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Papers by Artemio Soto-Breceda
Investigative Ophthalmology & Visual Science, Jul 22, 2019
Retinal prostheses aim to provide visual percepts through electrical stimulation of the retina to... more Retinal prostheses aim to provide visual percepts through electrical stimulation of the retina to blind people affected by diseases caused by photoreceptor degeneration. Two challenges presented by current devices are a lack of selectivity in the activation of retinal ganglion cells (RGCs) and neural adaptation in the retina, which is believed to be the cause of fading-an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to (1) understand the neural adaptation generated in RGCs during electrical stimulation, (2) obtain the preferred stimulation parameters (waveform) of each morphological class of RGCs and (3) use the preferred waveform of each morphological class to selectively activate different neurons. RGCs have been classified by morphology into 4 main groups: A, B, C and D. We performed an spike-triggered covariance (STC) analysis on the responses of 44 RGCs to extracellular electrical white noise and 43 RGCs to intracellular white noise. We then recovered their temporal electrical receptive fields (tERF), or waveform. A number of RGCs were stimulated with all the previously recovered waveforms to test the efficacy of each waveform on each other. The waveform recovered from the responses to intracellular stimulation have shown that RGCs can be classified into their respective morphological types by using a K-means clustering algorithm. Extracellular stimulation did not result in waveforms with a clear correlation between clusters and morphological classes. Cells from B and D morphological types had lower thresholds when stimulated with the waveform recovered from cells in the same morphological class. A-RGCs on the contrary, did not seem to share the same temporal features in their waveform with other A-type neurons. Further studies involving a larger data set might determine whether the waveform could preferentially stimulate cells from a specific morphological class. Current visual prostheses use electrical pulses with fixed frequencies and amplitudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IPI), the latter taken from an exponential distribu-A special mention to Ludovico Einaudi who kept me company and inspired me during the long hours of thesis writing and experimental work since day one of these four years of PhD. Finally, I would like to thank Marcela, who has never let me down and has been the greatest support during this journey, nothing would have been possible without her. Thank you for teaching me more about life than any University could ever have.
Journal of Neuroscience Methods, 2020
Background: Peripheral autonomic nerves control visceral organs and convey information regarding ... more Background: Peripheral autonomic nerves control visceral organs and convey information regarding their functional states and are, therefore, potential targets for new therapeutic and diagnostic approaches. Conventionally recorded multi-unit nerve activity in vivo undergoes slow differential drift of signal and noise amplitudes, making accurate monitoring of nerve activity for more than tens of minutes problematic. New Method: We describe an on-line drift compensation algorithm that utilizes recursive least-squares to estimate the relative change in spike amplitude due to changes in the nerve-electrode interface over time. Results: We tested and refined our approach using simulated data and in vivo recordings from nerves supplying the small intestine under control conditions and in response to gut inflammation over several hours. The algorithm is robust to changes in recording conditions and signal-to-noise ratio and applicable to both single and multi-unit recordings. In uncompensated records, drift prevented "spike families" and single units from being discriminated accurately over hours. After rescaling, these were successfully tracked throughout recordings (up to 3 h). Comparison with existing Methods: Existing methods are subjective or compensate for drift using spatial information and spike shape data which is not practical in multi-unit peripheral nerve recordings. In contrast, this method is objective and applicable to data from a single differential multi-unit recording. In comparisons using simulated data the algorithm performed as well as or better than existing methods. Conclusions: Results suggest our drift compensation algorithm is widely applicable and robust, though conservative, when differentiating prolonged responses from drift in signal. Extracellular nerve recordings; drift compensation; chronic nerve recordings; closed-loop; multi-unit activity; spike discrimination; recursive least squares; real-time
Biomaterials, 2019
Implantable medical devices are now in regular use to treat or ameliorate medical conditions, inc... more Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.
Sensing and Bio-Sensing Research, 2019
Biomedical electronic implants require a power source to operate. Miniaturised implants can precl... more Biomedical electronic implants require a power source to operate. Miniaturised implants can preclude batteries and as implant dimensions reduce further, inductive power transfer no longer becomes the optimum strategy for wireless power delivery. Wide dipole antennas are proposed as an alternative power transmitter for long and thin implants. A miniaturised bioelectronic device measuring 1 mm by 1 mm by 20 mm was fabricated, wirelessly powered and used to stimulate retinal ganglion cells to provide biological validation of its functionality. Optimised wide dipole antennas operating in the GHz range for implant depths of 5 mm to 35 mm in 5 mm steps were simulated, fabricated and measured. Saline solution was used as a biological tissue phantom for power transfer efficiency measurements. The maximum safe deliverable power to the device was 1.7 mW in simulation and 1.3 mW in measurement at power transfer efficiencies of 15% and 11% respectively. The work herein confirms that wide dipole transmitting antennas are suitable for radiative near field power transfer to long and thin implants. This power transfer technique could be used for implants that are injectable, deliverable via catheter and minimally invasive, advancing the aim to create smaller more innovative electronic implantable devices.
