Improving Real-Time Lower Limb Motor Imagery Detection Using tDCS and an Exoskeleton

The aim of this work was to test if a novel transcranial direct current stimulation (tDCS) montage boosts the accuracy of lower limb motor imagery (MI) detection by using a real-time brain-machine interface (BMI) based on electroencephalographic (EEG) signals. The tDCS montage designed was composed of two anodes and one cathode: one anode over the right cerebrocerebellum, the other over the motor cortex in Cz, and the cathode over FC2 (using the International 10–10 system). The BMI was designed to detect two MI states: relax and gait MI; and was based on finding the power at the frequency which attained the maximum power difference between the two mental states at each selected EEG electrode. Two different single-blind experiments were conducted, E1 and a pilot test E2. E1 was based on visual cues and feedback and E2 was based on auditory cues and a lower limb exoskeleton as feedback. Twelve subjects participated in E1, while four did so in E2. For both experiments, subjects were separated into two equally-sized groups: sham and active tDCS. The active tDCS group achieved 12.6 and 8.2% higher detection accuracy than the sham group in E1 and E2, respectively, reaching 65 and 81.6% mean detection accuracy in each experiment. The limited results suggest that the exoskeleton (E2) enhanced the detection of the MI tasks with respect to the visual feedback (E1), increasing the accuracy obtained in 16.7 and 21.2% for the active tDCS and sham groups, respectively. Thus, the small pilot study E2 indicates that using an exoskeleton in real-time has the potential of improving the rehabilitation process of cerebrovascular accident (CVA) patients, but larger studies are needed in order to further confirm this claim

Enhancing Dancing: Examining The Potency Of A Combined Action Observation And Brain Stimulation Intervention

Research supports the idea that action observation (AO)-based training can be an effective component of physical training and rehabilitation. While much is known about the benefits of AO for simple movements, less is known about the utility of AO-based training for complex, whole-body sequences of movements. Additionally, positive motor performance and neurophysiological findings are associated with anodal-transcranial direct current stimulation (A-tDCS). Therefore, it may be valuable to investigate the combination of these two approaches to further enhance motor learning. It is unknown how this combination, utilizing an alternative electrode arrangement of t-DCS (bihemispheric anodal corticomotor tDCS [BAC-tDCS]), would affect learning of a complex, whole-body task. The first aim of this dissertation was to assess the replicability/reliability of dance sequence performance scoring using the X-box One KinectTM game Dance Central Spotlight. In Study 1, test-retest reliability was assessed as participants completed three thirty-second trials of repetitive arm flapping in synchrony with a metronome. The results revealed a good to excellent degree of test-retest reliability demonstrating that Dance Central Spotlight could be used as a primary measurement tool for future studies to obtain reliable measures for complex, whole-body motor tasks such as dance. The purpose of the second study was to determine whether AO prior to action execution would improve an individual’s performance on a complex, whole-body task (i.e., dance). In Study 2, participants observed one dance before performing both dances (DANCEA and DANCEB) in a post-test. Participants returned after a washout period (M = 5.40 weeks, SD = 1.42) to observe the opposite dance and complete another post-test. Performance scores were significantly better when individuals had viewed the dance sequence prior to execution compared to when they had not observed the sequence prior to execution. This outcome was observed for DANCEA, which was perceived to be more difficult, but not for DANCEB. The third aim was to examine the relationship between motor learning and a combined non-invasive brain stimulation/AO-based intervention with a complex, whole-body motor skill. Additionally, this study attempted to test the hypothesis that prior physical activity, as assessed by the International Physical Activity Questionnaire (IPAQ), alters the modulatory effects of this combined treatment. In a counterbalanced, cross-over design, participants received either BAC-tDCS or sham during observation of a chosen dance. After a washout period (M = 5.09 weeks, SD = 1.72), participants received the opposite intervention during observation of the dance. Participants performed the dance for Immediate and 1 Week Post-tests. Performance scores were better at 1 Week Post-test than Immediate Post-test, but performance scores did not differ between AO/BAC-tDCS and AO/Sham. There was a moderate, positive correlation between physical activity and overall improvement in dance performance scores after AO/Sham but not AO/BAC-tDCS. An interaction effect was seen between time (Immediate Post-test and 1 Week Post-test) and order in which participants received the intervention (AO/BAC-tDCS and AO/Sham). This investigation indicated that AO may be able to improve learning of a relatively difficult complex, whole-body sequence of movements. Furthermore, it is feasible to combine an AO-based learning intervention with BAC-tDCS, but further research must be done to assess the effectiveness as an order or learning effect may have clouded these results. Lastly, prior physical activity levels should be considered in individuals as it is unclear how one’s history of physical activity may affect their rate of motor learning

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

Transcranial direct current stimulation to improve the dysfunction of descending pain modulatory system related to opioids in chronic non-cancer pain : an integrative review of neurobiology and meta-analysis

