Machine learning approach for Migraine Aura Complexity Score prediction based on magnetic resonance imaging data.

BACKGROUND: Previous studies have developed the Migraine Aura Complexity Score (MACS) system. MACS shows great potential in studying the complexity of migraine with aura (MwA) pathophysiology especially when implemented in neuroimaging studies. The use of sophisticated machine learning (ML) algorithms, together with deep profiling of MwA, could bring new knowledge in this field. We aimed to test several ML algorithms to study the potential of structural cortical features for predicting the MACS and therefore gain a better insight into MwA pathophysiology. METHODS: The data set used in this research consists of 340 MRI features collected from 40 MwA patients. Average MACS score was obtained for each subject. Feature selection for ML models was performed using several approaches, including a correlation test and a wrapper feature selection methodology. Regression was performed with the Support Vector Machine (SVM), Linear Regression, and Radial Basis Function network. RESULTS: SVM achieved a 0.89 coefficient of determination score with a wrapper feature selection. The results suggest a set of cortical features, located mostly in the parietal and temporal lobes, that show changes in MwA patients depending on aura complexity. CONCLUSIONS: The SVM algorithm demonstrated the best potential in average MACS prediction when using a wrapper feature selection methodology. The proposed method achieved promising results in determining MwA complexity, which can provide a basis for future MwA studies and the development of MwA diagnosis and treatment.

Somatosensory Event-Related Potential as an Electrophysiological Correlate of Endogenous Spatial Tactile Attention: Prospects for Electrotactile Brain-Computer Interface for Sensory Training.

Tactile attention tasks are used in the diagnosis and treatment of neurological and sensory processing disorders, while somatosensory event-related potentials (ERP) measured by electroencephalography (EEG) are used as neural correlates of attention processes. Brain-computer interface (BCI) technology provides an opportunity for the training of mental task execution via providing online feedback based on ERP measures. Our recent work introduced a novel electrotactile BCI for sensory training, based on somatosensory ERP; however, no previous studies have addressed specific somatosensory ERP morphological features as measures of sustained endogenous spatial tactile attention in the context of BCI control. Here we show the morphology of somatosensory ERP responses induced by a novel task introduced within our electrotactile BCI platform i.e., the sustained endogenous spatial electrotactile attention task. By applying pulsed electrical stimuli to the two proximal stimulation hotspots at the user's forearm, stimulating sequentially the mixed branches of radial and median nerves with equal probability of stimuli occurrence, we successfully recorded somatosensory ERPs for both stimulation locations, in the attended and unattended conditions. Waveforms of somatosensory ERP responses for both mixed nerve branches showed similar morphology in line with previous reports on somatosensory ERP components obtained by stimulation of exclusively sensory nerves. Moreover, we found statistically significant increases in ERP amplitude on several components, at both stimulation hotspots, while sustained endogenous spatial electrotactile attention task is performed. Our results revealed the existence of general ERP windows of interest and signal features that can be used to detect sustained endogenous tactile attention and classify between spatial attention locations in 11 healthy subjects. The current results show that features of N140, P3a and P3b somatosensory ERP components are the most prominent global markers of sustained spatial electrotactile attention, over all subjects, within our novel electrotactile BCI task/paradigm, and this work proposes the features of those components as markers of sustained endogenous spatial tactile attention in online BCI control. Immediate implications of this work are the possible improvement of online BCI control within our novel electrotactile BCI system, while these finding can be used for other tactile BCI applications in the diagnosis and treatment of neurological disorders by employing mixed nerve somatosensory ERPs and sustained endogenous electrotactile attention task as control paradigms.

Novel electrotactile brain-computer interface with somatosensory event-related potential based control.

