D. Neumann

Tunable retina encoders for retina implants: why and how

Current research towards retina implants for partial restoration of vision in blind humans with retinal degenerative dysfunctions focuses on implant and stimulation experiments and technologies. In contrast, our approach takes the availability of an epiretinal multi-electrode neural interface for granted and studies the conditions for successful joint information processing of both retinal prosthesis and brain. Our proposed learning retina encoder (RE) includes information processing modules to simulate the complex mapping operation of parts of the 5-layered neural retina and to provide an iterative, perception-based dialog between RE and human subject. Alternative information processing technologies in the learning RE are being described, which allow an individual optimization of the RE mapping operation by means of iterative tuning with learning algorithms in a dialog between implant wearing subject and RE. The primate visual system is modeled by a retina module (RM) composed of spatio-temporal (ST) filters and a central visual system module (VM). RM performs a mapping 1 of an optical pattern P1 in the physical domain onto a retinal output vector R1(t) in a neural domain, whereas VM performs a mapping 2 of R1(t) in a neural domain onto a visual percept P2 in the perceptual domain. Retinal ganglion cell properties represent non-invertible ST filters in RE, which generate ambiguous output signals. VM generates visual percepts only if the corresponding R1(t) is properly encoded, contains sufficient information, and can be disambiguated. Based on the learning RE and the proposed visual system model, a novel retina encoder (RE*) is proposed, which considers both ambiguity removal and miniature eye movements during fixation. Our simulation results suggest that VM requires miniature eye movements under control of the visual system to retrieve unambiguous patterns P2 corresponding to P1. For retina implant applications, RE* can be tuned to generate optimal ganglion cell codes for epiretinal stimulation.

Lipid nanocapsules for dermal application: A comparative study of lipid-based versus polymer-based nanocarriers

Lipid nanocapsules (LNC) are colloidal carriers providing controlled release profiles and improved bioavailability for many drug substances and diverse administration routes. However, they have not been explored before for transdermal application. Here, we study the behavior of LNC as a transdermal drug delivery system using ibuprofen as a model drug. A comparison to other lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and polymeric nanocarriers has been made. It was found that LNC could increase the flux rate of ibuprofen 21.9±0.5 compared to 5.8±0.4 μg/cm(2)h in case of drug solution. Similar flux rates were obtained for SLN and NLC with average values of 22.9±0.5 and 22.5±2.0 μg/cm(2)h, respectively. On the other side, comparison to polymeric nanoparticles showed that the polymer-based carriers of the same particle size had lower permeation-enhancing effect with a flux rate of 10.62±1.84 μg/cm(2)h. Polymeric carriers had fourfold higher accumulation in the skin compared to that of the LNC and twice the accumulation of SLN and NLC. These results would suggest that the LNC can be considered as efficient as SLN and NLC for the transdermal drug delivery while polymeric nanoparticles are more suitable for localized drug delivery to the skin.

Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion

A new predictive micro-scale solubility and process model for amorphous solid dispersions (ASDs) by hot-melt extrusion (HME) is presented. It is based on DSC measurements consisting of an annealing step and a subsequent analysis of the glass transition temperature (Tg). The application of a complex mathematical model (BCKV-equation) to describe the dependency of Tg on the active pharmaceutical ingredient (API)/polymer ratio, enables the prediction of API solubility at ambient conditions (25°C). Furthermore, estimation of the minimal processing temperature for forming ASDs during HME trials could be defined and was additionally confirmed by X-ray powder diffraction data. The suitability of the DSC method was confirmed with melt rheological trials (small amplitude oscillatory system). As an example, ball milled physical mixtures of dipyridamole, indomethacin, itraconazole and nifedipine in poly(vinylpyrrolidone-co-vinylacetate) (copovidone) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used.

A "drug cocktail" delivered by microspheres for the local treatment of rat glioblastoma.

For the treatment of glioblastoma multiforme, an “anticancer drug cocktail” delivered by biodegradable poly-lactide-co-glycolide (PLGA)-microspheres is proposed. Celecoxib, etoposide, and elacridar were encapsulated by an oil/water emulsification solvent evaporation method. Drug-loaded microspheres were analyzed for their physicochemical properties and evaluated in a rat glioblastoma model. Microspheres had a mean diameter 10–20 µm, and encapsulation rates varied upon lipophilicity of the drug (celecoxib: 97.4 ± 0.4%; elacridar: 98.1 ± 0.3%; and etoposide: 38.7 ± 8.3%). Drug release of celecoxib and elacridar resulted in a burst (t50: 3.1 h and 1.0 h, respectively) while etoposide release was slower (t50: 45.3 h). The comparison of celecoxib (p = 0.021) and etoposide microspheres (p = 0.002) as well as their combination (p = 0.011) led to a significant increase in the probability of survival compared to blank microspheres. Local delivery of celecoxib and etoposide microspheres was found to be suitable for the treatment of glioblastoma in rats although simultaneous drug administration did not improve the therapeutic outcome.

