Cortical Hot Spots Research Articles

Mixtures of Dirichlet processes for joint spatial modelling of transcranial magnetic stimulation mapping data

Abstract A patient’s responses to Transcranial Magnetic Stimulation (TMS) pulses on the motor cortex have a complex spatial pattern, making it challenging to understand the response patterns across multiple patients. We developed a mixture of Dirichlet process models to distinguish between patient-specific and shared spatial patterns across multiple patients to provide insight into consistent response patterns essential for developing personalized treatment procedures. The Metropolis–Hastings within Gibbs sampler of the Markov Chain Monte Carlo algorithm was developed for estimation. The model was used to analyse the TMS data of 3 healthy subjects. The study revealed that the primary motor cortex of the hand consistently emerges as a promising region for eliciting optimal responses. This area serves as a key target for brain mapping using TMS to identify cortical hotspots. However, the excitability patterns in this region can vary significantly among patients.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.

195 Targeting Thalamocortical Circuits For Closed-Loop Stimulation in Lennox-Gastaut Syndrome

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy associated with frequent seizures, cognitive impairment, and high burden of care. Electrical stimulation of the thalamus can be an effective treatment for LGS, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. METHODS: Brain network maps from 3 group-level studies of LGS were averaged to define the area of peak overlap: combined electroencephalography-functional MRI (EEG-fMRI) of paroxysmal fast activity, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) of hypometabolism, and structural connectivity associated with efficacy in a previous trial of deep brain stimulation. The resulting “hotspot” was used as a seed in a normative fMRI connectivity analysis to identify connected networks. Two patients underwent bilateral thalamocortical implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analyzed for presence and synchrony of epileptiform activity. RESULTS: Peak overlap was in bilateral premotor cortex. Functional connectivity of this hotspot revealed a network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-fMRI and FDG-PET. Intracranial electrophysiology showed characteristic epileptiform activity of LGS in the cortical hotspot that preceded or co-occurred with similar thalamic activity. CONCLUSIONS: Premotor cortex shows peak involvement in LGS, and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for neuromodulation therapies, including thalamocortical stimulation. Compared to thalamus-only stimulation, addition of this cortical target may allow more rapid detections and responsive stimulations of seizures, and broader modulation of the brain network underlying LGS to achieve greater seizure control.

Transcranial magnetic stimulation mapping of the motor cortex: comparison of five estimation algorithms.

There are currently five different kinds of transcranial magnetic stimulation (TMS) motor mapping algorithms available, from ordinary point-based algorithms to advanced field-based algorithms. However, there have been only a limited number of comparison studies conducted, and they have not yet examined all of the currently available algorithms. This deficiency impedes the judicious selection of algorithms for application in both clinical and basic neuroscience, and hinders the potential promotion of a potential superior algorithm. Considering the influence of algorithm complexity, further investigation is needed to examine the differences between fMRI peaks and TMS cortical hotspots that were identified previously. Twelve healthy participants underwent TMS motor mapping and a finger-tapping task during fMRI. The motor cortex TMS mapping results were estimated by five algorithms, and fMRI activation results were obtained. For each algorithm, the prediction error was defined as the distance between the measured scalp hotspot and optimized coil position, which was determined by the maximum electric field strength in the estimated motor cortex. Additionally, the study identified the minimum number of stimuli required for stable mapping. Finally, the location difference between the TMS mapping cortical hotspot and the fMRI activation peak was analyzed. The projection yielded the lowest prediction error (5.27 ± 4.24 mm) among the point-based algorithms and the association algorithm yielded the lowest (6.66 ± 3.48 mm) among field-based estimation algorithms. The projection algorithm required fewer stimuli, possibly resulting from its suitability for the grid-based mapping data collection method. The TMS cortical hotspots from all algorithms consistently deviated from the fMRI activation peak (20.52 ± 8.46 mm for five algorithms). The association algorithm might be a superior choice for clinical applications and basic neuroscience research, due to its lower prediction error and higher estimation sensitivity in the deep cortical structure, especially for the sulcus. It also has potential applicability in various other TMS domains, including language area mapping and more. Otherwise, our results provide further evidence that TMS motor mapping intrinsically differs from fMRI motor mapping.

