Lessons learned from an fMRI-guided rTMS study on performance in a numerical Stroop task.

The Stroop task is a well-established tool to investigate the influence of competing visual categories on decision making. Neuroimaging as well as rTMS studies have demonstrated the involvement of parietal structures, particularly the intraparietal sulcus (IPS), in this task. Given its reliability, the numerical Stroop task was used to compare the effects of different TMS targeting approaches by Sack and colleagues (Sack AT 2009), who elegantly demonstrated the superiority of individualized fMRI targeting. We performed the present study to test whether fMRI-guided rTMS effects on numerical Stroop task performance could still be observed while using more advanced techniques that have emerged in the last decade (e.g., electrical sham, robotic coil holder system, etc.). To do so we used a traditional reaction time analysis and we performed, post-hoc, a more advanced comprehensive drift diffusion modeling approach. Fifteen participants performed the numerical Stroop task while active or sham 10 Hz rTMS was applied over the region of the right intraparietal sulcus (IPS) showing the strongest functional activation in the Incongruent > Congruent contrast. This target was determined based on individualized fMRI data collected during a separate session. Contrary to our assumption, the classical reaction time analysis did not show any superiority of active rTMS over sham, probably due to confounds such as potential cumulative rTMS effects, and the effect of practice. However, the modeling approach revealed a robust effect of rTMS on the drift rate variable, suggesting differential processing of congruent and incongruent properties in perceptual decision-making, and more generally, illustrating that more advanced computational analysis of performance can elucidate the effects of rTMS on the brain where simpler methods may not.

Educating the next generation of psychiatrists in the use of clinical neuromodulation therapies: what should all psychiatry residents know?

A variety of neuromodulation treatments are available today and more are on the way, but are tomorrow's psychiatrists prepared to incorporate these tools into their patients' care plans? This article addresses the need for training in clinical neuromodulation for general psychiatry trainees. To ensure patient access to neuromodulation treatments, we believe that general psychiatrists should receive adequate education in a spectrum of neuromodulation modalities to identify potential candidates and integrate neuromodulation into their multidisciplinary care plans. We propose curricular development across the four FDA-cleared modalities currently available in psychiatric practice: electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). With a focus on psychiatry residency training, the article delineates core learning components for each neuromodulation technique. For each modality, we review the clinical training status, the respective FDA-cleared indications, mechanisms of action, clinical indications and contraindications, adverse effects, informed consent process, dosing considerations, and clinical management guidelines. The approach outlined in this article aims to contribute to the development of a well-rounded generation of psychiatry trainees with the capacity to navigate the growing field of neuromodulation. Whether or not a psychiatrist specializes in delivering neuromodulation therapies themselves, it is incumbent on all psychiatrists to be able to identify patients who should be referred to neuromodulation therapies, and to provide comprehensive patient care before, during and after clinical neuromodulation interventions to optimize outcomes and prevent relapse.

Clinical Outcomes of Magnetic Seizure Therapy vs Electroconvulsive Therapy for Major Depressive Episode: A Randomized Clinical Trial.