Objective: A brain computer interface (BCI) allows users to control external devices using non-invasive brain recordings, such as electroencephalography (EEG). We developed and tested a novel electrotactile BCI prototype based on somatosensory event-related potentials (sERP) as control signals, paired with a tactile attention task as a control paradigm. Approach: A novel electrotactile BCI comprises commercial EEG device, an electrical stimulator and custom software for EEG recordings, electrical stimulation control, synchronization between devices, signal processing, feature extraction, selection, and classification. We tested a novel BCI control paradigm based on tactile attention on a sensation at a target stimulation location on the forearm. Tactile stimuli were electrical pulses delivered at two proximal locations on the user's forearm for stimulating branches of radial and median nerves, with equal probability of the target and distractor stimuli occurrence, unlike in any other ERP-based BCI design. We proposed a compact electrical stimulation electrodes configuration for delivering electrotactile stimuli (target and distractor) using 2 stimulation channels and 3 stimulation electrodes. We tested the feasibility of a single EEG channel BCI control, to determine pseudo-online BCI performance, in ten healthy subjects. For optimizing the BCI performance we compared the results for two classifiers, sERP averaging approaches, and novel dedicated feature extraction/selection methods via cross-validation procedures. Main results: We achieved a single EEG channel BCI classification accuracy in the range of 75.1 to 88.1% for all subjects. We have established an optimal combination of: single trial averaging to obtain sERP, feature extraction/selection methods and classification approach. Significance: The obtained results demonstrate that a novel electrotactile BCI paradigm with equal probability of attended (target) and unattended (distractor) stimuli and proximal stimulation sites is feasible. This method may be used to drive restorative BCIs for sensory retraining in stroke or brain injury, or assistive BCIs for communication in severely disabled users.

Accessible Dyslexia Detection with Real-Time Reading Feedback through Robust Interpretable Eye-Tracking Features.

Developing reliable, quantifiable, and accessible metrics for dyslexia diagnosis and tracking represents an important goal, considering the widespread nature of dyslexia and its negative impact on education and quality of life. In this study, we observe eye-tracking data from 15 dyslexic and 15 neurotypical Serbian school-age children who read text segments presented on different color configurations. Two new eye-tracking features were introduced that quantify the amount of spatial complexity of the subject's gaze through time and inherently provide information regarding the locations in the text in which the subject struggled the most. The features were extracted from the raw eye-tracking data (x, y coordinates), from the original data gathered at 60 Hz, and from the downsampled data at 30 Hz, examining the compatibility of features with low-cost or custom-made eye-trackers. The features were used as inputs to machine learning algorithms, and the best-obtained accuracy was 88.9% for 60 Hz and 87.8% for 30 Hz. The features were also used to analyze the influence of background/overlay color on the quality of reading, and it was shown that the introduced features separate the dyslexic and control groups regardless of the background/overlay color. The colors can, however, influence each subject differently, which implies that an individualistic approach would be necessary to obtain the best therapeutic results. The performed study shows promise in dyslexia detection and evaluation, as the proposed features can be implemented in real time as feedback during reading and show effectiveness at detecting dyslexia with data obtained using a lower sampling rate.

ERP Indicators of Phonological Awareness Development in Children: A Systematic Review.

Phonological awareness is the ability to correctly recognize and manipulate phonological structures. The role of phonological awareness in reading development has become evident in behavioral research showing that it is inherently tied to measures of phonological processing and reading ability. This has also been shown with ERP research that examined how phonological processing training can benefit reading skills. However, there have not been many attempts to systematically review how phonological awareness itself is developed neurocognitively. In the present review, we screened 224 papers and systematically reviewed 40 papers that have explored phonological awareness and phonological processing using ERP methodology with both typically developing and children with reading problems. This review highlights ERP components that can be used as neurocognitive predictors of early developmental dyslexia and reading disorders in young children. Additionally, we have presented how phonological processing is developed neurocognitively throughout childhood, as well as which phonological tasks can be used to predict the development of phonological awareness prior to developing reading skills. Neurocognitive measures of early phonological processing can serve as supplemental diagnostic sources to behavioral measures of reading abilities because they show different aspects of phonological sensitivity when compared to behavioral measures.

