Can interface conditions be modified by support surfaces to minimise the risk of pressure ulcer development?

PhDThe characteristics of a patient support interface can influence the susceptibility of subjects, particularly there who are immobilised and insensate, to pressure ulcer development. Accordingly, externally powered alternating pressure air mattresses (APAM) are utilised to produce intermittent pressure relief and control of the interface microclimate. These conditions will permit adequate blood and lymph flow within the soft tissues and favourable conditions at the loaded skin surface and thus minimise the risk of ulcer formation. Two sets of measurements were performed. Tissue viability was estimated, from a measure of transcutaneous gas tensions and sweat content, from healthy volunteers subjected to various alternating pressure regimens. The latter was achieved by two different strategies a) a custom–made controller which imposes the pressure profile on the subject and b) a prototype APAMs incorporating a novel sensor, which adjusts the profile according to individual subject characteristics. The latter prototype was placed on an articulated hospital bed, with an adjustable Head of Bed (HOB) angle. The second set of measurements involved monitoring the microclimate, namely temperature and humidity, at the interface loaded with a human analogue model supported on an APAM system. The interface was saturated with moisture to simulate sweating. The human studies, involving healthy subjects with BMI values ranging from 18.9 to 42.5 kg/m2, revealed significant differences in soft tissue response under various support surface profile by both strategies. In many cases, the TcPO2 levels either remained fairly stable during the loaded period or fluctuated at a periodicity equivalent to the cycle period of the APAM system, with the corresponding TcPCO2 levels remaining within the normal basal range. These findings were associated with II maximum interface pressures generally not exceeding 50 mmHg (6.67 kPa). By contrast in some cases, there was a significant compromise to the TcPO2 levels during the loaded period, which was often associated with an increase in TcPCO2 levels. These cases generally corresponded with the internal pressures in the mattress prescribed at a maximum amplitude of 100 / 0 mmHg or when the Head of Bed angle was raised to 45º or above. Changes in prototype covering sheet and air flow rates of the APAM system were found to influence both interface temperature and humidity. These results revealed enhanced levels of humidity often reaching 100% RH at the high simulated sweat rates. By contrast, at the lower sweat rate of 1.5 ml/min, the nature of the prototype covering sheets had an effect on the interface humidity profile, with values considerably reduced in the latter stages of the monitoring period. These results were compared with a compartmental model, which predicted the transport of moisture and heat using various mattress support systems. The results offer the potential for the development of intelligent APAM systems, whose characteristics can be adjusted to an individual morphology. These systems will need to be designed to ensure adequate tissue viability and maintain appropriate microclimate at the loaded interface. Such an approach will be directed at those subjects considered to be at high/medium risk of developing pressure ulcers

Bio-magnetic imaging using highly sensitive quantum magnetometers

This thesis describes the experimental results of highly sensitive quantum magnetometers, known as optically pumped magnetometers (OPMs), for bio-magnetic measurements. First, I show that commercially available OPMs can achieve enhanced spatio-temporal resolution compared to superconducting quantum interference devices (SQUIDs) when recording visual-evoked fields, using a standard visual paradigm. The improved resolution enabled the observation of novel neuronal findings in healthy participants. As OPMs were not originally developed for this neurophysiological application, the technology is not optimised for it, and the product design limits the final performance. In our lab, we developed a modular OPM sensor to surpass these limitations in terms of bandwidth and scalability. I tested the performance of this prototype for bio-magnetic measurements, and validated its use through a series of alpha-rhythm experiments over the visual cortex. Finally, I designed an experiment to explore the possibility of measuring the spinal cord evoked response using both the modular and the commercially available OPMs. Using peripheral nerve stimulations, I demonstrate the importance of the broader bandwidth for spinal cord measurements compared to the brain ones, and thus highlight the suitability of the modular OPM sensor for more sensitive measurements. Preliminary in-vivo spinal cord data using the commercial OPMs show simultaneous evoked fields of the brain and spinal cord

