Papers by Ander Ramos-murguialday
Trials, May 15, 2023
Background Evidence suggests that patients suffering from different mental disorders benefit from... more Background Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. Methods The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis.
During the last decades, spinal cord stimulation (SCS) has attracted much attention due to its ca... more During the last decades, spinal cord stimulation (SCS) has attracted much attention due to its capability to modulate the motor and sensory networks. The potential of this technique has been proved, and several investigations have focused on applying it for restoring lower limb function. The majority of SCS approaches are based on electrical stimulation, and few studies have explored magnetic fields for non-invasive SCS. This paper presents a trans-spinal magnetic stimulation (ts-MS) protocol and studies its effects on spinal circuits with seven healthy subjects, considering central and peripheral nervous systems. Motor evoked potentials (MEP) and trans-spinal motor evoked potentials (ts-MEP) were assessed before and after the ts-MS intervention to characterize excitatory responses. After the intervention, we found an increase of almost 30% (not statistically significant) in MEP amplitude, but no changes in ts-MEP amplitude. Further research is required to confirm, in a larger population of subjects, the potential of this technology, which could be used to improve rehabilitation therapies for patients with motor disabilities.
Frontiers in Bioengineering and Biotechnology, Oct 31, 2022
Brain-controlled neuromodulation has emerged as a promising tool to promote functional recovery i... more Brain-controlled neuromodulation has emerged as a promising tool to promote functional recovery in patients with motor disorders. Brainmachine interfaces exploit this neuromodulatory strategy and could be used for restoring voluntary control of lower limbs. In this work, we propose a noninvasive brain-spine interface (BSI) that processes electroencephalographic (EEG) activity to volitionally control trans-spinal magnetic stimulation (ts-MS), as an approach for lower-limb neurorehabilitation. This novel platform allows to contingently connect motor cortical activation during leg motor imagery with the activation of leg muscles via ts-MS. We tested this closed-loop system in 10 healthy participants using different stimulation conditions. This BSI efficiently removed stimulation artifacts from EEG regardless of ts-MS intensity used, allowing continuous monitoring of cortical activity and real-time closed-loop control of ts-MS. Our BSI induced afferent and efferent evoked responses, being this activation ts-MS intensity-dependent. We demonstrated the feasibility, safety and usability of this non-invasive BSI. The presented system represents a novel non-invasive means of brain-controlled neuromodulation and opens the door towards its integration as a therapeutic tool for lower-limb rehabilitation.
Date Signature I need to thank all the people of the Institute of Medical Psychology and Behavior... more Date Signature I need to thank all the people of the Institute of Medical Psychology and Behavioral Neurobiology and specially the ALS and Stroke groups. I would like to thank Sebastian Halder, Jürgen Mellinger and Jürgen Dax for his help, advice and expertise towards the development of the robotic orthosis, its communication with the BCI2000 module and the set up of the online proprioceptive BCI. During the ALS project an invaluable group of researchers from the Max Planck Biological Cybernetics, the Institute of Medical Psychology and Behavioral Neurobiology, the Neuro Team of the Computer Science Department and the Neurosurgery Department of the University of Tübingen shared frustration, jokes, dinners, meetings, late and very late nights and many working hours. Specially, my thanks to Femke Nijboer, Michael Bensch, Suzanne Maartens, Jason Faquar and Jeremy Hill. Obviously the project would have not been possible without the advice of Prof. Bernhard Schölkopf, Prof. Alireza Gharabaghi and Prof. Niels Birbaumer and our volunteer GR. The development and experiments of the proprioceptive BCI would not have been possible without the help and hard work and dedication of Ernesto Soares, Eva Hammer and Silvia Kofler. I must thank all the students, faculty and staff from Professor Birbaumer's lab for their partnership, help and support. I must thank every person involved as well in the stroke project and the BCCI project for their help, hard work, discussions, advice, partnership, understanding and friendship. I want to thank all of my friends for just being there always (it doesn't matter where). I greatly appreciate the invaluable support I received from the Fatronik Technological Foundation, now called Tecnalia Research and Innovation, which made possible my stay at the University of Tübingen. They have supported and helped me during this whole process. I want to specially mention Jose Miguel Azkoitia and Thierry Keller, who both believed in my potential and always supported me.
BMC Psychiatry, Oct 30, 2021
Background: Mental disorders are prevalent and cause considerable burden of disease. Exercise has... more Background: Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD). Methods: This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and costeffectiveness of the manualized, group-based six-months exercise intervention "ImPuls", among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be blockrandomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be selfreported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and costutility ratios.
