Continuous Theta-burst Transcranial Magnetic Stimulation Research Articles

Role ofmedial prefrontal cortex andprimary somatosensory cortex inself andother-directed vicarious social touch: a TMS study.

Conflicting evidence points to the contribution of several key nodes of the 'social brain' to the processing of both discriminatory and affective qualities of interpersonal touch. Whether the primary somatosensory cortex (S1) and the medial prefrontal cortex (mPFC), two brain areas vital for tactile mirroring and affective mentalizing, play a functional role in shared representations of C-tactile (CT) targeted affective touch is still a matter of debate. Here, we used offline continuous theta-burst transcranial magnetic stimulation (cTBS) to mPFC, S1 and vertex (control) prior to participants providing ratings of vicarious touch pleasantness for self and others delivered across several body sites at CT-targeted velocities. We found that S1-cTBS led to a significant increase in touch ratings to the self, with this effect being positively associated to levels of interoceptive awareness. Conversely, mPFC-cTBS reduced pleasantness ratings for touch to another person. These effects were not specific for CT-optimal (slow) stroking velocities, but rather they applied to all types of social touch. Overall, our findings challenge the causal role of the S1 and mPFC in vicarious affective touch and suggest that self- vs other-directed vicarious touch responses might crucially depend on the specific involvement of key social networks in gentle tactile interactions.

DLPFC-PPC-cTBS effects on metacognitive awareness

BackgroundNeuroimaging and lesion studies suggested that the dorsolateral prefrontal and posterior parietal cortices mediate visual metacognitive awareness. The causal evidence provided by non-invasive brain stimulation, however, is inconsistent. Objective/hypothesisHere we revisit a major figure discrimination experiment adding a new Kanizsa figure task trying to resolve whether bilateral continuous theta-burst transcranial magnetic stimulation (cTBS) over these regions affects perceptual metacognition. Specifically, we tested whether subjective visibility ratings and/or metacognitive efficiency are lower when cTBS is applied to these two regions in comparison to an active control region. MethodsA within-subjects design including three sessions spaced by one-week intervals was implemented. In each session, every participant was administered bilateral cTBS to either prefrontal, control or parietal cortices. Two concurrent tasks were performed, a real and an illusory figure task, stabilising objective performance with use of an adaptive staircase procedure. ResultsWhen performing the replicated task, cTBS was found insufficient to disrupt neither visibility ratings nor metacognitive efficiency. However, with use of Kanizsa style illusory figures, cTBS over the dorsolateral prefrontal, but not over the posterior parietal cortex, was observed to significantly diminish metacognitive efficiency. Conclusion(s)Real and illusory figure tasks demonstrated different cTBS effects. A possible explanation is the involvement of the prefrontal cortex in the creation of expectations, which is necessary for efficient metacognition. Failure to replicate previous findings for the real figure task, however, cannot be said to support, conclusively, the notion that these brain regions have a causal role in metacognitive awareness. This inconsistent finding may result from certain limitations of our study, thereby suggesting the need for yet further investigation.

Human microsaccade cueing modulation in visual- and memory-delay saccade tasks after theta burst transcranial magnetic stimulation over the frontal eye field

Microsaccades that occur during periods of fixation are modulated by various cognitive processes and have an impact on visual processing. A network of brain areas is involved in microsaccade generation, including the superior colliculus and frontal eye field (FEF) which are involved in modulating microsaccade rate and direction after the appearance of a visual cue (referred to as microsaccade cueing modulation). Although the neural mechanisms underlying microsaccade cueing modulations have been demonstrated in monkeys, limited research has investigated a causal role of these areas in humans. By applying continuous theta-burst transcranial magnetic stimulation (cTBS) over the right FEF and vertex, we investigated the role of human FEF in modulating microsaccade responses after the appearance of a visual target in a visual- and memory-delay saccade task. After target appearance, microsaccade rate was initially suppressed but then increased in both cTBS conditions. More importantly, in the visual-delay task, microsaccades after target appearance were directed to the ipsilateral side more often with FEF, compared to vertex stimulation. Moreover, microsaccades were directed towards the target location, then to the opposite location of the target in both tasks, with larger effects in the visual-, compared to, memory-delay task. This microsaccade direction modulation was delayed after FEF stimulation in the memory-delay task. Overall, some microsaccade cueing modulations were moderately disrupted after FEF cTBS, suggesting a causal role for involvement of the human FEF in microsaccade generation after presentation of salient stimuli.

Non-invasive Brain Stimulation and Prism Adaptation in Art Constructive Errors in Painting.

This study aimed to investigate the influence of neglect and the effect of prism adaptation (PA) combined with continuous Theta-burst transcranial magnetic stimulation (cTBS) on the art constructive errors in painting rehabilitation of stroke patients with neglect. Fourteen patients with neglect and art constructive errors in painting secondary to stroke were randomly assigned to the rehabilitation group and received PA combined with the inhibitory protocol of cTBS over the intact parietal cortex; the control group received PA combined with sham cTBS for two weeks in ten daily sessions. Patients were assessed for art constructive errors in painting in figure copying test (FCT), and coloring test (CT) before and after the intervention. Art constructive errors in painting were classified into omission, deformation, size, neglect of warm colors, and perseveration of errors. Neglect was evaluated using the line bisection task (LBT), figure copying test (FCT), and coloring test (CT). All patients showed a significant improvement in art constructive errors in painting (measured using the pattern of painting' errors in FCT and CT), and neglect (measured using LBT, FCT, and CT) (P<0.05). Omission, neglect of warm colors, and deformation were the most frequent errors. Neglect and rehabilitation influence the painting system in stroke patients. Both approaches improved art constructive errors in painting and neglect symptoms.

Adrenomedullary responses to non-invasive cortical stimulation in humans

Abstract Introduction: The discovery of cortical adrenomedullary projections in cebus monkeys suggests that similar pathways exist in humans. Notably, the major corticoadrenomedullary projection regions have human equivalents that can be stimulated non-invasively with repetitive transcranial magnetic stimulation (rTMS). If rTMS can be used to selectively modulate adrenomedullary activity, there may be significant therapeutic benefits for stress-, affective-, or neuroimmune-related disorders. Purpose: To assess resting and stress-induced adrenomedullary neuroendocrine responses to continuous (cTBS) and intermittent (iTBS) theta burst TMS in humans. Methods: 39 healthy young adults (14W) were randomly assigned to three counterbalanced sessions of iTBS (n=19) or cTBS (n=20). Stimulation was applied to motor cortical areas that contain the majority of adrenomedullary projections in non-human primates (primary motor cortex trunk region (M1TRUNK) and presupplementary motor area (preSMA)). The M1 leg region (M1LEG) was used as a spatial control. Stimulation locations were determined based on TMS-evoked electromyographic responses in the rectus abdominus (M1TRUNK) and vastus lateralis (M1LEG) or using a combination of fMRI activity and metanalytical structural coordinates (preSMA). All TMS procedures were performed with a 96mm curved double coil and stereotactic navigation. TBS was applied as 600 biphasic TMS pulses at 80% AMT. Corticoadrenomedullary activity and corticospinal excitability (CSE) were assayed before and after TBS, immediately after maximal exercise, and 60min and 90min after TBS based on plasma epinephrine concentrations and median MEP AUC, respectively. Initial analysis of adrenomedullary responses to rTMS were made with a 2 (protocol) x 3 (visit) x 5 (time-point) mixed methods ANOVA. Results and Conclusions: As expected, exercise resulted in a large epinephrine increase (p<0.0001, 8-fold) overall. Ongoing analysis indicates that target-specific changes in adrenomedullary activity are likely, and similar to CSE, may often be paradoxical. Our preliminary results also suggest that adrenomedullary responses to subthreshold rTMS are principally stress inducible. Research Category and Technology and Methods Translational Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Adrenal Medulla, Cortex, Sympathetic Nervous System, Non-Invasive Brain Stimulation

Investigating the role of human frontal eye field in the pupil light reflex modulation by saccade planning and working memory.

