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In transcranial magnetic stimulation (TMS), pulsed magnetic fields are applied to the brain, typically requiring high-power stimulators with high voltages and low series impedance. TMS pulse generators for small animal coils, are underexplored, with limited dedicated circuits and simulation models. Here, we present a new design for a high-power TMS pulse generator for small animals, utilizing a pre-charged supercapacitor that is sufficient to produce repeated pulses for TMS applications without the need for recharging. This approach eliminates the need for expensive high-voltage components and a high-voltage power supply. In this paper, we detail the design approach and basic block diagrams of a supercapacitor (SC) based TMS pulse generator, along with its experimental results. The findings indicate that the new circuit enables a complete test using just a single charge of an SC module. The proposed circuit functions as a versatile pulse-shaping device, where the MOSFET is treated as a dynamically varying resistor element rather than a traditional switch; allowing pulse parameter variations. We analyze a novel circuit for generating and controlling TMS pulses in small animal coils, and demonstrate its effectiveness through experimental results., (Creative Commons Attribution license.)

Objectives: This study aimed to investigate the analgesic effects of H-coil repetitive transcranial magnetic stimulation (rTMS) primarily targeting the hand area of the primary motor cortex (M1) in patients with peripheral neuropathic pain. Given that the H-coil has a wider reach than conventional coils, there is a possibility that targeting the hand motor cortex also may stimulate prefrontal areas. Thus, we also aimed to examine whether rTMS with an M1 target could produce effects on psychologic outcomes., Materials and Methods: In total, 17 patients were randomly assigned to receive active or sham H-coil rTMS in a counterbalanced order. After a nine-week washout period, they crossed over to either active or sham rTMS, according to a double-blind crossover design. Each treatment period consisted of five daily rTMS sessions and a one- and three-week follow-up visit. The primary outcome was average usual pain intensity. Secondary outcomes included pain unpleasantness, dynamic and static mechanical allodynia, anxiety and depression, sleep, pain catastrophizing, function, and patients' impression of change. Effects of rTMS were investigated using linear mixed model analyses., Results: We found two significant interactions between treatment and time, indicating that active H-coil rTMS induced significant analgesic effects (t [134] = -2.18; p = .03; d = -0.10) and significant reductions in anxiety and depression compared with sham stimulation over the treatment course (t [73] = -2.14; p = .04; d = -0.09). The analgesic effect occurred two weeks after the treatment, and the effect on anxiety and depression occurred three weeks after treatment. No other significant interactions were found for the secondary variables., Conclusions: Five days of H-coil rTMS targeting the hand area of M1 induced statistically significant effects on pain intensity. Moreover, rTMS improved symptoms of anxiety and depression, possibly because of the wide and deep reach of the H-coil., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT05488808., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The increasing demand for precise neuromodulation necessitates advancements in techniques to achieve higher spatial resolution. Magnetic stimulation, offering low signal attenuation and minimal tissue damage, plays a significant role in neuromodulation. Conventional transcranial magnetic stimulation (TMS), though noninvasive, lacks the spatial resolution and neuron selectivity required for spatially precise neuromodulation. To address these limitations, the next generation of magnetic neurostimulation technologies aims to achieve submillimeter-resolution and selective neuromodulation with high temporal resolution. Invasive and nanoinvasive magnetic neurostimulation are two next-generation approaches: invasive methods use implantable microcoils, while nanoinvasive methods use magnetic nanoparticles (MNPs) to achieve high spatial and temporal resolution of magnetic neuromodulation. This review will introduce the working principles, technical details, coil designs, and potential future developments of these approaches from an engineering perspective. Furthermore, the review will discuss state-of-the-art microfabrication in depth due to its irreplaceable role in realizing next-generation magnetic neuromodulation. In addition to reviewing magnetic neuromodulation, this review will cover through-silicon vias (TSV), surface micromachining, photolithography, direct writing, and other fabrication technologies, supported by case studies, providing a framework for the integration of magnetic neuromodulation and microelectronics technologies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Electromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC)., Objective: To compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil., Methods: Nine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120 % RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal while stimulating the primary motor cortex., Results: RMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100 % coil-specific RMT sounded like Cool-B65 at 34 % RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS- DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation., Conclusions: The stimulation efficiency of qTMS-DCC matched Cool-B65 while having substantially lower perceived loudness and auditory-evoked potentials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.L.K.M., L.M.K, S.M.G, and A.V.P. are inventors on patents and patent applications on quiet TMS. L.M.K. has received patent royalties from Nexstim and consulting fees from Ampa Health. N.B.P serves on the medical and scientific advisory board of the Dystonia Medical Research Foundation. S.M.G. is inventor on patents on brain stimulation technology and has received research funding, royalties, or consulting fees from Magstim, Rogue Research, and Ampa Health. A.V.P. is an inventor on patents on TMS technology and has received equity options, scientific advisory board membership, and consulting fees from Ampa Health; patent royalties and consulting fees from Rogue Research; consulting fees and equity options from Magnetic Tides; and consulting fees from Soterix Medical; equipment loan from MagVenture; and research funding from Motif. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone "deep" TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD)., Methods: Sixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted., Results: Subjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups., Conclusions: SMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Magnetic stimulation, represented by transcranial magnetic stimulation (TMS), is used to treat neurological diseases. Various strategies have been explored to improve the spatial resolution of magnetic stimulation. While reducing the coil size is the most impactful approach for increasing the spatial resolution, it decreases the stimulation intensity and increases heat generation., Objective: We aim to demonstrate the feasibility of magnetic stimulation using an epidurally implanted millimeter-sized coil and that it does not damage the cortical tissue via heating even when a repetitive stimulation protocol is used., Methods: A coil with dimensions of 3.5 × 3.5 × 2.6 mm 3 was epidurally implanted on the left motor cortex of rat, corresponding to the right hindlimb. Before and after epidural magnetic stimulation using a quadripulse stimulation (QPS) protocol, changes in the amplitude of motor evoked potentials (MEPs) elicited by a TMS coil were compared., Results: The experimental group showed an average increase of 88 % in MEP amplitude in the right hindlimb after QPS, whereas the MEP amplitude in the left hindlimb increased by 18 % on average. The control group showed no significant change in MEP amplitude after QPS in either hindlimb. The temperature changes at the coil surface remained <2 °C during repetitive stimulation, meeting the thermal safety limit for implantable medical devices., Conclusion: These results demonstrate the feasibility of epidural magnetic stimulation using an implantable coil to induce neuromodulation effects. This novel method is expected to be a promising alternative for focal magnetic stimulation with an improved spatial resolution and lowered stimulus current than previous magnetic stimulation methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although transcranial magnetic stimulation (TMS) has become a valuable method for non-invasive brain stimulation, the cellular basis of TMS activation of neurons is still not fully understood. In vitro preparations have been used to understand the biophysical mechanisms of TMS, but in many cases these studies have encountered substantial difficulties in activating neurons., Objective/hypothesis: The hypothesis of this work is that conductivity boundaries can have large effects on the electric field in commonly used in vitro preparations. Our goal was to analyze the resulting difficulties in in vitro TMS using a simulation study, using a charge-based boundary element model., Methods: We decomposed the total electric field into the sum of the primary electric field, which only depends on coil geometry and current, and the secondary electric field arising from conductivity boundaries, which strongly depends on tissue and chamber geometry. We investigated the effect of the conductivity boundaries on the electric field strength for a variety of in vitro experimental settings to determine the sources of difficulty., Results: We showed that conductivity boundaries can have large effects on the electric field in in vitro preparations. Depending on the geometry of the air-saline and the saline-tissue interfaces, the secondary electric field can significantly enhance, or attenuate the primary electric field, resulting in a much stronger or weaker total electric field inside the tissue; we showed this using a realistic preparation. Submerged chambers are generally much more efficient than interface chambers since the secondary field due to the thin film of saline covering the tissue in the interface chamber opposes the primary field and significantly reduces the total field in the tissue placed in the interface chamber. The relative dimensions of the chamber and the TMS coil critically determine the total field; the popular setup with a large coil and a small chamber is particularly sub-optimal because the secondary field due to the air-chamber boundary opposes the primary field, thereby attenuating the total field. The form factor (length vs width) of the tissue in the direction of the induced field can be important since a relatively narrow tissue enhances the total field at the saline-tissue boundary., Conclusions: Overall, we found that the total electric field in the tissue is higher in submerged chambers, higher if the chamber size is larger than the coil and if the shorter tissue dimension is in the direction of the electric field. Decomposing the total field into the primary and secondary fields is useful for designing in vitro experiments and interpreting the results., Competing Interests: Declaration of competing interest Dr. Sergey Makaroff and Dr. Yoshio Okada are named inventors in patents and patent applications related to TMS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the cortex. Concurrent functional magnetic resonance imaging can show changes in TMS-induced activity in the whole brain, with the potential to inform brain function research and to guide the development of TMS therapy. However, the interaction of the strong current pulses in the TMS coil in the static main magnetic field of the MRI produces high Lorentz forces, which may damage the coil enclosure and compromise the patient's safety. We studied the time-dependent mechanical behavior and durability of two multi-locus TMS (mTMS) coil arrays inside a high-field MRI bore with finite element modeling. In addition, coil arrays were built and tested based on the simulation results. We found that the current pulses produce shock waves and time-dependent stress distribution in the coil plates. The intensity and location of the maximum stress depend on the current waveform, the coil combination, and the transducer orientation relative to the MRI magnetic field. We found that 30% glass-fiber-filled polyamide is the most durable material out of the six options studied. In addition, novel insights for more durable TMS coil designs were obtained. Our study contributes to a comprehensive understanding of the underlying mechanisms responsible for the structural failure of mTMS coil arrays during stimulation within high static magnetic fields. This knowledge is essential for developing mechanically stable and safe mTMS-MRI transducers., (Creative Commons Attribution license.)