Background: Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS). Objectives: This integrative review with meta-analysis aimed: (i) To discuss the potential mechanisms involved in analgesic tolerance and opioid-induced hyperalgesia (OIH). (ii) To examine how the opioid can affect the function of DPIS. (ii) To show evidence about the tDCS as an approach to treat acute and chronic pain. (iii) To discuss the effect of tDCS on DPIS and how it can counter-regulate the OIH. (iv) To draw perspectives for the future about the tDCS effects as an approach to improve the dysfunction in the DPIS in chronic non-cancer pain. Methods: Relevant published randomized clinical trials (RCT) comparing active (irrespective of the stimulation protocol) to sham tDCS for treating chronic non-cancer pain were identified, and risk of bias was assessed. We searched trials in PubMed, EMBASE and Cochrane trials databases. tDCS protocols accepted were application in areas of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), or occipital area. Results: Fifty-nine studies were fully reviewed, and 24 with moderate to the high-quality methodology were included. tDCS improved chronic pain with a moderate effect size [pooled standardized mean difference; −0.66; 95% confidence interval (CI) −0.91 to −0.41]. On average, active protocols led to 27.26% less pain at the end of treatment compared to sham [95% CI; 15.89–32.90%]. Protocol varied in terms of anodal or cathodal stimulation, areas of stimulation (M1 and DLPFC the most common), number of sessions (from 5 to 20) and current intensity (from 1 to 2mA). The time of application was 20min in 92% of protocols. Conclusion: In comparison with sham stimulation, tDCS demonstrated a superior effect in reducing chronic pain conditions. They give perspectives that the top-down neuromodulator effects of tDCS are a promising approach to improve management in refractory chronic not-cancer related pain and to enhance dysfunctional neuronal circuitries involved in the DPIS and other pain dimensions and improve pain control with a therapeutic opioid-free. However, further studies are needed to determine individualized protocols according to a biopsychosocial perspective

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches

Effective EEG analysis for advanced AI-driven motor imagery BCI systems

Developing effective signal processing for brain-computer interfaces (BCIs) and brain-machine interfaces (BMIs) involves factoring in three aspects of functionality: classification performance, execution time, and the number of data channels used. The contributions in this thesis are centered on these three issues. Contributions are focused on the classification of motor imagery (MI) data, which is generated during imagined movements. Typically, EEG time-series data is segmented for data augmentation or to mimic buffering that happens in an online BCI. A multi-segment decision fusion approach is presented, which takes consecutive temporal segments of EEG data, and uses decision fusion to boost classification performance. It was computationally lightweight and improved the performance of four conventional classifiers. Also, an analysis of the contributions of electrodes from different scalp regions is presented, and a subset of channels is recommended. Sparse learning (SL) classifiers have exhibited strong classification performance in the literature. However, they are computationally expensive. To reduce the test-set execution times, a novel EEG classification pipeline consisting of a genetic-algorithm (GA) for channel selection and a dictionary-based SL module for classification, called GABSLEEG, is presented. Subject-specific channel selection was carried out, in which the channels are selected based on training data from the subject. Using the GA-recommended subset of EEG channels reduced the execution time by 60% whilst preserving classification performance. Although subject-specific channel selection is widely used in the literature, effective subject-independent channel selection, in which channels are detected using data from other subjects, is an ideal aim because it leads to lower training latency and reduces the number of electrodes needed. A novel convolutional neural network (CNN)-based subject-independent channels selection method is presented, called the integrated channel selection (ICS) layer. It performed on-a-par with or better than subject-specific channel selection. It was computationally efficient, operating 12-17 times faster than the GA channel selection module. The ICS layer method was versatile, performing well with two different CNN architectures and datasets.Developing effective signal processing for brain-computer interfaces (BCIs) and brain-machine interfaces (BMIs) involves factoring in three aspects of functionality: classification performance, execution time, and the number of data channels used. The contributions in this thesis are centered on these three issues. Contributions are focused on the classification of motor imagery (MI) data, which is generated during imagined movements. Typically, EEG time-series data is segmented for data augmentation or to mimic buffering that happens in an online BCI. A multi-segment decision fusion approach is presented, which takes consecutive temporal segments of EEG data, and uses decision fusion to boost classification performance. It was computationally lightweight and improved the performance of four conventional classifiers. Also, an analysis of the contributions of electrodes from different scalp regions is presented, and a subset of channels is recommended. Sparse learning (SL) classifiers have exhibited strong classification performance in the literature. However, they are computationally expensive. To reduce the test-set execution times, a novel EEG classification pipeline consisting of a genetic-algorithm (GA) for channel selection and a dictionary-based SL module for classification, called GABSLEEG, is presented. Subject-specific channel selection was carried out, in which the channels are selected based on training data from the subject. Using the GA-recommended subset of EEG channels reduced the execution time by 60% whilst preserving classification performance. Although subject-specific channel selection is widely used in the literature, effective subject-independent channel selection, in which channels are detected using data from other subjects, is an ideal aim because it leads to lower training latency and reduces the number of electrodes needed. A novel convolutional neural network (CNN)-based subject-independent channels selection method is presented, called the integrated channel selection (ICS) layer. It performed on-a-par with or better than subject-specific channel selection. It was computationally efficient, operating 12-17 times faster than the GA channel selection module. The ICS layer method was versatile, performing well with two different CNN architectures and datasets

Social and Affective Neuroscience of Everyday Human Interaction

This Open Access book presents the current state of the art knowledge on social and affective neuroscience based on empirical findings. This volume is divided into several sections first guiding the reader through important theoretical topics within affective neuroscience, social neuroscience and moral emotions, and clinical neuroscience. Each chapter addresses everyday social interactions and various aspects of social interactions from a different angle taking the reader on a diverse journey. The last section of the book is of methodological nature. Basic information is presented for the reader to learn about common methodologies used in neuroscience alongside advanced input to deepen the understanding and usability of these methods in social and affective neuroscience for more experienced readers