Effect of Neuroanatomy on Intermittent Theta Burst Stimulation Motor Evoked Potentials

<h3>Research Objectives</h3> Previous work noted that there are significant variabilities in motor response to intermittent theta-burst stimulation (iTBS). It is possible this variability results from individual neuroanatomical differences. The current objective was to investigate the effect of individual neuroanatomy on first dorsal interosseous (FDI) and biceps brachii motor evoked potentials (MEPs) in response to iTBS. <h3>Design</h3> Cross-sectional study using a convenience sample. <h3>Setting</h3> Research laboratory. <h3>Participants</h3> Ten healthy individuals (7 females, 23.5 ± 5 years) participated in this study. Participants completed two iTBS sessions (one each targeting the FDI and biceps cortical hotspots) and an MRI on separate days. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> MEPs were calculated using data acquired with a Magstim Super Rapid2 Plus1 stimulator via a 70 mm double air film coil to the primary motor cortex and electromyography signals were measured from dominant FDI and biceps. Head models were generated from T1 & T2 weighted MRI. Diffusion tensor imaging was used to determine fiber tract geometry for FDI and biceps corticospinal tracts. We then established neuroanatomical parameters including: fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD). Cortical electric field strength (EFS) was calculated using simulated stimulation of head models and finite element analysis. <h3>Results</h3> For the FDI, there was no effect of iTBS (p = 0.223) but individual changes in corticomotor excitability scaled with stimulation type and resting motor potential (p < 0.001), EFS (p = 0.001), BSD (p = 0.004), and FTSA (p = 0.011). iTBS had a faciliatory response on the biceps and was dependent on FTSA (p < 0.001) and TFC (p < 0.001). <h3>Conclusions</h3> Our results show that MRI-based measures of neuroanatomy, specifically cortical architecture and tract anatomy, impact how the motor system responds to iTBS, subject to target-specific cortical control organization. MRI-based modeling of individual neuroanatomy may be a useful approach in selection of motor targets when designing iTBS-based therapies. <h3>Author(s) Disclosures</h3> None.

Effect of Neuroanatomy on Transcranial Magnetic Stimulation Resting Motor Thresholds

<h3>Research Objectives</h3> Previous research has demonstrated that anatomical complexities of cortical regions determine transcranial magnetic stimulation (TMS) induced electric fields in the brain, which impact the response to TMS-based therapies. The current objective was to investigate the effect of individual neuroanatomy on first dorsal interosseous (FDI) and biceps brachii resting motor thresholds (RMT) in response to TMS. <h3>Design</h3> Cross-sectional study using a convenience sample. <h3>Setting</h3> Research laboratory. <h3>Participants</h3> Ten healthy individuals (7 females, 23.5 ± 5 years) participated in this study. Each participant completed two TMS sessions (one each targeting the FDI and biceps cortical hotspots) and an MRI of the head on separate days. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> RMTs were determined using a Magstim Super BiStim stimulator via a 70 mm figure-of-eight coil to the left primary motor cortex and electromyography signals were measured from right FDI and biceps. Head models were generated based on T1 & T2 weighted MRI, while diffusion tensor imaging was used to determine fiber tract geometry for FDI and biceps corticospinal tracts. Via the models, we established neuroanatomical parameters including: fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD). Cortical electric field strength (EFS) was calculated using simulated stimulation of head models and finite element analysis. <h3>Results</h3> For the FDI, RMT was dependent on the interaction between individually modeled parameters: 1) EFS and FTSA (p = 0.036), and 2) EFS and TFC (p = 0.004). For the biceps, RMT was dependent on the interaction between 1) EFS and FTSA (p = 0.022) and 2) EFS and BSD (p = 0.010). <h3>Conclusions</h3> Our study results show that MRI-based measures of neuroanatomy, specifically cortical architecture and tract anatomy, differentially impact how the motor system responds to TMS. MRI-based modeling of individual neuroanatomy may be a useful approach to select appropriate motor targets when designing TMS based therapies. <h3>Author(s) Disclosures</h3> None.

Short-interval intracortical inhibition in human primary motor cortex: A multi-locus transcranial magnetic stimulation study

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.

Intracortical Inhibition and Surround Inhibition in the Motor Cortex: A TMS-EEG Study.