Objective: The objective of this study was to analyze the safety and efficacy of using a robotic hip exoskeleton designed by Samsung Electronics Co., Ltd., Korea, called the Gait Enhancing and Motivating System-Hip (GEMS-H), in assistance mode only with the poststroke population in an outpatient-rehabilitation setting., Methods: Forty-one participants with an average age of 60 and average stroke latency of 6.5 years completed this prospective, single arm, interventional, longitudinal study during the COVID-19 pandemic. Significant modifications to the traditional outpatient clinical environment were made to adhere to organizational physical distancing policies as well as guidelines from the Centers for Disease Control. All participants received gait training with the GEMS-H in assistance mode for 18 training sessions over the course of 6-8 weeks. Performance-based and self-reported clinical outcomes were assessed at four time points: baseline, midpoint (after 9 training sessions), post (after 18 training sessions), and 1-month follow up. Daily step count was also collected throughout the duration of the study using an ankle-worn actigraphy device. Additionally, corticomotor excitability was measured at baseline and post for 4 bilateral lower limb muscles using transcranial magnetic stimulation., Results: By the end of the training program, the primary outcome, walking speed, improved by 0.13 m/s (p < 0.001). Secondary outcomes of walking endurance, balance, and functional gait also improved as measured by the 6-Minute Walk Test (47 m, p < 0.001), Berg Balance Scale (2.93 points, p < 0.001), and Functional Gait Assessment (1.80 points, p < 0.001). Daily step count significantly improved with and average increase of 1,750 steps per day (p < 0.001). There was a 35% increase in detectable lower limb motor evoked potentials and a significant decrease in the active motor threshold in the medial gastrocnemius (-5.7, p < 0.05) after training with the device., Conclusions: Gait training with the GEMS-H exoskeleton showed significant improvements in walking speed, walking endurance, and balance in persons with chronic stroke. Day-to-day activity also improved as evidenced by increased daily step count. Additionally, corticomotor excitability changes suggest that training with this device may help correct interhemispheric imbalance typically seen after stroke., Trial Registration: This study is registered with ClinicalTrials.gov (NCT04285060)., (© 2024. The Author(s).)

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) has important applications both in the exploration of mental disorder causes and the treatment of mental disorders. During the stimulation, the TMS system generates the intracranial time-varying induced E-field (E-field), which alters the membrane potential of neurons and subsequently exerts neural regulatory effects. The temporal waveform of the induced E-fields is directly related to the stimulation effect. To meet the needs of scientific research on diversified stimulation waveforms and flexible adjustable stimulation parameters, a novel efficient pulse magnetic stimulation circuit (the EPMS circuit) design based on asymmetric cascaded multilevel technology is proposed in this paper. Based on the transient analysis of the discharge circuit, this circuit makes it possible to convert the physical quantity (the intracranial induced E-field) that needs to be measured after magnetic stimulation into easily analyzable electrical signals (the discharge voltage at both ends of the stimulation coil in the TMS circuit). This EPMS circuit can not only realize monophasic and biphasic cosine-shaped intracranial induced E-fields, which are widely used in the market, but also realize three types of new intracranial induced E-field stimulation waveform with optional amplitude and adjustable pulse width, including monophasic near-rectangular, biphasic near-rectangular and monophasic/biphasic ladder-shaped stimulation waveform, which breaks through the limitation of the stimulation waveform of traditional TMS systems. Among the new waveforms produced by the EPMS circuit, further research was conducted on the dynamic response characteristics of neurons under the stimulation of the biphasic four-level waveform (the BFL waveform) with controllable parameters. The relationship between TMS circuit parameters (discharge voltage level and duration) and corresponding neural response characteristics (neuron membrane potential change and neuronal polarizability ratio) was explained from a microscopic perspective. Accordingly, the biological physical quantities (neuronal membrane potential) that are difficult to measure can be transformed into easily analyzable electrical signals (the discharge voltage level and duration). Results showed that compared with monophasic and biphasic cosine induced E-fields with the same energy loss, the neuron polarization ratio is decreased by 54.5% and 87.5%, respectively, under the stimulation of BFL waveform, which could effectively enhance the neuromodulation effect and improve the stimulation selectivity.

