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Effects of Covert and Overt Paradigms in Clinical Language fMRI

Rationale and Objectives

The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging (fMRI) language paradigms on language localization and lateralization.

Materials and Methods

Fourteen healthy volunteers were enrolled prospectively and underwent language fMRI using visually triggered covert and overt sentence generation (SG) and word generation (WG) paradigms. Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis. Regions of interest for Broca’s area, Wernicke’s area, and their contralateral homologues were drawn. The Euclidean coordinates of the center of gravidity ( x , y , and z ) of the respective blood oxygenation level–dependent (BOLD) activation cluster, and the correlation of the measured hemodynamic response to the applied reference function ( r ), relative BOLD signal change as BOLD signal characteristics were measured in each region of interest. Regional lateralization indexes were calculated for Broca’s area, Wernicke’s area, and their contralateral homologues separately. Wilcoxon’s signed-rank test was applied for statistical comparisons ( P values < .05 were considered significant). Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility.

Results

Overall activation rates for the four paradigms were 89% for covert SG, 82% for overt SG, 89% for covert WG, and 100% for overt WG. When comparing covert and overt paradigms, language localization was significantly different in 17% (Euclidean coordinates) and 19% (BOLD signal characteristics), respectively. Language lateralization was significantly different in 75%. Intrasubject and intersubject reproducibility was excellent, with 3.3% significant differences among all five parameters for language localization and 0% significant differences for language lateralization using covert paradigms.

Conclusions

Covert language paradigms (SG and WG) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days. Their overt counterparts achieved confirmatory localization but lower lateralization capabilities. Reference data for presurgical application are provided.

The localization and lateralization of essential brain language areas are crucial in the presurgical assessment of patients harboring brain tumors and epilepsy . Noninvasive functional magnetic resonance imaging (fMRI) provides this information prior to treatment and therefore supports the selection of candidates for surgery as well as the planning and performance of function-preserving treatment . fMRI has proven validity for this application but is not standardized yet.

The goal of this study was to investigate the effects of overt paradigms in clinical standardized fMRI compared to covert paradigms in terms of language lateralization and localization. The reproducibility of clinical language fMRI for different measurements performed during the same scanning session and on different days was assessed. Robust reference data are provided for the sentence generation (SG) and word generation (WG) paradigms conducted in a covert as well as an overt manner.

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Materials and methods

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Figure 1, Examples for the (a) sentence generation (SG) and (b) word generation (WG) paradigms. For the SG paradigm, the patient is supposed to say “The car is fast” once he or she sees the red racing car. For the WG paradigm, the patient is shown the word “flowers” and should name flowers that come into his or her mind, such as “pink,” “tulip,” “rose,” and so on.

Table 1

Set of Visual Triggers for SG and WG Paradigms

Trigger Defined Sentence (SG) or Instance (WG) Picture (SG) Ashtray Smoking is not healthy. Bodybuilder The bodybuilder is strong. Clown The clown is funny. Sundae The sundae is sweet. Elephant The elephant is heavy. Red racing car The car is fast. Fire The fire is hot. Lion The lion is dangerous. Model The model is beautiful. Pair of scissors The scissors are sharp edged. Lemon The lemon is sour. Snail The snail creeps slowly. Generic term or category (WG) Cars Ford, Porsche, Mercedes Occupations Physician, nurse, engineer Flowers Pink, tulip, rose Colors Green, red, blue Vegetables Tomato, artichoke, potato Countries United States, Switzerland, Canada Months January, December, August Names John, Kate, Cathrin Fruits Apple, banana, apricot Politicians Roosevelt, Jefferson, Thatcher Cities New York, Chicago, Berlin Animals Dog, cat, bee

SG, sentence generation; WG, word generation.

The same sets of triggers were used for covert and overt speech, modified from Stippich et al .

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Results

Comparison of Covert and Overt Paradigms

Data basis

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Figure 2, Example of increased motion artifact in overt (b) versus covert (a) paradigms. The increased motion artifact in overt sentence generation as displayed along the frontal convexity and the temporal pole (b) is obscuring the blood oxygenation level–dependent activation in A (asterisk). a, anterior; p, posterior; sag, sagittal.

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Activation rates

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Statistical comparisons

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Figure 3, Comparison of language lateralization in overt versus covert paradigms for Broca's area versus its right-hemisphere homologue (a) and Wernicke's area versus its right-hemisphere homologue (b) . Mean lateralization index (LI) values and standard deviations of 14 right-handed volunteers are shown. ∗ P < .05. SG co , covert sentence generation; SG ov , overt sentence generation; WG co , covert word generation; WG ov , overt word generation.

