Effect of the Interindividual Variability on Computational Modeling of Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. This paper investigates how normal variations in anatomy may affect the current flow through the brain. This was done by applying electromagnetic computational methods to human models of different age and gender and by comparing the electric field and current density amplitude distributions within the tissues. Results of this study showed that the general trend of the spatial distributions of the field amplitude shares some gross characteristics among the different human models for the same electrode montages. However, the physical dimension of the subject and his/her morphological and anatomical characteristics somehow influence the detailed field distributions such as the field values

Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines☆

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from “normal-lean” to “super-obese” (20.9 to 53.5 kg/m2). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population

Effects of transcranial direct current stimulation over left dorsolateral pFC on the attentional blink depend on individual baseline performance

Selection mechanisms that dynamically gate only relevant perceptual information for further processing and sustained representation in working memory are critical for goal-directed behavior. We examined whether this gating process can be modulated by anodal transcranial direct current stimulation (tDCS) over left dorsolateral pFC (DLPFC)a region known to play a key role in working memory and conscious access. Specifically, we examined the effects of tDCS on the magnitude of the so-called attentional blink (AB), a deficit in identifying the second of two targets presented in rapid succession. Thirty-four participants performed a standard AB task before (baseline), during, and after 20 min of 1-mA anodal and cathodal tDCS in two separate sessions. On the basis of previous reports linking individual differences in AB magnitude to individual differences in DLPFC activity and on suggestions that effects of tDCS depend on baseline brain activity levels, we hypothesized that anodal tDCS over left DLPFC would modulate the magnitude of the AB as a function of individual baseline AB magnitude. Indeed, individual differences analyses revealed that anodal tDCS decreased the AB in participants with a large baseline AB but increased the AB in participants with a small baseline AB. This effect was only observed during (but not after) stimulation, was not found for cathodal tDCS, and could not be explained by regression to the mean. Notably, the effects of tDCS were not apparent at the group level, highlighting the importance of taking individual variability in performance into account when evaluating the effectiveness of tDCS. These findings support the idea that left DLPFC plays a critical role in the AB and in conscious access more generally. They are also in line with the notion that there is an optimal level of prefrontal activity for cognitive function, with both too little and too much activity hurting performance

Optimizing the neuroplastic effects of cathodal transcranial direct current stimulation over the primary motor cortex and transferability to prefrontal cortex

