Preliminary evaluation of SensHand V1 in assessing motor skills performance in Parkinson Disease

Nowadays, the increasing old population 65+ as well as the pace imposed by work activities lead to a high number of people that have particular injuries for limbs. In addition to persistent or temporary disabilities related to accidental injuries we must take into account that part of the population suffers from motor deficits of the hands due to stroke or diseases of various clinical nature. The most recurrent technological solutions to measure the rehabilitation or skill motor performance of the hand are glove-based devices, able to faithfully capture the movements of the hand and fingers. This paper presents a system for hand motion analysis based on 9-axis complete inertial modules and dedicated microcontroller which are fixed on fingers and forearm. The technological solution presented is able to track the patients' hand motions in real-time and then to send data through wireless communication reducing the clutter and the disadvantages of a glove equipped with sensors through a different technological structure. The device proposed has been tested in the study of Parkinson's disease

Development of EEG-based technologies for the characterization and treatment of neurological diseases affecting the motor function

This thesis presents a set of studies applying signal processing and data mining techniques in real-time working systems to register, characterize and condition the movement-related cortical activity of healthy subjects and of patients with neurological disorders affecting the motor function. Patients with two of the most widespread neurological affections impairing the motor function are considered here: patients with essential tremor and patients who have suffered a cerebro-vascular accident. The different chapters in the presented thesis show results regarding the normal cortical activity associated with the planning and execution of motor actions with the upper-limb, and the pathological activity related to the patients' motor dysfunction (measurable with muscle electrodes or movement sensors). The initial chapters of the book present i) a revision of the basic concepts regarding the role of the cerebral cortex in the motor control and the way in which the electroencephalographic activity allows its analysis and conditioning, ii) a study on the cortico-muscular interaction at the tremor frequency in patients with essential tremor under the effects of a drug reducing their tremor, and finally iii) a study based on evolutionary algorithms that aims to identify cortical patterns related to the planning of a number of motor tasks performed with a single arm. In the second half of the thesis book, two brain-computer interface systems to be used in rehabilitation scenarios with essential tremor patients and with patients with a stroke are proposed. In the first system, the electroencephalographic activity is used to anticipate voluntary movement actions, and this information is integrated in a multimodal platform estimating and suppressing the pathological tremors. In the second case, a conditioning paradigm for stroke patients based on the identification of the motor intention with temporal precision is presented and tested with a cohort of four patients along a month during which the patients undergo eight intervention sessions. The presented thesis has yielded advances from both the technological and the scientific points of view in all studies proposed. The main contributions from the technological point of view are: ¿ The design of an integrated upper-limb platform working in real-time. The platform was designed to acquire information from different types of noninvasive sensors (EEG, EMG and gyroscopic sensors) characterizing the planning and execution of voluntary movements. The platform was also capable of processing online the acquired data and generating an electrical feedback. ¿ The development of signal processing and classifying techniques adapted to the kind of signal recorded in the two kinds of patients considered in this thesis (patients with essential tremor and patients with a stroke) and to the requirements of online processing and real-time single-trial function desired for BCI applications. Especially in this regard, an original methodology to detect onsets of voluntary movements using slow cortical potentials and cortical rhythms has been presented. ¿ The design and validation in real-time of asynchronous BCI systems using motor planning EEG segments to anticipate or detect when patients begin a voluntary movement with the upper-limb. ¿ The proof of concept of the advantages of an EEG system integrated in a multimodal human-robot interface architecture that constitutes the first multimodal interface using the combined acquisition of EEG, EMG and gyroscopic data, which allows the concurrent characterization of different parts of the body associated with the execution of a movement. The main scientific contributions of this thesis are: ¿ The study of the EEG-based anticipation of voluntary movements presented in Chapter 5 of the thesis was the first demonstration (to the author's knowledge) of the capacity of the EEG signal to provide reliable movement predictions based on single-trial classification of online data of healthy subjects and ET patients. This study also provides, for the first time, the results of a BCI system tested in ET patients and it represents an original approach to BCI applications for this group of patients. ¿ It has been presented the first neurophysiological study using EEG and EMG data to analyze the effects of a drug on cortical activity and tremors of patients with ET. In addition, the obtained results have shown for the first time that a significant correlation exists between the dynamics of specific cortical oscillations and pathological tremor manifestation as a consequence of the drug effects. ¿ It has been proposed for the first time an experiment to inspect whether the EEG signal carries enough information to classify up to seven different tasks performed with a single limb. Both the methodology applied and the validation procedure are also innovative in this sort of studies. ¿ It has been demonstrated for the first time the relevance of combining different cortical sources of information (such as BP and ERD) to estimate the initiation of voluntary movements with the upper-limb. In this line, special relevance may be given to the positive results achieved with stroke patients, improving the results presented by similar previous EEG-based studies by other research groups. It has also been proposed for the first time an upper-limb intervention protocol for stroke patients using BP and ERD patterns to provide proprioceptive feedback tightly associated with the patients' expectations of movement. The effects of the proposed intervention have been studied with a small group of patients

