Optic radiation structure and anatomy in the normally developing brain determined using diffusion MRI and tractography

The optic radiation (OR) is a component of the visual system known to be myelin mature very early in life. Diffusion tensor imaging (DTI) and its unique ability to reconstruct the OR in vivo were used to study structural maturation through analysis of DTI metrics in a cohort of 90 children aged 5–18 years. As the OR is at risk of damage during epilepsy surgery, we measured its position relative to characteristic anatomical landmarks. Anatomical distances, DTI metrics and volume of the OR were investigated for age, gender and hemisphere effects. We observed changes in DTI metrics with age comparable to known trajectories in other white matter tracts. Left lateralization of DTI metrics was observed that showed a gender effect in lateralization. Sexual dimorphism of DTI metrics in the right hemisphere was also found. With respect to OR dimensions, volume was shown to be right lateralised and sexual dimorphism demonstrated for the extent of the left OR. The anatomical results presented for the OR have potentially important applications for neurosurgical planning

Sex differences in white matter development during adolescence: A DTI study

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13–18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure

Sex effects on structural maturation of the limbic system and outcomes on emotional regulation during adolescence

Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders.Peer reviewe

Brain white matter development, associations to maternal perinatal psychological distress and emotional attention at the age of 5 years

Development of the brain white matter (WM) is highly plastic, and myelination continues from the second trimester into early adulthood which predisposes the brain to effects of both adverse and supporting factors during early life. Maternal perinatal psychological distress is acknowledged as an important contributor to the offspring’s development. Furthermore, sex is known to affect the WM microstructure as well as the emergence of psychopathologies. Understanding the normal variation of microstructure in the developing brain WM is a prerequisite for recognizing alterations inflicted by early adversity that have possible long-term programming effects on behavioral and socio-emotional outcomes. This study aimed to 1) investigate the incidence, risk factors and consequences of incidental findings in brain magnetic resonance imaging of infants; 2) optimize data acquisition parameters and pre-processing pipeline of diffusion tensor imaging (DTI) protocol applied with children; 3) describe the normal microstructural features of WM in infants and 5-year-old children; 4) investigate the associations between WM integrity and exposure to maternal perinatal psychological distress; 5) explore the associations of WM integrity and child’s emotional attention. Vacuum assistance and vaginal birth were observed to increase the risk for subdural hemorrhages (incidence 6.9%) with no effects on early neurological development. In 5-year-olds, higher WM integrity in widespread regions was observed in girls, and we found marked asymmetry in the WM, resembling patterns previously shown in adults. Maternal perinatal psychological distress showed sexand timing-specific associations with WM integrity: prenatal symptoms predicting higher integrity in boys and postnatal symptoms lower integrity in girls. Maternal postpartum anxiety increased girls’ vigilance toward fearful faces, which was also associated with reduced WM integrity. The results imply that maternal psychological distress affects WM development with effects especially on girls. Collectively, these studies provide fundamental insight for future studies addressing the mediating mechanisms and longer-term effects between the observed associations.Aivojen valkean aineen kehitys, äidin raskauden ympärillä esiintyvän psykologisen stressin vaikutus ja tunneperäinen huomion kohdentaminen 5-vuotiailla Aivojen valkean aineen kehitys jatkuu toiselta raskauskolmannekselta varhaiseen aikuisuuteen, mikä altistaa sen muovautuvuutensa vuoksi sekä epäsuotuisten että tukevien tekijöiden vaikutukselle varhaisen elämän aikana. Äidin raskauden ympärillä esiintyvä psykologinen stressi on tunnettu jälkeläisten kehitykseen vaikuttava tekijä. Lisäksi sukupuoli vaikuttaa valkean aineen rakenteeseen ja psykiatristen häiriöiden ilmaantuvuuteen. Kehittyvien aivojen rakenteen normaalivaihtelun ymmärtäminen on oleellista, jotta voidaan tunnistaa aikaisten vastoinkäymisten aiheuttamia muutoksia sekä niiden mahdollisia pitkäaikaisia ohjelmoivia vaikutuksia käytökseen ja tunnepohjaisiin toimintoihin. Tämän väitöskirjan tavoitteena oli 1) raportoida vastasyntyneiden aivojen magneettikuvien sattumalöydösten esiintyvyyttä, riskitekijöitä ja neurologisia seurauksia; 2) optimoida lasten diffuusiotensorikuvantamisaineiston keräämistä ja esikäsittelyä; 3) tarkastella 5-vuotiaiden valkean aineen normaalipiirteitä; 4) tutkia äidin raskauden ympärillä esiintyvän psykologisen stressin vaikutusta jälkeläisten valkean aineen rakenteeseen; ja 5) selvittää valkean aineen yhteyksiä lapsen tunnepohjaiseen huomion kohdentamiseen silmänliikemittausten avulla. Imukuppiavustus ja alatiesynnytys lisäsivät sattumalöydöksinä havaittujen kovakalvonalaisten vuotojen (6.9 %) riskiä, mutta eivät vaikuttaneet varhaiseen neurologiseen kehitykseen. 5-vuotiaiden tyttöjen valkean aineen integriteetti oli laajaalaisesti korkeampi poikiin verrattuna, ja epäsymmetrisyys vastasi aiemmin aikuisilla havaittua rakennetta. Äidin psykologinen stressi liittyi jälkeläisten valkean aineen integriteettiin sukupuoli- ja ajankohtariippuvaisesti: pojilla raskaudenaikainen altistus lisäsi valkean aineen integriteettiä, kun taas tytöillä raskaudenjälkeinen altistus vähensi sitä. Äidin raskauden jälkeinen ahdistus lisäsi tyttöjen tarkkaavaisuutta pelokkaisiin ilmeisiin, joka liittyi myös alentuneeseen valkean aineen integriteettiin. Aiempia tutkimustuloksia tukien äidin psykologisen stressin havaittiin muovaavan valkean aineen kehitystä etenkin tytöillä, ja tämä luo pohjaa mekanismien ja kausaliteetin tarkastelulle myös tulevissa tutkimuksissa

