Frédérique Liégeois

Language fMRI abnormalities associated with FOXP2 gene mutation.

Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Brocas area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Brocas area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.

A direct test for lateralization of language activation using fMRI: comparison with invasive assessments in children with epilepsy.

This study introduces a direct method of assessing cerebral lateralization for language based on fMRI activation. The method, derived from a voxel-based morphometry study by C. H. Salmond et al. (2000, Hum. Brain Mapping 11, 223-232), bases lateralization on the direct statistical comparison of the magnitude of task-induced activation in homotopic regions of the two hemispheres. Lateralization results obtained with this direct method were compared to those obtained with a widely used method which involves the calculation of a laterality index (LI) based on the number of significantly activated voxels in the inferior frontal gyrus of each hemisphere. In order to compare the validity of the two methods, a covert verb-generation task was performed by eight children with epilepsy whose language lateralization was examined using invasive techniques. Lateralization results derived from fMRI activation showed that the calculation of a LI presented some limitations. Importantly, the LI value was dependent on the activation threshold chosen to calculate that LI. As a consequence, the correlation between the LI and the invasive methods could vary with the chosen threshold. By contrast, the proposed direct method gave some indication of the reliability of the lateralization and provided results that, in all eight children, were consistent with those obtained using invasive techniques. It is suggested that the direct method could be used in future fMRI studies to establish hemispheric lateralization for cognitive functions.

Total brain white matter is a major determinant of IQ in adolescents born preterm

In preterm infants, white matter (WM) abnormalities detected on magnetic resonance imaging (MRI) at term‐age are associated with early developmental delay. We set out to study this association in adolescents born pre‐term, by examining intellectual outcome in relation to markers of brain injury, focusing on the effects of WM reduction.

Interhemispheric temporal lobe connectivity predicts language impairment in adolescents born preterm

Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses showed that a combination of anatomical measures of temporal interhemispheric connectivity (through the splenium of the corpus callosum and anterior commissure) explained 57% of the variance in language abilities. This supports recent theories emphasizing the importance of interhemispheric connections for language, particularly in the developing brain.

Speaking with a single cerebral hemisphere: fMRI language organization after hemispherectomy in childhood.

Speech-related fMRI activation was examined in six hemispherectomy patients (three left LX, three right RX, four with congenital and two with late-acquired hemiplegia) operated in childhood for the relief of drug-resistant epilepsy. Although the temporal and sensorimotor pattern of activation was similar to that found in neurologically intact control participants, activation in Brocas area and its right homolog varied greatly. Involvement of pars triangularis and orbitalis was found in the three cases with best outcome (two RX, one LX), whereas pars opercularis alone was activated in the two remaining LX patients. The results suggest that distinct subregions of Brocas area and their right homologs can subserve speech and language, and that this variability may determine functional outcome.

Cortical lateralization during verb generation: a combined ERP and fMRI study.

Lateralization of scalp-recorded event-related potentials (ERPs) and functional MRI (fMRI) activation was investigated using a verb generation task in 10 healthy right-handed adults. ERPs showed an early transient positivity in the left inferior temporal region (500-1250 ms) following auditory presentation of the stimulus noun. A sustained slow cortical negativity of later onset (1250-3000 ms) was then recorded, most pronounced over left inferior frontal regions. fMRI data were in agreement with both ERP effects, showing left lateralized activation in inferior and superior temporal as well as inferior frontal cortices. Lateralized ERP effects occurred during the verb generation task but not during passive word listening or during word- and nonword repetition. Thus, ERPs and fMRI provided convergent evidence regarding language lateralization, with ERPs revealing the temporal sequence of posterior to anterior cortical activation during semantic retrieval.

Neural bases of childhood speech disorders: Lateralization and plasticity for speech functions during development

Current models of speech production in adults emphasize the crucial role played by the left perisylvian cortex, primary and pre-motor cortices, the basal ganglia, and the cerebellum for normal speech production. Whether similar brain-behaviour relationships and leftward cortical dominance are found in childhood remains unclear. Here we reviewed recent evidence linking motor speech disorders (apraxia of speech and dysarthria) and brain abnormalities in children and adolescents with developmental, progressive, or childhood-acquired conditions. We found no evidence that unilateral damage can result in apraxia of speech, or that left hemisphere lesions are more likely to result in dysarthria than lesion to the right. The few studies reporting on childhood apraxia of speech converged towards morphological, structural, metabolic or epileptic anomalies affecting the basal ganglia, perisylvian and rolandic cortices bilaterally. Persistent dysarthria, similarly, was commonly reported in individuals with syndromes and conditions affecting these same structures bilaterally. In conclusion, for the first time we provide evidence that longterm and severe childhood speech disorders result predominantly from bilateral disruption of the neural networks involved in speech production.

