A computational model for real-time calculation of electric field due to transcranial magnetic stimulation in clinics

The aim of this paper is to propose an approach for an accurate and fast (real-time) computation of the electric field induced inside the whole brain volume during a transcranial magnetic stimulation (TMS) procedure. The numerical solution implements the admittance method for a discretized realistic brain model derived from Magnetic Resonance Imaging (MRI). Results are in a good agreement with those obtained using commercial codes and require much less computational time. An integration of the developed codewith neuronavigation toolswill permit real-time evaluation of the stimulated brain regions during the TMSdelivery, thus improving the efficacy of clinical applications

TMS with fast and accurate electronic control : Measuring the orientation sensitivity of corticomotor pathways

Background: Transcranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing. Objective: We aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability. Methods: We designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custommade electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3 degrees steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude. Results: The two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity. Conclusion: The developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols. (C) 2022 The Authors. Published by Elsevier Inc.Peer reviewe

Deep transcranial magnetic stimulation : improved coil design and assessment of the induced fields using MIDA model

Stimulation of deep brain structures by transcranial magnetic stimulation (TMS) is a method for activating deep neurons in the brain and can be beneficial for the treatment of psychiatric and neurological disorders. To numerically investigate the possibility for deeper brain stimulation (electric fields reaching the hippocampus, the nucleus accumbens, and the cerebellum), combined TMS coils using the double-cone coil with the Halo coil (HDA) were modeled and investigated. Numerical simulations were performed using MIDA: a new multimodal imaging-based detailed anatomical model of the human head and neck. The 3D distributions of magnetic flux density and electric field were calculated. The percentage of volume of each tissue that is exposed to electric field amplitude equal or greater than 50% of the maximumamplitude of E in the cortex for each coil was calculated to quantify the electric field spread (V50). Results show that only the HDA coil can spread electric fields to the hippocampus, the nucleus accumbens, and the cerebellum with V50 equal to 0.04%, 1.21%, and 6.2%, respectively

Occupational exposure to electromagnetic fields: risk assessment of operators performing Transcranial Magnetic Stimulation (TMS) treatments

The assessment of the risk from occupational exposure to electromagnetic fields (EMF) has attracted the attention of those involved in safety in the workplace, in particular after the updating of European legislation, with the publication for EMFs, of Directive 2013/35/EU1 of the European Parliament and of the Council, which made the risk assessment mandatory for this type of physical agents. The issue is made even more relevant by the proliferation of industrial and health applications using EMF even of considerable intensity. However, the rapid technological development has not always been accompanied by adequate growth in the culture of prevention and safety. Many devices expose both operators and persons of the general public to significant risks, but often, these risks are not adequately reported by the manufacturer, nor mentioned in the instruction manual, as would be expressly required by the harmonized standards. In this general framework is placed this Ph.D. research project, whose aim is to analyze possible conditions of risk in the workplace, considering only the environment where the EMF sources potentially expose the operator to risk. The research project involves a joint collaboration between two Institutions: the National Institute for Insurance against Accidents at Work - INAIL and of course Sapienza University of Rome. The project is developed in a multidisciplinary manner, providing experimental and numerical investigations to achieve the required goals, also considering the literature review and comparison for a more realistic analysis of the risk, in terms of human exposure to EMF. The work is based on a multiphysics approach to obtain a complete evaluation of the risk in the workplace, with the prospective to improve the current approach in the assessment of the risk and eventually suggest some indications to the operator for better use of the device under test. Therefore, the starting point has been a review of the workplaces to identify any gaps and critical issues in relation to the risk assessment and therefore for which it is considered necessary to deepen the protectionist issues. A literature analysis of the state of the art on the risk in the workplace is first carried out. This has been followed by numerical and accurate modeling of the device under test as well as the workers in a real reproduced work condition of exposure. Of paramount importance is the understanding of all the parameters that can affect the distribution of the induced EM quantities, which are essential for the risk assessment and the verification of compliance with the regulations system. To do this, it was necessary to study human exposure in-depth, also using different human body models available for dosimetric analysis on dedicated software. All the research has traveled on two parallel tracks, on the one hand, the need to fill the scientific gaps in the research area of exposure assessment of workers and on the other one to take into account the regulatory aspects, essential for a correct evaluation of professional exposure. Therefore, as a last step of the overall work, a possible new protocol of risk assessment analysis is proposed to move forward on the improvement of safety and security in the workplace

Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain—At the Tipping Point?

The term “neuropathic pain” (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials

Intermittent theta burst stimulation increases reward responsiveness in individuals with higher hedonic capacity

Background: Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. Objective: In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. Methods: We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. Results: As expected, the participants developed a response bias towards the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individuals trait hedonic capacity, the more the response bias towards the rich stimulus increased after the active stimulation. Conclusion: When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system

Cortical stimulation consolidates and reactivates visual experience: neural plasticity from magnetic entrainment of visual activity

Delivering transcranial magnetic stimulation (TMS) shortly after the end of a visual stimulus can cause a TMS-induced ‘replay’ or ‘visual echo’ of the visual percept. In the current study, we find an entrainment effect that after repeated elicitations of TMS-induced replay with the same visual stimulus, the replay can be induced by TMS alone, without the need for the physical visual stimulus. In Experiment 1, we used a subjective rating task to examine the phenomenal aspects of TMS-entrained replays. In Experiment 2, we used an objective masking paradigm to quantitatively validate the phenomenon and to examine the involvement of low-level mechanisms. Results showed that the TMS-entrained replay was not only phenomenally experienced (Exp.1), but also able to hamper letter identification (Exp.2). The findings have implications in several directions: (1) the visual cortical representation and iconic memory, (2) experience-based plasticity in the visual cortex, and (3) their relationship to visual awareness

Multi-locus transcranial magnetic stimulation—theory and implementation

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation. Objective: To overcome the limitations of physical TMS-coil movement by introducing electronic targeting. Methods: We propose electronic stimulation targeting using a set of large overlapping coils and introduce a matrix-factorisation-based method to design such sets of coils. We built one such device and demonstrated the electronic stimulation targeting in vivo. Results: The demonstrated two-coil transducer allows translating the stimulated spot along a 30-mmlong line segment in the cortex; with five coils, a target can be selected from within a region of the cortex and stimulated in any direction. Thus, far fewer coils are required by our approach than by previously suggested ones, none of which have resulted in practical devices. Conclusion: Already with two coils, we can adjust the location of the induced electric field maximum along one dimension, which is sufficient to study, for example, the primary motor cortex. (C) 2018 The Author(s). Published by Elsevier Inc.Peer reviewe

Transcranial magnetic stimulation set-up for small animals

Transcranial magnetic stimulation (TMS) is widely applied on humans for research and clinical purposes. TMS studies on small animals, e.g., rodents, can provide valuable knowledge of the underlying neurophysiological mechanisms. Administering TMS on small animals is, however, prone to technical difficulties, mainly due to their small head size. In this study, we aimed to develop an energy-efficient coil and a compatible experimental set-up for administering TMS on rodents. We applied a convex optimization process to develop a minimum-energy coil for TMS on rats. As the coil windings of the optimized coil extend to a wide region, we designed and manufactured a holder on which the rat lies upside down, with its head supported by the coil. We used the set-up to record TMS-electromyography, with electromyography recorded from limb muscles with intramuscular electrodes. The upside-down placement of the rat allowed the operator to easily navigate the TMS without the coil blocking their field of view. With this paradigm, we obtained consistent motor evoked potentials from all tested animals.Peer reviewe