Machine learning based brain signal decoding for intelligent adaptive deep brain stimulation

Sensing enabled implantable devices and next-generation neurotechnology allow real-time adjustments of invasive neuromodulation. The identification of symptom and disease-specific biomarkers in invasive brain signal recordings has inspired the idea of demand dependent adaptive deep brain stimulation (aDBS). Expanding the clinical utility of aDBS with machine learning may hold the potential for the next breakthrough in the therapeutic success of clinical brain computer interfaces. To this end, sophisticated machine learning algorithms optimized for decoding of brain states from neural time-series must be developed. To support this venture, this review summarizes the current state of machine learning studies for invasive neurophysiology. After a brief introduction to the machine learning terminology, the transformation of brain recordings into meaningful features for decoding of symptoms and behavior is described. Commonly used machine learning models are explained and analyzed from the perspective of utility for aDBS. This is followed by a critical review on good practices for training and testing to ensure conceptual and practical generalizability for real-time adaptation in clinical settings. Finally, first studies combining machine learning with aDBS are highlighted. This review takes a glimpse into the promising future of intelligent adaptive DBS (iDBS) and concludes by identifying four key ingredients on the road for successful clinical adoption: i) multidisciplinary research teams, ii) publicly available datasets, iii) open-source algorithmic solutions and iv) strong world-wide research collaborations.Fil: Merk, Timon. Charité – Universitätsmedizin Berlin; AlemaniaFil: Peterson, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Matemática Aplicada del Litoral. Universidad Nacional del Litoral. Instituto de Matemática Aplicada del Litoral; Argentina. Harvard Medical School; Estados UnidosFil: Köhler, Richard. Charité – Universitätsmedizin Berlin; AlemaniaFil: Haufe, Stefan. Charité – Universitätsmedizin Berlin; AlemaniaFil: Richardson, R. Mark. Harvard Medical School; Estados UnidosFil: Neumann, Wolf Julian. Charité – Universitätsmedizin Berlin; Alemani

Characterization of \u3ci\u3eMEF2C\u3c/i\u3e-Related Disorders: Genotype, Phenotype, and Gene Pathway Dysregulation