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Table 2

Language Localization and Lateralization of B and W Using Covert and Overt Paradigms

ROI Paradigm_n_ ∗ x__y__z__r dS% LI B SG cov 13 −47.69 ± 6.85 12.62 ± 9.70 10.00 ± 10.31 0.70 ± 0.11 2.14 ± 1.74 0.65 ± 0.44 SG ov 11 −41.09 ± 12.14 11.36 ± 8.88 13.82 ± 8.91 0.69 ± 0.10 1.71 ± 1.16 0.24 ± 0.81 WG cov 13 −45.69 ± 7.15 14.46 ± 8.69 16.31 ± 13.83 0.77 ± 0.10 1.63 ± 0.67 0.83 ± 0.37 WG ov 14 −44.36 ± 8.92 15.57 ± 8.54 17.00 ± 7.72 0.71 ± 0.11 1.84 ± 0.70 0.66 ± 0.37 W SG cov 12 −56.50 ± 5.42 −39.75 ± 7.33 15.00 ± 12.88 0.73 ± 0.11 1.72 ± 0.88 0.65 ± 0.72 SG ov 12 −56.17 ± 5.25 −34.58 ± 9.06 8.25 ± 10.14 0.64 ± 0.11 1.70 ± 0.91 −0.06 ± 0.76 WG cov 12 −53.42 ± 6.91 −41.42 ± 7.27 19.75 ± 9.30 0.72 ± 0.12 1.47 ± 0.76 0.58 ± 0.55 WG ov 14 −56.00 ± 7.39 −35.43 ± 9.80 11.14 ± 9.91 0.74 ± 0.10 2.18 ± 1.34 0.06 ± 0.65 BR SG cov 12 45.00 ± 9.21 18.00 ± 10.60 13.17 ± 11.61 0.61 ± 0.11 1.37 ± 1.36 SG ov 11 48.91 ± 11.17 11.09 ± 10.20 11.55 ± 10.66 0.63 ± 0.08 2.04 ± 1.70 WG cov 12 46.33 ± 8.18 14.50 ± 9.10 11.25 ± 10.58 0.63 ± 0.11 1.54 ± 1.34 WG ov 14 47.93 ± 6.96 9.86 ± 7.91 11.36 ± 10.16 0.66 ± 0.11 1.59 ± 0.75 WR SG cov 10 58.10 ± 7.62 −27.70 ± 10.51 15.90 ± 18.27 0.58 ± 0.10 1.44 ± 0.91 SG ov 13 53.08 ± 6.64 −26.69 ± 6.26 4.31 ± 10.77 0.66 ± 0.09 1.37 ± 0.41 WG cov 13 54.46 ± 5.94 −29.31 ± 15.06 7.15 ± 11.44 0.62 ± 0.10 1.17 ± 0.75 WG ov 13 48.15 ± 27.36 −25.54 ± 7.15 6.85 ± 8.69 0.75 ± 0.07 1.89 ± 0.59

B, Broca’s area; BR, right-hemisphere homologue of Broca’s area; dS%, relative blood oxygenation level–dependent signal change; LI, lateralization index; ROI, region of interest; SG cov , covert sentence generation; SG ov , overt sentence generation; W, Wernicke’s area; WG cov , covert word generation; WG ov , overt word generation; WR, right-hemisphere homologue of Wernicke’s area.

Data are expressed as mean ± standard deviation.

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Reproducibility of Language Localization, Lateralization and BOLD Signals

Data basis

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Activation rates

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Statistical comparisons

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Figure 4, Reproducibility of language localization ( x , y , and z as the Euclidean coordinates of the center of gravidity) and blood oxygenation level–dependent (BOLD) signal characteristics ( r as the correlation of the measured hemodynamic response to the applied reference function, dS% as the relative BOLD signal change) in Broca's area as a representative instance using covert sentence generation (SG cov ) (a–c) and covert word generation (WG cov ) (d–f) . For reasons of clarity in (c) and (f) , standard deviations (St dev) are listed in the table beyond the figures. 1 st , initial measurement; 2 nd , measurement during the same scanning session to test for intrasession reproducibility; 3 rd , measurement on another day to test for intersession reproducibility. ∗ P < .05.

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Figure 5, Reproducibility of lateralization index (LI) regarding covert sentence generation (a) and covert word generation (b) between the three measurements in Broca's area (b) versus its right-hemisphere homologue (BR) and Wernicke's area (W) versus its right-hemisphere homologue (WR). 1 st , initial measurement; 2 nd , measurement during the same scanning session to test for intrasession reproducibility; 3 rd , measurement on another day to test for intersession reproducibility.

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Discussion

Comparison of Covert and Overt SG and WG

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Reproducibility of Language Localization, Lateralization and BOLD Signal Characteristics

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Study Limitations

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Conclusions

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