Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation

BackgroundTranscranial 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.ObjectiveTo develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region.MethodsWe 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.ResultsThe 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.ConclusionThe developed mTMS system enables electronically targeted brain stimulation within a cortical region.     

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.

Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback

BackgroundTranscranial magnetic stimulation (TMS) is widely used in brain research and treatment of various brain dysfunctions. However, the optimal way to target stimulation and administer TMS therapies, for example, where and in which electric field direction the stimuli should be given, is yet to be determined.ObjectiveTo develop an automated closed-loop system for adjusting TMS parameters (in this work, the stimulus orientation) online based on TMS-evoked brain activity measured with electroencephalography (EEG).MethodsWe developed an automated closed-loop TMS–EEG set-up. In this set-up, the stimulus parameters are electronically adjusted with multi-locus TMS. As a proof of concept, we developed an algorithm that automatically optimizes the stimulation orientation based on single-trial EEG responses. We applied the algorithm to determine the electric field orientation that maximizes the amplitude of the TMS–EEG responses. The validation of the algorithm was performed with six healthy volunteers, repeating the search twenty times for each subject.ResultsThe validation demonstrated that the closed-loop control worked as desired despite the large variation in the single-trial EEG responses. We were often able to get close to the orientation that maximizes the EEG amplitude with only a few tens of pulses.ConclusionOptimizing stimulation with EEG feedback in a closed-loop manner is feasible and enables effective coupling to brain activity.     

Cerebellar Transcranial Magnetic Stimulation: The Role of Coil Geometry and Tissue Depth

BackgroundWhile transcranial magnetic stimulation (TMS) coil geometry has important effects on the evoked magnetic field, no study has systematically examined how different coil designs affect the effectiveness of cerebellar stimulation.HypothesisThe depth of the cerebellar targets will limit efficiency. Angled coils designed to stimulate deeper tissue are more effective in eliciting cerebellar stimulation.MethodsExperiment 1 examined basic input–output properties of the figure-of-eight, batwing and double-cone coils, assessed with stimulation of motor cortex. Experiment 2 assessed the ability of each coil to activate cerebellum, using cerebellar-brain inhibition (CBI). Experiment 3 mapped distances from the scalp to cerebellar and motor cortical targets in a sample of 100 subjects' structural magnetic resonance images.ResultsExperiment 1 showed batwing and double-cone coils have significantly lower resting motor thresholds, and recruitment curves with steeper slopes than the figure-of-eight coil. Experiment 2 showed the double-cone coil was the most efficient for eliciting CBI. The batwing coil induced CBI only at higher stimulus intensities. The figure-of-eight coil did not elicit reliable CBI. Experiment 3 confirmed that cerebellar tissue is significantly deeper than primary motor cortex tissue, and we provide a map of scalp-to-target distances.ConclusionsThe double-cone and batwing coils designed to stimulate deeper tissue can effectively stimulate cerebellar targets. The double-cone coil was found to be most effective. The depth map provides a guide to the accessible regions of the cerebellar volume. These results can guide coil selection and stimulation parameters when designing cerebellar TMS studies.     

Targeting of White Matter Tracts with Transcranial Magnetic Stimulation

BackgroundTMS activations of white matter depend not only on the distance from the coil, but also on the orientation of the axons relative to the TMS-induced electric field, and especially on axonal bends that create strong local field gradient maxima. Therefore, tractography contains potentially useful information for TMS targeting.Objective/methodsHere, we utilized 1-mm resolution diffusion and structural T1-weighted MRI to construct large-scale tractography models, and localized TMS white matter activations in motor cortex using electromagnetic forward modeling in a boundary element model (BEM).ResultsAs expected, in sulcal walls, pyramidal cell axonal bends created preferred sites of activation that were not found in gyral crowns. The model agreed with the well-known coil orientation sensitivity of motor cortex, and also suggested unexpected activation distributions emerging from the E-field and tract configurations. We further propose a novel method for computing the optimal coil location and orientation to maximally stimulate a pre-determined axonal bundle.ConclusionsDiffusion MRI tractography with electromagnetic modeling may improve spatial specificity and efficacy of TMS.     