Role of fMRI in the decision‐making process: Epilepsy surgery for children

Functional MRI (fMRI) is increasingly being used to evaluate children and adolescents who are candidates for surgical treatment of intractable epilepsy. It has the advantage of being noninvasive and well tolerated by young people. By identifying important functional regions within the brain, including unpredictable patterns of functional reorganization, it can aid in surgical decision‐making. Here we illustrate this using a number of case studies from the pediatric epilepsy surgery program at our institution. We describe how fMRI, used in conjunction with conventional investigative methods such as neuropsychological assessment, MRI, and electrophysiology, can 1) help to improve functional outcome by enabling resective surgery that spares functional cortex, 2) guide surgical intervention by revealing when reorganization of function has occurred, and 3) show when abnormal cortex is also functionally active, and hence that surgery may not be the best option. Altogether, these roles have reduced the need for invasive procedures that can be both risky and distressing for young people with epilepsy. In our experience, fMRI has significantly contributed to the decision‐making process, and improved the counseling and management of young people with intractable epilepsy. J. Magn. Reson. Imaging 2006.

Influence of motor functional magnetic resonance imaging on the surgical management of children and adolescents with symptomatic focal epilepsy.

OBJECTIVETo determine the clinical value of motor functional magnetic resonance imaging (fMRI) in the presurgical evaluation of a large group of children and adolescents with epilepsy caused by lesions close to the central sulcus. METHODSForty-three patients (19 males; mean age, 13 years) with lesional focal epilepsy underwent motor fMRI as part of a multidisciplinary standardized presurgical evaluation between 2000 and 2006. fMRI data were analyzed using statistical parametric mapping (SPM2) and screened for the presence of movement-related artifacts. The ways in which the results of motor fMRI influenced the decision-making process were reviewed. RESULTSThe success rate of motor fMRI was 93% and data were of high quality in 67.5% of the patients. Together with other clinical considerations, motor fMRI results contributed to the surgical management of 32 patients (74%). They helped 1) to determine the type of surgery in 23 patients (72%; 12 cases with and 11 cases without invasive functional mapping), 2) to indicate a reduced benefit-risk ratio with the consequence that surgery was not further considered in 5 patients (16%), and 3) to indicate that surgery was not an appropriate option because of the high risk of motor function deficit in 4 patients (12%). CONCLUSIONMotor fMRI can be performed with a high degree of success and good data quality in this population of patients. It has an important additive role in the discussion of the feasibility of resective surgery contributing to the decision-making process for children with epilepsy caused by brain lesions close to the central sulcus.

Role of cerebellum in fine speech control in childhood: Persistent dysarthria after surgical treatment for posterior fossa tumour

Dysarthria following surgical resection of childhood posterior fossa tumour (PFT) is most commonly documented in a select group of participants with mutism in the acute recovery phase, thus limiting knowledge of post-operative prognosis for this population of children as a whole. Here we report on the speech characteristics of 13 cases seen long-term after surgical treatment for childhood PFT, unselected for the presence of post-operative mutism (mean time post-surgery=6y10m, range 1;4-12;6 years, two had post-operative mutism), and examine factors affecting outcome. Twenty-six age- and sex- matched healthy controls were recruited for comparison. Participants in both groups had speech assessments using detailed perceptual and acoustic methods. Over two-thirds of the group (69%) with removal of PFT had a profile of typically mild dysarthria. Prominent speech deficits included consonant imprecision, reduced rate, monopitch and monoloudness. We conclude that speech deficits may persist even up to 10 years post-surgery in participants who have not shown mutism in the acute phase. Of cases with unilateral lesions, poorer outcomes were associated with right cerebellar tumours compared to left, consistent with the notion based on adult data that speech is controlled by reciprocal right cerebellar/left frontal interactions. These results confirm the important role of the cerebellum in the control of fine speech movements in children.