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2010. 10. 05. Electrophysiology 2010. 10. 05 Electroencephalography Magnetoencephalography 2010. 10. 07 Source Localization The study of the electrical properties of biological cells and tissues. Change of Voltage or Current Target: From Single Ion Channel to Whole Organ Living organisms, Cultured tissue, Cultured cell Sensory receptor, Neuron, Muscle Electrocardiography - for the heart Electroencephalography - for the brain Electrocorticography - from the cerebral cortex Electromyography - for the muscles Electrooculography - for the eyes Electroretinography - for the retina Electroantennography - for the olfactory receptors in arthropods Classical electrophysiological techniques Electrode, Patch clamp Optical electrophysiological techniques Voltage sensitive dye (potentiometric dyes) Size: Micrometers in diameter Solid conductors (disc or needle/single or array) Printed circuit board Hollow tubes filled with an electrolyte glass pipettes filled with potassium chloride solution A patch clamp recording reveals transitions between two conductance states of a single ion channel: closed (at top) and open (at bottom). Glass micropipettes Size: small enough to penetrate a single cell with minimum damage to the cell (< 1 micrometre) Resistance: low enough so that small neuronal signals can be discerned from thermal noise in the electrode tip (several megaohms) Filled with a solution that has a similar ionic composition to the intracellular fluid of the cell. Ion Channel Closed Ion Channel Opened Resolution changes with size of electrode. Electrode size↑, then Resolution↓ One electrode can measure only one position which the electrode is inserted. Measuring point is limited. If we cannot insert electrode, we cannot measure. Dyes which change their spectral properties in response to voltage changes. Be able to provide linear measurements of firing activity of single neurons and large neuronal populations. Site of action potential origin, Action potential velocity and direction, Spatial and temporal variations in membrane potential Used to monitor the electrical activity inside cell organelles where it is not possible to insert an electrode, such as the mitochondria. Mouse heart Mouse cerebellum Hippocampal slices Measurement of population signals from many areas may be taken simultaneously Such multisite recordings may provide precise information on action potential initiation and propagation (including direction and velocity), and on the entire branching structure of a neuron. In certain preparations the pharmacological effects of the dyes may be completely reversed by removing the staining pipette and allowing the neuron 1–2 hours for recovery. May respond very differently in each trial Must be tested optimized Often fail to penetrate through connective tissue or move through intracellular spaces Water soluble dyes, such as ANNINE-6plus, do not suffer this problem. Noise is a problem and in certain preparations the signal may be significantly obscured. It can be solved with spatial filtering algorithms. Cells may be permanently affected by treatments. Lasting pharmacological effects are possible, and the photodynamics of the dyes can be damaging. Recording of electrical activity along the scalp produced by the firing of neurons within the brain. A typical adult human EEG signal is about 10µV to 100 µV in amplitude when measured from the scalp and is about 10–20 mV when measured from subdural electrodes (EcoG). Extracellular ionic current Cortical neuron Dendritic electrical activity Post-synaptic potential Electrode Differential Amplifier Filter Analog to Digital Converter PC Electrode: Attached to an Individual wire. Use cap or net which electrodes are embedded. Conductive gel is used to reduce impedance. Position of each electrode: International 10–20 system Differential Amplifier: Difference between reference electrode and each electrode Gain: Typically 1,000–100,000 times, or 60–100 dB Filter Analog to Digital Converter Sampling rate: 256-20kHz Linear method Event-related potential Power spectrum Non-linear method Time delay embedding Approximate entropy Partial-directed coherence Source localization Measuring brain response that is directly the result of a thought or perception. Summing all responses of event, then noise is canceled out. Using fast Fourier transformation, observing composition of each frequency component. delta(1-4Hz), theta(4-8Hz), alpha(8-12Hz), beta(12-30Hz), gamma(30-50Hz) Statistical parameter for quantifying the regularity of data. Predictability of subsequent amplitudes of the EEG based on knowledge of the previous amplitudes. Non-negative value in a time series. Higher value signifies more complexity and irregularity in the data. Quantifying degree of coupling between each electrode. Connectivity Hardware: costs are significantly lower, mobile, silent, no claustrophobia High temporal resolution (order of milliseconds) Relatively tolerant of subject movement Measures the brain's electrical activity directly EEG can detect covert processing (which does not require a response) subjects who are incapable of making a motor response when the subject is not attending to the stimuli elucidate stages of processing Activity of one neuron does not recorded because the activity is too fast and small. Poor spatial resolution. Less sensitive to deeper in the cortex, inside sulci, in midline or deep structures, and tangential to the skull The meninges, cerebrospinal fluid and skull obscuring