FIACH: A biophysical model for automatic retrospective noise control in fMRI.

Different noise sources in fMRI acquisition can lead to spurious false positives and reduced sensitivity. We have developed a biophysically-based model (named FIACH: Functional Image Artefact Correction Heuristic) which extends current retrospective noise control methods in fMRI. FIACH can be applied to both General Linear Model (GLM) and resting state functional connectivity MRI (rs-fcMRI) studies. FIACH is a two-step procedure involving the identification and correction of non-physiological large amplitude temporal signal changes and spatial regions of high temporal instability. We have demonstrated its efficacy in a sample of 42 healthy children while performing language tasks that include overt speech with known activations. We demonstrate large improvements in sensitivity when FIACH is compared with current methods of retrospective correction. FIACH reduces the confounding effects of noise and increases the study's power by explaining significant variance that is not contained within the commonly used motion parameters. The method is particularly useful in detecting activations in inferior temporal regions which have proven problematic for fMRI. We have shown greater reproducibility and robustness of fMRI responses using FIACH in the context of task induced motion. In a clinical setting this will translate to increasing the reliability and sensitivity of fMRI used for the identification of language lateralisation and eloquent cortex. FIACH can benefit studies of cognitive development in young children, patient populations and older adults.

Maturation of language networks in children: A systematic review of 22years of functional MRI.

Understanding how language networks change during childhood is important for theories of cognitive development and for identifying the neural causes of language impairment. Despite this, there is currently little systematic evidence regarding the typical developmental trajectory for language from the field of neuroimaging. We reviewed functional MRI (fMRI) studies published between 1992 and 2014, and quantified the evidence for age-related changes in localisation and lateralisation of fMRI activation in the language network (excluding the cerebellum and subcortical regions). Although age-related changes differed according to task type and input modality, we identified four consistent findings concerning the typical maturation of the language system. First, activation in core semantic processing regions increases with age. Second, activation in lower-level sensory and motor regions increases with age as activation in higher-level control regions reduces. We suggest that this reflects increased automaticity of language processing as children become more proficient. Third, the posterior cingulate cortex and precuneus (regions associated with the default mode network) show increasing attenuation across childhood and adolescence. Finally, language lateralisation is established by approximately 5years of age. Small increases in leftward lateralisation are observed in frontal regions, but these are tightly linked to performance.

Reduced language connectivity in pediatric epilepsy.

OBJECTIVE: Functional connectivity (FC) among language regions is decreased in adults with epilepsy compared to controls, but less is known about FC in children with epilepsy. We sought to determine if language FC is reduced in pediatric epilepsy, and examined clinical factors that associate with language FC in this population. METHODS: We assessed FC during an age-adjusted language task in children with left-hemisphere focal epilepsy (n = 19) compared to controls (n = 19). Time series data were extracted for three left regions of interest (ROIS) and their right homologues: inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and Wernicke's area (WA) using SPM8. Associations between FC and factors such as cognitive performance, language dominance, and epilepsy duration were assessed. RESULTS: Children with epilepsy showed decreased interhemispheric connectivity compared to controls, particularly between core left language regions (IFG, WA) and their right hemisphere homologues, as well as decreased intrahemispheric right frontal FC. Increased intrahemispheric FC between left IFG and left WA was a positive predictor of language skills overall, and naming ability in particular. FC of language areas was not affected by language dominance, as the effects remained only when examining participants with left language dominance. Overall FC did not differ according to duration of epilepsy or age of onset. SIGNIFICANCE: FC during a language task is reduced in children, similar to findings in adults. In specific, children with left focal epilepsy demonstrated decreased interhemispheric FC in temporal and frontal language connections and decreased intrahemispheric right frontal FC. These differences were present near the onset of epilepsy. Greater FC between left language centers is related to better language ability. Our results highlight that connectivity of language areas has a developmental pattern and is related to cognitive ability.

Vulnerability of the ventral language network in children with focal epilepsy.

Children with focal epilepsy are at increased risk of language impairment, yet the neural substrate of this dysfunction is not yet known. Using functional magnetic resonance imaging we investigated the impact of focal epilepsy on the developing language system using measures of network topology (spatial organization of activation) and synchrony (functional connectivity). We studied healthy children (n = 48, 4-12 years, 24 females) and children with focal epilepsy (n = 21, 5-12 years, nine females) with left hemisphere language dominance. Participants performed an age-adjusted auditory description decision task during functional magnetic resonance imaging, to identify perisylvian language regions. Mean signal change was extracted from eight left perisylvian regions of interest and compared between groups. Paired region of interest functional connectivity analysis was performed on time course data from the same regions, to investigate left network synchrony. Two principal component analyses were performed to extract (i) patterns of activation (using mean signal change data); and (ii) patterns of synchronized regions (using functional connectivity data). For both principal component analyses two components (networks) were extracted, which mapped onto the functional anatomy of dorsal and ventral language systems. Associations among network variables, age, epilepsy-related factors and verbal ability were assessed. Activated networks were affected by age and epilepsy [F(2,60) = 3.74, P = 0.03]: post hoc analyses showed, for healthy children, activation in both ventral and dorsal networks decreased with age (P = 0.02). Regardless of age and task performance, children with epilepsy showed reduced activation of the ventral network (P < 0.001). They also showed a trend for increased activation of the dorsal network (P = 0.08) associated with improved task performance (r = 0.62, P = 0.008). Crucially, decreased activation of the ventral network in patients predicted poorer language outcome ([Formula: see text] = 0.47, P = 0.002). This suggests childhood onset epilepsy preferentially alters maturation of the ventral language system, and this is related to poorer language ability.

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.