Spatiotemporal Eye-Tracking Feature Set for Improved Recognition of Dyslexic Reading Patterns in Children.

Considering the detrimental effects of dyslexia on academic performance and its common occurrence, developing tools for dyslexia detection, monitoring, and treatment poses a task of significant priority. The research performed in this paper was focused on detecting and analyzing dyslexic tendencies in Serbian children based on eye-tracking measures. The group of 30 children (ages 7-13, 15 dyslexic and 15 non-dyslexic) read 13 different text segments on 13 different color configurations. For each text segment, the corresponding eye-tracking trail was recorded and then processed offline and represented by nine conventional features and five newly proposed features. The features were used for dyslexia recognition using several machine learning algorithms: logistic regression, support vector machine, k-nearest neighbor, and random forest. The highest accuracy of 94% was achieved using all the implemented features and leave-one-out subject cross-validation. Afterwards, the most important features for dyslexia detection (representing the complexity of fixation gaze) were used in a statistical analysis of the individual color effects on dyslexic tendencies within the dyslexic group. The statistical analysis has shown that the influence of color has high inter-subject variability. This paper is the first to introduce features that provide clear separability between a dyslexic and control group in the Serbian language (a language with a shallow orthographic system). Furthermore, the proposed features could be used for diagnosing and tracking dyslexia as biomarkers for objective quantification.

P3 latency as a biomarker for the complexity of migraine with aura: Event-related potential study.

BACKGROUND: This study aimed to compare the P3 component between patients who have migraines with aura and healthy subjects, and to compare different subtypes of migraine with aura relative to the complexity of migraine aura. METHODS: Average Migraine Aura Complexity Score was calculated for each MwA patient. Visual oddball paradigm was used to elicit the P3 component. P3 amplitudes and latencies elicited from frequent and rare stimuli, as well as from difference wave, were compared with healthy subjects. Subsequently, subtypes of migraine with aura were compared and Average Migraine Aura Complexity Score was used to explore the connection between features of the P3 and complexity of migraine with aura. RESULTS: 37 patients who have migraine with aura (16 with simple aura and 21 with complex aura) patients and 28 healthy subjects were studied. Patients who have migraine with aura had significantly prolonged latencies compared to healthy subjects (411 ± 39 ms vs 372 ± 34 ms, p < 0.001) relative to a rare condition. Patients who have complex aura significantly differs from patients who have simple aura (427 ± 34 ms vs 389 ± 35 ms, p = 0.004) and healthy subjects (372 ± 34 ms, p < 0.001) relative to P3 latency in a rare condition and the patients who have complex aura significantly differs from healthy subjects (442 ± 37 ms vs 394 ± 33 ms, p < 0.001) relative to P3 latency in difference wave. P3 latency from rare condition positively correlated with the Average Migraine Aura Complexity Score (p < 0.001). CONCLUSIONS: Visual oddball paradigm, particularly rare stimuli, could serve as a potential new tool for deep profiling of different clinical complexities among patients who have migraine with aura. Also, the present pattern of P3 components provided new evidence for the cognitive dysfunctions in patients who have migraine with aura.

Participant-specific classifier tuning increases the performance of hand movement detection from EEG in patients with amyotrophic lateral sclerosis.

