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Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects.Materials and Methods: We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 ± 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up.Results: We investigated changes in motor rhythms during arm elevation and thumb opposition tasks and found significant changes in beta power of the affected thumb's opposition, specifically after real cTBS. Our results are consistent with an excitatory response (increase in event-related desynchronization) in the sensorimotor cortical areas of the affected hemisphere, after stimulation. Neither peak-to-peak amplitude of motor-evoked potentials nor motor performance were significantly altered.Conclusions: Consistently with the theoretical prediction, this contralateral inhibitory stimulation paradigm changes neurophysiology, leading to a significant excitatory impact on the cortical oscillatory patterns of the contralateral hemisphere. These proof-of-concept results provide evidence for the potential role of continuous TBS in the neurorehabilitation of post-stroke patients. We suggest that these changes in ERS/ERD patterns should be further explored in future phase IIb/phase III clinical trials, in larger samples of poststroke patients.

Implicit and explicit motor learning processes work interactively in everyday life to promote the creation of highly automatized motor behaviors. The cerebellum is crucial for motor sequence learning and adaptation, as it contributes to the error correction and to sensorimotor integration of on-going actions. A non-invasive cerebellar stimulation has been demonstrated to modulate implicit motor learning and adaptation. The present study aimed to explore the potential role of cerebellar theta burst stimulation (TBS) in modulating explicit motor learning and adaptation, in healthy subjects. Cerebellar TBS will be applied immediately before the learning phase of a computerized task based on a modified Serial Reaction Time Task (SRTT) paradigm. Here, we present a study protocol aimed at evaluating the behavioral effects of continuous (cTBS), intermittent TBS (iTBS), or sham Theta Burst Stimulation (TBS) on four different conditions: learning, adaptation, delayed recall and re-adaptation of SRTT. We are confident to find modulation of SRTT performance induced by cerebellar TBS, in particular, processing acceleration and reduction of error in all the conditions induced by cerebellar iTBS, as already known for implicit processes. On the other hand, we expect that cerebellar cTBS could induce opposite effects. Results from this protocol are supposed to advance the knowledge about the role of non-invasive cerebellar modulation in neurorehabilitation, providing clinicians with useful data for further exploiting this technique in different clinical conditions.

Nicotine addiction, like other substance use disorders (SUD’s), is associated with deficits in prefrontal mediated inhibitory control. The strength of inhibitory control task-based functional connectivity (tbFC) between the right inferior frontal gyrus (r.IFG) and thalamus (corticothalamic circuit) mediates the association between successful inhibition and smoking relapse vulnerability. However, the potential efficacy of theta burst stimulation (TBS) to the r.IFG, a treatment known to alter clinical symptoms among neuropsychiatric patients, has not been reported in a SUD population. This study utilized fMRI guided neuronavigation to examine the effects of TBS on inhibitory control among nicotine dependent individuals. Participants (N=12) were scanned while performing an inhibitory control task known to elicit inhibition-related activity in the r.IFG. Using a randomized, counterbalanced cross-over design, participants then received TBS over two visits: excitatory (iTBS) on one visit and inhibitory (cTBS) TBS on the other visit. The effects of each TBS condition on subsequent inhibitory control task performance were examined. A significant condition x time interaction was identified on trials requiring inhibitory control (F (1,10) = 7.27, p = .022, D = 1.63). iTBS improved inhibitory control, whereas cTBS impaired inhibitory control. Brain stimulation did not influence performance in control conditions including novelty detection and response execution. This is the first study to demonstrate that non-invasive neural stimulation using iTBS to the r.IFG enhances baseline inhibitory control among individuals with a SUD. Further research is needed to directly examine the potential parametric effects of TBS on corticothalamic tbFC in individuals with a SUD.

Objectives: A neurophysiologic biomarker for autism spectrum disorder (ASD) is highly desirable and can improve diagnosis, monitoring, and assessment of therapeutic response among children with ASD. We investigated the utility of continuous theta-burst stimulation (cTBS) applied to the motor cortex (M1) as a biomarker for children and adolescents with high-functioning (HF) ASD compared to their age- and gender-matched typically developing (TD) controls. We also compared the developmental trajectory of long-term depression- (LTD-) like plasticity in the two groups. Finally, we explored the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism on cTBS aftereffects in a subset of the ASD group.Methods: Twenty-nine children and adolescents (age range 10–16) in ASD (n = 11) and TD (n = 18) groups underwent M1 cTBS. Changes in MEP amplitude at 5–60 min post-cTBS and their cumulative measures in each group were calculated. We also assessed the relationship between age and maximum cTBS-induced MEP suppression (ΔMEPMax) in each group. Finally, we compared cTBS aftereffects in BDNF Val/Val (n = 4) and Val/Met (n = 4) ASD participants.Results: Cumulative cTBS aftereffects were significantly more facilitatory in the ASD group than in the TD group (PFDR’s < 0.03). ΔMEPMax was negatively correlated with age in the ASD group (r = −0.67, P = 0.025), but not in the TD group (r = −0.12, P = 0.65). Cumulative cTBS aftereffects were not significantly different between the two BDNF subgroups (P-values > 0.18).Conclusions: The results support the utility of cTBS measures of cortical plasticity as a biomarker for children and adolescents with HF-ASD and an aberrant developmental trajectory of LTD-like plasticity in ASD.