A novel maturation index based on neonatal diffusion tensor imaging reflects typical perinatal white matter development in humans

Human birth presents an abrupt transition from intrauterine to extrauterine life. Here we introduce a novel Maturation Index (MI) that considers the relative importance of gestational age at birth and postnatal age at scan in a General Linear Model. The MI is then applied to Diffusion Tensor Imaging (DTI) in newborns for characterizing typical white matter development in neonates. DTI was performed cross-sectionally in 47 neonates (gestational age at birth=39.1±1.6 weeks [GA], postnatal age at scan=25.5±12.2days [SA]). Radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA) along 27 white matter fiber tracts were considered. The MI was used to characterize inflection in maturation at the time of birth using GLM estimated rates of change before and after birth. It is proposed that the sign (positive versus negative) of MI reflects the period of greatest maturation rate. Two general patterns emerged from the MI analysis. First, RD and AD (but not FA) had positive MI on average across the whole brain (average MIAD=0.31±0.42, average MIRD=0.22±0.34). Second, significant regions of negative MI in RD and FA (but not AD) were observed in the inferior corticospinal regions, areas known to myelinate early. Observations using the proposed method are consistent with proposed models of the white matter maturation process in which pre-myelination is described by changes in AD and RD due to oligodendrocyte proliferation while true myelination is characterized by changes in RD and FA due to myelin formation

A structural MRI study of human brain development from birth to two years

pre-printBrain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2- 4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders

Resting-State Functional Connectivity in Youth With Gender Dysphoria

Current developmental models of gender identity and gender dysphoria (GD) lack sex-specific profiles of brain function that differentiate between typically-developing and cross-gender identified youth, as postulated by models like the unified theory of the origins of sex differences (Arnold, 2009) and the neurobiological theory of the origins of transsexuality (Swaab & Garcia-Falgueras, 2009). Previously, investigators have used brain imaging modalities such as Resting-State functional Magnetic Resonance Imaging (R-fMRI) to demonstrate differences in resting-state functional connectivity (RSFC) between typically-developing male and female youth, and between typically-developing and GID-diagnosed youth. In the present pilot study, I used R-fMRI to investigate differences in RSFC between typically-developing and cross-gender identified male and female youth subgroups, with the hypothesis that GID-diagnosed subgroups would demonstrate connectivity patterns in between those of typically-developing males and females. Eleven youth diagnosed with gender identity disorder (four males, ages 9 to 20 years; seven females, ages 12 to 20 years) were matched on age and assigned gender with 11 typically-developing youth. All participants completed written informed consent to undergo the IRB-approved research procedures. R-fMRI were collected while the participants were lying down and resting, with their eyes closed. Primary analyses focused on 14 brain regions selected because they showed sex differences most frequently or reliably in previous studies of R-fMRI in typically-developing youth. Statistical analysis used a 2 x 2 mixed effects analysis (assigned female versus assigned male x typically-developing versus GID-diagnosed), with-individual level connectivity maps as the dependent variable. Results showed that significant interaction effects of functional connectivity patterns were associated with 6 of the 14 selected brain regions. GID-diagnosed assigned females exhibited connectivity patterns similar to those of typically-developing males associated with the right medial superior frontal gyrus, right supplementary motor area, left lingual gyrus, right lingual gyrus, left middle frontal gyrus, left medial superior frontal gyrus, left cuneus, right thalamus, left dorsolateral superior frontal gyrus, and left inferior frontal gyrus, triangular part. GID-diagnosed assigned males exhibited functional connectivity patterns similar to those of typically-developing females associated with the right medial superior frontal gyrus and right supplementary motor area; in between those of typically-developing females and males associated with left lingual gyrus, right lingual gyrus, left middle frontal gyrus, left medial superior frontal gyrus, right medial superior frontal gyrus, left dorsolateral superior frontal gyrus, and left inferior frontal gyrus, triangular part; and similar to typically-developing males associated with the right lingual gyrus and left middle frontal gyrus. The right precuneus, hypothesized to show robust findings, did not reveal any effects. In the current study, GID-diagnosed assigned males tended toward demasculinized effects (quantitative interactions showing differences of magnitude), whereas GID-diagnosed assigned females tended toward masculinized effects (qualitative interactions showing differences in direction of correlation). The current findings support the view that brain development associated with gender dysphoria proceeds along separate but overlapping sex-related regions for GID-diagnosed assigned females and males and provide further evidence of greater cross-gender brain differentiation in assigned females at an earlier age than in assigned males (possibly due to earlier onset of puberty in females). These data suggest that any future use of patterns of brain function for diagnosing gender dysphoria may require separate criteria (e.g., different sets of brain regions) for assigned males and assigned females but will require replication on larger samples

White matter microstructure correlates with autism trait severity in a combined clinical–control sample of high-functioning adults

AbstractDiffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical–neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p=0.004), whilst MD and RD were positively related to AQ (p=0.002; p=0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits

Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography.

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients