Anodal transcranial direct current stimulation over S1 differentially modulates proprioceptive accuracy in young and old adults

Background: Proprioception is a prerequisite for successful motor control but declines throughout the lifespan. Brain stimulation techniques such as anodal transcranial direct current stimulation (a-tDCS) are capable of enhancing sensorimotor performance across different tasks and age groups. Despite such growing evidence for a restorative potential of tDCS, its impact on proprioceptive accuracy has not been studied in detail yet. Objective: This study investigated online effects of a-tDCS over S1 on proprioceptive accuracy in young (YA) and old healthy adults (OA). Methods: The effect of 15 min of a-tDCS vs. sham on proprioceptive accuracy was assessed in a cross-over, double blind experiment in both age groups. Performance changes were tested using an arm position matching task in a robotic environment. Electrical field (EF) strengths in the target area S1 and control areas were assessed based on individualized simulations. Results: a-tDCS elicited differential changes in proprioceptive accuracy and EF strengths in the two groups: while YA showed a slight improvement, OA exhibited a decrease in performance during a-tDCS. Stronger EF were induced in target S1 and control areas in the YA group. However, no relationship between EF strength and performance change was found. Conclusion: a-tDCS over S1 elicits opposing effects on proprioceptive accuracy as a function of age, a result that is important for future studies investigating the restorative potential of a-tDCS in healthy aging and in the rehabilitation of neurological diseases that occur at advanced age. Modeling approaches could help elucidate the relationship between tDCS protocols, brain structure and performance modulation

Brain-machine interfaces for rehabilitation in stroke: A review

BACKGROUND: Motor paralysis after stroke has devastating consequences for the patients, families and caregivers. Although therapies have improved in the recent years, traditional rehabilitation still fails in patients with severe paralysis. Brain-machine interfaces (BMI) have emerged as a promising tool to guide motor rehabilitation interventions as they can be applied to patients with no residual movement. OBJECTIVE: This paper reviews the efficiency of BMI technologies to facilitate neuroplasticity and motor recovery after stroke. METHODS: We provide an overview of the existing rehabilitation therapies for stroke, the rationale behind the use of BMIs for motor rehabilitation, the current state of the art and the results achieved so far with BMI-based interventions, as well as the future perspectives of neural-machine interfaces. RESULTS: Since the first pilot study by Buch and colleagues in 2008, several controlled clinical studies have been conducted, demonstrating the efficacy of BMIs to facilitate functional recovery in completely paralyzed stroke patients with noninvasive technologies such as the electroencephalogram (EEG). CONCLUSIONS: Despite encouraging results, motor rehabilitation based on BMIs is still in a preliminary stage, and further improvements are required to boost its efficacy. Invasive and hybrid approaches are promising and might set the stage for the next generation of stroke rehabilitation therapies.This study was funded by the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ13GW0053)andAMORSA(FKZ16SV7754), the Deutsche Forschungsgemeinschaft (DFG), the fortüne-Program of the University of Tübingen (2422-0-0 and 2452-0-0), and the Basque GovernmentScienceProgram(EXOTEK:KK2016/00083). NIL was supported by the Basque Government’s scholarship for predoctoral students

