Early seizure onset and atypical handedness, as well as the location and nature of pathologic substrate, are important factors in language reorganization.

Neural networks for processing language often are reorganized in patients with epilepsy. However, the extent and location of within and between hemisphere re-organization are not established. We studied 45 patients, all with a left hemisphere seizure focus (mean age 22.8, seizure onset 13.3), and 19 normal controls (mean age 24.8) with an fMRI word definition language paradigm to assess the location of language processing regions. Individual patient SPM maps were compared to the normal group in a voxel-wise comparison; a voxel was considered to be significant if its z-value exceeded mid R:2mid R:. Subsequently, we used principal component analysis with hierarchical clustering of variance patterns from individual difference maps to identify four patient sub-groups. One did not differ from normal controls; one had increased left temporal activation on the margin of regions activated in controls; two others had recruitment in right inferior frontal gyrus, middle frontal gyrus and temporal cortex. Right hemisphere activation in these two groups occurred in homologues of left hemisphere regions that sustained task activation. Our study used novel data driven methods to find evidence for constraints on inter-hemispheric reorganization of language in recruitment of right homologues, and, in a subpopulation of patients, evidence for intra-hemispheric reorganization of language limited to the margins of typical left temporal regional activation. These methods may be applied to investigate both normal and pathological variance in other developmental disorders and cognitive domains.

Patients had lower asymmetry indices than healthy controls, reflecting increased recruitment of homologous right hemisphere areas for language processing. Greater right hemisphere activation may reflect greater cognitive effort in patient populations, the effect of epilepsy, or its treatment. Regional activation patterns reflect adaptive efforts at recruiting more widespread language processing networks that are differentially affected based on hemisphere of seizure focus.

Objective: To investigate interhemispheric and intrahemispheric reorganization in patients with localization-related epilepsy. Method:We studied 50 patients with a left hemispheric focus and 20 normal right-handed controls with a 3T echoplanar imaging blood oxygen level dependent functional MRI auditory-based word definition decision task. Data were analyzed using SPM 2. Using region of interest for Broca and Wernicke areas and an asymmetry index (AI), patients were categorized as left language (LL; AI Ն0.20) or atypical language (AL; AI Ͻ0.20) for region. The point maxima activation for normal controls (p Ͻ0.05 corrected FDR) was identified in Broca and midtemporal regions and then used as a point of reference for individual point maxima identified at p Ͻ 0.001, uncorrected. Results:Patient groups showed increased frequency of having activation in right homologues.Activation in AL groups occurred in homologous right regions; distances for point maxima activation in homologous regions were the same as point maxima distances in normal control activation in left regions. Distances for LL patient in left regions showed a trend for differences for midtemporal gyrus (6 mm posterior, 3 mm superior) but variability around mean difference distance was significant. There was no effect of age at epilepsy onset, duration, or pathology on activation maxima. The ability to process language typically resides in the left hemisphere. Conclusions:1,2 Atypical language dominance occurs in 4%-6% of the normal right-handed population and 22%-24% of normal left-handed individuals.3,4 MRI is effective in determining language lateralization as well as identifying the location of language processing areas. 5,6 Functional MRI (fMRI) may also be used to describe the effects of epilepsy on language networks as well as assisting in presurgical planning. [7][8][9] Patients with epilepsy, regardless of handedness, have a high likelihood of atypical language.3,10,11 Early cortical injury or epileptic activity may ultimately lead to language reorganization. 11,12 The younger the brain insult, if focal, the more likely the reorganization of language functions occurs with preservation of function. 2,13 Patients with a seizure focus in the left temporal lobe are more likely to have language activation in the right hemisphere.

Listening and reading comprehension of paragraph-length material are considered higher-order language skills fundamental to social and academic functioning. Using ecologically relevant language stimuli that were matched for difficulty according to developmental level, we analyze the effects of task, age, neuropsychological skills, and post-task performance on fMRI activation and hemispheric laterality. Areas of supramodal language processing are identified, with the most robust region being left-lateralized activation along the superior temporal sulcus. Functionally, this conjunction has a role in semantic and syntactic processing, leading us to refer to this conjunction as "comprehension cortex." Different from adults, supramodal areas for children include less extensive inferior frontal gyrus but more extensive right cerebellum and right temporal pole. Broader neuroanatomical pathways are recruited for reading, reflecting the more active processing and larger set of cognitive demands needed for reading compared to listening to stories. ROI analyses reveal that reading is a less lateralized language task than listening in inferior frontal and superior temporal areas, which likely reflects the difficulty of the task as children in this study are still developing their reading skills. For listening to stories, temporal activation is stable by age four with no correlations with age, neuropsychological skills or post-task performance. In contrast, frontal activation during listening to stories occurs more often in older children, and frontal activation is positively correlated with better performance on comprehension questions, suggesting that the activation of frontal networks may reflect greater integration and depth of story processing.

Functional magnetic resonance imaging (fMRI) represents a useful tool for studying brain functions and the neural basis of cognition in healthy children and in those in disease states. Functional magnetic resonance imaging is a relatively new use of existing magnetic resonance imaging technology that allows scientists and practitioners to observe the brain at work. It is based on the observation that local increases in blood flow are related to neural activity. This review considers principles of functional magnetic resonance imaging, issues relevant to imaging children, and research using functional magnetic resonance imaging to examine cognitive processing in pediatric populations. The focus is specifically on language studies to review strengths, limitations, and practical applications of this technology with children. Future directions for functional magnetic resonance imaging are presented.

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