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

The timing and developmental factors underlying the establishment of language dominance are poorly understood. We investigated the degree of lateralization of traditional fronto-temporal and modulatory prefrontal-cerebellar regions of the distributed language network in children (n=57) ages 4 to 12 – a critical period for language consolidation. We examined the relationship between the strength of language lateralization and neuropsychological measures and task performance. The fundamental language network is established by four with ongoing maturation of language functions as evidenced by strengthening of lateralization in the traditional frontotemporal language regions; temporal regions were strongly and consistently lateralized by seven, while frontal regions had greater variability and were less strongly lateralized through age ten. In contrast, the modulatory prefrontal-cerebellar regions were the least strongly lateralized and degree of lateralization was not associated with age. Stronger core language skills were significantly correlated with greater right lateralization in the cerebellum.

FMRI in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with Epilepsy, Attention Deficit/ Hyperactivity Disorder (ADHD), Autism Spectrum Disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (Epilepsy: 80%; ADHD (off methylphenidate): 77%; ADHD (on methylphenidate): 81%; ASD: 70%; TYP: 87%). Ten to 18-year-olds had a significantly greater scan success rate than 4-6-year-olds; adolescents (13-18-year-olds) demonstrated greater scan success rates than 7-9-year-olds. Success rate for completing an entire battery of experimental runs (n=2-6), varied between 50-59% for patient populations and 69% for TYP (79% when excluding 4-6-year-olds). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20-30% more children should be recruited in these patient groups, but only 10-20% for TYP for research studies. Studies with 4-6-year-olds may require 20-40% additional participants; studies with 10-18-year-olds may require 10-15% additional participants.Functional magnetic resonance imaging (fMRI) is an established tool in the study of brain function in children with developmental disorders, acquired disorders, and typical development (TYP) and has a clinical application in pre-surgical planning for children with Epilepsy (Medina et al., 2007). Unlike structural MRI where participants are required to lie still (and may do so while sleeping), fMRI requires awake and cooperative participants which precludes the use of sedation. There is a paucity of data examining the success rate of scanning children in fMRI paradigms.Address Correspondence: Benjamin E. Yerys, Children's National Medical Center, Children's Research Institute -Neuroscience, 111 Michigan Ave, NW, Washington, DC 20010, byerys@cnmc.org, Phone: 301-738-8940. NIH Public Access Author ManuscriptHum Brain Mapp. Author manuscript; available in PMC 2010 October 1. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptOne study has examined scan success rate in over 200 TYP children between 5-to 18-years of age (Byars et al., 2002). This study defined scan success as children completing at least one of four fMRI tasks and an anatomical reference scan. Children between the ages of five and six had a success rate of 47%; children between the ages of seven and nine had a success rate of 76%; and children above the age of ten had a success rate of 96%. It is unk...

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.

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.