Sensors and Actuators A: Physical, 2018
Up to 16 Individually addressable and wirelessly powered optogenetic channels Above 10mW of mea... more Up to 16 Individually addressable and wirelessly powered optogenetic channels Above 10mW of measured light output power Inductive multichannel resonant topology removes complex electronics from implant Ability to multiplex and pulse channels by modulating transmission signal Biological validation in porcine tissue, human embryonic kidney cells and retinal ganglion cells
Journal of neural engineering, Jan 19, 2018
Retinal prostheses aim to provide visual percepts to blind people affected by diseases caused by ... more Retinal prostheses aim to provide visual percepts to blind people affected by diseases caused by photoreceptor degeneration. One of the main challenges presented by current devices is neural adaptation in the retina, which is believed to be the cause of fading - an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to understand the neural adaptation generated in retinal ganglion cells (RGCs) during electrical stimulation. Current visual prostheses use electrical pulses with fixed frequencies and amplitudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IP...
2013 Pan American Health Care Exchanges (PAHCE), 2013
ABSTRACT The purpose of this document is to describe and explain the design of a tracking system ... more ABSTRACT The purpose of this document is to describe and explain the design of a tracking system which allows the objective measurement of the kinematic and force variables in tasks oriented to ENT (ear, nose and throat) minimally invasive surgery. The designed device consists of a software and hardware system which records the surgeon's skills while executing training tasks for otorhinolaryngologic surgery on unanimated models. A set of movement, position and pressure sensors, records the path followed by the tip of the surgical instrument. From the records made by these sensors, six different parameters (time, depth perception, path length, motion smoothness, response orientation and force) are calculated and the performance of the surgeon is quantitatively registered. It resulted feasible to determine the skills of the surgeon following this approach.
Journal of Neural Engineering
Objective. Retinal prostheses have had limited success in vision restoration through electrical s... more Objective. Retinal prostheses have had limited success in vision restoration through electrical stimulation of surviving retinal ganglion cells (RGCs) in the degenerated retina. This is partly due to non-preferential stimulation of all RGCs near a single stimulating electrode, which include cells that conflict in their response properties and their contribution to visiual processing. Our study proposes a stimulation strategy to preferentially stimulate individual RGCs based on their temporal electrical receptive fields (tERFs). Approach. We recorded the responses of RGCs using whole-cell patch clamping and demonstrated the stimulation strategy, first using intracellular stimulation, then via extracellular stimulation. Main results. We successfully reconstructed the tERFs according to the RGC response to Gaussian white noise current stimulation. The characteristics of the tERFs were extracted and compared based on the morphological and light response types of the cells. By re-deliver...
Investigative Ophthalmology & Visual Science, Jul 22, 2019
Retinal prostheses aim to provide visual percepts through electrical stimulation of the retina to... more Retinal prostheses aim to provide visual percepts through electrical stimulation of the retina to blind people affected by diseases caused by photoreceptor degeneration. Two challenges presented by current devices are a lack of selectivity in the activation of retinal ganglion cells (RGCs) and neural adaptation in the retina, which is believed to be the cause of fading-an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to (1) understand the neural adaptation generated in RGCs during electrical stimulation, (2) obtain the preferred stimulation parameters (waveform) of each morphological class of RGCs and (3) use the preferred waveform of each morphological class to selectively activate different neurons. RGCs have been classified by morphology into 4 main groups: A, B, C and D. We performed an spike-triggered covariance (STC) analysis on the responses of 44 RGCs to extracellular electrical white noise and 43 RGCs to intracellular white noise. We then recovered their temporal electrical receptive fields (tERF), or waveform. A number of RGCs were stimulated with all the previously recovered waveforms to test the efficacy of each waveform on each other. The waveform recovered from the responses to intracellular stimulation have shown that RGCs can be classified into their respective morphological types by using a K-means clustering algorithm. Extracellular stimulation did not result in waveforms with a clear correlation between clusters and morphological classes. Cells from B and D morphological types had lower thresholds when stimulated with the waveform recovered from cells in the same morphological class. A-RGCs on the contrary, did not seem to share the same temporal features in their waveform with other A-type neurons. Further studies involving a larger data set might determine whether the waveform could preferentially stimulate cells from a specific morphological class. Current visual prostheses use electrical pulses with fixed frequencies and amplitudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IPI), the latter taken from an exponential distribu-A special mention to Ludovico Einaudi who kept me company and inspired me during the long hours of thesis writing and experimental work since day one of these four years of PhD. Finally, I would like to thank Marcela, who has never let me down and has been the greatest support during this journey, nothing would have been possible without her. Thank you for teaching me more about life than any University could ever have.
