7th Dutch Bio-Medical Engineering Conference
January 24th & 25th 2019, Egmond aan Zee, the Netherlands
10:30   Sensors and pain
Chair: Allan Veale
15 mins
Psychophysical and Neurophysiological Correlates of Nociceptive Paired-Pulse Facilitation
Boudewijn van den Berg, Jan Buitenweg
Abstract: Introduction: When peripheral nociceptive nerve fibers are stimulated by two consecutive pulses instead of one, the subjective detection probability increases much more than would be expected based on probability summation [1]. The additional increase in detection probability is most likely related to short-term synaptic facilitation. As this facilitation might occur at synaptic connection in the spinal cord, it can be expected that this facilitation can also be observed by an altered neurophysiological response in the EEG. We investigate if facilitation of the detection probability can be reproduced in a new experiment where we simultaneously measure detection probability and EEG, and assess if changes in detection probability are associated with changes of neurophysiological activity measured by EEG. Methods: Single and double-pulse stimuli are applied to 30 healthy subjects via intra-epidermal electrocutaneous stimulation. Nociceptive detection thresholds are tracked by randomized application of 450 stimuli around the detection threshold according to the adaptive probing paradigm [2], while simultaneously recording a 128-channel EEG. The detection probability of single-pulse and double-pulse stimuli are computed using logistic regression with respect to the responses. Neurophysiological facilitation is measured by subtracting the contribution of the first pulse from the contribution of the second pulse to the EEG response. Both contributions are computed using linear mixed regression. The Medical Ethics Committee Twente approved all experimental procedures. Results: The first and the second pulse of a nociceptive stimulus around the detection threshold significantly increase the detection probability and the EEG response. However, the second pulse has a larger effect on both measures. The detection probability increases much more than one would expect based on probability summation and there is a positive difference between the second-pulse and the first-pulse contribution to the EEG with a central topography at 420ms. Conclusion: Nociceptive paired-pulse facilitation can be observed by an increase in subjective detection probability and a larger contribution of the second pulse of a stimulus to the EEG response. Both types of observations might contribute to the study of medication and pathologies potentially influencing synaptic facilitation. REFERENCES 1. Doll, R.J., Maten, A. C., Spaan, S. P., Veltink, P. H., & Buitenweg, J. R., Effect of temporal stimulus properties on the nociceptive detection probability using intra-epidermal electrical stimulation. Experimental brain research, 234(1), 2016: p. 219-227. 2. Doll, R.J., Buitenweg, J. R., Meijer, H. G., & Veltink, P. H., Tracking of nociceptive thresholds using adaptive psychophysical methods. Behavior research methods, 46(1), 2014: p. 55-66.
15 mins
CUTASTIM: a Superficial Stimulation Electrode for Pain Sensitivity Measurements – an Explorative Study
Niels Jansen, Jan R. Buitenweg
Abstract: Introduction: Electric Quantitative Sensory Testing (eQST) studies have shown that central sensitization plays a key role in the maintenance [1] and development [2] of chronic pain. At present, the electrodes used for eQST measurements produce non-specific, deep stimulation of the skin and underlying structures. For eQST, however, it is deemed advantageous to more selectively stimulate cutaneous nociceptors [3]. Recently, the CutaStim has been developed to stimulate the epidermal skin more selectively during electric pain sensitivity measurements [4]. The present study aims to explore the performance of the CutaStim during eQST measurements. Methods: CutaStim electrodes were produced according to large-scale production principles. The CutaStim realizations were then tested with chronic pain (CP, N=11) patients and healthy subjects (HC, N=18) at the Roessingh Rehabilitation Centre and compared to the results obtained with the Red Dot 2560 (conventionally used electrode, RD). Participants were measured two times, wherein the measurements were approximately one week apart from each other. The Medical Ethics Committee Twente approved all experimental procedures. Results: The CS was found to have a lower test-retest reliability in the HC (0.134, 95% CI [-0.516 0.702]) and CP (0.454, 95% CI [-0.579 0.951]) groups as compared to the RD electrode (HC: 0.768, 95% CI [0.30 0.94], CP: 0.828, 95% CI [0.281 0.973]). At the retest, the pain threshold measured with the CutaStim was found to statistically lower with the CP as compared to the HC group. No differences in EPT between the HC and CP groups were established when measured with the RD electrode. Conclusion: Overall, it can be concluded that the CutaStim did not perform as expected. A potential explanation for these results is that an eQST measurement with the CS does not result in an obvious transition from a non-nociceptive to a nociceptive stimulus, which is what defines the pain threshold. From this study, it is concluded that in the presently used setting, the CS is not an improvement for eQST measurements. More measurements should however still be performed to better interpret the findings. Future research should focus on acquiring this additional data and finding an explanation for the present results.
