Reprint of "Cortical reorganization of language functioning following perinatal left MCA stroke" [Brain and Language 105 (2008) 99-111].

OBJECTIVE: Functional MRI was used to determine differences in patterns of cortical activation between children who suffered perinatal left middle cerebral artery (MCA) stroke and healthy children performing a silent verb generation task. METHODS: Ten children with prior perinatal left MCA stroke (age 6-16 years) and ten healthy age matched controls completed an executive language activation task. fMRI scans were acquired on a 3T scanner using T2* weighted gradient echo, echo-planar imaging (EPI) sequence. Random effects analysis and independent component analysis (ICA) were used to compute activation maps. RESULTS: Both analysis methods demonstrated alternative activation of cortical areas in children with perinatal stroke. Following perinatal stroke, typical left dominant productive language areas in the inferior frontal gyrus were displaced to anatomical identical areas in the right hemisphere (p=.001). In addition, stroke patients showed more bilateral activation in superior temporal and anterior cingulate gyri and increased activation in primary visual cortex when compared to healthy controls. There was no relation between lesion size and the degree of right hemisphere activation. ICA showed that the healthy controls had a negative correlation with the time course in the right inferior frontal gyrus in the same region that was activated in stroke subjects. INTERPRETATION: This functional MRI study in children revealed novel patterns of cortical language reorganization following perinatal stroke. The addition of ICA is complementary to Random Effects Analysis, allowing for the exploration of potential subtle differences in pathways in functional MRI data obtained from both healthy and pathological groups.

Cortical reorganization of language functioning following perinatal left MCA stroke.

OBJECTIVE: Functional MRI was used to determine differences in patterns of cortical activation between children who suffered perinatal left middle cerebral artery (MCA) stroke and healthy children performing a silent verb generation task. METHODS: Ten children with prior perinatal left MCA stroke (age 6-16 years) and ten healthy age matched controls completed an executive language activation task. fMRI scans were acquired on a 3T scanner using T2* weighted gradient echo, echo-planar imaging (EPI) sequence. Random effects analysis and independent component analysis (ICA) were used to compute activation maps. RESULTS: Both analysis methods demonstrated alternative activation of cortical areas in children with perinatal stroke. Following perinatal stroke, typical left dominant productive language areas in the inferior frontal gyrus were displaced to anatomical identical areas in the right hemisphere (p=.001). In addition, stroke patients showed more bilateral activation in superior temporal and anterior cingulate gyri and increased activation in primary visual cortex when compared to healthy controls. There was no relation between lesion size and the degree of right hemisphere activation. ICA showed that the healthy controls had a negative correlation with the time course in the right inferior frontal gyrus in the same region that was activated in stroke subjects. INTERPRETATION: This functional MRI study in children revealed novel patterns of cortical language reorganization following perinatal stroke. The addition of ICA is complementary to Random Effects Analysis, allowing for the exploration of potential subtle differences in pathways in functional MRI data obtained from both healthy and pathological groups.

Prosodic processing by children: an fMRI study.

Prosodic information in the speech signal carries information about linguistic structure as well as emotional content. Although children are known to use prosodic information from infancy onward to assist linguistic decoding, the brain correlates of this skill in childhood have not yet been the subject of study. Brain activation associated with processing of linguistic prosody was examined in a study of 284 normally developing children between the ages of 5 and 18 years. Children listened to low-pass filtered sentences and were asked to detect those that matched a target sentence. fMRI scanning revealed multiple regions of activation that predicted behavioral performance, independent of age-related changes in activation. Likewise, age-related changes in task activation were found that were independent of differences in task accuracy. The overall pattern of activation is interpreted in light of task demands and factors that may underlie age-related changes in task performance.

Sex differences in the activation of language cortex during childhood.

Sex differences have been well documented in the behavioral literature but have occurred inconsistently in the neuroimaging literature. This investigation examined the impact of subject age, language task, and cortical region on the occurrence of sex differences in functional magnetic resonance imaging. Two hundred and five (104 m, 101 f) right handed, monolingual English speaking children between the ages of 5 and 18 years were enrolled in this study. The study used fMRI at 3T to evaluate BOLD signal variation associated with sex, age, and their interaction. Children completed up to four language tasks, which involved listening to stories, prosody processing, single word vocabulary identification, and verb generation. A sex difference for behavioral performance was found for the prosodic processing task only. Brain activation in the classical left hemisphere language areas of the brain and their right homologues were assessed for sex differences. Although left lateralization was present for both frontal and temporal regions for all but the prosody task, no significant sex differences were found for the degree of lateralization. Sex x age interaction effects were found for all but the task involving single word vocabulary. However effect sizes associated with the sex differences were small, which suggests that relatively large sample sizes would be needed to detect these effects reliably.

BOLD fMRI signal increases with age in selected brain regions in children.

To determine whether the BOLD signal used in fMRI is age dependent in childhood, 332 healthy children (age 4.9-18.9 years) performed tasks in a periodic block design during 3 T fMRI: (1) a verb generation task interleaved with a finger tapping task; (2) a word-picture matching task interleaved with an image discrimination task. Significant correlations between percent signal change in BOLD effect and age occurred in left Broca's, middle frontal, Wernicke's, and inferior parietal regions, and anterior cingulate during the verb generation task; in precentral, postcentral, middle frontal, supplementary motor, and precuneus regions during the finger tapping task; and in bilateral lingula gyri during the word-picture matching task. Thus, BOLD effect increases with age in children during sensorimotor and language tasks.

Practical aspects of conducting large-scale functional magnetic resonance imaging studies in children.

The potential benefits of functional magnetic resonance imaging (MRI) for the investigation of normal development have been limited by difficulties in its use with children. We describe the practical aspects, including failure rates, involved in conducting large-scale functional MRI studies with normal children. Two hundred and nine healthy children between the ages of 5 and 18 years participated in a functional MRI study of language development. Reliable activation maps were obtained across the age range. Younger children had significantly higher failure rates than older children and adolescents. It is concluded that it is feasible to conduct large-scale functional MRI studies of children as young as 5 years old. These findings can be used by other research groups to guide study design and plans for recruitment of young subjects.