Metabolic correlates of cognitive function in children with unilateral Sturge-Weber syndrome: Evidence for regional functional reorganization and crowding.

To evaluate metabolic changes in the ipsi- and contralateral hemisphere in children showing a cognitive profile consistent with early reorganization of cognitive function, we evaluated the regional glucose uptake, interhemispheric metabolic connectivity, and cognitive function in children with unilateral SWS. Interictal 2-deoxy-2[18 F]fluoro-D-glucose (FDG)-PET scans of 27 children with unilateral SWS and mild epilepsy and 27 age-matched control (non-SWS children with epilepsy and normal FDG-PET) were compared using statistical parametric mapping (SPM). Regional FDG-PET abnormalities calculated as SPM(t) scores in the SWS group were correlated with cognitive function (IQ) in left- and right-hemispheric subgroups. Interhemispheric metabolic connectivity between homotopic cortical regions was also calculated. Verbal IQ was substantially (≥10 points difference) higher than non-verbal IQ in 61% of the right- and 71% of the left-hemispheric SWS group. FDG SPM(t) scores in the affected hemisphere showed strong positive correlations with IQ in the left-hemispheric, but not in right-hemispheric SWS group in several frontal, parietal, and temporal cortical regions. Significant positive interhemispheric metabolic connectivity, present in controls, was diminished in the SWS group. In addition, the left-hemispheric SWS group showed inverse metabolic interhemispheric correlations in specific parietal, temporal, and occipital regions. FDG SPM(t) scores in the same regions of the right (unaffected) hemisphere showed inverse correlations with IQ. These findings suggest that left-hemispheric lesions in SWS often result in early reorganization of verbal functions while interfering with ("crowding") their non-verbal cognitive abilities. These cognitive changes are associated with specific metabolic abnormalities in the contralateral hemisphere not directly affected by SWS.

Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug-resistant epilepsy.

OBJECTIVE: We analyzed long-term changes of lobar glucose metabolic abnormalities in relation to clinical seizure variables and development in a large group of children with medically refractory epilepsy. METHODS: Forty-one children (25 males) with drug-resistant epilepsy had a baseline positron emission tomography (PET) scan at a median age of 4.7 years; the scans were repeated after a median of 4.3 years. Children with progressive neurological disorders or space-occupying lesion-related epilepsy and those who had undergone epilepsy surgery were excluded. The number of affected lobes on 2-deoxy-2(18 F)-fluoro-D-glucose-PET at baseline and follow-up was correlated with epilepsy variables and developmental outcome. RESULTS: On the initial PET scan, 24 children had unilateral and 13 had bilateral glucose hypometabolism, whereas 4 children had normal scans. On the follow-up scan, 63% of the children showed an interval expansion of the hypometabolic region, and this progression was associated with persistent seizures. In contrast, 27% showed less extensive glucose hypometabolism at follow-up; most of these subjects manifested a major interval decrease in seizure frequency. Delayed development was observed in 21 children (51%) at baseline and 28 (68%) at follow-up. The extent of glucose hypometabolism at baseline correlated with developmental levels at the time of both baseline (r = .31, P = .05) and follow-up scans (r = .27, P = .09). SIGNIFICANCE: In this PET study of unoperated children with focal epilepsy, the lobar pattern of glucose hypometabolism changed over time in 90% of the cases. The results support the notion of an expansion of metabolic dysfunction in children with persistent frequent seizures and its association with developmental delay, and support that optimized medical treatment to control seizures may contribute to better neurocognitive outcome if no surgery can be offered.

Cognitive and motor outcomes in children with unilateral Sturge-Weber syndrome: Effect of age at seizure onset and side of brain involvement.