Importance: Electroconvulsive therapy (ECT) is highly effective and rapid in treating depression, but it carries a risk of significant cognitive adverse effects. Magnetic seizure therapy (MST), an investigational antidepressant treatment, may maintain the robust antidepressant efficacy of ECT while substantially reducing adverse effects due to its enhanced focality and weaker stimulation strength; however, previous clinical trials of MST were limited by small sample sizes. Objective: To compare the antidepressant efficacy of MST vs ultrabrief pulse right unilateral (RUL) ECT. Design, Setting, and Participants: A between-participants, double-blinded, randomized clinical trial was conducted at 3 academic hospitals from June 2007 to August 2012. Adults aged 18 to 90 years who were referred for treatment with ECT, had a major depressive episode in the context of major depressive disorder or bipolar disorder, and had a baseline 24-item Hamilton Depression Rating Scale (HDRS-24) total score of 18 or higher were included. Participants were randomly assigned 1:1 to treatment with MST or ultrabrief pulse RUL ECT. After the treatment course, patients were naturalistically followed up for up to 6 months to examine the durability of clinical effects. Interventions: Treatment with MST, applied at 100 Hz at 100% of the maximum device power for 10 seconds, or ultrabrief pulse RUL ECT, applied at 6 times seizure threshold. Main Outcomes and Measures: The primary outcome was change from baseline in HDRS-24 total score, with patients followed up for up to 6 months. A reduction of at least 50% in the HDRS-24 score indicated response, and at least a 60% decrease in the HDRS-24 score and a total score of 8 or less indicated remission. Results: Of the 73 participants (41 [56.2%] female; mean [SD] age, 48 [14.1] years), 35 were randomized to MST and 38 to ECT. Among them, 53 (72.6%) were classified as completers (29 in the MST group and 24 in the ECT group). Both MST and ECT demonstrated clinically meaningful antidepressant effects. In the intent-to-treat sample, 18 participants (51.4%) in the MST group and 16 (42.1%) in the ECT group met response criteria; 13 (37.1%) in the MST group and 10 (26.3%) in the ECT group met remission criteria. Among completers, 17 of 29 (58.6%) in the MST group and 15 of 24 (62.5%) in the ECT group met response criteria; 13 of 29 (44.8%) in the MST group and 10 of 24 (41.7%) in the ECT group met remission criteria. There was no significant difference between MST and ECT for either response or remission rates. However, the mean (SD) number of treatments needed to achieve remission was 9.0 (3.1) with MST and 6.7 (3.3) with ECT, a difference of 2.3 treatments (t71.0 = 3.1; P = .003). Both MST and ECT showed a sustained benefit over a 6-month follow-up period, again with no significant difference between them. Compared with MST, ECT had significantly longer time to orientation after treatment (threshold level: F1,56 = 10.0; P = .003) and greater severity of subjective adverse effects, particularly in the physical and cognitive domains. Conclusions and Relevance: This randomized clinical trial found that the efficacy of MST was indistinguishable from that of ultrabrief pulse RUL ECT, the safest form of ECT currently available. These results support the continued development of MST and provide evidence for advantages relative to state-of-the-art ECT. Trial Registration: ClinicalTrials.gov Identifier: NCT00488748.

Network-level dynamics underlying a combined rTMS and psychotherapy treatment for major depressive disorder: An exploratory network analysis.

Background: Despite the growing use of repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression, there is a limited understanding of the mechanisms of action and how potential treatment-related brain changes help to characterize treatment response. To address this gap in understanding we investigated the effects of an approach combining rTMS with simultaneous psychotherapy on global functional connectivity. Method: We compared task-related functional connectomes based on an idiographic goal priming task tied to emotional regulation acquired before and after simultaneous rTMS/psychotherapy treatment for patients with major depressive disorders and compared these changes to normative connectivity patterns from a set of healthy volunteers (HV) performing the same task. Results: At baseline, compared to HVs, patients demonstrated hyperconnectivity of the DMN, cerebellum and limbic system, and hypoconnectivity of the fronto-parietal dorsal-attention network and visual cortex. Simultaneous rTMS/psychotherapy helped to normalize these differences, which were reduced after treatment. This finding suggests that the rTMS/therapy treatment regularizes connectivity patterns in both hyperactive and hypoactive brain networks. Conclusions: These results help to link treatment to a comprehensive model of the neurocircuitry underlying depression and pave the way for future studies using network-guided principles to significantly improve rTMS efficacy for depression.

Effects of Online Single Pulse Transcranial Magnetic Stimulation on Prefrontal and Parietal Cortices in Deceptive Processing: A Preliminary Study.

