Cells in the brain, called neurons, constantly talk to each other through a combination of tiny electric currents and chemicals, regardless of whether a person is awake or asleep. Magnetic Source Imaging (MSI), uses a technique called Magnetoencephalography (MEG) to measure the activity of these neurons. By measuring small magnetic fields in the brain, the location or source of neuron activity can be measured when a person is reading a story, remembering a list of words, or a variety of other tasks.

The Nature of Activation Imaged

Signaling among neurons constitutes one of the basic forms of activation that can be imaged with the current methods. It consists of electrochemical events that take place at the synapses, in the axon and the dendrites of neurons. With the exception of the phenomenon of neurotransmitter release and uptake, which does not involve directly electrical activity, all others involve flow of electrically charged particles, or ions, which results in electrical current.

Were we to view directly the variation of the electrical currents at each and every set of cells in the brain, which are referred to as current sources, and were we to plot these variations as a function of time, we would obtain the typical picture of activation that we have considered before. That is, we would find that the amount of signaling each source is producing changes from moment to moment in an apparently random manner but within certain limits. We consider the randomness in that variation only apparent because we do not know what is the purpose of each ripple of activation, or to what end each source is signaling at each point in time. We assume, however, that signaling always serves to mediate some function or other, or that the pattern of signaling throughout the brain that corresponds to each of the many functions that are taking place simultaneously, is contained in this apparently random variation and that special procedures are necessary to isolate it, extract it and image it. But we have also commented on the fact that, at times, abnormal deviations in activation that clearly exceed the normal range of its variation take place, and that these do not require any special procedures for their isolation and extraction. In the following paragraphs we will describe how we record and image , with the method of MEG, such deviations in signalling that are visible in the baseline activation profile and then we will describe how we extract function-specific signalling patterns.

Let us then assume that a set of cells that are typically not synchronized, begin to signal in unison. Their combined electrical currents will create a large deviation, much beyond the typical range. Such a phasic deviation could well be an epileptiform discharge.

Fig 1. A schematic rendering of the electromagnetic signals recorded on the head surface echoing the electrical currents inside the brain. A transient deviation in electromagnetic signal intensity over a particular region of the head surface reflects the coordinated signaling activity of a large set of neurons somewhere in the brain.

In such cases, using MEG, one can answer questions like: where is the source of this deviation (i.e, what area of the brain is epileptogenic)? Needless to say, the pattern of activation of the brain itself is hidden from our view. We have no direct access to the source currents themselves. We only have indirect access to the degree that these currents give rise to another form of electromagnetic energy which can travel outside the head where it can be captured and recorded, as shown in Figure 1, namely the magnetic flux.

Recording the Magnetic Flux

The magnetic flux is recorded by means of magnetometers. These are superconducting loops of wire positioned over the head surface. As the flux lines thread through the loop, they create in it current by induction. The strength of the current is proportional to the density of the flux at that point, so that knowing the value of the induced current, we have a measure of the flux strength at that point. If a sufficient number of magnetometers are placed at regular intervals over the entire head surface, then the shape of the entire distribution created by a brain activity source can be determined.

On the basis of the surface flux distribution, the position and strength of the brain source that produced it can be estimated. Once the estimates are made, the estimated source (i.e. the activated brain region) is identified using the following procedure: Three fiducial points are defined on the subjects head surface. Usually they are clear anatomical landmarks like the two pre-auricular points and the nasion. These three points define the coordinate system that includes the brain and the position of the magnetometers relative to it. The line between the pre-auricular points defines the y-axis of the coordinate system. The line between the nasion and the mid point of the x-axis and perpendicular to it, defines the x-axis and the line perpendicular to the x-y plane, passing through the intersection of the x and y axes, defines the z-axis of the coordinate system, as shown in Figure 2.

Fig 2. The system of Cartesian coordinates, anchored on fiducial landmarks, defines the space that contains the brain activity sources. The position of each source can therefore be specified with reference to these coordinates.

Thus, the exact position of the recorded distribution or the exact distance of each point of the head surface from the origin of the z-y-z coordinates is known. Also, the position of the source is defined with reference to this coordinate system and so is its relative orientation. Usually, lipid markers (e.g. vitamin pills) are attached on these three fiducial points, and a structural MRI is taken, either before or after the MEG recording session. The positions of the markers are visible on the MRI scans. Therefore, the relative position of all brain structures with respect to the position of the source of activity is also known. Given this fact, co-registration of the MEG-derived active source and the structural MRI is possible: The position of the source or sources can be projected onto the appropriate MRI slices resulting in composite images of the type shown in Figure 3.