Introduction: Transcranial magnetic stimulation (TMS) is a popular method for the noninvasive stimulation of neurons in the brain. It has become a standard instrument in experimental brain research and has been approved for a range of diagnostic and therapeutic applications. These applications require appropriately shaped coils. Various applications have been established or approved for specific coil designs with their corresponding spatial electric field distributions. However, the specific coil implementation may no longer be appropriate from the perspective of available material and manufacturing opportunities or considering the latest understanding of how to achieve induced electric fields in the head most efficiently. Furthermore, in some cases, field measurements of coils with unknown winding or a user-defined field are available and require an actual implementation. Similar applications exist for magnetic resonance imaging coils., Objective: This work aims at introducing a complete formalism free from heuristics, iterative optimization, and ad-hoc or manual steps to form practical stimulation coils with individual turns to either equivalently match an existing coil or produce a given field. The target coil can reside on practically any sufficiently large or closed surface adjacent to or around the head., Methods: The method derives an equivalent field through vector projection exploiting the well-known Huygens' and Love's equivalence principle. In contrast to other coil design or optimization approaches recently presented, the procedure is an explicit forward Hilbert-space vector projection or basis change. For demonstration, we map a commercial figure-of-eight coil as one of the most widely used devices and a more intricate coil recently approved clinically for addiction treatment (H4) onto a bent surface close to the head for highest efficiency and lowest field energy., Results: The resulting projections are within ≤4% of the target field and reduce the necessary pulse energy by more than 40%.

(1) Background: This study evaluates the effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in improving gait in post-stroke hemiplegic patients, using wearable sensor technology for objective gait analysis. (2) Methods: A total of 72 stroke patients were randomized into control, sham stimulation, and LF-rTMS groups, with all receiving standard medical treatment. The LF-rTMS group underwent stimulation on the unaffected hemisphere for 6 weeks. Key metrics including the Fugl-Meyer Assessment Lower Extremity (FMA-LE), Berg Balance Scale (BBS), Modified Barthel Index (MBI), and gait parameters were measured before and after treatment. (3) Results: The LF-rTMS group showed significant improvements in the FMA-LE, BBS, MBI, and various gait parameters compared to the control and sham groups ( p < 0.05). Specifically, the FMA-LE scores improved by an average of 5 points (from 15 ± 3 to 20 ± 2), the BBS scores increased by 8 points (from 35 ± 5 to 43 ± 4), the MBI scores rose by 10 points (from 50 ± 8 to 60 ± 7), and notable enhancements in gait parameters were observed: the gait cycle time was reduced from 2.05 ± 0.51 s to 1.02 ± 0.11 s, the stride length increased from 0.56 ± 0.04 m to 0.97 ± 0.08 m, and the walking speed improved from 35.95 ± 7.14 cm/s to 75.03 ± 11.36 cm/s (all p < 0.001). No adverse events were reported. The control and sham groups exhibited improvements but were not as significant. (4) Conclusions: LF-rTMS on the unaffected hemisphere significantly enhances lower-limb function, balance, and daily living activities in subacute stroke patients, with the gait parameters showing a notable improvement. Wearable sensor technology proves effective in providing detailed, objective gait analysis, offering valuable insights for clinical applications in stroke rehabilitation.

Background: The operation of a transcranial magnetic stimulation (TMS) coil produces high-intensity impulse sounds. In TMS, a magnetic field is generated by a short-duration pulse in the range of thousands of amperes in the TMS coil. When placed in a strong magnetic field, such as inside a magnetic resonance imaging (MRI) bore, the interaction of the magnetic field and the current in the TMS coil can cause strong forces on the coil casing. The strengths of these forces depend on the coil orientation in the main magnetic field (B 0 ). Part of the energy in this process is dissipated in the form of acoustic noise., Objective: Our objective was to measure the sound pressure levels (SPL) of TMS "click" sounds created by commercial TMS stimulators and coils in a typical environment and inside a 3-T MRI scanner and advance the knowledge of the acoustic behaviour of TMS to safely conduct TMS alone as well as concurrently with functional MRI (fMRI)., Methods: We report SPL measurements of two commercial MRI-compatible TMS systems in the 3-T B 0 field of an MRI scanner and in the earth's magnetic field. Also, we present the acoustic noise measurements of four commercial TMS stimulators and three different TMS coils in a typical operational environment without the B 0 field., Results: The maximum peak SPL measured was 158 dB(C) inside the 3-T MRI scanner. Outside the scanner, the maximum peak SPL was 117 dB(C). Inside the scanner, the peak SPL increased by 21-45 dB(C) depending on the stimulator and the orientation of the electric field relative to the B field., Conclusions: Hearing protection is obligatory during concurrent TMS-fMRI experiments and highly recommended during any TMS experiment. The manufacturing of quieter TMS systems is encouraged to reduce the risk of hearing damage and other unwanted effects., Competing Interests: Declaration of competing interest Risto J. Ilmoniemi is founder, past CEO, advisor, and a minority shareholder of Nexstim Plc. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective. Magnetic stimulation using implantable devices may offer a promising alternative to other stimulation methods such as transcranial magnetic stimulation (TMS) or electric stimulation using implantable devices. This alternative may increase the selectivity of stimulation compared to TMS, and eliminate the need to expose tissue to metals in the body, as is required in electric stimulation using implantable devices. However, previous studies of magnetic stimulation of the sciatic nerve used large coils, with a diameter of several tens of mm, and a current intensity in the order of kA. Approach. Since such large coils and high current intensity are not suitable for implantable devices, we investigated the feasibility of using a smaller implantable coil and lower current to elicit neuronal responses. A coil with a diameter of 3 mm and an inductance of 1 mH was used as the implantable stimulator. Main results. Before in vivo experiments, we used 3D computational models to estimate the minimum stimulus intensity required to elicit neuronal responses, resulting in a threshold current above 3.5 A. In in vivo experiments, we observed successful nerve stimulation via compound muscle action potentials elicited in hind-limb muscles when the applied current was above 3.8 A, a significantly reduced current than that used in conventional magnetic stimulation. Significance. We report the feasibility of magnetic stimulation using an implantable millimeter-sized coil and low current of a few amperes to elicit neural responses in peripheral nerves. The proposed method is expected to be an alternative to TMS, with the merit of improved selectivity in stimulation, and to electrical stimulation based on implantable devices, with the merit of avoiding the exposure of conducting metals to neural tissues., (© 2023 IOP Publishing Ltd.)