Transcranial magnetic stimulation (TMS) was used to test the functional role of parietal and prefrontal cortical regions activated during a playing card Guilty Knowledge Task (GKT). Single-pulse TMS was applied to 15 healthy volunteers at each of three target sites: left and right dorsolateral prefrontal cortex and midline parietal cortex. TMS pulses were applied at each of five latencies (from 0 to 480 ms) after the onset of a card stimulus. TMS applied to the parietal cortex exerted a latency-specific increase in inverse efficiency score and in reaction time when subjects were instructed to lie relative to when asked to respond with the truth, and this effect was specific to when TMS was applied at 240 ms after stimulus onset. No effects of TMS were detected at left or right DLPFC sites. This manipulation with TMS of performance in a deception task appears to support a critical role for the parietal cortex in intentional false responding, particularly in stimulus selection processes needed to execute a deceptive response in the context of a GKT. However, this interpretation is only preliminary, as further experiments are needed to compare performance within and outside of a deceptive context to clarify the effects of deceptive intent.

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

Using diffusion tensor imaging to effectively target TMS to deep brain structures.

TMS has become a powerful tool to explore cortical function, and in parallel has proven promising in the development of therapies for various psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp, though clearly more distant regions are likely to be influenced by structurally connected stimulation sites. In this study, we sought to develop a novel paradigm to individualize TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. In ten subjects, structural diffusion imaging tractography data were used to identify an accessible cortical target in the right frontal pole that demonstrated both anatomic and functional connectivity to right Brodmann area 25 (BA25). Concurrent TMS-fMRI interleaving was used with a series of single, interleaved TMS pulses applied to the right frontal pole at four intensity levels ranging from 80% to 140% of motor threshold. In nine of ten subjects, TMS to the individualized frontal pole sites resulted in significant linear increase in BOLD activation of BA25 with increasing TMS intensity. The reliable activation of BA25 in a dosage-dependent manner suggests the possibility that the careful combination of imaging with TMS can make use of network properties to help overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures.

Network-based rTMS to modulate working memory: The difficult choice of effective parameters for online interventions.

BACKGROUND: Online repetitive transcranialmagnetic stimulation (rTMS) has been shown to modulate working memory (WM) performance in a site-specific manner, with behavioral improvements due to stimulation of the dorsolateral prefrontal cortex (DLPFC), and impairment from stimulation to the lateral parietal cortex (LPC). Neurobehavioral studies have demonstrated that subprocesses of WM allowing for the maintenance and manipulation of information in the mind involve unique cortical networks. Despite promising evidence of modulatory effects of rTMS on WM, no studies have yet demonstrated distinct modulatory control of these two subprocesses. The current study therefore sought to explore this possibility through site-specific stimulation during an online task invoking both skills. METHODS: Twenty-nine subjects completed a 4-day protocol, in which active or sham 5Hz rTMS was applied over the DLPFC and LPC in separate blocks of trials while participants performed tasks that required either maintenance alone, or both maintenance and manipulation (alphabetization) of information. Stimulation targets were defined individually based on fMRI activation and structural network properties. Stimulation amplitude was adjusted using electric field modeling to equate induced current in the target region across participants. RESULTS: Despite the use of advanced techniques, no significant differences or interactions between active and sham stimulation were found. Exploratory analyses testing stimulation amplitude, fMRI activation, and modal controllability showed nonsignificant but interesting trends with rTMS effects. CONCLUSION: While this study did not reveal any significant behavioral changes in WM, the results may point to parameters that contribute to positive effects, such as stimulation amplitude and functional activation.

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee.

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.

