Elsevier

Epilepsy & Behavior

Volume 12, Issue 3, April 2008, Pages 427-433
Epilepsy & Behavior

Asymmetry of language activation relates to regional callosal morphology following early cerebral injury

https://doi.org/10.1016/j.yebeh.2007.12.020Get rights and content

Abstract

The anatomical factors underlying reorganization of language representation are yet to be elucidated, although correlations between asymmetric structures and language lateralization have been identified. Previous research has implicated the corpus callosum in the development of language lateralization. This study examined the relationship between callosal morphology and language asymmetry, using letter fluency functional magnetic resonance imaging, in 13 patients with focal epilepsy and 8 healthy controls. Regional callosal thickness was determined without relying on a priori delineation of callosal segments. We predicted that language asymmetry measured by fMRI activation laterality scores would be correlated with regional callosal thickness in both groups. However, only the degree of language activation asymmetry was significantly correlated with callosal thickness in the isthmus and the midbody of patients, and there was a significant interaction between the groups with respect to callosal thickness and language activation asymmetry. These data suggest that callosal pathways may be important for language reorganization in the context of early cerebral injury.

Introduction

Asymmetric, left hemisphere representation of language in the normal human brain is well recognized. Although deviations from left hemisphere language representation occur in neurologically normal individuals [1], changes in the pattern of language representation may assume clinical significance in those with cerebral lesions. For example, in the setting of epilepsy surgery, alterations in language representation may affect clinical decision making and the counseling of patients regarding postoperative cognitive prognosis. The neurobiological basis for deviations in language representation in either the normal or the diseased brain is not well understood. It is important to bear in mind that deviations in language representation in the presence of pathology may differ in nature and underlying neurobiology from atypical representation in healthy controls. For example, a recent study has shown that when it occurs, right frontal lobe language activation occurs at different sites in patients with focal epilepsy compared with controls with atypical language representation [2].

Important clues to the mechanisms underlying changes in language representation are likely to come from identifying associated clinical factors and changes in brain structure and function. In the setting of cerebral injury, bilateral or right-sided language representation is more likely with a range of disease-related factors such as early age at injury [3], [4], [5] and acquired lesions as opposed to malformations of cortical development [3], [6]. The potential for both hemispheres to harbor language representation raises the possibility that hemispheric interaction is important in the control and development of language lateralization in normal subjects and language reorganization in patients with cerebral pathology. As the principal structure mediating interaction between the hemispheres, the corpus callosum has been a focus of attention. The relationship between the corpus callosum and hemispheric specialization for language has been investigated, in normal subjects, by examining the link between callosal size and indices of functional lateralization in the brain, but the findings have been conflicting. For example, bilateral representation has been associated with increased callosal size, and a role for increased communication between the hemispheres has been postulated [7]. Other investigators, however, suggest that greater callosal size increases contralateral inhibition, resulting in greater asymmetry of well-lateralized tasks in normal subjects [8], [9], [10].

In the current study, we examined the relationship between regional callosal thickness and asymmetry in language representation in subjects with intractable epilepsy, comparing them with neurologically normal control subjects. The current research differs from previous studies because of the disease population studied and the more refined methods of callosal morphometry and assessment of hemispheric language representation that were used. For callosal measurements, a semiautomated technique was used to segment the corpus callosum and measure its transverse thickness at automatically defined nodes along its anterior–posterior extent. The method we used did not make any assumptions about the shape of the corpus callosum. This contrasts with previous studies that employed Witelson’s method or its variants [11], which assume that dorsal–rostral deviations remain constant, dividing the callosum into five geometric sections along an anterior–posterior line. The relationship between regional thickness and language lateralization was assessed using a robust, nonparametric method of statistical inference unlike in previous studies that assumed that callosal measurements are independent [12]. Instead of relying on surrogate and imprecise markers of language representation (such as handedness), we used functional MRI (fMRI) activation as a measure of hemispheric asymmetry in language. Functional MRI has been validated against the gold standard for preoperative diagnosis of language dominance, the Wada test [13].

Section snippets

Participants

Two groups of participants were studied. The first group comprised eight neurologically normal controls whose average age was 25 (range: 21–30). The four male controls were right-handed. Of the four female controls, one was left-handed. The second group comprised patients undergoing presurgical evaluation in the Comprehensive Epilepsy Program (CEP) of Austin Hospital. They were included in the study if they had well-characterized focal epilepsy on the basis of clinical history and ictal

Results

The mean FSIQ of patients, as measured by the Wechsler Adult Intelligence Scale—Revised, was 92 (SD = 10). Performance on the COWAT (available for 11 patients) was, on average, 33.5 (SD = 10.8) and 50.5 (SD = 17.5) for controls, a significant group difference (t(17) = –2.6, P = 0.017).

The average language activation asymmetry index for the patients was 35.7 (SD = 65.7, range = –100 to 100), indicating that the group as a whole showed predominantly left-lateralized activation. This was similar to the leftward

Discussion

This study demonstrates that corpus callosum morphology is related to asymmetries of cerebral language representation in patients with focal epilepsy. A unique contribution of the research is the finding that the degree of asymmetry of language-based activation, rather than the direction (laterality, or left vs right), correlated with measures of callosal morphology. In addition, the correlations were regionally specific, occurring in the anterior midbody and the isthmus of the corpus callosum.

Acknowledgment

Dr. Wood was supported by an NHMRC Australian Clinical Postdoctoral Training Fellowship (ID 251755).

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