MEF2C­-related disorders are characterized by intellectual disability, developmental delay, lack of speech, seizures, stereotypic movements, hypotonia, and brain abnormalities and are caused by pathogenic alterations involving the MEF2C gene. Despite published cases, MEF2C­-related disorders are difficult to recognize clinically. These studies sought to further characterize MEF2C­-related disorders by investigating the genotypes, phenotypes, and gene functions (or dysfunctions) associated with the disorder. Tremors have been reported in some patients with MEF2C­-related disorders, but the concept of tremors has been complicated by vague definitions and numerous categorization methods. We performed a concept analysis following the Walker and Avant method to clarify the concept and develop an operational definition of tremors. We concluded that tremors are a movement disorder characterized by shaking motions that are involuntary, oscillatory, rhythmic, non-painful, always present although vary in severity, and can be repressed by changing posture or going into a rest position. We then performed a systematic literature review to record the genotypes and comprehensive phenotype of MEF2C­-related disorders reported in the literature. Forty-three articles characterizing 117 patients met the inclusion criteria. Common features included intellectual disability, developmental delay, seizures, hypotonia, absent speech, inability to walk, stereotypic movements, and MRI abnormalities. Nonclassical findings included question mark ear, jugular pit, and a unique neuroendocrine finding. Next, we developed a survey based on validated instruments to gather developmental and clinical information from the parents of children with MEF2C-related disorders. Seventy-three parents completed the survey. Limited speech, seizures, bruxism, repetitive movements, and high pain tolerance were some of the prominent features identified from the survey data. Statistical analyses showed that patients with MEF2C variants were similarly affected as patients with deletions and females showed higher verbal abilities. This natural history study details phenotypic and developmental information of the largest single cohort reported to date. Lastly, we discussed current techniques used to investigate the mouse Mef2c gene expression and regulation in the brain. Previous unbiased RNA sequencing of whole cortex from Mef2c global heterozygous mice showed hundreds of dysregulated genes, particularly autism risk genes and microglial genes. The Cowan lab is currently performing single nuclei RNA sequencing (snRNAseq) to better understand the role of Mef2c in neurons and microglia. Techniques used include nuclei dissociation, fluorescence-activated cell sorting, library preparation and sequencing, and bioinformatic analysis of the snRNAseq data. Additional research techniques include perfusion fixation, brain extraction and slicing, and immunohistochemistry. These studies characterize the phenotype and document the severity of the disorder. The information reported will help providers diagnose and care for patients with MEF2C-related disorders. Additionally, the systematic review and survey data can be useful for further genotype-phenotype correlations, as baseline data for treatment trials, and to develop future studies

Empowering patients in self-management of parkinson's disease through cooperative ICT systems

The objective of this chapter is to demonstrate the technical feasibility and medical effectiveness of personalised services and care programmes for Parkinson's disease, based on the combination of mHealth applications, cooperative ICTs, cloud technologies and wearable integrated devices, which empower patients to manage their health and disease in cooperation with their formal and informal caregivers, and with professional medical staff across different care settings, such as hospital and home. The presented service revolves around the use of two wearable inertial sensors, i.e. SensFoot and SensHand, for measuring foot and hand performance in the MDS-UPDRS III motor exercises. The devices were tested in medical settings with eight patients, eight hyposmic subjects and eight healthy controls, and the results demonstrated that this approach allows quantitative metrics for objective evaluation to be measured, in order to identify pre-motor/pre-clinical diagnosis and to provide a complete service of tele-health with remote control provided by cloud technologies. © 2016, IGI Global. All rights reserved

ESTIMATION OF STRETCH REFLEX CONTRIBUTIONS OF WRIST USING SYSTEM IDENTIFICATION AND QUANTIFICATION OF TREMOR IN PARKINSON'S DISEASE PATIENTS

"The brain's motor control can be studied by characterizing the activity of spinal motor nuclei to brain control, expressed as motor unit activity recordable by surface electrodes". When a specific area is under consideration, the first step in investigation of the motor control system pertinent to it is the system identification of that specific body part or area. The aim of this research is to characterize the working of the brain's motor control system by carrying out system identification of the wrist joint area and quantifying tremor observed in Parkinson's disease patients. We employ the ARMAX system identification technique to gauge the intrinsic and reflexive components of wrist stiffness, in order to facilitate analysis of problems associated with Parkinson's disease. The intrinsic stiffness dynamics comprise majority of the total stiffness in the wrist joint and the reflexive stiffness dynamics contribute to the tremor characteristic commonly found in Parkinson's disease patients. The quantification of PD tremor entails using blind source separation of convolutive mixtures to obtain sources of tremor in patients suffering from movement disorders. The experimental data when treated with blind source separation reveals sources exhibiting the tremor frequency components of 3-8 Hz. System identification of stiffness dynamics and assessment of tremor can reveal the presence of additional abnormal neurological signs and early identification or diagnosis of these symptoms would be very advantageous for clinicians and will be instrumental to pave the way for better treatment of the disease