Conditions for numerically accurate TMS electric field simulation

BackgroundComputational simulations of the E-field induced by transcranial magnetic stimulation (TMS) are increasingly used to understand its mechanisms and to inform its administration. However, characterization of the accuracy of the simulation methods and the factors that affect it is lacking.ObjectiveTo ensure the accuracy of TMS E-field simulations, we systematically quantify their numerical error and provide guidelines for their setup.MethodWe benchmark the accuracy of computational approaches that are commonly used for TMS E-field simulations, including the finite element method (FEM) with and without superconvergent patch recovery (SPR), boundary element method (BEM), finite difference method (FDM), and coil modeling methods.ResultsTo achieve cortical E-field error levels below 2%, the commonly used FDM and 1st order FEM require meshes with an average edge length below 0.4 mm, 1st order SPR-FEM requires edge lengths below 0.8 mm, and BEM and 2nd (or higher) order FEM require edge lengths below 2.9 mm. Coil models employing magnetic and current dipoles require at least 200 and 3000 dipoles, respectively. For thick solid-conductor coils and frequencies above 3 kHz, winding eddy currents may have to be modeled.ConclusionBEM, FDM, and FEM all converge to the same solution. Compared to the common FDM and 1st order FEM approaches, BEM and 2nd (or higher) order FEM require significantly lower mesh densities to achieve the same error level. In some cases, coil winding eddy-currents must be modeled. Both electric current dipole and magnetic dipole models of the coil current can be accurate with sufficiently fine discretization.     

Rotational field TMS: Comparison with conventional TMS based on motor evoked potentials and thresholds in the hand and leg motor cortices

BackgroundTranscranial magnetic stimulation (TMS) is a rapidly expanding technology utilized in research and neuropsychiatric treatments. Yet, conventional TMS configurations affect primarily neurons that are aligned parallel to the induced electric field by a fixed coil, making the activation orientation-specific. A novel method termed rotational field TMS (rfTMS), where two orthogonal coils are operated with a 90° phase shift, produces rotation of the electric field vector over almost a complete cycle, and may stimulate larger portion of the neuronal population within a given brain area.ObjectiveTo compare the physiological effects of rfTMS and conventional unidirectional TMS (udTMS) in the motor cortex.MethodsHand and leg resting motor thresholds (rMT), and motor evoked potential (MEP) amplitudes and latencies (at 120% of rMT), were measured using a dual-coil array based on the H7-coil, in 8 healthy volunteers following stimulation at different orientations of either udTMS or rfTMS.ResultsFor both target areas rfTMS produced significantly lower rMTs and much higher MEPs than those induced by udTMS, for comparable induced electric field amplitude. Both hand and leg rMTs were orientation-dependent.ConclusionsrfTMS induces stronger physiologic effects in targeted brain regions at significantly lower intensities. Importantly, given the activation of a much larger population of neurons within a certain brain area, repeated application of rfTMS may induce different neuroplastic effects in neural networks, opening novel research and clinical opportunities.     

Modulation of motor learning by a paired associative stimulation protocol inducing LTD-like effects

BackgroundPaired associative stimulation (PAS) induces long-term potentiation (LTP)-like effects when interstimulus intervals (ISIs) between electrical peripheral nerve stimulation and transcranial magnetic stimulation (TMS) to M1 are approximately 21–25 ms (PAS_LTP). It was previously reported that two forms of motor learning (i.e., mode-free and model-based learning) can be differentially modulated by PAS_LTP depending on the different synaptic inputs to corticospinal neurons (CSNs), which relate to posterior-to-anterior (PA) or anterior-to-posterior (AP) currents induced by TMS (PA or AP inputs, respectively). However, the effects of long-term depression (LTD)-inducing PAS with an ISI of approximately 10 ms (PAS_LTD) on motor learning and its dependency on current direction have not yet been tested.ObjectiveTo investigate whether, and how, PAS_LTD affects distinct types of motor learning.MethodsEighteen healthy volunteers participated. We adopted the standard PAS using suprathreshold TMS with the target muscle relaxed, as well as subthreshold PAS during voluntary contraction, which was suggested to selectively recruit PA or AP inputs depending on the orientation of the TMS coil. We examined the effects of suprathreshold and subthreshold PAS_LTD on the performance of model-free and model-based learning, as well as the corticospinal excitability, indexed as the amplitudes of motor evoked potentials (MEPs).ResultsPAS_LTD inhibited model-free learning and MEPs only when subthreshold AP currents were applied. The PAS_LTD protocols tested here showed no effects on model-based learning.ConclusionsPAS_LTD affected model-free learning, presumably by modulating CSN excitability changes, rather than PA inputs, which are thought to be related to model-free learning.     