A generalized workflow for conducting electric field-optimized, fMRI-guided, transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cerebral cortex that has applications in psychiatry, such as in the treatment of depression and anxiety. Although many TMS targeting methods that use figure-8 coils exist, many do not account for individual differences in anatomy or are not generalizable across target sites. This protocol combines functional magnetic resonance imaging (fMRI) and iterative electric-field (E-field) modeling in a generalized approach to subject-specific TMS targeting that is capable of optimizing the stimulation site and TMS coil orientation. To apply this protocol, the user should (i) operationally define a region of interest (ROI), (ii) generate the head model from the structural MRI data, (iii) preprocess the functional MRI data, (iv) identify the single-subject stimulation site within the ROI, and (iv) conduct E-field modeling to identify the optimal coil orientation. In comparison with standard targeting methods, this approach demonstrates (i) reduced variability in the stimulation site across subjects, (ii) reduced scalp-to-cortical-target distance, and (iii) reduced variability in optimal coil orientation. Execution of this protocol requires intermediate-level skills in structural and functional MRI processing. This protocol takes ~24 h to complete and demonstrates how constrained fMRI targeting combined with iterative E-field modeling can be used as a general method to optimize both the TMS coil site and its orientation.

Structural Controllability Predicts Functional Patterns and Brain Stimulation Benefits Associated with Working Memory.

The brain is an inherently dynamic system, and much work has focused on the ability to modify neural activity through both local perturbations and changes in the function of global network ensembles. Network controllability is a recent concept in network neuroscience that purports to predict the influence of individual cortical sites on global network states and state changes, thereby creating a unifying account of local influences on global brain dynamics. While this notion is accepted in engineering science, it is subject to ongoing debates in neuroscience as empirical evidence linking network controllability to brain activity and human behavior remains scarce. Here, we present an integrated set of multimodal brain-behavior relationships derived from fMRI, diffusion tensor imaging, and online repetitive transcranial magnetic stimulation (rTMS) applied during an individually calibrated working memory task performed by individuals of both sexes. The modes describing the structural network system dynamics showed direct relationships to brain activity associated with task difficulty, with difficult-to-reach modes contributing to functional brain states in the hard task condition. Modal controllability (a measure quantifying the contribution of difficult-to-reach modes) at the stimulated site predicted both fMRI activations associated with increasing task difficulty and rTMS benefits on task performance. Furthermore, fMRI explained 64% of the variance between modal controllability and the working memory benefit associated with 5 Hz online rTMS. These results therefore provide evidence toward the functional validity of network control theory, and outline a clear technique for integrating structural network topology and functional activity to predict the influence of stimulation on subsequent behavior.SIGNIFICANCE STATEMENT The network controllability concept proposes that specific cortical nodes are able to steer the brain into certain physiological states. By applying external perturbation to these control nodes, it is theorized that brain stimulation is able to selectively target difficult-to-reach states, potentially aiding processing and improving performance on cognitive tasks. The current study used rTMS and fMRI during a working memory task to test this hypothesis. We demonstrate that network controllability correlates with fMRI modulation because of working memory load and with the behavioral improvements that result from a multivisit intervention using 5 Hz rTMS. This study demonstrates the validity of network controllability and offers a new targeting approach to improve efficacy.

Site-Specific Effects of Online rTMS during a Working Memory Task in Healthy Older Adults.

The process of manipulating information within working memory is central to many cognitive functions, but also declines rapidly in old age. Improving this process could markedly enhance the health-span in older adults. The current pre-registered, randomized and placebo-controlled study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) applied at 5 Hz over the left lateral parietal cortex to enhance working memory manipulation in healthy elderly adults. rTMS was applied, while participants performed a delayed-response alphabetization task with two individually titrated levels of difficulty. Coil placement and stimulation amplitude were calculated from fMRI activation maps combined with electric field modeling on an individual-subject basis in order to standardize dosing at the targeted cortical location. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. When compared to the results from our previous study, in which rTMS was applied over the left prefrontal cortex, we found equivalent effect sizes but opposite directionality suggesting a site-specific effect of rTMS. These results demonstrate engagement of cortical working memory processing using a novel TMS targeting approach, while also providing prescriptions for future studies seeking to enhance memory through rTMS.

Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety.