15 mins
Modulating the Perception of Pain Using Virtual Reality
Robert-Jan Doll, Ingrid Koopmans, Geert Jan Groeneveld
Abstract: The perception of pain is a complex combination of neurological, physiological, and psychological factors. Analgesics can be used to inhibit the perception of pain by not only modulating the neurophysiological components of pain (i.e., nociception), but also the affective components. At the Centre for Human Drug Research (CHDR), we developed and validated a battery of pain-tasks (PainCart) primarily targeting nociception. While the PainCart is suitable for studying the pharmacological effects on the nociceptive system, a task studying more affective components of pain is missing. Here, we propose a task which can potentially capture the affective component of pain by means of Virtual Reality. One of the tasks in the PainCart is an electrical stimulation task. During this task, the amplitude of the electrical stimuli is continuously increased. Subjects indicate the momentary perceived pain by a Visual Analogue Scale (VAS). Enhancing the perceived stimulus strength (but not the actual presented strength) might be achieved by means of visual and auditory feedback. In a Virtual Reality environment, subjects are seated in a virtual environment that looks identical to the ‘real’ environment. Furniture, such as the chair and the PainCart are included in the simulation. Two electrodes are placed on the left tibial bone in both environments. During the stimulation task, the electrical stimulation is visually represented by sparks and skin burn in an increasing intensity. Matching sound effects with increasing intensity are played alongside the visualization. Increasing and decreasing the slope in which the visual and auditory representation is presented to a subject might affect their pain perception. Here, we will present the preliminary results of a study where subjects are immersed in the Virtual Reality environment. Electrical stimulation will be applied as described above and subjects are presented various versions of visual/auditory feedback in a randomized order. The versions will include a placebo-variant of the feedback (i.e., no feedback on stimulus strength), and variants with varying rates at which the intensity of the feedback is presented. The pain detection and pain tolerance thresholds will be compared between the different versions.
15 mins
Microstimulation in a Spiking Neural Network Model of the Superior Colliculus Elicits Normometric Eye Saccades
John van Opstal, Bahadir Kasap
Abstract: The midbrain superior colliculus (SC) generates saccadic eye movements to sensory stimuli through a population of cells in its topographically organized motor map. Supra-threshold electrical microstimulation in the SC reveals that each stimulation site produces a normometric saccade vector, with little effect of the stimulation parameters. Interestingly, the kinematics of electrically evoked saccades (E-saccades) are indistinguishable from natural, visual-evoked saccades (V-saccades). These findings support models, in which the saccade vector is determined by a center-of-gravity computation of activated neurons, while its trajectory and kinematics arise from downstream feedback circuits. Recent single- unit recordings from our lab, however, indicated that the SC population also specifies instantaneous kinematics. These results support an alternative model, in which the desired saccade trajectory, including its kinematics, follows from instantaneous summation of movement effects of all SC spike trains. But how to reconcile this model with microstimulation results? Although it is thought that microstimulation activates a large population of SC neurons, the mechanism through which it arises is unknown. We developed a spiking neural network model of the SC, in which microstimulation directly activates a relatively small set of neurons around the electrode tip, which subsequently sets up a large population response through lateral synaptic interactions. We show that through this mechanism the population drives an E-saccade with normal kinematics that are largely independent of the stimulation parameters. Only at very low stimulus intensities the network recruits a small cell population with low firing rates, resulting in small saccades with abnormally slow kinematics, as observed in experiments.