Objective.Brain-computer interface (BCI) systems can be employed to provide motor and communication assistance to patients suffering from neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS). Movement related cortical potentials (MRCPs), which are naturally generated during movement execution, can be used to implement a BCI triggered by motor attempts. Such BCI could assist impaired motor functions of ALS patients during disease progression, and facilitate the training for the generation of reliable MRCPs. The training aspect is relevant to establish a communication channel in the late stage of the disease. Therefore, the aim of this study was to investigate the possibility of detecting MRCPs associated to movement intention in ALS patients with different levels of disease progression from slight to complete paralysis.Approach.Electroencephalography signals were recorded from nine channels in 30 ALS patients at various stages of the disease while they performed or attempted to perform hand movements timed to a visual cue. The movement detection was implemented using offline classification between movement and rest phase. Temporal and spectral features were extracted using 500 ms sliding windows with 50% overlap. The detection was tested for each individual channel and two surrogate channels by performing feature selection followed by classification using linear and non-linear support vector machine and linear discriminant analysis.Main results.The results demonstrated that the detection performance was high in all patients (accuracy 80.5 ± 5.6%) but that the classification parameters (channel, features and classifier) leading to the best performance varied greatly across patients. When the same channel and classifier were used for all patients (participant-generic analysis), the performance significantly decreased (accuracy 74 ± 8.3%).Significance.The present study demonstrates that to maximize the detection of brain waves across ALS patients at different stages of the disease, the classification pipeline should be tuned to each patient individually.

The effect of colour on reading performance in children, measured by a sensor hub: From the perspective of gender.

In recent decades reported findings regarding gender differences in reading achievement, cognitive abilities and maturation process in boys and girls are conflicting. As reading is one of the most important processes in the maturation of an individual, the aim of the study was to better understand gender differences between primary school students. The study evaluates differences in Heart Rate Variability (HRV), Electroencephalography (EEG), Electrodermal Activities (EDA) and eye movement of participants during the reading task. Taking into account that colour may affect reading skills, in that it affects the emotional and physiological state of the body, the research attempts to provide a better understanding of gender differences in reading through examining the effect of colour, as applied to reading content. The physiological responses of 50 children (25 boys and 25 girls) to 12 different background and overlay colours of reading content were measured and summarised during the reading process. Our findings show that boys have shorter reading duration scores and a longer Saccade Count, Saccade Duration Total, and Saccade Duration Average when reading on a coloured background, especially purple, which could be caused by their motivation and by the type of reading task. Also, the boys had higher values for the Delta band and the Whole Range of EEG measurements in comparison to the girls when reading on coloured backgrounds, which could reflect the faster maturation of the girls. Regarding EDA measurements we did not find systematic differences between groups either on white or on coloured/overlay background. We found the most significant differences arose in the HRV parameters, namely (SDNN (ms), STD HR (beats/min), RMSSD (ms), NN50 (beats), pNN50 (%), CVRR) when children read the text on coloured/overlay backgrounds, where the girls showed systematically higher values on HRV measurements in comparison to the boys, mostly with yellow, red, and orange overlay colours.

Online control of an assistive active glove by slow cortical signals in patients with amyotrophic lateral sclerosis.

Objective.A brain-computer interface (BCI) allows users to control external devices using brain signals that can be recorded non-invasively via electroencephalography (EEG). Movement related cortical potentials (MRCPs) are an attractive option for BCI control since they arise naturally during movement execution and imagination, and therefore, do not require an extensive training. This study tested the feasibility of online detection of reaching and grasping using MRCPs for the application in patients suffering from amyotrophic lateral sclerosis (ALS).Approach.A BCI system was developed to trigger closing of a soft assistive glove by detecting a reaching movement. The custom-made software application included data collection, a novel method for collecting the input data for classifier training from the offline recordings based on a sliding window approach, and online control of the glove. Eight healthy subjects and two ALS patients were recruited to test the developed BCI system. They performed assessment blocks without the glove active (NG), in which the movement detection was indicated by a sound feedback, and blocks (G) in which the glove was controlled by the BCI system. The true positive rate (TPR) and the positive predictive value (PPV) were adopted as the outcome measures. Correlation analysis between forehead EEG detecting ocular artifacts and sensorimotor area EEG was conducted to confirm the validity of the results.Main results.The overall median TPR and PPV were >0.75 for online BCI control, in both healthy individuals and patients, with no significant difference across the blocks (NG versus G).Significance.The results demonstrate that cortical activity during reaching can be detected and used to control an external system with a limited amount of training data (30 trials). The developed BCI system can be used to provide grasping assistance to ALS patients.

