This study aimed to develop an open-source algorithm for the pressure-reactivity index (PRx) to monitor cerebral autoregulation (CA) in pediatric severe traumatic brain injury (sTBI) and compared derived optimal cerebral perfusion pressure (CPPopt) with real-time CPP in relation to long-term outcome. Retrospective study in children (< 18 years) with sTBI admitted to the pediatric intensive care unit (PICU) for intracranial pressure (ICP) monitoring between 2016 and 2023. ICP was analyzed on an insult basis and correlated with outcome. PRx was calculated as Pearson correlation coefficient between ICP and mean arterial pressure. CPPopt was derived as weighted average of CPP-PRx over time. Outcome was determined via Pediatric Cerebral Performance Category (PCPC) scale at one year post-injury. Logistic regression and mixed effect models were developed to associate PRx and CPPopt with outcome. In total 50 children were included, 35 with favorable (PCPC 1–3) and 15 with unfavorable outcome (PCPC 4–6). ICP insults correlated with unfavorable outcome at 20 mmHg for 7 min duration. Mean CPPopt yield was 75.4% of monitoring time. Mean and median PRx and CPPopt yield associated with unfavorable outcome, with odds ratio (OR) 2.49 (1.38–4.50), 1.38 (1.08–1.76) and 0.95 (0.92–0.97) (p < 0.001). PRx thresholds 0.0, 0.20, 0.25 and 0.30 resulted in OR 1.01 (1.00–1.02) (p < 0.006). CPP in optimal range associated with unfavorable outcome on day one (0.018, p = 0.029) and four (-0.026, p = 0.025). Our algorithm can obtain optimal targets for pediatric neuromonitoring that showed association with long-term outcome, and is now available open source.

Background: Amyotrophic lateral sclerosis (ALS) is a lethal progressive neurodegenerative disease characterized by upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Their varying degree of involvement results in a clinical heterogenous picture, making clinical assessments of UMN signs in patients with ALS often challenging. We therefore explored whether instrumented assessment using robotic manipulation could potentially be a valuable tool to study signs of UMN involvement. Methods: We examined the dynamics of the wrist joint of 15 patients with ALS and 15 healthy controls using a Wristalyzer single-axis robotic manipulator and electromyography (EMG) recordings in the flexor and extensor muscles in the forearm. Multi-sinusoidal torque perturbations were applied, during which participants were asked to either relax, comply or resist. A neuromuscular model was used to study muscle viscoelasticity, e.g. stiffness (k) and viscosity (b), and reflexive properties, such as velocity, position and force feedback gains (kv, kp and kf, respectively) that dominated the responses. We further obtained clinical signs of LMN (muscle strength) and UMN (e.g. reflexes, spasticity) dysfunction, and evaluated their relation with the estimated neuromuscular model parameters. Results: Only force feedback gains (kf) were elevated in patients (p = 0.033) compared to controls. Higher kf, as well as the resulting reflexive torque (Tref), were both associated with more severe UMN dysfunction in the examined arm (p = 0.040 and p < 0.001). Patients with UMN symptoms in the examined arm had increased kf and Tref compared to controls (both p = 0.037). Neither of these measures was related to muscle strength, but muscle stiffness (k) was lower in weaker patients (p = 0.012). All these findings were obtained from the relaxed test. No differences were observed during the instructions comply and resist. Conclusions: This findings are proof-of-concept that instrumented assessment using robotic manipulation is a feasible technique in ALS, which may provide quantitative, operator-independent measures relating to UMN symptoms. Elevated force feedback gains, driving larger reflexive muscle torques, appear to be particularly indicative of clinically established levels of UMN dysfunction in the examined arm.

