320-Channel Active Probe for High-Resolution Neuromonitoring and Responsive Neurostimulation

We present a 320-channel active probe for high-spatial-resolution neuromonitoring and responsive neurostimulation. The probe comprises an integrated circuit (IC) cell array bonded to the back side of a pitch-matched microelectrode array. The IC enables up to 256-site neural recording and 64-site neural stimulation at the spatial resolution of 400 μm and 200 μm, respectively. It is suitable for direct integration with electrode arrays with the shank pitch of integer multiples of 200 μm. In the presented configuration, the IC is bonded with a 8 × 8 400 μm-pitch Utah electrode array (UEA) and up to additional 192 recording channels are used for peripheral neuromonitoring. The 0.35 μm CMOS circuit array has a total die size of 3.5 mm × 3.65 mm. Each stimulator channel employs a current memory for simultaneous multi-site neurostimulation, outputs 20 μA-250 μA square or arbitrary waveform current, occupies 0.02 mm 2, and dissipates 2.76 μW quiescent power. Each fully differential recording channel has two stages of amplification and filtering and an 8-bit single-slope ADC, occupies 0.035 mm 2 , and consumes 51.9 μW. The neural probe has been experimentally validated in epileptic seizure propagation studies in a mouse hippocampal slice in vitro and in responsive neurostimulation for seizure suppression in an acute epilepsy rat model in vivo .

[1]  Teresa H. Y. Meng,et al.  HermesE: A 96-Channel Full Data Rate Direct Neural Interface in 0.13 $\mu$ m CMOS , 2012, IEEE Journal of Solid-State Circuits.

[2]  José Luis Perez Velazquez,et al.  Experimental observation of increased fluctuations in an order parameter before epochs of extended brain synchronization , 2011, Journal of biological physics.

[3]  Alan B. Grebene,et al.  Analog Integrated Circuit Design , 1978 .

[4]  Maysam Ghovanloo,et al.  A compact large Voltage-compliance high output-impedance programmable current source for implantable microstimulators , 2005, IEEE Transactions on Biomedical Engineering.

[5]  Pedram Mohseni,et al.  A Battery-Powered Activity-Dependent Intracortical Microstimulation IC for Brain-Machine-Brain Interface , 2011, IEEE Journal of Solid-State Circuits.

[6]  Scott K. Arfin,et al.  An Energy-Efficient, Adiabatic Electrode Stimulator With Inductive Energy Recycling and Feedback Current Regulation , 2012, IEEE Transactions on Biomedical Circuits and Systems.

[7]  Peter A. Tass,et al.  Optimal number of stimulation contacts for coordinated reset neuromodulation , 2013, Front. Neuroeng..

[8]  M. Morrell,et al.  Intracranial stimulation therapy for epilepsy , 2009, Neurotherapeutics.

[9]  Moo Sung Chae,et al.  Design Optimization for Integrated Neural Recording Systems , 2008, IEEE Journal of Solid-State Circuits.

[10]  Karim Abdelhalim Wireless Neural Recording and Stimulation SoCs for Monitoring and Treatment of Intractable Epilepsy , 2013 .

[11]  Felice T. Sun,et al.  Responsive cortical stimulation for the treatment of epilepsy , 2011, Neurotherapeutics.

[12]  O. Bertrand,et al.  Oscillatory Synchrony between Human Extrastriate Areas during Visual Short-Term Memory Maintenance , 2001, The Journal of Neuroscience.

[13]  S. J. Daubert,et al.  Operation and analysis of current copier circuits , 1990 .

[14]  Jean Gotman,et al.  High-frequency (80–500Hz) oscillations and epileptogenesis in temporal lobe epilepsy , 2011, Neurobiology of Disease.

[15]  Bruce C. Wheeler,et al.  Stimulus-Artifact Elimination in a Multi-Electrode System , 2008, IEEE Transactions on Biomedical Circuits and Systems.

[16]  David A. Johns,et al.  Analog Integrated Circuit Design , 1996 .

