Adaptive Language Mapping Paradigms for Presurgical Language Mapping

Language Mapping Paradigms

Each of the 4 paradigms involved a simple 2-condition block design with 6 blocks per condition and 20 seconds per block, for a total scan time of exactly 4 minutes.

The adaptive semantic paradigm has been described in detail previously,¹³ but in brief, there were 2 conditions: a semantic matching task and a perceptual matching task. In the semantic matching condition, participants saw 2 words in the middle of the screen, one above the other, and were instructed to press a button if the words were semantically related (eg, boy-girl) and to do nothing if the words were unrelated (eg, walnut-bicycle). In the perceptual matching condition, participants saw 2 strings of symbols in the middle of the screen, one above the other, and were instructed to press a button if the 2 strings were identical (eg, [ΔΘδЂϞ-ΔΘδЂϞ]) and to do nothing if they were different (eg, [ΔΘδЂϞ-ϞΔƕƘΔ]). Each condition had 7 levels of difficulty, and participants progressed to the next level every time they made 2 consecutive correct responses and stepped back 2 levels every time they made an error. Difficulty was modulated in the semantic condition by manipulating word frequency, concreteness, length, age of acquisition, degree of semantic relatedness, and presentation rate and, in the perceptual condition, by manipulating the degree of similarity of mismatching items and presentation rate.

The adaptive phonological paradigm has also been described previously.¹⁵ The language condition was a rhyme judgment task in which participants saw 2 pseudowords in the middle of the screen, one above the other, and were instructed to press a button if the pseudowords rhymed (eg, mulky-tulkie) and to do nothing if they did not (eg, shofy-sheffy). Difficulty was modulated by manipulating pseudoword length, orthographic transparency, stress pattern, and presentation rate. The perceptual control condition was the same as for the semantic paradigm.

Both adaptive paradigms were implemented in Matlab (MathWorks) using Psychtoolbox^16,17 and are freely available online at https://langneurosci.org/alm.

The sentence completion paradigm was implemented as recommended by the American Society of Functional Neuroradiology,² and the stimuli were downloaded from their Web site (https://www.asfnr.org/paradigms). In the language condition, participants saw 4 sentences per block (5 seconds each) with a blank space instead of the final word and were instructed to silently think of one or more words that could fit into the blank. In the control condition, participants saw scrambled letters matching the sentences in the number of characters and placement of spaces and were instructed to do nothing.

The word generation paradigm was also presented as recommended,² with the stimuli provided. In the language condition, participants saw a letter in the middle of the screen (2 per block, 10 seconds each) and were instructed to think of as many words as possible that start with that letter. In the control condition, participants saw symbols in the middle of the screen and were instructed to do nothing.

Before scanning, patients were trained on all 4 paradigms by 1 of the 3 authors. Training items were not repeated in the scanning session. For the adaptive paradigms, each trial type was demonstrated and discussed; then patients practiced a few blocks with actual task timing and adaptive features.^13,15 The sentence completion and word generation paradigms were practiced out loud to ensure task compliance; then the patient was instructed to perform the tasks silently in the scanner. In the scanner, the order of the 4 paradigms was counterbalanced across participants, to ensure that results were not confounded by presentation order. We cycled through 4 presentation orders so that each of the 4 paradigms was equally likely to be performed first, second, third, or fourth.

Neuroimaging

MR imaging data were acquired on a Philips Achieva 3T scanner (n = 57) or a Philips Ingenia Elition 3T scanner (n = 16) (Philips Healthcare) with 32-channel head coils at Vanderbilt University Medical Center. All paradigms were controlled by a laptop computer (Thinkpad T490s; Lenovo) running Matlab (Mathworks) Version R2019a and Psychtoolbox Version 3.0.16.^16,17 Visual stimuli were presented using a projector and a screen in front of the bore (n = 57) or on a monitor positioned behind the bore (n = 16), either of which patients viewed through a mirror mounted on the head coil. In the adaptive paradigms, patients responded on an MR imaging–compatible button box connected to the laptop.