Preferential Activation of Unique Motor Cortical Networks With Transcranial Magnetic Stimulation: A Review of the Physiological,Functional, and Clinical Evidence

ObjectivesThe corticospinal volley produced by application of transcranial magnetic stimulation (TMS) over primary motor cortex consists of a number of waves generated by trans-synaptic input from interneuronal circuits. These indirect (I)-waves mediate the sensitivity of TMS to cortical plasticity and intracortical excitability and can be assessed by altering the direction of cortical current induced by TMS. While this methodological approach has been conventionally viewed as preferentially recruiting early or late I-wave inputs from a given populations of neurons, growing evidence suggests recruitment of different neuronal populations, and this would strongly influence interpretation and application of these measures. The aim of this review is therefore to consider the physiological, functional, and clinical evidence for the independence of the neuronal circuits activated by different current directions.Materials and MethodsTo provide the relevant context, we begin with an overview of TMS methodology, focusing on the different techniques used to quantify I-waves. We then comprehensively review the literature that has used variations in coil orientation to investigate the I-wave circuits, grouping studies based on the neurophysiological, functional, and clinical relevance of their outcomes.ResultsReview of the existing literature reveals significant evidence supporting the idea that varying current direction can recruit different neuronal populations having unique functionally and clinically relevant characteristics.ConclusionsFurther research providing greater characterization of the I-wave circuits activated with different current directions is required. This will facilitate the development of interventions that are able to modulate specific intracortical circuits, which will be an important application of TMS.     

Atlas of optimal coil orientation and position for TMS: A computational study

Background

Transcranial magnetic stimulation (TMS) activates target brain structures in a non-invasive manner. The optimal orientation of the TMS coil for the motor cortex is well known and can be estimated using motor evoked potentials. However, there are no easily measurable responses for activation of other cortical areas and the optimal orientation for these areas is currently unknown.

Evaluation of an image-guided, robotically positioned transcranial magnetic stimulation system

The emergence of transcranial magnetic stimulation (TMS) as a tool for investigating the brain has been remarkable over the past decade. While many centers are now using TMS, little has been done to automate the delivery of planned TMS stimulation for research and/or clinical use. We report on an image-guided robotically positioned TMS system (irTMS) developed for this purpose. Stimulation sites are selected from functional images overlaid onto anatomical MR images, and the system calculates a treatment plan and robotically positions the TMS coil following that plan. A new theory, stating that cortical response to TMS is highest when the induced E-field is oriented parallel to cortical columns, is used by the irTMS system for planning the position and orientation of the TMS coil. This automated approach to TMS planning and delivery provides a consistent and optimized method for TMS stimulation of cortical regions of the brain. We evaluated the positional accuracy and utility of the irTMS system with a B-shaped TMS coil. Treatment plans were evaluated for sites widely distributed about a head phantom with well-defined landmarks. The overall accuracy in positioning the planned site of the TMS coil was approximately 2 mm, similar to that reported for the robot alone. The estimated maximum range of error in planned vs. delivered E-field strength was +4%, suggesting a high degree of accuracy and reproducibility in the planned use of the irTMS system.     

Transcranial Magnetic Stimulation-EEG Biomarkers of Poststroke Upper-Limb Motor Function

BackgroundMotor evoked potentials obtained with transcranial magnetic stimulation (TMS) can provide valuable information to inform stroke neurophysiology and recovery but are difficult to obtain in all stroke survivors due to high stimulation thresholds.ObjectiveTo determine whether transcranial magnetic stimulation evoked potentials (TEPs) evoked using a lower stimulus intensity, below that necessary for recording motor evoked potentials, could serve as a marker of poststroke upper-limb motor function and were different compared to healthy adults.MethodsEight chronic stroke survivors (66 ± 21 years) and 15 healthy adults (53 ± 10 years) performed a motor function task using a customized grip-lift manipulandum. TMS was applied to the lesioned motor cortex, with TEPs recorded using simultaneous high-definition electroencephalography (EEG).ResultsStroke participants demonstrated greater hold ratio with the manipulandum. Cluster-based statistics revealed larger P30 amplitude in stroke participants, with significant clusters over frontal (P = .016) and parietal-occipital electrodes (P = .023). There was a negative correlation between the N45 peak amplitude and hold ratio in stroke participants (r = ?.83, P = .02), but not controls.ConclusionsTEPs can be recorded using lower stimulus intensities in chronic stroke. The global P30 TEP response differed between stroke participants and healthy controls, with results suggesting that the TEP can be used as a biomarker of upper-limb behavior.     

