Paper Submission & Registration
8th Dutch Bio-Medical Engineering Conference
16:30   Neurophysiology
Chair: John van Opstal
15 mins
Multisine frequency modulation of intra-epidermal electric pulse sequences to study nociceptive processing: Methods and limitations
Boudewijn van den Berg, Mana Manoochehri, Mindy Kasting, Alfred Schouten, Frans van der Helm, Jan Buitenweg
Abstract: In the past decades, researchers have tried to study how the sensation of pain emerges from a peripheral nociceptive input. A frequent approach has been to study the evoked brain response to a single painful stimulus. However, such a stimulus is very different from the continuous pain sensation evoked by tissue damage. Brain responses to a continuous stimulus can be studied by adding a frequency tag to the stimulus. As such, the brain response evoked by such a stimulus can be identified based on its frequency content. By adding multiple frequency tags, also other properties such as the delay and nonlinearity of a system can be studied. Recently, we developed a method to stimulate nociceptive skin afferents with a frequency modulated pulse sequence. Nociceptive afferent nerve fibers are targeted by using intra-epidermal electric pulses at twice the detection threshold. By modulating this pulse sequence with a multisine waveform, we add multiple frequencies to the signal, allowing us to study the brain response to intra-epidermal stimulation, and explore non-linearity of the nociceptive system. In a proof-of-principle experiment, we demonstrated that multisine modulation of an intra-epidermal pulse sequence evokes significant brain activity at each of the three base frequencies. However, we also found significant stimulation artefact, which concentrates near the EEG ground electrode. Furthermore, lower frequencies (3 Hz and 7 Hz) were found to have a better signal-to-noise ratio than the higher frequency (13 Hz). As such, we found that it is possible to study pain processing using multisine modulated intra-epidermal pulse sequences. When using this technique, stimulus artefacts should be minimized and mapped, in order to prevent any interference with stimulus-related brain activity. The signal-to-noise ratio of brain responses might be improved by a smart choice of modulation frequencies.
15 mins
Cortical plasticity of visual evoked potentials in patients with neurofibromatosis type 1
J. Castricum, J.H.M. Tulen, A.M. Heuvelmans, D.C.G. Straver, G. Geleijnse, Y. Elgersma
Abstract: NF1 is an autosomal dominant genetic disorder and is characterized by a wide variability in clinical manifestations. Many patients with Neurofibromatosis type 1 (NF1) suffer from cognitive deficits that can affect their quality of life. Impairment in visuospatial perception has been frequently associated with NF1. It is unknown whether there is a primary dysfunction of the visual pathways in NF1 adults which, if present, could contribute to the learning disabilities in NF1. Based on studies in NF1 mice, it is hypothesized that the underlying cause of these cognitive disabilities results from increased neuronal inhibition that affects synaptic plasticity. Whether such changes in neuronal plasticity are also underlying the cognitive deficits in NF1 patients is unknown. Cortical plasticity in humans can be investigated by studying visual evoked potentials (VEPs) in response to visual stimulation. We will study visual cortex plasticity as measured by the change in VEP after a modulation block compared to the baseline in individuals with NF1. We intend to present the preliminary results of 20 out of 30 planned controls (67%) and 12 out of 30 planned patients with NF1 (40%) between 18-55 years old. VEPs were evoked by blocks of 20 seconds of checkerboard reversals at two baseline measurements, and six measurements spread evenly over 30 min after a 10-min modulation block of checkerboard reversals. VEP plasticity is determined by measuring the increase of the VEP peak amplitudes after the modulation block compared to baseline. The study might contribute to neurophysiological outcome measures in intervention studies. To our knowledge, this will be the first study to investigate cortical plasticity by measuring VEPs in patients with NF1.
15 mins
Freezing of gait detection in patients with Parkinson’s disease using multi-modal physiological signals
Ying Wang, Floris Beuving, Jorik Nonnekes, Mike X Cohen, Xi Long, Ronald M Aarts, Richard Van Wezel
Abstract: Freezing-of-gait (freezing episodes) is a commonly-seen symptom in the moderate and advanced phase of Parkinson’s disease. When experiencing freezing episodes, patients suddenly lose their moving forward ability, which may lead to frequent falling and even bone fracture in daily life. The currently used treatments of freezing episodes, such as levodopa and external auditory or visual cues, are still with moderate efficacy. The efficacy could be improved through a reliable freezing evaluation. A reliable freezing evaluation in daily life can be supported by basic-science studies in characterizing the freezing episodes and can be assisted by a 24/7 evidence-support freezing detection system. In this study, multiple modality (multi-modal) features from brain, eye, heart, motion, and gait activity were analysed in 15 participants with idiopathic Parkinson’s disease. The features were extracted from the dataset including 551 freezing episodes provoked by turning in place. We first implemented statistical analysis on 248 of the 551 to determine which multi-modal features were associated with freezing episodes. The features significantly associated with freezing episodes were ranked and applied in the freezing detection with RUSBoost classifier. Eye-stabilization speed during turning and lower-body trembling measure were found to be significantly associated with freezing episodes and used for freezing detection. Through a leave-one-subject-out cross-validation, satisfying performances in the freezing detection were achieved with a sensitivity of 97% ± 3%, a specificity of 96% ± 7%, a precision of 73% ± 21%, a Matthews correlation coefficient of 0.82 ± 0.15, and an area under the Precision-Recall curve of 0.94 ± 0.05. According to the Precision-Recall curves, the proposed freezing detection method using the multi-modal features performed better than using single-modal features. In future studies, it is needed to further validate and improve the detection system using multi-modal features in a real-life situation.
15 mins
Development of dorsal root ganglion (DRG) multichannel stimulator prototype for use in early clinical trials
Konstantina Kolovou-Kouri, Sadaf Soloukey, Biswadjiet S. Harhangi, Wouter A. Serdijn, Vasiliki Giagka
Abstract: Spinal Cord Injury (SCI) is characterized by a disruption of the spinal pathways connecting the brain to the rest of the body. This can result in an impairment or complete loss of sensory and/or motor functions, depending on the level and severity of the injury. The most common approach of attempting motor recovery using neuromodulation has been through epidural spinal cord electrical stimulation (eSCS), with or without rehabilitation and robotic assistance¹,². Dorsal Root Ganglion (DRG) stimulation is a relatively new neuromodulation treatment, which has already been established as a safe and effective treatment for chronic pain. However, its application for motor recovery after SCI has remained unexplored territory. A recent study by Soloukey et al.³ showed the first promising results using L4-level DRG-stimulation to evoke strong and reproducible motor responses in the upper leg muscles of patients with motor complete SCI. The current work presents the development of a prototype stimulator intended for use in early clinical trials for the purpose of further exploring the effects of multi-level DRG-stimulation on motor recovery after SCI. The prototype stimulator is created using commercially available components, focussing primarily on the safety considerations for the use of the prototype in a clinical research environment. The prototype allows for access to multiple leads in parallel to facilitate faster, sequential stimulation, catering for a maximum of 16 leads at once. The final system is equipped with a microcontroller for the programming of the stimulation parameters, a Bluetooth module for the communication with external components (Graphical User Interface (GUI) on a local PC) and tailored connections to the stimulating DRG-leads. The safety and well-being of the patient is set as a first priority, leading to a tailored design and development of the stimulator accordingly. Parameters like the patient’s comfort when connected to the device, the safety of the patient and the medical personnel with regards to powering the device through the mains, and protection from any current or DC voltage leakage, are discussed. The prototype is currently undergoing safety evaluation and the complete system design together with these results will be presented during the conference.

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