Distributed source modeling of language with magnetoencephalography: application to patients with intractable epilepsy

Abstract

Purpose: To examine distributed patterns of language processing in healthy controls and patients with epilepsy using magnetoencephalography (MEG), and to evaluate the concordance between laterality of distributed MEG sources and language laterality as determined by the intracarotid amobarbital procedure (IAP).

Methods: MEG was performed in 10 healthy controls using an anatomically constrained, noise-normalized distributed source solution (dynamic statistical parametric map, dSPM). Distributed source modeling of language was then applied to eight patients with intractable epilepsy. Average source strengths within temporoparietal and frontal lobe regions of interest (ROIs) were calculated, and the laterality of activity within ROIs during discrete time windows was compared to results from the IAP.

Results: In healthy controls, dSPM revealed activity in visual cortex bilaterally from approximately 80 to 120 ms in response to novel words and sensory control stimuli (i.e., false fonts). Activity then spread to fusiform cortex approximately 160-200 ms, and was dominated by left hemisphere activity in response to novel words. From approximately 240 to 450 ms, novel words produced activity that was left-lateralized in frontal and temporal lobe regions, including anterior and inferior temporal, temporal pole, and pars opercularis, as well as bilaterally in posterior superior temporal cortex. Analysis of patient data with dSPM demonstrated that from 350 to 450 ms, laterality of temporoparietal sources agreed with the IAP 75% of the time, whereas laterality of frontal MEG sources agreed with the IAP in all eight patients.

Discussion: Our results reveal that dSPM can unveil the timing and spatial extent of language processes in patients with epilepsy and may enhance knowledge of language lateralization and localization for use in preoperative planning.

Figure 1

Average dynamic statistical parametric maps of cortical responses to novel words (top), false fonts (middle), and the novel words vs false fonts (bottom) for 10 healthy controls. Activity is seen bilaterally in occipital cortex ~80-120ms. By ~160ms, activity to novel words peaks in the left ventral occipital-temporal area (white arrow). By ~240ms, activity is observed within the left superior, middle, and inferior temporal lobe, in addition to left prefrontal cortex and is greater for novel words relative to false fonts. Activity is also seen within the right temporal lobe by ~240ms in both conditions. By ~350 ms, activity to novel words remains left lateralized in temporal cortex, but is bilateral in multiple frontal regions. The bottom panel demonstrates the absolute power differences in the mean waveforms. As can be seen, there is an absence of activity in this subtraction condition from ~80-120ms. This initial response was followed by a left-lateralized pattern of activity after ~240ms in left temporal (green arrows) and prefrontal (blue arrow) believed to reflect lexical, syntactic, and semantic processing. In each condition, significance thresholds are set at a minimum of p < 10^-8 (full red), with p< 10^-18 indicating peak activity (full yellow). These values represent significance levels associated with the noise-normalized dipole strength and can be conceptualized as estimates of the signal-to-noise at each vertex.

Figure 2

Noise-normalized dipole strengths from 0-600ms for novel words (blue) and false fonts (red) within selected regions of interest for the healthy control group. Significance (*) denotes regions producing a significant condition x hemisphere interaction. Main effects of condition are indicated by (“ ^ ”).

Figure 3

Noise-normalized dipole strengths and laterality indices for each temporal, parietal, and frontal lobe subregion averaged across the patients for the 240-280ms and 350-450ms time windows. Positive values for the laterality indices reflect left > right activity.

Figure 4

Dynamic statistical parametric maps and laterality indices calculated from 350-450ms for each of the eight patients. Activity is displayed on the inflated surface of each hemisphere. Sulci and gyri are shown in dark and light gray, respectively. Color bars range from moderate (orange) to high (yellow) activity and are relative to each patient's baseline. Values on the color bars represent significance values associated with the noise-normalized dipole strength at each vertex on the cortical surface. Laterality indices represent the difference between the hemispheres where positive values reflect greater left hemisphere activity and negative values greater right hemisphere activity.