Novel Bidirectional Body - Machine Interface to Control Upper Limb Prosthesis

Objective. The journey of a bionic prosthetic user is characterized by the opportunities and limitations involved in adopting a device (the prosthesis) that should enable activities of daily living (ADL). Within this context, experiencing a bionic hand as a functional (and, possibly, embodied) limb constitutes the premise for mitigating the risk of its abandonment through the continuous use of the device. To achieve such a result, different aspects must be considered for making the artificial limb an effective support for carrying out ADLs. Among them, intuitive and robust control is fundamental to improving amputees’ quality of life using upper limb prostheses. Still, as artificial proprioception is essential to perceive the prosthesis movement without constant visual attention, a good control framework may not be enough to restore practical functionality to the limb. To overcome this, bidirectional communication between the user and the prosthesis has been recently introduced and is a requirement of utmost importance in developing prosthetic hands. Indeed, closing the control loop between the user and a prosthesis by providing artificial sensory feedback is a fundamental step towards the complete restoration of the lost sensory-motor functions. Within my PhD work, I proposed the development of a more controllable and sensitive human-like hand prosthesis, i.e., the Hannes prosthetic hand, to improve its usability and effectiveness. Approach. To achieve the objectives of this thesis work, I developed a modular and scalable software and firmware architecture to control the Hannes prosthetic multi-Degree of Freedom (DoF) system and to fit all users’ needs (hand aperture, wrist rotation, and wrist flexion in different combinations). On top of this, I developed several Pattern Recognition (PR) algorithms to translate electromyographic (EMG) activity into complex movements. However, stability and repeatability were still unmet requirements in multi-DoF upper limb systems; hence, I started by investigating different strategies to produce a more robust control. To do this, EMG signals were collected from trans-radial amputees using an array of up to six sensors placed over the skin. Secondly, I developed a vibrotactile system to implement haptic feedback to restore proprioception and create a bidirectional connection between the user and the prosthesis. Similarly, I implemented an object stiffness detection to restore tactile sensation able to connect the user with the external word. This closed-loop control between EMG and vibration feedback is essential to implementing a Bidirectional Body - Machine Interface to impact amputees’ daily life strongly. For each of these three activities: (i) implementation of robust pattern recognition control algorithms, (ii) restoration of proprioception, and (iii) restoration of the feeling of the grasped object's stiffness, I performed a study where data from healthy subjects and amputees was collected, in order to demonstrate the efficacy and usability of my implementations. In each study, I evaluated both the algorithms and the subjects’ ability to use the prosthesis by means of the F1Score parameter (offline) and the Target Achievement Control test-TAC (online). With this test, I analyzed the error rate, path efficiency, and time efficiency in completing different tasks. Main results. Among the several tested methods for Pattern Recognition, the Non-Linear Logistic Regression (NLR) resulted to be the best algorithm in terms of F1Score (99%, robustness), whereas the minimum number of electrodes needed for its functioning was determined to be 4 in the conducted offline analyses. Further, I demonstrated that its low computational burden allowed its implementation and integration on a microcontroller running at a sampling frequency of 300Hz (efficiency). Finally, the online implementation allowed the subject to simultaneously control the Hannes prosthesis DoFs, in a bioinspired and human-like way. In addition, I performed further tests with the same NLR-based control by endowing it with closed-loop proprioceptive feedback. In this scenario, the results achieved during the TAC test obtained an error rate of 15% and a path efficiency of 60% in experiments where no sources of information were available (no visual and no audio feedback). Such results demonstrated an improvement in the controllability of the system with an impact on user experience. Significance. The obtained results confirmed the hypothesis of improving robustness and efficiency of a prosthetic control thanks to of the implemented closed-loop approach. The bidirectional communication between the user and the prosthesis is capable to restore the loss of sensory functionality, with promising implications on direct translation in the clinical practice