Background: Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition., Objective: We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities., Methods: Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group)., Results: The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up., Conclusion: These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

Objective: Here we bring a neurophysiological diagnostic tool, based on pathophysiologically-relevant brain region, that is critical for reducing the variability between clinicians, and necessary for quantitative measures of ADHD severity., Methods: 54 healthy and 57 ADHD adults participated in the study. Electroencephalography (EEG) was recorded when combined with transcranial magnetic stimulation (TMS) over the right prefrontal cortex and also recorded during the Stop Signal task., Results: TMS evoked potentials (TEPs) and the event related potential (ERP) components in the Stop Signal task were found to be significantly reduced in ADHD relative to the matched healthy controls. Stop signal reaction time (SSRT) and stopping accuracy was found to correlate with the ERP signal, and ADHD severity correlated with the TEP signal. Cortical activity (early TEP and Stop Signal ERP) diagnostic model yielded accuracy of 72%., Conclusion: TEPs and ERPs reveal that right PFC excitability was associated with ADHD severity, and with behavioral impulsivity - as a hallmark of ADHD pathology. This electrophysiological biomarker supports the potential of objective diagnosis for ADHD., Significance: Such tools would allow better assessment of treatment efficacy and prognosis, may advance understanding of the pathophysiology of the disease and better the public's attitudes and stigma towards ADHD., Trial Registration: Trial to Evaluate the Efficacy of the HLPFC Coil Deep Transcranial Magnetic Stimulation System in Treating Attention Deficit and Hyperactivity Disorder (ADHD) in Adults, https://clinicaltrials.gov/ct2/show/NCT01737476, ClinicalTrials.govnumberNCT01737476., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Transcranial Magnetic Stimulation (TMS) inverse problem (TMS-IP) investigated in this study aims to focus the TMS induced electric field close to a specified target point defined on the gray matter interface in the M1 HAND area while otherwise minimizing it. The goal of the study is to numerically evaluate the degree of improvement of the TMS-IP solutions relative to the well-known sulcus-aligned mapping (a projection approach with the 90 ∘ local sulcal angle). In total, 1536 individual TMS-IP solutions have been analyzed for multiple target points and multiple subjects using the boundary element fast multipole method (BEM-FMM) as the forward solver. Our results show that the optimal TMS inverse-problem solutions improve the focality - reduce the size of the field "hot spot" and its deviation from the target - by approximately 21-33% on average for all considered subjects, all observation points, two distinct coil types, two segmentation types, two intracortical observation surfaces under study, and three tested values of the field threshold. The inverse-problem solutions with the maximized focality simultaneously improve the TMS mapping resolution (differentiation between neighbor targets separated by approximately 10 mm) although this improvement is quite modest. Coil position/orientation and conductivity uncertainties have been included into consideration as the corresponding de-focalization factors. The present results will change when the levels of uncertainties change. Our results also indicate that the accuracy of the head segmentation critically influences the expected TMS-IP performance., (Published by Elsevier Inc.)

Objectives: Previous studies have examined the effect of transcranial direct current stimulation (tDCS) on the in-vivo concentrations of neuro-metabolites assessed through magnetic resonance spectroscopy (MRS) in neurological and psychiatry disorders. This review aims to systematically evaluate the data on the effect of tDCS on MRS findings and thereby attempt to understand the potential mechanism of tDCS on neuro-metabolites., Methods: The relevant literature was obtained through PubMed and cross-reference (search till June 2020). Thirty-four studies were reviewed, of which 22 reported results from healthy controls and 12 were from patients with neurological and psychiatric disorders., Results: The evidence converges to highlight that tDCS modulates the neuro-metabolite levels at the site of stimulation, which, in turn, translates into alterations in the behavioural outcome. It also shows that the baseline level of these neuro-metabolites can, to a certain extent, predict the outcome after tDCS. However, even though tDCS has shown promising effects in alleviating symptoms of various psychiatric disorders, there are limited studies that have reported the effect of tDCS on neuro-metabolite levels., Conclusions: There is a compelling need for more systematic studies examining patients with psychiatric/neurological disorders with larger samples and harmonised tDCS protocols. More studies will potentially help us to understand the tDCS mechanism of action pertinent to neuro-metabolite levels modulation. Further, studies should be conducted in psychiatric patients to understand the neurological changes in this population and potentially unravel the neuro-metabolite × tDCS interaction effect that can be translated into individualised treatment.

The evaluation of transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) promises valuable information about fundamental brain related mechanisms and may serve as a diagnostic tool for clinical monitoring of therapeutic progress or surgery procedures. However, reports about spontaneous fluctuations of MEP amplitudes causing high intra-individual variability have led to increased concerns about the reliability of this measure. One possible cause for high variability of MEPs could be neuronal oscillatory activity, which reflects fluctuations of membrane potentials that systematically increase and decrease the excitability of neuronal networks. Here, we investigate the dependence of MEP amplitude on oscillation power and phase by combining the application of single pulse TMS over the primary motor cortex with concurrent recordings of electromyography and electroencephalography. Our results show that MEP amplitude is correlated to alpha phase, alpha power as well as beta phase. These findings may help explain corticospinal excitability fluctuations by highlighting the modulatory effect of alpha and beta phase on MEPs. In the future, controlling for such a causal relationship may allow for the development of new protocols, improve this method as a (diagnostic) tool and increase the specificity and efficacy of general TMS applications., Competing Interests: The authors declare no competing conflict of interest.

