Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

Kozai, Takashi D. Y.; Jaquins-Gerstl, Andrea S.; Vazquez, Alberto L.; Michael, Adrian C.; Cui, X. Tracy

doi:10.1021/cn500256e

Cited by 622Neuroscience and Neural EngineeringElectrochemical sensors and biosensorsElectrochemical Analysis and Applications

Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

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Kozai, Takashi D. Y., Jaquins-Gerstl, Andrea S., Vazquez, Alberto L., Michael, Adrian C., Cui, X. Tracy·2015·ACS Chemical Neuroscience

DOI 10.1021/cn500256ePMC PMC4304489

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Abstract

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity.

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High power density, constrained by size, is essential to avoid tissue damage and foreign body responses that can affect signal quality across central nervous system sensors over acute and chronic time frames.
“High power density, constrained by size, is essential to avoid tissue damage and foreign body responses, which can further affect the signal quality across all central nervous system sensors over both acute and chronic time frames (Bazaka and Jacob, 2012; Kozai et al., 2015).”
From Comparative analysis of energy transfer mechanisms for neural implants (2024) · cites this paper as Kozai et al., 2015
The Size section says smaller implants can reduce tissue strain and inflammatory responses, while the Introduction says insertion injury and tissue responses can impair signal quality. The paper also describes effects over acute and chronic periods. It does not say that high power density is essential to prevent those effects; the size discussion concerns the implant’s physical dimensions, not its power density. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Intracortical microelectrodes face a decline in recording quality over time.
“Intracortical microelectrodes, used in applications ranging from recent advances in speech-to-text with ALS patients (Willett et al., 2023), allowing primates to play pong (Play Studio, n.d.) to clinical trials for motor deficit treatments (Gilja et al., 2015) face a decline in recording quality over time (Chestek et al., 2011; Jorfi et al., 2014; Kozai et al., 2015).”
From Comparative analysis of energy transfer mechanisms for neural implants (2024) · cites this paper as Kozai et al., 2015
Common sources of recording failures in the CNS include demyelination of adjacent neurons, breakdown of the blood-brain barrier around the implant site, neuronal loss, degradation of the electrode, and formation of a glial sheath around implanted electrodes.
“Common sources of recording failures in the CNS include demyelination of the adjacent neurons, breakdown of the blood-brain barrier around the implant site, neuronal loss, degradation of the electrode, and formation of a glial sheath around implanted electrodes.64,65”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [65]

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Authors: Kozai, T. D. Y., Jaquins-Gerstl, A. S., Vazquez, A. L., Michael, A. C., & Cui, X. T.
Affiliations: University of Pittsburgh (US)
University of Pittsburgh , , , , , ,
Corresponding author: Kozai, Takashi D. Y.
ORCID: Kozai, Takashi D. Y.
Vazquez, Alberto L.
Michael, Adrian C.
Cui, X. Tracy
Venue: ACS Chemical Neuroscience
Publisher: American Chemical Society (ACS)
Published: 2014-12-29
Volume: 6
Issue: 1
Pages: 48-67
ISSN: 1948-7193 (ISSN-L)
DOI: 10.1021/cn500256e
PMC: PMC4304489
OpenAlex: W2090157379
Cited by: 622
References: 230
Citations by year: 2026: 63 · 2025: 68 · 2024: 79 · 2023: 73 · 2022: 38 · 2021: 63 · 2020: 65 · 2019: 56 · 2018: 50 · 2017: 33 · 2016: 20 · 2015: 12 · 2014: 1
FWCI: 2.51
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: other-oa
pubs.acs.org/page/policy/authorchoice_termsofuse.html (vor, 365 d)
Locations: ACS Chemical Neuroscience (publishedVersion, other-oa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (K01 1K01NS066131, R01 5R01NS062019)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
Physical Sciences › Chemistry › Electrochemistry › Electrochemical Analysis and Applications
Keywords: neural implants, implantable biosensors, blood-brain barrier disruption, foreign body reaction, glial activation, signal sensitivity, signal stability, microelectrodes, microdialysis probe, fast-scan cyclic voltammetry, electrophysiology, neurodegeneration, chronic implantation, central nervous system, neuroinflammation
MeSH terms: Animals, Brain, Brain Chemistry, Humans, Microelectrodes, Electrophysiological Phenomena

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Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

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