PURPOSE: Most children with Sturge-Weber syndrome (SWS) develop seizures that may contribute to neurocognitive status. In this study, we tested the hypothesis that very early seizure onset has a particularly detrimental effect on the cognitive and/or motor outcomes of children with unilateral SWS. We also tested whether side of SWS brain involvement modulates the effect of seizure variables on the pattern of cognitive abnormalities. METHODS: Thirty-four children (22 girls; mean age 6.1years) with unilateral SWS and history of epilepsy in a longitudinal cohort underwent neurological and cognitive evaluations. Global intelligent quotient (GIQ), verbal intelligent quotient (VIQ), nonverbal intelligent quotient (IQ), and motor function were correlated with epilepsy variables, side and extent of brain involvement on magnetic resonance imaging (MRI). RESULTS: Mean age at seizure onset was 1.3years (0.1-6years) and mean IQ at follow-up was 86 (45-118). Age at seizure onset showed a logarithmic association with IQ, with maximum impact of seizures starting before age 1year, both in uni- and multivariate regression analyses. In the left SWS group (N=20), age at seizure onset was a strong predictor of nonverbal IQ (p=0.001); while early seizure onset in the right-hemispheric group had a more global effect on cognitive functions (p=0.02). High seizure frequency and long epilepsy duration also contributed to poor outcome IQ independently in multivariate correlations. Children with motor involvement started to have seizures at/before 7months of age, while frontal lobe involvement was the strongest predictor of motor deficit in a multivariate analysis (p=0.017). CONCLUSION: These findings suggest that seizure onset prior to age 1year has a profound effect on severity of cognitive and motor dysfunction in children with SWS; however, the effect of seizures on the type of cognitive deficit is influenced by laterality of brain involvement.

Clinical and metabolic correlates of cerebral calcifications in Sturge-Weber syndrome.

AIM: To evaluate clinical and metabolic correlates of cerebral calcifications in children with Sturge-Weber syndrome (SWS). METHOD: Fifteen children (11 females, four males; age range 7mo-9y, mean 4y 1mo) with unilateral SWS underwent baseline and follow-up magnetic resonance imaging (MRI) with susceptibility weighted imaging (SWI), glucose metabolism positron emission tomography (PET), and neurocognitive assessment (mean follow-up 1y 8mo). Calcified brain volumes measured on SWI were correlated with areas of abnormal glucose metabolism, seizure variables, and cognitive function (IQ). RESULTS: Ten children had brain calcification at baseline and 11 at follow-up. Mean calcified brain volume increased from 1.69 to 2.47cm3 (p=0.003) in these children; the rate of interval calcified volume increase was associated with early onset of epilepsy (Spearman's rho [rs ]=-0.63, p=0.036). Calcified brain regions showed a variable degree of glucose hypometabolism with the metabolic abnormalities often extending to non-calcified cerebral lobes. Larger calcified brain volumes at baseline were associated with longer duration of epilepsy (rs =0.69, p=0.004) and lower outcome IQ (rs =-0.53, p=0.042). INTERPRETATION: Brain calcifications are common and progress faster in children with SWS with early epilepsy onset, and are associated with a variable degree of hypometabolism, which is typically more extensive than the calcified area. Higher calcified brain volumes may indicate a risk for poorer neurocognitive outcome.

Postoperative axonal changes in the contralateral hemisphere in children with medically refractory epilepsy: A longitudinal diffusion tensor imaging connectome analysis.

To determine brain plasticity changes due to resective epilepsy surgery in children, we performed a longitudinal connectome analysis on the pattern of axonal connectivity in the contralateral hemisphere. Pre- and postoperative diffusion tensor imaging (DTI) data were acquired from 35 children with intractable focal epilepsy. A total of 54 brain regions of interest (ROIs) were generated in the hemisphere contralateral to the resection. Within a 54 × 54 connectivity matrix, a pairwise connectivity score was calculated for each connection between two ROIs, based on the DTI fiber streamline number in each connection. A permuted Spearman's ρ-rank analysis was used to identify specific inter-regional connections showing a significant association between the postoperative change of connectivity score and clinical variables. Nineteen connections in the contralateral hemisphere showed postoperative increases in the strength of connectivity. Postoperative increase in connectivity between insular-inferior frontal operculum regions as well as that between superior frontal orbital and mid frontal orbital regions were both significantly associated with a larger surgical resection volume (ρ > +0.40) and a younger patient age (ρ > -0.34). These increases were more robust in patients with frontal resection and in those achieving seizure freedom. Neuropsychological evaluation on subsets of patients revealed that such increases in connectivity were associated with preserved or improved cognitive functions such as visual memory and planning. Resective epilepsy surgery may lead to increased contralateral axonal connectivity in children with focal epilepsy. Our data lead to a hypothesis that such increased connectivity may be an imaging marker of postoperative brain plasticity to compensate for cognitive function. Hum Brain Mapp 37:3946-3956, 2016. © 2016 Wiley Periodicals, Inc.

