RESUMO
This study investigated whether current state-of-the-art deep reasoning network analysis on psychometry-driven diffusion tractography connectome can accurately predict expressive and receptive language scores in a cohort of young children with persistent language concerns (n = 31, age: 4.25 ± 2.38 years). A dilated convolutional neural network combined with a relational network (dilated CNN + RN) was trained to reason the nonlinear relationship between "dilated CNN features of language network" and "clinically acquired language score". Three-fold cross-validation was then used to compare the Pearson correlation and mean absolute error (MAE) between dilated CNN + RN-predicted and actual language scores. The dilated CNN + RN outperformed other methods providing the most significant correlation between predicted and actual scores (i.e., Pearson's R/p-value: 1.00/<.001 and .99/<.001 for expressive and receptive language scores, respectively) and yielding MAE: 0.28 and 0.28 for the same scores. The strength of the relationship suggests elevated probability in the prediction of both expressive and receptive language scores (i.e., 1.00 and 1.00, respectively). Specifically, sparse connectivity not only within the right precentral gyrus but also involving the right caudate had the strongest relationship between deficit in both the expressive and receptive language domains. Subsequent subgroup analyses inferred that the effectiveness of the dilated CNN + RN-based prediction of language score(s) was independent of time interval (between MRI and language assessment) and age of MRI, suggesting that the dilated CNN + RN using psychometry-driven diffusion tractography connectome may be useful for prediction of the presence of language disorder, and possibly provide a better understanding of the neurological mechanisms of language deficits in young children.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Aprendizado Profundo , Imagem de Tensor de Difusão , Transtornos da Linguagem/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Adolescente , Córtex Cerebral/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Transtornos da Linguagem/patologia , Transtornos da Linguagem/fisiopatologia , Masculino , Rede Nervosa/patologia , PsicometriaRESUMO
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.
Assuntos
Encéfalo/metabolismo , Cognição/fisiologia , Síndrome de Sturge-Weber/metabolismo , Síndrome de Sturge-Weber/psicologia , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fluordesoxiglucose F18 , Lateralidade Funcional , Glucose , Humanos , Inteligência/fisiologia , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Síndrome de Sturge-Weber/diagnóstico por imagem , Síndrome de Sturge-Weber/tratamento farmacológicoRESUMO
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.
Assuntos
Glicemia/metabolismo , Encéfalo/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Metabolismo Energético/fisiologia , Adolescente , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/tratamento farmacológico , Deficiências do Desenvolvimento/fisiopatologia , Progressão da Doença , Dominância Cerebral/efeitos dos fármacos , Dominância Cerebral/fisiologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Eletroencefalografia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
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.
Assuntos
Idade de Início , Encéfalo/diagnóstico por imagem , Cognição , Inteligência , Imageamento por Ressonância Magnética/métodos , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/psicologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Epilepsia/etiologia , Epilepsia/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Lateralidade Funcional , Humanos , Lactente , Testes de Inteligência , Estudos Longitudinais , Masculino , Análise Multivariada , Estudos Prospectivos , Convulsões/complicações , Convulsões/etiologia , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/fisiopatologiaRESUMO
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.
Assuntos
Encefalopatias/fisiopatologia , Encéfalo/diagnóstico por imagem , Calcinose/fisiopatologia , Síndrome de Sturge-Weber/fisiopatologia , Encefalopatias/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Pré-Escolar , Cognição , Progressão da Doença , Feminino , Seguimentos , Glucose/metabolismo , Humanos , Lactente , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Síndrome de Sturge-Weber/diagnóstico por imagem , Fatores de TempoRESUMO
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.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/cirurgia , Adolescente , Axônios , Criança , Pré-Escolar , Conectoma , Imagem de Tensor de Difusão , Epilepsia Resistente a Medicamentos/parasitologia , Epilepsias Parciais/parasitologia , Feminino , Lateralidade Funcional , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/cirurgia , Testes Neuropsicológicos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). STUDY DESIGN: Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. RESULTS: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. CONCLUSIONS: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00873509.
Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Buspirona/administração & dosagem , Desenvolvimento Infantil/efeitos dos fármacos , Agonistas do Receptor de Serotonina/administração & dosagem , Buspirona/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Serotonina/sangue , Agonistas do Receptor de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
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.
Assuntos
Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Imagem de Tensor de Difusão/métodos , Vias Neurais/patologia , Lobo Parietal/patologia , Lobo Temporal/patologia , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologiaRESUMO
BACKGROUND: Postcontrast magnetic resonance imaging (MRI), obtained under anesthesia, is often used to evaluate brain parenchymal and vascular abnormalities in young children, including those with Sturge-Weber syndrome. However, anesthesia and contrast administration may carry risks. We explored the feasibility and potential diagnostic value of a noncontrast, nonsedate MRI acquisition in Sturge-Weber syndrome children and their siblings with a wide range of cognitive and behavioral functioning. METHODS: Twenty children (10 with Sturge-Weber syndrome and 10 healthy siblings; age: 0.7-13.5 years) underwent nonsedate 3-tesla (T) brain MRI acquisition with noncontrast sequences (including susceptibility-weighted imaging) prospectively along with neuropsychology assessment. All images were evaluated for quality, and MRI abnormalities identified in the Sturge-Weber syndrome group were compared to those identified on previous clinical pre- and postcontrast MRI. RESULTS: Nineteen participants (95%) completed the MRI with good (n = 18) or adequate (n = 1) quality, including all children with Sturge-Weber syndrome and all 5 children ≤5 years of age. The Sturge-Weber syndrome group had lower cognitive functions than the controls, and both groups had several children with behavioral issues, without an apparent effect on the success and quality of the MR images. Susceptibility-weighted imaging detected key venous vascular abnormalities and calcifications and, along with the other noncontrast sequences, provided diagnostic information comparable to previous clinical MRI performed with contrast administration under anesthesia. CONCLUSION: This study demonstrates the feasibility and the potential diagnostic value of a nonsedate, noncontrast MRI acquisition protocol in young children including those with cognitive impairment and/or behavioral concerns. This approach can facilitate clinical trials in children where safe serial MRI is warranted.
RESUMO
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.
Assuntos
Síndrome de Sturge-Weber , Criança , Humanos , Pré-Escolar , Síndrome de Sturge-Weber/complicações , Convulsões/complicações , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/patologiaRESUMO
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.
Assuntos
Síndrome de Angelman/patologia , Mapeamento Encefálico/métodos , Encéfalo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Vias Neurais/patologia , Síndrome de Angelman/fisiopatologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologiaRESUMO
OBJECTIVE: To investigate whether abnormal regional white matter architecture in the perisylvian region could be used as an easy and sensitive quantitative method to demonstrate language pathway abnormalities in children with developmental delay (DD). STUDY DESIGN: We performed diffusion tensor imaging in 15 DD subjects (age, 61.1 ± 20.9 months) and 15 age-matched typically developing (TD) children (age, 68.4 ± 19.2 months). With diffusion tensor imaging color-coded orientation maps, we quantified the fraction of fibers in the perisylvian region that are oriented in anteroposterior (AP) and mediolateral (ML) directions, and their ratio (AP/ML) was calculated. RESULTS: The AP/ML ratio was more sensitive than tractography in characterizing perisylvian regional abnormalities in DD children. The AP/ML ratio of the left perisylvian region was significantly lower in DD children compared with TD children (P = .03). The ML component of bilateral perisylvian regions was significantly higher in DD children compared with TD children (P = .01 [left] and P = .004 [right]). No significant difference was found in the AP component in the two groups. A significant negative correlation of the left ML component with Vineland communication skills was observed (r = -0.657, P = .011). CONCLUSIONS: The AP/ML ratio appears to be a sensitive indicator of regional white matter architectural abnormalities in the perisylvian region of DD children.