This article discusses the contribution of fMRI- and fMRI-EEG-neurofeedback into recovery of motor function in two subacute stroke patients during the early post-stroke period. Premotor and supplementary motor zones of the cortex were chosen as the targets of voluntary control. Patient 1 received 6 sessions of motor imagery-based fMRI neurofeedback of secondary motor areas activity and Patient 2 received a similar course with the addition of μ- and β-EEG activity suppression. Both reduced the motor deficit severity, improved on the quality of life, and increased the C3/C4 coherence to other central leads within EEG μ-band. Patient 1 reliably increased the fMRI signal in target areas and improved on the strength and speed of hand movements. Patient 2 (fMRI-EEG) mastered the EEG activity regulation to a greater degree. The authors conclude that pure fMRI neurofeedback and bi-modal fMRI-EEG neurofeedback produce different clinical effects in motor rehabilitation, which confirms the prospect of the closed-loop stroke treatment., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Burn survivors experience myriad associated symptoms such as pain, pruritus, fatigue, impaired motor strength, post-traumatic stress, depression, anxiety, and sleep disturbance. Many of these symptoms are common and remain chronic, despite current standard of care. One potential novel intervention to target these post burn symptoms is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation (NIBS) technique that modulates neural excitability of a specific target or neural network. The aim of this work is to review the neural circuits of the aforementioned clinical sequelae associated with burn injuries and to provide a scientific rationale for specific NIBS targets that can potentially treat these conditions. We ran a systematic review, following the PRISMA statement, of tDCS effects on burn symptoms. Only three studies matched our criteria. One was a feasibility study assessing cortical plasticity in chronic neuropathic pain following burn injury, one looked at the effects of tDCS to reduce pain anxiety during burn wound care, and one assessed the effects of tDCS to manage pain and pruritus in burn survivors. Current literature on NIBS in burn remains limited, only a few trials have been conducted. Based on our review and results in other populations suffering from similar symptoms as patients with burn injuries, three main areas were selected: the prefrontal region, the parietal area and the motor cortex. Based on the importance of the prefrontal cortex in the emotional component of pain and its implication in various psychosocial symptoms, targeting this region may represent the most promising target. Our review of the neural circuitry involved in post burn symptoms and suggested targeted areas for stimulation provide a spring board for future study initiatives., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Repeated neuromuscular electrical stimulation in type 1 Myotonic Dystrophy (DM1) has previously been shown to cause an increase in strength and a decrease in hyperexcitability of the tibialis anterior muscle., Objective: In this proof-of-principle study our objective was to test the hypothesis that noninvasive repetitive transcranial magnetic stimulation of the primary motor cortex (M1) with a new portable wearable multifocal stimulator causes improvement in muscle function in DM1 patients., Methods: We performed repetitive stimulation of M1, localized by magnetic resonance imaging, with a newly developed Transcranial Rotating Permanent Magnet Stimulator (TRPMS). Using a randomized within-patient placebo-controlled double-blind TRPMS protocol, we performed unilateral active stimulation along with contralateral sham stimulation every weekday for two weeks in 6 adults. Methods for evaluation of muscle function involved electromyography (EMG), hand dynamometry and clinical assessment using the Medical Research Council scale., Results: All participants tolerated the treatment well. While there were no significant changes clinically, EMG showed significant improvement in nerve stimulus-evoked compound muscle action potential amplitude of the first dorsal interosseous muscle and a similar but non-significant trend in the trapezius muscle, after a short exercise test, with active but not sham stimulation., Conclusions: We conclude that two-week repeated multifocal cortical stimulation with a new wearable transcranial magnetic stimulator can be safely conducted in DM1 patients to investigate potential improvement of muscle strength and activity. The results obtained, if confirmed and extended by future safety and efficacy trials with larger patient samples, could offer a potential supportive TRPMS treatment in DM1.

Currently, simulations of the induced currents in the brain produced by transcranial magnetic stimulation (TMS) are used to elucidate the regions reached by stimuli. However, models commonly found in the literature are too general and neglect imperfections in the windings. Aiming to predict the stimulation sites in patients requires precise modeling of the electric field (E-field), and a proper calibration to adequate to the empirical data of the particular coil employed. Furthermore, most fabricators do not provide precise information about the coil geometries, and even using X-ray images may lead to subjective interpretations. We measured the three components of the vector magnetic field induced by a TMS figure-8 coil with spatial resolutions of up to 1 mm. Starting from a computerized tomography-based coil model, we applied a multivariate optimization algorithm to automatically modify the original model and obtain one that optimally fits the measurements. Differences between models were assessed in a human brain mesh using the finite-elements method showing up to 6% variations in the E-field magnitude. Our calibrated model could increase the precision of the estimated E-field induced in the brain during TMS, enhance the accuracy of delivered stimulation during functional brain mapping, and improve dosimetry for repetitive TMS. Graphical Abstract Geometrical model of TMS coil based on TAC images is optimally deformed to match magnetic field measurements. The calibrated model's induced electric field in the brain differs from the original.

Abnormal neural activity, particularly in the rostrodorsal anterior cingulate cortex (rdACC), appears to be responsible for intense alcohol craving. Neuromodulation of the rdACC using cortical implants may be an option for individuals with treatment-resistant alcohol dependence. This study assessed the effectiveness and feasibility of suppressing alcohol craving using cortical implants of the rdACC using a controlled one-group pre- and post-test study design. Eight intractable alcohol-dependent participants (four males and four females) were implanted with two Lamitrode 44 electrodes over the rdACC bilaterally connected to an internal pulse generator (IPG). The primary endpoint, self-reported alcohol craving reduced by 60.7% (p = 0.004) post- compared to pre-stimulation. Adverse events occurred in four out of the eight participants. Electrophysiology findings showed that among responders, there was a post-stimulation decrease (p = 0.026) in current density at the rdACC for beta 1 band (13-18 Hz). Results suggest that rdACC stimulation using implanted electrodes may potentially be a feasible method for supressing alcohol craving in individuals with severe alcohol use disorder. However, to further establish safety and efficacy, larger controlled clinical trials are needed.

Background and Purpose: Repetitive transcranial magnetic stimulation (rTMS) may promote recovery of motor function after stroke by inducing functional reorganization of cortical circuits. The objective of this study was to examine whether multifocal cortical stimulation using a new wearable transcranial rotating permanent magnet stimulator (TRPMS) can promote recovery of motor function after stroke by inducing functional reorganization of cortical circuits., Methods: Thirty 30 patients with chronic ischemic stroke and stable unilateral weakness were enrolled in a Phase 1/2a randomized double-blind sham-controlled clinical trial to evaluate safety and preliminary efficacy. Bilateral hemispheric stimulation was administered for 20 sessions 40 min each over 4 weeks. The primary efficacy endpoint was the change in functional MRI BOLD activation immediately after end of treatment. Secondary efficacy endpoints were clinical scales of motor function, including the Fugl-Meyer motor arm score, ARAT, grip strength, pinch strength, gait velocity, and NIHSS., Results: TRPMS treatment was well-tolerated with no device-related adverse effects. Active treatment produced a significantly greater increase in the number of active voxels on fMRI than sham treatment (median +48.5 vs -30, p = 0.038). The median active voxel number after active treatment was 8.8-fold greater than after sham (227.5 vs 26, p = 0.016). Although the statistical power was inadequate to establish clinical endpoint benefits, numerical improvements were demonstrated in 5 of 6 clinical scales of motor function. The treatment effects persisted over a 3-month duration of follow-up., Conclusions: Multifocal bilateral TRPMS was safe and showed significant fMRI changes suggestive of functional reorganization of cortical circuits in patients with chronic ischemic stroke. A larger randomized clinical trial is warranted to verify recovery of motor function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used for the treatment of a great variety of neurological disorders. The technique involves applying a magnetic field in certain areas of the cerebral cortex in order to modify neuronal excitability outside the skull. However, the exact brain mechanisms underlying rTMS effects are not completely elucidated. For that purpose, and in order to generate a pulsed magnetic field, a half-bridge converter controlled by a microcontroller has been designed to apply rTMS in small animals. Moreover, the small size of the rodent head makes it necessary to design a magnetic transducer, with the aim of focusing the magnetic field on selected brain areas using a specific and a small magnetic head. Using such devices, our purpose was to compare the effects of five different rTMS dosages on rat brain metabolic activity. The experimental results showed that one day of stimulation leads to an enhancement of brain metabolic activity in cortical areas, meanwhile with three days of stimulation it is possible to also modify subcortical zones, results that were not found when extending the number of rTMS applications up to seven days. In consequence, the number of pulses delivered might be an important parameter in rTMS protocols, highlighting its importance in rTMS impact.