Fig 3. A typical image representing a cluster of sources of phasic abnormal events (like epileptiform discharges) on a patient's MRI.

The Averaging Procedure

As mentioned in the first section of this tutorial, additional procedures are necessary to extract activation patterns specific to particular brain functions, embeded in the global, baseline activation profile. Also mentioned, was the fact that in the case of MEG, such extraction is accomplished with the “averaging procedure.” This procedure will be explained using, as an example, a simple sensory function like vision, occasioned by light stimuli.

Averaging is applied to the flux recorded on each and every surface point during the phenomena that define either a motor or a sensory function, in this case, during presentation of light flashes (and the resulting visual experiences).

Fig 4. A schematic representation of the on-going record of magnetic flux over the head. Each trace represents a record of magnetic flux from a single scalp location. At successive points in time, a sensory event is repeated n number of times. Yet no obvious changes in the record of the flux attend each repetition of the event.

In Figure 4, we cannot see any appreciable change in the flux when a phenomenon happens, unlike the case of epileptiform discharges considered before. This is because the amount of additional neural signaling, due to the sensory responses to the light stimuli, is minute as compared to the background signaling which corresponds to all concurrent functions of the brain. We assume, however, the following: First, that each time the flash occurs there must be an additional pattern of neural signaling that is embedded in the seemingly random variation of the background flux that we record. Second, that this pattern remains essentially the same every time the flash is presented since the stimulus is identical in all its repetitions. Third, that whereas at those particular times that the stimulus occurs, the signaling specific to the stimulus is almost the same, all other signaling reflected in the flux that corresponds to other, concurrent functions, cannot be the same but must vary randomly since, at those particular times, it is highly unlikely that other functions occur in synchrony with the reaction to the stimulus. Fourth, that at any given time, the several superimposed patterns corresponding to the several functions that jointly constitute the global flux are independent of each other and, as such, it is their sum that constitutes the recorded global, baseline flux.

Averaging is successful only to the degree that these assumptions are correct, and this appears to be the case with functions such as simple movement and sensory reaction, as well as more complex ones like language or memory.

The process of averaging involves the following steps: First, the flux is recorded from each point of the head surface, during several presentations of the same sensory stimulus. Each epoch of flux, that is, each portion of activity beginning a few milliseconds before and extending several milliseconds after each repetition of the stimulus, is separately stored.

The epochs are digitized by converting the intensity of the flux at each successive time point into numbers. Averaging of all the epochs collected at each surface location is then accomplished by adding the digitized epochs and dividing by their total number. If the four above mentioned assumptions are correct, what emerges as the average epoch is a waveform, or an evoked response of a particular shape, as shown in Figure 5.

Fig 5. Average evoke responses to auditory and visual stimuli. Responses consist of early and late components.

The evoked responses consist of early and late components. The former correspond to activation of the sensory cortex specific to each type of stimulus and the latter, typically, to activation of the association cortex. That is, the former enable identification of the mechanism of simple sensory and the latter of higher functions.

Identification of such mechanisms is accomplished through the following steps: The surface distribution of averaged flux at each and all successive time points during the evolution of the evoked response is successively analyzed such that sources that produced each of the successive distributions over the time interval of the response can be calculated and projected onto the structural images of the head as described above. Figure 6 shows some examples of functional images for different simple sensory functions.

Fig 6. Typical MEG images displaying signs of the mechanisms of the visual auditory and somatosensory functions. Each symbol represents the computed source location of the averaged magnetic flux recorded at a given point in time after the presentation of a visual, auditory or somatic stimulus. As expected, sources of visual responses are located in mesial occipital cortex, and the sources of auditory responses in the superior temporal plane, bilaterally. Stimulation of each of three fingers in each hand is associated with anatomically distinct sources in the contralateral parietal lobe.

To extract the activity specific to a higher function, the same averaging procedure may be used to obtain the late components of evoked responses, as follows. Let us assume that we wish to image the mechanism of verbal memory. To do so, we may present word stimuli to subjects with instructions to, say, identify words that occur more than once in a session. Evoked responses to these stimuli may be recorded and averaged as before. If the study is successful, the early components of the evoked response ought to be accounted for by sources in the primary auditory cortex, whereas the sources at the late components ought to outline the mechanism of the function that was occasional by the task, in this case verbal episodic memory.