Ricardo Nuno Salvador

Neuroelectrics · Brain modeling team

Objective: We provide a systematic framework for quantifying the effect of externally applied weak electric fields on realistic neuron compartment models as captured by physiologically relevant quantities such as the membrane potential or transmembrane current as a function of the orientation of the field. Approach: We define a response function...

Intracranial electrodes are used clinically for diagnostic or therapeutic purposes, notably in drug-refractory epilepsy (DRE) among others. Visualization and quantification of the energy delivered through such electrodes is key to understanding how the resulting electric fields modulate neuronal excitability, i.e. the ratio between excitation and i...

Objective: Stereotactic-EEG (SEEG) and scalp EEG recordings can be modeled using mesoscale neural mass population models (NMM). However, the relationship between those mathematical models and the physics of the measurements is unclear. In addition, it is challenging to represent SEEG data by combining NMMs and volume conductor models due to the in...

Work in the last two decades has shown that neural mass models (NMM) can realistically reproduce and explain epileptic seizure transitions as recorded by electrophysiological methods (EEG, SEEG). In previous work, advances were achieved by increasing excitation and heuristically varying network inhibitory coupling parameters in the models. Based on...

Objective We provide a systematic framework for the quantification of the effect of externally applied weak electric fields on realistic neuron compartment models as captured by physiologically relevant quantities such as the membrane potential or transmembrane current as a function of the orientation of the field. Approach We define a response fu...

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its sp...

Objective Stereotactic-EEG (SEEG) and scalp EEG recordings can be modeled using mesoscale neural mass population models (NMM). However, the relationship between those mathematical models and the physics of the measurements is unclear. In addition, it is challenging to represent SEEG data by combining NMMs and volume conductor models due to the inte...

Objective In epilepsy, multichannel transcranial direct electrical stimulation (tDCS) is applied to decrease cortical activity through the delivery of weak currents using several scalp electrodes. We investigated the long-term effects of personalized, multisession, stereotactic-EEG (SEEG)-targeted multichannel tDCS on seizure frequency (SF) and fun...

Objective: Metal implants impact the dosimetry assessment in electrical stimulation techniques. Therefore, they need to be included in numerical models. While currents in the body are ionic, metals only allow electron transport. In fact, charge transfer between tissues and metals requires electric fields to drive electrochemical reactions at the i...

Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic tool in several neuropsychiatric disorders, but its mechanisms of action remain incompletely understood and its effectiveness is highly variable from subject to subject. Some of this inter-subject variance is thought to stem from individual differences in head ana...

The prospect of personalized computational modeling in neurological disorders, and in particular in epilepsy, is poised to revolutionize the field. Work in the last two decades has demonstrated that neural mass models (NMM) can realistically reproduce and explain epileptic seizure transitions as recorded by electrophysiological methods (EEG, SEEG)....

Background Alzheimer’s disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clear...

Background Metal implants impact the dosimetry assessment in electrical stimulation techniques. Therefore, they need to be included in numerical models. While currents in the body are ionic, metals only allow electron transport. In fact, charge transfer between tissues and metals requires electric fields to drive the electrochemical reactions at th...

Methodological studies investigating transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) in paediatric populations are limited. Therefore, we investigated in a paediatric population whether stimulation success of multichannel tDCS over the lDLPFC depends on concurrent task performance and individual...

Combining non-invasive brain stimulation (NIBS) with resting-state functional magnetic resonance imaging (rs-fMRI) is a promising approach to characterize and potentially optimize the brain networks subtending cognition that changes as a function of age. However, whether multifocal NIBS approaches are able to modulate rs-fMRI brain dynamics in aged...

Introduction. Non-invasive neuromodulation via transcranial direct current stimulation (tDCS) is a promising method for modulating plasticity. For the first time multichannel tDCS was used to investigate a larger number of children and young adolescents. Previous studies suggest that tDCS affects cognitive functions. It is assumed that the inferior...

Introduction. Transcranial direct current stimulation (tDCS) is a non-invasive method of modulating brain activity. Previous studies with common tDCS montages have shown that there are positive effects on the left inferior dorsolateral prefrontal cortex (lDLPFC) for both healthy and clinical population like improvement of the working memory. Nevert...

Objective Among older adults, the ability to stand or walk while performing cognitive tasks (i.e., dual-tasking) requires coordinated activation of several brain networks. In this multi-center, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-...

Purpose: Animal and proof-of-principle human studies suggest that cathodal transcranial direct current stimulation may suppress seizures in drug-resistant focal epilepsy. The present study tests the safety, tolerability, and effect size of repeated daily cathodal transcranial direct current stimulation in epilepsy have not been established, limiti...

