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PhD Dissertation_Bozorgzadeh.pdf (16.48 MB)

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Integrated Microsystems for High-Fidelity Sensing and Manipulation of Brain Neurochemistry

Bozorgzadeh, Bardia
http://rave.ohiolink.edu/etdc/view?acc_num=case1432223568

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, EECS - Electrical Engineering.
This project has developed two integrated microsystems fabricated in a 0.35-µm two-poly four-metal CMOS process for high-fidelity sensing and manipulation of brain neurochemistry. In particular, first, a system-on-chip (SoC) has been developed for neurochemical pattern generation in vivo. This SoC uniquely integrates electrical stimulation with embedded timing management for generation of neurochemical patterns and 400V/s fast-scan cyclic voltammetry (FSCV) sensing at a carbon-fiber microelectrode (CFM), for subsequent assessment of fidelity in the generated profiles, and manages a novel switched-electrode scheme that eliminates the possibility of large stimulus artifacts adversely affecting electrochemistry. The SoC also leverages the discontinuous sampling inherent in FSCV to reduce the sensing power consumption by 87.5% to 9.3µW from 2.5V using a duty-cycled, 3rd-order, continuous-time, delta-sigma modulator (CT-ΔΣM) with an input-referred noise current of 78pArms (dc – 5 kHz) within an input current range of ±950nA. Utilizing a transfer function that relates electrical stimulation of dopamine axons traversing the medial forebrain bundle (MFB) to evoked extracellular dopamine dynamics in the dorsal striatum of the forebrain, the correlation coefficient between predicted and measured dopamine temporal profiles was found to be 0.95 in an anesthetized rat. Next, the second SoC has been developed for closed-loop regulation of brain dopamine. This SoC uniquely integrates neurochemical sensing, on-the-fly chemometrics, and feedback-controlled electrical microstimulation to mimic a “neurochemical thermostat” by maintaining brain levels of electrically evoked dopamine between two user-set thresholds. The SoC incorporates a 90µW, custom-designed, digital signal processing (DSP) unit for real-time processing of neurochemical data obtained by 400V/s FSCV at a CFM. Specifically, the DSP unit executes a chemometrics algorithm based upon principal component regression (PCR) to resolve in real time electrically evoked brain dopamine levels from pH change and CFM background-current drift, two common interferents encountered with FSCV at a CFM in vivo. Further, the DSP unit directly links the chemically resolved dopamine levels to the activation of the electrical microstimulator in on-off-keying (OOK) fashion. Measured results from benchtop testing, flow injection analysis (FIA), and biological experiments with an anesthetized rat are presented.
Pedram Mohseni (Advisor)
Swarup Bhunia (Committee Member)
Soumyajit Mandal (Committee Member)
Paul Garris (Committee Member)
124 p.
Electrical Engineering
chemometrics, closed-loop neuromodulation, digital signal processor, dopamine regulation, fast-scan cyclic voltammetry, interferent differentiation, neurochemical sensing, pattern generation, principal component regression, system-on-chip

Recommended Citations

Citations

  • Bozorgzadeh, B. (2015). Integrated Microsystems for High-Fidelity Sensing and Manipulation of Brain Neurochemistry [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1432223568

    APA Style (7th edition)

  • Bozorgzadeh, Bardia. Integrated Microsystems for High-Fidelity Sensing and Manipulation of Brain Neurochemistry. 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1432223568.

    MLA Style (8th edition)

  • Bozorgzadeh, Bardia. "Integrated Microsystems for High-Fidelity Sensing and Manipulation of Brain Neurochemistry." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1432223568

    Chicago Manual of Style (17th edition)

case1432223568
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© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.
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