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.

To understand the neural mechanism of repetitive transcranial magnetic stimulation (rTMS), the after-effects following one session or multiple days of stimulation have been widely investigated. However, the relation between the short-term effect (STE) and long-term effect (LTE) of rTMS is largely unknown. This study aims to explore whether the after-effects of 5-day rTMS on supplementary motor area (SMA) network could be predicted by one-session response. A primary cohort of 38 healthy participants underwent five daily sessions of real or sham continuous theta-burst stimulation (cTBS) on the left SMA. Resting-state functional magnetic resonance imaging (fMRI) data were acquired at the first (before and after the first stimulation) and sixth experimental day. The SMA connectivity changes after the first cTBS and after 5 days of stimulation were defined as STE and LTE, respectively. Compared to the baseline, significant STE and LTE were found in the bilateral paracentral gyrus (ParaCG) after real stimulation, suggesting shared neural correlates of short- and long-term stimulations. Region-of-interest analysis indicated that the resting-state functional connectivity between SMA and ParaCG increased after real stimulation, while no significant change was found after sham stimulation. Leave-one-out cross-validation indicated that the LTE in ParaCG could be predicted by the STE after real but not sham stimulations. In an independent cohort, the after-effects of rTMS on ParaCG and short- to long-term prediction were reproduced at the region-of-interest level. These imaging evidences indicate that one-session rTMS can aid to predict the regions responsive to long-term stimulation and the individualized response degree.

Objectives Transcranial magnetic stimulation (TMS) holds potential promise as a therapeutic modality for disorders of addiction. Our previous findings indicate that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsal-lateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC can reduce drug craving for methamphetamine. One major issue with rTMS is the duration of treatment and hence potential dropout rate. Theta burst stimulation (TBS) has been recently shown to be non-inferior relative to repetitive transcranial magnetic stimulation for major depression. Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left or right dorsolateral prefrontal cortex on methamphetamine craving in abstinent-dependent subjects. Methods In this randomized single-blind pilot study, 83 abstinent methamphetamine-dependent subjects from a long-term residential treatment program were randomly allocated into three groups: intermittent theta burst stimulation (iTBS) over the left DLPFC (active group), continuous theta burst stimulation (cTBS) over the left DLPFC (active control group), or cTBS over the right DLPFC (active group) was administered twice daily over 5 days for a total of 10 sessions. We measured the primary outcome of cue-induced craving and secondarily sleep quality, depression, anxiety, impulsivity scores, and adverse effects. Results We show a pre- vs. postintervention effect on craving, which, on paired t tests, showed that the effect was driven by iTBS of the left DLPFC and cTBS of the right DLPFC, reducing cue-induced craving but not cTBS of the left DLPFC. We did not show the critical group-by-time interaction. The secondary outcomes of depression, anxiety, and sleep were unrelated to the improvement in craving in the left iTBS and right cTBS group. In the first two sessions, self-reported adverse effects were higher with left iTBS when compared to right cTBS. The distribution of craving change suggested greater clinical response (50% improvement) with right cTBS and a bimodal pattern of effect with left iTBS, suggesting high interindividual variable response in the latter. Conclusion Accelerated twice-daily TBS appears feasible and tolerable at modulating craving and mood changes in abstinent methamphetamine dependence critically while reducing session length. We emphasize the need for a larger randomized controlled trial study with a sham control to confirm these findings and longer duration of clinically relevant follow-up. Clinical trial registration Chinese Clinical Trial Registry number, 17013610.