its intracranial source. Mathematically impossible to reconstruct a unique intracranial current source for a given EEG signal,as some currents produce potentials that cancel each other out. (inverse problem) How to use high temporal resolution of EEG? How to improve low spatial resolution? How to combine EEG with other method which has high spatial resolution? http://en.wikipedia.org/wiki/Electrophysiology http://en.wikipedia.org/wiki/Voltage_sensitive_dye http://en.wikipedia.org/wiki/Patch_clamp http://www.infovisual.info/03/041_en.html http://www.ipmc.cnrs.fr/~duprat/neurophysiology/patch.h tm http://www.rikenresearch.riken.jp/eng/hom/5546 http://ajpheart.physiology.org/cgi/content/full/284/3/H892 http://www.physiology.wisc.edu/faculty/jackson.html http://en.wikipedia.org/wiki/Electroencephalography http://www.bem.fi/book/ http://en.wikipedia.org/wiki/Local_field_potential http://brain.fuw.edu.pl/~suffa/Modeling_SW.html 대표적인 예: Alan Lloyd Hodgkin and Andrew Fielding Huxley, giant axon of Atlantic squid, first applications of the "voltage clamp" technique. Voltage clamp 세포 안과 밖의 전위 차이 측정. 대부분의 이온 채널이 voltage gated ion channels Current clamp 전류를 흘려주고 반응을 관찰. 뉴런이 어떻게 반응 을 하는지. Cell-attached or on-cell patch Whole-cell recording or whole-cell patch EEG can be used simultaneously with fMRI so that high-temporalresolution data can be recorded at the same time as high-spatialresolution data, however, since the data derived from each occurs over a different time course, the data sets do not necessarily represent the exact same brain activity. There are technical difficulties associated with combining these two modalities, including the need to remove the MRI gradient artifact present during MRI acquisition and the ballistocardiographic artifact (resulting from the pulsatile motion of blood and tissue) from the EEG. Furthermore, currents can be induced in moving EEG electrode wires due to the magnetic field of the MRI.\ EEG can be recorded at the same time as MEG so that data from these complementary high-time-resolution techniques can be combined. 2010. 10. 07. Electrophysiology 2010. 10. 05 Electroencephalography Magnetoencephalography 2010. 10. 07 Source Localization 5 aT (5×10−18 T) High acquisition rate (kHz) Typically 300 sensors Cooling with liquid helium Josephson junction Two superconductors linked by a non-conducting barrier. Josephson effect Phenomenon of electric current across two superconductors in Josephson junction. Cortical activity: 10 fT Human alpha rhythm: 103 fT Magnetic noise in an urban environment: 108 fT or 10 µT. Aluminium, Mu-metal (approximately 75% nickel, 15% iron, plus copper and molybdenum) Different source: Intracellular and radial vs Extracellular and both tangential and radial MEG: Less distorted, Better spatial resolution, Reference-free MEG: More sensitive to superficial cortical activity Intensity of magnetic field decreases with distance more than electric field. Neocortical epilepsy + + - - + Source localization is an ILL-DEFINED PROBLEM A solution exists The solution is unique The solution depends continuously on the data If then If then If then If then And on and on and on and … EEG, radial MEG, radial EEG, tangential Forward Model Experimental DATA Which forward solutions fit the DATA better (less error)? Forward DATA Iterative Process Until solution stops getting better (error stabilises) error Inverse Solution iteration The "equivalent current dipole'' methods assume that the potentials are generated by a few dipolar sources. The "distributed source'' methods assume that potentials are generated by a large number of dipolar sources distributed within the brain or on the cortical surface. Discrete model: Single instantaneous dipole: fixed, moving Multiple spatiotemporal dipole (BESA) Distributed model: current density reconstruction LORETA (low resolution electromagnetic tomography) FOCUSS (focal underdetermined solution) MUSIC (multiple signal classification) Find position of dipole (x, y, z) and value of dipole moment vector(Qx, Qy, Qz) with optimization algorithm. Assume a small number of dipoles, typically less than ten, perhaps bilateral. ECD methods useful for subcortical reconstruction It is hard to estimate number of ECD. Optimisation problem is highly nonlinear. It is possible to converge local maximum. Need prior information. Because it does not use anatomical information, dipole is localized at outside of cerebral cortex often. Place a dipole perpendicular to cortical surface at each vertex. For each dipole, we only need to estimate the strength. To find sources, need to solve a linear optimization problem. But we have fewer sensors than sources. Constraints needed. How to use high temporal resolution of EEG/MEG? How to combine EEG with other method which has high spatial resolution? How to improve low spatial resolution? (better source localization) http://en.wikipedia.org/wiki/Magnetoencephalography http://en.wikipedia.org/wiki/SQUID http://en.wikipedia.org/wiki/Josephson_effect http://100.naver.com/100.nhn?docid=240769 http://web.mit.edu/kitmitmeg/whatis.html http://www.neurevolution.net/2007/08/20/magnetoencephalograp hy/ http://nextbigfuture.com/2007_10_28_archive.html http://neuroactivity.org/neuroimaging/meg/ http://elecmech.snu.ac.kr/research_bio_bio.htm http://en.wikipedia.org/wiki/Overdetermined_system http://en.wikipedia.org/wiki/Well-posed_problem http://en.wikipedia.org/wiki/Inverse_problem http://apps.mni.mcgill.ca/research/gotman/source.html http://www.slideshare.net/yunks128/meg-3394230