Objective: Accurate estimation of stiffness across anatomical levels (i.e., joint, muscle, and tendon) in vivo has long been a challenge in biomechanics. Recent advances in electromyography (EMG)-driven musculoskeletal modeling have allowed the non-invasive estimation of stiffness during dynamic joint rotations. Nevertheless, validation has been limited to the joint level due to a lack of simultaneous in vivo experimental measurements of muscle and tendon stiffness. Methods: With a focus on the triceps surae, we employed a novel perturbation-based experimental technique informed by dynamometry and ultrasonography to derive reference stiffness at the joint, muscle, and tendon levels simultaneously. Here, we propose a new EMG-driven model-based approach that does not require external joint perturbation, nor ultrasonography, to estimate multi-level stiffness. We present a novel set of closed-form equations that enables the person-specific tuning of musculoskeletal parameters dictating biological stiffness, including passive force-length relationships in modeled muscles and tendons. Results: Calibrated EMG-driven musculoskeletal models estimated the reference data with average normalized root-mean-square error ≈ 20%. Moreover, only when calibrated tendons were approximately four times more compliant than typically modeled, our approach could estimate multi-level reference stiffness. Conclusion: EMG-driven musculoskeletal models can be calibrated on a larger set of reference data to provide more realistic values for the biomechanical variables across multiple anatomical levels. Moreover, the tendon models that are typically used in musculoskeletal modeling are too stiff. Significance: Calibrated musculoskeletal models informed by experimental measurements give access to an augmented range of biomechanical variables that might not be easily measured with sensors alone.

Background: After mild stroke persistent balance limitations may occur, creating a risk factor for fear of falling, falls, and reduced activity levels. Objective. To investigate whether individuals in the chronic phase after mild stroke show balance and gait limitations, elevated fall risk, reduced balance confidence, and physical activity levels compared to healthy controls. Methods: An observational case-control study was performed. Main outcomes included the Mini-Balance Evaluation Systems Test (mini-BEST), Timed Up and Go (TUG), 10-m Walking Test (10-MWT), and 6-item version Activity-specific Balance Confidence (6-ABC) scale which were measured in 1 session. Objectively measured daily physical activity was measured for 7 consecutive days. Fall rate in daily life was recorded for 12 months. Individuals after a mild stroke were considered eligible when they: (1) sustained a transient ischemic attack or stroke longer than 6 months ago, resulting in motor and/or sensory loss in the contralesional leg at the time of stroke, (2) showed (near-) complete motor function, that is, ≥24 points on the Fugl-Meyer Assessment—Lower Extremity (range: 0-28). Results: Forty-seven healthy controls and 70 participants after mild stroke were included. Participants with stroke fell more than twice as often as healthy controls, had a 2 point lower median score on the mini-BEST, were 1.7 second slower on TUG, 0.6 km/h slower on the 10-MWT, and had a 12% lower 6-ABC score. Intensity for both total activity (8%) as well as walking activity (6%) was lower in the participants with stroke, while no differences were found in terms of duration. Conclusions: Individuals in the chronic phase after a mild stroke demonstrate persistent balance limitations and have an increased fall risk. Our results point at an unmet clinical need in this population.

Human hands are complex biomechanical systems that allow for dexterous tasks with many degrees of freedom. Coordination of the fingers is essential for many activities of daily living and involves integrating sensory signals. During this sensory integration, the central nervous system deals with the uncertainty of sensory signals. When handling compliant objects, force and position are related. Interactions with stiff objects result in reduced position changes and increased force changes compared to compliant objects. Literature has shown sensory integration of force and position at the shoulder. Nevertheless, differences in sensory requirements between proximal and distal joints may lead to different proprioceptive representations, hence findings at proximal joints cannot be directly transferred to distal joints, such as the digits. Here, we investigate the sensory integration of force and position during pinching. A haptic manipulator rendered a virtual spring with adjustable stiffness between the index finger and the thumb. Participants had to blindly reproduce a force against the spring. In both visual reference trials and blind reproduction trials, the relation between pinch force and spring compression was constant. However, by covertly changing the spring characteristics in catch trials into an adjusted force-position relation, the participants’ weighting of force and position could be revealed. In agreement with previous studies on the shoulder, participants relied more on force sense in trials with higher stiffness. This study demonstrated stiffness-dependent sensory integration of force and position feedback during pinching.