[17]  Jan M. Rabaey,et al.  A 0.013mm2 5μW DC-coupled neural signal acquisition IC with 0.5V supply , 2011, 2011 IEEE International Solid-State Circuits Conference.

[18]  A.-T. Avestruz,et al.  A 5 $\mu$ W/Channel Spectral Analysis IC for Chronic Bidirectional Brain–Machine Interfaces , 2008, IEEE Journal of Solid-State Circuits.

[19]  P Kahane,et al.  Intracranial EEG and human brain mapping , 2003, Journal of Physiology-Paris.

[20]  Reid R. Harrison,et al.  A Versatile Integrated Circuit for the Acquisition of Biopotentials , 2007, 2007 IEEE Custom Integrated Circuits Conference.

[21]  K. Wise,et al.  A low-profile three-dimensional neural stimulating array with on-chip current generation , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[22]  Michael P. Flynn,et al.  A 64 Channel Programmable Closed-Loop Neurostimulator With 8 Channel Neural Amplifier and Logarithmic ADC , 2010, IEEE Journal of Solid-State Circuits.

[23]  R. Racine,et al.  Modification of seizure activity by electrical stimulation. II. Motor seizure. , 1972, Electroencephalography and clinical neurophysiology.

[24]  Mohsen Mollazadeh,et al.  Micropower CMOS Integrated Low-Noise Amplification, Filtering, and Digitization of Multimodal Neuropotentials , 2009, IEEE Transactions on Biomedical Circuits and Systems.

[25]  Roubik Gregorian,et al.  Introduction to CMOS OP-AMPs and Comparators , 1999 .

[26]  Qing Bai,et al.  Single-unit neural recording with active microelectrode arrays , 2001, IEEE Transactions on Biomedical Engineering.

[27]  Brian Litt,et al.  Flexible, Foldable, Actively Multiplexed, High-Density Electrode Array for Mapping Brain Activity in vivo , 2011, Nature Neuroscience.

[28]  Maurits Ortmanns,et al.  Charge Balancing in Functional Electrical Stimulators: A Comparative Study , 2007, 2007 IEEE International Symposium on Circuits and Systems.

[29]  R. Shapley,et al.  Spatial Spread of the Local Field Potential and its Laminar Variation in Visual Cortex , 2009, The Journal of Neuroscience.

[30]  C A Grimbergen,et al.  High-quality recording of bioelectric events , 1991, Medical and Biological Engineering and Computing.

[31]  Ruslana Shulyzki,et al.  256-site active neural probe and 64-channel responsive cortical stimulator , 2011, 2011 IEEE Custom Integrated Circuits Conference (CICC).

[32]  T. Seese,et al.  Characterization of tissue morphology, angiogenesis, and temperature in the adaptive response of muscle tissue to chronic heating. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[33]  Jan M. Rabaey,et al.  A 0.013 ${\hbox {mm}}^{2}$, 5 $\mu\hbox{W}$ , DC-Coupled Neural Signal Acquisition IC With 0.5 V Supply , 2012, IEEE Journal of Solid-State Circuits.

[34]  Timothy G. Constandinou,et al.  A partial-current-steering biphasic stimulation driver for neural prostheses , 2008, 2008 IEEE International Symposium on Circuits and Systems.

[35]  Karim Abdelhalim,et al.  Phase-Synchronization Early Epileptic Seizure Detector VLSI Architecture , 2011, IEEE Transactions on Biomedical Circuits and Systems.

[36]  Maysam Ghovanloo,et al.  An Experimental Study of Voltage, Current, and Charge Controlled Stimulation Front-End Circuitry , 2007, 2007 IEEE International Symposium on Circuits and Systems.

[37]  Karim Abdelhalim,et al.  915-MHz wireless 64-channel neural recording SoC with programmable mixed-signal FIR filters , 2011, 2011 Proceedings of the ESSCIRC (ESSCIRC).

[38]  R. Genov,et al.  256-Channel Neural Recording and Delta Compression Microsystem With 3D Electrodes , 2009, IEEE Journal of Solid-State Circuits.

