See you at SfN

posted Nov 2, 2018, 10:11 AM by Bionic Lab   [ updated Nov 2, 2018, 10:12 AM ]

November 5, 2018, 8:00 AM
271.09. Calcium activation of frequency dependent, phasic, localized, and dense population of cortical neurons by continuous electrical stimulation
1Bioengineering, 2Biomed. Engin., 3Radiology, Univ. of Pittsburgh, Pittsburgh, PA; 4Neurologic Surgery, Mayo Clin., Rochester, MN
Session: Nanosymposium: 271 - Brain-Machine Interface

November 7, 2018, 8:00 AM

658.12. A time course study of melatonin's effect on microglia responses to neural implants as revealed by two-photon imaging

Univ. of Pittsburgh, Oakland, PA
Session: Poster: 658 - Neurotoxicity, Inflammation, and Neuroprotection: Neuroinflammation: Microglia
November 7, 2018, 1:00 PM
769.01. Microelectrode implantation induces pericyte reactivity and vascular bed reorganization as revealed by two-photon microscopy
Dept. of Bioengineering, Univ. of Pittsburgh, Pittsburgh, PA
Session: Poster: 769 - Histologic Responses to Electrode Insertion

November 7, 2018, 1:00 PM
736.23. Effect of APOE lipoproteins on microglial response to intracranial infusion of Aβ - in vivo two-photon imaging and transcriptomic analysis
1Envrn. & Occup. Hlth., 2Bioengineering, Univ. of Pittsburgh, Pittsburgh, PA
Session: Poster: 736 - Alzheimer's Disease and Other Dementias: Neuroinflammation

Upcoming Gordon Conference on Neuroelectronic Interface

posted Feb 8, 2018, 9:47 AM by Bionic Lab   [ updated Feb 8, 2018, 9:47 AM ]

PITTSBURGH (February 6, 2018) ... Takashi Kozai, assistant professor of bioengineering at the University of Pittsburgh Swanson School of Engineering, will act as co-vice chair at the inaugural Gordon Research Conference on Neuroelectronic Interfaces. The meeting will take place March 25-30, 2018 in Galveston, Texas.

Neuroelectronic interfaces -commonly known as brain-machine (or brain-computer) interfaces- create a direct communication line from the central nervous system to the outside world. This connection allows scientists to research ways to rehabilitate those with paralysis, other forms of motor dysfunction, or limb loss.

“One major limitation for practical clinical translation, despite nearly 60 years of chronic neural interface research, is that there remains a poor understanding of the complex biological and material failure modes across all classes of microelectrode arrays,” Kozai explains. “Among several classes of multi-modal problems encountered, the strong foreign body response, scar tissue formation, and implant material breakdown over time are critical obstacles. These issues ultimately lead to an electrical decoupling of implanted devices from the brain and a loss of signal.” 

“Our inaugural Gordon Research Conference (GRC) on Neuroelectronic Interfaces will challenge the international field to turn back to the drawing board of basic materials research armed with emerging basic neurosciences knowledge,” Kozai says.

The event will bring together a multi-disciplinary team of leading experts in cellular neuroscience, brain pathology, neuro-technology and materials science to discuss and eventually solve these challenges in order to achieve a chronically useful and reliable neural interface.

Kozai leads the Bio-Integrating Optoelectric Neural Interface & Cybernetics Lab (B.I.O.N.I.C. Lab) in the Swanson School of Engineering. The lab takes a multidisciplinary approach to better understand interactions at micro-scale neural interfaces and develop next-generation neural technologies that reduce or reverse negative tissue interactions.

“As both scientific knowledge and technological advances progress, we’re finding that many of the assumptions that were made in the field are limited in scope, or incomplete,” Kozai says. “As a result, we see more and more of these dogmas fall apart as we push the limits of engineering.”

As part of the five-day event, Kozai will lead a discussion on “Biomechanics of the Device-Tissue Interface.” The program also includes Xinyan Tracy Cui, William Kepler Whiteford Professor of Bioengineering at Pitt, who will present a talk titled “Biomimetic Strategy for Seamless Neural Electrode-Tissue Integration.”

“The Gordon Research Conference is unlike most other conferences in that you get to spend a week sitting shoulder to shoulder with the leaders in the field to discuss new ideas and emerging research and development,” Kozai says. “We’ve been fortunate enough to bring together an all-star list of the world’s expert scientists and engineers.”

Applications for this meeting must be submitted by February 25, 2018.


