Electrophysiologic Basis of EEG 24-25.pdf

Electrophysiologic Basis of EEG Azra Zafar FCPS Medicine, FCPS Neurology Associate Professor College of Medicine, division of Neurology Imam Abdulrahman Bin Faisal University...

Electrophysiologic Basis of EEG Azra Zafar FCPS Medicine, FCPS Neurology Associate Professor College of Medicine, division of Neurology Imam Abdulrahman Bin Faisal University Consultant Neurologist Department of Neurology, King Fahd University Hospital  Objectives Electrophysiology of neuron Generation of action potential Generation of EEG signals What is EEG ? Electroencephalography is a graphic representation of the difference in voltage between two different cerebral locations plotted over time. https://youtu.be/tZcKT4l_JZk Which part of the cortical neurons generate the EEG signal ? What is the physiological substrate of this, at the cellular level? Extracellular currents of the dendritic membrane of the pyramidal neurons in cortical layers IV-V.  Cortical Neuron as a Dipole +/- -/+ Electrophysiologic Basis of EEG Electrophysiologic Basis of EEG Electrophysiologic Basis of EEG EEG signals are generated by the transmembrane ion currents in the pyramidal neurons (cortical layers IV-V). The black ellipsoids symbolize the volume conduction of the return currents in the tissue between the generator (red arrow) and the recording EEG electrode (cup containing conductive paste) on the scalp. The box to the right is a schematic representation of the local field potentials in the cortical generator. Excitatory post- synaptic potentials (EPSP, in green) have extracellular negativity at the synapse (active sink) due to the influx of Na+ ions, and extracellular positivity at the passive source, due to the compensatory current. Inhibitory post-synaptic potentials (IPSP, in red) have extracellular positivity (active source) due to the influx of Cl- or efflux of K+ ions, and extracellular negativity at the passive sink, due to the compensatory currents. Epileptic Disorders, Volume: 22, Issue: 6, Pages: 697-715, First published: 21 January 2021, DOI: (10.1684/epd.2020.1217)  Electrophysiologic Basis of EEG Resting potential of neuron Synapse Excitatory post synaptic potential (EPSP) Inhibitory post synaptic potential (IPSP) Presynaptic terminal Post synaptic terminal Synaptic cleft  The Resting Potential of the Neuron Cortical neurons have a resting electrical charge (membrane potential) that results from the difference in electrical potential between the interior of the cell and the extracellular space. Resting potential of the neuron usually measures -65/70 mv range -40 to -80 mv The Resting Potential of the Neuron Na Na Na Na + Na + + + Na Na Na Na + Na Na Na + + + + Na + + + Na + + K K K + + + K K K K + + + + K K + K + +  Receptors Receptor Excitatory Inhibitory Glutamate GABA NMDA Non-NMDA GABAA GABAB Requires both glutamate & glycine Requires glutamate binding sites to be occupied No co-transporter required Binds NMDA Binds quisqualate & kainate Plugged by Mg2+ (unplugs when Na+ & K+ only depolarized) Allows passage of Na+ , K+ , and Ca2+  Receptors Receptor Excitatory Inhibitory Glutamate GABA NMDA Non-NMDA GABAA GABAB Allows chloride into cell Allows K+ out of BZD & BARB binding sites cell synapse  Action Potentials Action potentials occur when the neuronal membrane is depolarized beyond a critical threshold. When it reaches the axon terminal, it causes the release of a neurotransmitter which in turn causes an IPSP or EPSP to occur in the other neurons with which it synapses. Action Potential in Neurons The Action Potential  The post synaptic Action Potential Excitatory action potential/EPSP result when excitatory neurotransmitters bind to excitatory receptors Inhibitory action potential/IPSP result when inhibitory neurotransmitters bind to inhibitory receptors  Post-Synaptic Potentials Excitatory post-synaptic potentials (EPSPs) allow sodium +/ calcium into the cell Net result is depolarization of the neuron Inhibitory post-synaptic potentials (IPSPs) allow either chloride into the cell or potassium out of the cell Net result is hyperpolarization of the neuron Multiple EPSP’s