The Relation between Physiological Parameters and Colour Modifications in Text Background and Overlay during Reading in Children with and without Dyslexia.

Reading is one of the essential processes during the maturation of an individual. It is estimated that 5-10% of school-age children are affected by dyslexia, the reading disorder characterised by difficulties in the accuracy or fluency of word recognition. There are many studies which have reported that coloured overlays and background could improve the reading process, especially in children with reading disorders. As dyslexia has neurobiological origins, the aim of the present research was to understand the relationship between physiological parameters and colour modifications in the text and background during reading in children with and without dyslexia. We have measured differences in electroencephalography (EEG), heart rate variability (HRV), electrodermal activities (EDA) and eye movements of the 36 school-age (from 8 to 12 years old) children (18 with dyslexia and 18 of control group) during the reading task in 13 combinations of background and overlay colours. Our findings showed that the dyslexic children have longer reading duration, fixation count, fixation duration average, fixation duration total, and longer saccade count, saccade duration total, and saccade duration average while reading on white and coloured background/overlay. It was found that the turquoise background, turquoise overlay, and yellow background colours are beneficial for dyslexic readers, as they achieved the shortest time duration of the reading tasks when these colours were used. Additionally, dyslexic children have higher values of beta (15-40 Hz) and the broadband EEG (0.5-40 Hz) power while reading in one particular colour (purple), as well as increasing theta range power while reading with the purple overlay. We have observed no significant differences between HRV parameters on white colour, except for single colours (purple, turquoise overlay, and yellow overlay) where the control group showed higher values for mean HR, while dyslexic children scored higher with mean RR. Regarding EDA measure, we found systematically lower values in children with dyslexia in comparison to the control group. Based on the present results, we can conclude that both pastel and intense background/overlays are beneficial for reading of both groups and all sensor modalities could be used to better understand the neurophysiological origins in dyslexic children.

The Sensor Hub for Detecting the Developmental Characteristics in Reading in Children on a White vs. Colored Background/Colored Overlays.

This study investigated the influence of white vs. 12 background and overlay colors on the reading process in twenty-four school-age children. Previous research reported that colors could affect reading skills as an important factor in the emotional and physiological state of the body. The aim of the study was to assess developmental differences between second and third grade students of an elementary school, and to evaluate differences in electroencephalography (EEG), ocular, electrodermal activities (EDA) and heart rate variability (HRV). Our findings showed a decreasing trend with age regarding EEG power bands (Alpha, Beta, Delta, Theta) and lower scores of reading duration and eye-tracking measures in younger children compared to older children. As shown in the results, HRV parameters showed higher scores in 12 background and overlay colors among second than third grade students, which is linearly correlated to the level of stress and is readable from EDA measures as well. Our study showed the calming effect on second graders of turquoise and blue background colors. Considering other colors separately for each parameter, we assumed that there are no systematic differences in reading duration, EEG power band, eye-tracking and EDA measures.

Dynamics of movement-related cortical potentials and sensorimotor oscillations during palmar grasp movements.