[39]  Maysam Ghovanloo,et al.  An Inductively Powered Scalable 32-Channel Wireless Neural Recording System-on-a-Chip for Neuroscience Applications , 2010, IEEE Transactions on Biomedical Circuits and Systems.

[40]  Mark R. Bower,et al.  Microseizures and the spatiotemporal scales of human partial epilepsy. , 2010, Brain : a journal of neurology.

[41]  Reid R. Harrison,et al.  A Wireless Integrated Circuit for 100-Channel Charge-Balanced Neural Stimulation , 2009, IEEE Transactions on Biomedical Circuits and Systems.

[42]  J. Wyatt,et al.  Minimally Invasive Retinal Prosthesis , 2006, 2006 IEEE International Solid State Circuits Conference - Digest of Technical Papers.

[43]  K. Cheung Implantable microscale neural interfaces , 2007, Biomedical microdevices.

[44]  Florian Solzbacher,et al.  Preliminary Study of the Thermal Impact of a Microelectrode Array Implanted in the Brain , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[45]  Daryl R Kipke,et al.  Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants , 2007, Journal of neural engineering.

[46]  Andreas Demosthenous,et al.  An Integrated Implantable Stimulator That is Fail-Safe Without Off-Chip Blocking-Capacitors , 2008, IEEE Transactions on Biomedical Circuits and Systems.

[47]  Karim Abdelhalim,et al.  Low-distortion super-GOhm subthreshold-MOS resistors for CMOS neural amplifiers , 2013, 2013 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[48]  E. J. Tehovnik Electrical stimulation of neural tissue to evoke behavioral responses , 1996, Journal of Neuroscience Methods.

[49]  Karim Abdelhalim,et al.  The 128-Channel Fully Differential Digital Integrated Neural Recording and Stimulation Interface , 2010, IEEE Transactions on Biomedical Circuits and Systems.

[50]  Mohamad Sawan,et al.  A Highly Flexible System for Microstimulation of the Visual Cortex: Design and Implementation , 2007, IEEE Transactions on Biomedical Circuits and Systems.

[51]  Yong Lian,et al.  A 1V 22µW 32-channel implantable EEG recording IC , 2010, 2010 IEEE International Solid-State Circuits Conference - (ISSCC).

[52]  Maysam Ghovanloo,et al.  A Low-Noise Preamplifier with Adjustable Gain and Bandwidth for Biopotential Recording Applications , 2007, 2007 IEEE International Symposium on Circuits and Systems.

[53]  Berj L. Bardakjian,et al.  Real-time seizure monitoring and spectral analysis microsystem , 2006, 2006 IEEE International Symposium on Circuits and Systems.

[54]  S. Hafizovic,et al.  CMOS microelectrode array for bidirectional interaction with neuronal networks , 2006, IEEE Journal of Solid-State Circuits.

[55]  J. Weiland,et al.  A variable range bi-phasic current stimulus driver circuitry for an implantable retinal prosthetic device , 2005, IEEE Journal of Solid-State Circuits.

[56]  K. Najafi,et al.  A Modular 32-site wireless neural stimulation microsystem , 2004, IEEE Journal of Solid-State Circuits.

[57]  Refet Firat Yazicioglu,et al.  A 160μW 8-channel active electrode system for EEG monitoring , 2011, 2011 IEEE International Solid-State Circuits Conference.

[58]  Refet Firat Yazicioglu,et al.  A $160~\mu {\rm W}$ 8-Channel Active Electrode System for EEG Monitoring , 2011, IEEE Transactions on Biomedical Circuits and Systems.

[59]  Anantha Chandrakasan,et al.  An 8-channel scalable EEG acquisition SoC with fully integrated patient-specific seizure classification and recording processor , 2012, 2012 IEEE International Solid-State Circuits Conference.

[60]  C A Grimbergen,et al.  High-quality recording of bioelectric events , 1990, Medical and Biological Engineering and Computing.