Advancements in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, ... more Advancements in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, and optogenetics are revolutionizing scientific understanding of the brain while enabling treatments and preventative measures for a variety of neurological disorders. The grand challenge in neural interface engineering is to seamlessly integrate the interface between neurobiology and engineered technology to record from and modulate neu-rons over chronic timescales. However, the biological inflammatory response to implants, neural degeneration, and long-term material stability diminishes the quality of the interface overtime. Recent advances in functional materials are aimed at engineering solutions for chronic neural interfaces, yet, the development and deployment of neural interfaces designed from novel materials have introduced new challenges that have been largely unad-dressed. Many engineering efforts that solely focus on optimizing individual probe design parameters, such as softness or flexibility, downplay critical multi dimensional interactions between different physical properties of the device that contribute to overall performance and biocompatibility. Moreover, the use of these new materials present substantial new difficulties that must be addressed before regulatory approval for use in human patients is achievable. In this review, the interdependence of different electrode components is highlighted to demonstrate the current material-based challenges facing the field of neural interface engineering.
Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily ... more Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technology limitations, there is a need for decoding algorithms which a) are not dependent upon a large number of neurons for control, b) are adaptable to alternative sources of neuronal input such as local field potentials, and c) require only marginal training data for daily calibrations. Moreover, practical algorithms must recognize when the user is not intending to generate a control output and eliminate poor training data. In this study, we introduce and evaluate a Bayesian Maximum-Likelihood Estimation (bMLE) strategy to address the issues of isolating quality training data and self-paced control. Six animal subjects demonstrate that a multiple state classification task, loosely based on the standard centerout task, can be accomplished with fewer than five engaged neurons while requiring less than ten trials for algorithm training. In addition, untrained animals quickly obtained accurate device control utilizing local field potentials as well as neurons in cingulate cortex, two non-traditional neural inputs.
The ability to control a prosthetic device directly from the neocortex has been demonstrated in r... more The ability to control a prosthetic device directly from the neocortex has been demonstrated in rats, monkeys and humans. Here we investigate whether neural control can be accomplished in situations where (1) subjects have not received prior motor training to control the device (nave user) and (2) the neural encoding of movement parameters in the cortex is unknown to the
ABSTRACT A system for stimulating a baroreflex of a patient that includes a first light source wi... more ABSTRACT A system for stimulating a baroreflex of a patient that includes a first light source with a first emitter for emitting a first light, the first emitter at a first location proximate a target tissue having baroreceptor cells, and a second light source including a second emitter and for emitting a second light, the second emitter at a second location proximate the target tissue. The system also includes a control circuit coupled to the first and the second light sources, the control circuit configured to activate the first and the second light sources such that the first light traverses a first pathway to arrive at and penetrate the first portion of the target tissue and the second light-like traverses a second pathway to arrive at and penetrate the second portion of the target tissue, thereby stimulating the baroreceptor cells and activating a baroreflex of the patient.
... lab with Kevin Page 4. iv and Rio. Rachel Miriani also deserves special thanks. Rachel has wo... more ... lab with Kevin Page 4. iv and Rio. Rachel Miriani also deserves special thanks. Rachel has worked with me on most of my experiments and lord knows I can be stubborn about experiments. She has been a good friend and a ...
ABSTRACT Devices and methods of use for introduction and implantation of an electrode as part of ... more ABSTRACT Devices and methods of use for introduction and implantation of an electrode as part of a minimally invasive technique. An implantable baroreflex activation system includes a control system having an implantable housing, an electrical lead, attachable to the control system, and an electrode structure. The electrode structure is near one end of the electrical lead, and includes a monopolar electrode, a backing material having an effective surface area larger than the electrode, and a releasable pivotable interface to mate with an implant tool. The electrode is configured for implantation on an outer surface of a blood vessel and the control system is programmed to deliver a baroreflex therapy via the monopolar electrode to a baroreceptor within a wall of the blood vessel.
Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily ... more Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technological limitations, there is a need for decoding algorithms which (a) are not dependent upon a large number of neurons for control, (b) are adaptable to alternative sources of neuronal input such as
Conductive polymer coatings can be used to modify traditional electrode recording sites with the ... more Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward
2013 6th International IEEE/EMBS Conference on Neural Engineering (NER), 2013
The ability to selectively deposit platinum black (PtB) on iridium microelectrodes and functional... more The ability to selectively deposit platinum black (PtB) on iridium microelectrodes and functionalize the surface for the purposes of choline sensing was investigated in this study. Platinum black was deposited by cycling 100-200 times between 0.5 V and -0.7 V in a solution of 1 mM K2PtCl6 in 0.1 M KCl. Deposition of PtB showed good chemical stability as well as good adhesion following insertion into agarose gel as a model for brain insertion. Electrode sites were also tested for their oxidative capabilities of hydrogen peroxide during which they showed high current change in response to small concentration changes - attributable to the high surface area of the PtB. Sites were then coated with an enzyme solution containing choline oxidase, and a permselective layer of meta-phenylenediamine was added to filter interferents. Electrode sites yielded a high sensitivity to choline compared to interferents including ascorbic acid and dopamine.