BackgroundShort-latency intracortical inhibition (SICI) and motor surround inhibition (mSI) are cortical phenomena that have been investigated with transcranial magnetic stimulation (TMS). mSI is believed to be necessary for the execution of fine finger movements, SICI may participate in mSI genesis, and however, the mechanisms underlying both mSI and SICI are not entirely clear.ObjectiveWe explored the cortical physiology of SICI and mSI in healthy subjects by TMS-evoked cortical potentials (TEPs).Methods:Single (sp) and paired-pulse (pp) TMS were delivered on the ADM muscle cortical hotspot while recording EEG and EMG. Three conditions were tested: spTMS and ppTMS at rest, and spTMS at the onset of an index finger movement. SICI and mSI were calculated on the ADM motor evoked potential (MEP) and two groups were defined based on the presence of mSI. Average TEPs were calculated for each condition and for five regions of interest.ResultsAt movement onset we observed a widespread reduction of the inhibitory late component N100 suggesting cortical facilitation associated with motor performance. At motor cortex level, SICI and mSI are associated with similar modulation of TEPs consisting in a reduction of P30 and an increase of N45 amplitude.ConclusionOur findings suggest that SICI and mSI modulate cortical excitability with shared inhibitory mechanisms.

Proceedings #41: HD-tDCS Effect on Motor Evoked Potential Amplitude Elicited by Neuronavigated TMS

In a previous validation study, we observed that along with increased amplitude of TMS-Motor Evoked Potential (MEP), anodal stimulation with High-Definition transcranial Direct Current Stimulation (HD-tDCS) produced a MEP variability that was 5 times greater when compared to the sham condition. This outcome was attributed to anatomical gyri and sulci variability across participants, and/or imprecise coil and central anode positioning. In this study, we controlled for coil and electrode placement by employing a neuronavigated TMS system, aiming to obtain a clearer picture of the HD-tDCS effect. Ninety neuronavigated TMS pulses (baseline) were delivered at the cortical hotspot of the right First Digital Interosseous (FDI). Next, 2mA anodal or sham stimulation was delivered through a Soterix 4X1 HD-tDCS system (Soterix Medical Inc. New York, NY), with electrodes arranged on a 4X1-ring configuration with the central electrode precisely placed over the TMS target. Then, 90 MEPs were recorded again. We observed a non-significant trend of post/pre MEP ratio increase in the anodal group, along with a larger variability in comparison to the sham group. These preliminary results with neuronavigated TMS are similar to our previous results without neuronavigation and support the hypothesis that individual anatomical differences account for the greater variability found in the anodal group. Increasing the sample size and including a cathodal condition in a future study will help clarify the observed trends.

Magnifying the View of the Hand Changes Its Cortical Representation. A Transcranial Magnetic Stimulation Study.

Changes in the perceived size of a body part using magnifying lenses influence tactile perception and pain. We investigated whether the visual magnification of one's hand also influences the motor system, as indexed by transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). In Experiment 1, MEPs were measured while participants gazed at their hand with and without magnification of the hand. MEPs were significantly larger when participants gazed at a magnified image of their hand. In Experiment 2, we demonstrated that this effect is specific to the hand that is visually magnified. TMS of the left motor cortex did not induce an increase of MEPs when participants looked at their magnified left hand. Experiment 3 was performed to determine if magnification altered the topography of the cortical representation of the hand. To that end, a 3 × 5 grid centered on the cortical hot spot (cortical location at which a motor threshold is obtained with the lowest level of stimulation) was overlaid on the participant's MRI image, and all 15 sites in the grid were stimulated with and without magnification of the hand. We confirmed the increase in the MEPs at the hot spot with magnification and demonstrated that MEPs significantly increased with magnification at sites up to 16.5 mm from the cortical hot spot. In Experiment 4, we used paired-pulse TMS to measure short-interval intracortical inhibition and intracortical facilitation. Magnification was associated with an increase in short-interval intracortical inhibition. These experiments demonstrate that the visual magnification of one's hand induces changes in motor cortex excitability and generates a rapid remapping of the cortical representation of the hand that may, at least in part, be mediated by changes in short-interval intracortical inhibition.

P234 Identification of parietal and frontal cortical regions of the human brain that contribute to perceptual conflict by causal TMS

The dorsal fronto-parietal attention network of the human brain plays a central role in tasks with conflicting visual stimuli, such as the flanker task. It is assumed to mediate spatial attention on the target and the distractor and thus influence the saliency of the target and resulting response times (RT) of subjects. Here we causally localized contributing ‘hot spots’ within the parietal and frontal cortical regions of the network using online Transcranial Magnetic Stimulation (TMS). Using a visual flanker task, subjects (n = 12) were instructed to identify a central target (‘>’ vs). Subjects responded faster to congruent than incongruent stimuli, indicating the presence of a flanker effect. Subject-specific hot spots were identified where TMS pulses significantly reduced the flanker effect for contralateral but not ipsilateral flankers. One, or two adjacent, hot spots were identified for all subjects in parietal as well as frontal regions. We conclude that online TMS can selectively disrupt attentional control of the contralateral visual field and identify contributing cortical hot spots with high spatial precision.