Studies on the respiratory modulation of sympathetic activity

Sympathetic activity is modulated by central respiratory drive. Studies using whole nerve recordings in the rat have demonstrated different patterns of respiratory modulation in various sympathetic nerves. These regional differences in the discharge patterns of sympathetic outflows may result from either varying proportions of sympathetic neurones with a particular respiratory-related discharge pattern contributing to each whole-nerve activity or sympathetic preganglionic neurones (SPNs) projecting into different nerves having characteristic respiratory modulations. The present study has investigated the respiratory-related discharge patterns of a group of SPNs projecting to the lumbar sympathetic chain (LSC). Furthermore, the hypothesis that caudal raphe nuclei (raphe obscurus, pallidus and magnus) convey central respiratory drive onto sympathetic outflow has been examined. In anaesthetized and vagotomized rats extracellular recordings were made from identified SPNs projecting to or through the lumbar sympathetic chain between L4 and L5 ganglia, and from caudal raphe neurones with axons projecting to the spinal cord. The respiratory-related firing patterns were analysed. Differences in patterns of respiratory modulation and the proportion of SPNs with a certain pattern of respiratory modulation were found between SPNs recorded in the present study and SPNs located in upper thoracic spinal segments reported previously. These findings provide an explanation of the regional differences of respiratory modulation in various sympathetic nerves. Many caudal raphe-spinal neurones with respiratory-related activity could be activated antidromically from the area of the intermediolateral cell column (IML) and activity in some of these neurons correlated to the 2 to 6 Hz rhythm of cervical sympathetic activity. The findings are consistent with the idea that caudal raphe neurones within the region from which I recorded in this study are part of a supraspinal network that contributes to the 2 to 6 Hz component of sympathetic nerve activity. Therefore some raphe-spinal neurones may relay both "respiratory" and "sympathetic" rhythmic components to the sympathetic outflow. These spinally- projecting neurones in caudal raphe nuclei are different from those in the rostral ventrolateral medulla (RVLM) as they have no baroreceptor-related activity. Additionally, they do not have the "typical" characteristics of 5-HT containing neurones which have slow conduction velocities, and slow regular firing characteristics: the majority had small myelinated axons as indicated by their conduction velocities and relatively high discharge rates and irregular firing characteristics

Afferent information modulates spinal network activity in vitro and in preclinical animal models

Primary afferents are responsible for the transmission of peripheral sensory information to the spinal cord. Spinal circuits involved in sensory processing and in motor activity are directly modulated by incoming input conveyed by afferent fibres. Current neurorehabilitation exploits primary afferent information to induce plastic changes within lesioned spinal circuitries. Plasticity and neuromodulation promoted by activity-based interventions are suggested to support both the functional recovery of locomotion and pain relief in subjects with sensorimotor disorders. The present study was aimed at assessing spinal modifications mediated by afferent information. At the beginning of my PhD project, I adopted a simplified in vitro model of isolated spinal cord from the newborn rat. In this preparation, dorsal root (DR) fibres were repetitively activated by delivering trains of electrical stimuli. Responses of dorsal sensory-related and ventral motor-related circuits were assessed by extracellular recordings. I demonstrated that electrostimulation protocols able to activate the spinal CPG for locomotion, induced primary afferent hyperexcitability, as well. Thus, evidence of incoming signals in modulating spinal circuits was provided. Furthermore, a robust sensorimotor interplay was reported to take place within the spinal cord. I further investigated hyperexcitability conditions in a new in vivo model of peripheral neuropathic pain. Adult rats underwent a surgical procedure where the common peroneal nerve was crushed using a calibrated nerve clamp (modified spared nerve injury, mSNI). Thus, primary afferents of the common peroneal nerve were activated through the application of a noxious compression, which presumably elicited ectopic activity constitutively generated in the periphery. One week after surgery, animals were classified into two groups, with (mSNI+) and without (mSNI-) tactile hypersensitivity, based on behavioral tests assessing paw withdrawal threshold. Interestingly, the efficiency of the mSNI in inducing tactile hypersensitivity was halved with respect to the classical SNI model. Moreover, mSNI animals with tactile hypersensitivity (mSNI+) showed an extensive neuroinflammation within the dorsal horn, with activated microglia and astrocytes being significantly increased with respect to mSNI animals without tactile hypersensitivity (mSNI-) and to sham-operated animals. Lastly, RGS4 (regulator of G protein signaling 4) was reported to be enhanced in lumbar dorsal root ganglia (DRGs) and dorsal horn ipsilaterally to the lesion in mSNI+ animals. Thus, a new molecular marker was demonstrated to be involved in tactile hypersensitivity in our preclinical model of mSNI. Lastly, we developed a novel in vitro model of newborn rat, where hindlimbs were functionally connected to a partially dissected spinal cord and passively-driven by a robotic device (Bipedal Induced Kinetic Exercise, BIKE). I aimed at studying whether spinal activity was influenced by afferent signals evoked during passive cycling. I first demonstrated that BIKE could actually evoke an afferent feedback from the periphery. Then, I determined that spinal circuitries were differentially affected by training sessions of different duration. On one side, a short exercise session could not directly activate the locomotor CPG, but was able to transiently facilitate an electrically-induced locomotor-like activity. Moreover, no changes in reflex or spontaneous activity of dorsal and ventral networks were promoted by a short training. On the other side, a long BIKE session caused a loss in facilitation of spinal locomotor networks and a depression in the area of motor reflexes. Furthermore, activity in dorsal circuits was long-term enhanced, with a significant increase in both electrically-evoked and spontaneous antidromic discharges. Thus, the persistence of training-mediated effects was different, with spinal locomotor circuits being only transiently modulated, whereas dorsal activity being strongly and stably enhanced. Motoneurons were also affected by a prolonged training, showing a reduction in membrane resistance and an increase in the frequency of post-synaptic currents (PSCs), with both fast- and slow-decaying synaptic inputs being augmented. Changes in synaptic transmission onto the motoneuron were suggested to be responsible for network effects mediated by passive training. In conclusion, I demonstrated that afferent information might induce changes within the spinal cord, involving both neuronal and glial cells. In particular, spinal networks are affected by incoming peripheral signals, which mediate synaptic, cellular and molecular modifications. Moreover, a strong interplay between dorsal and ventral spinal circuits was also reported. A full comprehension of basic mechanisms underlying sensory-mediated spinal plasticity and bidirectional interactions between functionally different spinal networks might lead to the development of neurorehabilitation strategies which simultaneously promote locomotor recovery and pain relief

