Fundamentals of Central Nervous System Recording. Joseph E. O Doherty BME Neural Prosthetic Systems

Transcription

1 Fundamentals of Central Nervous System Recording Joseph E. O Doherty BME Neural Prosthetic Systems

2 The Problem Spaghetti & Meatballs Rall 1962 (after Ramon y Cajal)

3 Outline 1. Origin of Extracellular Potentials 2. Electrodes 3. Spike Discrimination

4 Extracellular Potentials Henze 2000

5 Bioelectric Current Loops Current across membrane leads to current loops in extracellular tissue Current distribution affected by extracellular anisotropies and inhomogeneities Most easily described described mathematically in a small volume near fiber, complicated in the volume conductor Barr 2006

6 Current Loops in CNS Current flow is highest where it enters or leaves the cell (sources and sinks) Flows intracellularly down axon or dendrites, crosses membrane and generally returns to the soma This system is called the volume conductor Humphrey 1979

7 Movement of the Local Current Loop Propagation occurs when a local current loop initiates AP in an adjacent region This in turn causes the current loop itself to propagate to the adjacent region Barr 2006

8 Extracellular Potential & Current Distribution Total membrane current is biphasic Outward current on the leading edge of the AP Shape explained by considering the capacitative and ionic currents separately Capacitative current dominates outwards Ionic current dominates inwards Barr 2006

9 Membrane Current Distribution Assume electrode exists at a single point Sum-of-dipoles approximation Assume homogeneity of medium V e = V e = J 4πσ e J 4πσ e r ( 1 r + 1 ) r V e = J 4πσ e n i J m,i r i S m Humphrey 1979

10 Extracellular Waveforms for a Cortical Pyramidal Neuron In far field, fiber approximation holds In dendritic arbor, for this geometry, sources are concentrated and dominate At axon hillock, there is a large sink of current that dominates At the axon, fiber approximation holds again. Humphrey 1979

11 Extracellular Waveforms for a Stellate Neuron In far field, fiber approximation holds In dendritic arbor is diffuse so there is no concentrated source At soma, the current sink dominates Waveform shape described by geometry of neuron and electrode location Humphrey 1979

12 Amplitude of Extracellular Spikes & Electrode Distance Humphrey 1979

13 Firing Rate of Extracellular Spikes & Electrode Distance Waveform size determined by distance from electrode Also geometry Firing rate not affected by electrode location Abeles 1977

14 Best Location for Recordings Generally near soma or site of AP initiation is best location for recordings across cell types Within a small distance from cell Other techniques needed for measuring neurotransmitter release, etc Branchaud 2006

15 Volume of Tissue Measured Buzsaki 2004

16 Outline 1. Origin of Extracellular Potentials 2. Electrodes 3. Spike Discrimination

17 Microelectrode Humphrey 1979

18 Principle of operation of metal electrodes Kipke 2004

19 Single electrode Recordings Find single units Conduct experiment Move electrodes to new location Repeat

20 Tetrodes Jog 2002

21 Tetrodes Jog 2002

22 Electrode Arrays

23 Early Electrode Arrays Chorover 1972

24 Duke Microwire Arrays Typically tungsten with teflon coating Stainless steel also good Platinum-iridium often too soft to penetrate cortex at small diameters Lehew 2007

25 Array Implantation Oliveira 2007

26 Array Implantation Oliveira 2007

27 Array Implantation Oliveira 2007

28 Utah Array Silicon micro-machined shanks Can be manufactured cheaply and precisely Limited fabrication depth Norman Pat

29 Michigan Probe Hetke 2002 Hetke 2002

30 Outline 1. Origin of Extracellular Potentials 2. Electrodes 3. Spike Discrimination

31 Spike Discrimination Lewicki 1998

32 Detecting Spikes with Thresholds Assumes that electrode is not moving with respect to tissue Assumes waveform does not change amplitude What if spike amplitude differences are smaller than noise level? Humphrey 1979

33 Optimal Thresholding Lewicki 1998

34 Spike Discrimination Lewicki 1998

35 Clustering Features Lewicki 1998

36 Principal Components Lewicki 1998

37 Principal Components Lewicki 1998

38 Automatic Clustering Lewicki 1998

39 Closely Spaced Electrodes Each electrode has a limited field of view On many arrays they do not overlap What if they do overlap? Increased spike discrimination ability Anderson 2004

40 Blind Source Separation Lewicki 1998

41 Review 1. Extracellular potentials arise due to electric currents 2. Capacitative and ionic currents contribute to different phases of waveform 3. Spike shape depends mostly on morphology 4. Larger cells have larger spikes 5. Closer cells have larger spikes 6. Multiple spikes can be detected and discriminated on a single channel 7. Closely spaced electrodes can allow for sophisticated spike discrimination

42 Bibliography Abeles, M. & Goldstein, M.H. (1977) Multispike train analysis. Proceedings of the IEEE 65(5): Anderson, D.J. (2004) Neural recording on closed spaced arrays, in Neuroprosthetics theory and practice. Horch, K.W. & Dhillon, G.S., Editors. World Scientific. Barr, R.C. (2006) Basic Electrophysiology, in Biomedical engineering fundamentals, Third Edition. Bronzino, J.D., Editor. CRC Press. Branchaud E.A. et al. (2006) An Algorithm for Autonomous Isolation of Neurons in Extracellular Recordings. Biomedical Robotics and Biomechatronics Buzsáki, G. (2004) Large-scale recording of neuronal ensembles. Nat. Neurosci. 7(5): Chorover S.L. & DeLuca A.M. (1972) A sweet new multiple electrode for chronic single unit recording in moving animals. Physiol Behav. 9(4): Henze D.A. et al. (2000) Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J. Neurophysiol. 84(1): Jog M.S. et al. (2002) Tetrode technology: advances in implantable hardware, neuroimaging, and data analysis techniques. Journal of Neuroscience Methods. 117(2): Kipke, D.R. et al. (2004) CNS recording electrodes and techniques, in Neuroprosthetics theory and practice. Horch, K.W. & Dhillon, G.S., Editors. World Scientific. Lehew, G. & Nicolelis, M.A.L. (2007) State-of-the-Art Microwire Array Design for Chronic Neural Recordings in Behaving Animals, in Methods for Neural Ensemble Recordings, Second Edition. Nicolelis, M.A.L., Editor. CRC Press. Lewicki, M.S. (1998) A review of methods for spike sorting: the detection and classification of neural action potentials. Network (Bristol, England) 9(4):R53-R78. Oliveira, L.M.O. & Dimitrov, D. (2007) Surgical Techniques for Chronic Implantation of Microwire Arrays in Rodents and Primates, in Methods for Neural Ensemble Recordings, Second Edition. Nicolelis, M.A.L., Editor. CRC Press. Rall, W. (1962) Electrophysiology of a dendritic neuron model. Biophys. J. 2: Hetke, J.F. & Anderson D.J. (2002) Silicon microelectrodes for extracellular recording, in Handbook of neuroprosthetic methods. Finn, W.E. & LoPresti, P.G., Editors. CRC Press.