Results on the spatial resolution of repetitive transcranial magnetic stimulation for cortical language mapping during object naming in healthy subjects.

BackgroundThe spatial resolution of repetitive navigated transcranial magnetic stimulation (rTMS) for language mapping is largely unknown. Thus, to determine a minimum spatial resolution of rTMS for language mapping, we evaluated the mapping sessions derived from 19 healthy volunteers for cortical hotspots of no-response errors. Then, the distances between hotspots (stimulation points with a high error rate) and adjacent mapping points (stimulation points with low error rates) were evaluated.ResultsMean distance values of 13.8 ± 6.4 mm (from hotspots to ventral points, range 0.7–30.7 mm), 10.8 ± 4.8 mm (from hotspots to dorsal points, range 2.0–26.5 mm), 16.6 ± 4.8 mm (from hotspots to apical points, range 0.9–27.5 mm), and 13.8 ± 4.3 mm (from hotspots to caudal points, range 2.0–24.2 mm) were measured.ConclusionsAccording to the results, the minimum spatial resolution of rTMS should principally allow for the identification of a particular gyrus, and according to the literature, it is in good accordance with the spatial resolution of direct cortical stimulation (DCS). Since measurement was performed between hotspots and adjacent mapping points and not on a finer-grained basis, we only refer to a minimum spatial resolution. Furthermore, refinement of our results within the scope of a prospective study combining rTMS and DCS for resolution measurement during language mapping should be the next step.

FV 3. Higher concordance of navigated transcranial magnetic stimulation (nTMS) than of functional MRI with intraoperative direct cortical stimulation (DCS) for delineating the primary motor area

Objective To optimize the outcome after brain tumour surgery not only with regard to completeness of resection but also to postoperative motor functions and, thus, quality of life, individual assessment of the surgery-related functional risk is mandatory. Therefore, navigated transcranial magnetic stimulation (nTMS) has been used more and more as a reasonable alternative to functional magnetic resonance imaging (fMRI) over the last years. We compared the congruency of nTMS vs. fMRI results for non-invasively mapping the primary motor cortex (M1) prior to surgery with the gold standard method of direct cortical simulation (DCS). Methods 32 patients with intracerebral tumours underwent nTMS and fMRI prior to surgery. The cortical hotspots (HS) and Centres of Gravity (CoG) of M1 of the hand, the foot and the tongue representation were determined for each localizer technique and controlled by DCS. Euclidean distances (ED) between nTMS/fMRI and the respective DCS HS/CoG’s were computed in 3D. Moreover, nTMS, fMRI and DCS maps were projected onto the cortical surface following normalization to a standard brain. After smoothing, overlap volumes between both nTMS and fMRI with DCS functional maps (voxels) were calculated. Results CoG’s of the nTMS maps were located significantly closer to the respective DCS CoG’s as compared to fMRI ( p ± 6.0/17.3 ± 9.6 mm) and the foot (nTMS-DCS/fMRI-DCS: 16.2 ± 20/21.7 ± 17 mm) representation. However, comparison of hotspots did not reveal statistically significant differences. Regarding the overlap of entire functional maps, nTMS showed a higher agreement with DCS as compared to fMRI ( p ± 17%/57 ± 34%; p Conclusions Comparison of both M1 CoG’s and volume overlaps suggest that nTMS agrees better with the gold standard of intraoperative DCS as compared to fMRI, especially regarding the hand and the foot representation and, thus, is recommendable for presurgical M1 mapping. However, both methods should be regarded as complementary, particularly in respect of the tongue representation which is less easy to depict by nTMS.

Detecting a Cortical Fingerprint of Parkinson's Disease for Closed-Loop Neuromodulation.

