Study of the Functional Brain Connectivity and Lower-Limb Motor Imagery Performance After Transcranial Direct Current Stimulation

The use of transcranial direct current stimulation (tDCS) has been related to the improvement of motor and learning tasks. The current research studies the effects of an asymmetric tDCS setup over brain connectivity, when the subject is performing a motor imagery (MI) task during five consecutive days. A brain–computer interface (BCI) based on electroencephalography is simulated in offline analysis to study the effect that tDCS has over different electrode configurations for the BCI. This way, the BCI performance is used as a validation index of the effect of the tDCS setup by the analysis of the classifier accuracy of the experimental sessions. In addition, the relationship between the brain connectivity and the BCI accuracy performance is analyzed. Results indicate that tDCS group, in comparison to the placebo sham group, shows a higher significant number of connectivity interactions in the motor electrodes during MI tasks and an increasing BCI accuracy over the days. However, the asymmetric tDCS setup does not improve the BCI performance of the electrodes in the intended hemisphereThis research has been carried out in the framework of the project Walk — Controlling lower-limb exoskeletons by means of BMIs to assist people with walking disabilities (RTI2018-096677-B-I00Funded by the Spanish Ministry of Science and Innovation, the Spanish State Agency of Research and the European Union through the European Regional Development Fund;by the Consellería de Innovación, Universidades, Ciencia y Sociedad Digital (Generalitat Valenciana) and the European Social Fund in the framework of the project ‘Desarrollo de nuevas interfaces cerebro-m´aquina para la rehabilitaci`on de miembro inferior’ (GV/2019/009).Also, the Mexican Council of Science and Technology (CONACyT) provided J. A. Gaxiola-Tirado his scholarshi

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function161CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465686/2014-1Não tem2014/50909-8; 13/10187–0; 14/10134–7The authors thank the Ministry of Education (MEC), FAPESP - São Paulo Research Foundation, Universidade Estadual de Londrina, Universidade Federal do Rio Grande do Norte and Universidade Federal do ABC for its support. Postdoctoral scholarships to DGSM from the Coordination for the Improvement of Higher Education Personnel (CAPES). Source(s) of financial support: This study was partially funded by grants to MB from NIH (NIH-NIMH 1R01MH111896, NIH-NINDS 1R01NS101362, NIH-NCI U54CA137788/U54CA132378, R03 NS054783) and New York State Department of Health (NYS DOH, DOH01-C31291GG), CEPID/BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology (Process: 13/07559–3) to LML, Brazilian National Research Council (CNPq, Grant # 465686/2014-1) and the São Paulo Research Foundation (Grant # 2014/50909-8) to MSC, and Postdoctoral scholarships to AHO from FAPESP - Sao Paulo Research Foundation (Process: 13/10187–0 and 14/10134–7

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function

Multisensory Stimulation in Stroke Rehabilitation

The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, and various kinds of music therapy. Non-invasive brain stimulation has showed promising preliminary results in aphasia and neglect. Patient heterogeneity and the interaction of age, gender, genes, and environment are discussed. Randomized controlled longitudinal trials starting earlier post-stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation. It is proposed that we should pay more attention to age, gender, and laterality in clinical studies

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

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 (tDCS) to Improve Lower Limb Motor Recovery Following Stroke: A Review and Study Proposal

Strokes are the result of restricted blood flow to particular areas of the brain classified by their cause. The neural damage they cause are of growing concern as the number of young adults experiencing strokes has increased by 11% in the last decade. Following stroke, there is an imbalance of inhibitory and excitatory neuronal activity, and disruption of neural networks. These changes lead to neuronal death and loss of synaptic connections that, depending on which part of the brain is affected, result in behavioral deficits such as weakness, limb hemiparesis, and loss of coordination, as well as speech and cognitive impairments. However, this loss of function can be partly recovered due to neuroplastic processes. Non-invasive brain stimulation (NIBS) is an approach that involves implanting electrodes into targeted areas of the brain which are connected to an implantable pulse generator on the skin that delivers chronic electric pulse. There are different forms of stimulation, but one with some established success in improving upper and lower limb mobility, as well as some cognitive symptoms, is transcranial direct current stimulation (tDCS). For the treatment of stroke, tDCS aims to increase excitability of the lesioned areas to improve contralesional mobility. While past research has focused on stimulating well established motor regions, such as the cerebellum, motor cortex, and basal ganglia, sensory systems also play a key role in sending information through the ascending dorsal column medial lemniscal pathway, posterior and anterior spinocerebellar tracts, and spinoreticular tracts. Here is a review of the current research on the integration of sensory and motor information in order to carry out desired movement, a discussion about how these networks are being targeted by tDCS after stroke to help patients regain lower limb movement, and finally, a proposed study in which improvements in balance, gait, and postural stability after anodal tDCS continue up to a year post-treatment in chronic ischemic stroke patients

A Systemic Review of Functional Near-Infrared Spectroscopy for Stroke: Current Application and Future Directions

Background: Survivors of stroke often experience significant disability and impaired quality of life. The recovery of motor or cognitive function requires long periods. Neuroimaging could measure changes in the brain and monitor recovery process in order to offer timely treatment and assess the effects of therapy. A non-invasive neuroimaging technique near-infrared spectroscopy (NIRS) with its ambulatory, portable, low-cost nature without fixation of subjects has attracted extensive attention.Methods: We conducted a comprehensive literature review in order to review the use of NIRS in stroke or post-stroke patients in July 2018. NCBI Pubmed database, EMBASE database, Cochrane Library and ScienceDirect database were searched.Results: Overall, we reviewed 66 papers. NIRS has a wide range of application, including in monitoring upper limb, lower limb recovery, motor learning, cortical function recovery, cerebral hemodynamic changes, cerebral oxygenation, as well as in therapeutic method, clinical researches, and evaluation of the risk for stroke.Conclusions: This study provides a preliminary evidence of the application of NIRS in stroke patients as a monitoring, therapeutic, and research tool. Further studies could give more emphasize on the combination of NIRS with other techniques and its utility in the prevention of stroke

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