Frontiers in Neuroscience, Jan 15, 2021
Cerebral Cortex, Dec 31, 2021
Deciphering and analyzing the neural correlates of different movements from the same limb using e... more Deciphering and analyzing the neural correlates of different movements from the same limb using electroencephalography (EEG) would represent a notable breakthrough in the field of sensorimotor neurophysiology. Functional movements involve concurrent posture co-ordination and head and eye movements, which create electrical activity that affects EEG recordings. In this paper, we revisit the identification of brain signatures of different reaching movements using EEG and present, test, and validate a protocol to separate the effect of head and eye movements from a reaching task-related visuomotor brain activity. Ten healthy participants performed reaching movements under two different conditions: avoiding head and eye movements and moving with no constrains. Reaching movements can be identified from EEG with unconstrained eye and head movement, whereas the discriminability of the signals drops to chance level otherwise. These results show that neural patterns associated with different arm movements could only be extracted from EEG if the eye and head movements occurred concurrently with the task, polluting the recordings. Although these findings do not imply that brain correlates of reaching directions cannot be identified from EEG, they show the consequences that ignoring these events can have in any EEG study that includes a visuomotor task.
Clinical Neurophysiology, Oct 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Human Brain Mapping, Nov 28, 2019
In the present work, we investigated the relationship of oscillatory sensorimotor brain activity ... more In the present work, we investigated the relationship of oscillatory sensorimotor brain activity to motor recovery. The neurophysiological data of 30 chronic stroke patients with severe upper-limb paralysis are the basis of the observational study presented here. These patients underwent an intervention including movement training based on combined brain-machine interfaces and physiotherapy of several weeks recorded in a double-blinded randomized clinical trial. We analyzed the alpha oscillations over the motor cortex of 22 of these patients employing multilevel linear predictive modeling. We identified a significant correlation between the evolution of the alpha desynchronization during rehabilitative intervention and clinical improvement. Moreover, we observed that the initial alpha desynchronization conditions its modulation during intervention: Patients showing a strong alpha desynchronization at the beginning of the training improved if they increased their alpha desynchronization. Patients showing a small alpha desynchronization at initial training stages improved if they decreased it further on both hemispheres. In all patients, a progressive shift of desynchronization toward the ipsilesional hemisphere correlates significantly with clinical improvement regardless of lesion location. The results indicate that initial alpha desynchronization might be key for stratification of patients undergoing BMI interventions and that its interhemispheric balance plays an important role in motor recovery.
Frontiers in Bioengineering and Biotechnology
Brain-controlled neuromodulation has emerged as a promising tool to promote functional recovery i... more Brain-controlled neuromodulation has emerged as a promising tool to promote functional recovery in patients with motor disorders. Brain-machine interfaces exploit this neuromodulatory strategy and could be used for restoring voluntary control of lower limbs. In this work, we propose a non-invasive brain-spine interface (BSI) that processes electroencephalographic (EEG) activity to volitionally control trans-spinal magnetic stimulation (ts-MS), as an approach for lower-limb neurorehabilitation. This novel platform allows to contingently connect motor cortical activation during leg motor imagery with the activation of leg muscles via ts-MS. We tested this closed-loop system in 10 healthy participants using different stimulation conditions. This BSI efficiently removed stimulation artifacts from EEG regardless of ts-MS intensity used, allowing continuous monitoring of cortical activity and real-time closed-loop control of ts-MS. Our BSI induced afferent and efferent evoked responses, b...
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PLOS ONE, Apr 17, 2013
Several works have reported on the reconstruction of 2D/3D limb kinematics from low-frequency EEG... more Several works have reported on the reconstruction of 2D/3D limb kinematics from low-frequency EEG signals using linear regression models based on positive correlation values between the recorded and the reconstructed trajectories. This paper describes the mathematical properties of the linear model and the correlation evaluation metric that may lead to a misinterpretation of the results of this type of decoders. Firstly, the use of a linear regression model to adjust the two temporal signals (EEG and velocity profiles) implies that the relevant component of the signal used for decoding (EEG) has to be in the same frequency range as the signal to be decoded (velocity profiles). Secondly, the use of a correlation to evaluate the fitting of two trajectories could lead to overly-optimistic results as this metric is invariant to scale. Also, the correlation has a non-linear nature that leads to higher values for sinus/cosinus-like signals at low frequencies. Analysis of these properties on the reconstruction results was carried out through an experiment performed in line with previous studies, where healthy participants executed predefined reaching movements of the hand in 3D space. While the correlations of limb velocity profiles reconstructed from low-frequency EEG were comparable to studies in this domain, a systematic statistical analysis revealed that these results were not above the chance level. The empirical chance level was estimated using random assignments of recorded velocity profiles and EEG signals, as well as combinations of randomly generated synthetic EEG with recorded velocity profiles and recorded EEG with randomly generated synthetic velocity profiles. The analysis shows that the positive correlation results in this experiment cannot be used as an indicator of successful trajectory reconstruction based on a neural correlate. Several directions are herein discussed to address the misinterpretation of results as well as the implications on previous invasive and non-invasive works.
