Theta Burst Transcranial Magnetic Stimulation Research Articles

Evaluation of evoked responses to pulse-matched high frequency and intermittent theta burst transcranial magnetic stimulation using simultaneous functional near-infrared spectroscopy.

Transcranial magnetic stimulation (TMS) is a noninvasive method used to excite or inhibit cortical activity for experimental, diagnostic, and therapeutic interventions. However, nonmotor regions of the brain targeted in TMS therapies, such as the dorsolateral prefrontal cortex (DLPFC), offer no extrinsic response to stimulation, resulting in a need for a practical method for the evaluation of treatment. We sought to determine the capability of a continuous-wave light emitting diodes (LED)-based functional near-infrared spectroscopy (fNIRS) system to measure evoked cortical hemoglobin changes in the DLPFC during the simultaneous application of TMS to the left-DLPFC under brief stimulation paradigms used in the clinic. Seventeen healthy participants received short TMS trains at F3 in four different stimulation conditions (single pulse, high frequency, intermittent theta burst, and sham) while adjacent fNIRS measurements were recorded. Ten 2-s trains of each stimulation type were delivered with an intertrial interval of 40s. Results indicated that high-frequency stimulation produces a larger and more evident response than other measured conditions. These findings show that a continuous-wave LED-based fNIRS system can be used to measure TMS-evoked responses and that future TMS applications can benefit from concurrent assessment of localized cortical activation changes.

A causal account of the brain network computations underlying strategic social behavior.

During competitive interactions, humans have to estimate the impact of their own actions on their opponent's strategy. Here we provide evidence that neural computations in the right temporoparietal junction (rTPJ) and interconnected structures are causally involved in this process. By combining inhibitory continuous theta-burst transcranial magnetic stimulation with model-based functional MRI, we show that disrupting neural excitability in the rTPJ reduces behavioral and neural indices of mentalizing-related computations, as well as functional connectivity of the rTPJ with ventral and dorsal parts of the medial prefrontal cortex. These results provide a causal demonstration that neural computations instantiated in the rTPJ are neurobiological prerequisites for the ability to integrate opponent beliefs into strategic choice, through system-level interaction within the valuation and mentalizing networks.

Modulation of cognitive cerebello-cerebral functional connectivity by lateral cerebellar continuous theta burst stimulation

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

Research on the effects of the continuous theta-burst transcranial magnetic stimuli on brain network in emotional processing

The aim of this study is to explore the effects of continuous theta-burst transcranial magnetic stimulation (cTBS) on functional brain network in emotion processing. Before and after the intervention of cTBS over left dorsolateral prefrontal cortex (DLPFC) of ten participants who were asked to perform the emotion gender recognition task, we recorded their scalp electroencephalograms (EEG). Then we used the phase synchronization of EEG to measure the connectivity between two nodes. We then calculated the network efficiency to describe the efficiency of information transmission in brain regions. Our research showed that after the intervention of cTBS and the stimulation of the emotion face picture, there was an obvious enhancement in the event-related spectral perturbation after stimuli onset in beta band in 100-300 ms. Under the stimulation of different emotion picture, the values of global phase synchronization for negative and neutral stimuli were enhanced compared to positive ones. And the increased small-worldness was found in emotional processing. In summary, based on the effect of activity change in the left DLPFC on emotion processing brain network, the emotional processing mechanism of brain networks were preliminary explored and it provided the reference for the research of emotion processing brain network in the future.

Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurological and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications of TMS and theoretical models of functional connectivity.

Important methodological issues regarding the use of transcranial magnetic stimulation to investigate interoceptive processing: a Comment on Pollatos et al. (2016).

Comment on: Changes in interoceptive processes following brain stimulation by Pollatos, Herbert, Mai & Kammer, 2016

Decision making and emotional processing following Theta Burst Transcranial Magnetic Stimulation on medial prefrontal cortex.

Decision making and emotional processing following Theta Burst Transcranial Magnetic Stimulation on medial prefrontal cortex.

