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In Vivo Imaging to Characterize Dynamic Tissue Responses after Neural Electrode Implantation

Eles, James (2019) In Vivo Imaging to Characterize Dynamic Tissue Responses after Neural Electrode Implantation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Implantable neural electrodes are promising technologies to restore motor, sensory, and cognitive function in many neural pathologies through brain-computer interfacing (BCI). Many BCI applications require electrode implantation within neural tissue to resolve and/or modulate the physiological activity of individual neurons via electrical recording and stimulation. This invasive implantation leads to acute and long-term deterioration of both the electrode device as well as the neurons surrounding the device. Ultimately, damage to the electrode and neural tissue results in electrode recording failure within the first years after implantation.
Many strategies to improve BCI longevity focus on mitigating tissue damage through improving neuronal survival or reducing inflammatory activity around implants. Despite incremental improvements, electrode failure persists as an obstacle to wide-spread clinical deployment of BCIs. This can be partly attributed to an incomplete understanding of the biological correlates of recording performance. These correlates have largely been identified through post-mortem histological staining, which cannot capture dynamic changes in cellular physiology and morphology.
In the following dissertation, we use longitudinal two-photon in vivo imaging to quantify how neurons, microglia, and meningeal immune cells are affected by an intracortical electrode during and after implantation in mouse cortex. We go beyond conventional histological techniques to show the time-course of neuronal injury and microglial recruitment after implantation. Neuronal injury occurs instantaneously, with prolonged, high calcium levels evident in neurons within 100 µm of implants. Microglial activation occurs within minutes of implantation and subsequent microglial encapsulation of electrodes can be modulated by bioactive surface coatings. Within the first day post-implant, there is high trafficking of peripheral immune cells through venules at the surface of the brain as well as along the electrode’s shank at the surface of the brain. Over the next month, calcium activity in neurons increases while the collagenous meningeal tissues at the surface of the brain thicken. We further show that meningeal thickening can have profound implications for devices implanted into non-human primates as well. In sum, these results define new potential therapeutic targets and windows that could improve the longevity of implantable neural electrodes.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Eles, Jamesjre35@pitt.edujre35
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCui, XTxic11@pitt.eduXIC110000-0002-0470-2005
Committee MemberBatista,
Committee MemberMarra, Kaceykgm5@pitt.edukgm5
Committee MemberKozai, Takashitdk18@pitt.edutdk18
Committee MemberVazquez, Albertoalv15@pitt.edualv15
Date: 21 June 2019
Date Type: Publication
Defense Date: 29 August 2018
Approval Date: 21 June 2019
Submission Date: 27 November 2018
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 237
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Brain-computer interface; Foreign body response; Mechanical trauma; Microelectrode implants; Neuron calcium imaging; Two-photon microscopy; Biomimetic coatings; Protein immobilization; Surface modification
Date Deposited: 21 Jun 2020 05:00
Last Modified: 21 Jun 2020 05:00


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