Proprioceptive feedback facilitates motor imagery-related operant learning of sensorimotor β-band modulation

Motor imagery (MI) activates the sensorimotor system independent of actual movements and might be facilitated by neurofeedback. Knowledge on the interaction between feedback modality and the involved frequency bands during MI-related brain self-regulation is still scarce. Previous studies compared the cortical activity during the MI task with concurrent feedback (MI with feedback condition) to cortical activity during the relaxation task where no feedback was provided (relaxation without feedback condition). The observed differences might, therefore, be related to either the task or the feedback. A proper comparison would necessitate studying a relaxation condition with feedback and a MI task condition without feedback as well. Right-handed healthy subjects performed two tasks, i.e., MI and relaxation, in alternating order. Each of the tasks (MI vs. relaxation) was studied with and without feedback. The respective event-driven oscillatory activity, i.e., sensorimotor desynchronization (during MI) or synchronization (during relaxation), was rewarded with contingent feedback. Importantly, feedback onset was delayed to study the task-related cortical activity in the absence of feedback provision during the delay period. The reward modality was alternated every 15 trials between proprioceptive and visual feedback. Proprioceptive input was superior to visual input to increase the range of task-related spectral perturbations in the α- and β-band, and was necessary to consistently achieve MI-related sensorimotor desynchronization (ERD) significantly below baseline. These effects occurred in task periods without feedback as well. The increased accuracy and duration of learned brain self-regulation achieved in the proprioceptive condition was specific to the β-band. MI-related operant learning of brain self-regulation is facilitated by proprioceptive feedback and mediated in the sensorimotor β-band

State-dependent modulation of cortico-spinal networks

Beta-band rhythm (13-30 Hz) is a dominant oscillatory activity in the sensorimotor system. Numerous studies reported on links between motor performance and the cortical and cortico-spinal beta rhythm. However, these studies report divergent beta-band frequencies and are, additionally, based on differently performed motor-tasks (e.g., motor imagination, muscle contraction, reach, grasp, and attention). This diversity blurs the role of beta in the sensorimotor system. It consequently challenges the development of beta-band activity-dependent stimulation protocols in the sensorimotor system. In this vein, we studied the functional role of beta-band cortico-cortical and cortico-spinal networks during a motor learning task. We studied how the contribution of cortical and spinal beta changes in the course of learning, and how this modulation is affected by afferent feedback to the sensorimotor system. We furthermore researched the relationship to motor performance. Consider that we made our study in the absence of any residual movement to allow our findings to be translated into rehabilitation programs for severely affected stroke patients. This thesis, at first, investigates evoked responses after transcranial magnetic stimulation (TMS). This revealed two different beta-band networks, i.e., in the low and high beta-band reflecting cortical and cortico-spinal activity. We, then, used a broader frequency range in the beta-band to trigger passive opening of the hand (peripheral feedback) or cortical stimulation (cortical feedback). While a unilateral hemispheric increase in cortico-spinal synchronization was observed in the group with peripheral feedback, a bilateral hemispheric increase in cortico-cortical and cortico-spinal synchronization was observed for the group with cortical feedback. An improvement in motor performance was found in the peripheral group only. Additionally, an enhancement in the directed cortico-spinal synchronization from cortex to periphery was observed for the peripheral group. Similar neurophysiological and behavioral changes were observed for stroke patients receiving peripheral feedback. The results 6 suggest two different mechanisms for beta-band activity-dependent protocols depending on the feedback modality. While the peripheral feedback appears to increase the synchronization among neural groups, cortical stimulation appears to recruit dormant neurons and to extend the involved motor network. These findings may provide insights regarding the mechanism behind novel activity-dependent protocols. It also highlights the importance of afferent feedback for motor restoration in beta-band activity-dependent rehabilitation programs

Pre-movement contralateral EEG low beta power is modulated with motor adaptation learning

Various neuroimaging studies aim to understand the complex nature of human motor behavior. There exists a variety of experimental approaches to study neurophysiological correlates of performance during different motor tasks. As distinct from studies based on visuomotor learning, we investigate changes in electroencephalographic (EEG) activity during an actual physical motor adaptation learning experiment. Based on statistical analysis of EEG signals collected during a force-field adaptation task performed with the dominant hand, we observe a modulation of pre-movement upper alpha (10-12 Hz) and lower beta (13-16 Hz) powers over the contralateral region. This modulation is observed to be stronger in lower beta range and, through a regression analysis, is shown to be related with motor adaptation performance on a subject-specific level

Die Bedeutung kognitiver Belastung und adaptiver Schwierigkeitsanpassung für Neurofeedback-basiertes Training

