Cortical Underpinnings of Electrocorticography

Electrodes placed on the surface of the brain are commonly used to map cortical activity.  Microfabricated versions of electrocorticography (ECoG) arrays have the potential to provide greater coverage and resolution, but how do the signals they record relate to the firing of neurons within the cortex?  I used two methods to answer this question:

1.  Localized modulation of pyramidal neurons with optogenetics in transgenic mice.

Localizing neural activity from an array of electrodes is a theoretically difficult inverse problem.  Therefore I utilized optogenetic mice to precisely activate neurons at different depths within the cortex while recording potentials from the surface of the brain with a 4x4 microfabricated electrocorticography array (a).  The transgenic mice had expression especially in layer 2/3 and 5 pyramidal neurons (b & c).  The potentials recorded by the electrode array depended on the stimulus location, the depth of the fiber, and the intensity of light (78 mW/mm^2 and 25 mW/mm^2 for (d) and (e), respectively).  The dipole theory of cortical activation is consistent with our results.  Understanding how the depth of neuronal depolarization is reflected in recordings from an array on the surface of the brain informs interpretation of such neural interfaces when they are used  to study epilepsy, brain-computer interfaces, and other applications.  Reference: Richner TJ, Thongpang S, Brodnick SK, Schendel AA, Falk RW, Krugner-Higby LA and Williams JC. Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity. Journal of Neural Engineering 2014; 11: 016010.

Localizing neural activity from an array of electrodes is a theoretically difficult inverse problem.  Therefore I utilized optogenetic mice to precisely activate neurons at different depths within the cortex while recording potentials from the surface of the brain with a 4x4 microfabricated electrocorticography array (a).  The transgenic mice had expression especially in layer 2/3 and 5 pyramidal neurons (b & c).  The potentials recorded by the electrode array depended on the stimulus location, the depth of the fiber, and the intensity of light (78 mW/mm^2 and 25 mW/mm^2 for (d) and (e), respectively).  The dipole theory of cortical activation is consistent with our results.  Understanding how the depth of neuronal depolarization is reflected in recordings from an array on the surface of the brain informs interpretation of such neural interfaces when they are used  to study epilepsy, brain-computer interfaces, and other applications.  Reference: Richner TJ, Thongpang S, Brodnick SK, Schendel AA, Falk RW, Krugner-Higby LA and Williams JC. Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity. Journal of Neural Engineering 2014; 11: 016010.

2. Simultaneous ECoG and intracortical electrophysiological recordings.

I found that many cortical neurons are phase coupled to low frequency signals at the surface of the cortex by simultaneously recording 32 signals from the surface of the brain and an additional 32 channels spanning the layers of cortex.  In this example, one signal from the surface (micro-ECoG) and one signal from within the cortex (intracortical) are shown.  The phase relationship can be seen even before filtering with the spikes tending to fall within the troughs.  I used spectral coherence to further analyze the relationship between spikes and frequency bands.  

I found that many cortical neurons are phase coupled to low frequency signals at the surface of the cortex by simultaneously recording 32 signals from the surface of the brain and an additional 32 channels spanning the layers of cortex.  In this example, one signal from the surface (micro-ECoG) and one signal from within the cortex (intracortical) are shown.  The phase relationship can be seen even before filtering with the spikes tending to fall within the troughs.  I used spectral coherence to further analyze the relationship between spikes and frequency bands.  

Neurovascular Coupling

The brain consumes a vast amount of energy for its size and dynamically redistributes its blood supply to areas that need it most.  This is the basis of fMRI and other hemodynamic methods of measuring brain activity.  I researched neurovascular and neurometabolic coupling using two newly developed microscopes in collaboration with Ramin Pashaie's lab:

1. Optogenetic investigation of neurovascular coupling with a spatial light modulator microscope

We developed a fluorescence microscope that incorporated a light projector that enabled us to apply precise patterns for optogenetic modulation of the cortex.  We applied large (a), medium (b) and small (c) photostimulus patterns while imaging the response of arteries and veins (d).  Branches of the middle cerebral artery dilated rapidly while the venous response was slower and more muted (e).  We replicated the experiment in optogenetic and wild type mice and found large significant effect (f).  Reference: Richner TJ, Baumgartner R, Brodnick SK, Azimipour M, Krugner-Higby LA, Eliceiri KW, Williams JC and Pashaie R. Patterned optogenetic modulation of neurovascular and metabolic signals. Journal of Cerebral Blood Flow and Metabolism 2014.

We developed a fluorescence microscope that incorporated a light projector that enabled us to apply precise patterns for optogenetic modulation of the cortex.  We applied large (a), medium (b) and small (c) photostimulus patterns while imaging the response of arteries and veins (d).  Branches of the middle cerebral artery dilated rapidly while the venous response was slower and more muted (e).  We replicated the experiment in optogenetic and wild type mice and found large significant effect (f).  Reference: Richner TJ, Baumgartner R, Brodnick SK, Azimipour M, Krugner-Higby LA, Eliceiri KW, Williams JC and Pashaie R. Patterned optogenetic modulation of neurovascular and metabolic signals. Journal of Cerebral Blood Flow and Metabolism 2014.

2.  Optogenetics + Optical Coherence Tomography

Spectral domain optical coherence tomography uses a wide bandwidth infrared laser to make interferometry measurements of tissue refractive index.  We used a custom OCT microscope to image the cortical hemodynamic response in 3D following optogenetic activation.  The middle cerebral artery (MCA) traverses the cranial window from the anteriolateral corner (a).  Following a two second optogenetic stimulus the MCA dilates (b).  A closer view of the yellow square before (c) and after (d) photostimulation.  This custom microscope developed in the lab of Ramin Pashaie can be used to dissect neurovascular coupling in a cell type-specific manner.

Spectral domain optical coherence tomography uses a wide bandwidth infrared laser to make interferometry measurements of tissue refractive index.  We used a custom OCT microscope to image the cortical hemodynamic response in 3D following optogenetic activation.  The middle cerebral artery (MCA) traverses the cranial window from the anteriolateral corner (a).  Following a two second optogenetic stimulus the MCA dilates (b).  A closer view of the yellow square before (c) and after (d) photostimulation.  This custom microscope developed in the lab of Ramin Pashaie can be used to dissect neurovascular coupling in a cell type-specific manner.