We hypothesized that re-entry into the cell cycle may be associated with reactive gliosis surroun... more We hypothesized that re-entry into the cell cycle may be associated with reactive gliosis surrounding neural prostheses, and that administration of a cell cycle inhibitor (flavopiridol) at the time of surgery would reduce this effect. We investigated the effects of flavopiridol on recording quality and impedance over a 28-day time period and conducted histology at 3 and 28 days post-implantation. Flavopiridol reduced the expression of a cell cycle protein (cyclin D1) in microglia surrounding probes at the 3-day time point. Impedance at 1 kHz was decreased by drug administration across the study period compared to vehicle controls. Correlations between recording (SNR, units) and impedance metrics revealed a small, but statistically significant, inverse relationship between these variables. However, the relationship between impedance and recording quality was not sufficiently strong for flavopiridol to result in an improvement in SNR or the number of units detected. Our data indicate that flavopiridol is an effective, easily administered treatment for reducing impedance in vivo, potentially through inhibiting microglial encapsulation of implanted devices. This strategy may be useful in stimulation applications, where reduced impedance is desirable for achieving activation thresholds and prolonging the lifetime of the implanted power supply. While improvements in recording quality were not observed, a combination of flavopiridol with a second strategy which enhances neuronal signal detection may enhance these results in future studies.
The ability to control a prosthetic device directly from the neocortex has been demonstrated in r... more The ability to control a prosthetic device directly from the neocortex has been demonstrated in rats, monkeys and humans. Here we investigate whether neural control can be accomplished in situations where (1) subjects have not received prior motor training to control the device (naïve user) and (2) the neural encoding of movement parameters in the cortex is unknown to the prosthetic device (naïve controller). By adopting a decoding strategy that identifies and focuses on units whose firing rate properties are best suited for control, we show that naïve subjects mutually adapt to learn control of a neural prosthetic system. Six untrained Long-Evans rats, implanted with silicon micro-electrodes in the motor cortex, learned cortical control of an auditory device without prior motor characterization of the recorded neural ensemble. Single-and multi-unit activities were decoded using a Kalman filter to represent an audio 'cursor' (90 ms tone pips ranging from 250 Hz to 16 kHz) which subjects controlled to match a given target frequency. After each trial, a novel adaptive algorithm trained the decoding filter based on correlations of the firing patterns with expected cursor movement. Each behavioral session consisted of 100 trials and began with randomized decoding weights. Within 7 ± 1.4 (mean ± SD) sessions, all subjects were able to significantly score above chance (P < 0.05, randomization method) in a fixed target paradigm. Training lasted 24 sessions in which both the behavioral performance and signal to noise ratio of the peri-event histograms increased significantly (P < 0.01, ANOVA). Two rats continued training on a more complex task using a bilateral, two-target control paradigm. Both subjects were able to significantly discriminate the target tones (P < 0.05, Z-test), while one subject demonstrated control above chance (P < 0.05, Z-test) after 12 sessions and continued improvement with many sessions achieving over 90% correct targets. Dynamic analysis of binary trial responses indicated that early learning for this subject occurred during session 6. This study demonstrates that subjects can learn to generate neural control signals that are well suited for use with external devices without prior experience or training.
Conductive polymer coatings can be used to modify traditional electrode recording sites with the ... more Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard 'Michigan' probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.
We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, g... more We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, gold recording electrodes with initial impedances outside of the effective recording range. Smaller electrode sites enable more densely packed arrays, increasing the number of input and output channels to and from the brain. Moreover, smaller electrode sizes promote smaller probe designs; decreasing the dimensions of the implanted probe has
Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily ... more Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technology limitations, there is a need for decoding algorithms which a) are not dependent upon a large number of neurons for control, b) are adaptable to alternative sources of neuronal input such as local field potentials, and c) require only marginal training data for daily calibrations. Moreover, practical algorithms must recognize when the user is not intending to generate a control output and eliminate poor training data.