Die Behandlungsmöglichkeiten neurologischer und neuropsychiatrischer Erkrankungen haben sich in den letzten Jahrzehnten deutlich verbessert, sind aber immer noch eingeschränkt. Eine Dysregulation oder Störung der Neuroplastizität ist bei vielen psychischen und Hirnfunktionsstörungen beteiligt. Hier sind nicht-invasive Hirnstimulationstechniken relevant, die die Plastizität des Gehirns modulieren, ohne die physische Integrität des Schädels zu beeinträchtigen. Eine davon, die transkranielle Gleichstromstimulation (tDCS), hat in mehreren klinischen Pilotstudien vielversprechende Ergebnisse zur Verminderung von Symptomen auf der Grundlage von Störungen des Zentralnervensystems gezeigt. Diese Effekte sind jedoch häufig moderat, zeigen eine nichtlineare Dosisabhängigkeit und eine interindividuelle Variabilität. Um die Wirksamkeit dieses Verfahrens zu verbessern, sind länger anhaltende und homogenere Effekte erforderlich. Dies erfordert neuartige, verbesserte Interventionsstrategien. Darüber hinaus wurden die neuromodulatorischen Wirkungen von tDCS auf den primären motorischen Kortex bisher weitgehend als Grundlage für die Anwendung dieser Intervention auf andere Hirnregionen herangezogen, während eine direkte Untersuchung der physiologischen Wirkungen von tDCS auf nichtmotorische Regionen weitgehend fehlt. Die Arbeit zielt darauf ab, diese Herausforderungen durch den Einsatz innovativer neurophysiologischer und mathematischer Techniken anzugehen, um die Wirksamkeit des kathodalen tDCS über dem primären motorischen Kortex zu verbessern, aber auch die Übertragbarkeit der Ergebnisse auf den präfrontalen Kortex zu untersuchen. Zu diesem Zweck titrierten wir im ersten Schritt systematisch kathodale tDCS-Parameter für das humane motorische Kortexmodell mit unterschiedlichen Intensitäten (1, 2 und 3 mA) und Stimulationsdauern (15, 20 und 30 min). Die Ergebnisse zeigten intensitätsabhängige nichtlineare Effekte, bei denen die Stimulation mit 1 mA eine signifikante Verringerung der Amplitude der motorisch evozierten Potentiale (MEP) induzierte, während die Stimulation mit 2 mA zu einer signifikanten Erhöhung der kortikospinalen Erregbarkeit führte. Protokolle mit höherer Stimulationsintensität (insbesondere Stimulation mit 3 mA) induzierten erneut eine signifikante Verringerung der Erregbarkeit, die etwa eineinhalb Stunden nach der Stimulation andauerte, und waren daher effizienter als die anderen Protokolle. Im zweiten Schritt haben wir untersucht, ob wiederholte tDCS-Protokolle mit unterschiedlichen Intervallen die Nacheffekte verlängern können. Wir verglichen die Auswirkungen von Einzelinterventionen mit konventioneller (1 mA für 15 Minuten) und optimierter kathodaler tDCS (3 mA für 20 Minuten) mit den Auswirkungen einer wiederholten Anwendung in Intervallen von 20 Minuten und 24 Stunden auf die Erregbarkeit des primären motorischen Kortex, basierend auf tierexperimentellen Befunden, dass kurze, aber nicht lange Intervalle zwischen einzelnen Interventionen eine langanhaltende Plastizität erzeugen. Die Ergebnisse zeigten, dass die Dauer der Nacheffekte wiederholter konventioneller und optimierter Protokolle mit kurzen Intervallen im Vergleich zu den jeweiligen Einzelinterventionsprotokollen nahezu unverändert blieb. Für das lange Intervall (24 h) veränderte die Stimulation mit dem herkömmlichen Protokoll die jeweiligen Nachwirkungen nicht signifikant, während sie die Wirksamkeit des optimierten Protokolls im Vergleich zu den jeweiligen Einzelinterventionen verringerte. Ein wichtiges Ergebnis der ersten Studie waren die beobachteten nichtlinearen intensitätsabhängigen Effekte von tDCS, die eine Erklärung für teilweise heterogene Ergebnisse der kathodalen Stimulation bieten können, allerdings hinsichtlich ihrer neurophysiologischen Grundlagen bisher nur unzureichend untersucht waren. Im dritten Schritt haben wir daher die zugrunde liegenden Mechanismen dieser nonlinearen Effekte untersucht. Da tDCS eine NMDA-Rezeptor-abhängige Neuroplastizität erzeugt, die Kalzium-abhängig ist, kann eine solche Nichtlinearität möglicherweise durch unterschiedliche durch die Intervention induzierte Kalziumkonzentrationen erklärt werden, die die Richtung der Plastizität steuern. Wir verabreichten daher den Kalziumkanalblocker Flunarizin in niedrigen (2,5 mg), mittleren (5 mg) oder hohen (10 mg) Dosierungen vor der kathodalen tDCS des motorischen Kortex mit 3 mA für 20 Minuten. Die Ergebnisse zeigten, dass die durch kathodale tDCS hoher Intensität induzierten inhibitorischen Nachwirkungen bei niedrigen, mittleren bzw. hohen Dosierungen eines Kalziumblockers nicht verändert, verringert oder in eine Erregbarkeitserhöhung modifiziert wurden, was die Kalzium-abhängige Direktionalität von tDCS-induzierter Neuroplastizität bestätigt. Das Ergebnis der ersten und zweiten Studie zeigten eine relevante interindividuelle Variabilität der tDCS-Effekte, die eine weitere Quelle für die begrenzte Wirksamkeit dieser Intervention sein könnte. Jüngste In-vivo-Experimente und Computerstudien am Menschen zeigten, dass das tDCS-induzierte elektrische Feld (EF) stark von der individuellen Anatomie des Gehirns und den Leitfähigkeitseigenschaften des Gewebes abhängt. Die EF-Variabilität könnte daher ein wichtiger Faktor für heterogene Ergebnisse der tDCS sein. Im vierten Schritt, basierend auf neurophysiologischen Daten, die in früheren Studien unserer Gruppe erhoben wurden, die tDCS-induzierte MEP- (induziert durch transkranielle Magnetstimulation (TMS)) und zerebrale Blutfluss-Veränderungen (CBF; gemessen durch funktionelle Magnetresonanztomographie (MRT) über arterielles Spin-Labelling) erfaßten, untersuchten wir den Zusammenhang zwischen einzelnen anatomischen Faktoren, tDCS-induziertem EF und den jeweiligen physiologischen Parametern auf der Ebene des Individuums. Zu diesem Zweck wurde für jeden Teilnehmer ein MRT-basiertes realistisches Kopfmodell entworfen, um 1) anatomische Faktoren zu berechnen und 2) die tDCS- und TMS-induzierten elektrischen Felder (EF) zu simulieren. Anschließend untersuchten wir auf regionaler Ebene, welche einzelnen anatomischen Faktoren die simulierten EFs erklären. Schließlich untersuchten wir, welche spezifischen anatomischen und / oder EF-Faktoren die neurophysiologischen Ergebnisse der tDCS vorhersagten. Die Ergebnisse zeigten, dass von den untersuchten anatomischen Faktoren höhere EF-Werte mit einem geringeren Abstand zwischen Elektrode und Kortex (ECD) und einer geringeren Dicke des Liquor cerebrospinalis (CSF) verbunden waren. Zusätzlich waren CSF-Dicke und ECD negativ korreliert, während EFs positiv mit tDCS-induzierten physiologischen Veränderungen korreliert waren. Schließlich untersuchten wir im fünften Schritt die Übertragbarkeit der durch kathodale tDCS induzierten Neuroplastizität vom motorischen auf den präfrontalen Kortex. Die neurophysiologischen Wirkungen von tDCS auf den primärmotorischen Kortex wurden bereits in einer vielzahl von Studien untersucht. Viel weniger ist jedoch hinsichtlich physiologischer Effekte der tDCS auf nichtmotorische Bereiche wie den präfrontalen Kortex bekannt, der eine wichtige Basis für vielfältige kognitive Funktionen darstellt und dessen Dysfunktionen an neuropsychiatrischen Störungen beteiligt sind. Zu diesem Zweck wurde kathodale tDCS mit niedrigen, mittleren und hohen Dosierungen oder eine Placebo-Stimulation über dem primärmotorischen und dorsolateralen präfrontalen Kortex appliziert. Die Nacheffekte der tDCS wurden mittels TMS-Elektroenzephalographie (EEG) und TMS-MEP auf regionaler Ebene für die Ergebnisparameter TMS-evozierte Potentiale (TEP), TMS-evozierte Oszillationen und MEP-Amplitudenänderungen bewertet. Die Ergebnisse zeigten eine dosisabhängige nichtlineare neurophysiologische Wirkung der tDCS über dem motorischen Kortex, die nicht vollständig auf die Ergebnisse der tDCS über dem präfrontalen tDCS übertragbar war. Niedrige und hohe Dosierungen der tDCS über dem motorischen Kortex reduzierten frühe positive TEP-Peaks und MEP-Amplituden, während eine Erhöhung der Amplituden dieser Potentiale für primärmotorische tDCS mit mittlerer Dosierung beobachtet wurde. Im Gegensatz dazu reduzierte präfrontale tDCS mit niedriger, mittlerer