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Objective: To assess sex-specific differences in early brain structure and function of preterm infants after red blood cell (RBC) transfusions.Study Design: A single-center subset of infants with a birth weight <1000 g and gestational age 22-29 weeks were enrolled from the National Institute of Child Health and Human Development's Neonatal Research Network Transfusion of Prematures Trial. Hemoglobin (Hb) concentration obtained directly before each transfusion (pretransfusion Hb [ptHb]) was obtained longitudinally throughout each infant's neonatal intensive care unit stay and used as a marker of degree of anemia (n = 97). Measures of regional brain volumes using magnetic resonance imaging were obtained at ∼40 weeks postmenstrual age or at hospital discharge, if earlier (n = 29). Measures of brain function were obtained at 12 months corrected age using the Bayley Scales of Infant & Toddler Development, 3rd Edition (n = 34).Results: PtHb was positively correlated with neonatal cerebral white matter volume in males (B = +0.283; P = .006), but not females (B = -0.099; P = .713), resulting in a significant sex interaction (P = .010). Bayley-III gross motor scores and a pooled mean score were significantly lower in association with higher ptHb in females (gross motor score: B = -3.758; P = .013; pooled mean score: B = -1.225; P = .030), but not males (gross motor score: B = +1.758; P = .167; pooled mean score: B = +0.621; P = .359). Higher ptHb was associated with descriptively lower performance on multiple Bayley-III subscales in females, but not in males.Conclusions: This study demonstrates sex-specific associations between an early marker of anemia and RBC transfusion status (ie, ptHb) with both neonatal white matter volume and early cognitive function at age 12 months in preterm infants. [ABSTRACT FROM AUTHOR]

We have developed a fast and reliable pipeline to automatically parcellate the cortical surface into sub-regions. The pipeline can be used to study brain changes associated with psychiatric and neurological disorders. First, a genus zero cortical surface for one hemisphere is generated from the magnetic resonance images at the parametric boundary of the white matter and the gray matter. Second, a hemisphere-specific surface atlas is registered to the cortical surface using geometry features mapped in the spherical domain. The deformation field is used to warp statistic labels from the atlas to the subject surface. The Dice index of the labeled surface area is used to evaluate the similarity between the automated labels with the manual labels on the subject. The average Dice across 24 regions on 14 testing subjects is 0.86. Alternative evaluations have also chosen to show the accuracy and flexibility of the present method. The point-wise accuracy of 14 testing subjects is above 86% in average. The experiment shows that the present method is highly consistent with FreeSurfer (>99% of the surface area), using the same set of labels. [ABSTRACT FROM AUTHOR]

Individuals with nonsyndromic cleft lip with or without cleft palate (CL/P) have altered brain structure compared with healthy controls. Preliminary evidence suggests that the corpus callosum may be dysmorphic in orofacial clefting; however, this midline brain structure has not been systematically assessed in this population. The goal of the present study was to carry out a morphometric assessment of the corpus callosum and its relationship to cognitive performance in a well-characterized patient cohort with orofacial cleft. Midline brain images were obtained from previously collected MRI scans of 24 CL/P subjects and 40-adult-male controls. Eight landmarks on the corpus callosum were digitized on each image and their x, y coordinate locations saved. A geometric morphometrics analysis was applied to the landmark coordinate data to test for shape differences across groups. The relationship between corpus callosum shape and IQ was explored with nonparametric correlation coefficients. Results revealed significant differences in mean corpus callosum shape between CL/P cases and controls ( P = 0.029). The CL/P corpus callosum was characterized by increased overall convexity resulting from a superior and posterior displacement. Within CL/P cases, increased corpus callosum shape dysmorphology was moderately correlated with reduced performance IQ (r = 0.546). These results provide additional evidence that midline brain changes may be an important part of the orofacial cleft phenotype. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Isolated cleft lip and/or palate (ICLP) is one of the most common congenital birth defects in the USA, affecting roughly 1 in 600 births annually. Along with the facial deformity, this population has been found to have abnormal neurodevelopment and gross structural abnormalities in the brain, particularly within the cerebellum. The current study examined cerebellar structure within the two primary subtypes of ICLP: cleft lip with/without cleft palate (CL/P) and cleft palate alone (CPO). A large sample of 107 subjects aged 7 to 27 years with ICLP was compared to 127 healthy controls. Samples were separated by sex. Brain structure was obtained via magnetic resonance imaging. For males, after controlling for intracranial volume, cerebellum volume was significantly lower in the ICLP group ( F = 12.351, p = 0.001). Regionally in the cerebellum, males with ICLP had proportionally larger anterior lobes ( F = 4.022, p = 0.047) and smaller superior posterior lobes ( F = 5.686, p = 0.019). CL/P males showed only a reduction in overall cerebellum volume, with no regional changes. CPO males showed only regional changes, with no reduction in overall volume. Females with ICLP showed no overall or regional cerebellar abnormalities. However, females with CPO did have significantly lower cerebellum volumes than controls. The results reveal both global and regional cerebellar abnormalities within subjects with ICLP. They also establish the existence of abnormal cerebellar morphologies that are dependent on cleft subtype as well as sex. This lends further support to the claim that CL/P and CPO are distinct conditions. [ABSTRACT FROM AUTHOR]