Advancements in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, ... more Advancements in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, and optogenetics are revolutionizing scientific understanding of the brain while enabling treatments and preventative measures for a variety of neurological disorders. The grand challenge in neural interface engineering is to seamlessly integrate the interface between neurobiology and engineered technology to record from and modulate neu-rons over chronic timescales. However, the biological inflammatory response to implants, neural degeneration, and long-term material stability diminishes the quality of the interface overtime. Recent advances in functional materials are aimed at engineering solutions for chronic neural interfaces, yet, the development and deployment of neural interfaces designed from novel materials have introduced new challenges that have been largely unad-dressed. Many engineering efforts that solely focus on optimizing individual probe design parameters, such as softness or flexibility, downplay critical multi dimensional interactions between different physical properties of the device that contribute to overall performance and biocompatibility. Moreover, the use of these new materials present substantial new difficulties that must be addressed before regulatory approval for use in human patients is achievable. In this review, the interdependence of different electrode components is highlighted to demonstrate the current material-based challenges facing the field of neural interface engineering.
Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily ... more Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technology limitations, there is a need for decoding algorithms which a) are not dependent upon a large number of neurons for control, b) are adaptable to alternative sources of neuronal input such as local field potentials, and c) require only marginal training data for daily calibrations. Moreover, practical algorithms must recognize when the user is not intending to generate a control output and eliminate poor training data. In this study, we introduce and evaluate a Bayesian Maximum-Likelihood Estimation (bMLE) strategy to address the issues of isolating quality training data and self-paced control. Six animal subjects demonstrate that a multiple state classification task, loosely based on the standard centerout task, can be accomplished with fewer than five engaged neurons while requiring less than ten trials for algorithm training. In addition, untrained animals quickly obtained accurate device control utilizing local field potentials as well as neurons in cingulate cortex, two non-traditional neural inputs.
The ability to control a prosthetic device directly from the neocortex has been demonstrated in r... more The ability to control a prosthetic device directly from the neocortex has been demonstrated in rats, monkeys and humans. Here we investigate whether neural control can be accomplished in situations where (1) subjects have not received prior motor training to control the device (nave user) and (2) the neural encoding of movement parameters in the cortex is unknown to the
ABSTRACT A system for stimulating a baroreflex of a patient that includes a first light source wi... more ABSTRACT A system for stimulating a baroreflex of a patient that includes a first light source with a first emitter for emitting a first light, the first emitter at a first location proximate a target tissue having baroreceptor cells, and a second light source including a second emitter and for emitting a second light, the second emitter at a second location proximate the target tissue. The system also includes a control circuit coupled to the first and the second light sources, the control circuit configured to activate the first and the second light sources such that the first light traverses a first pathway to arrive at and penetrate the first portion of the target tissue and the second light-like traverses a second pathway to arrive at and penetrate the second portion of the target tissue, thereby stimulating the baroreceptor cells and activating a baroreflex of the patient.
... lab with Kevin Page 4. iv and Rio. Rachel Miriani also deserves special thanks. Rachel has wo... more ... lab with Kevin Page 4. iv and Rio. Rachel Miriani also deserves special thanks. Rachel has worked with me on most of my experiments and lord knows I can be stubborn about experiments. She has been a good friend and a ...
ABSTRACT Devices and methods of use for introduction and implantation of an electrode as part of ... more ABSTRACT Devices and methods of use for introduction and implantation of an electrode as part of a minimally invasive technique. An implantable baroreflex activation system includes a control system having an implantable housing, an electrical lead, attachable to the control system, and an electrode structure. The electrode structure is near one end of the electrical lead, and includes a monopolar electrode, a backing material having an effective surface area larger than the electrode, and a releasable pivotable interface to mate with an implant tool. The electrode is configured for implantation on an outer surface of a blood vessel and the control system is programmed to deliver a baroreflex therapy via the monopolar electrode to a baroreceptor within a wall of the blood vessel.
Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily ... more Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technological limitations, there is a need for decoding algorithms which (a) are not dependent upon a large number of neurons for control, (b) are adaptable to alternative sources of neuronal input such as
Conductive polymer coatings can be used to modify traditional electrode recording sites with the ... more Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward
2013 6th International IEEE/EMBS Conference on Neural Engineering (NER), 2013
The ability to selectively deposit platinum black (PtB) on iridium microelectrodes and functional... more The ability to selectively deposit platinum black (PtB) on iridium microelectrodes and functionalize the surface for the purposes of choline sensing was investigated in this study. Platinum black was deposited by cycling 100-200 times between 0.5 V and -0.7 V in a solution of 1 mM K2PtCl6 in 0.1 M KCl. Deposition of PtB showed good chemical stability as well as good adhesion following insertion into agarose gel as a model for brain insertion. Electrode sites were also tested for their oxidative capabilities of hydrogen peroxide during which they showed high current change in response to small concentration changes - attributable to the high surface area of the PtB. Sites were then coated with an enzyme solution containing choline oxidase, and a permselective layer of meta-phenylenediamine was added to filter interferents. Electrode sites yielded a high sensitivity to choline compared to interferents including ascorbic acid and dopamine.