Touching on elements for a non-invasive sensory feedback system for use in a prosthetic hand

Hand amputation results in the loss of motor and sensory functions, impacting activities of daily life and quality of life. Commercially available prosthetic hands restore the motor function but lack sensory feedback, which is crucial to receive information about the prosthesis state in real-time when interacting with the external environment. As a supplement to the missing sensory feedback, the amputee needs to rely on visual and audio cues to operate the prosthetic hand, which can be mentally demanding. This thesis revolves around finding potential solutions to contribute to an intuitive non-invasive sensory feedback system that could be cognitively less burdensome and enhance the sense of embodiment (the feeling that an artificial limb belongs to one’s own body), increasing acceptance of wearing a prosthesis.A sensory feedback system contains sensors to detect signals applied to the prosthetics. The signals are encoded via signal processing to resemble the detected sensation delivered by actuators on the skin. There is a challenge in implementing commercial sensors in a prosthetic finger. Due to the prosthetic finger’s curvature and the fact that some prosthetic hands use a covering rubber glove, the sensor response would be inaccurate. This thesis shows that a pneumatic touch sensor integrated into a rubber glove eliminates these errors. This sensor provides a consistent reading independent of the incident angle of stimulus, has a sensitivity of 0.82 kPa/N, a hysteresis error of 2.39±0.17%, and a linearity error of 2.95±0.40%.For intuitive tactile stimulation, it has been suggested that the feedback stimulus should be modality-matched with the intention to provide a sensation that can be easily associated with the real touch on the prosthetic hand, e.g., pressure on the prosthetic finger should provide pressure on the residual limb. A stimulus should also be spatially matched (e.g., position, size, and shape). Electrotactile stimulation has the ability to provide various sensations due to it having several adjustable parameters. Therefore, this type of stimulus is a good candidate for discrimination of textures. A microphone can detect texture-elicited vibrations to be processed, and by varying, e.g., the median frequency of the electrical stimulation, the signal can be presented on the skin. Participants in a study using electrotactile feedback showed a median accuracy of 85% in differentiating between four textures.During active exploration, electrotactile and vibrotactile feedback provide spatially matched modality stimulations, providing continuous feedback and providing a displaced sensation or a sensation dispatched on a larger area. Evaluating commonly used stimulation modalities using the Rubber Hand Illusion, modalities which resemble the intended sensation provide a more vivid illusion of ownership for the rubber hand.For a potentially more intuitive sensory feedback, the stimulation can be somatotopically matched, where the stimulus is experienced as being applied on a site corresponding to their missing hand. This is possible for amputees who experience referred sensation on their residual stump. However, not all amputees experience referred sensations. Nonetheless, after a structured training period, it is possible to learn to associate touch with specific fingers, and the effect persisted after two weeks. This effect was evaluated on participants with intact limbs, so it remains to evaluate this effect for amputees.In conclusion, this thesis proposes suggestions on sensory feedback systems that could be helpful in future prosthetic hands to (1) reduce their complexity and (2) enhance the sense of body ownership to enhance the overall sense of embodiment as an addition to an intuitive control system

