The electrical diagnosis of peripheral nerve injury, and some applications of electronics to physiology and clinical medicine

In the summer of 1941 the Scottish E. M. S. Hospitals organization established a special Unit for the reception and treatment of patients suffering from peripheral nerve injury at Gogarburn Hospital on the outskirts of Edinburgh. In connection with this specialized type of injury, relatively rare in peacetime but assuming considerable importance in War, invitations were issued to various Persons sroecializing in ancillary branches of Medicine and Surgery to attend the clinical meetings of the Peripheral Nerve Unit, to consider applications of their work to this particular problem, and to have access to the patient for the assessment of their methods.Peripheral nerve injury diagnosis and treatment involves a considerable field of application for methods which have been primarily developed as physiological techniques, particularly in the use of modern electrical apparatus, and the Director of the Unit, Professor J. R. Learmonth, invited me to attend the clinical meetings, and to make a study on the patients of modern methods of electrical diagnosis, and this opportunity, gladly accepted, has furnished me with a wealth of problems and of material ever since.This thesis accordingly presents such of these problems as have at present been worked out to the extent of being of clinical or laboratory use

Strength–duration relationship for intra- versus 3 extracellular stimulation with microelectrodes

Abstract—Chronaxie, a historically introduced excitability time parameter for electrical stimulation, has been assumed to be closely related to the time constant of the cell membrane. Therefore, it is perplexing that significantly larger chronaxies have been found for intracellular than for extracellular stimulation. Using compartmental model analysis, this controversy is explained on the basis that extracellular stimulation also generates hyperpolarized regions of the cell membrane hindering a steady excitation as seen in the intracellular case. The largest inside/outside chronaxie ratio for microelectrode stimulation is found in close vicinity of the cell. In the case of monophasic cathodic stimulation, the length of the primarily excited zone which is situated between the hyperpolarized regions increases with electrode–cell distance. For distant electrodes this results in an excitation process comparable to the temporal behavior of intracellular stimulation. Chronaxie also varies along the neural axis, being small for electrode positions at the nodes of Ranvier and axon initial segment and larger at the soma and dendrites. As spike initiation site can change for short and long pulses, in some cases strength–duration curves have a bimodal shape, and thus, they deviate from a classical monotonic curve as described by the formulas of Lapicque or Weis

Artificial vision: feasibility of an episcleral retinal prosthesis & implications of neuroplasticity

Background. A visual prosthesis is a conceptual device designed to activate residual functional neurons in the visual pathway of blind individuals to produce artificial vision. Such device, when applied to stimulate the vitreous surface of the retina, has proven feasible in producing patterned light perception in blind individuals suffering from dystrophic diseases of the retina, such as aged-related macular degeneration (AMD). However the practicality of such approach has been challenged by the difficulty of surgical access and the risks of damaging the neuroretina. Positioning a visual implant over the scleral surface of the eye could present a safer alternative but this stimulation modality has not been tested in diseased retinas. Additionally, recent research has shown that the adult neocortex retains substantial plasticity following a disruption to its visual input and the potential deterioration in visual capabilities as a result of such experience modification may undermine the overall bionic rescue strategy. Methods. Two animal models mimicking the principal pathologies found in AMD, namely photoreceptor degeneration and reduced retinal ganglion cell mass, were used to evaluate the efficacy of trans-scleral stimulation of the retina by recording electrical evoked potentials in the visual cortex. The visual performance following the loss of pattern vision induced by bilateral eyelid suturing in adult mice was examined by analysing visual evoked potentials. Findings. Spatially differentiated cortical activations were obtained notwithstanding the underlying retinopathy in the experiment animals. The charge density thresholds were found to be similar to controls and below the bioelectric safety limit. After prolonged visual deprivation (weeks) in the mouse, the visual cortical responses evoked by either electrical or photic stimuli were both significantly reduced. An assessment of different visual capabilities using patterned stimuli demonstrated that whilst visual acuity and motion sensitivity were preserved, significant depression in luminance and contrast sensitivities was detected. Conclusion. Trans-scleral stimulation of the retina is a feasible approach for the development of a visual prosthesis. Following visual loss the adult brain exhibits significant experience-dependent modifications. These new insights may force a revision on the current bionic rescue strategy

