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BACKGROUND: The rise of a new generation of intelligent neuroprostheses, brain-computer interfaces (BCI) and adaptive closed-loop brain stimulation devices hastens the clinical deployment of neurotechnologies to treat neurological and neuropsychiatric disorders. However, it remains unclear how these nascent technologies may impact the subjective experience of their users. To inform this debate, it is crucial to have a solid understanding how more established current technologies already affect their users. In recent years, researchers have used qualitative research methods to explore the subjective experience of individuals who become users of clinical neurotechnology. Yet, a synthesis of these more recent findings focusing on qualitative methods is still lacking. METHODS: To address this gap in the literature, we systematically searched five databases for original research articles that investigated subjective experiences of persons using or receiving neuroprosthetics, BCIs or neuromodulation with qualitative interviews and raised normative questions. RESULTS: 36 research articles were included and analysed using qualitative content analysis. Our findings synthesise the current scientific literature and reveal a pronounced focus on usability and other technical aspects of user experience. In parallel, they highlight a relative neglect of considerations regarding agency, self-perception, personal identity and subjective experience. CONCLUSIONS: Our synthesis of the existing qualitative literature on clinical neurotechnology highlights the need to expand the current methodological focus as to investigate also non-technical aspects of user experience. Given the critical role considerations of agency, self-perception and personal identity play in assessing the ethical and legal significance of these technologies, our findings reveal a critical gap in the existing literature. This review provides a comprehensive synthesis of the current qualitative research landscape on neurotechnology and the limitations thereof. These findings can inform researchers on how to study the subjective experience of neurotechnology users more holistically and build patient-centred neurotechnology.
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Interfaces Cerebro-Computador , Investigación Cualitativa , Humanos , AutoimagenRESUMEN
Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.
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Trastornos Relacionados con Sustancias , Humanos , Animales , Alemania , Conducta Adictiva , AlcoholismoRESUMEN
BACKGROUND: Prior work has shown that transcranial alternating current stimulation (tACS) of parietooccipital alpha oscillations (8-14 Hz) can modulate working memory (WM) performance as a function of the phase lag to endogenous oscillations. However, leveraging this effect using real-time phase-tuned tACS has not been feasible so far due to stimulation artifacts preventing continuous phase tracking. OBJECTIVES AND HYPOTHESIS: We aimed to develop a system that tracks and adapts the phase lag between tACS and ongoing parietooccipital alpha oscillations in real-time. We hypothesized that such real-time phase-tuned tACS enhances working memory performance, depending on the phase lag. METHODS: We developed real-time phase-tuned closed-loop amplitude-modulated tACS (CLAM-tACS) targeting parietooccipital alpha oscillations. CLAM-tACS was applied at six different phase lags relative to ongoing alpha oscillations while participants (N = 21) performed a working memory task. To exclude that behavioral effects of CLAM-tACS were mediated by other factors such as sensory co-stimulation, a second group of participants (N = 25) received equivalent stimulation of the forehead. RESULTS: WM accuracy improved in a phase lag dependent manner (p = 0.0350) in the group receiving parietooccipital stimulation, with the strongest enhancement observed at 330° phase lag between tACS and ongoing alpha oscillations (p = 0.00273, d = 0.976). Moreover, across participants, modulation of frontoparietal alpha oscillations correlated both in amplitude (p = 0.0248) and phase (p = 0.0270) with the modulation of WM accuracy. No such effects were observed in the control group receiving frontal stimulation. CONCLUSIONS: Our results demonstrate the feasibility and efficacy of real-time phase-tuned CLAM-tACS in modulating both brain activity and behavior, thereby paving the way for further investigation into brain-behavior relationships and the exploration of innovative therapeutic applications.
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Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.