und hoher Dosierung die frühen positiven TEP-Amplituden gleichermaßen. Darüber hinaus wurden für beide kortikalen Bereiche keine tDCS-induzierten neuromodulatorischen Effekte auf späte TEP-Amplituden (mit Ausnahme präfrontaler tDCS mit niedriger Dosierung) oder TMS-evozierte Oszillationen beobachtet. Zusammengenommen hat diese Arbeit unter Verwendung innovativer neurophysiologischer, Computergestützter und bildgebender Verfahren wichtige Aspekte in Bezug auf tDCS-induzierte neuroplastische Effekte untersucht, und liefert neue Erkenntnisse für zukünftige Anwendungen von tDCS in Grundlagen- und klinischen Studien.Major advances have been made in treatment of neurological and neuropsychiatric disorders; they have however still significant limitations. A vast body of evidence shows a dysregulation or disruption of neuroplasticity in mental and brain disorders. Here, non-invasive brain stimulation techniques come into play, which modulate brain plasticity without disrupting the integrity of the skull. One of those, transcranial direct current stimulation (tDCS), has shown promising results in several pilot clinical studies to improve symptoms of central nervous system disorders; but, in general, effects are often moderate, show nonlinear dosage-dependency, and interindividual variability. For improving the efficacy of this tool, more sustained, and homogeneous effects are required. This requires novel, improved intervention strategies. In addition, neuromodulatory effects of tDCS over the primary motor cortex were largely taken as a template so far for the use of this intervention over other brain regions, whereas a direct exploration of the physiological effects of tDCS on non-motor regions is largely missing. The thesis aims to address these challenges, by utilizing advanced neurophysiological and computational techniques, aiming to improve the efficacy of cathodal tDCS over the primary motor cortex, but also to explore the transferability of the results to the prefrontal cortex. To this end, we at the first step systematically titrated cathodal tDCS parameters for the human motor cortex model with different intensities (1, 2, and 3mA) and durations (15, 20 and 30 min). The results revealed intensity-dependent nonlinear effects, in which stimulation with 1 mA induced a significant motor evoked potentials (MEP) amplitude diminution, while stimulation with 2 mA resulted in a significant corticospinal excitability enhancement. Protocols with higher stimulation intensity (specifically stimulation with 3 mA) induced again a significant excitability diminution lasting for about one and half hour after stimulation, and thus were more efficient than the other protocols. At the second step, we explored if repeated tDCS protocols with different intervals can prolong the after-effects. We compared the impact of single interventions of conventional (1mA for 15min) and optimized cathodal tDCS (3mA for 20min) with the effects of repeated application with intervals of 20 min and 24 hours on primary motor cortex excitability, based on the assumption derived from animal models that short, but not long intervals induce late phase plasticity. The results revealed that the duration of after-effects of repeated conventional and optimized protocols with short intervals remained nearly unchanged, as compared to the respective single intervention protocols. For the long interval (24 h), stimulation with the conventional protocol did not significantly alter respective after-effects, while it reduced the efficacy of the optimized protocol, as compared with respective single interventions. One important outcome of the first study were the observed nonlinear intensity-dependent effects of tDCS, which might be an explanation for sometimes heterogeneous outcomes of cathodal stimulation, and are not well explained at the neurophysiological level. At the third step we therefore explored the underlaying mechanisms of this nonlinearity. Since tDCS generates NMDA receptor-dependent neuroplasticity, which has calcium channel properties, such non-linearity can likely be explained by different levels of calcium concentration induced by the intervention, which control for the directionality of plasticity. We therefore administrated the calcium channel blocker flunarizine in low (2.5 mg), medium (5 mg) or high (10 mg) dosages before cathodal motor cortex tDCS of 3mA for 20min. The results revealed that the inhibitory after-effects induced by high intensity cathodal tDCS were unchanged, diminished, or converted to excitability enhancement with low, medium and high dosages of a calcium blocker, respectively, which confirms the calcium-dependent directionality of tDCS-induced neuroplasticity. The outcome of the first and second studies showed also relevant inter-individual variability of tDCS effects, which could be another source of limited efficacy of this intervention. Recent human in-vivo experiments and computational studies indicated that the tDCS-induced electrical field (EF) depends strongly on individual brain anatomy and tissue conductivity properties. EF variability might thus be an important factor for heterogeneous outcomes of tDCS. At the fourth step, based on neurophysiological data obtained in former studies of our group, which explored tDCS-altered MEP (induced by transcranial magnetic stimulation (TMS)) and cerebral blood flow (CBF; measured by functional magnetic resonance imaging (MRI) via arterial spin labeling), we investigated the association between individual anatomical factors and tDCS-induced EF, and the respective physiological outcomes at the level of the individual. To this end, for each participant, a MRI-based realistic head model was designed to 1) calculate anatomical factors and 2) simulate the tDCS- and TMS-induced electrical fields (EF). We then investigated at the regional level which individual anatomical factors explain the simulated EFs. Finally, we explored which specific anatomical and/or EF factors predicted the neurophysiological outcomes of tDCS. The results indicated that, of the included anatomical factors, higher EF values were associated with lower electrode to cortex distance (ECD), and cerebrospinal fluid (CSF) thickness. In addition, CSF thickness, and ECD were negatively correlated, whereas EFs were positively correlated with tDCS-induced physiological changes. Finally, at the fifth step, we explored the transferability of cathodal tDCS-induced neuroplasticity from the motor to the prefrontal cortex. Neurophysiological effects of tDCS have been extensively studied over the primary motor cortex. Much less is however known for its effects over non-motor areas, such as the prefrontal cortex, which is the neuronal foundation for many high-level cognitive functions, and involved in neuropsychiatric disorders. To this end, cathodal tDCS was applied with low, medium, and high dosages, or as sham stimulation, and applied over the primary motor and dorsolateral prefrontal cortex. After-effects of tDCS were evaluated via TMS-electroencephalography (EEG), and TMS-MEP at the regional level, for the outcome parameters TMS-evoked potentials (TEP), TMS-evoked oscillations, and MEP amplitude alterations. The results indicated a dosage-dependent nonlinear neurophysiological effect of motor cortex tDCS, which was not one-to-one transferable to the results of prefrontal tDCS. Low and high dosages of motor cortex tDCS reduced early positive TEP peaks, and MEP amplitudes, while an enhancement was observed for medium dosage motor cortex tDCS (early positive TEP peak and MEP amplitudes). In contrast, prefrontal low, medium and high dosage tDCS uniformly reduced the early positive TEP peak amplitudes. Furthermore, for both cortical areas, tDCS-induced neuromodulatory effects were not observed for late TEP peaks (with the exception of low-dosage prefrontal tDCS), nor TMS-evoked oscillations. Taken together, using advanced neurophysiological, computational and neuroimaging techniques, this thesis has addressed important challenges regarding tDCS-induced neuroplastic effects, and thus provides new insight for future applications of tDCS in basic and clinical studies