and IPSP’s summate to determine the membrane potential at any given time EPSP/Excitatory Post-Synaptic Potentials Excitatory Post-Synaptic Potentials The influx of positively charged ions, Na+/Ca+ into the cell leaving a negative extracellular charge IPSP/Inhibitory Post-Synaptic Potentials Inhibitory Post-Synaptic Potentials The influx of negative charged ion, Cl-, into the cell, or efflux of K+ leaving a positive extracellular charge EPSPs and IPSPs turn the neuron into a dipole A dipole is a construct consisting of a positive charge at one end and a negative charge at the opposite end. Pyramidal neurons have a single long axis with a positive pole and a negative pole and can be conceptualized as a dipole. The apical dendrite comprises one end of the dipole and the basal dendrite/soma the other. The Dipole Creates an Electric Current  https://www.youtube.com/watch?v=tIzF2tWy6KI https://www.youtube.com/watch?v=W2hHt_PXe5o https://youtu.be/6qS83wD29PY 2-Minute Neuroscience: Action Potential - YouTube  Dipole Created by EPSPs Apical dendrite + - EPSP EPSP - + Som a Thalamus Axo Horizonta n l fiber  Action Potential in Neurons, Animation https://www.youtube.com/watch?v=iBDXOt_uHTQ Action Potential in the Neuron – YouTube https://www.youtube.com/watch?v=oa6rvUJlg7o Summation of action potential Schematic drawing of the scalp EEG registering negative (a) and positive (b) deflections Schematic drawing of the scalp EEG registering negative (a) and positive (b) deflections elicited from summated EPSPs and IPSPs derived from pooled pyramidal cells. Cells releasing glutamate and GABA provide excitatory and inhibitory superficial and deep synaptic connections resulting in an electrophysiological sink or source. EEG electroencephalography, EPSP Excitatory PostSynaptic Potentials, GABA Gamma- AminoButyric Acid, IPSPs Inhibitory PostSynaptic Potentials (Figure courtesy of Anteneh Feyissa M.D. and Mayo Clinic. From Tatum WO, Rubboli G, Kaplan PW, et al.  synapse The Essential EEG Concepts you MUST master - YouTube  Summation of Postsynaptic Potentials - YouTube  Volume conduction The process of current flow between the electrical generator and the recording electrode through the tissues (conductors) is called “volume conduction” Measured voltage depends upon the orientation of dipole and resistance offered by the conductors. Volume conduction  Electrical Fields Surrounding the neuron in concentric ellipses are electric fields. The fields are represented at right angles to the flow of current. The farther from the neuron, the lower the potential of the field. Current Flow in the Neuron - + Electric Fields  Basis for EEG Recording The summation of electrical potentials created by the pyramidal neurons and transmitted through the volume conductor are the basis for scalp EEG. Comparison of simultaneous scalp and cortical recordings of normal activity suggest that at least 6 cm2 of cortex with synchronous activity is required to create a reliably recorded scalp potential. Smaller areas can occasionally be recorded at the scalp if they have high intensity and highly synchronized electric potentials (eg. epileptiform spikes)  The EPSP – IPSP Sequence: A Fundamental Brain Circuit 1. Excitatory neuron releases glutamate, which activates non-NMDA (Q or quisqualate) receptor on dendrite of post-synaptic excitatory neuron, producing an EPSP 2. EPSP results in action potential in post-synaptic excitatory neuron 3. This excitatory neuron stimulates a GABAergic interneuron, which feeds back to excitatory neuron with IPSP  The EPSP – IPSP Sequence: A Fundamental Brain Circuit 1. Excitatory neuron releases glutamate, which activates non-NMDA (Q or quisqualate) receptor on dendrite of post-synaptic excitatory neuron, producing an EPSP 2. EPSP results in action potential in post-synaptic excitatory neuron 3. This excitatory neuron stimulates a GABAergic interneuron, which feeds back to excitatory neuron with IPSP +  The EPSP – IPSP Sequence: A Fundamental Brain Circuit 1. Excitatory neuron releases glutamate, which activates non-NMDA (Q or quisqualate) receptor on dendrite of post-synaptic excitatory neuron, producing an