Cortical Orchestra Conducted by Purpose and Function

학위논문(박사)--서울대학교 대학원 :자연과학대학 협동과정 뇌과학전공,2020. 2. 정천기.촉각과 자기수용감각은 우리의 생존 및 일상생활에 절대적인 영향을 미치는 중요한 감각 기능이다. 말초신경계에서 이 두 가지 기능들에 필요한 정보를 수집하고 전달하는 기계적 수용기 및 그 구심성 신경들에 대한 신호 전달 메커니즘 및 그 특징들은 상대적으로 잘 알려져 있는 편이다. 그러나, 촉각과 자기수용감각을 형성하기 위한 인간 뇌의 피질에서의 정보 처리 메커니즘에 대하여 우리가 현재 알고 있는 바는 극히 일부분이다. 이 논문에서 제시하는 일련의 연구들은 인간 뇌 피질 단계에서 촉각과 자기수용감각의 지각적 처리과정에 대한 거시적 신경계 정보처리 메커니즘을 다룬다. 첫 번째 연구에서는 뇌피질뇌파를 이용하여 인간 일차 및 이차 체성감각 피질에서 인공적인 자극과 일상생활에서 접할 수 있는 자극을 포함하는 다양한 진동촉감각 및 질감 자극에 대한 거시적 신경계 정보처리 특성을 밝혔다. 이 연구에서는 일차 및 이차 체성감각 피질의 촉감각 주파수 특이적인 하이-감마 영역 신경활동이 자극 주파수에 따라 각각 상이한 시간적 다이나믹스를 가지고 변화하는 것을 확인하였다. 또한, 이러한 하이-감마 활동은 성긴 질감과 미세한 입자감을 가진 자연스러운 질감 자극에 대해서도 진동촉감각의 경우와 유사한 패턴을 보였다. 이러한 결과들은 인간의 진동촉감각이 매우 단순한 형태에 자극일지라도 대뇌 체성감각 시스템에 있어 거시적인 다중 영역에서의 계층적 정보처리를 동반한다는 점을 시사한다. 두 번째 연구에서는 인간의 움직임과 관련된 두정엽 영역에서의 하이-감마 뇌활성이 자기수용감각과 같은 말초신경계로부터의 체성감각 피드백을 주로 반영하는지, 아니면 움직임 준비 및 제어를 위한 피질 간 신경 프로세스에 대한 활동을 반영하는지를 조사하였다. 연구 결과, 자발적 운동 중 대뇌 운동감각령에서의 하이-감마 활동은 일차 체성감각피질이 일차 운동피질보다 더 지배적인 것으로 나타났다. 또한 이 연구에서는, 움직임과 관련된 일차 체성감각피질에서의 하이-감마 뇌활동은 말초신경계로부터의 자기수용감각과 촉각에 대한 신경계 정보처리를 주로 반영하는 것을 밝혔다. 이러한 연구들을 바탕으로, 마지막 연구에서는 인간 대뇌에서의 체성감각 지각 프로세스에 대한 거시적 피질 간 네트워크를 규명하고자 하였다. 이를 위해, 51명의 뇌전증 환자에게서 체성감각을 유발했던 뇌피질전기자극 데이터와 46명의 환자에게서 촉감각 자극 및 운동 수행 중에 측정한 뇌피질뇌파 하이-감마 매핑 데이터를 종합적으로 분석하였다. 그 결과, 체성감각 지각 프로세스는 대뇌에서 넓은 영역에 걸쳐 분포하는 체성감각 관련 네트워크의 신경 활성을 수반한다는 것을 알아냈다. 또한, 뇌피질전기자극을 통한 대뇌 지도와 하이-감마 매핑을 통한 대뇌 지도는 서로 상당한 유사성을 보였다. 흥미롭게도, 뇌피질전기자극과 하이-감마 활동을 종합한 뇌지도들로부터 체성감각 관련 뇌 영역의 공간적 분포가 체성감각 기능에 따라 서로 달랐고, 그에 해당하는 각 영역들은 서로 뚜렷하게 다른 시간적 다이나믹스를 가지고 순차적으로 활성화되었다. 이러한 결과들은 체성감각에 대한 거시적 신경계 프로세스가 그 지각적 기능에 따라 뚜렷이 다른 계층적 네트워크를 가진다는 점을 시사한다. 더 나아가, 본 연구에서의 결과들은 체성감각 시스템의 지각-행동 관련 신경활동 흐름에 관한 이론적인 가설에 대하여 설득력 있는 증거를 제시하고 있다.Tactile and proprioceptive perceptions are crucial for our daily life as well as survival. At the peripheral level, the transduction mechanisms and characteristics of mechanoreceptive afferents containing information required for these functions, have been well identified. However, our knowledge about the cortical processing mechanism for them in human is limited. The present series of studies addressed the macroscopic neural mechanism for perceptual processing of tactile and proprioceptive perception in human cortex. In the first study, I investigated the macroscopic neural characteristics for various vibrotactile and texture stimuli including artificial and naturalistic ones in human primary and secondary somatosensory cortices (S1 and S2, respectively) using electrocorticography (ECoG). I found robust tactile frequency-specific high-gamma (HG, 50–140 Hz) activities in both S1 and S2 with different temporal dynamics depending on the stimulus frequency. Furthermore, similar HG patterns of S1 and S2 were found in naturalistic stimulus conditions such as coarse/fine textures. These results suggest that human vibrotactile sensation involves macroscopic multi-regional hierarchical processing in the somatosensory system, even during the simplified stimulation. In the second study, I tested whether the movement-related HG activities in parietal region mainly represent somatosensory feedback such as proprioception from periphery or primarily indicate cortico-cortical neural processing for movement preparation and control. I found that sensorimotor HG activities are more dominant in S1 than in M1 during voluntary movement. Furthermore, the results showed that movement-related HG activities in S1 mainly represent proprioceptive and tactile feedback from periphery. Given the results of previous two studies, the final study aimed to identify the large-scale cortical networks for perceptual processing in human. To do this, I combined direct cortical stimulation (DCS) data for eliciting somatosensation and ECoG HG band (50 to 150 Hz) mapping data during tactile stimulation and movement tasks, from 51 (for DCS mapping) and 46 patients (for HG mapping) with intractable epilepsy. The results