Real world efficacy and safety of various accelerated deep TMS protocols for major depression.

There is growing interest in accelerated rTMS dosing regimens, wherein multiple sessions of rTMS are applied per day. This Phase IV study evaluated the safety, efficacy, and durability of various accelerated Deep TMS protocols used in clinical practice. Data were aggregated from 111 patients with major depressive disorder (MDD) at 4 sites. Patients received one of several accelerated Deep TMS protocols (2x/day, 3x/day, 5x/day, 10x/day). Self-assessment questionnaires (PHQ-9, BDI-II) and clinician-based rating scales (HDRS-21, MADRS) were collected. On average, accelerated TMS led to an 80.2% response and 50.5% remission rate in the first month based on the most rated scale for each patient. There was no significant difference between protocols (Response: 2x/day:89.6%; 3x/day:75%; 5x/day:81%; 10x/day:67.6%). Response occurred after 10 (3x/day), 20 (5x/day), and 31 sessions (10x/day) on average- all of which occur on day 3-4 of treatment. Of patients with longer term follow up, durability was found in 86.7% (n = 30; 60 days) and 92.9% (n = 14; 180 days). The protocols were well-tolerated with no reported serious adverse events. Accelerated Deep TMS protocols are found to be safe, effective therapeutic options for MDD. They offer treatment resistant patients a treatment option with a rapid onset of action and with long durability.

Transcranial Magnetic Stimulation as a Tool to Promote Smoking Cessation and Decrease Drug and Alcohol Use.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, drug-free, neural-circuit-based therapeutic tool that was recently cleared by the United States Food and Drug Associate for the treatment of smoking cessation. TMS has been investigated as a tool to reduce consumption and craving for many other substance use disorders (SUDs). This review starts with a discussion of neural networks involved in the addiction process. It then provides a framework for the therapeutic efficacy of TMS describing the role of executive control circuits, default mode, and salience circuits as putative targets for neuromodulation (via targeting the DLPFC, MPFC, cingulate, and insula bilaterally). A series of the largest studies of TMS in SUDs are listed and discussed in the context of this framework. Our review concludes with an assessment of the current state of knowledge regarding the use of rTMS as a therapeutic tool in reducing drug, alcohol, and nicotine use and identifies gaps in the literature that need to be addressed in future studies. Namely, while the presumed mechanism through which TMS exerts its effects is by modulating the functional connectivity circuits involved in executive control and salience of drug-related cues, it is also possible that TMS has direct effects on subcortical dopamine, a hypothesis that could be explored in greater detail with PET imaging.

Deep TMS H1 Coil treatment for depression: Results from a large post marketing data analysis.

Phase IV study evaluated Deep TMS for major depression in community settings. Data were aggregated from 1753 patients at 21 sites, who received Deep TMS (high frequency or iTBS) using the H1 coil. Outcome measures varied across subjects and included clinician-based scales (HDRS-21) and self-assessment questionnaires (PHQ-9, BDI-II). 1351 patients were included in the analysis, 202 received iTBS. For participants with data from at least 1 scale, 30 sessions of Deep TMS led to 81.6% response and 65.3% remission rate. 20 sessions led to 73.6% response and 58.1% remission rate. iTBS led to 72.4% response and 69.2% remission. Remission rates were highest when assessed with HDRS (72%). In 84% of responders and 80% of remitters, response and remission was sustained in the subsequent assessment. Median number of sessions (days) for onset of sustained response was 16 (21 days) and for sustained remission 17 (23 days). Higher stimulation intensity was associated with superior clinical outcomes. This study shows that beyond its proven efficacy in RCTs, Deep TMS with the H1 coil is effective for treating depression under naturalistic conditions, and the onset of improvement is usually within 20 sessions. However, initial non-responders and non-remitters benefit from extended treatment.

Transcranial Magnetic Stimulation in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) patients need novel therapeutic interventions since most experience residual symptoms despite treatment. Converging evidence suggest that OCD involves dysfunction of limbic cortico-striato-thalamo-cortical loops, including the medial prefrontal cortex (mPFC) and dorsal anterior cingulate cortex (dACC), that tends to normalize with successful treatment. Recently, three repetitive transcranial magnetic stimulation (rTMS) coils were FDA-cleared for treatment-refractory OCD. This review presents on-label and off-label clinical evidence and relevant physical characteristics of the three coils. The Deep TMS™ H7 Coil studies' point to efficacy of mPFC-dACC stimulation, while no clear target stems from the small heterogenous D-B80 and figure-8 coils studies.

Detailed measurements and simulations of electric field distribution of two TMS coils cleared for obsessive compulsive disorder in the brain and in specific regions associated with OCD.

