A Frequency-Selective CMOS IC-Based Pulse Generator for Recording and Imaging in the Auditory Cortex In Vivo
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1
Hokkaido University, Graduate School of Information Science and Technology, Japan
Motivation
Cochlear implants use arrays of small electrodes that directly stimulate auditory nerve fibers through
the cochlea. However, these implants cannot restore hearing in individuals with severely impaired
peripheral auditory systems or auditory fibers. In this study, to overcome such difficulties, we
pro-duced an integrated microsystem that converted acoustic pressure variations into electrical
signals and directly stimulated neurons in the auditory cortex (AC). Such integrated devices must
include a multielectrode stimulation system designed to use the structure of tonotopically organized
fields lo-cated in the AC area, which is several square millimeters in size. Here, as a part of such an
integrated system, we used complementary metal oxide semiconductor (CMOS) IC technology to
specifically develop a multisite stimulator to activate neurons in the AC.
Materials and Methods
The total system of the CMOS IC-based stimulator consisted of three components: (a) a compact
CMOS IC board and (b) a multielectrode array (MEA) substrate as the tissue-electrode interface, and
(c) a power supply board. The MEA substrate was microfabricated by a method described previously
and subsequently attached directly to the CMOS IC board. A typical microelectrode substrate had
two/four needle shanks of 5.0/7.0 mm in length, and each shank respectively had 8/4 square
stimulation sites (60 ƒÊm ~ 60 ƒÊm); i.e., 16 stimulation sites in total. The CMOS IC chip was
originally designed for both recording and stimulation [1] and placed on a print circuit board (PCB;
size: 25 mm ~ 30 mm). Here, to focus on the stimulation function alone and to simplify control
functions, the stimulation function was only used in the CMOS IC-based pulse generator (CIBPG).
The CMOS IC chip com-prised 16 independent stimulation channels and any subset of the channels
could be stimulated. To create a compact and programmable pulse generator, stimulation channels
and parameters of pulse patterns were programmed via a field-programmable gate array (FPGA)
board from a PC. The chip could generate defined mono/bi-polar voltage pulses below an amplitude
of 2.5 V with 5-bit resolution. In addition, before stimulation, amplitude and timing parameters
including pulse width, inter-pulse intervals, and the total duration of the stimulus were predefined
and uploaded into the chip from the FPGA board. Two batteries (total size, 25 mm ~ 30 mm)
supplied 3.7 V at 400 mAh to the power supply board. In our system, the measured power
consumption of the chip was 22 ƒÊW/channel at 2.5 V for 16 channels. The triggering signals could be
independently applied from the power supply board or an external trigger source by selecting one of
switches.
To characterize the precision and reliability of pulse patterns generated by the CIBPG, we recorded
and analyzed timings of the initial pulses and durations, as well as the amplitudes of repetitive pulse
trains. Finally, to examine if the stimulation intensity was sufficient to evoke neural activity, we
recorded and imaged the activity in the rodent AC [2].
Results
First, we examined the precision and reliability of pulse patterns generated by the CIBPG. Because
the highest clock frequency of the DA converter in the CIBPG was 16 kHz, the shortest configurable
pulse width (PWs) was restricted to 62.5 ƒÊs. To measure PWs pulse timing, we programmed the
device to deliver a train of three PWs pulses in succession, separated by 62.5-ƒÊs intervals on the
tested output channels, whenever a trigger signal was detected. In this test, the output channels were
connected to a digital oscilloscope (DO) with a sampling rate of 100 MHz, and each device was
triggered 100 times every 1 s by a function generator. The measured pulse widths ranged from 59.6
ƒÊs to 65.6 ƒÊs, and 99% of pulses were within 3.0 ƒÊs of 62.5 ƒÊs.
@Additionally, in experiments with precisely timed events across channels, it is useful to produce
signals that occur simultaneously. To this end, we measured the synchronous events of output
channel updates by comparing PWs pulses triggered on two different output channels. We set the first
and eighth output channels to a resting voltage of -2.5 V, delivered 100 +2.5-V pulses, and captured
the rising waveform of each pulse with the DO. On all trials, the output voltage on both channels
settled within 100 mV of +2.5 V after 3.5 ƒÊs. This measurement also confirmed that DAC and output
amplifier slew rates were fast enough to produce 62.5-ƒÊs pulses useful for most applications in
neuroscience research.
@Moreover, we carried out in vivo recordings and demonstrated that our pulse generator via the
MEAs actually evoked neural responses of the rodent auditory cortex. The experiment utilized an
optical imaging system to show that characteristic frequencies of the tonotopic organization in the
AC were specified by tone bursts with various frequencies [2]. Subsequently, we determined whether
our system could evoke propagation of neural activity at a specific AC area comprising tonotopic
organized fields. The results showed that electric stimulation induced a reminiscent of activity
propagation evoked by sound stimulation, indicating that our system is useful as a neural stimulator.
Discussion/Conclusion
Here, we describe a CMOS IC-based pulse generator system designed for electric stimulation of
neural tissue in combination with MEAs. Also, a custom-made multielectrode arrays were fabricated
and electric properties of the multielectrode arrays were evaluated. In particular, we report that our
device delivered short voltage pulses whose timings were generated precisely and synchronously
between multiple channels. Additionally, the electric stimulation properties such as the amplitude and
pulse width were sufficient to stimulate the tested neurons in the rodent AC. Thus, our total system
can be used as a prototype of future auditory prostheses applied to the central nervous system.
References
[1] T. Tateno and J. Nishikawa, Frontier in Neuroengineering, 7:39 (2014). doi:
10.3389/fneng.2014.00039.
[2] M. Noto, J. Nishikawa, and T. Tateno, Neuroscience Vol. 318, No. 24 March 2016, pp 58-83
(2016).
Acknowledgements
T. T. was supported by the Suzuken Memorial Foundation (Japan) and a Grant-in-Aid for Scientific
Research (B) (No.15H02772) and Exploratory Research (No. 15K12091) (Japan).
Keywords:
evoked response,
microelectrode,
multisite stimulation,
Keywords: auditory cortex
Conference:
MEA Meeting 2016 |
10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul, 2016.
Presentation Type:
Poster Presentation
Topic:
MEA Meeting 2016
Citation:
Osanai
H,
Takahashi
S,
Iwaki
R and
Tateno
T
(2016). A Frequency-Selective CMOS IC-Based Pulse Generator for Recording and Imaging in the Auditory Cortex In Vivo.
Front. Neurosci.
Conference Abstract:
MEA Meeting 2016 |
10th International Meeting on Substrate-Integrated Electrode Arrays.
doi: 10.3389/conf.fnins.2016.93.00089
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Received:
22 Jun 2016;
Published Online:
24 Jun 2016.
*
Correspondence:
Dr. Hiroyuki Osanai, Hokkaido University, Graduate School of Information Science and Technology, Sapporo, Japan, h-osanai@ist.hokudai.ac.jp