Formaldehyde in the industrial environment

Consideration has been given to the toxicity of formaldehyde in the industrial environment. The available literature has been reviewed critically against a background of technological awareness of the usefulness of the material and the factors which influence the assessment of absorption by the body fluids following exposure are examined. Data from experimental work carried out in a number of factory locations has been analysed in an attempt to establish the relationships between somatic absorption and levels of formaldehyde found in ambient air. [Continues.]</div

Ultrahigh Field Functional Magnetic Resonance Electrical Impedance Tomography (fMREIT) in Neural Activity Imaging

abstract: A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization. The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging. Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise. Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Dinámica Cerebral. La actividad cerebral en función de las condiciones dinámicas de la excitabilidad nerviosa. Tomo segundo

This book can be cited as: Gonzalo J. (1945/2010/2022), "Dinámica Cerebral", Tomo segundo, Consejo Superior de investigaciones Cientificas, Madrid 1945, in: "Dinámica Cerebral" facsimile edition, Gonzalo I. (Ed), Red Temática en Tecnologías de Computación Artificial/Natural, Universidad de Santiago de Compostela 2010 (Open Access http://dspace.usc.es/handle/10347/4341). "Brain Dynamics" Volume 2, Gonzalo I. (Ed and English translation), Madrid 2022 (Open Access in this web page).This volume is the English translation of Volume 2 of the book "Dinámica Cerebral" written in Spanish by Justo Gonzalo Rodríguez-Leal (Barcelona 1910 – Madrid 1986), first published in 1950. The volume, devoted to tactile functions, is the continuation of Volume 1 (on general aspects and visual functions, English translation Open Access in https:/eprints.ucm.es/id/eprint/63730/) to which it refers continuously. A facsimile Spanish edition includindg Vol. 1, 2 and supplements was published by the Red Temática en Tecnologías de Computación Artificial/Natural (RTNAC) and the University of Santiago de Compostela in 2010, and whose on-line Open-Access version (http://dspace.usc.es/handle/10347/4341 ) maintains a significant rate of visits since its publication. The author, after specialization in neurology and brain pathology in Austria and Germany (1933-35) developed a research on the human cerebral cortex. The interest of the research described here lies, as in Volume 1, in the fact that it is surprisingly of current interest, apart from its undoubted historical interest. Some aspects were ahead of discoveries that were made later. It is remarkable that some of the phenomena exposed are still unknown and that the proposed functional dynamic unit of the cortex is closely related to current trends in the study of the brain. This volume deals with tactile functions and further elaborates on concepts introduced in Volume 1. The tactile phenomenology in cases of central syndrome is described. This syndrome, already studied in Volume 1, is the result of a unilateral lesion in an association area in the left parieto-occipital cortex, equidistant from the visual, tactile and auditory primary areas. It consists of a multisensory alteration (visual, tactile, auditory) although the lesion does not involve specific areas, all functions being affected, from simple excitability to more complex functions, bilaterally and symmetrically. In particular, the striking phenomenon in which the visual image is tilted or nearly inverted (see Vol. 1), is now extended to the phenomenon of localization of stimuli in the tactile system. Inversion in tactile space is studied in detail in cases of central syndrome, being generalized to all sensory systems of a spatial nature, once confirmed in the auditory system. Similarly to what happens in vision, the tactile phenomena in the mentioned syndrome have a dynamic character since the disorders vary with the intensity of the stimulus and with the facilitation by other stimulus. The phenomenon of facilitation by muscular effort is particularly noticeable. The greater the deficit in brain excitability (due to the lesion), the greater the effect of facilitation. In the process of tactile localization of a stimulus, up to five phases are distinguished, from simple sensation to specific localization (passing through inversion), as stimulation increases. This process is described as a spiral development of the organization of the sensory field (tactile and also visual). As in vision, a continuity is found between the various functions that appear according to physiological requirements. Likewise, a continuity is established between sensory functions and gnosis, both being based on the same physiological laws. The schema function is studied in detail and considered in diverse degree according to the somatic model, postural model and praxis model. In addition to the patients directly studied by the author, a reference case is also the famous Schneider patient of Goldstein and Gelb studied in 1918 and 1919, which deserves publications even at present, and which the author interpreted under the central syndrome. This syndrome is also related to Gerstmann's syndrome. In subsequent research, the author found 35 cases that also fit the central syndrome. In a later publication (English translation, Open Access in https://eprints.ucm.es/id/eprint/30931/ ) the author exposed a model based on functional gradients through the cortex, according to which, its specificity is distributed in a continuous gradation, and in agreement with a continuous transition between the central syndrome and other cortical syndromes. The author continued to develop a functional brain model applying the principle of similarity of a dynamic system to the central syndrome, the latter being understood as a change of scale in nervous excitability with respect to a normal individual. This concept was already introduced in the preceding Vol. 1 and also in this Vol. 2. A preface introduces some aspects of this research, its author and his subsequent research.Depto. de ÓpticaFac. de Ciencias FísicasFALSEunpu