Standard Non-Personalized Electric Field Modeling of Twenty Typical tDCS Electrode Configurations via the Computational Finite Element Method: Contributions and Limitations of Two Different Approaches

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation procedure to modulate cortical excitability and related brain functions. tDCS can effectively alter multiple brain functions in healthy humans and is suggested as a therapeutic tool in several neurological and psychiatric diseases. However, variability of results is an important limitation of this method. This variability may be due to multiple factors, including age, head and brain anatomy (including skull, skin, CSF and meninges), cognitive reserve and baseline performance level, specific task demands, as well as comorbidities in clinical settings. Different electrode montages are a further source of variability between tDCS studies. A procedure to estimate the electric field generated by specific tDCS electrode configurations, which can be helpful to adapt stimulation protocols, is the computational finite element method. This approach is useful to provide a priori modeling of the current spread and electric field intensity that will be generated according to the implemented electrode montage. Here, we present standard, non-personalized model-based electric field simulations for motor, dorsolateral prefrontal, and posterior parietal cortex stimulation according to twenty typical tDCS electrode configurations using two different current flow modeling software packages. The resulting simulated maximum intensity of the electric field, focality, and current spread were similar, but not identical, between models. The advantages and limitations of both mathematical simulations of the electric field are presented and discussed systematically, including aspects that, at present, prevent more widespread application of respective simulation approaches in the field of non-invasive brain stimulatio