Blood Oxygenation Changes Modulated by Coil Orientation During Prefrontal Transcranial Magnetic Stimulation

BackgroundPrefrontal transcranial magnetic stimulation (TMS) is being investigated as a treatment for several neurological and psychiatric disorders. The direction of the cortical current induced by TMS can be modulated by the coil orientation and this influences the extent of neural depolarization. Although the optimal coil orientation has previously been established for motor cortex, identifying an optimal coil orientation for prefrontal areas is more challenging due to the absence of a motor response. The current study used near infra-red spectroscopy (NIRS) to investigate the impact of coil orientation on TMS induced changes in prefrontal blood oxygenation (HbO). It was hypothesized that a greater change in HbO would be observed when current was induced in a posterior to anterior direction.MethodsSingle pulse and trains of 1 Hz repetitive TMS (rTMS) were administered to the left prefrontal cortex while simultaneously recording HbO response bilaterally. The effect of coil orientation was examined at 45°, 135°, and 225° counterclockwise from midline.ResultsGreatest changes in HbO were observed at a 45° orientation when both single and rTMS were applied, and only minor changes were observed at 135° and 225°. Application of short trains of rTMS at 45° resulted in transient increases in HbO that were significantly greater in magnitude than when the coil orientation was reversed.ConclusionsThe utility of NIRS for examining the TMS evoked physiological response at non-motor areas is highlighted in this study. Prefrontal HbO response evoked by TMS is sensitive to the direction of induced cortical current and it appears that the de facto 45° angle utilized in most clinical studies may prove to be optimal.     

Age-related Differences in Short- and Long-interval Intracortical Inhibition in a Human Hand Muscle

BackgroundEffects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) amplitude.ObjectiveTo investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP amplitudes.MethodsIn 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%–150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the amplitude of the MEP produced by the test alone TMS.ResultsWhen pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP amplitude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle.ConclusionsAdvancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP amplitude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle.     

Transcranial electrical stimulation motor threshold can estimate individualized tDCS dosage from reverse-calculation electric-field modeling

BackgroundUnique amongst brain stimulation tools, transcranial direct current stimulation (tDCS) currently lacks an easy or widely implemented method for individualizing dosage.ObjectiveWe developed a method of reverse-calculating electric-field (E-field) models based on Magnetic Resonance Imaging (MRI) scans that can estimate individualized tDCS dose. We also evaluated an MRI-free method of individualizing tDCS dose by measuring transcranial magnetic stimulation (TMS) motor threshold (MT) and single pulse, suprathreshold transcranial electrical stimulation (TES) MT and regressing it against E-field modeling. Key assumptions of reverse-calculation E-field modeling, including the size of region of interest (ROI) analysis and the linearity of multiple E-field models were also tested.MethodsIn 29 healthy adults, we acquired TMS MT, TES MT, and anatomical T1-weighted MPRAGE MRI scans with a fiducial marking the motor hotspot. We then computed a “reverse-calculated tDCS dose” of tDCS applied at the scalp needed to cause a 1.00 V/m E-field at the cortex. Finally, we examined whether the predicted E-field values correlated with each participant’s measured TMS MT or TES MT.ResultsWe were able to determine a reverse-calculated tDCS dose for each participant using a 5 × 5 x 5 voxel grid region of interest (ROI) approach (average = 6.03 mA, SD = 1.44 mA, range = 3.75–9.74 mA). The Transcranial Electrical Stimulation MT, but not the Transcranial Magnetic Stimulation MT, significantly correlated with the ROI-based reverse-calculated tDCS dose determined by E-field modeling (R² = 0.45, p < 0.001).ConclusionsReverse-calculation E-field modeling, alone or regressed against TES MT, shows promise as a method to individualize tDCS dose. The large range of the reverse-calculated tDCS doses between subjects underscores the likely need to individualize tDCS dose. Future research should further examine the use of TES MT to individually dose tDCS as an MRI-free method of dosing tDCS.     

