An Optoelectronic Stimulator for Retinal Prosthesis

Retinal prostheses require the presence of viable population of cells in the inner retina. Evaluations of retina with Age-Related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) have shown a large number of cells remain in the inner retina compared with the outer retina. Therefore, vision loss caused by AMD and RP is potentially treatable with retinal prostheses. Photostimulation based retinal prostheses have shown many advantages compared with retinal implants. In contrary to electrode based stimulation, light does not require mechanical contact. Therefore, the system can be completely external and not does have the power and degradation problems of implanted devices. In addition, the stimulating point is flexible and does not require a prior decision on the stimulation location. Furthermore, a beam of light can be projected on tissue with both temporal and spatial precision. This thesis aims at fi nding a feasible solution to such a system. Firstly, a prototype of an optoelectronic stimulator was proposed and implemented by using the Xilinx Virtex-4 FPGA evaluation board. The platform was used to demonstrate the possibility of photostimulation of the photosensitized neurons. Meanwhile, with the aim of developing a portable retinal prosthesis, a system on chip (SoC) architecture was proposed and a wide tuning range sinusoidal voltage-controlled oscillator (VCO) which is the pivotal component of the system was designed. The VCO is based on a new designed Complementary Metal Oxide Semiconductor (CMOS) Operational Transconductance Ampli er (OTA) which achieves a good linearity over a wide tuning range. Both the OTA and the VCO were fabricated in the AMS 0.35 µm CMOS process. Finally a 9X9 CMOS image sensor with spiking pixels was designed. Each pixel acts as an independent oscillator whose frequency is controlled by the incident light intensity. The sensor was fabricated in the AMS 0.35 µm CMOS Opto Process. Experimental validation and measured results are provided

Neuro-electronic technology in medicine and beyond

This dissertation looks at the technology and social issues involved with interfacing electronics directly to the human nervous system, in particular the methods for both reading and stimulating nerves. The development and use of cochlea implants is discussed, and is compared with recent developments in artificial vision. The final sections consider a future for non-medicinal applications of neuro-electronic technology. Social attitudes towards use for both medicinal and non-medicinal purposes are discussed, and the viability of use in the latter case assessed

Concurrent TMS-fMRI: Technical Challenges, Developments, and Overview of Previous Studies

Transcranial magnetic stimulation (TMS) is a promising treatment modality for psychiatric and neurological disorders. Repetitive TMS (rTMS) is widely used for the treatment of psychiatric and neurological diseases, such as depression, motor stroke, and neuropathic pain. However, the underlying mechanisms of rTMS-mediated neuronal modulation are not fully understood. In this respect, concurrent or simultaneous TMS-fMRI, in which TMS is applied during functional magnetic resonance imaging (fMRI), is a viable tool to gain insights, as it enables an investigation of the immediate effects of TMS. Concurrent application of TMS during neuroimaging usually causes severe artifacts due to magnetic field inhomogeneities induced by TMS. However, by carefully interleaving the TMS pulses with MR signal acquisition in the way that these are far enough apart, we can avoid any image distortions. While the very first feasibility studies date back to the 1990s, recent developments in coil hardware and acquisition techniques have boosted the number of TMS-fMRI applications. As such, a concurrent application requires expertise in both TMS and MRI mechanisms and sequencing, and the hurdle of initial technical set up and maintenance remains high. This review gives a comprehensive overview of concurrent TMS-fMRI techniques by collecting (1) basic information, (2) technical challenges and developments, (3) an overview of findings reported so far using concurrent TMS-fMRI, and (4) current limitations and our suggestions for improvement. By sharing this review, we hope to attract the interest of researchers from various backgrounds and create an educational knowledge base

ENCODING OF SALTATORY TACTILE VELOCITY IN THE ADULT OROFACIAL SOMATOSENSORY SYSTEM

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement. High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable pneumotactile array consisting of 7 TAC-Cells was used to present 5 stimulus conditions: 5 cm/s, 25 cm/s, 65 cm/s, ALL-ON synchronous activation, and ALL-OFF. The spatial organization of cerebral and cerebellar blood oxygen level-dependent (BOLD) response as a function of stimulus velocity was analyzed using general linear modeling (GLM) of pooled group fMRI signal data. The sequential saltatory inputs to the lower face produced localized, predominantly contralateral BOLD responses in primary somatosensory (SI), secondary somatosensory (SII), primary motor (MI), supplemental motor area (SMA), posterior parietal cortices (PPC), and insula, whose spatial organization and intensity were highly dependent on velocity. Additionally, ipsilateral sensorimotor, insular and cerebellar BOLD responses were prominent during the lowest velocity (5 cm/s). Advisor: Steven M. Barlo