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Mapeamento Encefálico/métodos , Deficiências do Desenvolvimento/complicações , Imagem de Tensor de Difusão , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Sensibilidade e EspecificidadeRESUMO
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.
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Linhagem , Transtornos de Tique/genética , Síndrome de Tourette/genética , Doença Crônica , Análise Mutacional de DNA , Saúde da Família , Feminino , Ligação Genética , Proteínas de Choque Térmico HSP40/genética , Humanos , Masculino , Proteínas Mitocondriais/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Alinhamento de Sequência/métodos , Transtornos de Tique/complicações , Síndrome de Tourette/complicaçõesRESUMO
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.
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Encéfalo/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/fisiopatologia , Adolescente , Axônios/patologia , Encéfalo/patologia , Criança , Transtornos Globais do Desenvolvimento Infantil/patologia , Pré-Escolar , Imagem de Tensor de Difusão , Feminino , Humanos , Lactente , Masculino , Vias Neurais/patologia , Adulto JovemRESUMO
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.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Emoções/fisiologia , Expressão Facial , Música/psicologia , Estimulação Acústica , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa , Adulto JovemRESUMO
PURPOSE: To determine the relationship between calcified cortex and perfusion status of white matter and seizure severity in patients with Sturge-Weber Syndrome (SWS), a sporadic neurocutaneous disorder characterized by a leptomeningeal angioma, progressive brain ischemia, and a high incidence of seizures using susceptibility weighted imaging (SWI) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI). MATERIALS AND METHODS: Fifteen children (ages: 0.9-10 years) with unilateral SWS prospectively underwent magnetic resonance imaging (MRI). The degree of cortical calcification was assessed using SWI while perfusion status was quantified using DSC-PWI images (asymmetries of various perfusion parameters). Comparisons between calcification, perfusion status, and seizure variables were performed. RESULTS: Patients with severely calcified cortex demonstrated significantly lower perfusion in the ipsilateral white matter (mean asymmetry: -0.52 ± 0.22) as compared to patients with only mildly calcified cortex or no calcification (mean asymmetry: 0.08 ± 0.25). Patients with severely calcified cortex also suffered from a higher seizure burden (a composite measure of seizure frequency and epilepsy duration; P = 0.01) and a trend for earlier seizure onset and longer epilepsy duration. CONCLUSION: Severe calcification in the affected hemisphere is related to severely decreased perfusion in underlying white matter and is associated with more severe epilepsy in SWS patients.
Assuntos
Calcinose/diagnóstico , Córtex Cerebral/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Convulsões/diagnóstico , Síndrome de Sturge-Weber/diagnóstico , Análise de Variância , Calcinose/etiologia , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Convulsões/etiologia , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Síndrome de Sturge-Weber/complicaçõesRESUMO
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.
Assuntos
Imagem de Tensor de Difusão/métodos , Leucoencefalopatias/patologia , Síndrome de Sturge-Weber/patologia , Anisotropia , Criança , Pré-Escolar , Transtornos Cognitivos/fisiopatologia , Humanos , Testes de Inteligência , Destreza Motora , Síndrome de Sturge-Weber/fisiopatologiaRESUMO
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.
Assuntos
Lesões Encefálicas/etiologia , Lateralidade Funcional , Inteligência , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/psicologia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/patologia , Mapeamento Encefálico , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Convulsões/diagnóstico , Convulsões/etiologia , Estatísticas não Paramétricas , Síndrome de Sturge-Weber/diagnóstico por imagem , Síndrome de Sturge-Weber/patologiaRESUMO
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.
Assuntos
Mapeamento Encefálico , Córtex Cerebral/metabolismo , Imagem de Difusão por Ressonância Magnética , Vias Neurais/metabolismo , Carência Psicossocial , Adolescente , Anisotropia , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Estatística como AssuntoRESUMO
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.