15 mins
Rapid Systolic Blood Pressure Changes after Standing Up Associate with Impaired Physical Performance in Geriatric Outpatients
Arjen Mol, Esmee Reijnierse, Marijke Trappenburg, Richard van Wezel, Andrea Maier, Carel Meskers
Abstract: Background: Orthostatic hypotension (OH) is a prevalent condition in older adults and is associated with impaired physical performance and falls. The ability of older adults to compensate for rapid changes in systolic blood pressure (SBP; i.e. SBP drop rate and SBP variability) may be important for physical performance. This study investigates the association of rapid SBP changes after standing up with physical performance. Methods and Results: Consecutive patients who visited the Center Of Geriatric Amsterdam (COGA) in 2014 and 2015 were included. The following SBP parameters were computed in two intervals (0-15 seconds and 15-180 seconds) after standing up: steepness of steepest SBP decline (SBPmax drop rate); ratio of standing and supine SBP variability (SBPvariability ratio); magnitude of largest SBP drop (SBPdrop magnitude). Physical performance was assessed using the following measures: chair stand time (CST), timed up and go time (TUG), walking speed, handgrip strength and tandem stance performance. 109 patients (45% male; age: mean 81.7 years (SD 7.0)) were included. SBPmax drop rate (0-15 seconds) was associated with slower CST (p < 0.001), TUG (p = 0.022) and walking speed (p = 0.024). SBPvariability ratio (0-15 seconds) was associated with slower CST (p = 0.005). SBPdrop magnitude was not associated with physical performance. Conclusions: SBP parameters reflecting rapid systolic blood pressure changes were more strongly associated with physical performance compared to SBP drop magnitude in geriatric outpatients. These results support the hypothesis of an inadequate cerebral autoregulation during rapid SBP changes and advocate the use of continuous BP measurements.
15 mins
Smart Glasses for Visual Cueing in Augmented Reality: an On-Demand Turning Aid for Freezing of Gait in Parkinson’s Disease.
Jaap de Ruyter van Steveninck, Hizirwan Salim, Sabine Janssen, Tjitske Heida, Richard van Wezel
Abstract: Freezing of gait (FOG) is a debilitating motor symptom that occurs in up to 60% of PD patients.[1] The symptom can be defined as a short-lasting arrest of gait, accompanied with the subjective feeling of the feet being glued to the ground. FOG impairs mobility, is frequently associated with falls and injuries, and reduces quality of life. Several factors have shown to evoke FOG in people with Parkinson’s disease (PD-FOG), with ‘turning around’ being the most frequent trigger.[2] Pharmacological management and deep brain stimulation can partly reduce the symptom, but are difficult to optimally implement. Consequently, alternative therapeutic options remain necessary. External cueing has shown to be a valuable strategy to prevent or overcome freezing.[3] With external visual cues discrete targets or references in the external environment are attended by the patient and used as ‘suggestions’ for enforcing an appropriate amplitude of gait and presume to elicit a shift from habitual control towards a more goal-directed mode of action control. So far, visual cueing for PD-FOG has mostly been limited to a laboratory setting, because of the nature of the stimuli. In the current study, we use smart glasses and motion sensors for interactive visual cueing in augmented reality, aiding in turning around. The stimuli consist of targets surrounding the user, and a Pac-Man figure, whose movement is linked to body rotation. The targets can be interactively reached by turning around. This design promotes goal-directed gait control and maximizes the subject’s attention to gait and posture. This mobile visual cueing application could be an important step towards on-demand symptomatic treatment of PD-FOG in the home setting. [1] N. Giladi et al., "Freezing of gait in PD: prospective assessment in the DATATOP cohort," Neurology, vol. 56, no. 12, pp. 1712-21, Jun 26 2001. [2] S. G. Rahman, H.J. ; Quinn N.P. ; Jahanshahi, M. , "The factors that induce or overcome freezing of gait in Parkinson’s disease.," Behavioural Neurology vol. 19, pp. 127–136, 2008. [3] P. Ginis, E. Nackaerts, A. Nieuwboer, and E. Heremans, "Cueing for people with Parkinson's disease with freezing of gait: A narrative review of the state-of-the-art and novel perspectives," Ann Phys Rehabil Med, Sep 7 2017.