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BACKGROUND: The aging of the population and the progressive increase of life expectancy in developed countries is leading to a high incidence of age-related cerebrovascular diseases, which affect people's motor and cognitive capabilities and might result in the loss of arm and hand functions. Such conditions have a detrimental impact on people's quality of life. Assistive robots have been developed to help people with motor or cognitive disabilities to perform activities of daily living (ADLs) independently. Most of the robotic systems for assisting on ADLs proposed in the state of the art are mainly external manipulators and exoskeletal devices. The main objective of this study is to compare the performance of an hybrid EEG/EOG interface to perform ADLs when the user is controlling an exoskeleton rather than using an external manipulator. METHODS: Ten impaired participants (5 males and 5 females, mean age 52 ± 16 years) were instructed to use both systems to perform a drinking task and a pouring task comprising multiple subtasks. For each device, two modes of operation were studied: synchronous mode (the user received a visual cue indicating the sub-tasks to be performed at each time) and asynchronous mode (the user started and finished each of the sub-tasks independently). Fluent control was assumed when the time for successful initializations ranged below 3 s and a reliable control in case it remained below 5 s. NASA-TLX questionnaire was used to evaluate the task workload. For the trials involving the use of the exoskeleton, a custom Likert-Scale questionnaire was used to evaluate the user's experience in terms of perceived comfort, safety, and reliability. RESULTS: All participants were able to control both systems fluently and reliably. However, results suggest better performances of the exoskeleton over the external manipulator (75% successful initializations remain below 3 s in case of the exoskeleton and bellow 5s in case of the external manipulator). CONCLUSIONS: Although the results of our study in terms of fluency and reliability of EEG control suggest better performances of the exoskeleton over the external manipulator, such results cannot be considered conclusive, due to the heterogeneity of the population under test and the relatively limited number of participants.
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Actividades Cotidianas , Dispositivo Exoesqueleto , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Calidad de Vida , Reproducibilidad de los Resultados , EncéfaloRESUMEN
Transcranial alternating current stimulation (tACS) can influence perception and behavior, with recent evidence also highlighting its potential impact in clinical settings, but its underlying mechanisms are poorly understood. Behavioral and indirect physiological evidence indicates that phase-dependent constructive and destructive interference between the applied electric field and brain oscillations at the stimulation frequency may play an important role, but in vivo validation during stimulation was unfeasible because stimulation artifacts impede single-trial assessment of brain oscillations during tACS. Here, we attenuated stimulation artifacts to provide evidence for phase-dependent enhancement and suppression of visually evoked steady state responses (SSR) during amplitude-modulated tACS (AM-tACS). We found that AM-tACS enhanced and suppressed SSR by 5.77 ± 2.95%, while it enhanced and suppressed corresponding visual perception by 7.99 ± 5.15%. While not designed to investigate the underlying mechanisms of this effect, our study suggests feasibility and superiority of phase-locked (closed-loop) AM-tACS over conventional (open-loop) AM-tACS to purposefully enhance or suppress brain oscillations at specific frequencies.
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Estimulación Transcraneal de Corriente Directa , Humanos , Encéfalo/fisiología , Percepción Visual/fisiología , ArtefactosRESUMEN
BACKGROUND: Assistive hand exoskeletons are promising tools to restore hand function after cervical spinal cord injury (SCI) but assessing their specific impact on bimanual hand and arm function is limited due to lack of reliable and valid clinical tests. Here, we introduce the Berlin Bimanual Test for Tetraplegia (BeBiTT) and demonstrate its psychometric properties and sensitivity to assistive hand exoskeleton-related improvements in bimanual task performance. METHODS: Fourteen study participants with subacute cervical SCI performed the BeBiTT unassisted (baseline). Thereafter, participants repeated the BeBiTT while wearing a brain/neural hand exoskeleton (B/NHE) (intervention). Online control of the B/NHE was established via a hybrid sensorimotor rhythm-based brain-computer interface (BCI) translating electroencephalographic (EEG) and electrooculographic (EOG) signals into open/close commands. For reliability assessment, BeBiTT scores were obtained by four independent observers. Besides internal consistency analysis, construct validity was assessed by correlating baseline BeBiTT scores with the Spinal Cord Independence Measure III (SCIM III) and Quadriplegia Index of Function (QIF). Sensitivity to differences in bimanual task performance was assessed with a bootstrapped paired t-test. RESULTS: The BeBiTT showed excellent interrater reliability (intraclass correlation coefficients > 0.9) and internal consistency (α = 0.91). Validity of the BeBiTT was evidenced by strong correlations between BeBiTT scores and SCIM III as well as QIF. Wearing a B/NHE (intervention) improved the BeBiTT score significantly (p < 0.05) with high effect size (d = 1.063), documenting high sensitivity to intervention-related differences in bimanual task performance. CONCLUSION: The BeBiTT is a reliable and valid test for evaluating bimanual task performance in persons with tetraplegia, suitable to assess the impact of assistive hand exoskeletons on bimanual function.
