Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field. Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modelled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin. We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results. Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications

Correction of stray magnetic fields caused by cable currents is essential for human in-vivo brain magnetic resonance current density imaging (MRCDI)

Accurate mapping of current flows in the human brain is important for many neuroscientific applications. MRCDI is an emerging method, which combines MRI with externally applied alternating currents to derive current flow distributions based on measurements of the current-induced magnetic fields. However, inaccurate and inconsistent measurements occur unless the stray magnetic fields ca used by the currents flowing in the feeding cables are corrected [1] . Here, we explore the influences of the stray magnetic fields due to the cable - currents in realistic experimental MRCDI set - ups

Targeted multielectrode tDCS increases functional connectivity within the arcuate fasciculus network: An exploratory study and analysis

Non-invasive electrical stimulation can modulate not only targeted local intrinsic brain activity, but also activity in remote, yet connected brain regions. Such modulation of connected regions and/or entire networks may account for some of the treatment-induced changes in complex behaviors and cognitive processes. The current study tested whether strategically-placed electrodes delivering transcranial direct current stimulation (tDCS) to single or several nodal cortical regions within a structurally-defined network, the arcuate fasciculus network (AF-network), have the potential to strengthen functional connectivity between network regions more effectively than a single electrode placed over an individual nodal region within that same network. Concurrent tDCS-MR imaging was utilized to acquire resting-state fMRI while delivering 4 mA of direct current in multiple OFF-ON-OFF epochs with either a single- or multielectrode anodal montage over nodal cortical regions of the AF-network. Multielectrode anodal stimulation significantly changed functional connectivity between ipsilateral AF-network nodes while no single anodal electrode placed over one nodal region of the right AF-network did so. This significant change in functional connectivity was specific to the targeted right AF-network and could not be seen in other unrelated networks in the same hemisphere (e.g., the inferior longitudinal fasciculus). Functional connectivity measures were compared with electric field modeling measures to estimate target engagement. Regional homogeneity of current tangential to the cortical surface of the AF-network-targeted cortical nodes (J tangent) significantly predicted functional connectivity between these cortical nodes. Taking the anatomy and the drivers of a targeted network into account will help advance the efficacy of an intervention and precision medicine in general

Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates

Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information of the underlying biophysics in TES applications in humans and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG

A specification-based QoS-aware design framework for service-based applications

Effective and accurate service discovery and composition rely on complete specifications of service behaviour, containing inputs and preconditions that are required before service execution, outputs, effects and ramifications of a successful execution and explanations for unsuccessful executions. The previously defined Web Service Specification Language (WSSL) relies on the fluent calculus formalism to produce such rich specifications for atomic and composite services. In this work, we propose further extensions that focus on the specification of QoS profiles, as well as partially observable service states. Additionally, a design framework for service-based applications is implemented based on WSSL, advancing state of the art by being the first service framework to simultaneously provide several desirable capabilities, such as supporting ramifications and partial observability, as well as non-determinism in composition schemas using heuristic encodings; providing explanations for unexpected behaviour; and QoS-awareness through goal-based techniques. These capabilities are illustrated through a comparative evaluation against prominent state-of-the-art approaches based on a typical SBA design scenario

Reimbursement of innovative pharmaceuticals in English and Spanish hospitals-The example of isavuconazole.

Funder: Pfizer; Id: http://dx.doi.org/10.13039/100004319BACKGROUND: Kron et al (Mycoses, 64, 2021, 86) found cost savings for the use of the innovative pharmaceutical isavuconazole in the inpatient setting in Germany (Bismarck-based healthcare system). Little is known about the reimbursement of innovative pharmaceuticals in the inpatient setting of Beveridge-based healthcare systems. OBJECTIVES: The aim of this study was to evaluate the market access process and reimbursement of isavuconazole, exemplary for innovative pharmaceuticals, in England and Spain. PATIENTS/METHODS: Market access processes of both countries were described. Focussing on typical patient clusters for isavuconazole treatment, reimbursement data regarding inpatients with (i) allogeneic haematopoietic stem cell transplantation or (ii) acute myeloid leukaemia was considered. Data were publicly available and of high topicality (England 2020/2021, Spain 2018). Discounting and a currency conversion to Euro were applied. RESULTS: This study showed that market access processes of both countries are broadly similar. Further, full reimbursement of isavuconazole as an innovative pharmaceutical may lead to reduction in resource utilisation. Without medication costs, isavuconazole can thus result in cost savings for both patient clusters due to a reduction in length of stay. CONCLUSIONS: Expenses for innovative pharmaceuticals may be balanced or even lead to cost savings due to a reduction in length of stay. The latter contributes to a greater patient benefit. For both healthcare system, the analyses highlighted drugs' cost-effectiveness and assessing its added value into reimbursement decisions is highly relevant