Environmental factors may contribute as much as one-third of the variance in Huntington disease (HD) age of onset. Substance abuse is a risk factor for other neurodegenerative disorders; however, whether substance abuse influences HD age of onset is not well established. This study investigated the relationships between alcohol, drug, and tobacco abuse and HD age of onset in 136 participants with symptomatic HD. CAG repeat length was used as a covariate in all analyses, as it represents the most significant determinant of HD age of onset. The relationship between substance abuse, HD age of onset, and sex was also examined, as women may experience greater medical harm from substance abuse. Lifetime alcohol abuse and lifetime drug abuse were associated with earlier age of HD onset; a similar trend was seen for current tobacco abuse. For women, lifetime alcohol abuse was associated with earlier onset of HD, with a similar trend for lifetime drug abuse. However, alcohol, drug, and tobacco abuse were not significantly associated with age of onset in men. Further work is needed to determine whether substance abuse is a causative risk factor for earlier onset of HD, and why the environmental factors associated with age of onset vary by sex. [ABSTRACT FROM AUTHOR]

The amygdala's contribution to emotion, cognition and behavior depends on its interactions with subcortical and cortical regions. Amygdala lesions result in altered functional activity in connected regions, but it is not known whether there might be long-term structural sequelae as well. We hypothesized that developmental bilateral amygdala lesions would be associated with specific gray matter morphometric abnormalities in the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC) and the ventral visual stream. We conducted regions of interest and vertex-based analyses of structural MRI data acquired in two patients with long-standing focal bilateral amygdala lesions (S.M. and A.P.), compared to gender- and age-matched healthy comparison subjects. Both patients showed significant proportional increases in gray matter volume of the vmPFC. Cortical thickness was increased in the vmPFC and ACC and decreased in the ventral visual stream. There were no morphometric changes in dorsolateral prefrontal cortex or dorsal visual stream cortices. These findings support the hypothesis that cortical regions strongly connected with the amygdala undergo morphometric changes with long-standing amygdala damage. This is the first evidence in humans of the remote alteration of brain morphology in association with amygdala lesions, and will help in interpreting the structural and functional consequences of amygdala pathology in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Abstract: Structural magnetic resonance imaging studies provide evidence for sex differences in the human brain. Differences in surface area and the proportion of gray to white matter volume are observed, in particular in the parietal lobe. To our knowledge, no studies have examined sex differences in parietal lobe structure in younger populations or in the context of development. The present study evaluated sex differences in the structure of the parietal lobe in children aged 7 to 17 years. In addition, by adding a cohort of previously studied adults aged 18 to 50 years, sex differences in parietal lobe structure were examined across the age span of 7 to 50 years. Compared with the adult sample, the younger sample showed that the ratio of parietal lobe cortex to white matter was greater in female brains, but no sex differences in surface area. When examining the effects of age, surface area exhibited a significant sex-age interaction. In male brains, there was essentially no decrease in surfaces area over time, whereas in female brains, there was a significant decrease in surface area over time. These findings support the notion of structural sex differences in the parietal lobe, not only in the context of cross-sectional assessment but also in terms of differences in developmental trajectories. [Copyright &y& Elsevier]