Objective: Insula neurocircuitry alterations are reported in a range of neuropsychiatric disorders holding promise for clinical interventions. We measured, in a pilot study, acute neuroplastic modulations resulting from high- and low-frequency stimulation with repetitive transcranial magnetic stimulation (rTMS) delivered via an H-coil that targeted the right insula and overlying prefrontal cortex., Methods: Healthy, nonsmoking, adult participants (N = 28), in a within-participant, sham-controlled experiment, received a single rTMS session on four separate days. Participants received one session each of low- (1 Hz) and high (10 Hz)-frequency stimulation and two sessions of sham stimulation matched to each rTMS frequency. After each rTMS session, participants completed a functional magnetic resonance imaging (fMRI) scan while performing two cognitive tasks and a resting-state scan. The effect of rTMS was examined on task behavior as well as blood oxygenated level-dependent (BOLD) response during task performance and resting state. We expected low- and high-frequency stimulation to decrease and increase, respectively, insula and overlying cortical BOLD signal and network connectivity., Results/conclusions: There was no effect of rTMS, regardless of frequency, on task behavior or task-based BOLD response. There was an effect of rTMS compared to sham on rsFC between insula and medial prefrontal cortex, with connectivity reduced after rTMS compared to sham, regardless of frequency. Implications for using rTMS to the insula as a treatment for neuropsychiatric disorders are discussed in light of insula-medial prefrontal cortex connectivity., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: This clinical trial evaluates the efficacy and safety of a 6-week course of daily neuroAD™ therapy., Methods: 131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini-Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for a prospective, randomized, double-blind, sham-controlled, multicenter clinical trial. Structural brain MRIs were obtained for transcranial magnetic stimulation targeting. Baseline Alzheimer's disease assessment scale-cognitive (ADAS-Cog) and Clinical Global Impression of Change were assessed. 129 participants were randomized to active treatment plus standard of care (SOC) or sham treatments plus SOC., Results: Subjects with baseline ADAS-Cog ≤ 30 (~85% of study population) showed a statistically significant benefit favoring active over sham. Responder analysis showed 31.7% participants in the active group with ≤ -4 point improvement on ADAS-Cog versus 15.4% in the sham group., Discussion: neuroAD™ Therapy System provides a low-risk therapeutic benefit for patients with milder AD (baseline ADAS-Cog ≤30) beyond pharmacologic SOC., (© 2020 the Alzheimer's Association.)

Background: Rodent models are fundamental in unraveling cellular and molecular mechanisms of transcranial magnetic stimulation (TMS)-induced effects on the brain. However, proper translation of human TMS protocols to animal models have been restricted by the lack of rodent-specific focal TMS coils., Objective: We aimed to improve TMS focalization in rodent brain with a novel small, cooled, and rodent-specific TMS coil., Methods: A rodent-specific 25-mm figure-of-eight TMS coil was developed. Stimulation focalization was simulated in silico for the rodent coil and a commercial human 50-mm figure-of-eight TMS coil. Both coils were also compared in vivo by electromyography measurements of brachialis motor evoked potential (MEP) responses to TMS at different brain sites in anesthetized rats (n = 6). Focalization was determined from the coils' level of stimulation laterality. Differences in MEPs were statistically analyzed with repeated-measures, within-subjects, ANOVA., Results: In silico simulation results deemed the human coil insufficient for unilateral stimulation of the rat motor cortex, whereas lateralized electrical field induction was projected attainable with the rodent coil. Cortical, in vivo MEP amplitude measurements from multiple points in each hemisphere, revealed unilateral activation of the contralateral brachialis muscle, in absence of ipsilateral brachialis activation, with both coils., Conclusion: Computer simulations motivated the design of a smaller rodent-specific TMS coil, but came short in explaining the capability of a larger commercial human coil to induce unilateral MEPs in vivo. Lateralized TMS, as demonstrated for both TMS coils, corroborates their use in translational rodent studies, to elucidate mechanisms of action of therapeutic TMS protocols., (© 2019 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.)

Objective: Interleaving TMS (transcranial magnetic stimulation) with fMRI (functional Magnetic Resonance Imaging) is a promising technique to study functional connectivity in the human brain, but its development is being restricted by technical limitations, such as that due to the interaction of the TMS current pulses with the magnetic fields of an MRI scanner. In this work, a TMS coil design method capable of controlling Lorentz forces experienced by the coil in the presence of static magnetic fields is presented., Approach: The suggested approach is based on an existing inverse boundary element method (IBEM) for TMS coil design, in which new electromagnetic computational models of the Lorentz forces have been included to be controlled in the design process., Main Results: To demonstrate the validity of this technique, it has been used for the design and simulation of TMS coils wound on rectangular flat, spherical and hemispherical surfaces with improved mechanical stability. The obtained results confirm that TMS coils with reduced Lorentz forces inside the static main field of an MRI scanner can be produced, which is achieved to the detriment of other coil performance parameters., Significance: The proposed approach provides an efficient tool to design TMS stimulators of a wide range of coil geometries with improved mechanical stability, which can be extremely useful to overcome current limitations for interleaved TMS-fMRI.

Deep transcranial magnetic stimulation (dTMS) is a non-invasive technique used for the treatment of depression and obsessive compulsive disorder. In this study, we computationally evaluated group-level dosage for dTMS to characterize the targeted deep brain regions to overcome the limitations of using individualized head models to characterize coil performance in a population. We used an inter-subject registration method adapted to the deep brain regions that enable projection of computed electric fields (EFs) from individual realistic head models (n  =  18) to the average space of deep brain regions. The computational results showed consistent group-level hotspots of the EF in the deep brain regions. The halo circular assembly coils induced the highest EFs in deep brain regions (up to 50% of the maximum EF in the cortex) for optimized positioning. In terms of the trade-off between field spread and penetration, the performance of the H7 coil was the best. The computational model allowed the optimization of generalized dTMS-induced EF on deep region targets despite inter-individual differences while informing and possibly minimizing unintended stimulation of superficial regions and possible mixed stimulation effects from deep and cortical areas. These results will facilitate the decision process during dTMS interventions in clinical practice.