Background: Spasticity, i.e. stretch hyperreflexia, increases joint resistance similar to symptoms like hypertonia and contractures. Botulinum neurotoxin-A (BoNT-A) injections are a widely used intervention to reduce spasticity. BoNT-A effects on spasticity are poorly understood, because clinical measures, e.g. modified Ashworth scale (MAS), cannot differentiate between the symptoms affecting joint resistance. This paper distinguishes the contributions of the reflexive and intrinsic pathways to ankle joint hyper-resistance for participants treated with BoNT-A injections. We hypothesized that the overall joint resistance and reflexive contribution decrease 6 weeks after injection, while returning close to baseline after 12 weeks. Methods: Nine participants with spasticity after spinal cord injury or after stroke were evaluated across three sessions: 0, 6 and 12 weeks after BoNT-A injection in the calf muscles. Evaluation included clinical measures (MAS, Tardieu Scale) and motorized instrumented assessment using the instrumented spasticity test (SPAT) and parallel-cascade (PC) system identification. Assessments included measures for: (1) overall resistance from MAS and fast velocity SPAT; (2) reflexive resistance contribution from Tardieu Scale, difference between fast and slow velocity SPAT and PC reflexive gain; and (3) intrinsic resistance contribution from slow velocity SPAT and PC intrinsic stiffness/damping. Results: Individually, the hypothesized BoNT-A effect, the combination of a reduced resistance (week 6) and return towards baseline (week 12), was observed in the MAS (5 participants), fast velocity SPAT (2 participants), Tardieu Scale (2 participants), SPAT (1 participant) and reflexive gain (4 participants). On group-level, the hypothesis was only confirmed for the MAS, which showed a significant resistance reduction at week 6. All instrumented measures were strongly correlated when quantifying the same resistance contribution. Conclusion: At group-level, the expected joint resistance reduction due to BoNT-A injections was only observed in the MAS (overall resistance). This observed reduction could not be attributed to an unambiguous group-level reduction of the reflexive resistance contribution, as no instrumented measure confirmed the hypothesis. Validity of the instrumented measures was supported through a strong association between different assessment methods. Therefore, further quantification of the individual contributions to joint resistance changes using instrumented measures across a large sample size are essential to understand the heterogeneous response to BoNT-A injections.

Careful control of joint impedance, or dynamic joint stiffness, is crucial for successful performance of movement. Time-varying system identification (TV-SysID) enables quantification of joint impedance during movement. Several TV-SysID methods exist, but have never been systematically compared. Here, we simulate time-varying joint behavior and propose three performance metrics that enable to quantify and compare TV-SysID methods. Time-varying joint stiffness is simulated using a square wave and subsequently estimated with three TV-SysID methods: the ensemble, short data segment, and basis impulse response function method. These methods were compared based on (1) bias with respect to the simulated joint stiffness, (2) random error across 100 simulation trials, and (3) maximum adaptation speed in joint stiffness that can be captured. This approach revealed that each TV-SysID method has its own unique properties. The simulation method and performance metrics pave the way for developing a framework to quantify the strengths and weaknesses of TV-SysID algorithms for estimating joint impedance.

The simultaneous modulation of joint torque and stiffness enables humans to perform large repertoires of movements, while versatilely adapting to external mechanical demands. Multi-muscle force control is key for joint torque and stiffness modulation. However, the inability to directly measure muscle force in the intact moving human prevents understanding how muscle force causally links to joint torque and stiffness. Joint stiffness is predominantly estimated via joint perturbation-based experiments in combination with system identification techniques. However, these techniques provide joint-level stiffness estimations with no causal link to the underlying muscle forces. Moreover, the need for joint perturbations limits the generalizability and applicability to study natural movements. Here, we present an electromyography (EMG)-driven musculoskeletal modeling framework that can be calibrated to match reference joint torque and stiffness profiles simultaneously via a multi-term objective function. EMG-driven models calibrated on <2 s of reference torque and stiffness data could blindly estimate reference profiles across 100 s of data not used for calibration. Model calibrations using an objective function comprising torque and stiffness terms always provided less feasible solutions than an objective function comprising solely a torque term, thereby reducing the space of feasible muscle–tendon parameters. Results also showed the proposed framework's ability to estimate joint stiffness in unperturbed conditions, while capturing differences against stiffness profiles derived during perturbed conditions. The proposed framework may provide new ways for studying causal relationships between muscle force and joint torque and stiffness during movements in interaction with the environment, with broad implications across biomechanics, rehabilitation and robotics.