Objective: To assess the long-term outcome of brain structure in preterm infants, at an average age of 12 years, who received a red blood cell transfusion for anemia of prematurity. Design: As neonates, this cohort of infants participated in a clinical trial in which they received red blood cell transfusions based on a high pretransfusion hematocrit threshold (liberal group) or a low hematocrit threshold (restricted group). These 2 preterm groups were compared with a group of full-term healthy control children. Setting: Tertiary care hospital. Participants: Magnetic resonance imaging scans for 44 of the original 100 subjects were obtained. Intervention: Liberal vs restricted transfusion. Main Outcome Measures: Intracranial volume, total brain tissue, total cerebrospinal fluid, cerebral cortex and cerebral white matter volume, subcortical nuclei volume, and cerebellum volume. Results: Intracranial volume was substantially smaller in the liberal group compared with controls. Intracranial volume in the restricted group was not different from controls. Whole-cortex volume was not different in either preterm group compared with controls. Cerebral white matter was substantially reduced in both preterm groups, more so for the liberal group. The subcortical nuclei were substantially decreased in volume, equally so for both preterm groups compared with controls. When sex effects were evaluated, the girls in the liberal group had the most significant abnormalities. Conclusion: Red blood cell transfusions affected the long-term outcome of premature infants as indicated by reduced brain volumes at 12 years of age for neonates who received transfusions using liberal guidelines. [ABSTRACT FROM AUTHOR]

The estimation of premorbid abilities is an essential part of a neuropsychological evaluation, especially in neurodegenerative conditions. Although word pronunciation tests are one standard method for estimating the premorbid level, research suggests that these tests may not be valid in neurodegenerative diseases. Therefore, the current study sought to examine two estimates of premorbid intellect, the Wide Range Achievement Test (WRAT) Reading subtest and the Barona formula, in 93 patients with mild to moderate Huntington's disease (HD) to determine their utility and to investigate how these measures relate to signs and symptoms of disease progression. In 89% of participants, WRAT estimates were below the Barona estimates. WRAT estimates were related to worsening memory and motor functioning, whereas the Barona estimates had weaker relationships. Neither estimate was related to depression or functional capacity. Irregular word reading tests appear to decline with HD progression, whereas estimation methods based on demographic factors may be more robust but overestimate premorbid functioning. [ABSTRACT FROM AUTHOR]

Research into the neural underpinnings of fear and fear-related pathology has highlighted the role of the amygdala. For instance, bilateral damage to the amygdaloid complex is associated with decreased appreciation of danger and recognition of fear in humans, whereas enlarged amygdala volume is associated with internalizing syndromes. It is unknown whether amygdala volume and fearfulness are related in the absence of pathology. We examined the correlation between normal fearfulness and amygdala morphology in 116 healthy children and adolescents (60 boys, 56 girls, age 7–17 years). Fearfulness was measured using the parent ratings on the Pediatric Behavior Scale and amygdala volumes were determined by manual tracing. We found a positive correlation between right amygdala volume in girls (r = 0.29). This relationship was more robust and present bilaterally when analyses were limited to girls with a positive nuclear family history of depression (for left r = 0.63; for right r = 0.58). In boys there was no significant relationship which may suggest that biological mechanisms differ between sexes. Given the role of enlarged amygdala volume in pathology, these findings may indicate that variation in amygdala morphology marks susceptibility to internalizing disorders. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate potential abnormalities in brain structure of children and adolescents with unilateral clefts. Design: Case-control study. Setting: Tertiary care center. Participants: Boys aged 7 to 17 years with right (n=14) and left (n=19) clefts were compared with healthy agematched boys (n=57). Main Exposures: Structural brain measures were obtained using magnetic resonance imaging. Outcome Measure: It was explored whether laterality of clefts had a significant effect on brain structure. To this end, volumes of tissue types and various brain regions were evaluated. Results: Total white matter was significantly lower in boys with right clefts compared with boys with left clefts and healthy boys. Gross regional analyses demonstrated that reductions in white matter were evident in both the cerebellum and the cerebrum in boys with right clefts. Furthermore, within the cerebrum, white matter volumes were particularly low in the frontal lobes and the occipital lobes. Conclusions: These preliminary results suggest that right clefts may be associated with more abnormalities in brain structure. More generally, laterality of a birth defect may have a significant effect on a developing organism. [ABSTRACT FROM AUTHOR]

Previous studies report structural brain differences in individuals with nonsyndromic orofacial clefts (NSOFC) compared with healthy controls. These changes involve non-uniform shifts in tissue volume within the cerebral cortex and cerebellum, suggesting that the shape of the brain may be altered in cleft-affected individuals. To test this hypothesis, a landmark-based morphometric approach was utilized to quantify and compare brain shape in a sample of 31 adult males with cleft lip with or without cleft palate (CL/P), 14 adult males with cleft palate only (CPO) and 41 matched healthy controls. Fifteen midline and surface landmarks were collected from MRI brain scans and the resulting 3D coordinates were subjected to statistical shape analysis. First, a geometric morphometric analysis was performed in three steps: Procrustes superimposition of raw landmark coordinates, omnibus testing for group difference in shape, followed by canonical variates analysis (CVA) of shape coordinates. Secondly, Euclidean distance matrix analysis (EDMA) was carried out on scaled inter-landmark distances to identify localized shape differences throughout the brain. The geometric morphometric analysis revealed significant differences in brain shape among all three groups ( P << 0.001). From CVA, the major brain shape changes associated with clefting included selective enlargement of the anterior cerebrum coupled with a relative reduction in posterior and/or inferior cerebral portions, changes in the medio-lateral position of the cerebral poles, posterior displacement of the corpus callosum, and reorientation of the cerebellum. EDMA revealed largely similar brain shape changes. Thus, compared with controls, major brain shape differences were present in adult males with CL/P and CPO. These results both confirm and expand previous findings from traditional volumetric studies of the brain in clefting and provide further evidence that the neuroanatomical phenotype in individuals with NSOFC is a primary manifestation of the defect and not a secondarily acquired characteristic. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington's Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects. [ABSTRACT FROM AUTHOR]

Emerging data on the neural mechanisms of impulse control highlight brain regions involved in emotion and decision making, including the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC) and amygdala. Variation in the development of these regions may influence one's propensity for impulsivity and, by extension, one's vulnerability to disorders involving low impulse control (e.g. substance abuse). Here we test the hypothesis that lower impulse control is associated with structural differences in these regions, particularly on the right side, in 61 normal healthy boys aged 7–17. We assessed parent- and teacher-reported behavioral ratings of impulse control (motor impulsivity and non-planning behavior) in relation to vmPFC, ACC and amygdala volume, measured using structural magnetic resonance imaging and FreeSurfer. A regression analysis showed that the right vmPFC was a significant predictor of impulse control ratings. Follow-up tests showed (i) a significant correlation between low impulse control and decreased right vmPFC volume, especially the medial sector of the vmPFC and (ii) significantly lower right vmPFC volume in a subgroup of 20 impulsive boys relative to 20 non-impulsive boys. These results are consistent with the notion that right vmPFC provides a neuroanatomical correlate of the normal variance in impulse control observed in boys. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to assess neurological soft signs in children and adolescents with isolated cleft of the lip or palate (iCL/P) compared with healthy controls. Children with iCL/P were recruited through the university cleft clinic. Control subjects were recruited through advertisements. Of the 166 subjects who participated (age range 7 to 17 years, M = 12.5, SD = 3.2), 77 had iCL/P (48 male) and 89 were healthy controls (44 male). All participants took the Physical and Neurological Examination of Subtle Signs and selected tests of motor coordination. A multivariate analysis of variance assessed differences between subjects with and without iCL/P. Also, a Pearson correlation estimated the relationship between the neurological soft signs and age. Subjects with iCL/P scored significantly higher on all neurological soft signs variables. These higher scores were associated with younger age. Findings lend support to the hypothesis of aberrant brain development in children with iCL/P. [ABSTRACT FROM AUTHOR]