Relationship between genotype and arcuate fasciculus morphology in six young children with global developmental delay: Preliminary DTI stuy.

PURPOSE: To investigate whether different genetic mutations observed in children with global developmental delay (GD) are associated with unique patterns of the arcuate fasciculus dysmorphology. MATERIALS AND METHODS: Six children with GD (age: 36.8 ± 14.1 months, 5 boys) having mutations in MID1, CDK4, SFRP1, EN2, RXRG-GLRB, or MECP2, and five children with typical development (TD, age: 38.5 ± 20.5 months, 4 boys) underwent a 3 Tesla MRI including diffusion weighted imaging (DWI). Five language pathway segments in the left hemisphere, "C1 : Broca's to Wernicke's area," "C2 : Broca's to premotor area," "C3 : premotor to Wernicke's area," "C4 : Wernicke's to inferior parietal area," and "C5 : premotor to inferior parietal area" were objectively identified using the DWI "maximum a posteriori probability" classifier. RESULTS: Affinity propagation clustering analysis found that three arcuate pathway segments, C1,2,4 , of MID1, CDK4, EN2, and MECP2 had a similar pattern of volume ratio while those of SFRP1 and RXRG-GLRB had a heterogeneous pattern of volume ratio (net similarity = -0.01). Using receiver operating characteristic curve analysis, the fiber ratios of C1,2,4 showed a high probability to discriminate between GD and TD, yielding an accuracy of 0.91, 0.91, 1.00, respectively. The fiber volumes of C1 and C4 showed a strong correlation with expressive language (R2 = 0.6019; P-value = 0.033) and receptive language (R2 = 0.6379; P-value = 0.028), respectively. CONCLUSION: The findings of the present study provide preliminary evidence to suggest that different segments of the arcuate fasciculus are formed under the regulation of different genes which, when mutated, may result in developmental delay. J. Magn. Reson. Imaging 2016;44:1504-1512.

Deep Venous Remodeling in Unilateral Sturge-Weber Syndrome: Robust Hemispheric Differences and Clinical Correlates.

BACKGROUND: Enlarged deep medullary veins (EDMVs) in patients with Sturge-Weber syndrome (SWS) may provide compensatory venous drainage for brain regions affected by the leptomeningeal venous malformation (LVM). We evaluated the prevalence, extent, hemispheric differences, and clinical correlates of EDMVs in SWS. METHODS: Fifty children (median age: 4.5 years) with unilateral SWS underwent brain magnetic resonance imaging prospectively including susceptibility-weighted imaging (SWI); children aged 2.5 years or older also had a formal neurocognitive evaluation. The extent of EDMVs was assessed on SWI by using an EDMV hemispheric score, which was compared between patients with right and left SWS and correlated with clinical variables. RESULTS: EDMVs were present in 89% (24 of 27) of right and 78% (18 of 23) of left SWS brains. Extensive EDMVs (score >6) were more frequent in right (33%) than in left SWS (9%; P = 0.046) and commonly occurred in young children with right SWS. Patients with EDMV scores >4 had rare (less than monthly) seizures, whereas 35% (11 of 31) of patients with EDMV scores ≤4 had monthly or more frequent seizures (P = 0.003). In patients with right SWS and at least two LVM-affected lobes, higher EDMV scores were associated with higher intelligence quotient (P < 0.05). CONCLUSIONS: Enlarged deep medullary veins are common in unilateral SWS, but extensive EDMVs appear to develop more commonly and earlier in right hemispheric SWS. Deep venous remodeling may be a compensatory mechanism contributing to better clinical outcomes in some patients with SWS.

Relationship between aberrant brain connectivity and clinical features in Angelman Syndrome: a new method using tract based spatial statistics of DTI color-coded orientation maps.

AIM: In order to relate brain structural abnormalities to clinical features of Angelman Syndrome (AS), we determined the locations of abnormal regional white matter architecture in AS children using a sensitive and objective whole brain approach to analyze diffusion tensor imaging (DTI) color-coded orientation maps. METHODS: Using tract based spatial statistics (TBSS) of DTI color-coded orientation maps, the fraction of fibers oriented in the anteroposterior (AP), mediolateral (ML) and superioinferior (SI) directions were determined in whole brain white matter of 7 children with AS (mean age: 70±25.78 months, 5 males) and 7 children with typical development (TD, mean age: 79.8±17.25 months, 4 males). TBSS of FA map was also performed for comparison. RESULTS: Children with AS had a significantly lower AP component than the TD group in 9 clusters (3 bilateral and 3 unilateral). Bilateral clusters were located in inferior fronto-occipital fasciculus, anterior thalamic radiation and arcuate fasciculus regions. Unilateral clusters involved left brainstem, left cingulum and right uncinate regions. Similarly, children with AS had significantly lower ML component than the TD group in 4 clusters (2 in corpus callosum and 2 unilateral clusters). Unilateral clusters were located in the left cingulum and left anterior thalamic radiation regions. SI component was lower in children with AS in two clusters compared to TD (corticospinal tract and corpus callosum). FA map clusters mostly corresponded with component clusters. INTERPRETATION: Children with AS have a global impairment of white matter integrity including AP, ML and SI components in whole brain suggesting a potential underlying error with axon guidance mechanisms during brain development possibly due to loss of UBE3A gene expression. Some of this aberrant connectivity can be related to the clinical features of AS.

Exome sequencing of a pedigree with Tourette syndrome or chronic tic disorder.

Ten members of a 3-generation pedigree with 7 showing Tourette syndrome/chronic tic phenotype (TS-CTD) were evaluated with whole exome sequencing. We identified 3 novel, nonsynonymous single nucleotide variants in the MRPL3, DNAJC13, and OFCC1 genes that segregated with chronic tic phenotype. These variants were not present in 100 control subjects or in dbSNP/1000 Genomes databases. A novel variant in the 5' untranslated region of the OFCC1 gene was found in 2 TS-CTD patients from a different pedigree. Further studies will clarify the importance of variants in MRPL3, DNAJC13, and OFCC1 genes in TS.

Altered white matter structure of the dentatorubrothalamic pathway in children with autistic spectrum disorders.

Neuropathological studies have demonstrated decreased Purkinje cells in cerebellar cortex and changes in the dentate nucleus of the cerebellum, the projection target for the Purkinje cells, in autistic spectrum disorders (ASD). The dentatorubrothalamic tract is formed by efferents from the dentate nucleus projecting toward the red nucleus with axon collaterals to this nucleus and continuing to innervate the ventral lateral and ventral anterior nuclei of the thalamus. In the current study, we assessed whether the dentatorubrothalamic tract is altered in ASD using Q-ball imaging (QBI). The QBI tractography was performed in 13 children with high functioning ASD (HFA), 11 children with low functioning ASD (LFA), and 14 typically developing children (TD). Regions of interest in dentate nucleus and red nucleus in both hemispheres were objectively placed to sort bilateral dorsal-rostral (DR), dorsal-caudal (DC), ventral-rostral (VR), and ventral-caudal (VC) portions of the dentatorubrothalamic pathway. Group differences in fractional anisotropy (FA), axial diffusivity, radial diffusivity, and fiber volume of individual pathways were analyzed. Significantly reduced FA was found in children with LFA and HFA, compared to the TD group in tracts originating in all four subdivisions of the right dentate nucleus. Tract-based morphometry (TBM) analysis demonstrated significant reductions of FA in caudal midbrain (p<0.0001), dorsal-caudal dentate (p=0.0013), and ventral-caudal dentate (p=0.0061) on the right in the LFA group. The FA values in TBM segments of right VR and VC pathways were significantly correlated with communication skills in the combined HFA/LFA group, while there was a significant correlation found between TBM segments of right DR pathway and daily living skills (r=0.76; p=0.004). Decreased white matter integrity in dorsal portions of the dentatorubrothalamic tract may be related to motor features in ASD, while changes in the ventral portions are related more to communication behavior.

Congruence of happy and sad emotion in music and faces modifies cortical audiovisual activation.

BACKGROUND: The powerful emotion inducing properties of music are well-known, yet music may convey differing emotional responses depending on environmental factors. We hypothesized that neural mechanisms involved in listening to music may differ when presented together with visual stimuli that conveyed the same emotion as the music when compared to visual stimuli with incongruent emotional content. METHODS: We designed this study to determine the effect of auditory (happy and sad instrumental music) and visual stimuli (happy and sad faces) congruent or incongruent for emotional content on audiovisual processing using fMRI blood oxygenation level-dependent (BOLD) signal contrast. The experiment was conducted in the context of a conventional block-design experiment. A block consisted of three emotional ON periods, music alone (happy or sad music), face alone (happy or sad faces), and music combined with faces where the music excerpt was played while presenting either congruent emotional faces or incongruent emotional faces. RESULTS: We found activity in the superior temporal gyrus (STG) and fusiform gyrus (FG) to be differentially modulated by music and faces depending on the congruence of emotional content. There was a greater BOLD response in STG when the emotion signaled by the music and faces was congruent. Furthermore, the magnitude of these changes differed for happy congruence and sad congruence, i.e., the activation of STG when happy music was presented with happy faces was greater than the activation seen when sad music was presented with sad faces. In contrast, incongruent stimuli diminished the BOLD response in STG and elicited greater signal change in bilateral FG. Behavioral testing supplemented these findings by showing that subject ratings of emotion in faces were influenced by emotion in music. When presented with happy music, happy faces were rated as more happy (p=0.051) and sad faces were rated as less sad (p=0.030). When presented with sad music, happy faces were rated as less happy (p=0.008) and sad faces were rated as sadder (p=0.002). INTERPRETATION: Happy-sad congruence across modalities may enhance activity in auditory regions while incongruence appears to impact the perception of visual affect, leading to increased activation in face processing regions such as the FG. We suggest that greater understanding of the neural bases of happy-sad congruence across modalities can shed light on basic mechanisms of affective perception and experience and may lead to novel insights in the study of emotion regulation and therapeutic use of music.

Focal white matter abnormalities related to neurocognitive dysfunction: an objective diffusion tensor imaging study of children with Sturge-Weber syndrome.

White matter (WM) loss is associated with cognitive impairment in Sturge-Weber syndrome (SWS). In this study, we evaluated if cognitive and fine motor abnormalities are associated with impaired microstructural integrity in specific WM regions in SWS. Fifteen children with unilateral SWS (age: 3-12.4 y) and 11 controls (age: 6-12.8 y) underwent diffusion tensor imaging. Tract-based spatial statistics was used for objective comparisons of WM fractional anisotropy (FA) and mean diffusivity (MD) between the two groups. In the SWS group, WM FA and MD values were correlated with intelligence quotient (IQ) and fine motor scores, with age as a co-variate. Bilateral, multilobar WM areas showed decreased FA, whereas significant MD increases were confined to small ipsilateral posterior regions in SWS children. IQ in the SWS group (range: 47-128) was positively correlated with FA in the ipsilateral prefrontal WM and inversely associated with MD in the ipsilateral posterior parietal WM. A negative correlation between fine motor function and MD was found in ipsilateral frontal WM encompassing motor pathways. Microstructural WM abnormalities occur not only ipsilateral but also contralateral to the angioma in unilateral SWS. Nevertheless, cognitive and fine motor functions are related to diffusion abnormalities in specific ipsilateral, mostly frontal, WM regions.

Brain damage and IQ in unilateral Sturge-Weber syndrome: support for a "fresh start" hypothesis.

We tested the hypothesis that extent of severe hypometabolism measured by fluorodeoxyglucose PET has a U-shaped (nonlinear) relationship to IQ in children with unilateral Sturge-Weber syndrome. Thirty-five consecutive children (age range: 30-153 months) with Sturge-Weber syndrome and unilateral brain involvement were enrolled in the study. Participants underwent cognitive assessment and interictal fluorodeoxyglucose PET scans. Regression analyses tested whether a quadratic model best accounted for the relationship between extent of severe cortical hypometabolism and IQ, controlling for seizure variables. A significant quadratic relationship was found between IQ and extent of severe (but not total) hypometabolism. Seizure variables also contributed significant variance to cognitive functions. Results suggest that intermediate size of severe hemispheric hypometabolism is associated with the worst cognitive outcomes, and small or absent lesions, with the best cognitive outcomes. Children in whom a very large extent of the hemisphere is severely affected are likely to have relatively preserved cognitive function.

Altered water diffusivity in cortical association tracts in children with early deprivation identified with Tract-Based Spatial Statistics (TBSS).