Functional connectivity between prefrontal and parietal cortex drives visuo-spatial attention shifts

It is well established that the frontal eye-fields (FEF) in the dorsal attention network (DAN) guide top-down selective attention. In addition, converging evidence implies a causal role for the FEF in attention shifting, which is also known to recruit the ventral attention network (VAN) and fronto-striatal regions. To investigate the causal influence of the FEF as (part of) a central hub between these networks, we applied thetaburst transcranial magnetic stimulation (TBS) off-line, combined with functional magnetic resonance (fMRI) during a cued visuo-spatial attention shifting paradigm.We found that TBS over the right FEF impaired performance on a visual discrimination task in both hemifields following attention shifts, while only left hemifield performance was affected when participants were cued to maintain the focus of attention. These effects recovered ca. 20min post stimulation. Furthermore, particularly following attention shifts, TBS suppressed the neural signal in bilateral FEF, right inferior and superior parietal lobule (IPL/SPL) and bilateral supramarginal gyri (SMG). Immediately post stimulation, functional connectivity was impaired between right FEF and right SMG as well as right putamen. Importantly, the extent of decreased connectivity between right FEF and right SMG correlated with behavioural impairment following attention shifts.The main finding of this study demonstrates that influences from right FEF on SMG in the ventral attention network causally underly attention shifts, presumably by enabling disengagement from the current focus of attention.

Primary somatosensory cortex necessary for the perception of weight from other people's action: A continuous theta-burst TMS experiment

The presence of a network of areas in the parietal and premotor cortices, which are active both during action execution and observation, suggests that we might understand the actions of other people by activating those motor programs for making similar actions. Although neurophysiological and imaging studies show an involvement of the somatosensory cortex (SI) during action observation and execution, it is unclear whether SI is essential for understanding the somatosensory aspects of observed actions. To address this issue, we used off-line transcranial magnetic continuous theta-burst stimulation (cTBS) just before a weight judgment task. Participants observed the right hand of an actor lifting a box and estimated its relative weight. In counterbalanced sessions, we delivered sham and active cTBS over the hand region of the left SI and, to test anatomical specificity, over the left motor cortex (M1) and the left superior parietal lobule (SPL). Active cTBS over SI, but not over M1 or SPL, impaired task performance relative to sham cTBS. Moreover, active cTBS delivered over SI just before participants were asked to evaluate the weight of a bouncing ball did not alter performance compared to sham cTBS. These findings indicate that SI is critical for extracting somatosensory features (heavy/light) from observed action kinematics and suggest a prominent role of SI in action understanding.

P237 Modulating executive functions and working memory performance on clinical neuropsychological tasks with theta burst transcranial magnetic stimulation

Introduction Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation thanks to its ability to induce lasting effects on cortical excitability following a short delivery time. Nevertheless, its ability to inhibit (continuous protocol, cTBS) or facilitate (intermittent, iTBS) brain function from cortical areas other than the motor cortex remains to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (DLPFC) are particularly interesting given its involvement in working memory and executive processing, often impaired after brain injury, and also due to its role of hub of frontal areas, for which it is frequently chosen as a target for treatment and rehabilitation. Objective To explore the ability of cTBS and iTBS to modulate working memory and executive functions assessed with clinical neuropsychological tasks. Materials and methods 36 healthy participants performed 3 clinical neuropsychological tasks: Digits Backward, Stroop test and Tower of Hanoi (Fig. 1). Subjects were assessed twice, first at baseline 1 week prior to stimulation and immediately following a single session of either active cTBS, active iTBS or sham TBS, delivered to the left DLPFC. Results Following sham TBS participants’ performance improved in the Stroop test, with higher scores in Color and Color-Word conditions, as well as lower interference scores (Fig. 2), likely caused by practice effects. Both, iTBS and cTBS, yielded improvements in the Digits Backward task and the Word score of the Stroop test. Moreover, similarly to the sham group, following iTBS participants showed lower Interference scores. In contrast, expected improvements in color score were not induced. Finally, cTBS decreased the number of movements necessary to complete the Tower of Hanoi. Nonetheless, at difference with the sham group, no improvements were observed in the Interference score of Stroop test. Conclusions TBS over DLPFC modulates working memory performance and executive processes. Both protocols resulted in similar working memory and information processing speed outcomes, whereas their effect on executive functions differed: cTBS impaired inhibitory control but improved planning abilities in a spatial task, meanwhile, no specific effects were observed following iTBS. Download : Download high-res image (431KB) Download : Download full-size image Download : Download high-res image (217KB) Download : Download full-size image

Reproducibility of intermittent theta-burst, paired-pulse, and single-pulse transcranial magnetic stimulation measures in older clinical populations

Reproducibility of intermittent theta-burst, paired-pulse, and single-pulse transcranial magnetic stimulation measures in older clinical populations

P232 Effects of inhibitory theta burst TMS to different brain sites involved in visuospatial attention – A combined neuronavigated cTBS and behavioural study

