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Objective: Electric-field orientation is crucial for optimizing neuronal excitation in transcranial magnetic stimulation (TMS). Yet, the stimulus orientation effects on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are poorly understood due to technical challenges in manipulating the TMS-induced stimulus orientation within milliseconds. We aimed to assess the orientation sensitivity of SICI and ICF paradigms and identify optimal orientations for motor evoked potential (MEP) facilitation and suppression., Methods: We applied paired-pulse multi-channel TMS to 12 healthy subjects with conditioning and test stimuli in the same, opposite, and perpendicular orientations to each other at four interstimulus intervals (ISI) to generate refractoriness, SICI, and ICF., Results: MEP modulation was affected by the conditioning- and test-stimulus orientation, being strongest when both pulses were in the same direction. MEP modulation with 2.5-ms and 6.0-ms ISIs were more sensitive to orientation changes than 0.5- and 8.0-ms ISIs., Conclusion: SICI and ICF orientation sensitivity exhibit a complex dependence on the conditioning stimulus orientation, which might be explained by anatomical and morphological arrangements of inhibitory and excitatory neuronal populations., Significance: Distinct mechanisms mediating SICI and ICF are sensitive to stimulus orientation at specific ISIs, describing a structural-functional relationship that maximizes each effect at the cortical level., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [JON, LMK, and RJI are inventors of patents for mTMS technology. VHS is an inventor of patent applications for mTMS and TMS technologies. JON, RJI, and VHS have received unrelated consulting fees from Nexstim Plc. UZ received consulting fees from CorTec GmbH. The other authors declare no conflict of interest]., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Scalp cooling might increase the long-term potentiation (LTP)-like effect of transcranial direct current stimulation (tDCS) by reducing the threshold for after-effects according to metaplasticity and increasing electrical current density reaching the cortical neurons. We aimed to investigate whether priming scalp cooling potentiates the tDCS after-effect on motor cortex excitability., Methods: This study had a randomized, parallel-arms, sham-controlled, double-blinded design with an adequately powered sample of 105 healthy subjects. Corticomotor and intracortical excitability were assessed with motor evoked potentials (MEP) from transcranial magnetic stimulation (TMS) in short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) paradigms. Subjects were randomly allocated into six intervention groups, including anodal and cathodal tDCS (1-mA/20-min), scalp cooling, and sham. MEPs were recorded before, immediately, and 15 min after the interventions., Results: We did not observe changes in MEP amplitude from single-pulse TMS, SICI, and ICF with any intervention protocol., Conclusion: Anodal and cathodal tDCS did not have an LTP-like neuromodulatory effect on corticospinal and did not provide detectable GABAergic and glutamatergic neurotransmission changes, which were not influenced by priming scalp cooling., Significance: We provide strong evidence that tDCS (1-mA/20-min) does not alter corticomotor and intracortical excitability with or without priming scalp cooling., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The analysis of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) is crucial in research and clinical medical practice. MEPs are characterized by their latency and the treatment of a single patient may require the characterization of thousands of MEPs. Given the difficulty of developing reliable and accurate algorithms, currently the assessment of MEPs is performed with visual inspection and manual annotation by a medical expert; making it a time-consuming, inaccurate, and error-prone process. In this study, we developed DELMEP, a deep learning-based algorithm to automate the estimation of MEP latency. Our algorithm resulted in a mean absolute error of about 0.5 ms and an accuracy that was practically independent of the MEP amplitude. The low computational cost of the DELMEP algorithm allows employing it in on-the-fly characterization of MEPs for brain-state-dependent and closed-loop brain stimulation protocols. Moreover, its learning ability makes it a particularly promising option for artificial-intelligence-based personalized clinical applications., (© 2023. The Author(s).)

Most of the motor mapping procedures using navigated transcranial magnetic stimulation (nTMS) follow the conventional somatotopic organization of the primary motor cortex (M1) by assessing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the stimulation parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlapping motor maps in size (area and volume overlap degree) and topography (similarity and centroid Euclidean distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscle were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning., (© 2022. The Author(s).)

Background: Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer., Objective: To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region., Methods: We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand., Results: The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum., Conclusion: The developed mTMS system enables electronically targeted brain stimulation within a cortical region., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.O.N., L.M.K, and R.J.I. are inventors on patents and patent applications on mTMS technology. R.J.I. has been advisor and is a minority shareholder of Nexstim Plc., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coregistration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows non-invasive probing of brain circuits: TMS induces brain activation due to the generation of a properly oriented focused electric field (E-field) using a coil placed on a selected position over the scalp, while EEG captures the effects of the stimulation on brain electrical activity. Moreover, the combination of these techniques allows the investigation of several brain properties, including brain functional connectivity. The choice of E-field parameters, such as intensity, orientation, and position, is crucial for eliciting cortex-specific effects. Here, we evaluated whether and how the spatial pattern, i.e., topography and strength of functional connectivity, is modulated by the stimulus orientation. We systematically altered the E-field orientation when stimulating the left pre-supplementary motor area and showed an increase of functional connectivity in areas associated with the primary motor cortex and an E-field orientation-specific modulation of functional connectivity intensity. [ABSTRACT FROM AUTHOR]