Gaussian mixture modeling of hemispheric lateralization for language in a large sample of healthy individuals balanced for handedness

Abstract

Hemispheric lateralization for language production and its relationships with manual preference and manual preference strength were studied in a sample of 297 subjects, including 153 left-handers (LH). A hemispheric functional lateralization index (HFLI) for language was derived from fMRI acquired during a covert sentence generation task as compared with a covert word list recitation. The multimodal HFLI distribution was optimally modeled using a mixture of 3 and 4 Gaussian functions in right-handers (RH) and LH, respectively. Gaussian function parameters helped to define 3 types of language hemispheric lateralization, namely "Typical" (left hemisphere dominance with clear positive HFLI values, 88% of RH, 78% of LH), "Ambilateral" (no dominant hemisphere with HFLI values close to 0, 12% of RH, 15% of LH) and "Strongly-atypical" (right-hemisphere dominance with clear negative HFLI values, 7% of LH). Concordance between dominant hemispheres for hand and for language did not exceed chance level, and most of the association between handedness and language lateralization was explained by the fact that all Strongly-atypical individuals were left-handed. Similarly, most of the relationship between language lateralization and manual preference strength was explained by the fact that Strongly-atypical individuals exhibited a strong preference for their left hand. These results indicate that concordance of hemispheric dominance for hand and for language occurs barely above the chance level, except in a group of rare individuals (less than 1% in the general population) who exhibit strong right hemisphere dominance for both language and their preferred hand. They call for a revisit of models hypothesizing common determinants for handedness and for language dominance.

Figure 1. Histogram distribution of the manual preference strength variable assessed by the Edinburgh inventory score.

Self-reported left- (resp. right-) handers correspond light (resp. dark) grey bars.

Figure 2. Illustration of the fMRI paradigm used for assessing language hemispheric lateralization.

Subjects were presented during 1(left part) or a cartoon depicting a scene (right part). Right after presentation of a picture, the subject had to covertly generate either the list of the months of the year (right part) or a sentence describing the cartoon (left part). During this generation period, participants had to fixate a white-cross displayed at the center of the screen and to press the pad with their index finger when they had finished. Note that a reference task followed each event, consisting in sustaining visual fixation on the cross and pressing the pad when the fixation cross was switched to a square.

Figure 3. Probability map of the right-handed participants having a significant activation during sentence generation (SENT) as compared to recitation of a list of overlearned words (LIST) in the subgroup of 144 right-handers.

3D renderings of the probabilistic map of the individual SENT minus LIST contrast t-map after applying a t-threshold set at 1.96 (p<0.05, uncorrected) superimposed on the Caret anatomical template. L: left, R: right. The scale starts with 50% of overlap and the red areas correspond to a proportion larger than 80% of right-handers showing a significant activation.

Figure 4. Histogram distribution of hemispheric functional lateralization index (HFLI) in right-handers (RH, top panel), left-handers (LH, middle panel) and whole sample (RH+LH, bottom panel).

Solid lines are fits of these distributions by models of mixture of n Gaussian distributions (n = 3 for RH, n = 4 for LH and whole sample).

Figure 5. Plot of hemispheric functional lateralization for language as a function of manual preference strength.

Manual preference strength was assessed using the Edinburgh inventory, ranging from 100 (exclusive use of the right hand) to −100 (exclusive use of the left hand). Subjects also self-reported whether they consider themselves as right- handed (RH, squares) or left-handed (LH, circles). HFLI, an index of hemispheric functional lateralization for language measured with fMRI during covert generation of sentences compared to covert generation of list of words, was used for classifying subjects as « Typical » (HFLI>50, bright color symbols), « Ambilateral» (−20