Parkinson\u27s Symptoms quantification using wearable sensors

Parkinson’s disease (PD) is a common neurodegenerative disorder affecting more than one million people in the United States and seven million people worldwide. Motor symptoms such as tremor, slowness of movements, rigidity, postural instability, and gait impairment are commonly observed in PD patients. Currently, Parkinsonian symptoms are usually assessed in clinical settings, where a patient has to complete some predefined motor tasks. Then a physician assigns a score based on the United Parkinson’s Disease Rating Scale (UPDRS) after observing the motor task. However, this procedure suffers from inter subject variability. Also, patients tend to show fewer symptoms during clinical visit, which leads to false assumption of the disease severity. The objective of this study is to overcome this limitations by building a system using Inertial Measurement Unit (IMU) that can be used at clinics and in home to collect PD symptoms data and build algorithms that can quantify PD symptoms more effectively. Data was acquired from patients seen at movement disorders Clinic at Sanford Health in Fargo, ND. Subjects wore Physilog IMUs and performed tasks for tremor, bradykinesia and gait according to the protocol approved by Sanford IRB. The data was analyzed using modified algorithm that was initially developed using data from normal subjects emulating PD symptoms. For tremor measurement, the study showed that sensor signals collected from the index finger more accurately predict tremor severity compared to signals from a sensor placed on the wrist. For finger tapping, a task measuring bradykinesia, the algorithm could predict with more than 80% accuracy when a set of features were selected to train the prediction model. Regarding gait, three different analysis were done to find the effective parameters indicative of severity of PD. Gait speed measurement algorithm was first developed using treadmill as a reference. Then, it was shown that the features selected could predict PD gait with 85.5% accuracy

Computational methods toward early detection of neuronal deterioration

In today's world, because of developments in medical sciences, people are living longer, particularly in the advanced countries. This increasing of the lifespan has caused the prevalence of age-related diseases like Alzheimer’s and dementia. Researches show that ion channel disruptions, especially the formation of permeable pores to cations by Aβ plaques, play an important role in the occurrence of these types of diseases. Therefore, early detection of such diseases, particularly using non-invasive tools can aid both patients and those scientists searching for a cure. To achieve the goal toward early detection, the computational analysis of ion channels, ion imbalances in the presence of Aβ pores in neurons and fault detection is done. Any disruption in the membrane of the neuron, like the formation of permeable pores to cations by Aβ plaques, causes ionic imbalance and, as a result, faults occur in the signalling of the neuron.The first part of this research concentrates on ion channels, ion imbalances and their impacts on the signalling behaviour of the neuron. This includes investigating the role of Aβ channels in the development of neurodegenerative diseases. Results revealed that these types of diseases can lead to ionic imbalances in the neuron. Ion imbalances can change the behaviour of neuronal signalling. Therefore, by identifying the pattern of these changes, the disease can be detected in the very early stages. Then the role of coupling and synchronisation effects in such diseases were studied. After that, a novel method to define minimum requirements for synchronicity between two coupled neurons is proposed. Further, a new computational model of Aβ channels is proposed and developed which mimics the behaviour of a neuron in the course of Alzheimer's disease. Finally, both fault computation and disease detection are carried out using a residual generation method, where the residuals from two observers are compared to assess their performance

PT-Net: A Multi-Model Machine Learning Approach for Smarter Next-Generation Wearable Tremor Suppression Devices for Parkinson\u27s Disease Tremor

