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News Article | February 16, 2017
Site: phys.org

Grover and his research team have been focused on improving the resolution of EEG neural imaging technology, a portable and non-invasive brain imaging system. Credit: Carnegie Mellon University College of Engineering Writers and scientists throughout history have searched for an apt technological analogy for the human brain, often comparing it to a computer. For Pulkit Grover, Carnegie Mellon University assistant professor of electrical and computer engineering and the Center for Neural Basis of Cognition, this analogy couldn't be more fitting. Although Grover and his research team spend much of their time exploring how information flows through computer networks (such as coding systems, cyberphysical systems, and low-power wireless systems), they also apply these information theory principles to brain-imaging systems. This cross-disciplinary research approach bridges mathematical theory with clinical applications—striving to improve the treatment of neurological disorders such as epilepsy. "It is exciting to be applying my research in the neuroscience and neuroengineering space because I am tackling information theory challenges that have the potential to impact the quality of life of patients, or make a doctor's diagnosis faster and easier—that is the goal I'm always working toward," says Grover. Grover and his research team have been focused on improving the resolution of EEG neural imaging technology, a portable and non-invasive brain imaging system. This research goes against the trend in the field of neuroscience. Many researchers believe that EEG systems are fundamentally limited to imaging resolutions that are too low to be effective, and that it is impossible to improve the resolution of these systems beyond their current levels. "The current overarching view in both clinical and neuroscientific communities is that a different imaging modality needs to be invented. However, it is our view that the potential of EEG has been severely underestimated, and that EEG's low resolution became a self-fulfilling prophecy of sorts," explains Grover. "We are working towards building the first 'Ultra-Resolution EEG' platform. This platform offers important benefits that no other modality currently has, such as high spatiotemporal imaging resolution, while still being portable. It is also more than ten times cheaper than other imaging technologies such as MRI or Magnetoencephalography (MEG), which is important for doctors who will be using this for the treatment and monitoring of their patients." Recently, Grover and electrical and computer engineering Ph.D. student Praveen Venkatesh established the first-ever fundamental limits on EEG imaging, and showed that the reason that most neuroscientists believe EEG has inherently low-resolution is incorrect. These limits show how an earlier study was misunderstood at-large in the field to suggest that low-density systems (with a hundred or so electrodes) obtain the best possible imaging. Grover and Venkatesh explored the question of how many electrodes should be used in this system to provide the best imaging results. "If you improve both the data analysis and the number of electrodes for EEG systems, then you can improve the resolution dramatically," says Grover. "This new theory lays the foundation for exciting experimental work with our Carnegie Mellon BrainHub collaborators. The study, titled "An information-theoretic view of EEG sensing," was published in the Proceedings of the IEEE. The research was conducted as part of Carnegie Mellon's BrainHub, a university initiative that focuses on how the structure and activity of the brain give rise to complex behaviors. Grover and Venkatesh are collaborating extensively across the university to validate these fundamental results and bring them into practical systems. Their collaborators include Marlene Behrmann and Michael Tarr (professors of psychology and the Center for Neural Basis of Cognition), Shawn Kelly (senior systems scientist in the Engineering Research Accelerator), and Jeffrey Weldon (associate professor of electrical and computer engineering). They are also working with Mark Richardson, an epilepsy neurosurgeon at the University of Pittsburgh, to obtain clinical validation and establish relevance in epilepsy. The collaborative team published experimental validation of some of this work at the 2016 Information Theory and Applications Workshop. "To change the widespread perception of EEG technology and get these systems into clinical practice, we need more experimental validation of this theory," Grover concludes. "We are well on our way to getting these validations and I'm looking forward to what the future holds for this research." Explore further: High-resolution brain imaging could improve detection of concussions

Kozai T.D.Y.,University of Pittsburgh | Kozai T.D.Y.,Center for Neural Basis of Cognition | Kozai T.D.Y.,McGowan Institute for Regenerative Medicine | Catt K.,University of Pittsburgh | And 8 more authors.
Biomaterials | Year: 2015

Penetrating intracortical electrode arrays that record brain activity longitudinally are powerful tools for basic neuroscience research and emerging clinical applications. However, regardless of the technology used, signals recorded by these electrodes degrade over time. The failure mechanisms of these electrodes are understood to be a complex combination of the biological reactive tissue response and material failure of the device over time. While mechanical mismatch between the brain tissue and implanted neural electrodes have been studied as a source of chronic inflammation and performance degradation, the electrode failure caused by mechanical mismatch between different material properties and different structural components within a device have remained poorly characterized. Using Finite Element Model (FEM) we simulate the mechanical strain on a planar silicon electrode. The results presented here demonstrate that mechanical mismatch between iridium and silicon leads to concentrated strain along the border of the two materials. This strain is further focused on small protrusions such as the electrical traces in planar silicon electrodes. These findings are confirmed with chronic invivo data (133-189 days) in mice by correlating a combination of single-unit electrophysiology, evoked multi-unit recordings, electrochemical impedance spectroscopy, and scanning electron microscopy from traces and electrode sites with our modeling data. Several modes of mechanical failure of chronically implanted planar silicon electrodes are found that result in degradation and/or loss of recording. These findings highlight the importance of strains and material properties of various subcomponents within an electrode array. © 2014 Elsevier Ltd.