Purpose and methods The study sought to alter visual spatial attention in young healthy subjects by a neuronavigated inhibitory rTMS protocol (cTBS-600) to right brain areas thought to be involved in visual attentional processes, i.e. the temporoparietal junction (TPJ) and the posterior middle frontal gyrus (pMFG), and to test the reversibility of effects by an additional consecutive cTBS to the homologue left brain cortical areas. Results Healthy subjects showed a leftward bias of the egocentric perspective for both visual-perceptive and visual-exploratory tasks specifically for items presented in the left hemifield. cTBS to the right TPJ, and less systematically to the right pMFG reduced this bias for visuo-spatial and exploratory visuo-motor behaviour. Further, a consecutive cTBS to the left TPJ changed the bias again towards the left for a visual-perceptive task. Conclusions The evidence supports the notion of an involvement of the right TPJ (and pMFG) in spatial visual attention. The observations further indicate that inhibitory non-invasive brain stimulation (cTBS) to the left TPJ has a potential for reversing a rightward bias of spatial attention when the right TPJ is dysfunctional. Accordingly, the findings could have implications for therapeutic rTMS development for right brain damaged patients with visual neglect.

Continuous theta burst TMS as a tool to change decision-making in smokers

Continuous theta burst TMS as a tool to change decision-making in smokers

Theta-burst transcranial magnetic stimulation to the prefrontal or parietal cortex does not impair metacognitive visual awareness.

Neuroimaging studies commonly associate dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex with conscious perception. However, such studies only investigate correlation, rather than causation. In addition, many studies conflate objective performance with subjective awareness. In an influential recent paper, Rounis and colleagues addressed these issues by showing that continuous theta burst transcranial magnetic stimulation (cTBS) applied to the DLPFC impaired metacognitive (subjective) awareness for a perceptual task, while objective performance was kept constant. We attempted to replicate this finding, with minor modifications, including an active cTBS control site. Using a between-subjects design for both DLPFC and posterior parietal cortices, we found no evidence of a cTBS-induced metacognitive impairment. In a second experiment, we devised a highly rigorous within-subjects cTBS design for DLPFC, but again failed to find any evidence of metacognitive impairment. One crucial difference between our results and the Rounis study is our strict exclusion of data deemed unsuitable for a signal detection theory analysis. Indeed, when we included this unstable data, a significant, though invalid, metacognitive impairment was found. These results cast doubt on previous findings relating metacognitive awareness to DLPFC, and inform the current debate concerning whether or not prefrontal regions are preferentially implicated in conscious perception.

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

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

EP 71. The effect of intermittent theta burst stimulation over the dorsolateral prefrontal cortex on cortico-striatal connectivity

Aim Fronto-striatal loops play an important role in various cognitive and emotional processes. Intermittent theta burst transcranial magnetic stimulation has been shown to increase regional excitability as well as functional connectivity of connected areas ( Huang et al., 2005 ). The issue of choosing an optimal TMS intensity, which is interlinked with ethical and practical issues such as pain and muscle twitches, has not been explored in detail yet. Furthermore, the role of purely anatomical white matter tracts on functional connectivity has often not been taken into account when studying TMS effects. We therefore applied intermittent theta burst stimulation (iTBS) with different intensities and methods of determining the exact stimulation sites to systematically test optimal parameters combining strong fronto-striatal activity with minimal adverse effects. Methods Healthy subjects underwent iTBS at different intensities (90% and 120% of individual resting motor threshold). The excitatory iTBS protocol consisted of 600 pulses (2 s trains and 8 s pauses for 3.33 min) and was applied over the left dorsolateral prefrontal cortex (lDLPFC). Directly before and 7 min after stimulation a task-free resting state functional magnetic resonance imaging scan was conducted. The exact stimulation site was either determined using a lDLPFC standard coordinate or by extracting an individual lDLPFC coordinate from diffusion tensor imaging (DTI) data. The latter was done by analysing DTI data with FSL ( Smith et al., 2004 ) and finding individual tracts connecting the left caudate with the lDLPFC. Resting state data was analysed using the Data Processing Assistant for Resting-State fMRI (DPARSF; Chao-Gan, 2012 ) SPM toolbox, with the caudate and the stimulation sites as seed regions. Results and conclusion Our preliminary findings suggest that a sub-threshold stimulation intensity of 90% is sufficient to induce changes in functional connectivity of the fronto-striatal network when stimulation is applied over the lDLPFC. Furthermore, stimulation effects might be increased by determining an individual stimulation site based on DTI tracts, rather than using a standardised mean coordinate for all participants. By using sub-threshold intensities adverse effects such as pain and head movements due to muscle twitches can be reduced or avoided.