Inter-individual variability in current direction for common tDCS montages

The direction of applied electric current relative to the cortical surface is a key determinant of transcranial direct current stimulation (tDCS) effects. Inter-individual differences in anatomy affect the consistency of current direction at a cortical target, likely leading to inter-individual variability in current direction. However, the degree of this variability remains undetermined. Using current flow modelling (CFM), we quantified the inter-individual variability in tDCS current direction at a cortical target (left primary motor cortex, M1). Three montages targeting M1 using circular electrodes were compared: PA-tDCS directed current perpendicular to the central sulcus in a posterior-anterior direction relative to M1, ML-tDCS directed current parallel to the central sulcus in a medio-lateral direction, and conventional-tDCS applied electrodes over M1 and the contralateral forehead. In 50 healthy brain scans from the Human Connectome Project, we extracted current direction and intensity from the gray matter surface in the sulcal bank (M1BANK) and gyral crown (M1CROWN), and neighbouring primary somatosensory cortex (S1BANK and S1CROWN). Results confirmed substantial inter-individual variability in current direction (50%-150%) across all montages. Radial inward current produced by PA-tDCS was predominantly located in M1BANK, whereas for conventional-tDCS it was clustered in M1CROWN. The predominantly radial inward current in functionally distinct subregions of M1 raises the testable hypothesis that PA-tDCS and conventional-tDCS modulate cortical excitability through different mechanisms. We show that electrode locations can be used to closely approximate current direction in M1 and precentral gyrus, providing a landmark-based method for tDCS application to address the hypothesis without the need for MRI. By contrast, ML-tDCS current was more tangentially oriented, which is associated with little somatic polarization. Substantial inter-individual variability in current direction likely contributes to variable neuromodulation effects reported for these protocols, emphasising the need for individualised electrode montages, including the control of current direction

Anodal tDCS over the medial prefrontal cortex enhances behavioral adaptation after punishments during reversal learning through increased updating of unchosen choice options