According to the World Health Organization (WHO), Parkinson\u27s Disease (PD) is the second most common neurodegenerative condition that can cause tremors and other motor and non motor related symptoms. Medication and deep brain stimulation (DBS) are often used to treat tremor; however, medication is not always effective and has adverse effects, and DBS is invasive and carries a significant risk of complications. Wearable tremor suppression devices (WTSDs) have been proposed as a possible alternative, but their effectiveness is limited by the tremor models they use, which introduce a phase delay that decreases the performance of the devices. Additionally, the availability of tremor datasets is limited, which prevents the rapid advancement of these devices. To address the challenges facing the WTSDs, PD tremor data were collected at the Wearable Biomechatronics Laboratory (WearMe Lab) to develop methods and data-driven models to improve the performance of WTSDs in managing tremor, and potentially to be integrated with the wearable tremor suppression glove that is being developed at the WearMe Lab. A predictive model was introduced and showed improved motion estimation with an average estimation accuracy of 99.2%. The model was also able to predict motion with multiple steps ahead, negating the phase delay introduced by previous models and achieving prediction accuracies of 97%, 94%, 92%, and 90\% for predicting voluntary motion 10, 20, 50, and 100 steps ahead, respectively. Tremor and task classification models were also developed, with mean classification accuracies of 91.2% and 91.1%, respectively. These models can be used to fine-tune the parameters of existing estimators based on the type of tremor and task, increasing their suppression capabilities. To address the absence of a mathematical model for generating tremor data and limited access to existing PD tremor datasets, an open-source generative model was developed to produce data with similar characteristics, distribution, and patterns to real data. The reliability of the generated data was evaluated using four different methods, showing that the generative model can produce data with similar distribution, patterns, and characteristics to real data. The development of data-driven models and methods to improve the performance of wearable tremor suppression devices for Parkinson\u27s disease can potentially offer a noninvasive and effective alternative to medication and deep brain stimulation. The proposed predictive model, classification model, and the open-source generative model provide a promising framework for the advancement of wearable technology for tremor suppression, potentially leading to a significant improvement in the quality of life for individuals with Parkinson\u27s disease

Separating Signal from Noise in High-Density Diffuse Optical Tomography

High-density diffuse optical tomography (HD-DOT) is a relatively new neuroimaging technique that detects the changes in hemoglobin concentrations following neuronal activity through the measurement of near-infrared light intensities. Thus, it has the potential to be a surrogate for functional MRI (fMRI) as a more naturalistic, portable, and cost-effective neuroimaging system. As in other neuroimaging modalities, head motion is the most common source of noise in HD-DOT data that results in spurious effects in the functional brain images. Unlike other neuroimaging modalities, data quality assessment methods are still underdeveloped for HD-DOT. Therefore, developing robust motion detection and motion removal methods in its data processing pipeline is a crucial step for making HD-DOT a reliable neuroimaging modality. In particular, our lab is interested in using HD-DOT to study the brain function in clinical populations with metal implants that cannot be studied using fMRI due to their contraindications. Two of these populations are patients having movement disorders (Parkinson Disease or essential tremor) with deep brain stimulation (DBS) implants and individuals with cochlear implants (CI). These two groups both receive tremendous benefit from their implants at the statistical level; however, there is significant single-subject variability. Our overarching goal is to use HD-DOT to find the relationships between the neuronal function and the behavioral measures in these populations to optimize the contact location of these implant surgeries. However, one of the challenges in analyzing the data in these subjects, especially in patients with DBS, is their high levels of motion due to tremors when their DBS implant is turned off. This further motivates the importance of the methods presented herein for separating signal from noise in HD-DOT data. To this end, I will first assess the efficacy of state-of-the-art motion correction methods introduced in the fNIRS literature for HD-DOT. Then, I will present a novel global metric inspired by motion detection methods in fMRI called GVTD (global variance of the temporal derivatives). Our results show that GVTD-based motion detection not only outperforms other comparable motion detection methods in fNIRS, but also outperforms motion detection with accelerometers. I will then present my work on collecting and processing HD-DOT data for two clinical populations with metal implants in their brain and the preliminary results for these studies. Our results in PD patients show that HD-DOT can reliably map neuronal activity in this group and replicate previously published results using PET and fMRI. Our results in the CI users provide evidence for the recruitment of the prefrontal cortex in processing speech to compensate for the decreased activity in the temporal cortex. These findings support the theory of cognitive demand increase in effortful listening situations. In summary, the presented methods for separating signal from noise enable direct comparisons of HD-DOT images with those of fMRI in clinical populations with metal implants and equip this modality to be used as a surrogate for fMRI