The pupil constricts in response to an increase in global luminance level, commonly referred to as the pupil light reflex. Recent research has shown that these reflex responses are modulated by high-level cognition. There is larger pupil constriction evoked by a bright stimulus when the stimulus location spatially overlaps with the locus of attention, and these effects have been extended to saccade planning and working memory (here referred to as pupil local-luminance modulation). Although research in monkeys has further elucidated a central role of the frontal eye field (FEF) and superior colliculus in the pupil local-luminance modulation, their roles remain to be established in humans. Through applying continuous theta-burst transcranial magnetic stimulation over the right FEF (and vertex) to inhibit its activity, we investigated the role of the FEF in human pupil local-luminance responses. Pupil light reflex responses were transiently evoked by a bright patch stimulus presented during the delay period in the visual- and memory-delay tasks. In the visual-delay task, larger pupil constriction was observed when the patch location was spatially aligned with the target location in both stimulation conditions. More interestingly, after FEF stimulation, larger pupil constriction was obtained when the patch was presented in the contralateral, compared to the ipsilateral visual field of the stimulation. In contrast, FEF stimulation effects were absence in the memory-delay task. Linear mixed model results further found that stimulation condition, patch location consistency, and visual field significantly modulated observed pupil constriction responses. Together, our results constitute the first evidence of FEF modulation in human pupil local-luminance responses.

Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice

In this study, we provide causal evidence that the dorsolateral prefrontal cortex (DLPFC) supports the computation of subjective value in choices under risk via its involvement in probability weighting. Following offline continuous theta-burst transcranial magnetic stimulation (cTBS) of the DLPFC subjects (N = 30, mean age 23.6, 56% females) completed a computerized task consisting of 96 binary lottery choice questions presented in random order. Using the hierarchical Bayesian modeling approach, we then estimated the structural parameters of risk preferences (the degree of risk aversion and the curvature of the probability weighting function) and analyzed the obtained posterior distributions to determine the effect of stimulation on model parameters. On a behavioral level, temporary downregulation of the left DLPFC excitability through cTBS decreased the likelihood of choosing an option with higher expected reward while the probability of choosing a riskier lottery did not significantly change. Modeling the stimulation effects on risk preference parameters showed anecdotal evidence as assessed by Bayes factors that probability weighting parameter increased after the left DLPFC TMS compared to sham.

Neural effects of continuous theta-burst stimulation in macaque parietal neurons.

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal activity. Overall, we observed a pronounced, long-lasting, and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons also exhibiting periods of hyperexcitability during the recovery phase. These results provide the first experimental evidence of the effects of cTBS on single neurons in awake behaving monkeys, shedding new light on the reasons underlying cTBS variability.

Continuous Theta-Burst Stimulation to the Right Dorsolateral Prefrontal Cortex May Increase Potentiated Startle in Healthy Individuals

BackgroundConvergent neuroimaging and neuromodulation studies implicate the right dorsolateral prefrontal cortex (dlPFC) as a key region involved in anxiety-cognition interactions. However, neuroimaging data are correlational, and neuromodulation studies often lack appropriate methodological controls. Accordingly, this work was designed to explore the role of right prefrontal cognitive control mechanisms in the expression/regulation of anxiety using continuous theta-burst transcranial magnetic stimulation (cTBS) and threat of unpredictable shock. Based on prior neuromodulation studies, we hypothesized that the right dlPFC contributed to anxiety expression, and that cTBS should downregulate this expression. MethodsWe measured potentiated startle and performance on the Sternberg working memory paradigm in 28 healthy participants before and after 4 sessions (600 pulses/session) of active or sham cTBS. Stimulation was individualized to the right dlPFC site of maximal working memory–related activity and optimized using electric-field modeling. ResultsCompared with sham cTBS, active cTBS, which is thought to induce long-term depression–like synaptic changes, increased startle during threat of shock, but the effect was similar for predictable and unpredictable threat. As a measure of target (dis)engagement, we also showed that active but not sham cTBS decreased accuracy on the Sternberg task. ConclusionsCounter to our initial hypothesis, cTBS to the right dlPFC made individuals more anxious, rather than less anxious. Although preliminary, these results are unlikely to be due to transient effects of the stimulation, because anxiety was measured 24 hours after cTBS. In addition, these results are unlikely to be due to off-target effects, because target disengagement was evident from the Sternberg performance data.