Kozai T.D.Y.,University of Pittsburgh | Kozai T.D.Y.,Center for Neural Basis of Cognition | Kozai T.D.Y.,McGowan Institute for Regenerative Medicine | Gugel Z.,University of Pittsburgh | And 9 more authors.
Biomaterials | Year: 2014

Implantable neural electrodes must drastically improve chronic recording stability before they can be translated into long-term human clinical prosthetics. Previous studies suggest that sub-cellular sized and mechanically compliant probes may result in improved tissue integration and recording longevity. However, currently these design features are restricted by the opposing mechanical requirements needed for minimally damaging insertions. We designed a non-cytotoxic, carboxymethylcellulose (CMC) based dissolvable delivery vehicle (shuttle) to provide the mechanical support for insertion of ultra-small, ultra-compliant microfabricated neural probes. Stiff CMC-based shuttles rapidly soften immediately after being placed ~1mm above an open craniotomy as they absorb vapors from the brain. To address this, we developed a sophisticated targeting, high speed insertion (~80mm/s), and release system to implant these shuttles. After implantation, the goal is for the shuttle to dissolve away leaving only the electrodes behind. Here we show the histology of chronically implanted shuttles of large (300μm×125μm) and small (100μm×125μm) size at discrete time points over 12 weeks. Early time points show the CMC shuttle expanded after insertion as it absorbed moisture from the brain and slowly dissolved. At later time points neuronal cell bodies populate regions within the original shuttle tract. The large CMC shuttles show that the CMC expansion can cause extended secondary damage. On the other hand, the smaller CMC shuttles show limited secondary damage, wound closure by 4 weeks, absence of activated microglia at 12 weeks, as well as evidence suggesting neural regeneration at the implant site. This shuttle, therefore, shows great promise facilitating the implantation of nontraditional ultra-small, and ultra-compliant probes. © 2014 Elsevier Ltd.

Kozai T.D.Y.,University of Pittsburgh | Kozai T.D.Y.,Center for Neural Basis of Cognition | Kozai T.D.Y.,McGowan Institute for Regenerative Medicine | Li X.,University of Pittsburgh | And 8 more authors.
Biomaterials | Year: 2014

Chronic implantation of microelectrodes into the cortex has been shown to lead to inflammatory gliosis and neuronal loss in the microenvironment immediately surrounding the probe, a hypothesized cause of neural recording failure. Caspase-1 (aka Interleukin 1β converting enzyme) is known to play a key role in both inflammation and programmed cell death, particularly in stroke and neurodegenerative diseases. Caspase-1 knockout (KO) mice are resistant to apoptosis and these mice have preserved neurologic function by reducing ischemia-induced brain injury in stroke models. Local ischemic injury can occur following neural probe insertion and thus in this study we investigated the hypothesis that caspase-1 KO mice would have less ischemic injury surrounding the neural probe. In this study, caspase-1 KO mice were implanted with chronic single shank 3mm Michigan probes into V1m cortex. Electrophysiology recording showed significantly improved single-unit recording performance (yield and signal to noise ratio) of caspase-1 KO mice compared to wild type C57B6 (WT) mice over the course of up to 6 months for the majority of the depth. The higher yield is supported by the improved neuronal survival in the caspase-1 KO mice. Impedance fluctuates over time but appears to be steadier in the caspase-1 KO especially at longer time points, suggesting milder glia scarring. These findings show that caspase-1 is a promising target for pharmacologic interventions. © 2014 Elsevier Ltd.

Fisher L.E.,University of Pittsburgh | Fisher L.E.,Center for Neural Basis of Cognition | Ayers C.A.,Center for Neural Basis of Cognition | Ayers C.A.,University of Pittsburgh | And 6 more authors.
Journal of Neural Engineering | Year: 2014

Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 μA biphasic pulses, 200 μs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 μA for Group I and 6.3 ± 2.0 μA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 μA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 μA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 μA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets for sensory neuroprostheses with potential to achieve recruitment of a range of sensory fiber types over multiple months after implantation. © 2014 IOP Publishing Ltd.

Ayers C.A.,Center for Neural Basis of Cognition | Ayers C.A.,University of Pittsburgh | Fisher L.E.,Center for Neural Basis of Cognition | Fisher L.E.,University of Pittsburgh | And 3 more authors.
Journal of Neurophysiology | Year: 2016

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and mediumdiameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lowerlimb amputee. © 2016 the American Physiological Society.

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