For each of the 4 language mapping paradigms, sequences of T2*-weighted blood oxygen level–dependent echo-planar images were collected with the following parameters: 120 volumes + 5 initial volumes discarded; 35 or 36 axial slices in interleaved order; slice thickness = 3.5 mm with a 0.5-mm gap; FOV = 240 × 240 mm; matrix = 64 × 64; TR = 2000 ms; TE = 35 ms; flip angle = 78°; sensitivity-encoding factor = 2; voxel size = 3.75 × 3.75 × 4 mm.

For anatomic reference, T1-weighted (voxel size = 1 × 1 × 1 mm) and FLAIR images that were coplanar with the functional images (voxel size = 0.5 × 0.5 × 4 mm) were also acquired.

The imaging data were processed using standard methods as described previously.^13,15 The functional data were first preprocessed with AFNI: Slice timing and head motion were corrected, then the data were detrended and smoothed with a 6-mm full width at half maximum Gaussian kernel. Next, independent-component analysis was performed using the FSL tool MELODIC. Noise components were manually identified and removed using fsl_regfilt. All paradigms were modeled with boxcar functions convolved with a hemodynamic response function and fit to the data with the FMRISTAT program fmrilm. The 6 head-motion parameters were included as covariates, as were time-series from white matter and CSF regions to account for nonspecific global fluctuations and 3 cubic spline temporal trends. The T1-weighted anatomic images were warped to Montreal Neurological Institute space using unified segmentation in SPM12. Functional images were coregistered with structural images via coplanar FLAIR images using SPM and warped to Montreal Neurological Institute space. Individual activation maps were thresholded with a 5% relative threshold¹⁸ and a minimum cluster extent of 2 cm³, as described previously.^13,15

To compare the paradigms in terms of their ability to reveal hemispheric dominance, we calculated lateralization indices (LIs) in an extensive bilateral ROI (Fig 1) comprising the inferior, middle, and superior frontal gyri, supplementary motor area, precentral and postcentral gyri, all of the lateral parietal lobe, and all of the temporal lobe (lateral and medial) except for the dorsal (auditory) part of the superior temporal gyrus. This same a priori ROI has been used previously.¹³

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FIG 1.

ROIs. LIs were calculated on the basis of activation throughout the wide region shown in blue (or any of the other colors), while sensitivity was determined on the basis of activations in frontal (red), temporal (green), and anterior parietal (yellow) language regions.

Frontal, temporal, and anterior parietal language ROIs were defined to assess the sensitivity for detection of activation in these 3 language regions (Fig 1). These ROIs were defined in the dominant hemisphere, according to our clinical judgment of language lateralization based on all 4 paradigms, or in the left hemisphere in patients with bilateral language. Regions were deemed activated when there was ≥4 cm³ activation within the region. The frontal ROI was defined as the inferior frontal gyrus, as defined previously^13,15 on the basis of the Automated Anatomical Labelling atlas.¹⁹ The temporal ROI was defined previously^13,15 as the ventral part of the superior temporal gyrus, the middle temporal gyrus, and the angular gyrus; in this study, this ROI was expanded to also include the lateral and posterior parts of the inferior temporal and fusiform gyri (|x| ≥ 38, y ≤ −38). The anterior parietal ROI was defined as the supramarginal gyrus and the inferior parietal lobule, as previously defined;¹⁵ a language region within this territory has been shown to be critical for phonological encoding.^15,20-23

Language maps were defined as satisfactory when they met 3 conditions: 1) |LI| ≥ 0.25, in the correct direction or for patients with bilateral language,−0.25 < LI <0.25; these cutoffs are based on those proposed by Janecek et al;⁵ 2) frontal activation of ≥4 cm³ in the dominant hemisphere (left hemisphere for patients with bilateral language); and 3) temporal activation of ≥4 cm³ in the dominant hemisphere (left hemisphere for patients with bilateral language).

Test-retest reproducibility was assessed in a preliminary manner by splitting each run in half, analyzing the 2 halves separately, and calculating the Dice coefficient of similarity²⁴ between the 2 resultant activation maps. Head motion was compared between paradigms by calculating the mean framewise displacement for each run.

LIs, activation extents, Dice coefficients, and head-motion measures were compared among paradigms using repeated measures ANOVAs and post hoc paired t tests. The proportions of satisfactory language maps were compared with a χ² test, followed by post hoc Fisher exact tests.