Sources of electrical brain activity are localized groups or “patches” of neurons that have their electrical polarizations aligned and “oscillating,” or periodically reversing direction, substantially in unison. This electrical activity is propagated away from the sources, by conduction to other patches of neurons through a network of “tracts,” and by radiation through the various head tissues, namely brain, skull, and skin; and within the brain, gray matter, white matter, and cerebrospinal fluid. The conductive aspect of this electrical activity is responsible for physiological effects in the brain and/or elsewhere in the body.
It is important for understanding how source activity produces an effect, and for electrically stimulating the sources to cause that effect, to know where the sources are. The process of determining this is called “source localization.” It is typically carried out by electroencephalography (EEG), though other non-invasive techniques, such as magnetoencelephography (MEG), and functional magnetic resonance imaging (fMRI), are also used.
EEG is performed by placing electrodes on the surface of the head and measuring the surface potentials (voltages) that result from the radiative aspect of the source activity. These data are used to solve a mathematically “ill-posed” problem, known in the art as the “inverse problem.” The inverse problem is to infer from the surface fields a hypothetical source activity that is consistent with producing those fields.
Specifying the inverse problem requires formulating an anatomical model of the head defining the locations and extent of the different head tissues. Each of these tissue types has a known characteristic impedance, so the anatomical model allows for calculating impedances of the various paths that electromagnetic radiation from a source can take as it radiates through the head tissues, ultimately to be received at the head surface electrodes.
The anatomical head model may be obtained by use of standard (non-functional) MRI of a particular subject's brain, or it may be hypothesized as a generalized model. In either case, the inverse problem suffers generally from being insufficiently constrained for unambiguous solution.
Model sources, preferably dipolar current sources, are virtually disposed within the anatomical model at corresponding patches, and the positions and/or strengths of the sources are iteratively manipulated until a satisfactory agreement is reached between calculated values of surface potential and those that are actually measured.
A significant innovation in the field of EEG source localization is described in U.S. Pat. No. 6,330,470, according to which injected currents are used in combination with measured surface potentials are used for more precisely characterizing the internal impedances by taking advantage of reciprocity between measured surface potentials and injected currents.
Another significant innovation in the field of EEG source localization is described in U.S. patent application Publication No. 2009/0306532, incorporated by reference herein in its entirety, according to which a tractographic analysis is used as a constraint on the solutions to the inverse problem.
Further, the '532 publication introduced the idea that, just like tractography can be used as an aid in source localization, source localization can be used as an aid in tractography.
It is often useful for research or therapeutic purposes to cause the brain to produce a desired effect. This is accomplished by electrically stimulating the same sources that were recognized from a source localization procedure to produce that effect, by injecting currents through head-surface electrodes as required to target those sources. In such cases it is often desirable to use EEG as the source localization procedure because the same apparatus is easily adapted for applying electrical stimulation. Moreover, using the same electrodes for source localization and electrical stimulation allows for taking advantage of reciprocity between measured surface potentials and injected currents in the manner taught in U.S. Pat. No. 6,594,521, to improve the precision of the stimulation.
Summarizing, a patch of neurons defining a source may be more precisely located by use of methods such as described in the '470 patent and the '532 publication, and may be more precisely targeted for stimulation by application of methods such as those described in the '521 patent. It is an object of the present invention to combine these methodologies to further improve the precision of brain source localization.