The safety of transcranial magnetic stimulation with deep brain stimulation instruments

ObjectivesTranscranial magnetic stimulation (TMS) has been employed in patients with an implanted deep brain stimulation (DBS) device. We investigated the safety of TMS using simulation models with an implanted DBS device.MethodsThe DBS lead was inserted into plastic phantoms filled with dilute gelatin showing impedance similar to that of human brain. TMS was performed with three different types of magnetic coil. During TMS (1) electrode movement, (2) temperature change around the lead, and (3) TMS-induced current in various situations were observed. The amplitude and area of each evoked current were measured to calculate charge density of the evoked current.ResultsThere was no movement or temperature increase during 0.2 Hz repetitive TMS with 100% stimulus intensity for 1 h. The size of evoked current linearly increased with TMS intensity. The maximum charge density exceeded the safety limit of 30 μC/cm²/phase during stimulation above the loops of the lead with intensity over 50% using a figure-eight coil.ConclusionsStrong TMS on the looped DBS leads should not be administered to avoid electrical tissue injury. Subcutaneous lead position should be paid enough attention for forthcoming situations during surgery.     

Large-scale analysis of interindividual variability in single and paired-pulse TMS data

ObjectiveThis study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability.MethodsAuthors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data.Results687 healthy participant’s data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual’s single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT.ConclusionsThis large-scale analysis has identified a number of factors influencing participants’ responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data.SignificanceThis study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.     

Automated-parameterization of the motor evoked potential and cortical silent period induced by transcranial magnetic stimulation

ObjectiveTo standardize the characterization of motor evoked potential (MEP) and cortical silent period (CSP) recordings elicited with transcranial magnetic stimulation (TMS).MethodsA computer-based, automated-parameterization program (APP) was developed and tested which provides a comprehensive set of electromyography (EMG) magnitude and temporal measures. The APP was tested using MEP, CSP, and isolated CSP (iCSP) TMS stimulus–response data from a healthy adult population (N = 13).ResultsThe APP had the highest internal reliability (Cronbach’s alpha = .98) for CSP offset time compared with two prominent automated methods. The immediate post-CSP EMG recovery level was 49% higher than the pre-TMS EMG level. MEP size (peak amplitude, mean amplitude, peak-to-peak amplitude, and area) correlated higher with effective E-field (E_eff) than other intensity measures (r ≈ 0.5 vs. r ≈ 0.3) suggesting that E_eff is better suited for standardizing MEP stimulus–response relationships.ConclusionsThe APP successfully characterized individual and mean epochs containing MEP, CSP, and iCSP responses. The APP provided common signal and temporal measures consistent with previous studies and novel additional parameters.SignificanceWith the use of the APP modeling method and the E_eff, a standard approach for the analysis and reporting of MEP–CSP complex and iCSP measurements is achievable.     

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation

BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.     

Inhibitory and facilitatory connectivity from ventral premotor to primary motor cortex in healthy humans at rest – A bifocal TMS study

ObjectiveIn macaques, intracortical electrical stimulation of ventral premotor cortex (PMv) can modulate ipsilateral primary motor cortex (M1) excitability at short interstimulus intervals (ISIs).MethodsAdopting the same conditioning-test approach, we used bifocal transcranial magnetic stimulation (TMS) to examine intrahemispheric connectivity between left PMv and M1 in humans. A conditioning stimulus (CS) was applied to PMv at intensities of 80% and 90% of active motor threshold (AMT) and 90% and 110% of resting motor threshold (RMT). A supra-threshold test stimulus (TS) was given 2, 4, 6, 8 and 10 ms after the CS and the amplitude of the motor evoked potential (MEP) was measured to probe corticospinal excitability.ResultsThe CS facilitated corticospinal excitability in ipsilateral M1 when PMv was stimulated with 80% AMT 4 or 6 ms before the TS. At the same ISIs, the CS suppressed corticospinal excitability when the stimulus intensity was increased to 90% RMT. Conditioning effects were site-specific because conditioning the dorsal premotor cortex (PMd) at three different sites produced different effects. Using neuronavigated TMS the PMv site where applied CS produced changes in ipsilateral M1 excitability was located at the border between ventral Brodmann area (BA) 6 and BA 44, the human homologue of monkey’s PMv (area F5).ConclusionWe infer that the corticospinal motor output from M1 to contralateral hand muscles can be facilitated or inhibited by a CS over ipsilateral PMv.SignificanceThe fact that conditioning effects following PMd stimulation differ from those after PMv stimulation supports the concept that inputs from premotor cortices to M1 are functionally segregated.