showed that somatosensory perceptual processing involves neural activation of widespread somatosensory-related network in the cortex. In addition, the spatial distributions of DCS and HG functional maps showed considerable similarity in spatial distribution between high-gamma and DCS functional maps. Interestingly, the DCS-HG combined maps showed distinct spatial distributions depending on the somatosensory functions, and each area was sequentially activated with distinct temporal dynamics. These results suggest that macroscopic neural processing for somatosensation has distinct hierarchical networks depending on the perceptual functions. In addition, the results of the present study provide evidence for the perception and action related neural streams of somatosensory system. Throughout this series of studies, I suggest that macroscopic somatosensory network and structures of our brain are intrinsically organized by perceptual function and its purpose, not by somatosensory modality or submodality itself. Just as there is a purpose for human behavior, so is our brain.PART I. INTRODUCTION 1 CHAPTER 1: Somatosensory System 1 1.1. Mechanoreceptors in the Periphery 2 1.2. Somatosensory Afferent Pathways 4 1.3. Cortico-cortical Connections among Somatosensory-related Areas 7 1.4. Somatosensory-related Cortical Regions 8 CHAPTER 2: Electrocorticography 14 2.1. Intracranial Electroencephalography 14 2.2. High-Gamma Band Activity 18 CHAPTER 3: Purpose of This Study 24 PART II. EXPERIMENTAL STUDY 26 CHAPTER 4: Apparatus Design 26 4.1. Piezoelectric Vibrotactile Stimulator 26 4.2. Magnetic Vibrotactile Stimulator 29 4.3. Disc-type Texture Stimulator 33 4.4. Drum-type Texture Stimulator 36 CHAPTER 5: Vibrotactile and Texture Study 41 5.1. Introduction 42 5.2. Materials and Methods 46 5.2.1. Patients 46 5.2.2. Apparatus 47 5.2.3. Experimental Design 49 5.2.4. Data Acquisition and Preprocessing 50 5.2.5. Analysis 51 5.3. Results 54 5.3.1. Frequency-specific S1/S2 HG Activities 54 5.3.2. S1 HG Attenuation during Flutter and Vibration 62 5.3.3. Single-trial Vibration Frequency Classification 64 5.3.4. S1/S2 HG Activities during Texture Stimuli 65 5.4. Discussion 69 5.4.1. Comparison with Previous Findings 69 5.4.2. Tactile Frequency-dependent Neural Adaptation 70 5.4.3. Serial vs. Parallel Processing between S1 and S2 72 5.4.4. Conclusion of Chapter 5 73 CHAPTER 6: Somatosensory Feedback during Movement 74 6.1. Introduction 75 6.2. Materials and Methods 79 6.2.1. Subjects 79 6.2.2. Tasks 80 6.2.3. Data Acquisition and Preprocessing 82 6.2.4. S1-M1 HG Power Difference 85 6.2.5. Classification 86 6.2.6. Timing of S1 HG Activity 86 6.2.7. Correlation between HG and EMG signals 87 6.3. Results 89 6.3.1. HG Activities Are More Dominant in S1 than in M1 89 6.3.2. HG Activities in S1 Mainly Represent Somatosensory Feedback 94 6.4. Discussion 100 6.4.1. S1 HG Activity Mainly Represents Somatosensory Feedback 100 6.4.2. Further Discussion and Future Direction in BMI 102 6.4.3. Conclusion of Chapter 6 103 CHAPTER 7: Cortical Maps of Somatosensory Function 104 7.1. Introduction 106 7.2. Materials and Methods 110 7.2.1. Participants 110 7.2.2. Direct Cortical Stimulation 114 7.2.3. Classification of Verbal Feedbacks 115 7.2.4. Localization of Electrodes 115 7.2.5. Apparatus 116 7.2.6. Tasks 117 7.2.7. Data Recording and Processing 119 7.2.8. Mapping on the Brain 120 7.2.9. ROI-based Analysis 122 7.3. Results 123 7.3.1. DCS Mapping 123 7.3.2. Three and Four-dimensional HG Mapping 131 7.3.3. Neural Characteristics among Somatosensory-related Areas 144 7.4. Discussion 146 7.4.1. DCS on the Non-Primary Areas 146 7.4.2. Two Streams of Somatosensory System 148 7.4.3. Functional Role of ventral PM 151 7.4.4. Limitation and Perspective 152 7.4.5. Conclusion of Chapter 7 155 PART III. CONCLUSION 156 CHAPTER 8: Conclusion and Perspective 156 8.1. Perspective and Future Work 157 References 160 Abstract in Korean 173Docto