ENCODING OF SALTATORY TACTILE VELOCITY IN THE ADULT OROFACIAL SOMATOSENSORY SYSTEM

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement. High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable pneumotactile array consisting of 7 TAC-Cells was used to present 5 stimulus conditions: 5 cm/s, 25 cm/s, 65 cm/s, ALL-ON synchronous activation, and ALL-OFF. The spatial organization of cerebral and cerebellar blood oxygen level-dependent (BOLD) response as a function of stimulus velocity was analyzed using general linear modeling (GLM) of pooled group fMRI signal data. The sequential saltatory inputs to the lower face produced localized, predominantly contralateral BOLD responses in primary somatosensory (SI), secondary somatosensory (SII), primary motor (MI), supplemental motor area (SMA), posterior parietal cortices (PPC), and insula, whose spatial organization and intensity were highly dependent on velocity. Additionally, ipsilateral sensorimotor, insular and cerebellar BOLD responses were prominent during the lowest velocity (5 cm/s). Advisor: Steven M. Barlo

Connecting the Brain to Itself through an Emulation.

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical intra- and inter-regional circuits. By using machine learning algorithms and classic tasks known to activate quasi-orthogonal functional connectivity patterns, bedside testing can rapidly identify ensemble tuning properties and in turn cycle through a sequence of external module architectures to explore which can causatively alter perception and behavior. Whole brain emulation both (1) serves to augment human neural function, compensating for disease and injury as an auxiliary parallel system, and (2) has its independent operation bootstrapped by a human-in-the-loop to identify optimal micro- and macro-architectures, update synaptic weights, and entrain behaviors. In this manner, closed-loop brain-computer interface pilot clinical trials can advance strong artificial intelligence development and forge new therapies to restore independence in children and adults with neurological conditions

An Image Processing Approach Toward a Visual Intra-Cortical Stimulator

Abstract Visual impairment may be caused by various factors varying from trauma, birth-defects, and diseases. Until today there are no viable medical treatments for this condition; hence bio-medical approaches are being employed to overcome that. The Cortivision team has been working on an intra-cortical implant that can bypass the retina and optic nerve and directly stimulate the visual cortex. In this work we aimed to implement a modular, reusable, and parameterizable object recognition system that tends to ``simplify'' video data prior to stimulation; hence opening new horizons for partial vision restoration, navigational and even recognition abilities. We identified the Scale Invariant Feature Transform (SIFT) algorithm as being a robust candidate for our application's needs. A multithreaded software prototype of the SIFT and Lucas-Kanade tracker was implemented to ensure proper overall operation. The feature extractor, difference of Gaussians (DoG) part of the SIFT, being the most computationally expensive, was migrated to an FPGA implementation due to the real-time restrictions that is not achievable on a host machine. The VHDL implementation is highly parameterizable for different application needs and tradeoffs. We introduced a novel architecture employing the sub-kernel trick to reduce resource usage compared to preexisting architectures while still being comparably accurate to a software floating point implementation. In order to alleviate transmission bottlenecks, the system also includes a new parallel Huffman encoder design that is capable of performing lossless compression of both images and scale space image pyramids taking into account spatial and scale data correlations during the predictor phase. The encoder was able to achieve compression ratios of 27.3% on the Caltech-256 data-set. Furthermore, a new camera and fiducial markers setup based on image processing was proposed in order to target the phosphene map estimation problem which affects the quality of the final stimulation that is perceived by the patient.----------RÉSUMÉ Introduction et objectifs La déficience visuelle, qui est définie par la perte totale ou partielle de la vision, n'est actuellement pas médicalement traitable. Des approches biomédicales modernes sont utilisées pour stimuler électriquement la vision; ces approches peuvent être divisées en trois groupes principaux: le premier ciblant les implants rétiniens Humayun et al. (2003), Kim et al. (2004), Chow et al. (2004); Palanker et al. (2005), Toledo et al. (2005); Yanai et al. (2007), Winter et al. (2007); Zrenner et al. (2011), le deuxième ciblant les implants du nerf optique Veraart et al. (2003), Sakaguchi et al. (2009), et le troisième ciblant les implants intra-corticaux Doljanu et Sawan (2007); Coulombe et al. (2007); Srivastava et al. (2007). L’inconvénient principal des deux premiers groupes, c'est qu'ils ne sont pas suffisamment génériques pour surmonter la majorité des maladies de déficience visuelle, car ils dépendent du fait que le patient doit avoir un nerf optique intact et/ou une rétine partiellement opérationnelle ; ce qui n'est pas le cas pour le troisième groupe. L'équipe du Laboratoire Polystim Neurotechnologies travaille actuellement sur un implant intra-cortical qui stimule directement le cortex visuel primaire (région V1) ; le nom du projet global est Cortivision. Le système utilise une caméra, un module de traitement d'image, un transmetteur RF (radiofréquence) et un stimulateur implantable. Cette méthode est robuste et générique car elle contourne l'oeil et le nerf optique. Un des défis majeurs est le traitement d'image nécessaire pour «simplifier» les données antérieures à la stimulation, l'extraction de l’information utile en écartant les données superflues. Les pixels qui sont capturés par la caméra n'ont pas de correspondance un-à-un sur le cortex visuel comme dans une image rectangulaire, ils sont plutôt mis en correspondance avec une carte complexe de «phosphènes» Coulombe et al. (2007); Srivastava et al. (2007). Les phosphènes sont des points lumineux qui apparaissent dans le champ de vision du patient quand le cerveau est stimulé électriquement. Ces points changent en terme de taille, de luminosité et d’emplacement en fonction de la façon dont la stimulation électrique est effectuée (c'est à dire un changement dans la fréquence, la tension, la durée, etc. ...) et même par le placement physique des électrodes dans le cortex visuel. Les approches actuelles visent à stimuler des images de phosphènes monochromes à basse résolution. Sachant cela, nous nous attendons plutôt à une vision de faible qualité qui rend des activités comme naviguer, interpréter des objets, ou encore lire, difficile pour le patient. Ceci est principalement dû à la complexité de l’étalonnage de la carte phosphène et sa correspondance, et aussi à la non-trivialité de savoir comment simplifier les données à partir des images qui viennent de la camera de façon qu’on conserve seulement les données pertinentes. La Figure 1.1 est un exemple qui démontre la non-trivialité de transformer une image grise en stimulation phosphène