We hypothesized that re-entry into the cell cycle may be associated with reactive gliosis surroun... more We hypothesized that re-entry into the cell cycle may be associated with reactive gliosis surrounding neural prostheses, and that administration of a cell cycle inhibitor (flavopiridol) at the time of surgery would reduce this effect. We investigated the effects of flavopiridol on recording quality and impedance over a 28-day time period and conducted histology at 3 and 28 days post-implantation. Flavopiridol reduced the expression of a cell cycle protein (cyclin D1) in microglia surrounding probes at the 3-day time point. Impedance at 1 kHz was decreased by drug administration across the study period compared to vehicle controls. Correlations between recording (SNR, units) and impedance metrics revealed a small, but statistically significant, inverse relationship between these variables. However, the relationship between impedance and recording quality was not sufficiently strong for flavopiridol to result in an improvement in SNR or the number of units detected. Our data indicate that flavopiridol is an effective, easily administered treatment for reducing impedance in vivo, potentially through inhibiting microglial encapsulation of implanted devices. This strategy may be useful in stimulation applications, where reduced impedance is desirable for achieving activation thresholds and prolonging the lifetime of the implanted power supply. While improvements in recording quality were not observed, a combination of flavopiridol with a second strategy which enhances neuronal signal detection may enhance these results in future studies.
The ability to control a prosthetic device directly from the neocortex has been demonstrated in r... more The ability to control a prosthetic device directly from the neocortex has been demonstrated in rats, monkeys and humans. Here we investigate whether neural control can be accomplished in situations where (1) subjects have not received prior motor training to control the device (naïve user) and (2) the neural encoding of movement parameters in the cortex is unknown to the prosthetic device (naïve controller). By adopting a decoding strategy that identifies and focuses on units whose firing rate properties are best suited for control, we show that naïve subjects mutually adapt to learn control of a neural prosthetic system. Six untrained Long-Evans rats, implanted with silicon micro-electrodes in the motor cortex, learned cortical control of an auditory device without prior motor characterization of the recorded neural ensemble. Single-and multi-unit activities were decoded using a Kalman filter to represent an audio 'cursor' (90 ms tone pips ranging from 250 Hz to 16 kHz) which subjects controlled to match a given target frequency. After each trial, a novel adaptive algorithm trained the decoding filter based on correlations of the firing patterns with expected cursor movement. Each behavioral session consisted of 100 trials and began with randomized decoding weights. Within 7 ± 1.4 (mean ± SD) sessions, all subjects were able to significantly score above chance (P < 0.05, randomization method) in a fixed target paradigm. Training lasted 24 sessions in which both the behavioral performance and signal to noise ratio of the peri-event histograms increased significantly (P < 0.01, ANOVA). Two rats continued training on a more complex task using a bilateral, two-target control paradigm. Both subjects were able to significantly discriminate the target tones (P < 0.05, Z-test), while one subject demonstrated control above chance (P < 0.05, Z-test) after 12 sessions and continued improvement with many sessions achieving over 90% correct targets. Dynamic analysis of binary trial responses indicated that early learning for this subject occurred during session 6. This study demonstrates that subjects can learn to generate neural control signals that are well suited for use with external devices without prior experience or training.
Conductive polymer coatings can be used to modify traditional electrode recording sites with the ... more Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard 'Michigan' probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.
We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, g... more We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, gold recording electrodes with initial impedances outside of the effective recording range. Smaller electrode sites enable more densely packed arrays, increasing the number of input and output channels to and from the brain. Moreover, smaller electrode sizes promote smaller probe designs; decreasing the dimensions of the implanted probe has
Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily ... more Brain-machine interface decoding algorithms need to be predicated on assumptions that are easily met outside of an experimental setting to enable a practical clinical device. Given present technology limitations, there is a need for decoding algorithms which a) are not dependent upon a large number of neurons for control, b) are adaptable to alternative sources of neuronal input such as local field potentials, and c) require only marginal training data for daily calibrations. Moreover, practical algorithms must recognize when the user is not intending to generate a control output and eliminate poor training data.
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Papers by Kip Ludwig