The Neural Engine: A Reprogrammable Low Power Platform for Closed-Loop Optogenetics

Brain-machine Interfaces (BMI) hold great potential for treating neurological disorders such as epilepsy. Technological progress is allowing for a shift from open-loop, pacemaker-class, intervention towards fully closed-loop neural control systems. Low power programmable processing systems are therefore required which can operate within the thermal window of 2° C for medical implants and maintain long battery life. In this work, we have developed a low power neural engine with an optimized set of algorithms which can operate under a power cycling domain. We have integrated our system with a custom-designed brain implant chip and demonstrated the operational applicability to the closed-loop modulating neural activities in in-vitro and in-vivo brain tissues: the local field potentials can be modulated at required central frequency ranges. Also, both a freely-moving non-human primate (24-hour) and a rodent (1-hour) in-vivo experiments were performed to show system reliable recording performance. The overall system consumes only 2.93 mA during operation with a biological recording frequency 50 Hz sampling rate (the lifespan is approximately 56 hours). A library of algorithms has been implemented in terms of detection, suppression and optical intervention to allow for exploratory applications in different neurological disorders. Thermal experiments demonstrated that operation creates minimal heating as well as battery performance exceeding 24 hours on a freely moving rodent. Therefore, this technology shows great capabilities for both neuroscience in-vitro/in-vivo applications and medical implantable processing units.

[1]  Andrew Jackson,et al.  Spinal-cord injury: Neural interfaces take another step forward , 2016, Nature.

[2]  R. Rodrígueza,et al.  Feature extraction of electrocardiogram signals by applying adaptive threshold and principal component analysis , 2015 .

[3]  N. Bekhtereva,et al.  [Utilization of multiple electrodes implanted in the subcortical structure of the human brain for the treatment of hyperkinesis]. , 1963, Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova.

[4]  Timothy H. Lucas,et al.  Design of a Closed-Loop, Bidirectional Brain Machine Interface System With Energy Efficient Neural Feature Extraction and PID Control , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[5]  B. Jobst,et al.  Critical review of the responsive neurostimulator system for epilepsy , 2015, Medical devices.

[6]  W. Singer,et al.  Gamma-Phase Shifting in Awake Monkey Visual Cortex , 2010, The Journal of Neuroscience.

[7]  L. Lagae,et al.  Cardiac changes in epilepsy , 2010, Seizure.

[8]  Jessica A. Cardin,et al.  Optical neural interfaces. , 2014, Annual review of biomedical engineering.

[9]  Michele Simonato,et al.  Gene Therapy Tools for Brain Diseases , 2019, Front. Pharmacol..

[10]  A. L. Jacobson,et al.  Auto-threshold peak detection in physiological signals , 2001, 2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[11]  G. A. Hay,et al.  A model of visual threshold detection. , 1977, Journal of theoretical biology.

[12]  Xiaoli Li,et al.  Suppressing epileptic activity in a neural mass model using a closed-loop proportional-integral controller , 2016, Scientific Reports.

[13]  Karim Abdelhalim,et al.  Closed-Loop Neurostimulators: A Survey and A Seizure-Predicting Design Example for Intractable Epilepsy Treatment , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[14]  Ahmed Soltan,et al.  A Flash-FPGA based Rodent Control System for Closed-loop Optogenetic Control of Epilepsy , 2018, 2018 IEEE International Symposium on Circuits and Systems (ISCAS).

[15]  Pierre J. M. Cluitmans,et al.  Detection of Subtle Nocturnal Motor Activity From 3-D Accelerometry Recordings in Epilepsy Patients , 2007, IEEE Transactions on Biomedical Engineering.

[16]  Timothy G. Constandinou,et al.  On-Probe Neural Interface ASIC for Combined Electrical Recording and Optogenetic Stimulation , 2018, IEEE Transactions on Biomedical Circuits and Systems.