Background Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction, and stereotyped, repetitive behaviour and sensory interests. To date, there is no effective medication that can improve social communication and interaction in ASD, and effect sizes of behaviour-based psychotherapy remain in the low to mediu...

Transcranial direct current stimulation (tDCS) applied over the prefrontal cortex has been shown to improve behavioral responsiveness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS). However, one potential barrier of clinical response to tDCS is the timing of stimulation...

Background Transcranial direct current stimulation (tDCS), a neuromodulatory non-invasive brain stimulation technique, has shown promising results in basic and clinical studies. The known interindividual variability of the effects, however, limits the efficacy of the technique. Recently we reported neurophysiological effects of tDCS applied over th...

Experimental studies on transcutaneous spinal cord direct current and magnetic stimulation (tsDCS and tsMS, respectively) show promising results in the neuromodulation of spinal sensory and motor pathways, with possible clinical application in spinal functional rehabilitation. Modelling studies on the electric field (EF) distribution during tsDCS a...

Transcranial current stimulation (tCS or tES) protocols yield results that are highly variable across individuals. Part of this variability results from differences in the electric field (E-field) induced in subjects’ brains during stimulation. The E-field determines how neurons respond to stimulation, and it can be used as a proxy for predicting t...

Tumor-treating fields (TTFields) is an antimitotic cancer treatment technique used for glioblastoma multiforme (GBM) and malignant pleural mesothelioma. Although the frequency used is not as high as in hyperthermia, temperature increases due to the Joule effect might be meaningful given the necessary time that these fields should be applied for. Po...

In refractory epilepsy, transcranial direct electrical stimulation (tDCS) is applied to decrease cortical activity with two (conventional tDCS) or several electrodes (multifocal tDCS). We investigated effects of personalized multisession, SEEG-targeted multifocal tDCS on seizure frequency (SF) and scalp functional connectivity (Fc) as measured by E...

Anodal transcranial direct current stimulation (tDCS), applied over the left dorsolateral prefrontal cortex (lDLPFC), can produce significant effects on working memory (WM) performance and associated neurophysiological activity. However, results from previous studies are inconsistent and occasionally contradictory. This inconsistency may be attribu...

The brain is a complex, plastic, electrical network where dysfunctions result in neurological disorders. Transcranial electrical stimulation (tES or tCS, as often abbreviated) is a noninvasive neuromodulatory technique with the potential for network-oriented therapy. The creation of multichannel systems has delivered unprecedented control over the...

Dynamics within and between functional resting‐state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel,...

Objective Cathodal direct current stimulation (cDCS) induces long‐term depression (LTD)‐like reduction of cortical excitability (DCS‐LTD), which has been tested in the treatment of epilepsy with modest effects. In part, this may be due to variable cortical neuron orientation relative to the electric field. We tested, in vivo and in vitro , whether...

Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and proposed as a substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to model mesoscopic ephaptic activity in the human brain and explore its trajectory during...

Background: Advancing age affects the brain's resting-state functional networks. Combining non-invasive brain stimulation (NIBS) with neuroimaging is a promising approach to modulate activity across resting-state functional systems and explore their true contribution to cognitive function in aging. However, substantial individual variability in the...

Disorder of consciousness (DoC) refers to a group of clinical conditions that may emerge after brain injury, characterized by a varying decrease in the level of consciousness that can last from days to years. An understanding of its neural correlates is crucial for the conceptualization and application of effective therapeutic interventions. Here w...

The segmentation of structural MRI data is an essential step for deriving geometrical information about brain tissues. One important application is in transcranial direct current stimulation (e.g., tDCS), a non-invasive neuromodulatory technique where head modeling is required to determine the electric field (E-field) generated in the cortex to pre...

Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single-...

In TTFields therapy, Optune® is used to deliver the electric field to the tumor via 4 transducer arrays. This device monitors the temperature of the transducers and reduces the current whenever a transducer reaches 41ºC. Our aim is to quantify Optune's duty cycle and to predict the steady-state temperature distribution in the head during GBM treatm...

Background: Trans-spinal direct current stimulation (tsDCS) is a non-invasive technique with promising neuromodulatory effects on spinal cord (SC) circuitry. Computational studies are essential to guide effective tsDCS protocols for specific clinical applications. This study aims to combine modelling and experimental studies to determine the elect...