The FDA cleared deep transcranial magnetic stimulation (Deep TMS) with the H7 coil for obsessive-compulsive disorder (OCD) treatment, following a double-blinded placebo-controlled multicenter trial. Two years later the FDA cleared TMS with the D-B80 coil on the basis of substantial equivalence. In order to investigate the induced electric field characteristics of the two coils, these were placed at the treatment position for OCD over the prefrontal cortex of a head phantom, and the field distribution was measured. Additionally, numerical simulations were performed in eight Population Head Model repository models with two sets of conductivity values and three Virtual Population anatomical head models and their homogeneous versions. The H7 was found to induce significantly higher maximal electric fields (p<0.0001, t = 11.08) and to stimulate two to five times larger volumes in the brain (p<0.0001, t = 6.71). The rate of decay of electric field with distance is significantly slower for the H7 coil (p < 0.0001, Wilcoxon matched-pairs test). The field at the scalp is 306% of the field at a 3 cm depth with the D-B80, and 155% with the H7 coil. The H7 induces significantly higher intensities in broader volumes within the brain and in specific brain regions known to be implicated in OCD (dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and pre-supplementary motor area (pre-SMA)) compared to the D-B80. Significant field ≥ 80 V/m is induced by the H7 (D-B80) in 15% (1%) of the dACC, 78% (29%) of the pre-SMA, 50% (20%) of the dlPFC, 30% (12%) of the OFC and 15% (1%) of the IFG. Considering the substantial differences between the two coils, the clinical efficacy in OCD should be tested and verified separately for each coil.

Efficacy of Deep TMS with the H1 Coil for Anxious Depression.

(1) Background: While the therapeutic efficacy of Transcranial Magnetic Stimulation (TMS) for major depressive disorder (MDD) is well established, less is known about the technique's efficacy for treating comorbid anxiety. (2) Methods: Data were retrospectively analyzed from randomized controlled trials (RCTs) that used Deep TMS with the H1 Coil for MDD treatment. The primary endpoint was the difference relative to sham treatment following 4 weeks of stimulation. The effect size was compared to literature values for superficial TMS and medication treatments. (3) Results: In the pivotal RCT, active Deep TMS compared with sham treatment showed significantly larger improvements in anxiety score (effect size = 0.34, p = 0.03 (FDR)) which were sustained until 16 weeks (effect size = 0.35, p = 0.04). The pooled effect size between all the RCTs was 0.55, which compares favorably to alternative treatments. A direct comparison to Figure-8 Coil treatment indicated that treatment with the H1 Coil was significantly more effective (p = 0.042). In contrast to previously reported studies using superficial TMS and medication for which anxiety has been shown to be a negative predictor of effectiveness, higher baseline anxiety was found to be predictive of successful outcome for the H1-Coil treatment. (4) Conclusions: Deep TMS is effective in treating comorbid anxiety in MDD and, unlike alternative treatments, the outcome does not appear to be adversely affected by high baseline anxiety levels.

Deep TMS H7 Coil: Features, Applications & Future.

INTRODUCTION: Transcranial magnetic stimulation (TMS) uses magnetic pulses to induce electrical current in the underlying neuronal tissue. A variety of TMS coils exist on the market, differing primarily in configuration, orientation, and flexibility of the wire windings of the coil. Deep TMSTM utilizes H-Coils, flexible coils with different configurations for stimulating different brain regions implicated in different neuropsychiatric disorders. The H7 Coil, designed to target primarily the medial prefrontal cortex and the anterior cingulate cortex, is FDA-cleared for obsessive-compulsive disorder (OCD). It was chosen as the focus of this review since it recently showed promise in various neuropsychiatric populations in addition to growing understanding of its mechanism of action (MOA). AREAS COVERED: Here we assembled all peer-reviewed publications on the H7 Coil to showcase its efficacy in: (a) various OCD patient populations (e.g., different degrees of symptom severity, treatment resistance, comorbidities) (b) other neuropsychiatric populations (e.g., addiction, major depressive disorder and autism spectrum disorder). EXPERT OPINION: While substantial evidence pertaining to the H7 Coil's efficacy as well as its MOA has accumulated, much work remains. In the final section of this review, we highlight areas of ongoing and future research that will further elucidate the coil's MOA as well as its full efficacy potential.

Real-world efficacy of deep TMS for obsessive-compulsive disorder: Post-marketing data collected from twenty-two clinical sites.

BACKGROUND: Deep transcranial magnetic stimulation (dTMS) with the H7-coil was FDA cleared for obsessive-compulsive disorder (OCD) in August 2018 based on multicenter sham-controlled studies. Here we look at the efficacy of dTMS for OCD in real world practices. METHODS: All dTMS clinics were asked to supply their data on treatment details and outcome measures. The primary outcome measure was response, defined by at least a 30% reduction in the Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline to endpoint. Secondary outcome measures included first response, defined as the first time the YBOCS score has met response criteria, and at least one-month sustained response. Analyses included response rate at the endpoint (after 29 dTMS sessions), number of sessions and days required to reach first response and sustained response. RESULTS: Twenty-two clinical sites with H7-coils provided data on details of treatment and outcome (YBOCS) measures from a total of 219 patients. One-hundred-sixty-seven patients who had at least one post-baseline YBOCS measure were included in the main analyses. Overall first and sustained response rates were 72.6% and 52.4%, respectively. The response rate was 57.9% in patients who had YBOCS scores after 29 dTMS sessions. First response was achieved in average after 18.5 sessions (SD = 9.4) or 31.6 days (SD = 25.2). Onset of sustained one-month response was achieved in average after 20 sessions (SD = 9.8) or 32.1 days (SD = 20.5). Average YBOCS scores demonstrated continuous reduction with increasing numbers of dTMS sessions. CONCLUSIONS: In real-world clinical practice, the majority of OCD patients benefitted from dTMS, and the onset of improvement usually occurs within 20 sessions. Extending the treatment course beyond 29 sessions results in continued reduction of OCD symptoms, raising the prospect of value for extended treatment protocols in non-responders.