Optimal strategies for electrical stimulation with implantable neuromodulation devices

Electrical stimulation (ES) is a neuromodulation technique that uses electrical pulses to modulate the activity of excitable cells to provide a therapeutic effect. Many past and present ES applications use rectangular current waveforms that have been well studied and are easy to generate. However, an extensive body of scientific literature describes different stimulation waveforms and their potential benefits. A key measure of stimulation performance is the amplitude required to reach a certain percentual threshold of activation, as it directly influences important ES parameters such as energy consumption per pulse and charge density. The research summarized in this thesis was conducted to re-examine some of the most-commonly suggested ES waveform variations in a rodent in-vivo nerve-muscle preparation. A key feature of our experimental model is the ability to test stimulation with both principal electrode configurations, monopolar and bipolar, under computer control and in randomized order. Among the rectangular stimulation waveforms, we investigated the effect of interphase gaps (IPGs), asymmetric charge balanced pulses, and subthreshold conditioning pre-pulses. For all these rectangular waveforms, we surprisingly observed opposite effects in the monopolar compared to the bipolar stimulation electrode configuration. The rationale for this consistent observation was identified by analyzing electroneurograms (ENGs) of the stimulated nerve. In the monopolar configuration, biphasic pulses first evoked compound action potentials (eCAPs) as a response to the first field transition. In the bipolar electrode configuration, that is the mode in which many contemporary ES devices, including the envisioned miniaturized electroceuticals, operate, eCAPs were first elicited at the return electrode in response to the middle field transition of biphasic pulses. As all rectangular waveform variations achieve their effect by modulating the amplitude and timing of cathodic (excitatory) and anodic (inhibitory) field transitions, the inverted current profile at the bipolar return electrode explains these observed opposite effects. Further we investigated the claimed benefits of non-rectangular, Gaussian stimulation waveforms in our animal model. In our study only moderate energy savings of up to 17% were observed, a finding that is surprising in light of the predicted range of benefits of up to 60% energy savings with this novel waveform in question. Additionally, we identified a major disadvantage in terms of substantially increased maximum instantaneous power requirements with Gaussian compared to rectangular stimuli. We examined physiological changes in fast twitch muscle following motor nerve injury, and optimal stimulation strategies for activation of denervated muscle. While a high frequency doublet has previously been identified to enhance stimulation efficiency of healthy fast twitch muscle, an effect that has been termed “doublet effect”, we here show that this benefit is gradually lost in muscle during denervation. Lastly, the effect of long duration stimulation pulses, that are required to activate denervated muscle, on nerve is examined. We show that these long pulses can activate nerves up to three times when the three field transition within the biphasic pulses are separated by more than (i.e., when the phase width is above) the refractory period of that nerve. This observation challenges state-of-the-art computational models of extracellular nerve stimulation that do not seem to predict such multiple activations. Further, an undesired up to threefold co-activation of innervated structures nearby the denervated stimulation target warrants further research to study whether these co-activations can be lessened with alternative stimulation waveforms such as ramped sawtooth pulses