Machine Learning in Tremor Analysis: Critique and Directions

Tremor is the most frequent human movement disorder, and its diagnosis is based on clinical assessment. Yet finding the accurate clinical diagnosis is not always straightforward. Fine-tuning of clinical diagnostic criteria over the past few decades, as well as device-based qualitative analysis, has resulted in incremental improvements to diagnostic accuracy. Accelerometric assessments are commonplace, enabling clinicians to capture high-resolution oscillatory properties of tremor, which recently have been the focus of various machine-learning (ML) studies. In this context, the application of ML models to accelerometric recordings provides the potential for less-biased classification and quantification of tremor disorders. However, if implemented incorrectly, ML can result in spurious or nongeneralizable results and misguided conclusions. This work summarizes and highlights recent developments in ML tools for tremor research, with a focus on supervised ML. We aim to highlight the opportunities and limitations of such approaches and provide future directions while simultaneously guiding the reader through the process of applying ML to analyze tremor data. We identify the need for the movement disorder community to take a more proactive role in the application of these novel analytical technologies, which so far have been predominantly pursued by the engineering and data analysis field. Ultimately, big-data approaches offer the possibility to identify generalizable patterns but warrant meaningful translation into clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Clinical Decision Support Systems with Game-based Environments, Monitoring Symptoms of Parkinson’s Disease with Exergames

Parkinson’s Disease (PD) is a malady caused by progressive neuronal degeneration, deriving in several physical and cognitive symptoms that worsen with time. Like many other chronic diseases, it requires constant monitoring to perform medication and therapeutic adjustments. This is due to the significant variability in PD symptomatology and progress between patients. At the moment, this monitoring requires substantial participation from caregivers and numerous clinic visits. Personal diaries and questionnaires are used as data sources for medication and therapeutic adjustments. The subjectivity in these data sources leads to suboptimal clinical decisions. Therefore, more objective data sources are required to better monitor the progress of individual PD patients. A potential contribution towards more objective monitoring of PD is clinical decision support systems. These systems employ sensors and classification techniques to provide caregivers with objective information for their decision-making. This leads to more objective assessments of patient improvement or deterioration, resulting in better adjusted medication and therapeutic plans. Hereby, the need to encourage patients to actively and regularly provide data for remote monitoring remains a significant challenge. To address this challenge, the goal of this thesis is to combine clinical decision support systems with game-based environments. More specifically, serious games in the form of exergames, active video games that involve physical exercise, shall be used to deliver objective data for PD monitoring and therapy. Exergames increase engagement while combining physical and cognitive tasks. This combination, known as dual-tasking, has been proven to improve rehabilitation outcomes in PD: recent randomized clinical trials on exergame-based rehabilitation in PD show improvements in clinical outcomes that are equal or superior to those of traditional rehabilitation. In this thesis, we present an exergame-based clinical decision support system model to monitor symptoms of PD. This model provides both objective information on PD symptoms and an engaging environment for the patients. The model is elaborated, prototypically implemented and validated in the context of two of the most prominent symptoms of PD: (1) balance and gait, as well as (2) hand tremor and slowness of movement (bradykinesia). While balance and gait affections increase the risk of falling, hand tremors and bradykinesia affect hand dexterity. We employ Wii Balance Boards and Leap Motion sensors, and digitalize aspects of current clinical standards used to assess PD symptoms. In addition, we present two dual-tasking exergames: PDDanceCity for balance and gait, and PDPuzzleTable for tremor and bradykinesia. We evaluate the capability of our system for assessing the risk of falling and the severity of tremor in comparison with clinical standards. We also explore the statistical significance and effect size of the data we collect from PD patients and healthy controls. We demonstrate that the presented approach can predict an increased risk of falling and estimate tremor severity. Also, the target population shows a good acceptance of PDDanceCity and PDPuzzleTable. In summary, our results indicate a clear feasibility to implement this system for PD. Nevertheless, long-term randomized clinical trials are required to evaluate the potential of PDDanceCity and PDPuzzleTable for physical and cognitive rehabilitation effects