The right orbitofrontal cortex (rOFC) has been proposed as the region where conscious olfactory perception arises; however, evidence supporting this hypothesis has all been collected from neuroimaging and lesion studies in which only correlation and not a temporal pattern can be established. Continuous theta burst stimulation (cTBS) causes a reversible disruption of cortical activity and has been used successfully to disrupt orbitofrontal activity. To overcome intrinsic limitations of current experimental research, a crossover, double-blind, prospective and longitudinal study was carried out in which cTBS was applied over the rOFC to evaluate its effect on odorant stimuli detection. All subjects received real and sham cTBS. Experimental procedures were done in two different sessions with a separation of at least one week between them to avoid carryover and learning effects. A total of 15 subjects completed the experiment, and their data were included in the final analysis (10 women, 5 men, mean age 22.40 ± 3.41). Every session consisted of two different measures of the conscious olfactory perception task: A baseline measure and one 5 min after cTBS/sham. Compared to baseline, marks in the olfactory task during the sham cTBS session increased (p = 0.010), while marks during the real cTBS session decreased (p = 0.017). Our results support the hypothesis that rOFC is an important node of a complex network required for conscious olfactory perception to arise. However, the exact mechanism that explains our results is unclear and could be explained by the disruption of other cognitive functions related to the rOFC.

Cue-induced craving is a significant barrier to obtaining abstinence from cocaine. Neuroimaging research has shown that cocaine cue exposure evokes elevated activity in a network of frontal-striatal brain regions involved in drug craving and drug seeking. Prior research from our laboratory has demonstrated that when targeted at the medial prefrontal cortex (mPFC), continuous theta burst stimulation (cTBS), an inhibitory form of non-invasive brain stimulation, can decrease drug cue-related activity in the striatum in cocaine users and alcohol users. However, it is known that there are individual differences in response to repetitive transcranial magnetic stimulation (rTMS), with some individuals being responders and others non-responders. There is some evidence that state-dependent effects influence response to rTMS, with baseline neural state predicting rTMS treatment outcomes. In this single-blind, active sham-controlled crossover study, we assess the striatum as a biomarker of treatment response by determining if baseline drug cue reactivity in the striatum influences striatal response to mPFC cTBS. The brain response to cocaine cues was measured in 19 cocaine-dependent individuals immediately before and after real and sham cTBS (110% resting motor threshold, 3600 total pulses). Group independent component analysis (ICA) revealed a prominent striatum network comprised of bilateral caudate, putamen, and nucleus accumbens, which was modulated by the cocaine cue reactivity task. Baseline drug cue reactivity in this striatal network was inversely related to change in striatum reactivity after real (vs. sham) cTBS treatment (ρ = -.79; p < .001; R 2 Adj = .58). Specifically, individuals with a high striatal response to cocaine cues at baseline had significantly attenuated striatal activity after real but not sham cTBS (t 9 = -3.76; p ≤ .005). These data demonstrate that the effects of mPFC cTBS on the neural circuitry of craving are not uniform and may depend on an individual’s baseline frontal-striatal reactivity to cues. This underscores the importance of assessing individual variability as we develop brain stimulation treatments for addiction.

Contralateral intermittent theta burst stimulation (iTBS) can potentially improve swallowing disorders with unilateral lesion of the swallowing cortex. However, the after-effects of iTBS on brain excitability remain largely unknown. Here, we investigated the alterations of temporal dynamics of inter-regional connectivity induced by iTBS following continuous TBS (cTBS) in the contralateral suprahyoid muscle cortex. A total of 20 right-handed healthy subjects underwent cTBS over the left suprahyoid muscle motor cortex and then immediately afterward, iTBS was applied to the contralateral homologous area. All of the subjects underwent resting-state functional magnetic resonance imaging (Rs-fMRI) pre- and post-TBS implemented on a different day. We compared the static and dynamic functional connectivity (FC) between the post-TBS and the baseline. The whole-cortical time series and a sliding-window correlation approach were used to quantify the dynamic characteristics of FC. Compared with the baseline, for static FC measurement, increased FC was found in the precuneus (BA 19), left fusiform gyrus (BA 37), and right pre/post-central gyrus (BA 4/3), and decreased FC was observed in the posterior cingulate gyrus (PCC) (BA 29) and left inferior parietal lobule (BA 39). However, in the dynamic FC analysis, post-TBS showed reduced FC in the left angular and PCC in the early windows, and in the following windows, increased FC in multiple cortical areas including bilateral pre- and postcentral gyri and paracentral lobule and non-sensorimotor areas including the prefrontal, temporal and occipital gyrus, and brain stem. Our results indicate that iTBS reverses the aftereffects induced by cTBS on the contralateral suprahyoid muscle cortex. Dynamic FC analysis displayed a different pattern of alteration compared with the static FC approach in brain excitability induced by TBS. Our results provide novel evidence for us in understanding the topographical and temporal aftereffects linked to brain excitability induced by different TBS protocols and might be valuable information for their application in the rehabilitation of deglutition.

