Repeatability of language fMRI lateralization and localization metrics in brain tumor patients

Abstract

To assess the within-subject intra-scan session repeatability of language functional MRI (fMRI) activation maps in patients with brain tumors who were undergoing presurgical fMRI as part of their preoperative clinical workup. Sentence completion (SC) and silent word generation (SWG) tasks were used for language localization and hemispheric lateralization for identifying the primary language cortex. Within-subject repeatability for each of these paradigms was assessed in right-handed patients-37 for SC and 78 for SWG. Repeatability of activation maps between consecutive runs of the same task within the same scan session was evaluated by comparing lateralization indexes in holohemispheric and regional language areas. Displacement of center of activation between consecutive runs was also used to assess the repeatability of activation maps. Holohemispheric and regional language lateralization results demonstrated high intra-subject intra-scan repeatability when lateralization indices were calculated using threshold-dependent and threshold-independent approaches. The high repeatability is demonstrated both when centers of mass of activation are considered within key eloquent regions of the brain, such as Broca's area and Wernicke's area, as well as in larger more inclusive expressive and receptive language regions. We examined two well-known and widely accepted language tasks that are known to activate eloquent language cortex. We have demonstrated very high degree of repeatability at a single-subject level within single scan sessions of language mapping in a large cohort of brain tumor patients undergoing presurgical fMRI across several years at our institution.

Keywords: language fMRI; lateralization; presurgical mapping; repeatability; reproducibility.

Figure 1

Suprathreshold 50% AMPLE (activation mapping as a percentage of local excitation) language activation maps overlaid on the 3D surface of anatomical T1 MPRAGE obtained from two consecutive runs of sentence completion (SC) and silent word generation (SWG) fMRI tasks performed in the same scan session by a right‐handed patient with a right frontal mass [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Region of interest (ROI) selection: holohemispheric (holo)—left and right hemispheres excluding cerebellum; expressive (exp)—frontal regions; receptive (rec)—temporal and parietal regions; Broca's area (BA)—inferior frontal gyrus; Wernicke's area (WA)—temporal lobe gyri. An automated anatomical labeling (AAL) template was used for the automated atlas‐based parcellation of ROIs. Delineated ROIs are being shown overlaid on the MNI 2 mm template

Figure 3

Lateralization index LI = (L − H)/(L + H) where L refers to activation in the left hemisphere and R refers to the activation in the right hemisphere. Threshold‐independent LI (ThI LI) is calculated from the integrated Z‐score weighted distributions of all active voxels, and threshold‐dependent LI (ThD LI) is obtained using the integrated weighted distribution of 50% AMPLE (activation mapping as a percentage of local excitation) suprathreshold voxels in Z‐score activation maps. Hemispheric dominance for language function is determined by the LI values—left hemispheric dominance indicates LI ≥ 0.2, right hemispheric dominance indicates LI ≤ −0.2 and bilateral/mixed dominance indicates that −0.2 < LI < 0.2. ThI LI and ThD LI values from both sessions of sentence completion (SC) and silent word generation (SWG) language activation maps for holohemispheric and local regions of interest (ROIs) that is, expressive (Exp), receptive (Rec), Broca's area (BA), and Wernicke's area (WA) across the entire right‐handed patient population included in this study are displayed below. Each subject ThI LI or ThD LI value is depicted as an individual “x” or “o” symbol respectively in this plot

Figure 4

Left hemispheric threshold‐dependent center of mass (ThD COM), representing the center of mass of 50% AMPLE (activation mapping as a percentage of local excitation) suprathreshold activated voxels from both consecutive runs of sentence completion (SC) and silent word generation (SWG) language tasks, respectively, within the same scan session, is displayed for all right‐handed subjects. Individual subject ThD COM values for expressive (Exp), receptive (Rec), Broca's area (BA), and Wernicke's area (WA) regions of interest are depicted as dots on the 3D inflated sagittal surface of the MNI 2 mm anatomical template. The underlying gyral anatomy confirms the localization of activation areas [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Within‐subject lateralization index variability LI_VAR = |(LI1 − LI2)/(LI1 + LI2)| represents the variability in lateralization index (LI) from run 1 to run 2 in holohemispheric and local regions of interest (ROIs), that is, expressive (Exp), receptive (Rec), Broca's area (BA), and Wernicke's area (WA). The box plots of LI_VAR obtained across all right‐handed subjects is displayed. In each box, the central mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. Those patients with LI_VAR beyond 75th percentile are plotted individually using the “+” symbol. Note that cases for which LI_VAR > 1 were those where hemispheric dominance changed from one hemisphere to the other, that is, LI1 and LI2 are of opposite signs. The median values of LI _VAR across all right‐handed subjects in each holohemispheric and local ROIs are listed in c and d parts of the figure for the sentence completion (SC) and silent word generation (SWG) tasks, respectively

Figure 6

Within‐subject center of mass (COM) variability COM_VAR = || COM1 − COM2|| represents the variability in COM location from run 1 (COM1) to run 2 (COM2) in local regions of interest (ROIs), that is, expressive (Exp), receptive (Rec), Broca's area (BA), and Wernicke's area (WA). COM_VAR is referred to as the Euclidean distance (in mm) between COM1 and COM2. The box plots of COM_VAR obtained from COM1 and COM2 of left hemispheres across all right‐handed subjects is displayed. On each box, the central mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles of distance between COM1 and COM2 across subjects. Those patients with COM_VAR beyond 75th percentile are plotted individually using the “+” symbol. The median values of COM_VAR (i.e., distance between COM1 and COM2 in mm) across all subjects in each ROI are listed in c and d parts of the figure for sentence completion (SC) and silent word generation (SWG) tasks, respectively; note that these values are <5 mm for both Broca's area (BA) and Wernicke's area (WA)