In der vorliegenden Arbeit wurden die grundlegenden Eigenschaften und Wirkungen eines Brain-Machine-Interfaces (BMI), das im EEG gemessene Hirnaktivität in Bewegungen einer Handorthese umsetzt, bei gesunden Probanden untersucht. In der ersten Studie wurden die kortikalen Netzwerke von Probanden mittels EEG untersucht, bevor sie unterschiedliche motorische Aufgaben durchführten: Bewegungsvorstellung (Motor Imagery, MI), tatsächliche Bewegungen (Motor Execution, ME) und die Benutzung eines BMI (d.h. MI mit Feedback durch die Handorthese). Es konnte gezeigt werden, dass Ruhe EEG-Netzwerke die anschließende Fähigkeit der Probanden zu MI, ME und BMI-Anwendung vorhersagen können. Dabei überlappen sich die kortikalen Netzwerke für MI und ME zum Teil, zeigen jedoch auch relevante Unterschiede. In diesem Kontext kann die BMI-Anwendung die Netzwerke und Fähigkeiten von MI und ME überbrücken. In der zweiten Studie wurde das BMI Training mit einem etablierten EMG-basierten Neurofeedback Training verglichen, um die jeweilige kognitive Belastung zu ermitteln. Dabei unterschied sich die kognitive Belastung des BMI Feedbacks vom EMG Feedback und konnte insbesondere zu Frustration führen. Das Frustrationserleben korreliert aber über die verschiedenen Feedback Aufgaben hinweg und legt daher eine spezifische Eigenschaft des Teilnehmers (personal trait) nahe. Darüber hinaus konnte die kognitive Belastung unabhängig von der jeweiligen Aufgabe anhand kortikaler Netzwerke im EEG sowohl in Ruhe als auch während der Aufgabe bestimmt werden. In der dritten Studie erfolgte schließlich eine Schwierigkeits-Adaptation auf der Basis der kognitiven Belastung der Teilnehmer. Die von den Teilnehmern berichtete kognitive Belastung korrelierte dabei mit dem Schwierigkeitsgrad des BMI Trainings. Eine adaptive Schwierigkeitsanpassung des BMI erhöhte schließlich die Leistung und reduzierte die kognitive Belastung der Teilnehmer. Insgesamt wurden mit diesen Probandenstudien die Voraussetzungen geschaffen, ein adaptives Neurofeedback Training zu entwickeln, das langfristig in der Rehabilitation von Schlaganfallpatienten mit motorischen Einschränkungen der Hand eingesetzt werden kann

Power Spectral Density and Functional Connectivity Changes due to a Sensorimotor Neurofeedback Training: A Preliminary Study

Neurofeedback is a form of neuromodulation based on learning to modify some aspects of cortical activity. Sensorimotor rhythm (SMR) oscillation is one of the most used frequency bands in neurofeedback. Several studies have shown that subjects can learn to modulate SMR power to control output devices, but little is known about possible related changes in brain networks. The aim of this study was to investigate the enhanced performance and changes in EEG power spectral density at somatosensory cerebral areas due to a bidirectional modulation-based SMR neurofeedback training. Furthermore, we also analyzed the functional changes in somatosensory areas during resting state induced by the training as exploratory procedure. A six-session neurofeedback protocol based on learning to synchronize and desynchronize (modulate) the SMR was implemented. Moreover, half of the participants were enrolled in two functional magnetic resonance imaging resting-state sessions (before and after the training). At the end of the training, participants showed a successful performance enhancement, an increase in SMR power specific to somatosensory locations, and higher functional connectivity between areas associated with somatosensory activity in resting state. Our research increases the better understanding of the relation between EEG neuromodulation and functional changes and the use of SMR training in clinical practice.This work was supported by grants from Bial Foundation (#385-14), PSI2017-88388-C4-1-R (AEI/FEDER, UE), and the Spanish Ministerio de Economía, Industria y Competitividad (ref: PSI2013-48260-C3-1-R and PSI2014-57231-R)

Sensory threshold neuromuscular electrical stimulation fosters motor imagery performance

Motor imagery (MI) has been largely studied as a way to enhance motor learning and to restore motor functions. Although it is agreed that users should emphasize kinesthetic imagery during MI, recordings of MI brain patterns are not sufficiently reliable for many subjects. It has been suggested that the usage of somatosensory feedback would be more suitable than standardly used visual feedback to enhance MI brain patterns. However, somatosensory feedback should not interfere with the recorded MI brain pattern. In this study we propose a novel feedback modality to guide subjects during MI based on sensory threshold neuromuscular electrical stimulation (St-NMES). St-NMES depolarizes sensory and motor axons without eliciting any muscular contraction. We hypothesize that St-NMES does not induce detectable ERD brain patterns and fosters MI performance. Twelve novice subjects were included in a cross-over design study. We recorded their EEG, comparing St-NMES with visual feedback during MI or resting tasks. We found that St-NMES not only induced significantly larger desynchronization over sensorimotor areas (p<0.05) but also significantly enhanced MI brain connectivity patterns. Moreover, classification accuracy and stability were significantly higher with St-NMES. Importantly, St-NMES alone did not induce detectable artifacts, but rather the changes in the detected patterns were due to an increased MI performance. Our findings indicate that St-NMES is a promising feedback in order to foster MI performance and cold be used for BMI online applications