Movement-related cortical potentials (MRCP) and sensorimotor oscillatory electroencephalographic (EEG) activity (event-related desynchronization/synchronization-ERD/ERS) provide complementary information of the associated motor activity. The aim of this study was to provide comparative spatio-temporal analysis of both EEG phenomena associated with palmar grasping motions including hand opening and closing phases. Nine healthy participants were instructed to perform self-paced, right hand grasping movements. EEG was recorded from 28 sites synchronous with electromyography (EMG) of wrist/fingers extensors and flexors. Statistical analysis of the EEG data revealed significant differences (p < .05) between the idle state (baseline) and motor preparation/execution periods in majority of recorded channels. The earliest statistical significance in MRCPs was observed for channel FC3 at -460.9 ms, while the earliest significant ERD was observed at 164.1 ms for channel C3. MRCP and ERD/ERS topographies in our study are in line with the results of previous studies comparing MRCP and ERD/ERS spatio-temporal patterns during upper limb movements, however, results of our study show that MRCP significant differences compared to the baseline appear in most channels earlier than ERD (on average 613.6 ± 191.5 ms earlier). This implies an advantage of MRCP signals for grasping movements' prediction, which is in contrast to previous reports. Moreover, combined spatio-temporal information on MRCP and ERD/ERS presented in this paper may serve for future optimization of grasp movement prediction/detection hybrid algorithms in the context of restorative brain-computer interface technology.

Bilateral activations in operculo-insular area show temporal dissociation after peripheral electrical stimulation in healthy adults.

Interhemispheric transfer is necessary for sensory integration and coordination of body sides. We studied how somatosensory input from one body side may reach both body sides. First, we investigated with 17 healthy adults in which uni- and bilateral brain areas were involved in consecutive stages of automatic sensory processing of non-nociceptive peripheral stimulation. Somatosensory evoked fields (SEFs) to electrical stimulation were recorded with 306-channel magnetoencephalography in two conditions. First, SEFs were registered following sensory radial nerve (RN) stimulation to dorsal surface of the right hand and second, following median nerve (MN) stimulation at the right wrist. Cortical activations were located in contralateral postcentral gyrus after MN and RN stimulations and in bilateral operculo-insular area after RN stimulation. First component occurred earlier after MN than RN stimulation. Middle latency components had similar latencies with stronger activation in contralateral postcentral gyrus after MN than RN stimulation. Interestingly, long latency components located in bilateral operculo-insular area after RN stimulation showed latency difference between hemispheres, i.e. activation peaked earlier in contralateral than in ipsilateral side. Additional experiments comparing novel intracutaneous nociceptive, RN and MN electrical stimuli confirmed bilateral long latency activation elicited by each stimulus type and highlighted latency differences between hemispheres. Variations in activation of bilateral operculo-insular areas may corroborate their role in pain network and in multisensory integration. Our findings imply that these areas present a relay station in multisensory stimulus detection.

Long-Term Physical Activity May Modify Brain Structure and Function: Studies in Young Healthy Twins.

BACKGROUND: Physical activity (PA) is said to be beneficial to many bodily functions. However, the effects of PA in the brain are still inadequately known. The authors aimed to uncover possible brain modulation linked with PA. Here, they combine 4 of their studies with monozygotic twins, who were within-pair discordant in PA for a minimum of 1 year. METHODS: The authors performed brain imaging, brain electrophysiology, and cardiovascular and body composition assessments, and collected questionnaire-based data. The present synopsis elucidates the differences associated with differing PA history in conditions without genetic variability. They present new structural and electrophysiological results. Participants, healthy, 45 male monozygotic twins (mean age 34.5 [1.5] y) differed in aerobic capacity and fat percentage (P < .001). RESULTS: More active co-twins showed larger gray matter volumes in striatal, prefrontal, and hippocampal regions, and smaller gray matter volumes in the anterior cingulate area than less active co-twins. Functionally, visual and somatosensory automatic change detection processes differed between more and less active co-twins. CONCLUSIONS: In monozygotic twins, who differed in their PA history, differences were observed in identifiable anatomic brain locations involved with motor control and memory functions, as well as in electrophysiological measures detecting brain's automatic processes. Better aerobic capacity may modify brain morphology and sensory function.

Validation of computerized square-drawing based evaluation of motor function in patients with stroke.

