This first study on language and fronto-temporal volumes in children with epilepsy highlights discrepancies in brain regions associated with language skill in the children with epilepsy compared to the normal children. Thus, overall language functioning, measured by mean SLQ, was positively related to gray and white matter total brain and dorsolateral prefrontal cortex volumes in the normal group but to gray matter volumes of the inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus in the epilepsy group as a whole and in the subgroup with average linguistic skills. The presence of linguistic deficits within the epilepsy group was associated with smaller anterior superior temporal gyrus gray matter volumes and a negative association between language function and dorsolateral prefrontal gyrus gray matter volumes but not with seizure variables.
The association of SLQ with total brain volume and dorsolateral prefrontal volumes, both gray and white, in the control group supports Richardson and Price’s (33
) conclusion in their review of structural MRI studies of language function in the undamaged brain that “a higher quantity of the neural substrate being measured represents better performance on a given task.” In addition, the linguistic competence of normal adults (34
) and children (37
) involve executive functions subserved by the dorsolateral prefrontal cortex, such as attention and working memory. Functional magnetic resonance imaging (fMRI) studies of typically developing children also demonstrate increased cortical activity in the dorsolateral prefrontal cortex during syntax, semantics, and discourse coherence tasks (38
In the epilepsy group as a whole and in the subgroup with average SLQ scores the a relationship of SLQ with inferior frontal gyrus, posterior superior temporal gyrus, and temporal lobe gray matter volumes rather than with dorsolateral prefrontal volumes implies structural reorganization of the brain that subserves normal language function in these children. Several lines of evidence support this explanation of the study’s findings.
First, the inferior frontal gyrus, posterior superior temporal gyrus, and temporal lobe are involved in a wide range of linguistic skills (See reviews in (40
) and (41
)). Second, fMRI connectivity studies in typically developing children identify a normal age-related top down control of linguistic processing by the inferior frontal gyrus on posterior language-related regions of the temporal lobe, including the posterior superior temporal gyrus (8
). Third, the association of younger age of onset with atypical language representation in an fMRI study of 45 subjects with localization related epilepsy, aged 9 - 57 years, during a word definition task suggests that intra-hemispheric and inter-hemispheric reorganization of language processing occurs during childhood (43
). Fourth, recent fMRI studies also demonstrate decreased left lateralization of cortical activity, particularly in the inferior frontal region during a silent verb generation task in children with benign rolandic epilepsy (13
), as well as reduced resting connectivity in a language network that includes the left inferior frontal gyrus in adults with left temporal lobe epilepsy (44
Unlike the epilepsy subjects with normal linguistic scores, the structural reorganization involving a negative rather than positive relationship of language function with dorsolateral prefrontal gyrus gray matter volumes and smaller anterior temporal gyrus gray matter volumes in the children with linguistic deficits was related to language impairment. What determines functional versus dysfunctional language-related structural reorganization is yet to be determined. However, Mbwana et al. (43
) also identified limitations to the plasticity of language network reorganization in localization related epilepsy in their study of neural networks for processing language.
Thus, in addition to the previously reported abnormal lateralization of language in children with epilepsy (10
), our findings suggest differential involvement of language-related brain regions in normal and impaired linguistic functioning of children with epilepsy. Similar to the dissociation between IQ and fronto-temporal volumes in children with recent onset (45
) and chronic epilepsy (29
) compared to healthy control subjects, different brain regions also appear to be involved in the linguistic skill of children with epilepsy.
Smaller anterior superior temporal gyrus gray matter volumes and SLQ scores one standard deviation below the population mean and older age in the epilepsy subjects with language impairment imply abnormal maturation of this brain region in these children. Thus, there is an age-related decrease in activation of the anterior superior temporal gyrus during auditory processing of phonological tasks as healthy children use more abstract orthographic processing and invoke the posterior superior temporal gyrus and its connections with the inferior frontal gyrus (47
). Functional imaging studies of typically developing children also demonstrate participation of this brain region in the generation of verbs (48
) and the comprehension of an auditory narrative task (49
No evidence for a relationship between type of epilepsy and mean language scores for the epilepsy group as a whole and between seizure variables and the presence/absence of linguistic deficits, suggests that brain reorganization is unrelated to on-going illness effects. However, a prior study on a large sample of 182 children with epilepsy found an association of SLQ with seizure frequency, duration of illness, and history of prolonged seizures, but not with type of epilepsy and EEG findings (2
). Our findings in the current study, therefore, emphasize the importance of additional studies on larger samples of children with epilepsy to determine how brain structure and seizure variables affect the development of language in these children.
Despite significantly smaller orbital frontal gray matter volumes in the epilepsy compared to the normal group, we found no association of volumes in this brain region with either language skill or deficits. Yet, the orbital frontal gyrus plays a role in the propagation of complex partial seizures (50
), the onset of absence seizures (51
), semantics (52
), distinction between content and function words (54
), as well as in the discourse deficits found in children with epilepsy (55
). Different orbital frontal gyrus regions subserve diverse functions, including language and regulation of social behavior through the integration of factual knowledge and emotional patterns (See review in (56
)). Our negative findings might, therefore, reflect measurement of total rather than regional volumes within the orbital frontal gyrus.
The findings of our study are limited by the small sample size of the normal subjects (n = 34) relative to the epilepsy subjects (n = 69), SLQ based on different age-related forms of the TOLD, higher Performance IQ scores in the control group, the exclusion of normal subjects with a psychiatric diagnosis, and multiple statistical comparisons. Computing SLQ scores from three different age-related forms of the language instrument - the TOLD primary, the TOAL Intermediate, and the TOAL - limits generalization of the study’s findings, and does not rule out undiagnosed linguistic deficits.
Although we controlled for Performance IQ in the between group comparisons of SLQ and volumes, given the significant correlation of SLQ with Performance IQ, the different patterns of relationship between SLQ and fronto-temporal volumes might not be generalizable to epilepsy and normal subjects with similar mean PIQ scores. Exclusion of children with a psychiatric diagnosis in the normal group did not contribute to the different SLQ/fronto-temporal volume associations in the normal and epilepsy groups. Finally, although we computed multiple statistical comparisons, all statistical tests were two-tailed and a significance level of 0.05 was adopted for all inferences.
In conclusion, our findings demonstrate abnormal development of language related brain regions in medically treated children with epilepsy who have with average intelligence and no neuroradiological findings. In addition, they imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language.