Journal of Neuroscience Methods, 2020
Background: Peripheral autonomic nerves control visceral organs and convey information regarding ... more Background: Peripheral autonomic nerves control visceral organs and convey information regarding their functional states and are, therefore, potential targets for new therapeutic and diagnostic approaches. Conventionally recorded multi-unit nerve activity in vivo undergoes slow differential drift of signal and noise amplitudes, making accurate monitoring of nerve activity for more than tens of minutes problematic. New Method: We describe an on-line drift compensation algorithm that utilizes recursive least-squares to estimate the relative change in spike amplitude due to changes in the nerve-electrode interface over time. Results: We tested and refined our approach using simulated data and in vivo recordings from nerves supplying the small intestine under control conditions and in response to gut inflammation over several hours. The algorithm is robust to changes in recording conditions and signal-to-noise ratio and applicable to both single and multi-unit recordings. In uncompensated records, drift prevented "spike families" and single units from being discriminated accurately over hours. After rescaling, these were successfully tracked throughout recordings (up to 3 h). Comparison with existing Methods: Existing methods are subjective or compensate for drift using spatial information and spike shape data which is not practical in multi-unit peripheral nerve recordings. In contrast, this method is objective and applicable to data from a single differential multi-unit recording. In comparisons using simulated data the algorithm performed as well as or better than existing methods. Conclusions: Results suggest our drift compensation algorithm is widely applicable and robust, though conservative, when differentiating prolonged responses from drift in signal. Extracellular nerve recordings; drift compensation; chronic nerve recordings; closed-loop; multi-unit activity; spike discrimination; recursive least squares; real-time
Biomaterials, 2019
Implantable medical devices are now in regular use to treat or ameliorate medical conditions, inc... more Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.
Sensing and Bio-Sensing Research, 2019
Biomedical electronic implants require a power source to operate. Miniaturised implants can precl... more Biomedical electronic implants require a power source to operate. Miniaturised implants can preclude batteries and as implant dimensions reduce further, inductive power transfer no longer becomes the optimum strategy for wireless power delivery. Wide dipole antennas are proposed as an alternative power transmitter for long and thin implants. A miniaturised bioelectronic device measuring 1 mm by 1 mm by 20 mm was fabricated, wirelessly powered and used to stimulate retinal ganglion cells to provide biological validation of its functionality. Optimised wide dipole antennas operating in the GHz range for implant depths of 5 mm to 35 mm in 5 mm steps were simulated, fabricated and measured. Saline solution was used as a biological tissue phantom for power transfer efficiency measurements. The maximum safe deliverable power to the device was 1.7 mW in simulation and 1.3 mW in measurement at power transfer efficiencies of 15% and 11% respectively. The work herein confirms that wide dipole transmitting antennas are suitable for radiative near field power transfer to long and thin implants. This power transfer technique could be used for implants that are injectable, deliverable via catheter and minimally invasive, advancing the aim to create smaller more innovative electronic implantable devices.
Sensors and Actuators A: Physical, 2018
Up to 16 Individually addressable and wirelessly powered optogenetic channels Above 10mW of mea... more Up to 16 Individually addressable and wirelessly powered optogenetic channels Above 10mW of measured light output power Inductive multichannel resonant topology removes complex electronics from implant Ability to multiplex and pulse channels by modulating transmission signal Biological validation in porcine tissue, human embryonic kidney cells and retinal ganglion cells
Journal of neural engineering, Jan 19, 2018
Retinal prostheses aim to provide visual percepts to blind people affected by diseases caused by ... more Retinal prostheses aim to provide visual percepts to blind people affected by diseases caused by photoreceptor degeneration. One of the main challenges presented by current devices is neural adaptation in the retina, which is believed to be the cause of fading - an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to understand the neural adaptation generated in retinal ganglion cells (RGCs) during electrical stimulation. Current visual prostheses use electrical pulses with fixed frequencies and amplitudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IP...
2013 Pan American Health Care Exchanges (PAHCE), 2013
ABSTRACT The purpose of this document is to describe and explain the design of a tracking system ... more ABSTRACT The purpose of this document is to describe and explain the design of a tracking system which allows the objective measurement of the kinematic and force variables in tasks oriented to ENT (ear, nose and throat) minimally invasive surgery. The designed device consists of a software and hardware system which records the surgeon's skills while executing training tasks for otorhinolaryngologic surgery on unanimated models. A set of movement, position and pressure sensors, records the path followed by the tip of the surgical instrument. From the records made by these sensors, six different parameters (time, depth perception, path length, motion smoothness, response orientation and force) are calculated and the performance of the surgeon is quantitatively registered. It resulted feasible to determine the skills of the surgeon following this approach.
Journal of Neural Engineering
Objective. Retinal prostheses have had limited success in vision restoration through electrical s... more Objective. Retinal prostheses have had limited success in vision restoration through electrical stimulation of surviving retinal ganglion cells (RGCs) in the degenerated retina. This is partly due to non-preferential stimulation of all RGCs near a single stimulating electrode, which include cells that conflict in their response properties and their contribution to visiual processing. Our study proposes a stimulation strategy to preferentially stimulate individual RGCs based on their temporal electrical receptive fields (tERFs). Approach. We recorded the responses of RGCs using whole-cell patch clamping and demonstrated the stimulation strategy, first using intracellular stimulation, then via extracellular stimulation. Main results. We successfully reconstructed the tERFs according to the RGC response to Gaussian white noise current stimulation. The characteristics of the tERFs were extracted and compared based on the morphological and light response types of the cells. By re-deliver...