Biology subjects

Kochnev Goldstein, A.

Publications and source records attributed to Kochnev Goldstein, A..

7 recordsLinked to original sources

bioRxiv2026

Retinal Resistivity Mapped by Electrical Resistance Tomography

Retinal resistivity is a key parameter for modeling both the electric field in tissue and the resulting neural response - a crucial step in designing retinal prostheses, especially since both depend on resistivity nonlinearly. Previous studies using penetrating microelectrodes reported vastly different values, varying by as much as two orders of magnitude, likely due to parasitic capacitance in microelectrodes, compression of tissue and its rupture by the inserted probe, allowing the conductive medium to seep in and alter the measurement. To measure retinal resistivity without compression or rupture, we applied electrical resistance tomography using a planar multielectrode array with a 30 m pitch. Voltage waveforms generated in response to current injected from one electrode were measured on other electrodes in the array, at distances ranging from 30 to 600 m. Data from wild-type and degenerated rat retinas were analyzed using two methods: a commercial inversion software, Res2DInv, and a custom machine learning-based decoder, with healthy retina approximated as a 4-layer structure and degenerated retina - as a 3-layer one.

biophysics↗

bioRxiv2026

Identification of Direct and Network-Mediated Activation of Retinal Ganglion Cells from Visually Evoked Potentials Using Machine Learning

ObjectiveTo preserve the encoding of visual information in prosthetic vision as close to natural as possible, subretinal photovoltaic implants, which replace the lost photoreceptors, strive to stimulate the second-order retinal neurons, the bipolar cells, while avoiding direct activation of the downstream retinal ganglion cells. To assess the range of such selective subretinal activation, we implanted the devices in rodent models of retinal degeneration and measured the stimulation thresholds based on the visually evoked potentials. After assessment of the bipolar cell-mediated thresholds, direct activation of retinal ganglion cells was measured following intraocular injection of synaptic blockers. Since these chemicals are toxic to the retina, this procedure can only be done once in each animal. ApproachWe developed a machine-learning model that identifies the stimulation pathway directly from the recorded visually evoked potentials, eliminating the need for synaptic blockers. The model was trained on recordings from rats implanted with PRIMA subretinal arrays and evaluated on two additional implant architectures, a second rat species, and a different anesthesia protocol. Main ResultsThe classifier achieved a balanced accuracy of 92% in cross-validation on the training data. Generalization to all unseen experimental conditions yielded an average balanced accuracy of 91%. Integrated Gradients analysis showed that combined bipolar and ganglion cell responses were driven by the early P1 component, while bipolar cell responses relied on later waveform components, consistent with thalamocortical processing dynamics. SignificanceThe described computational alternative to pharmacological blockers should improve the experimental throughput, allow multiple recordings over the lifetime of the same animal, and might be applicable to optimization of the stimulation settings in patients.

bioengineering↗

bioRxiv2026

Remote and Independent Detection of Human Stress Using Sweat and AI

Previous studies exploring human sweat ducts as biological antennas in the sub-THz range have shown that the electromagnetic (EM) response of the skin is modulated by the persons mental and physical stress. These findings naturally raised hopes of a new remote avenue for detecting human stress. However, as those studies unmasked stress using correlations with well-established markers such as the Galvanic Skin Response (GSR), the question of whether the EM response could serve as an independent marker of stress remained unanswered. Here, we provide a positive answer to this question by showing that machine learning models trained on EM reflections from 21 participants, subjected to physical and mental stress, were able to estimate the presence of stress in a signal from a new participant, in a matter of seconds, with above 90% accuracy.

biophysics↗

bioRxiv2025

Residual photoreceptors affect the response of a degenerate retina to electrical stimulation

