Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex

McCreery, Douglas B.; Cogan, Stuart F.; Kane, Sheryl R.; Pikov, Victor

doi:10.1088/1741-2560/13/3/036012

Cited by 69 publications

(79 citation statements)

References 38 publications

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“…Nevertheless, a few lines of indirect evidence support the idea that glial encapsulation acts as a barrier to signal detection by implanted electrodes 37,43,60 . Astrogliosis, as identified by increased glial fibrillary acidic protein (GFAP) immunoreactivity, was associated with reduced recording quality of Utah-style arrays implanted in the rat cortex in a study that investigated the relationship between histology and recording quality 37 .…”

Section: Consequences Of Glial Encapsulationmentioning

confidence: 99%

Glial responses to implanted electrodes in the brain

et al. 2017

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The use of implants that can electrically stimulate or record electrophysiological or neurochemical activity in nervous tissue is rapidly expanding. Despite remarkable results in clinical studies and increasing market approvals, the mechanisms underlying the therapeutic effects of neuroprosthetic and neuromodulation devices, as well as their side effects and reasons for their failure, remain poorly understood. A major assumption has been that the signal-generating neurons are the only important target cells of neural-interface technologies. However, recent evidence indicates that the supporting glial cells remodel the structure and function of neuronal networks and are an effector of stimulation-based therapy. Here, we reframe the traditional view of glia as a passive barrier, and discuss their role as an active determinant of the outcomes of device implantation. We also discuss the implications that this has on the development of bioelectronic medical devices.

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Section: Consequences Of Glial Encapsulationmentioning

confidence: 99%

Glial responses to implanted electrodes in the brain

et al. 2017

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“…Neural implant tissue compatibility and functionality are not always highly correlated [34,99,100]. Therefore, validating the functional performance of novel neural electrode designs is critical for future applications.…”

Section: Discussionmentioning

confidence: 99%

Ultrasoft microwire neural electrodes improve chronic tissue integration

et al. 2017

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Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8 weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants.

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“…No published quantification of the insertion force and compression distance exists, but significant bleeding has been reported 15,16 . Potentially related to this issue, the histology clearly shows encapsulation around the shank tips 15,17,18 with a typical electrode-tip to axon distance of 40 to 150 µm. The resulting tissue restructuring around these microelectrodes prevents high-fidelity chronic recording, although it is still effective in recording population-based compound action potentials and for electrical stimulation 19 .…”

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confidence: 99%

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

Sperry

et al. 2018

Preprint

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The ability to deliver highly compliant biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural engineering.Bioelectronic devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of interest. We demonstrate that a novel diamond shuttle can deliver ultra-compliant polymer microelectrodes to intraneural structures with the smallest cross-sectional area and dimpling reported to date. This was demonstrated in vivo through rat dura mater and feline dura and dorsal root epineurium. The dorsal root ganglia are an especially relevant target for organ function and pain research, and unlike dura mater over the brain, its outer membrane cannot be removed surgically. We present a method of creating a unique diamond shuttle, only 11 microns thick with a T-beam vertical support, that pierces dura and epineurium. This T-beam structure reduced the cross-sectional area of the shuttle by 58% relative to an equivalently stiff silicon shuttle. We also discovered that higher frequency oscillation of the shuttle, at 200 Hz, significantly reduced tissue compression regardless of the insertion speed, while slow speeds independently also reduced tissue compression. Finally, we demonstrate the shuttle delivery of and neural recordings from ultra-fine, flexible arrays (5-µm thick, 65-µm wide) with 60 microelectrodes in a 1.2-mm span from different neural targets. This novel microelectrode shuttle has a large design space making it suitable for research in a variety of central and peripheral nervous system targets and animal models. IntroductionImplantable sensor arrays, especially when deployed in neural mapping studies, are most accurate and insightful when damage and disruption to nervous system circuitry is minimized. Minimizing damage and reactivity has been emphasized by recent global initiatives including the BRAIN Initiative, the NIH SPARC program, the GSK Innovation Challenge, and several DARPA funding programs, which have supported the development of new technology for mapping, monitoring, and/or controlling the nervous system with higher fidelity and longevity. Previous work demonstrated that size of an implant effects the neuron count and several glia markers of reactivity 12 . A precise implant size to tissue damage function is still missing, but evidence suggests that care should be taken to minimize the damage to blood vessels which densely permeate nervous tissue 3,4 . Central nervous system (CNS) neurons, for example, are located within ~15 µm of a capillary vessel 5-7 so damage to the blood-brain barrier is unavoidable.When designing an implantable device, the penetrating structure must be stiff enough to reach the desired target with accuracy and, more challenging, piercing a tough fibrous outer membrane protecting the neurons.These challenges have opposing solutions -make the device as fine as possible for minimal bleeding and cellular disruption, yet ens...

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Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex

Cited by 69 publications

References 38 publications

Glial responses to implanted electrodes in the brain

Glial responses to implanted electrodes in the brain

Ultrasoft microwire neural electrodes improve chronic tissue integration

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

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