Institutional rearing is associated with neurocognitive and behavioral difficulties. Although such difficulties are thought to reflect abnormal neurologic development resulting from early social deprivation (ED) and there is evidence for functional abnormality in children with histories of ED, the impact of early deprivation on brain anatomy has received little study in humans. The present study utilized an objective and sensitive neuroimaging analysis technique (Tract-Based Spatial Statistics) to evaluate white matter fractional anisotropy (FA) and diffusivity in a group of right-handed children with histories of ED (n = 17; mean age = 10.9 + 2.6 years) as compared with age-matched healthy controls (n = 15; mean age = 11.7 + or - 2.8 years). Participants underwent magnetic resonance imaging diffusion tensor imaging sequences and comprehensive neuropsychological evaluations. Results revealed reduced FA in frontal, temporal, and parietal white matter including components of uncinate and superior longitudinal fasciculi, in children with histories of ED, providing further support for limbic and paralimbic abnormalities in children with such histories. Furthermore, white matter abnormalities were associated with duration of time in the orphanage and with inattention and hyperactivity scores. It is suspected that the observed white matter abnormalities are associated with multiple depriving factors (e.g., poor prenatal care, postnatal stress) associated with institutional caregiving.

Alterations in frontal lobe tracts and corpus callosum in young children with autism spectrum disorder.

Major frontal lobe tracts and corpus callosum (CC) were investigated in 32 children with autism spectrum disorder (ASD, mean age: 5 years), 12 nonautistic developmentally impaired children (DI, mean age: 4.6 years), and 16 typically developing children (TD, mean age: 5.5 years) using diffusion tensor imaging tractography and tract-based spatial statistics. Various diffusion and geometric properties were calculated for uncinate fasciculus (UF), inferior fronto-occipital fasciculus (IFO), arcuate fasciculus (AF), cingulum (Cg), CC, and corticospinal tract. Fractional anisotropy was lower in the right UF, right Cg and CC in ASD and DI children; in right AF in ASD children; and in bilateral IFO in DI children, compared with TD children. Apparent diffusion coefficient was increased in right AF in both ASD and DI children. The ASD group showed shorter length of left UF and increased length, volume, and density of right UF; increased length and density of CC; and higher density of left Cg, compared with the TD group. Compared with DI group, ASD group had increased length, volume, and density of right UF; higher volume of left UF; and increased length of right AF and CC. Volume of bilateral UF and right AF and fiber density of left UF were positively associated with autistic features.

Abnormal water diffusivity in corticostriatal projections in children with Tourette syndrome.

The fronto-striato-thalamic circuit has been implicated in the pathomechanism of Tourette Syndrome (TS). To study white and gray matter comprehensively, we used a novel technique called Tract-Based Spatial Statistics (TBSS) combined with voxel-based analysis (VBA) of diffusion tensor MR images in children with TS as compared to typically developing controls. These automated and unbiased methods allow analysis of cerebral white matter and gray matter regions. We compared 15 right-handed children with TS (mean age: 11.6 ± 2.5 years, 12 males) to 14 age-matched right-handed healthy controls (NC; mean age: 12.29 ± 3.2 years, 6 males). Tic severity and neurobehavioral scores were correlated with FA and ADC values in regions found abnormal by these methods. For white matter, TBSS analysis showed regions of increased ADC in the corticostriatal projection pathways including left external capsule and left and right subcallosal fasciculus pathway in TS group compared to NC group. Within the TS group, ADC for the left external capsule was negatively associated with tic severity (r= -0.586, P = 0.02). For gray matter, VBA revealed increased ADC for bilateral orbitofrontal cortex, left putamen, and left insular cortex. ADC for the right and left orbitofrontal cortex was highly correlated with internalizing problems (r = 0.665; P = 0.009, r = 0.545; P = 0.04, respectively). Altogether, this analysis revealed focal diffusion abnormalities in the corticostriatal pathway and in gray matter structures involved in the fronto-striatal circuit in TS. These diffusion abnormalities could serve as a neuroimaging marker related to tic severity and neurobehavioral abnormalities in TS subjects.

Altered efficiency of white matter connections for language function in children with language disorder.