Anxiety disorders are the most prevalent mental disorders, with few effective neuropharmacological treatments, making treatments development critical. While noninvasive neuromodulation can successfully treat depression, few treatment targets have been identified specifically for anxiety disorders. Previously, we showed that shock threat increases excitability and connectivity of the intraparietal sulcus (IPS). Here we tested the hypothesis that inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting this region would reduce induced anxiety. Subjects were exposed to neutral, predictable, and unpredictable shock threat, while receiving double-blinded, 1 Hz active or sham IPS rTMS. We used global brain connectivity and electric-field modelling to define the single-subject targets. We assessed subjective anxiety with online ratings and physiological arousal with the startle reflex. Startle stimuli (103 dB white noise) probed fear and anxiety during the predictable (fear-potentiated startle, FPS) and unpredictable (anxiety-potentiated startle, APS) conditions. Active rTMS reduced both FPS and APS relative to both the sham and no stimulation conditions. However, the online anxiety ratings showed no difference between the stimulation conditions. These results were not dependent on the laterality of the stimulation, or the subjects' perception of the stimulation (i.e. active vs. sham). Results suggest that reducing IPS excitability during shock threat is sufficient to reduce physiological arousal related to both fear and anxiety, and are consistent with our previous research showing hyperexcitability in this region during threat. By extension, these results suggest that 1 Hz parietal stimulation may be an effective treatment for clinical anxiety, warranting future work in anxiety patients.

Using Transcranial Magnetic Stimulation to Test a Network Model of Perceptual Decision Making in the Human Brain.

Previous research has suggested that the lateral occipital cortex (LOC) is involved with visual decision making, and specifically with the accumulation of information leading to a decision. In humans, this research has been primarily based on imaging and electroencephalography (EEG), and as such only correlational. One line of such research has led to a model of three spatially distributed brain networks that activate in temporal sequence to enable visual decision-making. The model predicted that disturbing neural processing in the LOC at a specific latency would slow object decision-making, increasing reaction time (RT) in a difficult discrimination task. We utilized transcranial magnetic stimulation (TMS) to test this prediction, perturbing LOC beginning at 400 ms post-stimulus onset, a time in the model corresponding to LOC activation at a particular difficulty level, with the expectation of increased RT. Thirteen healthy adults participated in two TMS sessions in which left and right LOC were stimulated separately utilizing neuronavigation and robotic coil guidance. Participants performed a two-alternative forced-choice task selecting whether a car or face was present on each trial amidst visual noise pre-tested to approximate a 75% accuracy level. In an effort to disrupt processing, pairs of TMS pulses separated by 50 ms were presented at one of five stimulus onset asynchronies (SOAs): -200, 200, 400, 450, or 500 ms. Behavioral performance differed systematically across SOAs for RT and accuracy measures. As predicted, TMS at 400 ms resulted in a significant slowing of RT. TMS delivered at -200 ms resulted in faster RT, indicating early stimulation may result in priming and performance enhancement. Use of TMS thus causally demonstrated the involvement of LOC in this task, and more broadly with perceptual decision-making; additionally, it demonstrated the role of TMS in testing well-developed neural models of perceptual processing.

Device-Based Modulation of Neurocircuits as a Therapeutic for Psychiatric Disorders.

Device-based neuromodulation of brain circuits is emerging as a promising new approach in the study and treatment of psychiatric disorders. This work presents recent advances in the development of tools for identifying neurocircuits as therapeutic targets and in tools for modulating neurocircuits. We review clinical evidence for the therapeutic efficacy of circuit modulation with a range of brain stimulation approaches, including subthreshold, subconvulsive, convulsive, and neurosurgical techniques. We further discuss strategies for enhancing the precision and efficacy of neuromodulatory techniques. Finally, we survey cutting-edge research in therapeutic circuit modulation using novel paradigms and next-generation devices.

Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects.