Inhibiting Human Aversive Memory by Transcranial Theta-Burst Stimulation to the Primary Sensory Cortex

BackgroundPredicting adverse events from past experience is fundamental for many biological organisms. However, some individuals suffer from maladaptive memories that impair behavioral control and well-being, e.g., after psychological trauma. Inhibiting the formation and maintenance of such memories would have high clinical relevance. Previous preclinical research has focused on systemically administered pharmacological interventions, which cannot be targeted to specific neural circuits in humans. Here, we investigated the potential of noninvasive neural stimulation on the human sensory cortex in inhibiting aversive memory in a laboratory threat conditioning model. MethodsWe build on an emerging nonhuman literature suggesting that primary sensory cortices may be crucially required for threat memory formation and consolidation. Immediately before conditioning innocuous somatosensory stimuli (conditioned stimuli [CS]) to aversive electric stimulation, healthy human participants received continuous theta-burst transcranial magnetic stimulation (cTBS) to individually localized primary somatosensory cortex in either the CS-contralateral (experimental) or CS-ipsilateral (control) hemisphere. We measured fear-potentiated startle to infer threat memory retention on the next day, as well as skin conductance and pupil size during learning. ResultsAfter overnight consolidation, threat memory was attenuated in the experimental group compared with the control cTBS group. There was no evidence that this differed between simple and complex CS or that CS identification or initial learning were affected by cTBS. ConclusionsOur results suggest that cTBS to the primary sensory cortex inhibits threat memory, likely by an impact on postlearning consolidation. We propose that noninvasive targeted stimulation of the sensory cortex may provide a new avenue for interfering with aversive memories in humans.

Theta-burst transcranial magnetic stimulation for the treatment of unilateral neglect in stroke patients: A systematic review and best evidence synthesis.

Background:Unilateral neglect (UN) is a common and disabling disorder after stroke. UN is a strong and negative predictor of functional rehabilitative outcome. Non-invasive brain stimulation, such as theta-burst transcranial magnetic stimulation (TBS), is a promising rehabilitation technique for treating stroke-induced UN.Objective:To systematically review the available literature, researching whether TBS of the contra-lesional hemisphere is more effective than standard rehabilitation in improving symptoms of UN in patients with right hemisphere stroke.Review methods:A systematic review was conducted to retrieve randomized controlled trials (RCTs) that were relevant to the objective of this review. PubMed, Ovid and Cochrane Library electronic databases were comprehensively searched from inception up to February 2021. Of the included studies, methodological quality was assessed using the PEDro scale, whereafter a best evidence synthesis (BES) was conducted to summarize the results.Results:Nine RCTs investigating the effects of TBS on stroke-induced UN symptoms were included in this review. Seven studies assessing continuous TBS (cTBS) found significantly greater amelioration of UN symptoms in the TBS intervention group when compared to the control group; one study assessing cTBS found no such significant difference. One study assessing intermittent TBS (iTBS) found significant between-group differences in favor of the intervention. The BES yielded strong evidence in favor of cTBS, and limited evidence in favor of iTBS.Conclusions:The included studies in the present review allow the conclusion that TBS can have favorable effects on UN recovery in stroke patients. Its clinical use is recommended in conjunction with cognitive rehabilitation and occupational or physical rehabilitation as needed. However, many aspects for optimal usage of TBS therapy in clinical settings, such as exact TBS protocols, number of sessions, and treatment duration, are not clear.