Recent evidence suggests that deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) mediates its clinical effects by modulating cortical oscillatory activity, presumably via a direct cortico-subthalamic connection. This observation might pave the way for novel closed-loop approaches comprising a cortical sensor. Enhanced beta oscillations (13-35 Hz) have been linked to the pathophysiology of PD and may serve as such a candidate marker to localize a cortical area reliably modulated by DBS. However, beta-oscillations are widely distributed over the cortical surface, necessitating an additional signal source for spotting the cortical area linked to the pathologically synchronized cortico-subcortical motor network. In this context, both cortico-subthalamic coherence and cortico-muscular coherence (CMC) have been studied in PD patients. Whereas, the former requires invasive recordings, the latter allows for non-invasive detection, but displays a rather distributed cortical synchronization pattern in motor tasks. This distributed cortical representation may conflict with the goal of detecting a cortical localization with robust biomarker properties which is detectable on a single subject basis. We propose that this limitation could be overcome when recording CMC at rest. We hypothesized that—unlike healthy subjects—PD would show CMC at rest owing to the enhanced beta oscillations observed in PD. By performing source space analysis of beta CMC recorded during resting-state magnetoencephalography, we provide preliminary evidence in one patient for a cortical hot spot that is modulated most strongly by subthalamic DBS. Such a spot would provide a prominent target region either for direct neuromodulation or for placing a potential sensor in closed-loop DBS approaches, a proposal that requires investigation in a larger cohort of PD patients.

NIMG-71ROBUSTNESS AND VALIDITY OF M1 DETERMINATION BY NAVIGATED TRANSCRANIAL MAGNETIC STIMULATION (NTMS) AND FUNCTIONAL MRI AS COMPARED TO INTRAOPERATIVE DIRECT CORTICAL STIMULATION (DCS)

INTRODUCTION: Imaging of the primary motor representation (M1) prior to brain tumour surgery is helpful to achieve a maximum extent of resection whilst preserving motor functions. To date, functional magnetic resonance imaging (fMRI) has been the most commonly used localizer technique for primary motor functioning. However, navigated transcranial magnetic stimulation (nTMS) gains increasing acceptance due to its high resolution and little dependence on the patients' compliance. We compared the congruency of nTMS vs. fMRI results with the gold standard method of direct cortical simulation (DCS). METHODS: 32 patients with intracerebral tumours underwent nTMS and fMRI prior to surgery. The cortical hot spots (HS) and Centres of Gravity (CoG) of M1 of the hand, the foot and the tongue representation were determined for each localizer technique and controlled by DCS. Euclidean distances (ED) between nTMS / fMRI and the respective DCS HS / CoG's were computed in 3D. Feasibility of both fMRI and nTMS were assessed in relation to the DCS results. RESULTS: Regarding the hand and the tongue representation, the CoG's of the nTMS maps were located significantly closer to the respective DCS-CoG's as compared to fMRI (hand [nTMS-DCS/ fMRI-DCS]: 9.7 ± 6.0 / 17.3 ± 9.6; p = 0.001; tongue: 9.4 ± 4.9 / 16.9 ± 5.9; p < 0.001 ). For the foot representation, a similar statistical trend was observed (12.2 ± 6.5 / 19.2 ± 12.9; p = 0.1). However, comparison of hot-spots did not reveal statistically significant differences. The feasibility of non-invasive localizer methods (fMRI: 100% / nTMS: 99%) was superior to DCS (71%). CONCLUSIONS: NTMS is a highly robust method for M1 mapping and seems to be superior to fMRI for mapping areas adjacent to brain tumours. Probably due to the limited depth of nTMS stimulation effects, nTMS is less clearly favourable for localizing the foot representation.

Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.

Agonist contraction during intermittent theta burst stimulation enhances motor cortical plasticity of the wrist flexors

Differences in cortical control across the different muscles of the upper limb may mitigate the efficacy of TMS interventions targeting a specific muscle. The current study sought to determine whether weak concurrent contraction during TMS could enhance the efficacy of intermittent theta burst stimulation (iTBS) in the forearm flexors. Motor evoked potentials (MEP) were elicited from the flexor (FCR) and extensor carpi radialis (ECR) motor cortical hotspots before and after iTBS over the FCR cortical hotspot. During iTBS the FCR was either relaxed (iTBS-Relax) or tonically contracted to 10% of maximum voluntary force (iTBS-Contract). iTBS-Relax failed to produce consistent potentiation of MEPFCR amplitude. Individuals with a relatively lower RMTFCR compared RMTECR demonstrated MEPFCR facilitation post-iTBS-Relax. Individuals with relatively higher RMTFCR demonstrated less facilitation and even suppression of MEPFCR amplitude. iTBS-Contract facilitated MEPFCR amplitude but only for MEPFCR evoked from the ECR hotspot. Interactions between overlapping cortical representations determine the efficacy of iTBS. Tonic contraction increases the efficacy of iTBS by enhancing the volume of the cortical representation. However, metaplastic effects may attenuate the enhancement of MEP gain at the motor cortical hotspot. The use of TMS as an adjunct to physical therapy should account for inter-muscle interactions when targeting muscles of the forearm.