Physiotherapy and neuro rehabilitation on stroke evidence and needs

Scientific knowledge in the area of rehabilitation and physiotherapy for stroke is booming and leading to more sustainable models of practice. Several interventions show positive effects with strong scientific support. However, some issues remain to be clarified like what are the effects of PT on brain activity and what are the effects of hands on interventions. Also a general coherence of interventions and outcomes and outcomes measures need to improve. With the intent to clarify these questions and to give an overview of Physiotherapy evidence and needs on stroke rehabilitation, this thesis will present the state of the art on a literature review and the four studies developed on the context of this PhD: Physiotherapy Hands-on Interventions and Stroke - Systematic Review; Physiotherapy and Brain Activity on Stroke - Systematic Review; Brain activity during lower limb movement with physiotherapy manual facilitation – an fMRI study; ICF Linking Process for Categorization of Interventions and Outcomes Measures on Stroke Physiotherapy - Delphi panel. As innovative aspects of this thesis, we highlight: the organization within the ICF framework for the outcomes related with movement; the study of brain activity during a complex multijoint movement of lower limb; the study of immediate effects of manual facilitation of movement, as no similar studies was found on our literature search for this thesis. Regardless the limitations encountered, the non-conclusive findings and some non-identified evidence, it seems still valid to conclude that Physiotherapy is no longer a “black box”, instead is a evidence-based profession. Exists clear and evidence based information for clinical settings and scientific community, that hands off physiotherapy is relevant and has efficacy proved on the rehabilitation of stroke patients on the domains of Structure & Functions and Activities & Participation. This efficacy is extended to the brain activity, which validates the idea that PT can influence neuroplasticity process and consequently contribute for a better recovery in a neurobiological perspective with impact on human performance and autonomy.O conhecimento científico na area da intervenção em utentes com sequelas após Acidente Vascular Cerebral (AVC) e especificamente na área da Fisioterapia, tem crescido nos últimos ano, conduzindo a modelos de prática mais sustentados. São várias as intervneções da Fisioterapia com eficácia comprovada. Contudo, alguns aspectos ainda necessitam de clarificação, como seja quais os efeitos da Fisioterapia na actividade cerebral e quais são os efeitos das intervenções baseadas na manualidade do Fisioterapeuta. É ainda necessária, uma maior coerência entre as intervenções, as variáveis em estudo e os instrumentos de avaliação utilizados. Com o objectivo de contribuir para o esclarecimento destas questões e de oferecer uma visao global da evidência da intervenção da Fisioterapia e as necessidades de desenvolvimento na intervenção e utentes com AVC, esta tese apresenta um estado da arte na revisão de literature e os quarto estudos desenvolvidos no contexto deste doutoramento: Efeitos da Fisioterapia manual em utentes com AVC - revisão sistemática; Efeitos da Fisioterapia na actividade cerebral em utentes com AVC - revisão sistemática; Efeitos imediatos da facilitação manual na actividade cerebral - estudo com RMf; Processo de categorização de intervenções e intrumentos específicos da intervenção em utentes com AVC - Painel de Delphi. Como aspectos inovadores, salientamos a organização de acordo com a estrutura da CIF, para as variaveis relacionadas com o movimento; o estudo a actividade cerebral durante um movimento complexo e multi-articular do membro inferior; o estudo dos efeitos imediatos da facilitação manual na actividade cerebral. Independentemente das limitações encontradas, dos achados não conclusivos e alguns achados de não benefício de intervenções, parece-nos ser válido concluir que a Fisioterapia deixou de ser uma “caixa negra” sendo uma profissão científicamente suportada. Existe informação clara e suportada cientificamente, disponível para os locais de prática e para a comunidade científica, de que a Fisioterapia “hands off” é relevante e tem eficácia comprovada no contexto da intervenção em utentes com AVC, nos domínios da Estrutura e Função e da Actividade e Participação. Esta eficácia estende-se à actividade cerebral, validando a ideia de que a Fisioterapia pode influenciar a neuroplasticidade e consequentemente contribuir para uma recuperação neurobiológica mais adequada, com impacto no desempenho humano e autonomia

Event-related desynchronization during movement attempt and execution in severely paralyzed stroke patients: An artifact removal relevance analysis