Retinal ganglion cells : physiology and prosthesis

The retina is responsible for encoding different aspects of the visual world. Light enters the eyes and is converted by the photoreceptors into electrochemical signals. These signals are processed by the retinal network and proceed afferently to the brain via the axons of the retinal ganglion cells (RGCs). The RGCs outputs are in the form of action potentials (spikes), which encrypt the visual information in terms of spike shape, firing frequencies, and the firing patterns. When the photoreceptors are gone due to disease, vision is lost. The idea of a retinal prosthesis is to activate the surviving RGCs by electrical stimulation in order to recreate vision. In this thesis, I have studied the physiological properties of the RGCs, and reconstructed natural RGC spike trains by electrical stimulation. Chapter 1 introduces the anatomy of the retina and the retinal neurons. How the RGCs respond to light. Electrical stimulation is also discussed. A brief historical summary of the receptive field properties and cell physiology is also presented. Chapter 2 characterizes the intrinsic properties of 16 morphologically defined types of rat RGCs. The intrinsic properties include the biophysical properties due to morphology and dendritic stratification, in addition to physiological properties such as firing behaviours. These properties are also compared with the cat RGC intrinsic properties in order to investigate the variations between the morphologically similar RGCs of the two species. The results suggest that the RGCs among species, even with similar morphologies, do not have conservative intrinsic properties. Chapter 3 examines the details of the spiking properties of the different rat RGC types. Spikes are initiated at the axonal initial segment. A 'single' spike recorded at the soma consists of an axonal spike and a somatic spike. The existence of the two spikes can be recognized by two humps in the phase plot, and further revealed in the higher derivatives of the membrane potential. A principal component analysis shows that the parameters extracted from the phase plots are very useful for a model-independent rat RGC classification. Chapter 4 establishes the foundations for electrical stimulation of the retina. The question is to what extent optimum placement of the stimulating and reference electrodes might be affected by anatomical location. Here we placed the stimulating electrode above or below the retinal inner limiting membrane and found no statistical difference between the thresholds. In addition, reflective axonal spikes from the cut end are discussed. Chapter 5 combines the knowledge obtained in the previous chapters for the sole purpose of reproducing natural RGC outputs when using electrical stimulation. The light responses of the eye under saccadic movements were recorded and used to form the stimulus patterns. The reconstructions were performed on the brisk-transient (BT) and the brisk-sustained (BS) RGCs. Our results suggested that BT RGCs are more capable of following the stimulated stimulus patterns over a wide range of frequencies than the BS RGCs. Chapter 6 concludes the whole thesis

Microstimulation and multicellular analysis: A neural interfacing system for spatiotemporal stimulation

Willfully controlling the focus of an extracellular stimulus remains a significant challenge in the development of neural prosthetics and therapeutic devices. In part, this challenge is due to the vast set of complex interactions between the electric fields induced by the microelectrodes and the complex morphologies and dynamics of the neural tissue. Overcoming such issues to produce methodologies for targeted neural stimulation requires a system that is capable of (1) delivering precise, localized stimuli a function of the stimulating electrodes and (2) recording the locations and magnitudes of the resulting evoked responses a function of the cell geometry and membrane dynamics. In order to improve stimulus delivery, we developed microfabrication technologies that could specify the electrode geometry and electrical properties. Specifically, we developed a closed-loop electroplating strategy to monitor and control the morphology of surface coatings during deposition, and we implemented pulse-plating techniques as a means to produce robust, resilient microelectrodes that could withstand rigorous handling and harsh environments. In order to evaluate the responses evoked by these stimulating electrodes, we developed microscopy techniques and signal processing algorithms that could automatically identify and evaluate the electrical response of each individual neuron. Finally, by applying this simultaneous stimulation and optical recording system to the study of dissociated cortical cultures in multielectode arrays, we could evaluate the efficacy of excitatory and inhibitory waveforms. Although we found that the proximity of the electrode is a poor predictor of individual neural excitation thresholds, we have shown that it is possible to use inhibitory waveforms to globally reduce excitability in the vicinity of the electrode. Thus, the developed system was able to provide very high resolution insight into the complex set of interactions between the stimulating electrodes and populations of individual neurons.Ph.D.Committee Chair: Stephen P. DeWeerth; Committee Member: Bruce Wheeler; Committee Member: Michelle LaPlaca; Committee Member: Robert Lee; Committee Member: Steve Potte