Visual cortex cTBS increases mixed percept duration while a-tDCS has no effect on binocular rivalry.

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 (ACH) 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 increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.

Callosal anisotropy predicts attentional network changes after parietal inhibitory stimulation

Hemispatial neglect is thought to result from disruption of interhemispheric equilibrium. Right hemisphere lesions deactivate the right frontoparietal network and hyperactivate the left via release from interhemispheric inhibition. Support for this putative mechanism comes from neuropsychological evidence as well as transcranial magnetic stimulation (TMS) studies in healthy subjects, in whom right posterior parietal cortex (PPC) inhibition causes neglect-like, rightward, visuospatial bias. Concurrent TMS and fMRI after right PPC TMS show task-dependent changes but may fail to identify effects of stimulation in areas not directly activated by the specific task, complicating interpretations. We used resting-state functional connectivity (RSFC) after inhibitory TMS over the right PPC to examine changes in the networks underlying visuospatial attention and used diffusion-weighted imaging to measure the structural properties of relevant white matter pathways.In a crossover experiment in healthy individuals, we delivered continuous theta burst TMS to the right PPC and vertex as control condition. We hypothesized that PPC inhibitory stimulation would result in a rightward visuospatial bias, decrease frontoparietal RSFC, and increase the PPC RSFC with the attentional network in the left hemisphere. We also expected that individual differences in fractional anisotropy (FA) of the frontoparietal network and the callosal pathway between the PPCs would account for variability of the TMS-induced RSFC changes.As hypothesized, TMS over the right PPC caused a rightward shift in line bisection judgment and increased RSFC between the right PPC and the left superior temporal gyrus. This effect was inversely related to FA in the posterior corpus callosum. Local inhibition of the right PPC reshapes connectivity in the attentional network and depends significantly on interhemispheric connections.

Role of the somatosensory cortex in motor memory consolidation.

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.

The role of the inferior parietal lobule in writer's cramp.

Humans have a distinguishing ability for fine motor control that is subserved by a highly evolved cortico-motor neuronal network. The acquisition of a particular motor skill involves a long series of practice movements, trial and error, adjustment and refinement. At the cortical level, this acquisition begins in the parieto-temporal sensory regions and is subsequently consolidated and stratified in the premotor-motor cortex. Task-specific dystonia can be viewed as a corruption or loss of motor control confined to a single motor skill. Using a multimodal experimental approach combining neuroimaging and non-invasive brain stimulation, we explored interactions between the principal nodes of the fine motor control network in patients with writer's cramp and healthy matched controls. Patients and healthy volunteers underwent clinical assessment, diffusion-weighted MRI for tractography, and functional MRI during a finger tapping task. Activation maps from the task-functional MRI scans were used for target selection and neuro-navigation of the transcranial magnetic stimulation. Single- and double-pulse TMS evaluation included measurement of the input-output recruitment curve, cortical silent period, and amplitude of the motor evoked potentials conditioned by cortico-cortical interactions between premotor ventral (PMv)-motor cortex (M1), anterior inferior parietal lobule (aIPL)-M1, and dorsal inferior parietal lobule (dIPL)-M1 before and after inducing a long term depression-like plastic change to dIPL node with continuous theta-burst transcranial magnetic stimulation in a randomized, sham-controlled design. Baseline dIPL-M1 and aIPL-M1 cortico-cortical interactions were facilitatory and inhibitory, respectively, in healthy volunteers, whereas the interactions were converse and significantly different in writer's cramp. Baseline PMv-M1 interactions were inhibitory and similar between the groups. The dIPL-PMv resting state functional connectivity was increased in patients compared to controls, but no differences in structural connectivity between the nodes were observed. Cortical silent period was significantly prolonged in writer's cramp. Making a long term depression-like plastic change to dIPL node transformed the aIPL-M1 interaction to inhibitory (similar to healthy volunteers) and cancelled the PMv-M1 inhibition only in the writer's cramp group. These findings suggest that the parietal multimodal sensory association region could have an aberrant downstream influence on the fine motor control network in writer's cramp, which could be artificially restored to its normal function.