Theta burst stimulation (TBS) is a powerful variant of repetitive transcranial magnetic stimulation (rTMS), making it potentially useful for the treatment of swallowing disorders. However, how dose TBS modulate human swallowing cortical excitability remains unclear. Here, we aim to measure the after-effects of spontaneous brain activity at resting-state using the regional homogeneity (ReHo) approach in healthy subjects who underwent different TBS protocols over the suprahyoid muscle cortex. Sixty healthy subjects (23.45 ± 2.73 years, 30 males) were randomized into three groups which completed different TBS protocols. The TMS coil was applied over the cortex of the suprahyoid muscles. Data of resting-state functional MRI (Rs-fMRI) of the subjects were acquired before and after TBS. The ReHo was compared across sessions [continuous TBS (cTBS), intermittent TBS (iTBS) and cTBS/iTBS] and runs (pre/post TBS). In the comparison between pre- and post-TBS, increased ReHo was observed in the right lingual gyrus and right precuneus and decreased ReHo in the left cingulate gyrus in the cTBS group. In the iTBS group, increased ReHo values were seen in the pre-/postcentral gyrus and cuneus, and decreased ReHo was observed in the left cerebellum, brainstem, bilateral temporal gyrus, insula and left inferior frontal gyrus. In the cTBS/iTBS group, increased ReHo was found in the precuneus and decreased ReHo in the right cerebellum posterior lobe, left anterior cerebellum lobe, and right inferior frontal gyrus. In the post-TBS inter-groups comparison, increased ReHo was seen in right middle occipital gyrus and decreased ReHo in right middle frontal gyrus and right postcentral gyrus (cTBS vs. cTBS/iTBS). Increased ReHo was shown in left inferior parietal lobule and left middle frontal gyrus (cTBS vs. iTBS). Increased ReHo was shown in right medial superior frontal gyrus and decreased ReHo in right cuneus (cTBS/iTBS vs. iTBS). Our findings indicate cTBS had no significant influence on ReHo in the primary sensorimotor cortex, iTBS facilitates an increased ReHo in the bilateral sensorimotor cortex and a decreased ReHo in multiple subcortical areas, and no reverse effect exhibits when iTBS followed the contralateral cTBS over the suprahyoid motor cortex. The results provide a novel insight into the neural mechanisms of TBS on swallowing cortex.

A decision criterion establishes the minimum amount of memory evidence required for recognition. When a liberal criterion is set, items are recognized based on weak evidence whereas a conservative criterion requires greater memory strength for recognition. The decision criterion is a fundamental aspect of recognition memory but little is known about the underlying neural mechanisms of maintaining a criterion. We used continuous theta burst stimulation (cTBS) with the goal of inhibiting prefrontal cortex excitability while participants performed recognition tests. We hypothesized that inhibiting the right inferior frontal gyrus (rIFG), right middle frontal gyrus (rMFG), and right dorsolateral prefrontal cortex (rDLPFC) would cause participants to establish less conservative decision criteria without affecting recognition memory performance. Participants initially performed recognition memory tests while maintaining conservative decision criteria during fMRI scanning. Peak activity in the successful retrieval effect contrast (Hits > Correct Rejections) provided subject-specific cTBS target sites. During three separate sessions, participants completed the same recognition memory paradigm while maintaining conservative and liberal decision criteria both before and after cTBS. Across two experiments we failed to significantly alter decision criteria placement by applying cTBS to the rIFG, rMFG, and rDLPFC despite efforts to precisely target individualized brain areas. However, we unexpectedly improved discriminability following cTBS to the rDLPFC specifically when participants maintained a liberal criterion. Although this finding may guide future studies investigating the neural mechanisms underlying discriminability in recognition memory, cTBS proved ineffective at altering decision criteria.

Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). Los protocolos de estimulación en ráfaga Theta (TBS) son muy prometedores en la rehabilitación neuropsicológica. Sin embargo, su capacidad de disminuir (continua, cTBS) o aumentar (intermitente, iTBS) la excitabilidad cortical en áreas distintas de la corteza motora primaria, y su consistencia modulando los comportamientos humanos con tareas clínicamente relevantes, aún no se han establecido completamente. Los efectos conductuales de TBS sobre la corteza prefrontal dorsolateral (dlPFC) son particularmente interesantes debido a su participación en la memoria de trabajo (WM) y las funciones ejecutivas (EF), a menudo afectadas tras el daño cerebral frontal. Nuestro objetivo fue explorar la capacidad de cTBS e iTBS para modular WM y EF en individuos sanos, evaluados con pruebas neuropsicológicas clínicas. Els protocols d'estimulació en ràfega Theta (TBS) són molt prometedors en la rehabilitació neuropsicològica. No obstant això, la seva capacitat de disminuir (contínua, CTBS) o augmentar (intermitent, iTBS) l'excitabilitat cortical en àrees diferents de l'escorça motora primària, i la seva consistència modulant els comportaments humans amb tasques clínicament rellevants, encara no s'han establert completament. Els efectes conductuals de TBS sobre l'escorça prefrontal dorsolateral (dlPFC) són particularment interessants a causa de la seva participació en la memòria de treball (WM) i les funcions executives (EF), sovint afectades després del dany cerebral frontal. El nostre objectiu va ser explorar la capacitat de CTBS i iTBS per modular WM i EF en individus sans, avaluats amb proves neuropsicològiques clíniques.

Repetitive Transcranial Magnetic Stimulation (rTMS) is increasingly used to treat stroke, Parkinson's disease and depression (Fregni et al., 2005; Loo and Mitchell, 2005; Hallet, 2007; O'Reardon et al., 2007; Ridding and Rothwell, 2007). rTMS uses bursts of magnetic pulses to change the excitability and connection strengths of cortical neurons. However, the evidence to inform clinical application is highly inconsistent (Thut and Pascual-Leone, 2010; Hamada et al., 2013) and substantially based on trial and error. Systematic theory is lacking. Typically, in rTMS research, measurements of motor-evoked potential (MEP) are made, often in terms of the strength of the MEP and the length of the cortical silent period that follows. However, the MEP is probably a poor and certainly an indirect measure of changes in the brain (Nicolo et al., 2015), clouding our understanding of rTMS mechanisms. In practice, therefore, particular amplitudes and timing of pulses in an rTMS sequence are selected because they show promise in small subsets of people. However, even basics such as the sign of any change in the outcome measure (e.g., does the MEP increase or decrease?) is debated. Many results show a wide spread in responses. It has become common to talk about “responders” and “non-responders” although evidence for a binary distinction in these two groups is lacking—in reality there is usually a continuum of response often including potentiation in some and depression in others (Nettekoven et al., 2015). Moreover, Heroux et al. (2015) provide evidence that the irreproducibility of results may be due to small sample sizes, unscientific screening of subjects and data, and selective reporting of results. In rTMS a regular train of pulses is applied. There is considerable variation in possible stimulation sequences, leading to many parameters that could potentially affect the results. Pulses are applied at a particular amplitude (normally recorded as percent motor threshold, (%RMT), or sometimes percent machine output, themselves imprecise measures), at a given rate (pulses per second, or hertz, Hz), until a particular number of pulses have been applied. There are three numerical parameters here. Additionally, one can consider variation in coil shape, orientation and place of application. Different waveforms for the magnetic pulse are also available. Thus, for an ostensibly straightforward pulse sequence such as non-bursting rTMS, the parameter space is considerable. Fitzgerald et al. (2006) carried out a comprehensive review of rTMS effects. They concluded that low frequency (0.9–5 Hz) stimulation generally results in a decreased MEP, while high frequency stimulation (5–20 Hz) results in an increased MEP. Very low frequency stimulation gave no effect. The “ 5 Hz, potentiation” mantra is now well established in rTMS literature. More recently, bursting protocols have become popular. The quadripulse protocol (Tsutsumi et al., 2014) is one example—four pulses are applied in quick succession, with this pattern repeated at regular time intervals. Theta-burst stimulation (TBS) is another; bursts of pulses are applied at theta-band (4–8 Hz) frequency. A continuous theta-burst stimulation (cTBS) protocol adds two more parameters, the number of pulses in a burst and the burst frequency. Intermittent theta-burst stimulation (iTBS) protocols require a further two parameters. Here, the bursting protocol is applied for a given time (denoted ON time, often 2 s), then removed for a given time (denoted OFF time, often 8 s) before being active for another 2 s period, etc. Thus, the parameter space for describing intermittent bursting pulse sequences becomes vast. Experiments performed to date do not come close to spanning it.

The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC) in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS) or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group). For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group). Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke.

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

[Abstract] Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE), and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS) over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: (i) electric cervicomedullary stimulation (CMS), to test spinal excitability, (ii) paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition (SICI) and intracortical facilitation (ICF)], and (iii) continuous theta-burst stimulation (cTBS), to modulate the excitability of M1 cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500 ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.