Chaotic exploration and learning of locomotor behaviours

Recent developments in the embodied approach to understanding the generation of adaptive behaviour, suggests that the design of adaptive neural circuits for rhythmic motor patterns should not be done in isolation from an appreciation, and indeed exploitation, of neural-body-environment interactions. Utilising spontaneous mutual entrainment between neural systems and physical bodies provides a useful passage to the regions of phase space which are naturally structured by the neuralbody- environmental interactions. A growing body of work has provided evidence that chaotic dynamics can be useful in allowing embodied systems to spontaneously explore potentially useful motor patterns. However, up until now there has been no general integrated neural system that allows goal-directed, online, realtime exploration and capture of motor patterns without recourse to external monitoring, evaluation or training methods. For the first time, we introduce such a system in the form of a fully dynamic neural system, exploiting intrinsic chaotic dynamics, for the exploration and learning of the possible locomotion patterns of an articulated robot of an arbitrary morphology in an unknown environment. The controller is modelled as a network of neural oscillators which are coupled only through physical embodiment, and goal directed exploration of coordinated motor patterns is achieved by a chaotic search using adaptive bifurcation. The phase space of the indirectly coupled neural-body-environment system contains multiple transient or permanent self-organised dynamics each of which is a candidate for a locomotion behaviour. The adaptive bifurcation enables the system orbit to wander through various phase-coordinated states using its intrinsic chaotic dynamics as a driving force and stabilises the system on to one of the states matching the given goal criteria. In order to improve the sustainability of useful transient patterns, sensory homeostasis has been introduced which results in an increased diversity of motor outputs, thus achieving multi-scale exploration. A rhythmic pattern discovered by this process is memorised and sustained by changing the wiring between initially disconnected oscillators using an adaptive synchronisation method. The dynamical nature of the weak coupling through physical embodiment allows this adaptive weight learning to be easily integrated, thus forming a continuous exploration-learning system. Our result shows that the novel neuro-robotic system is able to create and learn a number of emergent locomotion behaviours for a wide range of body configurations and physical environment, and can re-adapt after sustaining damage. The implications and analyses of these results for investigating the generality and limitations of the proposed system are discussed

Learning and adaptation in brain machine interfaces

Balancing subject learning and decoder adaptation is central to increasing brain machine interface (BMI) performance. We addressed these complementary aspects in two studies: (1) a learning study, in which mice modulated “beta” band activity to control a 1D auditory cursor, and (2) an adaptive decoding study, in which a simple recurrent artificial neural network (RNN) decoded intended saccade targets of monkeys. In the learning study, three mice successfully increased beta band power following trial initiations, and specifically increased beta burst durations from 157 ms to 182 ms, likely contributing to performance. Though the task did not explicitly require specific movements, all three mice appeared to modulate beta activity via active motor control and had consistent vibrissal motor cortex multiunit activity and local field potential relationships with contralateral whisker pad electromyograms. The increased burst durations may therefore by a direct result of increased motor activity. These findings suggest that only a subset of beta rhythm phenomenology can be volitionally modulated (e.g. the tonic “hold” beta), therefore limiting the possible set of successful beta neuromodulation strategies. In the adaptive decoding study, RNNs decoded delay period activity in oculomotor and working memory regions while monkeys performed a delayed saccade task. Adaptive decoding sessions began with brain-controlled trials using pre-trained RNN models, in contrast to static decoding sessions in which 300-500 initial eye-controlled training trials were performed. Closed loop RNN decoding performance was lower than predicted by offline simulations. More consistent delay period activity and saccade paths across trials were associated with higher decoding performance. Despite the advantage of consistency, one monkey’s delay period activity patterns changed over the first week of adaptive decoding, and the other monkey’s saccades were more erratic during adaptive decoding than during static decoding sessions. It is possible that the altered session paradigm eliminating eye-controlled training trials led to either frustration or exploratory learning, causing the neural and behavioral changes. Considering neural control and decoder adaptation of BMIs in these studies, future work should improve the “two-learner” subject-decoder system by better modeling the interaction between underlying brain states (and possibly their modulation) and the neural signatures representing desired outcomes

Brain-computer interface technology and neuroelectrical imaging to improve motor recovery after stroke