Low-dimensional representations of neural time-series data with applications to peripheral nerve decoding

Bioelectronic medicines, implanted devices that influence physiological states by peripheral neuromodulation, have promise as a new way of treating diverse conditions from rheumatism to diabetes. We here explore ways of creating nerve-based feedback for the implanted systems to act in a dynamically adapting closed loop. In a first empirical component, we carried out decoding studies on in vivo recordings of cat and rat bladder afferents. In a low-resolution data-set, we selected informative frequency bands of the neural activity using information theory to then relate to bladder pressure. In a second high-resolution dataset, we analysed the population code for bladder pressure, again using information theory, and proposed an informed decoding approach that promises enhanced robustness and automatic re-calibration by creating a low-dimensional population vector. Coming from a different direction of more general time-series analysis, we embedded a set of peripheral nerve recordings in a space of main firing characteristics by dimensionality reduction in a high-dimensional feature-space and automatically proposed single efficiently implementable estimators for each identified characteristic. For bioelectronic medicines, this feature-based pre-processing method enables an online signal characterisation of low-resolution data where spike sorting is impossible but simple power-measures discard informative structure. Analyses were based on surrogate data from a self-developed and flexibly adaptable computer model that we made publicly available. The wider utility of two feature-based analysis methods developed in this work was demonstrated on a variety of datasets from across science and industry. (1) Our feature-based generation of interpretable low-dimensional embeddings for unknown time-series datasets answers a need for simplifying and harvesting the growing body of sequential data that characterises modern science. (2) We propose an additional, supervised pipeline to tailor feature subsets to collections of classification problems. On a literature standard library of time-series classification tasks, we distilled 22 generically useful estimators and made them easily accessible.Open Acces

Influence of transdermal current flow in tDCS-induced cutaneous adverse events

Significant contributors to the broad application of transcranial direct current stimulation (tDCS) are portability, ease-of-use, and tolerability; with adverse events limited to transient and mild cutaneous sensations (e.g. perception of burning, itching, and tingling) and erythema. However, the fundamental questions remain about the mechanism of transdermal current flow during transcranial electrical stimulation, including tDCS. Example of previously unexplained questions in tDCS include: 1) the relationship between tDCS-induced skin reddening (erythema) profile and local current density profile predicted by the model; 2) the source of burning sensation during tDCS and whether it is related to an actual skin heating; 3) the role of skin multi-layers and ultrastructures (blood vessels, sweat glands, and hair follicles) in current flow. The finite element modeling (FEM) of current flow using simplified tissue geometries predict higher current density at the electrode edge, but the experimental evidences for the cutaneous effects of tDCS (skin heating or skin reddening) are unclear. Prior skin models of cutaneous current flow lacked anatomical details that will a priori be expected to govern current flow patterns. In this dissertation we address the aforementioned questions by: first quantifying tDCS-induced skin erythema profile alongside FEM predicting local current density profile; then assess the extent of skin heating during tDCS, including the role of joule heating, and relate temperature increase (if any) to burning sensation; and finally develop a realistic skin model to address the role of complex skin tissue layers and ultrastructures in current flow. In the first study, we conclude that the tDCS-induced skin reddening profile is diffuse, higher in active stimulation than sham stimulation, and does not occur at the electrode edges suggesting two alternate hypothesis: 1) skin reddening profile is not related to local current density; and 2) skin current density is relatively uniform, so prior FEM models are incorrect. Next, we conduct phantom measurement suggesting no significant temperature increase due to joule heat as expected at the skin during tDCS. The in vitro human skin temperature measurement suggests that independent of tDCS polarity, temperature increases by about 1oC; an increase during tDCS that is less than the cooling produced following a room-temperature sponge application during the set-up. We conclude that any incremental temperature increase by tDCS may reflect vascular flare response due to current flow, cannot exceed the core body temperature, and is more than the offset by sponge-material coolness, thus, the sensation of skin “burning” during tDCS is not related to an actual increase in temperature. In the final study, we develop a detailed multi-layer skin model including sweat glands, hair follicles, and vasculature, and assess the role of multi-layers and ultrastructures in current flow. The FEM analysis predict that sweat glands eliminates localized current density around the electrode edges, and blood vessels uniformly distribution current across the modeled vasculature under the electrode. We expect that a current flow and bioheat model of such a detailed skin would increase the uniformity of current density and temperature predicted at the skin - consistent with the experimental measurement of skin reddening and skin heating