Transcranial direct current stimulation (tDCS) is a promising tool to improve and speed up motor rehabilitation after stroke, but inconsistent clinical effects refrain tDCS from clinical implementation. Therefore, this study aimed to assess the need for individualized tDCS configurations in stroke, considering interindividual variability in brain anatomy and motor function representation. We simulated tDCS in individualized MRI-based finite element head models of 21 chronic stroke subjects and 10 healthy age-matched controls. An anatomy-based stimulation target, i.e. the motor hand knob, was identified with MRI, whereas a motor function-based stimulation target was identified with EEG. For each subject, we simulated conventional anodal tDCS electrode configurations and optimized electrode configurations to maximize stimulation strength within the anatomical and functional target. The normal component of the electric field was extracted and compared between subjects with stroke and healthy, age-matched controls, for both targets, during conventional and optimized tDCS. Electrical field strength was significantly lower, more variable and more frequently in opposite polarity for subjects with stroke compared to healthy age-matched subjects, both for the anatomical and functional target with conventional, i.e. non-individualized, electrode configurations. Optimized, i.e. individualized, electrode configurations increased the electrical field strength in the anatomical and functional target for subjects with stroke but did not reach the same levels as in healthy subjects. Considering individual brain structure and motor function is crucial for applying tDCS in subjects with stroke. Lack of individualized tDCS configurations in subjects with stroke results in lower electric fields in stimulation targets, which may partially explain the inconsistent clinical effects of tDCS in stroke trials.

Knowledge on joint impedance during walking in various conditions is relevant for clinical decision-making and the development of robotic gait trainers, leg prostheses, leg orthotics and wearable exoskeletons. Whereas ankle impedance during walking has been experimentally assessed, knee and hip joint impedance during walking have not been identified yet. Here we developed and evaluated a lower limb perturbator to identify hip, knee and ankle joint impedance during treadmill walking. The lower limb perturbator (LOPER) consists of an actuator connected to the thigh via rods. The LOPER allows to apply force perturbations to a free-hanging leg, while standing on the contralateral leg, with a bandwidth of up to 39 Hz. While walking in minimal impedance mode, the interaction forces between LOPER and the thigh were low (<5N) and the effect on the walking pattern was smaller than the within-subject variability during normal walking. Using a non-linear multibody dynamical model of swing leg dynamics, the hip, knee and ankle joint impedance were estimated at three time points during the swing phase for nine subjects walking at a speed of 0.5 m/s. The identified model was well able to predict the experimental responses for the hip and knee, since the mean variance accounted (VAF) for was 99% and 96%, respectively. The ankle lacked a consistent response and the mean VAF of the model fit was only 77%, and therefore the estimated ankle impedance was not reliable. The averaged across-subjects stiffness varied between the three time points within 34-66 and 0-3.5 Nm/rad Nm/rad for the hip and knee joint respectively. The damping varied between 1.9-4.6 and 0.02-0.14 Nms/rad Nms/rad for hip and knee respectively. The developed LOPER has a negligible effect on the unperturbed walking pattern and allows to identify hip and knee impedance during the swing phase.

Joint impedance plays an important role in postural control and movement. However, current experimental knowledge on lower limb impedance during gait is limited to the ankle joint. We designed the LOwer limb PERturbator (LOPER) aimed to assess knee and hip joint impedance during gait. The LOPER applies force perturbations with a 39 Hz bandwidth, tested on a free-hanging leg. In minimal impedance mode, peak interaction forces during walking are low (&lt; 5 N). Also, this mode has a negligible effect on the gait pattern, as it is smaller than the within-subject variability during normal walking. In short, the LOPER is a transparent device able to elicit a clear response at both hip and knee joints to investigate lower limb dynamics. A second motor added to the LOPER could improve isolation of the perturbation contribution to knee and hip dynamics. People with neurological disorders can benefit from knowledge of joint impedance during gait through improved biomimetic devices and clinical decision making.

Recent studies have established the presence of nociceptive steady-state evoked potentials (SSEPs), generated in response to thermal or intra-epidermal electric stimuli. This study explores cortical sources and generation mechanisms of nociceptive SSEPs in response to intra-epidermal electric stimuli. Our method was to stimulate healthy volunteers (n = 22, all men) with 100 intra-epidermal pulse sequences. Each sequence had a duration of 8.5 s, and consisted of pulses with a pulse rate between 20 and 200 Hz, which was frequency modulated with a multisine waveform of 3, 7 and 13 Hz (n = 10, 1 excluded) or 3 and 7 Hz (n = 12, 1 excluded). As a result, evoked potentials in response to stimulation onset and contralateral SSEPs at 3 and 7 Hz were observed. The SSEPs at 3 and 7 Hz had an average time delay of 137 ms and 143 ms respectively. The evoked potential in response to stimulation onset had a contralateral minimum (N1) at 115 ms and a central maximum (P2) at 300 ms. Sources for the multisine SSEP at 3 and 7 Hz were found through beamforming near the primary and secondary somatosensory cortex. Sources for the N1 were found near the primary and secondary somatosensory cortex. Sources for the N2-P2 were found near the supplementary motor area. Harmonic and intermodulation frequencies in the SSEP power spectrum remained below a detectable level and no evidence for nonlinearity of nociceptive processing, i.e. processing of peripheral firing rate into cortical evoked potentials, was found.