Depressive brooding following a stressful event predicts negative affect and neuroendocrine responses related to psychological stress. The dorsolateral prefrontal cortex (DLPFC) has been associated with the top-down regulation of thoughts and emotions, and abnormal neural activity within this region has been associated with increased psychological stress and ruminative thinking. The aim of this study was to investigate whether the modulation of the DLPFC could have beneficial effects on ruminative thoughts and the endocrine response following a self-relevant stressor. Using a sham-controlled within-subjects crossover-design, two sessions of intermittent theta-burst stimulation (iTBS) were administered over the left DLPFC to thirty-eight healthy-volunteers after they were confronted with a social-evaluative stressor, the Trier Social Stress Test. To assess stress recovery, momentary rumination was measured before and after a resting period subsequent to the encounter with the stressor. In addition, cortisol levels were measured between and after the two iTBS sessions that were applied during the stress recovery phase. Overall, iTBS did not significantly influence ruminative thinking and cortisol secretion during the stress recovery phase. However, taking into account participants ruminative tendencies, our results revealed that for participants with higher levels of brooding ruminative thinking remained stable after iTBS, whereas in the sham condition there was a marginal significant increase in ruminative thinking. Moreover, only after iTBS, there was a significant reduction in cortisol secretion (i.e. a faster return to baseline as compared to sham) for high brooders during the recovery from the stressor. These results show that the prefrontal cortex plays a role in stress recovery mechanisms in individuals who are more vulnerable for psychopathology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Stimulating the cerebellum with transcranial magnetic stimulation is often perceived as uncomfortable. No study has systematically tested which coil design can effectively trigger a cerebellar response with the least discomfort., Objective: To determine the relationship between perceived discomfort and effectiveness of cerebellar stimulation using different coils: MagStim (70 mm, 110 mm-coated, 110-uncoated), MagVenture and Deymed., Methods: Using the cerebellar-brain inhibition (CBI) protocol, we conducted a CBI recruitment curve with respect to each participant's maximum tolerated-stimulus intensity (MTI) to assess how effective each coil was at activating the cerebellum., Results: Only the Deymed double-cone coil elicited CBI at low intensities (-20% MTI). At the MTI, the MagStim (110 mm coated/uncoated) and Deymed coils produced reliable CBI, whereas no CBI was found with the MagVenture coil., Conclusion: s: The Deymed double-cone coil was most effective at cerebellar stimulation at tolerable intensities. These results can guide coil selection and stimulation parameters when designing cerebellar TMS studies., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

With expanding knowledge of how neural circuitry is disrupted in substance use disorders (SUD), non-invasive brain stimulation (NIBS) techniques have emerged as potential strategies to directly modulate those neural circuits. There is some evidence supporting the two most common forms of NIBS, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), in the treatment of SUD. Yet results of recent studies have been mixed and critical methodological issues must be addressed before strong conclusions can be drawn. This review highlights recent evidence of NIBS for SUD, addressing the impact of stimulation on relevant clinical and cognitive outcomes in substance-using populations. Additionally, we aim to bring a clinical perspective to the opportunities and challenges of implementing neuromodulation in SUD treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Approximately 15% of all people will experience a depressive episode throughout their lives, and by 2020, depression will be the second largest cause of disability around the world. Transcranial magnetic stimulation (TMS) has been shown to be an effective option for treating this condition. Devices such as the double-cone coil may bring new insights regarding depression treatment., Methods: A literature search was performed on PubMed, ScienceDirect, Cochrane, LILACS, and Google Scholar by applying the descriptors "depression" AND "transcranial magnetic stimulation" AND "double cone-coil.", Results: Six studies were considered eligible (three clinical trials, two case series, and one isolated case report). All of them described treatments with transcranial magnetic stimulation by double-cone coil (DC-TMS) at 10 Hz over the dorsomedial prefrontal cortex, achieving response and remission rates of 40-52.4% and 34.7-47.6%, respectively. Two clinical trials investigated both intermittent theta-burst stimulation and 10 Hz TMS, suggesting a slight advantage of the latter. They also found no additional gains by combining both techniques., Conclusion: Despite the small number of controlled clinical trials and the small sample sizes, which limit the generalization of the obtained results, the collected data provide an optimistic perspective on the effectiveness of using DC-TMS for depression treatment., (© 2018 International Neuromodulation Society.)

Short-interval intracortical inhibition (SICI) has been studied with paired-pulse transcranial magnetic stimulation (TMS) by administering two pulses at a millisecond-scale interstimulus interval (ISI) to a single cortical target. It has, however, been difficult to study the interaction of nearby cortical targets with paired-pulse TMS. To overcome this limitation, we have developed a multi-locus TMS (mTMS) device, which allows controlling the stimulus location electronically. Here, we applied mTMS to study SICI in primary motor cortex with paired pulses targeted to adjacent locations, aiming to quantify the extent of the cortical region producing SICI in the location of a test stimulus. We varied the location and timing of the conditioning stimulus with respect to a test stimulus targeted to the cortical hotspot of the abductor pollicis brevis (APB) in order to study their effects on motor evoked potentials. We further applied a two-coil protocol with the conditioning stimulus given by an oval coil only to the surroundings of the APB hotspot, to which a subsequent test stimulus was administered with a figure-of-eight coil. The strongest SICI occurred at ISIs below 1 ms and at ISIs around 2.5 ms. These ISIs increased when the conditioning stimulus receded from the APB hotspot. Our two-coil paired-pulse TMS study suggests that SICI at ISIs of 0.5 and 2.5 ms originate from different mechanisms or neuronal elements., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Repetitive transcranial magnetic stimulation (rTMS) has become increasingly popular during the last decades mainly driven by the antidepressant effects of dorsolateral prefrontal cortex stimulation with "butterfly" coils. Only recently, alternative targets such as the dorsomedial prefrontal cortex (dmPFC) have been brought into focus and innovative coil designs such as the angled geometry of the double cone coil (DCC) have raised hope to reach even deeper located targets., Objective: To provide a systematic and comprehensive review on the application of rTMS stimulation of the dmPFC using the DCC in neuropathological and healthy samples., Methods: We systematically searched the MEDLINE® database (http://www.ncbi.nlm.nih.gov/pubmed/). Due to the heterogeneous naming of DCC stimulation over the dmPFC a variety of search terms was applied resulting in a numeral quantity of 340 hits., Results: DCC stimulation over the dmPFC has been proven to be safe and feasible in various neuropsychiatric disorders and in healthy subjects. Clinical results are encouraging, but have to be considered as preliminary as data from sham-controlled clinical trials and knowledge about the neurobiological underpinnings are still scarce., Conclusion: DCC stimulation over the dmPFC represents a promising approach in the fast evolving noninvasive brain stimulation techniques aiming at the functional modulation of brain areas vitally involved in affect, sensory autonomic, cognitive, and salience regulation. This may hold potential for both neuroscientific research and clinical applications in the treatment of psychiatric disorders., (© 2018 International Neuromodulation Society.)