Stroke is defined as a focal lesion in the brain caused by acute ischemia or hemorrhage. The events that characterize acute stroke as well as the spontaneous recovery process occurring in the subacute phase, demonstrate that the focal damage affects remote interconnected areas. On the other hand, interconnected areas largely contribute to reorganization of the central nervous system (CNS) along the recovery process (plasticity) throughout compensatory or restorative mechanisms which can also lead to unwanted effects (maladaptive plasticity). Such post-stroke brain reorganization occurring spontaneously or within a rehabilitation program, is the object of wide literature in the fields of neuroimaging and neurophysiology. Brain-Computer Interfaces (BCIs) allow recognition, monitoring and reinforcement of specific brain activities as recorded eg. via electroencephalogram (EEG) and use such brain activity to control external devices via a computer. Sensorimotor rhythm (SMR) based BCIs exploit the modulation occurring in the EEG in response to motor imagery (MI) tasks: the subject is asked to perform MI of eg. left or right hand in order to control a cursor on a screen. In the context of post-stroke motor rehabilitation, such recruitment of brain activity within the motor system through MI can be used to harness brain reorganization towards a better functional outcome. Since 2009 my research activity has been focused mainly on BCI applications for upper limb motor rehabilitation after stroke within national (Ministry of Health) and international (EU) projects. I conducted (or participated to) several basic and clinical studies involving both healthy subjects and stroke patients and employing a combination of neurophysiological techniques (EEG, transcranial magnetic stimulation – TMS) and BCI technology (De Vico Fallani et al., 2013; Kaiser et al., 2012; Morone et al., 2015; Pichiorri et al., 2011). Such studies culminated in a randomized controlled trial (RCT) conducted on subacute stroke patients in which we demonstrated that a one-month training with a BCI system, which was specifically designed to support upper limb rehabilitation after stroke, significantly improved functional outcome (upper limb motor function) in the target population. Moreover, we observed changes in brain activity and connectivity (from high-density EEG recordings) occurring in motor related frequency ranges that significantly correlated to the functional outcome in the target group (Pichiorri et al., 2015). Following these promising results, my activity proceeded along two main pathways during the PhD course. On one hand, efforts were made ameliorate the prototypal BCI system used in (Pichiorri et al., 2015); the current system (called Promotœr) is an all-in-one BCI training station with several improvements in usability for both the patient and the therapist (it is easier to use, employs wireless EEG system with reduced number of electrodes) (Colamarino et al., 2017a,b). The Promotœr system is currently employed in add-on to standard rehabilitation therapy in patients admitted at Fondazione Santa Lucia. Preliminary results are available on chronic stroke patients, partially retracing those obtained in the subacute phase (Pichiorri et al., 2015) as well as explorative reports on patients with upper limb motor deficit of central origin other than stroke (eg. spinal cord injury at the cervical level). In the last year, I submitted research projects related to the Promotœr system to private and public institutions. These projects foresee i) the addition of a proprioceptive feedback to the current visual one by means of Functional Electrical Stimulation (FES) ii) online evaluation of residual voluntary movement as recorded via electromyography (EMG), and iii) improvements in the BCI control features to integrate concepts derived from recent advancements in brain connectivity. On these themes, I recently obtained a grant from a private Swedish foundation. On the other hand, I conducted further analyses of data collected in the RCT (Pichiorri et al., 2015) to identify possible neurophysiological markers of good motor recovery. Specifically, I focused on interhemispheric connectivity (EEG derived) and its correlation with the integrity of the corticospinal tract (as assessed by TMS) and upper limb function (measured with clinical scales) in subacute stroke patients. The results of these analyses were recently published on an international peer-reviewed journal (Pichiorri et al., 2018). In the first chapter of this thesis, I will provide an updated overview on BCI application in neurorehabilitation (according to the current state-of-the-art). The content of this chapter is part of a wider book chapter, currently in press in Handbook of Clinical Neurology (Pichiorri and Mattia, in press). In the second chapter, I will report on the status of BCI applications for motor rehabilitation of the upper limb according to the approach I developed along my research activity, including ongoing projects and prliminary findings. In the third chapter I will present the results of a neurophysiological study on subacute stroke patients, exploring EEG derived interhemispheric connectivity as a possible neurophysiological correlate of corticospinal tract integrity and functional impairment of the upper limb. Overall this work aims to outline the current and potential role of BCI technology and EEG based neuroimaging in post-stroke rehabilitation mainly in relation to upper limb motor function, nonetheless touching upon possible different applications and contexts in neighboring research fields

Acetylcholine neuromodulation in normal and abnormal learning and memory: vigilance control in waking, sleep, autism, amnesia, and Alzheimer's disease

This article provides a unified mechanistic neural explanation of how learning, recognition, and cognition break down during Alzheimer's disease, medial temporal amnesia, and autism. It also clarifies whey there are often sleep disturbances during these disorders. A key mechanism is how acetylcholine modules vigilance control in cortical layer