Tremor is thought to be an effect of oscillatory activity within the sensorimotor network. To date, the underlying pathological brain networks are not fully understood. Disentangling tremor activity from voluntary motor output and sensorimotor feedback systems is challenging. To better understand the intrinsic sensorimotor fingerprint underlying tremor, we aimed to disentangle the sensorimotor system into driving (motor) and feedback/compensatory (sensory) neuronal involvement, and aimed to pinpoint tremor activity in essential tremor (ET) and tremor-dominant Parkinson's disease (PD) with a novel closed-loop approach. Eighteen ET patients, 14 tremor-dominant PD patients, and 18 healthy controls were included. An MR-compatible wrist manipulator was employed during functional MRI (fMRI) while muscle activity during (in)voluntary movements was concurrently recorded using electromyography (EMG). Tremor was quantified based on EMG and correlated to brain activity. Participants performed three tasks: an active wrist motor task, a passive wrist movement task, and rest (no wrist movement). The results in healthy controls proved that our experimental paradigm activated the expected motor and sensory networks separately using the active (motor) and passive (sensory) task. ET patients showed similar patterns of activation within the motor and sensory networks. PD patients had less activity during the active motor task in the cerebellum and basal ganglia compared to ET and healthy controls. EMG showed that in ET, tremor fluctuations correlated positively with activity in the inferior olive region, and that in PD tremor fluctuations correlated positively with cerebellar activity. Our novel approach with an MR-compatible wrist manipulator, allowed to investigate the involvement of the motor and sensory networks separately, and as such to better understand tremor pathophysiology. In ET sensorimotor network function did not differ from healthy controls. PD showed less motor-related activity. Focusing on tremor, our results indicate involvement of the inferior olive in ET tremor modulation, and cerebellar involvement in PD tremor modulation.

Joint impedance is a common way of representing human joint dynamics. Since ankle joint impedance varies within the gait cycle, time-varying system identification techniques can be used to estimate it. Commonly, time-varying system identification techniques assume repeatably of joint impedance over cyclic motions, without taking into consideration the inherent variability of human behavior. In this paper, a method that assumes smooth, cyclic joint impedance, yet allows for cycle-to-cycle variability, is proposed. The method was tested on isometric, cyclic experimental data from the ankle under conditions with a time variation comparable to the expected one during the gait cycle. The estimated model could describe the data with high accuracy (VAF of 94.96%) and retrieve realistic inertia, damping and stiffness parameters. The results provide motivation to further apply the method on experiments under dynamic conditions and to employ the proposed method as a tool for investigating the human joint dynamics during cyclic movements.

Background: People with brain or neural injuries, such as cerebral palsy or spinal cord injury, commonly have joint hyper-resistance. Diagnosis and treatment of joint hyper-resistance is challenging due to a mix of tonic and phasic contributions. The parallel-cascade (PC) system identification technique offers a potential solution to disentangle the intrinsic (tonic) and reflexive (phasic) contributions to joint impedance, i.e. resistance. However, a simultaneous neurophysiological validation of both intrinsic and reflexive joint impedances is lacking. This simultaneous validation is important given the mix of tonic and phasic contributions to joint hyper-resistance. Therefore, the main goal of this paper is to perform a group-level neurophysiological validation of the PC system identification technique using electromyography (EMG) measurements. Methods: Ten healthy people participated in the study. Perturbations were applied to the ankle joint to elicit reflexes and allow for system identification. Participants completed 20 hold periods of 60 seconds, assumed to have constant joint impedance, with varying magnitudes of intrinsic and reflexive joint impedances across periods. Each hold period provided a paired data point between the PC-based estimates and neurophysiological measures, i.e. between intrinsic stiffness and background EMG, and between reflexive gain and reflex EMG. Results: The intrinsic paired data points, with all subjects combined, were strongly correlated, with a range of r=[0.870.91] in both ankle plantarflexors and dorsiflexors. The reflexive paired data points were moderately correlated, with r=[0.640.69] in the ankle plantarflexors only. Conclusion: An agreement with the neurophysiological basis on which PC algorithms are built is necessary to support its clinical application in people with joint hyper-resistance. Our results show this agreement for the PC system identification technique on group-level. Consequently, these results show the validity of the use of the technique for the integrated assessment and training of people with joint hyper-resistance in clinical practice.