Tactile Modulation of the Sensory and Cortical Responses Elicited by Focal Cooling in Humans and Mice

Distinct sensory receptors transduce thermal and mechanical energies, but we have unified, coherent thermotactile experiences of the objects we touch. These experiences must emerge from the interaction of thermal and tactile signals within the nervous system. How do thermal and mechanical signals modify each other as they interact along the pathway from skin to conscious experience? In this thesis, we study how mechanical touch modulates cooling responses by combining psychophysics in humans and neural recordings in rodents. For this, we developed a novel stimulator to deliver focal, temperature-controlled cooling without touch. First, we used this method to study in humans the sensitivity to focal cooling with and without touch. We found that touch reduces the sensitivity to near-threshold cooling, which is perhaps analogous to the well-established ‘gating’ of pain by touch. Second, we studied the perceived intensity of cooling with and without touch. We found that tactile input enhances the perceived intensity of cooling. Third, we measured the responses of the mouse primary somatosensory cortex to cooling and mechanical stimuli using imaging and electrophysiological methods. We found multisensory stimuli elicited non-linear cortical responses at both the population and cellular level. Altogether, in this thesis, we show perceptual and cortical responses to non-tactile cooling for the first time. Based on our observations, we propose a new model to explain the interactions between cooling and mechanical signals in the nervous system. This thesis advances our understanding of how touch modulates cold sensations during thermotactile stimulation

Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach are demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility

Sensorimotor Mapping With MEG: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines

Published: November 2020In this article, we present the clinical indications and advances in the use of magnetoencephalography to map the primary sensorimotor (SM1) cortex in neurosurgical patients noninvasively. We emphasize the advantages of magnetoencephalography over sensorimotor mapping using functional magnetic resonance imaging. Recommendations to the referring physicians and the clinical magnetoencephalographers to achieve appropriate sensorimotor cortex mapping using magnetoencephalography are proposed. We finally provide some practical advice for the use of corticomuscular coherence, corticokinematic coherence, and mu rhythm suppression in this indication. Magnetoencephalography should now be considered as a method of reference for presurgical functional mapping of the sensorimotor cortex.X. De Ti ege is Post-doctorate Clinical Master Specialist at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). M. Bourguignon has been supported by the program Attract of Innoviris (Grant 2015-BB2B-10), by the Spanish Ministry of Economy and Competitiveness (Grant PSI2016- 77175-P), and by the Marie Sk1odowska-Curie Action of the European Commission (Grant 743562). H. Piitulainen has been supported by the Academy of Finland (Grants #266133 and #296240), the Jane and Aatos Erkko Foundation, and the Emil Aaltonen Foundation. The authors thank Professor Riitta Hari for her support in most of the research works published by the authors and presented in this article. The MEG project at the CUB H^opital Erasme is financially supported by the Fonds Erasme (Research convention “Les Voies du Savoir,” Fonds Erasme, Brussels, Belgium)