An Implantable Optical Stimulation Delivery System for Actuating an Excitable Biosubstrate

The use of light-activated modulation techniques, such as optogenetics, is growing in popularity for enabling basic neuroscience research. It is also being explored for advancing more applied applications like therapeutic neuromodulation. However, current hardware systems are generally limited to acute measurements or require external tethering of the system to the light source. This paper presents an implantable prototype for use in techniques that modulate neurological state through optically-activated channels and compounds. The prototype system employs a three chip custom IC architecture to manage information flow into the neural substrate, while also handling power dissipation and providing a chronic barrier to the tissue interface. In addition to covering the details of the IC architecture, we discuss system level design constraints and solutions, and in-vitro test results using our prototype system with an optogenetic model. Potential technical limitations for the broader adoption of these techniques will also be considered.

[1]  Jacob G. Bernstein,et al.  Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain , 2009, Neuron.

[2]  K. Deisseroth,et al.  Bi-stable neural state switches , 2009, Nature Neuroscience.

[3]  C. Lundberg,et al.  Lentiviral vectors for use in the central nervous system. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[4]  Murtaza Z Mogri,et al.  Targeting and Readout Strategies for Fast Optical Neural Control In Vitro and In Vivo , 2007, The Journal of Neuroscience.

[5]  Paul H. Stypulkowski,et al.  Electrical Stimulation as Therapy for Neurological Disorders The Basics of Implantable Neurological Stimulators , 2006 .

[6]  Patrick Degenaar,et al.  Optobionic vision—a new genetically enhanced light on retinal prosthesis , 2009, Journal of neural engineering.

[7]  Jean A. Tkach,et al.  Neurostimulation system used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations. , 2004, Investigative radiology.

[8]  J. Dostrovsky,et al.  Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus , 2004, Experimental Brain Research.

[9]  Dave Carlson,et al.  An implantable Bi-directional brain-machine interface system for chronic neuroprosthesis research , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[10]  M. Delong,et al.  Deep Brain Stimulation for Neurologic and Neuropsychiatric Disorders , 2006, Neuron.

[11]  Xue Han,et al.  High-performance genetically targetable optical neural silencing by proton pumps , 2010 .

[12]  Daniel R. Merrill,et al.  Electrical stimulation of excitable tissue: design of efficacious and safe protocols , 2005, Journal of Neuroscience Methods.

[13]  R.R. Harrison,et al.  A Low-Power Integrated Circuit for a Wireless 100-Electrode Neural Recording System , 2006, IEEE Journal of Solid-State Circuits.

[14]  Gabor C. Temes,et al.  Circuit techniques for reducing the effects of op-amp imperfections: autozeroing, correlated double sampling, and chopper stabilization , 1996, Proc. IEEE.

[15]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[16]  E. Bamberg,et al.  Channelrhodopsin-2, a directly light-gated cation-selective membrane channel , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[17]  K. Deisseroth,et al.  Molecular and Cellular Approaches for Diversifying and Extending Optogenetics , 2010, Cell.

[18]  Rafael Yuste,et al.  Photorelease of GABA with Visible Light Using an Inorganic Caging Group , 2008, Frontiers in neural circuits.

[19]  C. McIntyre,et al.  Current steering to control the volume of tissue activated during deep brain stimulation , 2008, Brain Stimulation.

[20]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[21]  E. Boyden,et al.  Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution , 2007, PloS one.

[22]  Roberto Etchenique,et al.  A New Inorganic Photolabile Protecting Group for Highly Efficient Visible Light GABA Uncaging , 2007, Chembiochem : a European journal of chemical biology.

[23]  K. Deisseroth,et al.  Ultrafast optogenetic control , 2010, Nature Neuroscience.

[24]  A.-T. Avestruz,et al.  A 2 $\mu\hbox{W}$ 100 nV/rtHz Chopper-Stabilized Instrumentation Amplifier for Chronic Measurement of Neural Field Potentials , 2007, IEEE Journal of Solid-State Circuits.

[25]  G. Feng,et al.  Next-Generation Optical Technologies for Illuminating Genetically Targeted Brain Circuits , 2006, The Journal of Neuroscience.

[26]  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.

[27]  P. Stypulkowski,et al.  Electrical stimulation as therapy for neurological disorders , 2006, IEEE Engineering in Medicine and Biology Magazine.

[28]  Maysam Ghovanloo,et al.  An Integrated Full-Wave CMOS Rectifier With Built-In Back Telemetry for RFID and Implantable Biomedical Applications , 2008, IEEE Transactions on Circuits and Systems I: Regular Papers.

[29]  Gregory Molnar,et al.  Creating support circuits for the nervous system: Considerations for “brain-machine” interfacing , 2009, 2009 Symposium on VLSI Circuits.

[30]  Rafael Yuste,et al.  RuBi-Glutamate: Two-Photon and Visible-Light Photoactivation of Neurons and Dendritic spines , 2009, Front. Neural Circuits.

[31]  A. Benabid,et al.  Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease , 2009, The Lancet Neurology.