Motorized assessment of the stretch reflex is instrumental to gain understanding of the stretch reflex, its physiological origin and to differentiate effects of neurological disorders, like spasticity. Both short-latency (M1) and medium-latency (M2) stretch reflexes have been reported to depend on the velocity and acceleration of an applied ramp-and-hold perturbation. In the upper limb, M2 has also been reported to depend on stretch duration. However, wrong conclusions might have been drawn in previous studies as the interdependence of perturbation parameters (amplitude, duration, velocity, and acceleration) possibly created uncontrolled, confounding effects. We disentangled the duration-, velocity-, and acceleration-dependence and their interactions of the M1 and M2 stretch reflex in the ankle plantarflexors. To disentangle the parameter interdependence, 49 unique ramp-and-hold joint perturbations elicited reflexes in 10 healthy volunteers during a torque control task. Linear mixed model analysis showed that M1 depended on acceleration, not velocity or duration, whereas M2 depended on acceleration, velocity, and duration. Simulations of the muscle spindle Ia afferents coupled to a motoneuron pool corroborated these experimental findings. In addition, this simulation model did show a nonlinear M1 velocity- and duration-dependence for perturbation parameters outside the experimental scope. In conclusion, motorized assessment of the stretch reflex or spasticity using ramp-and-hold perturbations should be systematically executed and reported. Our systematic motorized and simulation assessments showed that M1 and M2 depend on acceleration, velocity, and duration of the applied perturbation. The simulation model suggested that these dependencies emerge from: muscle-tendon unit and muscle cross-bridge dynamics, Ia sensitivity to force and yank, and motoneuron synchronization.

Objective: A role of the motor cortex in tremor generation in essential tremor (ET) is assumed, yet the directionality of corticomuscular coupling is unknown. Our aim is to clarify the role of the motor cortex. To this end we also study ‘familial cortical myoclonic tremor with epilepsy’ (FCMTE) and slow repetitive voluntary movements with a known cortical drive. Methods: Directionality of corticomuscular coupling (EEG-EMG) was studied with renormalized partial directed coherence (rPDC) during tremor in 25 ET patients, 25 healthy controls (mimicked) and in seven FCMTE patients; and during a self-paced 2 Hz task in eight ET patients and seven healthy controls. Results: Efferent coupling around tremor frequency was seen in 33% of ET patients, 45.5% of healthy controls, all FCMTE patients, and, around 2 Hz, in all ET patients and all healthy controls. Ascending coupling, seen in the majority of all participants, was weaker in ET than in healthy controls around 5–6 Hz. Conclusions: Possible explanations are that tremor in ET results from faulty subcortical output bypassing the motor cortex; rate-dependent transmission similar to generation of rhythmic movements; and/or faulty feedforward mechanism resulting from decreased afferent (sensory) coupling. Significance: A linear cortical drive is lacking in the majority of ET patients.

Objective. Large structural brain changes, such as chronic stroke lesions, alter the current pathways throughout the patients' head and therefore have to be taken into account when performing transcranial direct current stimulation simulations. Approach. We implement, test and distribute the first MATLAB pipeline that automatically generates realistic and individualized volume conduction head models of chronic stroke patients, by combining the already existing software SimNIBS, for the mesh generation, and lesion identification with neighborhood data analysis, for the lesion identification. To highlight the impact of our pipeline, we investigated the sensitivity of the electric field distribution to the lesion location and lesion conductivity in 16 stroke patients' datasets. Main results. Our pipeline automatically generates 1 mm-resolution tetrahedral meshes including the lesion compartment in less than three hours. Moreover, for large lesions, we found a high sensitivity of the electric field distribution to the lesion conductivity value and location. Significance. This work facilitates optimizing electrode configurations with the goal to obtain more focal brain stimulations of the target volumes in rehabilitation for chronic stroke patients.