Malignant brain neoplasms have a poor prognosis despite aggressive treatments. Animal models and evidence from human bodily tumors reveal that sustained reduction in tumor perfusion via electrical stimulation promotes tumor necrosis, therefore possibly representing a therapeutic option for patients with brain tumors. Here, we demonstrate that trans...

Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and recently proposed as substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to map ephaptic activity in the human brain and explore its trajectory during aging...

Tumor Treating Fields (TTFields) is a non-invasive technique that can be applied jointly with chemotherapy to treat glioblastoma (GBM). It consists on delivering an alternating current (900 mA) with a frequency of 200 kHz in two perpendicular directions alternately: Anterior-Posterior (AP) and Left-Right (LR) via capacitively coupled transducer arr...

Tumor Treating Fields (TTFields) is a non-invasive technique that can be applied jointly with chemotherapy to treat glioblastoma (GBM). It consists on delivering an alternating current (900 mA) with a frequency of 200 kHz in two perpendicular directions alternately: Anterior-Posterior (AP) and Left-Right (LR) via capacitively coupled transducer arr...

Experimental studies on transcutaneous spinal cord direct current and magnetic stimulation (tsDCS and tsMS) show promising results in the neuromodulation of spinal sensory and motor pathways, with possible application in spinal functional rehabilitation. Modelling studies on the electric field (EF) distribution during tsDCS and tsMS are powerful to...

This chapter provides a broad introduction to computational models that inform and optimize tDCS for both clinical researchers and translational engineers. The first section introduces the rationale for modeling; the next two sections address technical features of modeling relevant to engineers (and to clinicians interested in the limitations of mo...

This chapter summarizes the current knowledge about the biophysics of transcranial direct current stimulation (tDCS). It begins by illustrating the basic physical principles by which weak electric currents applied transcranially induce an electric field inside the brain. This knowledge, mainly derived from computational models, is essential to esti...

Personalization is rapidly becoming standard practice in medical diagnosis and treatment. This study is part of an ambitious program towards computational personalization of neuromodulatory interventions in neuropsychiatry. We propose to model the individual human brain as a network of neural masses embedded in a realistic physical matrix capable o...

Computational models of transcranial current stimulation (tCS) derived from MRI predict the electric field distribution in individual brains with reasonable accuracy and should be used to guide the selection of optimal stimulation parameters. Some recent advances that support this claim are: free toolboxes to generate individual head models for ele...

Providing objective metrics of conscious state is of great theoretical and practical interest. The Luminous project [1] aims to develop information-based metrics of consciousness and methods for its alteration using non-invasive brain stimulation (NIBS). We provide here a consensus overview on the scientific foundations, goals and methods of the pr...

Multifocal tDCS stimulation of network targets correlated with seed regions has been shown to lead to increased efficacy of stimulation as compared to traditional montages [1]. Optimization protocols suitable to distributed network targets have been previously developed and applied to these targets ([1], [2]). Moreover, we expect the application of...

Disorders of Consciousness (DOC) and other consciousness-related alterations can result from completely different events, like traumatic brain injuries (TBI) or functional changes (i.e. Amyotrophic lateral sclerosis or ALS) [1], and therefore lead to different levels and types of dysfunction. The networks underlying consciousness processes that are...

Tumor Treating Fields (TTFields) are a cancer treatment modality that uses alternating electric fields of intermediate frequency (~100-500 kHz) and low intensity (1-3 V/cm) to disrupt cell division. TTFields are delivered by transducer arrays placed on the skin close to the tumor and act regionally and non-invasively to inhibit tumor growth. TTFiel...

Objective: Our aim was to perform a computational study of the electric field (E-field) generated by transcutaneous spinal direct current stimulation (tsDCS) applied over the thoracic, lumbar and sacral spinal cord, in order to assess possible neuromodulatory effects on spinal cord circuitry related with lower limb functions. Approach. A realistic...

Noninvasive electrical stimulation of the central nervous system is attracting increasing interest from the clinical and academic communities as well as from high-tech companies. This interest was sparked by two landmark studies conducted in 2000 and 2001 at the University of G?ttingen, Germany. Michael Nitsche and Walter Paulus showed that by pass...

Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether...

Introduction Existing models of non-invasive brain stimulation focus almost exclusively on the calculation and analysis the electric field distribution. This information is necessary but insufficient to predict the effect of the stimulation, which also depends on the response of neurons and neuronal networks to the applied electric field. Objectiv...

Introduction Magnetic stimulation (MS) of the peripheral and central nervous system has driven an increasing clinical interest since the 1980’s. Modelling studies of the electric field (E-field) distributions and neuron mathematical models contributed to understand the physical effects underlying MS mechanisms. These results can improve coil design...