Patients with age-related macular degeneration (AMD) implanted with the PRIMA photovoltaic subretinal prosthesis demonstrated letter acuity closely matching the devices 100 {micro}m pixel size. Improving visual acuity requires smaller pixels, which, in turn, require relaxation of electric field confinement to maintain effective stimulation of bipolar cells. Eliminating local return electrodes broadens the electric field but may inadvertently engage residual photoreceptors adjacent to the implant, thereby altering electrically evoked visual percepts. Here we quantify the contribution of residual photoreceptors to electrically evoked retinal responses across various implant configurations. Monopolar photovoltaic arrays with 20 {micro}m pixels and bipolar arrays with 100 {micro}m pixels were implanted subretinally in Long Evans rats, resulting in local degeneration of photoreceptors directly above the device. Responses were compared with those obtained in RCS rats, which lack functional photoreceptors. Implants were activated by patterns of 880 nm laser at pulse durations varying from 0.5 to 10 ms. Visually evoked potentials were measured in scotopic and photopic conditions, with and without the intravitreal application of mGluR6 agonist L-AP4 to block photoreceptor-driven ON pathways. Experimental thresholds were interpreted using a computational model of retinal network activation in distinct electric field geometries. In locally degenerate retina stimulated with monopolar arrays, blocking photoreceptor input yielded a rheobase (0.06 mW/mm{superscript 2}) and chronaxie ([~]3 ms) of the stimulation threshold, matching that measured in fully degenerate RCS retina, indicating direct activation of bipolar cells. In contrast, when photoreceptor input was intact, stimulation thresholds decreased significantly, and dark adaptation further modulated the threshold in a pulse-duration dependent manner. Bipolar arrays provided identical thresholds in locally degenerate and fully degenerate retina (0.2 mW/mm{superscript 2}) when stimulation was confined to the implant center; however, shifting stimulation to the implants edge lowered the thresholds, revealing a contribution from adjacent photoreceptors. These findings demonstrate that residual photoreceptors can substantially influence responses evoked by subretinal prostheses in a degenerate retina, with direct consequences for perceptual uniformity in patients, such as edge brightening. These results provide guidance for design of the next-generation higher-resolution implants, supporting the use of local return electrodes to maximize resolution while minimizing the effect of photoreceptors in clinical applications.

neuroscience↗

bioRxiv2024

Accelerated Simulation of Multi-Electrode Arrays Using Sparse and Low-Rank Matrix Techniques

ObjectiveModeling of Multi-Electrode Arrays used in neural stimulation can be computationally challenging since it may involve incredibly dense circuits with millions of intercon-nected resistors, representing current pathways in an electrolyte (resistance matrix), coupled to nonlinear circuits of the stimulating pixels themselves. Here, we present a method for accelerating the modeling of such circuits with minimal error by using a sparse plus low-rank approximation of the resistance matrix. MethodsWe prove that thresholding of the resistance matrix elements enables its sparsification with minimized error. This is accomplished with a sorting algorithm, implying efficient O (N log (N)) complexity. The eigenvalue-based low-rank compensation then helps achieve greater accuracy without significantly increasing the problem size. Results: Utilizing these matrix techniques, we reduced the computation time of the simulation of multi-electrode arrays by about 10-fold, while maintaining an average error of less than 0.3% in the current injected from each electrode. We also show a case where acceleration reaches at least 133 times with additional error in the range of 4%, demonstrating the ability of this algorithm to perform under extreme conditions. ConclusionCritical improvements in the efficiency of simulations of the electric field generated by multi-electrode arrays presented here enable the computational modeling of high-fidelity neural implants with thousands of pixels, previously impossible. Significance: Computational acceleration techniques described in this manuscript were developed for simulation of high-resolution photovoltaic retinal prostheses, but they are also immediately applicable to any circuits involving dense connections between nodes, and, with modifications, more generally to any systems involving non-sparse matrices.

bioengineering↗

bioRxiv2024

Enhancing Prosthetic Vision by Upgrade of a Subretinal Photovoltaic Implant in situ

In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100m pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22m pixels increased the grating acuity from the 100m capability of PRIMA implants to 28m, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.

neuroscience↗

bioRxiv2022

Pixel size limit of the PRIMA implants: from humans to rodents and back

ObjectiveRetinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic Age-related Macular Degeneration (AMD) using the PRIMA subretinal implant, a 2x2 mm array of 100m-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which necessitates more intense stimulation. ApproachHere, we examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, as well as using a preclinical animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials were measured in RCS rats with photovoltaic implants of 100 and 75m pixels and compared to clinical thresholds with 100 m pixels. Electrical stimulation model calibrated by these clinical and rodent data was used to predict the performance of the implant with smaller pixels. Main ResultsWe found that PRIMA implants with 75m pixels under the maximum safe near-infrared (880nm) illumination of 8 mW/mm2 with 30% duty cycle (10ms pulses at 30Hz) should provide a similar perceptual brightness as with 100 m pixels under 3 mW/mm2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75m pixels is also similar under such illumination to that with 100m pixels in clinical settings, increasing the maximum acuity from 20/420 to 20/300. SignificanceComputational model of the photovoltaic subretinal prosthesis defines the minimum pixel size of the PRIMA implants as 75m. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75m will nearly quadrupole the number of pixels and thereby should significantly improve the visual performance. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.

bioengineering↗