, whereas the reverse response profile was apparent in a set of midline structures and right IFG. A third response profile was seen in left supramarginal gyrus in which activity was greater post-stimulation at both stimulation sites. Finally, whilst previous studies have shown a condition specific behavioral effect following cTBS to premotor cortex, we did not find a condition specific neural change in BOLD response. These data demonstrate a complex relationship between cTBS and activity in widespread neural networks and are discussed in relation to both emotional processing and the neural basis of cTBS.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated beneficial effects on motor learning. It would be important to obtain a similar enhancement for verbal learning. However, previous studies have mostly assessed short-term effects of rTMS on language performance and the effect on learning is largely unknown. This study examined whether an inhibition of the right Broca homologue has long-term impact on neural processes underlying the acquisition of new words in healthy individuals. Sixteen young participants trained a new-word learning paradigm with rare, mostly unknown objects and their corresponding words immediately after continuous theta burst stimulation (cTBS) or sham stimulation of right inferior frontal gyrus (IFG) in a cross-over design. Neural effects were assessed with electroencephalography (EEG) source power analyses during the naming task as well as coherence analyses at rest one day before and after training.Inhibition of the right Broca homologue did not affect new word learning performance at the group level. Behavioral and neural responses to cTBS were variable across participants and were associated with the magnitude of resting-state alpha-band coherence between the stimulated area and the rest of the brain before stimulation. Only participants with high intrinsic alpha-band coherence between the stimulated area and the rest of the brain before stimulation showed the expected inhibition during naming and greater learning performance. In conclusion, our study confirms that cTBS can induce lasting modulations of neural processes which are associated with learning, but the effect depends on the individual network state.

Increasing sensitivity of modern evaluation tools allows for the study of weaker electric stimulation effects on neural populations. In the current study we examined the effects of sham continuous theta burst (cTBS) transcranial magnetic stimulation to the left dorsolateral prefrontal cortex (DLPFC) upon somatosensory evoked potentials (SEP) and frontal-parietal phase coupling of alpha and beta bands. Sham TMS results in an induced electric field amplitude roughly 5% that of real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced the amplitude of the frontal P14-N30 SEP and increased local phase coupling in the alpha-beta frequency bands of left frontal cortex. In addition, both sham and real cTBS increased frontal-parietal phase coupling in the alpha-beta bands concomitant with an increase in amplitude of parietal P50-N70 complex. These data suggest that weak electric fields from sham cTBS can affect both local and downstream neuronal circuits, though in a different manner than high strength TMS. peerReviewed

Repetitive transcranial magnetic stimulation (TMS) has become a popular tool to modulate neuronal networks and associated brain functions in both clinical and basic research. Yet few studies have examined the potential effects of cortical stimulation on general levels of vigilance. In this exploratory study, we used theta-burst protocols, both continuous (cTBS) and intermittent (iTBS) patterns, to examine whether inhibition or excitation of the left dorso-lateral prefrontal cortex (dlPFC) was able to induce reliable and acute changes to vigilance measures, compared to the left dorso-lateral associative visual cortex (dlAVC) as a control site in line with previous work. Partially sleep restricted participants underwent four separate sessions in a single day, in a between subjects design for TBS stimulation type and within subjects for locaton, each consisting of maintenance of wakefulness test (MWT), a sleep latency test, and a psychomotor vigilance task (PVT). TBS significantly affected measures of sleep consolidation, namely latency to sleep stage 2 and sleep efficiency, but had no effects on sleep drive or psychomotor vigilance levels for either TBS type or location. Contrary to our initial hypothesis of the dlAVC as a control site, stimulation to this region resulted in the largest differential effects between stimulation types. Moreover, the effect of TBS was found to be consistent throughout the day. These data may provide the basis for further investigation into therapeutic applications of TBS in sleep disorders.

Background. By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. Objective. We critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. Method. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS) by means of neuronavigated continuous theta burst stimulation (cTBS). Individual structural magnetic resonance brain images (MRI) were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Results. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. Conclusions. The present findings do not support the hypothesis that the right inferior frontal sulcus is critically involved in deception.

Previous studies have established a role for premotor cortex in the processing of auditory emotional vocalizations. Inhibitory continuous theta burst transcranial magnetic stimulation (cTBS) applied to right premotor cortex selectively increases the reaction time to a same-different task, implying a causal role for right ventral premotor cortex (PMv) in the processing of emotional sounds. However, little is known about the functional networks to which PMv contribute across the cortical hemispheres. In light of these data, the present study aimed to investigate how and where in the brain cTBS affects activity during the processing of auditory emotional vocalizations. Using functional neuroimaging, we report that inhibitory cTBS applied to the right premotor cortex (compared to vertex control site) results in three distinct response profiles: following stimulation of PMv, widespread frontoparietal cortices, including a site close to the target site, and parahippocampal gyrus displayed an increase in activity, whereas the reverse response profile was apparent in a set of midline structures and right IFG. A third response profile was seen in left supramarginal gyrus in which activity was greater post-stimulation at both stimulation sites. Finally, whilst previous studies have shown a condition specific behavioral effect following cTBS to premotor cortex, we did not find a condition specific neural change in BOLD response. These data demonstrate a complex relationship between cTBS and activity in widespread neural networks and are discussed in relation to both emotional processing and the neural basis of cTBS.