Detection of Parkinson Disease Rest Tremor

Parkinson Disease (PD) is a debilitating and progressive movement disorder that is estimated to affect over six million worldwide. One of the most characteristic symptoms of PD is resting tremor, which involves unintentional and rhythmic muscle oscillations of an afflicted extremity while the muscles of said extremity are relaxed. This study involved measuring the rest tremor of 10 PD subjects, 10 Essential Tremor subjects, and 10 healthy control subjects using two devices. One device was an FDA approved accelerometry system to measure human tremor known as the TremorometerTM and the other was a consumer three-dimensional camera known as the Leap MotionTM Controller. The study compares tremor characteristics calculated from both devices to compare the Leap Motion Controller to the Tremorometer System. The tremor characteristics obtained from the Leap Motion Controller were also used in an attempt to classify the subjects used in the study as either PD or non-PD subjects

Technological advances in deep brain stimulation:Towards an adaptive therapy

Parkinson's disease (PD) is neurodegenerative movement disorder and a treatment method called deep brain stimulation (DBS) may considerably reduce the patient’s motor symptoms. The clinical procedure involves the implantation of a DBS lead, consisting of multiple electrode contacts, through which continuous high frequency (around 130 Hz) electric pulses are delivered in the brain. In this thesis, I presented the research which had the goal to improve current DBS technology, focusing on bringing the conventional DBS system a step closer to adaptive DBS, a personalized DBS therapy. The chapters in this thesis can be seen as individual building blocks for such an adaptive DBS system. After the general introduction, the first two chapters, two novel DBS lead designs are studied in a computational model. The model showed that both studied leads were able to exploit the novel distribution of the electrode contacts to shape and steer the stimulation field to activate more neurons in the chosen target compared to the conventional lead, and to counteract lead displacement. In the fourth chapter, an inverse current source density (CSD) method is applied on local field potentials (LFP) measured in a rat model. The pattern of CSD sources can act as a landmark within the STN to locate the potential stimulation target. The fifth and final chapter described the last building block of the DBS system. We introduced an inertial sensors and force sensor based measurement system, which can record hand kinematics and joint stiffness of PD patients. A system which can act as a feedback signal in an adaptive DBS system

Models and Analysis of Vocal Emissions for Biomedical Applications

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies

Tracking Rhythmicity in Biomedical Signals using Sequential Monte Carlo methods

Cyclical patterns are common in signals that originate from natural systems such as the human body and man-made machinery. Often these cyclical patterns are not perfectly periodic. In that case, the signals are called pseudo-periodic or quasi-periodic and can be modeled as a sum of time-varying sinusoids, whose frequencies, phases, and amplitudes change slowly over time. Each time-varying sinusoid represents an individual rhythmical component, called a partial, that can be characterized by three parameters: frequency, phase, and amplitude. Quasi-periodic signals often contain multiple partials that are harmonically related. In that case, the frequencies of other partials become exact integer multiples of that of the slowest partial. These signals are referred to as multi-harmonic signals. Examples of such signals are electrocardiogram (ECG), arterial blood pressure (ABP), and human voice. A Markov process is a mathematical model for a random system whose future and past states are independent conditional on the present state. Multi-harmonic signals can be modeled as a stochastic process with the Markov property. The Markovian representation of multi-harmonic signals enables us to use state-space tracking methods to continuously estimate the frequencies, phases, and amplitudes of the partials. Several research groups have proposed various signal analysis methods such as hidden Markov Models (HMM), short time Fourier transform (STFT), and Wigner-Ville distribution to solve this problem. Recently, a few groups of researchers have proposed Monte Carlo methods which estimate the posterior distribution of the fundamental frequency in multi-harmonic signals sequentially. However, multi-harmonic tracking is more challenging than single-frequency tracking, though the reason for this has not been well understood. The main objectives of this dissertation are to elucidate the fundamental obstacles to multi-harmonic tracking and to develop a reliable multi-harmonic tracker that can track cyclical patterns in multi-harmonic signals

Constructing a reference standard for sports science and clinical movement sets using IMU-based motion capture technology