The medial prefrontal cortex (mPFC) is thought to be central for flexible behavioral adaptation. However, the causal relationship between mPFC activity and this behavior is incompletely understood. We investigated whether transcranial direct current stimulation (tDCS) over the mPFC alters flexible behavioral adaptation during reward-based decision-making, targeting Montreal Neurological Institute (MNI) coordinates X = -8, Y = 62, Z = 12, which has previously been associated with impaired behavioral adaptation in alcohol-dependent patients. Healthy human participants (n = 61) received either anodal (n = 30) or cathodal (n = 31) tDCS versus sham tDCS while performing a reversal learning task. To assess the mechanisms of reinforcement learning (RL) underlying our behavioral observations, we applied computational models that varied with respect to the updating of the unchosen choice option. We observed that anodal stimulation over the mPFC induced increased choice switching after punishments compared with sham stimulation, whereas cathodal stimulation showed no effect on participants' behavior compared with sham stimulation. RL revealed increased updating of the unchosen choice option under anodal as compared with sham stimulation, which accounted well for the increased tendency to switch after punishments. Our findings provide a potential model for tDCS interventions in conditions related to flexible behavioral adaptation, such as addiction

Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts

Objective. Transcranial magnetic stimulation (TMS) is a promising non-invasive tool for modulating the brain activity. Despite the widespread therapeutic and diagnostic use of TMS in neurology and psychiatry, its observed response remains hard to predict, limiting its further development and applications. Although the stimulation intensity is always maximum at the cortical surface near the coil, experiments reveal that TMS can affect deeper brain regions as well. Approach. The explanation of this spread might be found in the white matter fiber tracts, connecting cortical and subcortical structures. When applying an electric field on neurons, their membrane potential is altered. If this change is significant, more likely near the TMS coil, action potentials might be initiated and propagated along the fiber tracts towards deeper regions. In order to understand and apply TMS more effectively, it is important to capture and account for this interaction as accurately as possible. Therefore, we compute, next to the induced electric fields in the brain, the spatial distribution of the membrane potentials along the fiber tracts and its temporal dynamics. Main results. This paper introduces a computational TMS model in which electromagnetism and neurophysiology are combined. Realistic geometry and tissue anisotropy are included using magnetic resonance imaging and targeted white matter fiber tracts are traced using tractography based on diffusion tensor imaging. The position and orientation of the coil can directly be retrieved from the neuronavigation system. Incorporating these features warrants both patient- and case-specific results. Significance. The presented model gives insight in the activity propagation through the brain and can therefore explain the observed clinical responses to TMS and their inter- and/or intra-subject variability. We aspire to advance towards an accurate, flexible and personalized TMS model that helps to understand stimulation in the connected brain and to target more focused and deeper brain regions

Individualisation of transcranial electric stimulation to improve motor function after stroke:Current challenges and future perspective

Transcranial electric stimulation (tES) is a non-invasive brain stimulation technique that could potentially improve motor rehabilitation after stroke. However, the effects of tES are in general stronger in healthy individuals compared to people with stroke. Interindividual variability in brain structure and function due to stroke potentially explain this difference in effects. This thesis describes the development of methods to facilitate the individualisation of tES in people with stroke and identifies objective neurophysiological correlates of motor learning that could potentially help to monitor the response to tES.In chapter 2, EEG correlates of explicit motor task learning were derived in healthy, young participants. Chapter 3 investigated the effects of 3 different tDCS configurations (sham, targeting contralateral M1 and targeting the full resting motor network) on corticospinal excitability. Both conventional and motor network tDCS did not increase corticospinal excitability relative to sham stimulation. Chapter 4 describes methods to create head models of people with stroke and assesses the effects of stroke lesions on the electric fields within stimulation targets. Chapter 5 describes a method to experimentally determine the electric conductivity of the stroke lesion. Finally, Chapter 6 analyses the electric fields generated by conventional tDCS in people with stroke and age-matched controls. It is shown that the one-size-fits-all approach results in more variable electric fields in people with stroke compared to controls. Optimisation of the electrode positions to maximise the electric field in stimulation targets increases the electric fields in people with stroke to the same level as found in healthy controls.This thesis shows anatomical and motor function variability exists between people with stroke due to differences in lesion characteristics. While there are several opportunities to individualise tES, more research is needed to investigate if this improves the effects of tES. As such, clinical implementation of tES seems unrealistic in the foreseeable future.<br/