The electroencephalogram (EEG) constitutes a relevant tool to study neural dynamics and to develop brain-machine interfaces (BMI) for rehabilitation of patients with paralysis due to stroke. However, the EEG is easily contaminated by artifacts of physiological origin, which can pollute the measured cortical activity and bias the interpretations of such data. This is especially relevant when recording EEG of stroke patients while they try to move their paretic limbs, since they generate more artifacts due to compensatory activity. In this paper, we study how physiological artifacts (i.e., eye movements, motion artifacts, muscle artifacts and compensatory movements with the other limb) can affect EEG activity of stroke patients. Data from 31 severely paralyzed stroke patients performing/attempting grasping movements with their healthy/paralyzed hand were analyzed offline. We estimated the cortical activation as the event-related desynchronization (ERD) of sensorimotor rhythms and used it to detect the movements with a pseudo-online simulated BMI. Automated state-of-the-art methods (linear regression to remove ocular contaminations and statistical thresholding to reject the other types of artifacts) were used to minimize the influence of artifacts. The effect of artifact reduction was quantified in terms of ERD and BMI performance. The results reveal a significant contamination affecting the EEG, being involuntary muscle activity the main source of artifacts. Artifact reduction helped extracting the oscillatory signatures of motor tasks, isolating relevant information from noise and revealing a more prominent ERD activity. Lower BMI performances were obtained when artifacts were eliminated from the training datasets. This suggests that artifacts produce an optimistic bias that improves theoretical accuracy but may result in a poor link between task-related oscillatory activity and BMI peripheral feedback. With a clinically relevant dataset of stroke patients, we evidence the need of appropriate methodologies to remove artifacts from EEG datasets to obtain accurate estimations of the motor brain activity.This study was funded by the fortüne-Program of the University of Tübingen (2422-0-1 and 2452-0-0), the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ 13GW0053) and AMORSA (FKZ 16SV7754), the Deutsche Forschungsgemeinschaft (DFG), the Basque Government Science Program (EXOTEK: KK 2016/00083). The work of A. Insausti-Delgado was supported by the Basque Government's scholarship for predoctoral students

The neural circuit basis of learning

The astounding capacity for learning ranks among the nervous system’s most impressive features. This thesis comprises studies employing varied approaches to improve understanding, at the level of neural circuits, of the brain’s capacity for learning. The first part of the thesis contains investigations of hippocampal circuitry – both theoretical work and experimental work in the mouse Mus musculus – as a model system for declarative memory. To begin, Chapter 2 presents a theory of hippocampal memory storage and retrieval that reflects nonlinear dendritic processing within hippocampal pyramidal neurons. As a prelude to the experimental work that comprises the remainder of this part, Chapter 3 describes an open source software platform that we have developed for analysis of data acquired with in vivo Ca2+ imaging, the main experimental technique used throughout the remainder of this part of the thesis. As a first application of this technique, Chapter 4 characterizes the content of signaling at synapses between GABAergic neurons of the medial septum and interneurons in stratum oriens of hippocampal area CA1. Chapter 5 then combines these techniques with optogenetic, pharmacogenetic, and pharmacological manipulations to uncover inhibitory circuit mechanisms underlying fear learning. The second part of this thesis focuses on the cerebellum-like electrosensory lobe in the weakly electric mormyrid fish Gnathonemus petersii, as a model system for non-declarative memory. In Chapter 6, we study how short-duration EOD motor commands are recoded into a complex temporal basis in the granule cell layer, which can be used to cancel Purkinje-like cell firing to the longer duration and temporally varying EOD-driven sensory responses. In Chapter 7, we consider not only the temporal aspects of the granule cell code, but also the encoding of body position provided from proprioceptive and efference copy sources. Together these studies clarify how the cerebellum-like circuitry of the electrosensory lobe combines information of different forms and then uses this combined information to predict the complex dependence of sensory responses on body position and timing relative to electric organ discharge

Forward optic flow is prioritised in visual awareness independently of walking direction

When two different images are presented separately to each eye, one experiences smooth transitions between them-a phenomenon called binocular rivalry. Previous studies have shown that exposure to signals from other senses can enhance the access of stimulation-congruent images to conscious perception. However, despite our ability to infer perceptual consequences from bodily movements, evidence that action can have an analogous influence on visual awareness is scarce and mainly limited to hand movements. Here, we investigated whether one's direction of locomotion affects perceptual access to optic flow patterns during binocular rivalry. Participants walked forwards and backwards on a treadmill while viewing highly-realistic visualisations of self-motion in a virtual environment. We hypothesised that visualisations congruent with walking direction would predominate in visual awareness over incongruent ones, and that this effect would increase with the precision of one's active proprioception. These predictions were not confirmed: optic flow consistent with forward locomotion was prioritised in visual awareness independently of walking direction and proprioceptive abilities. Our findings suggest the limited role of kinaesthetic-proprioceptive information in disambiguating visually perceived direction of self-motion and indicate that vision might be tuned to the (expanding) optic flow patterns prevalent in everyday life