Reward-driven enhancements in motor control are robust to TMS manipulation

A wealth of evidence describes the strong positive impact that reward has on motor control at the behavioural level. However, surprisingly little is known regarding the neural mechanisms which underpin these effects, beyond a reliance on the dopaminergic system. In recent work, we developed a task that enabled the dissociation of the selection and execution components of an upper limb reaching movement. Our results demonstrated that both selection and execution are concommitently enhanced by immediate reward availability. Here, we investigate what the neural underpinnings of each component may be. To this end, we aimed to alter the cortical excitability of the ventromedial prefrontal cortex and supplementary motor area using continuous theta-burst transcranial magnetic stimulation (cTBS) in a within-participant design (N = 23). Both cortical areas are involved in determining an individual’s sensitivity to reward and physical effort, and we hypothesised that a change in excitability would result in the reward-driven effects on action selection and execution to be altered, respectively. To increase statistical power, participants were pre-selected based on their sensitivity to reward in the reaching task. While reward did lead to enhanced performance during the cTBS sessions and a control sham session, cTBS was ineffective in altering these effects. These results may provide evidence that other areas, such as the primary motor cortex or the premotor area, may drive the reward-based enhancements of motor performance.

Somatosensory cortex participates in the consolidation of human motor memory.

Newly learned motor skills are initially labile and then consolidated to permit retention. The circuits that enable the consolidation of motor memories remain uncertain. Most work to date has focused on primary motor cortex, and although there is ample evidence of learning-related plasticity in motor cortex, direct evidence for its involvement in memory consolidation is limited. Learning-related plasticity is also observed in somatosensory cortex, and accordingly, it may also be involved in memory consolidation. Here, by using transcranial magnetic stimulation (TMS) to block consolidation, we report the first direct evidence that plasticity in somatosensory cortex participates in the consolidation of motor memory. Participants made movements to targets while a robot applied forces to the hand to alter somatosensory feedback. Immediately following adaptation, continuous theta-burst transcranial magnetic stimulation (cTBS) was delivered to block retention; then, following a 24-hour delay, which would normally permit consolidation, we assessed whether there was an impairment. It was found that when mechanical loads were introduced gradually to engage implicit learning processes, suppression of somatosensory cortex following training almost entirely eliminated retention. In contrast, cTBS to motor cortex following learning had little effect on retention at all; retention following cTBS to motor cortex was not different than following sham TMS stimulation. We confirmed that cTBS to somatosensory cortex interfered with normal sensory function and that it blocked motor memory consolidation and not the ability to retrieve a consolidated motor memory. In conclusion, the findings are consistent with the hypothesis that in adaptation learning, somatosensory cortex rather than motor cortex is involved in the consolidation of motor memory.

The Effect of Continuous Theta-Burst Transcranial Magnetic Stimulation Combined with Prism Adaptation on the Neglect Recovery in Stroke Patients

Objectives: This study was designed to investigate the effect of prism adaptation (PA) combined with continuous theta-burst transcranial magnetic stimulation (cTBS) on the neglect recovery of stroke patients with unilateral neglect. Methods: A total of 14 stroke patients with unilateral neglect were randomly assigned to 2 groups including an intervention group undergone PA combined with cTBS over the left intact parietal cortex and a control group. PA combined with sham cTBS was perfomed for 2 weeks in 10 daily sessions. Before and after the intervention, patients were evaluated for visuospatial neglect measured using the Star Cancellation Test (SCT), Line Bisection Task (LBT), Figure Copying Test, and Clock Drawing Task. Neurological function was evaluated using the Modified Rankin Scale (MRS). Results: Both groups (PA alone and PA+ cTBS) showed improvement in their neglected symptoms (measured by SCT, LBT, Figure Copying Test, and Clock Drawing Task), and in their disability in the neurological function (measured by MRS) (P< .05). Conclusions: The results of the present study showed that, transcranial magnetic stimulation did not increase the effect of PA on neglect symptoms in stroke patients.