EPSP 2. EPSP results in action potential in post-synaptic excitatory neuron 3. This excitatory neuron stimulates a GABAergic interneuron, which feeds back to excitatory neuron with IPSP +  The EPSP – IPSP Sequence: A Fundamental Brain Circuit 1. Excitatory neuron releases glutamate, which activates non-NMDA (Q or quisqualate) receptor on dendrite of post-synaptic excitatory neuron, producing an EPSP 2. EPSP results in action potential in post-synaptic excitatory neuron 3. This excitatory neuron stimulates a GABAergic interneuron, which feeds back to excitatory neuron with IPSP + _  The Paroxysmal Depolarizing Shift/ PDS 1. By summing together, EPSPs can depolarize neurons enough for voltage-regulated calcium channels to open, resulting in a longer duration depolarization 2. The influx of extracellular calcium leads to the opening of voltage- dependent sodium channels. The influx of sodium generates repetitive action potentials 3. Subsequent hyperpolarization mediated by GABAergic interneurons and calcium dependent K +channels limits the paroxysm temporally and spatially  Interictal Discharges Result from the Paroxysmal Depolarizing Shift (PDS) The neuronal correlate of the interictal discharge is the paroxysmal depolarizing shift Large amplitude (30 mic v) and long duration (100 ms) depolarization Run of action potentials ride on top Followed by after-hyperpolarization  PDS AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Paroxysmal Depolarizing Shift Hyper-polarization PD S Limit duration and - - + + - - extent of paroxysm  Tonic clonic seizure Glu Persistent depolarization w/o hyperpolarization GABA inhibition fatigues Glutamate excitation enhances  Paroxysmal Depolarizing Shift (PDS) The Mystery of the Epileptic Spike – YouTube α-Amino-3-hydroxy-5-Methyl-4-isoxazol-Propionic Acid receptors (AMPA) N-Methyl-D-Aspartate) (NMDA) receptors. SCALP TOPOGRAPHY/ ORIENTATION OF EPILEPTIC DISCHARGE The dipoles generating interictal epileptiform discharges have a specific orientation, with the negative pole being closer to the superficial cortical layers (far from the cell body) and the positive pole being closer to the deeper layers (closer to the cell body). SCALP TOPOGRAPHY/ ORIENTATION OF EPILEPTIC DISCHARGE The most plausible explanation for this specific orientation is the different distribution along the apical dendrites of the excitatory and inhibitory synapses of the cortico-cortical connections that generate the interictal epileptiform discharges, where the excitatory synapses are far from the cell body and the inhibitory synapses are close to the cell body. SCALP TOPOGRAPHY/ ORIENTATION OF EPILEPTIC DISCHARGE The position and orientation of the cortical area generating the EEG signal determines the distribution of the negative and positive potentials on the scalp. This is the scalp topography, which can be visualized using voltage maps or amplitude-based maps. Figure- how volume conduction of the currents generated by different orientations (radial, tangential) of the cortical generators determine the scalp topography. Schematic drawing showing the current flow generated by cortical sources (depicted here as green ellipsoids, at the center of the red cross-hair) with radial (A) and tangential (B) orientation. A) When the cortical source is on the convexity (radial orientation), the return currents generated along the apical dendrites demonstrate the direction shown in the figure, causing a relatively circumscribed area of negative potentials on the scalp, overlying the source. The rest of the scalp has low-amplitude, diffuse positive potentials. (B) When the cortical source is in the wall of a sulcus (tangential orientation), the return currents are parallel with the surface, as shown in the figure. This results in two areas with opposite polarity on the scalp. The negative polarity is in the direction of the cortical surface of the generator. The color scale for the arrows indicates the polarity: red=positive, blue=negative, and yellow=the transition between them. Epileptic Disorders, Volume: 22, Issue: 6, Pages: 697-715, First published: 21 January 2021, DOI: (10.1684/epd.2020.1217)