See the research being done at Pitt’s Human Neural Prosthetics Program:


Contact: Leah Russell

re:posted from:

Nature BME Highlights

posted Feb 8, 2018, 9:45 AM by Bionic Lab   [ updated Feb 8, 2018, 9:45 AM ]

PITTSBURGH (January 8, 2018) … Implanted devices send targeted electrical stimulation to the nervous system to interfere with abnormal brain activity, and it is commonly assumed that neurons are the only important brain cells that need to be stimulated by these devices. However, research published in Nature Biomedical Engineering reveals that it may also be important to target the supportive glial cells surrounding the neurons.
The collaboration was led by Erin Purcell, assistant professor of biomedical engineering at Michigan State University; Joseph W. Salatino, Purcell’s graduate student researcher; Kip A. Ludwig, associate director of technology at Mayo Clinic; and Takashi Kozai, assistant professor of bioengineering at the University of Pittsburgh’s Swanson School of Engineering.
“Glial cells are the most abundant in the central nervous system and critical to the function of the neuronal network,” Kozai says. “The most obvious function of glial cells has been related to their role in forming scar tissue to prevent the spread of injury and neuronal degeneration, but so much about their role in the brain is unknown.”
The study, “Glial responses to implanted electrodes in the brain” (doi:10.1038/s41551-017-0154-1)  suggests that these glial cells are more functional than previously thought. “From providing growth factor support and ensuring proper oxygen and nutrient delivery to the brain to trimming of obsolete synapses and recycling waste products, recent findings show that glial cells do much more to ensure brain activity is optimized,” Kozai says.
The slow, dim signals of glial cells are much more difficult to detect than the vibrant electrical activity of neurons. New advancements in technology allows researchers like Kozai to detect the subtleties of glial cell activity, and these observations are shedding new light on current issues plaguing implant devices and the treatment of neurological disease.
Kozai explains, “Dysfunction in glial cells has been implicated as a cause and/or major contributor to an increasing number of neurological and developmental diseases. Therefore, it stands to reason that targeting these glial cells (in lieu of or in combination with neurons) may dramatically improve current treatments.”
Kozai leads the Bionic Lab at Pitt, where researchers are investigating the biological tissue response to implantable technologies. Although there have been many advancements in neural implant technology in recent years, their underlying effects and reasons for their failure still puzzle scientists. By using advanced microscopy techniques, researchers can create more detailed neurological maps and imaging.
“By combining in vivo multiphoton microscopy and in vivo electrophysiology, our lab is better able to visualize how cells move and change over time in the living brain and explain how changes in these glial cells alter the visually evoked neural network activity,” says Kozai. “Using this approach to better understand these cells can help guide implant design and success.”
Kozai’s lab is currently working with Franca Cambi, professor of neurology at Pitt, on a project to understand the role of another type of glial cell on brain injury and neuronal activity. “Oligodendrocyte Progenitor Cells,” or OPCs, are progenitor cells—similar to stem cells—that have the capacity to differentiate during tissue repair.
“Although OPCs have been understudied in brain-computer interface, they form direct synapses with neurons and are critical to their repair,” explains Kozai. “As progenitor cells, they have the capacity to differentiate into a variety of cells, including neurons. The technology is advancing to the point in which we can have a much better understanding of how the brain works comprehensively, rather than just focusing on neurons because their electrical signals make them appear brighter when imaging the brain.”

re-posted from:

Society for Neuroscience

posted Nov 9, 2017, 6:32 PM by Bionic Lab   [ updated Nov 9, 2017, 6:33 PM ]

Come see our posters (including a dynamic poster) Tuesday November 14, 2017, 1:00 - 5:00 PM

595.14 / DP10/KK17 - Multi-scale, multi-modal analysis of the brain tissue-implant interface reveals new depths of the biological research field at the neuroelectronic interface [LINK]

595.03 / KK6 - In vivo 2-photon microscopy mapping of acute mechanical damage due to neural electrode array implantation [LINK]

595.07 / KK10 - CLARITY based 3D histology assessment of neural electrodes with antifouling coating implanted in mouse cortex [LINK]

Multimodal Microelectrode Failure Analysis Reveals Complex Relationship at the Neural Interface @ ECS

posted Oct 2, 2017, 2:58 AM by Bionic Lab   [ updated Oct 2, 2017, 2:59 AM ]

   Penetrating microelectrode arrays that can record extracellular action potentials from small, targeted groups of neurons are critical for basic neuroscience research and emerging clinical applications. However, these electrode devices suffer from reliability and variability issues which impact their performance on the order of months to years. The failure mechanisms of these electrodes are understood to be a complex combination of the biotic and abiotic failure modes.

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, BBB leakage, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. The resulting inflammation is a key hypothesized cause of neural recording failure. However, previous attempt so directly correlate recording performance, to impedance, and to histological outcomes have led counter-intuitive and sometimes conflicting outcomes.