Biosystems & biorobotics, Oct 13, 2016
Brain machine interfaces (BMIs) have previously been utilized to control rehabilitation robots wi... more Brain machine interfaces (BMIs) have previously been utilized to control rehabilitation robots with promising results. The design and development of more dexterous and user-friendly rehabilitation platforms is the next challenge to be tackled. We built a novel platform that uses an electro-encephalograpy-based BMI to control a multi-degree of freedom exoskeleton in a rehabilitation framework. Its applicability to a clinical scenario is validated here with six healthy subjects and a chronic stroke patient using motor imagery and movements attempts. Therefore, this study presents a potential system to carry out fully-featured motor rehabilitation therapies.
Scientific Reports, Nov 12, 2018
The motor impairment occurring after a stroke is characterized by pathological muscle activation ... more The motor impairment occurring after a stroke is characterized by pathological muscle activation patterns or synergies. However, while robot-aided myoelectric interfaces have been proposed for stroke rehabilitation, they do not address this issue, which might result in inefficient interventions. Here, we present a novel paradigm that relies on the correction of the pathological muscle activity as a way to elicit rehabilitation, even in patients with complete paralysis. Previous studies demonstrated that there are no substantial inter-limb differences in the muscle synergy organization of healthy individuals. We propose building a subject-specific model of muscle activity from the healthy limb and mirroring it to use it as a learning tool for the patient to reproduce the same healthy myoelectric patterns on the paretic limb during functional task training. Here, we aim at understanding how this myoelectric model, which translates muscle activity into continuous movements of a 7-degree of freedom upper limb exoskeleton, could transfer between sessions, arms and tasks. The experiments with 8 healthy individuals and 2 chronic stroke patients proved the feasibility and effectiveness of such myoelectric interface. We anticipate the proposed method to become an efficient strategy for the correction of maladaptive muscle activity and the rehabilitation of stroke patients.
Journal of Neuroengineering and Rehabilitation, Nov 20, 2018
Background: Brain machine interface (BMI) technology has demonstrated its efficacy for rehabilita... more Background: Brain machine interface (BMI) technology has demonstrated its efficacy for rehabilitation of paralyzed chronic stroke patients. The critical component in BMI-training consists of the associative connection (contingency) between the intention and the feedback provided. However, the relationship between the BMI design and its performance in stroke patients is still an open question. Methods: In this study we compare different methodologies to design a BMI for rehabilitation and evaluate their effects on movement intention decoding performance. We analyze the data of 37 chronic stroke patients who underwent 4 weeks of BMI intervention with different types of association between their brain activity and the proprioceptive feedback. We simulate the pseudo-online performance that a BMI would have under different conditions, varying: (1) the cortical source of activity (i.e., ipsilesional, contralesional, bihemispheric), (2) the type of spatial filter applied, (3) the EEG frequency band, (4) the type of classifier; and also evaluated the use of residual EMG activity to decode the movement intentions. Results: We observed a significant influence of the different BMI designs on the obtained performances. Our results revealed that using bihemispheric beta activity with a common average reference and an adaptive support vector machine led to the best classification results. Furthermore, the decoding results based on brain activity were significantly higher than those based on muscle activity. Conclusions: This paper underscores the relevance of the different parameters used to decode movement, using EEG in severely paralyzed stroke patients. We demonstrated significant differences in performance for the different designs, which supports further research that should elucidate if those approaches leading to higher accuracies also induce higher motor recovery in paralyzed stroke patients.