Differential magnetic resonance neurofeedback modulations across extrinsic (visual) and intrinsic (default-mode) nodes of the human cortex.

Previous advances in magnetic resonance imaging allow the analysis of blood oxygen level-dependent signals in real time, thus opening the possibility of feeding an index of these signals back to scanned human participants. However, it is still not known to what extent different cortical networks may differ in their sensitivity to such internally generated neurofeedback (NF). Here, we compare NF efficacy across six cortical regions including: early and high-order visual areas and the posterior parietal lobe, a prominent node of the default mode network (DMN). Our results reveal a consistent difference in NF activation across these areas. Sham controls ruled out a role of attention/arousal in these effects. These differences are suggestive of a relationship to the relative reliance on intrinsic information, moving from early visual cortex (lowest) to the DMN (highest). Interestingly, the visual parahippocampal place area showed NF activation closer to the DMN node. The results are compatible with the notion of the DMN as an intrinsically oriented system.

Neurocognitive biases and the patterns of spontaneous correlations in the human cortex.

When the brain is 'at rest', spatiotemporal activity patterns emerge spontaneously, that is, in the absence of an overt task. However, what these patterns reveal about cortical function remains elusive. In this article, we put forward the hypothesis that the correlation patterns among these spontaneous fluctuations (SPs) reflect the profile of individual a priori cognitive biases, coded as synaptic efficacies in cortical networks. Thus, SPs offer a new means for mapping personal traits in both neurotypical and atypical cases. Three sets of observations and related empirical evidence provide support for this hypothesis. First, SPs correspond to activation patterns that occur during typical task performance. Second, individual differences in SPs reflect individual biases and abnormalities. Finally, SPs can be actively remodeled in a long-term manner by focused and intense cortical training.

The day-after effect: long term, Hebbian-like restructuring of resting-state fMRI patterns induced by a single epoch of cortical activation.

During rest, the cerebral cortex displays rich, coordinated patterns of spontaneous activity. The mechanism that shapes these patterns is largely unknown. Here we demonstrate that a Hebbian-like, sustained process plays a role in focusing these coherent patterns. Human subjects used an fMRI-based neurofeedback (NF) paradigm to intensely activate the dorsal anterior cingulate cortex for a single epoch (30 min). Resting-state correlations between all of the cortical voxels' BOLD time courses (functional connectivity) were mapped before, immediately after, and one day after the NF session. We found that the single epoch of cortical activation induced a lasting restructuring of the functional connections according to a Hebbian-like rule. Therefore, the change (increase and decrease) in functional connectivity strength of cortical voxels during rest reflected the level of their prior coactivation during the NF epoch. Interestingly, the effect was significantly enhanced 1 d after the NF activation epoch. The effect was evident in each subject individually, indicating its potential as a diagnostic window into the personal history of prior brain activations of both healthy and abnormal individuals.

Stimulus-free thoughts induce differential activation in the human default network.

Despite extensive research of the Default network, a set of regions which tend to reduce their activity relative to rest in response to stimulus-driven tasks, its function is still debated. Specifically, it is still not clear to what extent the activation profile of this network is driven by processes related to external stimulation (inhibitory or anticipatory), or is driven by specific thought contents. To address this question, we examined the ability of thoughts, generated in the absence of external stimulation, to modulate default network activation. In a set of experiments, several types of long lasting stimulus-free thoughts were elicited by brief (<1s) auditory cues. Sustained (40s) brain activations, far outlasting the cue, were demonstrated during these stimulus-free conditions. Importantly, brain activity in the default network showed a striking modulation associated with stimulus-free thought content. More specifically, a preferential activation was observed in essentially the entire default network during volitional-prospection thoughts when compared to the other stimulus-free thought conditions. Furthermore, several regions of the default network showed long-lasting above rest activations during the volitional-prospection condition. Our results demonstrate that default network activation can be modulated in the absence of external stimuli, thus pointing to the importance of thought-content in default-network specialization. Furthermore, together with previous research, these results support the notion that intrinsically oriented processing is a core specialization of the default network. Finally, our stimulus-free experimental paradigm introduces a new method for studying default network functionality.