[17]  Ahmed Soltan,et al.  Opto‐electro‐thermal optimization of photonic probes for optogenetic neural stimulation , 2018, Journal of biophotonics.

[18]  Peter Hänggi,et al.  Stochastic resonance in biology. How noise can enhance detection of weak signals and help improve biological information processing. , 2002, Chemphyschem : a European journal of chemical physics and physical chemistry.

[19]  Qiang Wang,et al.  Wirelessly Operated, Implantable Optoelectronic Probes for Optogenetics in Freely Moving Animals , 2019, IEEE Transactions on Electron Devices.

[20]  Sara Reardon Light-controlled genes and neurons poised for clinical trials , 2016, Nature.

[21]  Ahmed Soltan,et al.  A Scalable Optoelectronic Neural Probe Architecture With Self-Diagnostic Capability , 2018, IEEE Transactions on Circuits and Systems I: Regular Papers.

[22]  Terrence J. Sejnowski,et al.  Mechanisms for Phase Shifting in Cortical Networks and their Role in Communication through Coherence , 2010, Front. Hum. Neurosci..

[23]  David Sussillo,et al.  Making brain–machine interfaces robust to future neural variability , 2016, Nature communications.

[24]  Ahmed Soltan,et al.  High density, high radiance μLED matrix for optogenetic retinal prostheses and planar neural stimulation , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[25]  Patrick Degenaar,et al.  Photocycles of Channelrhodopsin‐2 , 2009, Photochemistry and photobiology.

[26]  Sonja Grün,et al.  How local is the local field potential? , 2011, BMC Neuroscience.

[27]  D. Kleinfeld,et al.  Traveling Electrical Waves in Cortex Insights from Phase Dynamics and Speculation on a Computational Role , 2001, Neuron.

[28]  E. Fetz,et al.  Compact movable microwire array for long-term chronic unit recording in cerebral cortex of primates. , 2007, Journal of neurophysiology.

[29]  Brian Litt,et al.  Line length: an efficient feature for seizure onset detection , 2001, 2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[30]  Ahmed Soltan,et al.  A low power flash-FPGA based brain implant micro-system of PID control , 2017, 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[31]  Alexandre Yakovlev,et al.  Optogenetics in Silicon: A Neural Processor for Predicting Optically Active Neural Networks , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[32]  Ahmed Soltan,et al.  Fractional order PID system for suppressing epileptic activities , 2018, 2018 IEEE International Conference on Applied System Invention (ICASI).

[33]  K. Deisseroth,et al.  Optogenetics , 2013, Proceedings of the National Academy of Sciences.

[34]  T. Schlaepfer,et al.  Integrative Neuroscience Mini Review Article Origin and Evolution of Deep Brain Stimulation , 2022 .

[35]  Daniel Rivero,et al.  Automatic epileptic seizure detection in EEGs based on line length feature and artificial neural networks , 2010, Journal of Neuroscience Methods.

[36]  G Bard Ermentrout,et al.  Phase-response curves and synchronized neural networks , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[37]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[38]  Tao Xu,et al.  Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning , 2018, Journal of neural engineering.

[39]  Chi-Sang Poon,et al.  Internal models in sensorimotor integration: perspectives from adaptive control theory , 2005, Journal of neural engineering.

[40]  L. Shupe,et al.  The Neurochip-2: An Autonomous Head-Fixed Computer for Recording and Stimulating in Freely Behaving Monkeys , 2011, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[41]  J. Dreher,et al.  Decision Threshold Modulation in the Human Brain , 2010, The Journal of Neuroscience.

[42]  Yves De Koninck,et al.  A Wireless Headstage for Combined Optogenetics and Multichannel Electrophysiological Recording , 2017, IEEE Transactions on Biomedical Circuits and Systems.

[43]  Tadashi Yamazaki,et al.  Real-Time Simulation of Passage-of-Time Encoding in Cerebellum Using a Scalable FPGA-Based System , 2016, IEEE Transactions on Biomedical Circuits and Systems.