Much of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS). In a within-subject, crossover experiment, the study measured anxiety in healthy subjects before and after a session of 10 Hz rTMS to the right dorsolateral prefrontal cortex (dlPFC). It used threat of predictable and unpredictable shock to induce anxiety and anxiety potentiated startle to assess anxiety. Counter to our hypotheses, results showed an increase in anxiety-potentiated startle following active but not sham rTMS. These results suggest a mechanistic link between right dlPFC activity and physiological anxiety expression. This result supports current models of prefrontal asymmetry in affect, and lays the groundwork for further exploration into the cortical mechanisms mediating anxiety, which may lead to novel anxiety treatments.

Effects of online repetitive transcranial magnetic stimulation (rTMS) on cognitive processing: A meta-analysis and recommendations for future studies.

Online repetitive transcranial magnetic stimulation (rTMS), applied while subjects are performing a task, is widely used to disrupt brain regions underlying cognition. However, online rTMS has also induced "paradoxical enhancement". Given the rapid proliferation of this approach, it is crucial to develop a better understanding of how online stimulation influences cognition, and the optimal parameters to achieve desired effects. To accomplish this goal, a quantitative meta-analysis was performed with random-effects models fitted to reaction time (RT) and accuracy data. The final dataset included 126 studies published between 1998 and 2016, with 244 total effects for reaction times, and 202 for accuracy. Meta-analytically, rTMS at 10 Hz and 20 Hz disrupted accuracy for attention, executive, language, memory, motor, and perception domains, while no effects were found with 1 Hz or 5 Hz. Stimulation applied at and 10 and 20 Hz slowed down RTs in attention and perception tasks. No performance enhancement was found. Meta-regression analysis showed that fMRI-guided targeting and short inter-trial intervals are associated with increased disruptive effects with rTMS.

Accuracy of robotic coil positioning during transcranial magnetic stimulation.

OBJECTIVE: Robotic positioning systems for transcranial magnetic stimulation (TMS) promise improved accuracy and stability of coil placement, but there is limited data on their performance. Investigate the usability, accuracy, and limitations of robotic coil placement with a commercial system, ANT Neuro, in a TMS study. APPROACH: 21 subjects underwent a total of 79 TMS sessions corresponding to 160 hours under robotic coil control. Coil position and orientation were monitored concurrently through an additional neuronavigation system. MAIN RESULTS: Robot setup took on average 14.5 min. The robot achieved low position and orientation error with median 3.54 mm (overall, 1.34 mm without coil-head spacing) and 3.48°. The error increased over time at a rate of 0.4%/minute for both position and orientation. SIGNIFICANCE: Robotic TMS systems can provide accurate and stable coil position and orientation in long TMS sessions. Lack of pressure feedback and of manual adjustment of all coil degrees of freedom were limitations of this robotic system.

Low- and High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Resting-State Functional Connectivity Between the Postcentral Gyrus and the Insula.

The insular cortex supports the conscious awareness of physical and emotional sensations, and the ability to modulate the insula could have important clinical applications in psychiatry. Repetitive transcranial magnetic stimulation (rTMS) uses transient magnetic fields to induce electrical currents in the superficial cortex. Given its deep location in the brain, the insula may not be directly stimulated by rTMS; however, rTMS may modulate the insula via its functional connections with superficial cortical regions. Furthermore, low- versus high-frequency rTMS is thought to have opposing effects on cortical excitability, and the present study investigated these effects on brain activity and functional connectivity with the insula. Separate groups of healthy participants (n = 14 per group) received low (1 Hz)- or high (10 Hz)-frequency rTMS in five daily sessions to the right postcentral gyrus, a superficial region known to be functionally connected to the insula. Resting-state functional connectivity (RSFC) was measured pre- and post-rTMS. Both 1 and 10 Hz rTMS increased RSFC between the right postcentral gyrus and the left insula. These results suggest that low- and high-frequency rTMS has similar long-term effects on brain activity and RSFC. However, given the lack of difference, we cannot exclude the possibility that these effects are simply due to a nonspecific effect. Given this limitation, these unexpected results underscore the need for acoustic- and stimulation-matched sham control conditions in rTMS research.