Continuous theta burst stimulation over the supplementary motor area in refractory obsessive-compulsive disorder treatment: A randomized sham-controlled trial

BackgroundObsessive-compulsive disorder (OCD) is a complex disorder with 40 to 60 % of patients resistant to treatment. Theta burst transcranial magnetic stimulation (TBS) is a promising new technique that has been shown to induce potent and long lasting effects on cortical excitability. The present study evaluated for the first time therapeutic efficacy and tolerability of continuous TBS (cTBS) over the supplementary motor area (SMA) in treatment resistant OCD patients using a double blind, sham-controlled design. MethodsThirty treatment resistant OCD outpatients were randomized to receive either active cTBS or sham cTBS for 6 weeks (5 sessions per week). Each treatment session consisted of 600 stimuli at an intensity of 70% of resting motor threshold. Patients were evaluated at baseline, at the end of treatment (week 6), and follow-up (week 12). Response to treatment was defined as at least 25% decrease on the Yale-Brown Obsessive Compulsive Scale. ResultsThere was no significant difference between active and sham cTBS groups in treatment efficacy. Responder rates were not different between the two groups at week 6 (cTBS 28% versus sham 36%; p = 0.686) and week 12 (cTBS 28% versus sham 36%; p = 0.686). Depressive and anxious symptoms improvements were similar in the two groups. ConclusionThis study is the first controlled trial using cTBS in treatment resistant OCD patients. The use of cTBS over the SMA is safe but not sufficient to improve OCD symptoms. Further studies are needed to identify the optimal parameters to be used in OCD patients.

Randomized sham-controlled trial of continuous theta-burst transcranial magnetic stimulation (cTBS) in the treatment–resistant obsessive–compulsive disorder

Background Obsessive-compulsive disorder (OCD) is a complex disorder with 40 to 60% of patients refractory to treatment. Developing alternatives to classical therapies would be helpful, and neuromodulation techniques offer promising perspectives. Theta-burst transcranial magnetic stimulation (TBS) has been shown to induce potent and long lasting effects on cortical excitability. Cortical inhibition of supplementary motor area (SMA) with low-frequency repetitive transcranial magnetic stimulation (rTMS) showed clinical benefits in OCD. The aim of the present study is to evaluate therapeutic efficacy and tolerability of continuous TBS (cTBS) over the SMA in treatment-resistant OCD patients using a double blind, sham-controlled design. Methods Thirty treatment resistant OCD outpatients (15 women and 15 men) were randomized to receive either active cTBS or sham cTBS for 6 weeks (5 sessions per week). Each treatment session consisted of 1800 stimuli at an intensity of 70% of resting motor threshold. Patients were evaluated at baseline, end of treatment (week 6), and follow-up (week 12). Response to treatment was defined as at least 25% decrease on the Yale–Brown Obsessive Compulsive Scale (YBOCS). Results Treatment was well tolerated. However, there was no significant difference decrease in Y-BOCS scores, at baseline, weeks 6 and 12, between active and sham cTBS group. Responder rates were not different between groups at week 6 (cTBS 21% versus sham 36%; P = 0.678) and week 12 (cTBS 29% versus sham 36%; P = 1). Depressive and anxious symptoms improvement was also similar in the two groups. Conclusion This study is the first controlled trial using cTBS in OCD treatment refractory patients. Our results suggest that the use of cTBS over the SMA is safe but not sufficient to improve OCD symptoms. Further studies are needed to understand why cTBS is less efficient in reducing OCD symptoms compared to rTMS.