Motion analysis has improved greatly over the years through the development of low-cost inertia sensors. Such sensors have shown promising accuracy for both sport and medical applications, facilitating the possibility of a new reference standard to be constructed. Current gold standards within motion capture, such as high-speed camera-based systems and image processing, are not suitable for many movement-sets within both sports science and clinical movement analysis due to restrictions introduced by the movement sets. These restrictions include cost, portability, local environment constraints (such as light level) and poor line of sight accessibility. This thesis focusses on developing a magnetometer-less IMU-based motion capturing system to detect and classify two challenging movement sets: Basic stances during a Shaolin Kung Fu dynamic form, and severity levels from the modified UPDRS (Unified Parkinson’s Disease Rating Scale) analysis tapping exercise. This project has contributed three datasets. The Shaolin Kung Fu dataset is comprised of 5 dynamic movements repeated over 350 times by 8 experienced practitioners. The dataset was labelled by a professional Shaolin Kung Fu master. Two modified UPDRS datasets were constructed, one for each of the two locations measured. The modified UPDRS datasets comprised of 5 severity levels each with 100 self-emulated movement samples. The modified UPDRS dataset was labelled by a researcher in neuropsychological assessment. The errors associated with IMU systems has been reduced significantly through a combination of a Complementary filter and applying the constraints imposed by the range of movements available in human joints. Novel features have been extracted from each dataset. A piecewise feature set based on a moving window approach has been applied to the Shaolin Kung Fu dataset. While a combination of standard statistical features and a Durbin Watson analysis has been extracted from the modified UPDRS measurements. The project has also contributed a comparison of 24 models has been done on all 3 datasets and the optimal model for each dataset has been determined. The resulting models were commensurate with current gold standards. The Shaolin Kung Fu dataset was classified with the computational costly fine decision tree algorithm using 400 splits, resulting in: an accuracy of 98.9%, a precision of 96.9%, a recall value of 99.1%, and a F1-score of 98.0%. A novel approach of using sequential forward feature analysis was used to determine the minimum number of IMU devices required as well as the optimal number of IMU devices. The modified UPDRS datasets were then classified using a support vector machine algorithm requiring various kernels to achieve their highest accuracies. The measurements were repeated with a sensor located on the wrist and finger, with the wrist requiring a linear kernel and the finger a quadratic kernel. Both locations achieved an accuracy, precision, recall, and F1-score of 99.2%. Additionally, the project contributed an evaluation to the effect sensor location has on the proposed models. It was concluded that the IMU-based system has the potential to construct a reference standard both in sports science and clinical movement analysis. Data protection security and communication speeds were limitations in the system constructed due to the measured data being transferred from the devices via Bluetooth Low Energy communication. These limitations were considered and evaluated in the future works of this project

Investigation into the mechanisms of depressive illness

Functional and structural brain abnormalities have been reported in many imaging studies of depressive illness. However, the mechanisms by which these abnormalities give rise to symptoms remain unknown. The work described in this thesis focuses on such mechanisms, particularly with regard to neural predictive error signals. Recently, these signals have been reported to be present in many studies on animals and healthy humans. The central hypothesis explored in this thesis is that depressive illness comprises a disorder of associative learning. Chapter 2 reviews the brain regions frequently reported as abnormal in imaging studies of depressive illness, and the normal function of these particular brain regions. It is concluded that such regions comprise the neural substrate for associative learning and emotion. However, confidence in this conclusion is limited by considerable variability in the human imaging literature. Therefore, chapter 3 describes a meta-analysis, which tests the hypothesis that, consistent with the non-imaging literature, the ventromedial prefrontal cortex is most active during emotional experience. The results of the meta-analysis were clearly consistent with this hypothesis. Chapter 4 provides an introduction to neural predictive error signals from the general perspective of homeostatic physiological regulation. Both experimental evidence supporting the error signals, and various formal mathematical theories describing the error signals, are summarised. This provides the background to chapter 5, which describes an original fMRI study which tested the hypothesis that patients with depressive illness would exhibit abnormal predictive error signals in response to unexpected motivationally significant stimuli. Evidence of such abnormality was found. Chapter 6 describes a further original study using transcranial ultrasound and diffusion tensor imaging of the brainstem, which investigated reports of a subtle structural abnormality in depressed patients. If present, it might give rise to abnormal error signals. However, no structural abnormality was found. Finally, chapter 7 discusses the significance of these findings in the context of clinical features of depressive illness and a wide range of treatments, ranging from psychotherapy through antidepressants to physical treatments. A number of potential future studies are identified, which could clarify understanding of depressive illness