IEEE Transactions on Biomedical Engineering, 2017
Stroke survivors usually require motor rehabilitation therapy as, due to the lesion, they complet... more Stroke survivors usually require motor rehabilitation therapy as, due to the lesion, they completely or partially loss mobility in the limbs. Brain-Computer Interface technology offers the possibility of decoding the attempt to move paretic limbs in real time to improve existing motor rehabilitation. However, a major difficulty for the practical application of BCI to stroke survivors is that the brain rhythms that encode the motor states might be diminished due to the lesion. This study investigates the continuous decoding of natural attempt to move the paralyzed upper limb in stroke survivors from electroencephalographic signals of the unaffected contralesional motor cortex. Results: Experiments were carried out with the aid of six severely-affected chronic stroke patients performing/attempting self-selected reaching movements of the unaffected/affected upper limb. The EEG analysis showed significant cortical activation on the uninjured motor cortex when moving the contralateral unaffected arm and in the attempt to move the ipsilateral affected arm. Using this activity, significant continuous decoding of movement was obtained in 6 out of 6 participants in movements of the unaffected limb, and in 4 out of 6 participants in the attempt to move the affected limb. Conclusion: This work showed that it is possible to construct a decoder of the attempt to move the paretic arm for chronic stroke patients using the EEG activity of the healthy contralesional motor cortex. Significance: This decoding model could provide to stroke survivors with a natural, easy and intuitive way to achieve control of BCIs or robot-assisted rehabilitation devices.
Frontiers in Neurology, 2013
The recovery of functional movements following injury to the central nervous system (CNS) is mult... more The recovery of functional movements following injury to the central nervous system (CNS) is multifaceted and is accompanied by processes occurring in the injured and non-injured hemispheres of the brain or above/below a spinal cord lesion. The changes in the CNS are the consequence of functional and structural processes collectively termed neuroplasticity and these may occur spontaneously and/or be induced by movement practice. The neurophysiological mechanisms underlying such brain plasticity may take different forms in different types of injury, for example stroke vs. spinal cord injury (SCI). Recovery of movement can be enhanced by intensive, repetitive, variable, and rewarding motor practice. To this end, robots that enable or facilitate repetitive movements have been developed to assist recovery and rehabilitation. Here, we suggest that some elements of robot-mediated training such as assistance and perturbation may have the potential to enhance neuroplasticity. Together the elemental components for developing integrated robot-mediated training protocols may form part of a neurorehabilitation framework alongside those methods already employed by therapists. Robots could thus open up a wider choice of options for delivering movement rehabilitation grounded on the principles underpinning neuroplasticity in the human CNS.
Current Opinion in Neurology, Dec 1, 2008
Communication with patients suffering from locked-in syndrome and other forms of paralysis is an ... more Communication with patients suffering from locked-in syndrome and other forms of paralysis is an unsolved challenge. Movement restoration for patients with chronic stroke or other brain damage also remains a therapeutic problem and available treatments do not offer significant improvements. This review considers recent research in brain-computer interfaces (BCIs) as promising solutions to these challenges. Experimentation with nonhuman primates suggests that intentional goal directed movements of the upper limbs can be reconstructed and transmitted to external manipulandum or robotic devices controlled from a relatively small number of microelectrodes implanted into movement-relevant brain areas after some training, opening the door for the development of BCI or brain-machine interfaces in humans. Although noninvasive BCIs using electroencephalographic recordings or event-relatedbrain-potentials in healthy individuals and patients with amyotrophic lateral sclerosis or stroke can transmit up to 80 bits/min of information, the use of BCIs -invasive or noninvasive -in severely or totally paralyzed patients has met some unforeseen difficulties. Summary Invasive and noninvasive BCIs using recordings from nerve cells, large neuronal pools such as electrocorticogram and electroencephalography, or blood flow based measures such as functional magnetic resonance imaging and near-infrared spectroscopy show potential for communication in locked-in syndrome and movement restoration in chronic stroke, but controlled phase III clinical trials with larger populations of severely disturbed patients are urgently needed.
Nature Reviews Neurology, Aug 19, 2016
Brain-computer interfaces (BCIs) use brain activity to control external devices, thereby enabling... more Brain-computer interfaces (BCIs) use brain activity to control external devices, thereby enabling severely disabled patients to interact with the environment. A variety of invasive and noninvasive techniques for controlling BCIs have been explored, most notably EEG, and more recently, near-infrared spectroscopy. Assistive BCIs are designed to enable paralyzed patients to communicate or control external robotic devices, such as prosthetics; rehabilitative BCIs are designed to facilitate recovery of neural function. In this Review, we provide an overview of the development of BCIs and the current technology available before discussing experimental and clinical studies of BCIs. We first consider the use of BCIs for communication in patients who are paralyzed, particularly those with locked-in syndrome or complete locked-in syndrome as a result of amyotrophic lateral sclerosis. We then discuss the use of BCIs for motor rehabilitation after severe stroke and spinal cord injury. We also describe the possible neurophysiological and learning mechanisms that underlie the clinical efficacy of BCIs.
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