Maximal safe resection is the modern goal for surgery of intrinsic brain tumors located in or close to brain eloquent areas. Nowadays different neuroimaging techniques provide important anatomical and functional information regarding the brain functional organization that can be used to plan a customized surgical strategy to preserve functional networks, and to increase the extent of tumor resection. Among these techniques, navigated transcranial magnetic stimulation (nTMS) has recently gained great favor among the neurosurgical community for preoperative mapping and planning prior to brain tumor surgery. It represents an advanced neuroimaging technique based on the neurophysiological mapping of the functional cortical brain organization. Moreover, it can be combined with other neuroimaging techniques such as diffusion tensor imaging tractography, thus providing a reliable reconstruction of brain eloquent networks. Consequently, nTMS mapping may provide reliable noninvasive brain functional mapping, anticipating information that otherwise may be available to neurosurgeons only in the operating theater by using direct electrical stimulation. The authors describe the reliability and usefulness of the preoperative nTMS-based approach in neurosurgical practice, and briefly discuss their experience using nTMS as well as currently available evidence in the literature supporting its clinical use. In particular, special attention is reserved for the discussion of the role of nTMS as a novel tool for the preoperative neurophysiological mapping of motor and language networks prior to surgery of intrinsic brain tumors located in or close to eloquent networks, as well as for future and promising applications of nTMS in neurosurgical practice.

Recent experimental studies have shown that static magnetic field can be effective in modulating human brain functions. Following this discovery, a new noninvasive brain stimulation technique was developed: the transcranial static magnetic stimulation (tSMS). Various types of permanent magnets have been used in previous experimental studies, with the aim of validating the effectiveness of tSMS; nevertheless, the spatial distributions of magnetic field generated by these permanent magnets have not been fully investigated. In this study, we compared the distributions of magnetic field on the human cortical surface generated by five different cylindrical magnets (of various dimensions), using the finite element method. Our simulation results demonstrated that the magnitude of magnetic flux density induced in the cortical grey matter of the human brain is proportional to the volume of permanent magnets used, while the magnetic field gradient is not necessarily proportional to the volume of the magnets. Additionally, we showed that the use of magnets with internal holes might not be advantageous. The differences in magnetic field properties induced by various types of permanent magnets suggested that their careful selection, based on magnetic field simulations, might be necessary to increase the effectiveness of tSMS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Single coil-based systems for magnetic stimulation are widely used for neurostimulation in neuroscience research and clinical treatment of neurological diseases. However, parallelization of magnetic stimulation with multiple coils may generate far greater potential than a single coil, and could thus expand the scope of brain area stimulation. Therefore, we examined whether a multiple coil-based system could improve the effectiveness and focality of conventional single coil-based magnetic stimulation., Approach: We designed and tested a micromagnetic stimulation (µMS) device with multiple submillimeter-sized coils as a possible substitute for one large coil. Our design concept is spatially-distributed stimulation strategy involving the small number of coils to be able to mimic desired electric field profiles. To this end, the cost function of the error between the desired and coil-induced electric fields was firstly calculated, and coil currents were repetitively estimated to achieve the smaller number of coils under a certain criterion: a minimum error with spatial sparsity. Using these approaches, we evaluated the capability of our multi-channel µMS via numerical simulations and demonstrated responsive results in animal experiments., Main Results: Our approach can enhance control of neural excitation and improve the concentration of the excitation field induced by magnetic stimulation with reduced power consumption. Furthermore, in vivo electrophysiological recordings of mouse brain performed to evaluate our proposed approach for brain stimulation demonstrated experimentally that our multi-channel µMS device can yield more effective stimulation than the single-channel device. In addition, our device permitted electronic spatial adjustment of the stimulus shape and location without moving the coils., Significance: The development of new multichannel µMS-based therapeutic approaches may be useful because the µMS affects only a restricted brain area. Indeed, the small size of micro-coils and their finer focality with multichannel contribution might be suitable for chronic use, which is difficult using conventional large transcranial magnetic stimulation (TMS) with simple round or figure-eight coils. Thus, our findings support new opportunities to explore magnetic stimulation as a therapeutic approach for neurological disorders.

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.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has a good level of evidence of efficacy as a method for providing analgesic effects in patients with chronic pain. However, there is still no consensus regarding the parameters of stimulation to use and the detailed protocol to apply for therapeutic practice. In this article, we review the main technical points to address, and we propose a practical algorithm of how to use rTMS for chronic pain treatment in daily clinical practice., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Over the past few years extensive body of research was produced investigating the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic tinnitus with heterogeneous results. This heterogeneity is exemplified by two recently published large-scale clinical trials reporting different outcomes. Technical aspects of rTMS were suspected as a potential source for this incongruency. The aim of this systematic review is to examine the overall efficacy as well as to identify possible technical factors relevant for the effectiveness of rTMS tinnitus trials. Via a literature search appropriate original research papers were identified and rTMS parameters were extracted from each study arm for subsequent statistical analysis with respect to observed effects (significant vs. not significant pre-post rTMS effects). Our findings indicate that verum rTMS is superior to sham rTMS as demonstrated by the proportion of significant pre-post contrasts. Some relevant rTMS parameters (e.g., pulse waveform) are not reported. Lower rTMS stimulation intensity was associated with significant effects in verum rTMS arms. An additional stimulation of the DLPFC to the temporal cortex was not found to promote efficacy. Future research should consider differential effects of rTMS induced by technical parameters and strive for an exhaustive reporting of relevant rTMS parameters.

Background: Small variations in TMS parameters, such as pulse frequency and amplitude may elicit distinct neurophysiological responses. Assessing the mismatch between nominal and experimental parameters of TMS stimulators is essential for safe application and comparisons of results across studies., New Method: A search coil was used to assess exactness and precision errors of amplitude and timing parameters such as interstimulus interval, the period of pulse repetition, and intertrain interval of TMS devices. The method was validated using simulated pulses and applied to six commercial stimulators in single-pulse (spTMS), paired-pulse (ppTMS), and repetitive (rTMS) protocols, working at several combinations of intensities and frequencies., Results: In a simulated signal, the maximum exactness error was 1.7% for spTMS and the maximum precision error 1.9% for ppTMS. Three out of six TMS commercial devices showed exactness and precision errors in spTMS amplitude higher than 5%. Moreover, two devices showed amplitude exactness errors higher than 5% in rTMS with parameters suggested by the manufactures., Comparison With Existing Methods: Currently available tools allow characterization of induced electric field intensity and focality, and pulse waveforms of a single TMS pulse. Our method assesses the mismatch between nominal and experimental values in spTMS, ppTMS and rTMS protocols through the exactness and precision errors of amplitude and timing parameters., Conclusion: This study highlights the importance of evaluating the physical characteristics of TMS devices and protocols, and provides a method for on-site quality assessment of multiple stimulation protocols in clinical and research environments., (Copyright © 2019 Elsevier B.V. All rights reserved.)