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Dispositivo Exoesqueleto , Traumatismos de la Médula Espinal , Humanos , Psicometría , Reproducibilidad de los Resultados , Berlin , Mano , Cuadriplejía/diagnóstico , Cuadriplejía/rehabilitación , Traumatismos de la Médula Espinal/rehabilitaciónRESUMEN
Brain-computer interfaces (BCI) can provide real-time and continuous assessments of mental workload in different scenarios, which can subsequently be used to optimize human-computer interaction. However, assessment of mental workload is complicated by the task-dependent nature of the underlying neural signals. Thus, classifiers trained on data from one task do not generalize well to other tasks. Previous attempts at classifying mental workload across different cognitive tasks have therefore only been partially successful. Here we introduce a novel algorithm to extract frontal theta oscillations from electroencephalographic (EEG) recordings of brain activity and show that it can be used to detect mental workload across different cognitive tasks. We use a published data set that investigated subject dependent task transfer, based on Filter Bank Common Spatial Patterns. After testing, our approach enables a binary classification of mental workload with performances of 92.00 and 92.35%, respectively for either low or high workload vs. an initial no workload condition, with significantly better results than those of the previous approach. It, nevertheless, does not perform beyond chance level when comparing high vs. low workload conditions. Also, when an independent component analysis was done first with the data (and before any additional preprocessing procedure), even though we achieved more stable classification results above chance level across all tasks, it did not perform better than the previous approach. These mixed results illustrate that while the proposed algorithm cannot replace previous general-purpose classification methods, it may outperform state-of-the-art algorithms in specific (workload) comparisons.
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The development of brain-computer interface-controlled exoskeletons promises new treatment strategies for neurorehabilitation after stroke or spinal cord injury. By converting brain/neural activity into control signals of wearable actuators, brain/neural exoskeletons (B/NEs) enable the execution of movements despite impaired motor function. Beyond the use as assistive devices, it was shown that-upon repeated use over several weeks-B/NEs can trigger motor recovery, even in chronic paralysis. Recent development of lightweight robotic actuators, comfortable and portable real-world brain recordings, as well as reliable brain/neural control strategies have paved the way for B/NEs to enter clinical care. Although B/NEs are now technically ready for broader clinical use, their promotion will critically depend on early adopters, for example, research-oriented physiotherapists or clinicians who are open for innovation. Data collected by early adopters will further elucidate the underlying mechanisms of B/NE-triggered motor recovery and play a key role in increasing efficacy of personalized treatment strategies. Moreover, early adopters will provide indispensable feedback to the manufacturers necessary to further improve robustness, applicability, and adoption of B/NEs into existing therapy plans.
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Interfaces Cerebro-Computador , Dispositivo Exoesqueleto , Rehabilitación Neurológica , Robótica , Humanos , EncéfaloRESUMEN
The human brain is arguably one of the most complex systems in nature. To understand how it operates, it is essential to understand the link between neural activity and behavior. Experimental investigation of that link requires tools to interact with neural activity during behavior. Human neuroscience, however, has been severely bottlenecked by the limitations of these tools. While invasive methods can support highly specific interaction with brain activity during behavior, their applicability in human neuroscience is limited. Despite extensive development in the last decades, noninvasive alternatives have lacked spatial specificity and yielded results that are commonly fraught with variability and replicability issues, along with relatively limited understanding of the neural mechanisms involved. Here we provide a comprehensive review of the state-of-the-art in interacting with human brain activity and highlight current limitations and recent efforts to overcome these limitations. Beyond crucial technical and scientific advancements in electromagnetic brain stimulation, new frontiers in interacting with human brain activity such as task-irrelevant sensory stimulation and focal ultrasound stimulation are introduced. Finally, we argue that, along with technological improvements and breakthroughs in noninvasive methods, a paradigm shift towards adaptive closed-loop stimulation will be a critical step for advancing human neuroscience.