Human-administered clinical scales are commonly used for quantifying motor performance and determining the course of therapy in post-stroke individuals. Computerized methods aim to improve consistency, resolution and duration of patients' evaluation. The objective of this study was to test the validity of computerized square-drawing test (DT) for assessment of shoulder and elbow function by using novel set of DT-based kinematic measures and explore their relation with Wolf Motor Function Test (WMFT) scoring. Forty-seven stroke survivors were tested before and after the rehabilitation program. DT involved drawing a square in horizontal plane using a mechanical manipulandum and a digitizing board. Depending on the initial classification of patients into low or high performance groups, the two different outcome metrics were derived from DT kinematic data for evaluation of each group. Linear regression models applied to map DT outcome values to WMFT scores for both groups resulted with high correlation coefficients and low mean absolute prediction error. In conclusion, we have identified a set of kinematic measures suitable for fast and objective motor function evaluation and functional classification, strongly correlating with WMFT score in post-stroke individuals. The results support validation of square-drawing motor function assessment, encouraging its use in clinical settings.

Correction: Comparing the temporal dynamics of thematic and taxonomic processing using event-related potentials.

[This corrects the article DOI: 10.1371/journal.pone.0189362.].

Comparing the temporal dynamics of thematic and taxonomic processing using event-related potentials.

We report the results of a study comparing the temporal dynamics of thematic and taxonomic knowledge activation in a picture-word priming paradigm using event-related potentials. Although we found no behavioral differences between thematic and taxonomic processing, ERP data revealed distinct patterns of N400 and P600 amplitude modulation for thematic and taxonomic priming. Thematically related target stimuli elicited less negativity than taxonomic targets between 280-460 ms after stimulus onset, suggesting easier semantic processing of thematic than taxonomic relationships. Moreover, P600 mean amplitude was significantly increased for taxonomic targets between 520-600 ms, consistent with a greater need for stimulus reevaluation in that condition. These results offer novel evidence in favor of a dissociation between thematic and taxonomic thinking in the early phases of conceptual evaluation.

A decision support system for electrode shaping in multi-pad FES foot drop correction.

BACKGROUND: Functional electrical stimulation (FES) can be applied as an assistive and therapeutic aid in the rehabilitation of foot drop. Transcutaneous multi-pad electrodes can increase the selectivity of stimulation; however, shaping the stimulation electrode becomes increasingly complex with an increasing number of possible stimulation sites. We described and tested a novel decision support system (DSS) to facilitate the process of multi-pad stimulation electrode shaping. The DSS is part of a system for drop foot treatment that comprises a custom-designed multi-pad electrode, an electrical stimulator, and an inertial measurement unit. METHODS: The system was tested in ten stroke survivors (3-96 months post stroke) with foot drop over 20 daily sessions. The DSS output suggested stimulation pads and parameters based on muscle twitch responses to short stimulus trains. The DSS ranked combinations of pads and current amplitudes based on a novel measurement of the quality of the induced movement and classified them based on the movement direction (dorsiflexion, plantar flexion, eversion and inversion) of the paretic foot. The efficacy of the DSS in providing satisfactory pad-current amplitude choices for shaping the stimulation electrode was evaluated by trained clinicians. The range of paretic foot motion was used as a quality indicator for the chosen patterns. RESULTS: The results suggest that the DSS output was highly effective in creating optimized FES patterns. The position and number of pads included showed pronounced inter-patient and inter-session variability; however, zones for inducing dorsiflexion and plantar flexion within the multi-pad electrode were clearly separated. The range of motion achieved with FES was significantly greater than the corresponding active range of motion (p < 0.05) during the first three weeks of therapy. CONCLUSIONS: The proposed DSS in combination with a custom multi-pad electrode design covering the branches of peroneal and tibial nerves proved to be an effective tool for producing both the dorsiflexion and plantar flexion of a paretic foot. The results support the use of multi-pad electrode technology in combination with automatic electrode shaping algorithms for the rehabilitation of foot drop. TRIAL REGISTRATION: This study was registered at the Current Controlled Trials website with ClinicalTrials.gov ID NCT02729636 on March 29, 2016.