One reason is that many neurons remain quiescent during anesthetized or resting-state conditions. We previously demonstrated this by visually evoked stimulation paradigms of the contralateral eye in order to evaluate chronic recording performance of linear silicon electrode in the primary visual cortex. Additional, multiphoton analysis using GCaMP6 transgenic animals further confirmed these results. More recently, there has been a growing interesting recording during awake free-roaming conditions in the primary motor cortex in order to avoid resting-state related quiescent activity. However, this in turn leads to increases in Lenz’s Law related artefacts that have the same time constants and waveform shapes as action potentials in rodents, but not NHP. While behaviorally training animals to remain immobile could improve outcomes, it also introduces the potential for Experimenter Expectancy Effect bias on the outcomes.

The visual stimulation paradigm enable the use of current source density analysis to electrophysiologically identify Layer II/III, IV, and V in the cortex. This, in turn, allowed correlation of electrophysiological layers to the histological layers based on section depth and the differences in neural morphology and density. Our findings from electrophysiology, impedance spectroscopy, and post-mortem histology demonstrate a very poor relationship between histology and impedance to electrophysiology. For example, tissue with low-levels of glial encapsulation, healthy neuronal proximity, and low impedance can still have poor recording performance, even with neural activity is behaviorally driven.

Even when histology confirms a perfect tissue interface, cracking or delamination of insulation on the microelectrode has been linked to a drop in impedance and a loss of recording failure. In contrast, cracking of the electrical trace and delamination of the recording site has been linked to recording failure through a jump in electrical impedance. As such, several modes of mechanical failure of chronically implanted planar silicon electrodes were found that result in degradation and/or loss of recording. Our findings highlight the importance of strains and material properties of various subcomponents within an electrode array and the poor reliability of determining electrode viability through electrochemical impedance spectroscopy.

Interestingly, we discovered in a number of situations that even with good neural density, uncompromised electrode material, and good impedances, recording performance can sometimes completely degrade. New multimodal analysis demonstrates the importance of capturing dynamic information, such as with in vivo multiphoton study, and that the presence of neurons does not guarantee functional neural activity over time. We further demonstrate that the foundation of assumptions and simplification made in the field for neural interface research are not true or incomplete. To solve the longstanding chronic neural interface problem, we need to first understand the complexity of the problem.

  • © 2017 ECS - The Electrochemical Society

ACS Chemical Neuroscience: Most Cited Papers from 2015

posted Aug 22, 2017, 11:57 AM by Bionic Lab   [ updated Aug 22, 2017, 11:58 AM ]

"The most cited paper from 2015 thus far, is a review article from Kozai and co-workers at the University of Pittsburgh and the McGowan Center for Regenerative Medicine entitled “Brain tissue responses to neural implants impact signal sensitivity and intervention strategies” (DOI: 10.1021/cn500256e).(2) This review was in the biannual special issue on Monitoring Molecules, edited by Prof. Anne Andrews. The review focused on the complex molecular and cellular changes that occur when a device breaches the blood-brain barrier and is implanted. The review does a fantastic job summarizing the magnitude, variability, and time course (of acute, seconds to minutes, and chronic, week to months) of injuries and responses to the introduction of foreign bodies into the brain. The review ends with reflections on how and deeper understanding of these complex issues might lead to devices with improved sensitivity and longevity.(2) This is truly a must read."

Save the Date: GRC on Neuroelectronic Interfaces

posted Apr 19, 2017, 1:50 PM by Bionic Lab   [ updated Apr 19, 2017, 1:51 PM ]

1st Gordon Research Conference on Neuroelectronic Interfaces

posted Apr 4, 2017, 2:02 PM by Bionic Lab   [ updated Apr 4, 2017, 2:02 PM ]

Beyond Feasibility - Bridging the Gap in Neuroelectronic Interfaces


March 25-30, 2018


Hotel Galvez

Galveston, TX
  Site Information


Ulrich Hofmann &
Jeffrey R. Capadona

Vice Chairs:
Thomas Stieglitz &
Takashi Kozai

Application Deadline

Applications for this meeting must be submitted by February 25, 2018. Please apply early, as some meetings become oversubscribed (full) before this deadline. If the meeting is oversubscribed, it will be stated here. Note: Applications for oversubscribed meetings will only be considered by the Conference Chair if more seats become available due to cancellations.

Please note: The online application form for 2018 meetings will be available in April.

Meeting Description

Neuroelectronic interfaces bridge the central nervous system to the outside world and hold great potential for functional restoration in persons with paralysis, other forms of motor dysfunction, or limb loss. Such rehabilitative applications are commonly referred to as brain machine (or brain computer) interfaces. With a variety of signal transducing systems and processing algorithms, extracted neural signals were shown to be useful to drive external devices such as limb prostheses or computers. A number of types of recording electrode devices have been developed to access different forms of neural information through varying levels of invasiveness. However, many researchers believe that recording devices that penetrate into specific regions of the brain will provide the most useful control signals for complex BMI applications. Despite the potential that penetrating intracortical microelectrodes have shown, widespread implementation is impeded by the inability to consistently record high quality neural signals over clinically relevant time frames.