EP 145. Neuropeptide Y and the cellular effects of transcranial magnetic theta-burst stimulation in rat neocortex

Questions High-frequency transcranial magnetic stimulation with theta-burst stimulation (TBS) induces strong and highly synchronous cortical network activity principally able to trigger epileptiform activity or to cause over-excitation of distinct neurons. Our previous studies showed that intermittent TBS (iTBS) strongly reduces the expression of the calcium-binding protein parvalbumin (PV) in fast-spiking inhibitory interneurons (FSI). Since PV is expressed in an activity-dependent manner, strong activation of these neurons during iTBS might have triggered mechanisms to prevent permanent over-excitation. One well-described process is the reduction of glutamate release from excitatory terminals targeting FSI via the action of neuropeptide Y (NPY). Therefore, we first tested if iTBS increases the expression of NPY in rat cortex and second, if application of NPY to the lateral ventricle can counteract the cortical iTBS effect of reducing PV expression. Methods In the first study, frontal sections of rat brains previously treated with one to five blocks of iTBS (600 pulses per block, intervals of 15 min) were immunostained for NPY and PV. In the second study, rats received either 20 μ l NPY (24 nMol) or methylene blue as a control (MB) via intracranial injection to the left lateral ventricle (2 μ l/min) followed 60 min later by either verum or sham iTBS (3 blocks @ 15 min = 1800 pulses). Further 60 min later rats were perfused for PV immunostaining of their brains. Results iTBS gradually increased the number of NPY+ neurons in a dose-dependent fashion from about 60 cells/mm2 to about 130 cells/mm2 after five iTBS blocks. The same stimulation protocol was previously found to decrease the number of PV+ neurons by about 40% after five iTBS blocks (Volz et al., Brain Stimulation 2013). NPY injected into the lateral ventricle of the left forebrain (no diffusion to the right hemisphere) prevented the reduction of PV+ cells (−40%) by iTBS in the left but not in the right hemisphere and further increased the number of PV+ cells. A slight increase in PV+ cells was also evident in sham stimulated animals when comparing NPY with MB injections. Conclusions As expected, iTBS increased the expression of NPY likely due to the strong and highly synchronous activation of cortical networks. Since strong excitation is especially harmful to FSI, the reduction in PV expression indicates a post-stimulation depression of excitatory inputs and subsequent hypoactivity of these interneurons. The finding that NPY prevents the strong reduction in PV expression indicates that it is able to prevent over-excitation of FSI. This study has been supported by grants of the Deutsche Forschungsgemeinschaft (DFG): SFB 874 TP A4 and the Federal Ministry of Education and Research (BMBF): GCBS-WP1_Bochum (01EE1403B) to K. Funke.

Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

Effects of inhibitory theta burst TMS to different brain sites involved in visuospatial attention - a combined neuronavigated cTBS and behavioural study.

The study sought to alter visual spatial attention in young healthy subjects by a neuronavigated inhibitory rTMS protocol (cTBS-600) to right brain areas thought to be involved in visual attentional processes, i.e. the temporoparietal junction (TPJ) and the posterior middle frontal gyrus (pMFG), and to test the reversibility of effects by an additional consecutive cTBS to the homologue left brain cortical areas. Healthy subjects showed a leftward bias of the egocentric perspective for both visual-perceptive and visual-exploratory tasks specifically for items presented in the left hemifield. cTBS to the right TPJ, and less systematically to the right pMFG reduced this bias for visuo-spatial and exploratory visuo-motor behaviour. Further, a consecutive cTBS to the left TPJ changed the bias again towards the left for a visual-perceptive task. The evidence supports the notion of an involvement of the right TPJ (and pMFG) in spatial visual attention. The observations further indicate that inhibitory non-invasive brain stimulation (cTBS) to the left TPJ has a potential for reversing a rightward bias of spatial attention when the right TPJ is dysfunctional. Accordingly, the findings could have implications for therapeutic rTMS development for right brain damaged patients with visual neglect.

Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus.

Clinical effects of repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus are moderate. More precise coil localisation strategies, innovative stimulation protocols, and identification of predictors for treatment response were proposed as promising attempts to enhance treatment efficacy. In this pilot study we investigated neuronavigated continuous theta burst TMS (cTBS). Twenty-three patients received neuronavigated cTBS over the left primary auditory cortex in a randomized sham-controlled trial (verum = 12; sham = 11). Treatment response was evaluated with tinnitus questionnaires and numeric rating scales. Immediate change in numeric rating scales during the first session was used as predictor for treatment response. Tinnitus was significantly reduced after treatment, but there were no superior effects between verum vs. sham treatment. Immediate change in the first treatment session predicted the response to treatment only in the verum group. In our study, verum cTBS was not superior to sham which highlights the persistent need for improving non-invasive brain stimulation techniques for the treatment of tinnitus. Future research should focus on the transfer of positive single session effects to daily treatment trials.