Chapter 23 - Functional magnetic resonance imaging: focus localization
Introduction
Functional magnetic resonance imaging (fMRI) allows the exploration of the local vascular response, and indirectly the coupled neural response to particular stimuli. It utilizes differences in the paramagnetic properties of oxyhemoglobin and deoxyhemoglobin, known as blood oxygen level-dependent (BOLD) contrast, to generate images of cerebral activity (Ogawa and Lee, 1990). Oxyhemoglobin is diamagnetic (nonmagnetic), whereas deoxyhemoglobin is paramagnetic, creating minor distortions in the local magnetic field that reduce the MR signal from the vessel and immediately adjacent tissues. When an area of the brain is activated, there is a regional increase in neuronal activity that results in an increase in cerebral blood flow and cerebral blood volume which exceeds the rate of oxygen extraction from the blood, resulting in a decrease in the local deoxyhemoglobin concentration. These events reduce local magnetic field inhomogeneities, and ultimately increase MR image voxel (a three-dimensional volume element) intensity when the brain is imaged using specific MR sequences (e.g., gradient echo imaging). Currently, it is believed that the magnitude of the BOLD signal reflects more the synaptic input and intracortical processing of a given volume (i.e., its total/overall synaptic activity) than the spiking output of the neurons in that area (Logothetis et al., 2001), and hence the increase in synaptic activity accompanying epileptiform activity is believed to give rise to a BOLD signal. The temporal evolution of BOLD signal changes is in the form of a characteristic curve called the hemodynamic response function (HRF) (Fig. 23.1) (Menon, 2001, Logothetis, 2003). An HRF models the typical change in BOLD signal over time following a stimulus or an epileptiform discharge measured with electroencephalography (EEG). Immediately following a stimulus, the BOLD signal and the oxyhemoglobin concentration have been shown in some studies to decrease briefly, often called the “initial dip,” which is thought to reflect an increase in oxygen metabolism and oxygen extraction before blood flow increases to the area (Malonek and Grinvald, 1996, Yacoub and Hu, 2001). Following the initial dip is the characteristic increase in cerebral blood flow and cerebral blood volume that gives rise to an increase in BOLD signal, which returns slowly to baseline over several seconds, potentially dipping temporarily below baseline (called the poststimulus undershoot) (Malonek and Grinvald, 1996, Yacoub et al., 2006).
In a typical experimental setting, fMRI is used to detect changes in neuronal activity in response to tasks (e.g., cognitive and motor) or stimuli (e.g., visual and sensory). In the context of epilepsy, one can consider the control condition to occur when the EEG is at baseline and the experimental condition to correspond to the presence of an epileptic discharge. To be able to perform such an experiment, it is necessary to record EEG while the subject is in the scanner.
Section snippets
EEG–fMRI
fMRI has the advantage both of high spatial resolution and the ability to sample brain function with relatively good temporal resolution, albeit less than that of EEG. EEG delivers excellent information on the timing of the spikes but is not always capable of precisely locating the source of the discharge. Intracranial EEG gives more precise temporal and spatial information but is invasive, expensive, and limited to the implanted area. Combined EEG–fMRI is thus a very promising technique that
Ictal and preictal fMRI
Early fMRI studies of epilepsy focused on the ictal state, because, in the absence of EEG information, this state was easiest to identify, typically using prior anatomical information and searching for focal variance changes (Jackson et al., 1994, Detre et al., 1995, Detre et al., 1996, Krings et al., 2000). The first report appeared in 1994 (Jackson et al., 1994), and was of a 4-year-old boy with Rasmussen's encephalitis and recurrent simple partial seizures of the face. Single-slice fMRI was
Brain connectivity
Functional and effective connectivity are descriptions of the relationships between patterns of neural activity and therefore involve measurements of neural function. Functional connectivity is a descriptive measure of spatiotemporal correlations between spatially distinct regions of cerebral cortex (Friston et al., 1993), whereas effective connectivity is defined as the influence that one neural system exerts over another (Friston et al., 1993). Functional connectivity is a statistical
Conclusion
Precise seizure focus localization and unraveling different structures involved in the genesis of the epileptic process is a major challenge that faces epilepsy research. The combination of EEG and fMRI is a well-established method that offers the unique advantage of measuring noninvasively specific hemodynamic changes related to epileptic discharges, providing unique localizing information on seizure foci and different cortical and subcortical structures that may be involved in this process.
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