To characterize structural white matter substrates associated with language functions in children with language disorders (LD), a psychometry-driven diffusion tractography network was investigated with canonical correlation analysis (CCA), which can reliably predict expressive and receptive language scores from the nodal efficiency (NE) of the obtained network. The CCA found that the NE values of six regions: left inferior-frontal-opercular, left insular, left angular gyrus, left superior-temporal-gyrus, right hippocampus, and right cerebellar-lobule were highly correlated with language scores (ρexpressive/ρreceptive = 0.609/0.528), yielding significant differentiation of LD from controls using new imaging predictors uexpressive (F = 15.024, p = .0003) and ureceptive (F = 7.421, p = .009). This study demonstrates the utility of intrinsic language network analyses in distinguishing and potentially subtyping the type and severity of language deficit, especially in very young children (≤3 years) with LD. The use of structural imaging to identify children with persisting language disorder could prove useful in understanding the etiology of language disorder.

Diffusion tensor imaging of frontal lobe in autism spectrum disorder.

To investigate frontal lobe white matter in children with autism spectrum disorder (ASD), we performed diffusion tensor imaging (DTI) in 50 ASD children (mean age: 57.5 +/- 29.2 months, 43 males) and 16 typically developing children (mean age: 82.1 +/- 41.4 months, 11 males). The apparent diffusion coefficient (ADC) was significantly higher for whole frontal lobe (P = 0.011), long (P < 0.001) and short range (P = 0.0126) association fibers in ASD group. There was a trend toward statistical significance in the fractional anisotropy (FA) of whole frontal lobe fibers (P = 0.11). FA was significantly lower in ASD group for short range fibers (P = 0.0031) but not for long range fibers (P = not significant [NS]). There was no between-group difference in the number of frontal lobe fibers (short and long) (P = NS). The fiber length distribution was significantly more positively skewed in the normal population than in the ASD group (P < 0.001). The long range association fibers of frontal lobe were significantly longer in ASD group (P = 0.026 for both left and right hemispheres). Abnormal frontal FA and ADC may be due to white matter organization abnormalities in ASD. Lack of evidence for excessive short range connectivity in ASD in this study may need to be re-examined with future advances in DTI technology.

Absence of arcuate fasciculus in children with global developmental delay of unknown etiology: a diffusion tensor imaging study.

OBJECTIVE: To investigate cortical association tracts using diffusion tensor imaging (DTI) in children with global developmental delay of unknown etiology. STUDY DESIGN: We performed DTI in 20 patients (age range: 18-83 months, mean: 45 +/- 16 months, 12 males) with a history of global developmental delay and 10 typically developing children (age range: 26-99 months, mean: 54 +/- 24 months, 5 males). DTI tractography was performed to isolate major cortical association tracts. RESULTS: In 9 out of 20 patients, arcuate fasciculus (AF) was absent bilaterally and in another 2 patients, it was absent in left hemisphere. In contrast, AF was present bilaterally in all typically developing children. Fractional Anisotropy (FA) of inferior longitudinal fasciculus (ILF) was asymmetric in the control group but not in the developmental delay group (P = .04). FA was significantly reduced in right ILF in developmentally delayed children compared with controls (P = .03). FA of other association tracts was not different between patients and controls (P = NS). The apparent diffusion coefficient (ADC) showed no asymmetry for these tracts in controls or developmentally delayed children (P = NS). CONCLUSIONS: DTI can be used to identify absence of AF and inadequate maturation of ILF in children with global developmental delay of unknown etiology.

Diffusion tensor imaging of brain plasticity after occipital lobectomy.

Reorganization involving residual visual pathways with unilateral damage to the primary visual cortex was previously described. Using diffusion tensor imaging, we measured water diffusion-related changes in the optic radiation contralateral to occipital lobe ablation in children with intractable epilepsy. We studied 10 children who had undergone a resection of the unilateral occipital cortex and 13 control subjects. Diffusion tensor imaging was acquired using a 1.5 Tesla magnetic resonance scanner. Fiber bundles representing optic radiation were tracked. Diffusion parameters included mean fractional anisotropy, apparent diffusion coefficient, and diffusion parallel and perpendicular to the fiber tract. In the surgical group, fractional anisotropy values of optic radiation contralateral to the side of resection exhibited a significant positive partial correlation (r = 0.752, P = 0.019) with duration of time between surgery and diffusion tensor imaging acquisition, after controlling for age. The apparent diffusion coefficient and parallel diffusivity were higher in the surgical versus the control group, but did not differ among patients. After unilateral resection of the occipital lobe, the contralateral optic radiation undergoes significant changes in anisotropy. Such structural white-matter changes may represent an adaptive response because of unilateral occipital ablation, and may account for plasticity changes observed in functional magnetic resonance imaging.