Múltiples hallazgos han relacionado la fracción de la corteza cingular anterior situada por delante del cuerpo calloso con la fisiopatología del trastorno depresivo familiar. No obstante, son pocos los datos actuales que atribuyan la especificidad de estas anomalías a los trastornos depresivos o que caractericen su estabilidad a lo largo del tiempo. Método: Los autores estudiaron a 10 individuos diagnosticados de trastorno depresivo mayor con rasgos psicóticos, a los que se aplicaron protocolos de resonancia magnética (RM) y que participaron en un estudio longitudinal de psicosis de inicio reciente. Los individuos fueron equiparados por grupos a 10 individuos con esquizofrenia y a 10 individuos sanos de control. Se efectuaron las determinaciones volumétricas de las porciones anterior y posterior de la corteza prefrontal subgenual de estos 30 individuos. Se obtuvieron tomografías de control, efectuadas en promedio 4 años después del ingreso, de 7 individuos con trastorno depresivo mayor, 9 individuos con esquizofrenia y 5 individuos sanos de control. Resultados: Los volúmenes de la corteza prefrontal subgenual posterior del hemisferio izquierdo difirieron significativamente entre los grupos, correspondiendo el volumen más pequeño al grupo con trastorno depresivo mayor psicótico. Los volúmenes de la corteza prefrontal subgenual anterior no difirieron significativamente entre los grupos. Los pacientes con trastorno depresivo mayor tenían una mayor probabilidad de mostrar un aumento volumétrico de la corteza prefrontal subgenual posterior en la evaluación de seguimiento que los individuos de control o los pacientes con esquizofrenia. Conclusiones: Estos resultados se suman a otras pruebas que demuestran que las anomalías de la región subgenual del cíngulo anterior tienen un papel importante al menos en determinados tipos de trastornos del estado de ánimo. [ABSTRACT FROM PUBLISHER]

Abstract: This study compares globus pallidus (GP) volume between neuroleptic naïve patients with schizophrenia and healthy controls using structural MRI. The volume of the external segment of the GP (GPe) was positively correlated with the severity of global symptoms, as measured by the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms (SANS/SAPS, Andreasen and Olsen, 1982). The volume for the GP, GPe, and internal segment (GPi) did not differ between groups. [Copyright &y& Elsevier]

Background: The insular cortex is a limbic integration region engaged in emotional and cognitive functions. Previously, we found that neuroleptic-naïve subjects had abnormally small insular volumes compared with control subjects, with volume directly related to severity of psychotic symptoms. Methods: To further investigate insular cortex abnormalities and their functional correlates, we measured insular gray matter volume and cortical surface size, using magnetic resonance images among 30 patients with schizophrenia and a matched control group. The sample was designed to represent a variety of phenomenologic profiles to provide sufficient variance in multiple measures, including severity of illness and exposure to neuroleptics (typical only). Results: There were no significant differences in morphology between patients and control subjects; however, among patients, psychotic symptoms were inversely correlated with insular volume, replicating our previous finding in neuroleptic-naïve subjects. Neuroleptic exposure had a specific effect on insular morphology: increasing drug exposure (measured in dose-years) correlated with larger insular volume. Conclusions: This effect of neuroleptic exposure might account for the lack of difference in structural measures in this more chronic sample, whereas the initial study on neuroleptic-naïve subjects showed group differences. Further research is needed to investigate the potential relationship between changes in insula volume from neuroleptic exposure and clinical outcome. [Copyright &y& Elsevier]

Background: Many studies have shown that structural brain abnormalities in schizophrenia are already present by the time of index evaluation of first-episode patients. However, whether these abnormalities progressively worsen during the subsequent course of the disorder remains unresolved. Methods: To study the longitudinal progression of structural brain abnormalities, high-resolution multispectral magnetic resonance images obtained on 73 recent-onset schizophrenic patients and 23 controls were analyzed using state-of-the-art, well-validated, and highly reliable neuroimaging tools. The mean duration between initial and follow-up MRIs was 3 years. Repeated-measures analysis of covariance was carried out to determine (1) whether brain volume changes differed between patients and controls and (2) the significance of regional brain changes on functional outcome in schizophrenia. Results: We found accelerated enlargement in cortical sulcal cerebrospinal fluid spaces early in the course of schizophrenia. Instead of the usual trajectory of volume enlargement, patients showed progressive reduction in frontal lobe white matter volume. A reciprocal increase in frontal lobe cerebrospinal fluid volume also occurred at a more rapid rate in patients than in controls. In keeping with most of our a priori hypotheses, patients with poor outcome had greater lateral ventricular enlargement over time than patients with good outcome. Progressive decrement in frontal lobe white matter volume and enlargement in frontal lobe cerebrospinal fluid volume were associated with greater negative symptom severity. Reductions in frontal lobe gray and white matter volumes correlated with poorer executive functioning. Conclusions: There are ongoing changes in the brains of schizophrenic patients during the initial years after diagnosis despite ongoing antipsychotic drug treatment. These progressive changes seem to be most evident in the frontal lobes and to correlate with functional impairment.... [ABSTRACT FROM AUTHOR]