Neural Information Processing Efforts to Restore Vision in the Blind

Retina Implants belong to the most advanced and truly ‘visionary’ man-machine interfaces. Such neural prostheses for retinally blind humans with previous visual experience require technical information processing modules (in addition to implanted microcontact arrays for communication with the remaining intact central visual system) to simulate the complex mapping operation of the 5-layered retina and to generate a parallel, asynchronous data stream of neural impulses corresponding to a given optical input pattern. In this paper we propose a model of the human visual system from the information science perspective. We describe the unique information processing approaches implemented in a learning Retina Encoder (RE), which functionally mimics parts the central human retina and which allows an individual optimization of the RE mapping operation by means of iterative tuning using learning algorithms in a dialog between implant wearing subject and RE.

On Human Factors for Interactive Man-Machine Vision: Requirements of the Neural Visual System to transform Objects into Percepts

This paper combines recent findings from neuroscience of the primate visual system, neural computation simulations, and dialog-based man-machine tuning experiments in order to define the properties that are essential for novel interactive image acquisition and display systems for human visual augmentation challenges: e.g. a-Interactive Imagery Analysis, b-Visual Prosthetics, and c-Generation of realistic, dynamically explorable Objects. Technical systems need for elicitation of visual percepts in humans a detailed consideration of sensory and motor parameters of the human visual system and also learning control capabilities to provide an optimization of visual percepts in a feedback loop between a technical system and the human.

Retina encoder tuning and data encryption for learning retina implants

A retina encoder (RE) as part of a visual prosthesis (retina implant) for blind subjects with retinal degenerative disorders was implemented by an array of 256 tunable spatio-temporal filters (ST) to map visual patterns P1 onto encoded output patterns as functional approximation of retina information processing. These RE-output signals were fed into a visual system module (VM) to simulate the mapping (by the central visual system) of the retinal output onto visual percepts P2, which were visualized on a monitor. Alternative tuning strategies for roaming within the large spatio-temporal state space of RE were developed and tested. Initially, VM as neural network was trained to generate a P2 very similar to a selected set of P1s by feeding the corresponding RE-outputs into VM. RE tuning was tested by presenting a given small set of P1s to the serial coupling of RE and VM and by monitoring a modified Hamming distance between P2 and P1, while the ST-parameters were tuned. Human volunteers with normal vision were asked to approximate P2 to P1 directly, with random search, or by means of a dialog-based tuning with an evolutionary algorithm (EA). Typically, dialog-based EA tuning reached the optimal similarity between P2 and P1 (limited by the quality of VM) within less than 200 iterations. In contrast, manual tuning required considerably more iteration steps and converged to a smaller similarity between P2 and P1. Structure and function of our tunable RE offer not only an optimization of visual perception, but may also be important to serve as technical encryption unit (EU) in connection with the human central visual system as biological decryption unit (DU); an important feature to meet the authentication requirements of active medical devices.

Development of a neural net-based, personalized secure communication link

This paper describes a novel ultra-secure, unidirectional communication channel for use in public communication networks, which is based on a) learning algorithms in combination with neural nets for fabrication of a unique pair of modules for encryption and decryption, and b) in combination with decision trees for the decryption process, c) signal transformation from spatial to temporal patterns by means of ambiguous spatial-temporal filters (ST filters), d) absence of public- or private keys, and e) requirement of biometric data of one of the users for both generation of the pair of hardware/software modules and for the decryption by the receiver. To achieve these features we have implemented an encryption-unit (EU) using ST filters for encryption and a decryption unit (DU) using learning algorithms and decision trees for decryption.

Concerning the mapping of ambiguous retinal output vectors onto unambiguous visual percepts

Summary form only given. From a systems theory and computational neuroscience perspective, the primate foveal visual system in the photopic range consists of a retina module as a large ensemble of spatio-temporal (ST) filters represented by the receptive field (RF) properties of mostly P- and Mganglion cells feeding into a corresponding central visual system module (VM). VM in turn elicits visual percepts P2 corresponding to optical input patterns P1. Human visual perception, which transcends neuroscience and biophysics, is considered here as the result of a sequence of two unidirectional mapping operations. The paper outlines a novel retina encoder (RE*) for mapping of optical patterns P1 onto vectors of ambiguous output signals; RE* serves both as retina module simulator and as neuroprosthetic retinal replacement. The paper also identifies essential requirements for the mapping of an ambiguous signal vector onto an unambiguous pattern. It also discusses perceptual consequences of a low-dimensional (e.g. 100) vector of multiple ganglion cell activity generated by RE* in blind subjects with an epiretinal, learning retina implant, vs. the high-dimensional vector of single ganglion cell activity generated by the human retina during normal vision.