The last years showed both an increasing interest into the cellular reasons and pathological causes for this slow-down in bridging the translational gap on one side and a new range of materials and methods appearing from the developmental pipelines like Graphene and Nanomaterials on the other side. Therefore, our inaugural Gordon Research Conference (GRC) on Neuroelectronic Interfaces will challenge the international field to turn back to the drawing board of basic materials research armed with emerging fundamental neurosciences knowledge, and bring together a multi-disciplinary team of leading experts in cellular neuroscience, brain pathology, neuro-technology and materials science in order to discuss and eventually solve or discard the obstacles on the quest for a chronically useful and reliable neural interface.

Preliminary Program

The topics and speakers for the conference sessions are displayed below (italics denote discussion leaders). The Conference Chair is currently developing their detailed program, which will include the complete meeting schedule, as well as the talk titles for all speakers. The detailed program will be available by November 25, 2017. Please check back for updates.

  • Brain-Machine Interfaces
    (A. Ajiboye / Richard Andersen / Robert Kirsch / Miguel Nicolelis)
  • Neuropathology – The Brain's Response to Injury
    (Maria Asplund / Carola Haas / Alex Huang / Marco Prinz)
  • Brain Implants – State of the Art
    (Kip Ludwig / Cindy Chestek / Stephanie Lacour / Patrick Ruther / Philip Troyk)
  • Functional Materials and Brain
    (Simon Thiele / Polina Anikeeva / Elisa Castagnola / Jurgen Ruhe / Walter Voit)
  • Neurophotonics and Brain Implants
    (Justin Williams / Ilka Diester / Erin Purcell / Daniel Razansky / Cristin Welle)
  • Biomechanics of the Device-Tissue Interface
    (Kevin Otto / James Fawcett / Ellen Kuhl / Jit Muthuswamy)
  • Soft Matter Interactions in Brain Implants
    (Manfred Radmacher / Xinyan Cui / Yael Hanein)
  • Device Biologisation and Stem Cells
    (Ana Paula / D. Kacy Cullen / Davide Ricci / John Wolf)
  • Nanotools in Neural Interfacing
    (Joseph Pancrazio / Edward Boyden / Hilton Kaplan / Chong Xie)   

See you at SfN

posted Nov 11, 2016, 7:11 AM by Bionic Lab   [ updated Nov 11, 2016, 7:11 AM ]

Nov. 13, 2016, 11:00 AM
Short talk at Blackrock Microsystem Booth  (#1129) at SfN
Preclinical assessment of bioactive coatings on Utah Arrays in rodents

Nov. 14, 2016, 1:00 - 5:00 PM
438.07 / WW5 - Evaluation of neural cell adhesion molecule L1 coating for improved chronic recordings 
438.08 / WW6 - Dexamethasone retrodialysis attenuates microglial response to implanted probes In vivo
438.14 / WW12 - In vivo 2-photon imaging of neural implants: surface modification with L1CAM camouflages devices from microglial encapsulation 

Neuroadhesive L1 coating attenuates acute microglial attachment to neural electrodes as revealed by live two-photon microscopy. Biomaterials. (Accepted)

posted Nov 6, 2016, 12:56 PM by Bionic Lab   [ updated Nov 6, 2016, 12:57 PM ]

Eles JR, Vazquez AL, Snyder NR, Lagenaur C, Murphy MC, Kozai TDY*†, Cui XT*†.

Implantable neural electrode technologies for chronic neural recordings can restore functional control to paralysis and limb loss victims through brain-machine interfaces. These probes, however, have high failure rates partly due to the biological responses to the probe which generates an inflammatory scar and subsequent neuronal cell death. L1 is a neuronal specific cell adhesion molecule and has been shown to minimize glial scar formation and promote electrode-neuron integration when covalently attached to the surface of neural probes. In this work, the acute microglial response to L1-coated neural probes was evaluated in vivo by implanting coated devices into the cortex of mice with fluorescently labeled microglia, and tracking microglial dynamics with multi-photon microscopy for the ensuing 6 h in order to understand L1's cellular mechanisms of action. Microglia became activated immediately after implantation, extending processes towards both L1-coated and uncoated control probes at similar velocities. After the processes made contact with the probes, microglial processes expanded to cover 47.7% of the control probes' surfaces. For L1-coated probes, however, there was a statistically significant 83% reduction in microglial surface coverage. This effect was sustained through the experiment. At 6 h post-implant, the radius of microglia activation was reduced for the L1 probes by 20%, shifting from 130.0 to 103.5 μm with the coating. Microglia as far as 270 μm from the implant site displayed significantly lower morphological characteristics of activation for the L1 group. These results suggest that the L1 surface treatment works in an acute setting by microglial mediated mechanisms.

1-10 of 23