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Neurociencias , Estimulación Magnética Transcraneal , Encéfalo/fisiología , Mapeo Encefálico/métodos , Humanos , Estimulación Magnética Transcraneal/métodosRESUMEN
Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estudios Transversales , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Calidad de Vida , Recuperación de la Función , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Rehabilitación de Accidente Cerebrovascular/métodos , Extremidad SuperiorRESUMEN
Working memory (WM) is essential for reasoning, decision-making, and problem solving. Recently, there has been an increasing effort in improving WM through noninvasive brain stimulation (NIBS), especially transcranial direct and alternating current stimulation (tDCS/tACS). Studies suggest that tDCS and tACS can modulate WM performance, but large variability in research approaches hinders the identification of optimal stimulation protocols and interpretation of study results. Moreover, it is unclear whether tDCS and tACS differentially affect WM. Here, we summarize and compare studies examining the effects of tDCS and tACS on WM performance in healthy adults. Following PRISMA-selection criteria, our systematic review resulted in 43 studies (29 tDCS, 11 tACS, 3 both) with a total of 1826 adult participants. For tDCS, only 4 out of 23 single-session studies reported effects on WM, while 7 out of 9 multi-session experiments showed positive effects on WM training. For tACS, 10 out of 14 studies demonstrated effects on WM, which were frequency dependent and robust for frontoparietal stimulation. Our review revealed no reliable effect of single-session tDCS on WM but moderate effects of multi-session tDCS and single-session tACS. We discuss the implications of these findings and future directions in the emerging research field of NIBS and WM.
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Background: Hallucinogen persisting perception disorder (HPPD) is characterized by spontaneous recurrence of visual hallucinations or disturbances after previous consumption of hallucinogens, such as lysergic acid diethylamide (LSD). The underlying physiological mechanisms are unknown and there is no standardized treatment strategy available. Case Presentation: A 33-year-old male patient presented with persistent visual distortions (halos around objects, intensified colors, positive after images, and trails following moving objects) that developed after repeated use of hallucinogenic drugs at the age of 18. Symptoms developed gradually and worsened several months later, resulting in various pharmacological and psychosocial treatment attempts that remained unsuccessful, however. At presentation, 32-channel electroencephalography (EEG) showed increased delta activity over the occipital brain regions, reminiscent of occipital intermittent rhythmic delta activity (OIRDA) usually seen in children. Two sessions of cathodal (inhibitory) transcranial direct current stimulation (tDCS) over 30 min attenuated visual hallucinations and occipital delta activity by approximately 60%. The response persisted for over four weeks. Conclusion: Pathological delta activity over occipital brain regions may play an important role in the development and perpetuation of HPPD and can be attenuated by non-invasive brain stimulation.
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Lesion load of the corticospinal tract (CST-LL), a measure of overlap between a stroke lesion and the CST, is one of the strongest predictors of motor outcomes following stroke. CST-LL is typically calculated by using a probabilistic map of the CST originating from the primary motor cortex (M1). However, higher order motor areas also have projections that contribute to the CST and motor control. In this retrospective study, we examined whether evaluating CST-LL from additional motor origins is more strongly associated with post-stroke motor severity than using CST-LL originating from M1 only. We found that lesion load to both the ventral premotor (PMv) cortex and M1 were more strongly related to stroke motor severity indexed by Fugl-Meyer Assessment cut-off scores than CST-LL of M1 alone, suggesting that higher order motor regions add clinical relevance to motor impairment.
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Corteza Motora , Accidente Cerebrovascular , Humanos , Corteza Motora/patología , Tractos Piramidales/patología , Recuperación de la Función , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patologíaRESUMEN
Severe upper limb paresis can represent an immense burden for stroke survivors. Given the rising prevalence of stroke, restoration of severe upper limb motor impairment remains a major challenge for rehabilitation medicine because effective treatment strategies are lacking. Commonly applied interventions in Germany, such as mirror therapy and impairment-oriented training, are limited in efficacy, demanding for new strategies to be found. By translating brain signals into control commands of external devices, brain-computer interfaces (BCIs) and brain-machine interfaces (BMIs) represent promising, neurotechnology-based alternatives for stroke patients with highly restricted arm and hand function. In this mini-review, we outline perspectives on how BCI-based therapy can be integrated into the different stages of neurorehabilitation in Germany to meet a long-term treatment approach: We found that it is most appropriate to start therapy with BCI-based neurofeedback immediately after early rehabilitation. BCI-driven functional electrical stimulation (FES) and BMI robotic therapy are well suited for subsequent post hospital curative treatment in the subacute stage. BCI-based hand exoskeleton training can be continued within outpatient occupational therapy to further improve hand function and address motivational issues in chronic stroke patients. Once the rehabilitation potential is exhausted, BCI technology can be used to drive assistive devices to compensate for impaired function. However, there are several challenges yet to overcome before such long-term treatment strategies can be implemented within broad clinical application: 1. developing reliable BCI systems with better usability; 2. conducting more research to improve BCI training paradigms and 3. establishing reliable methods to identify suitable patients.