Alteraciones neuropsicológicas y daño cerebral en la infancia y adolescencia asociados al nacimiento prematuro

Prematurity is defined by the World Health Organization (WHO, 1977) as a delivery occurring before 37 completed weeks of gestation. White matter (WM) abnormalities and periventricular leukomalacia (PVL) are the most prominent pathologies in the preterm neonate. Compared with their term-peers, children born preterm have lower intelligence quotient (IQ) scores, although within the normal range. Moreover, domain-specific measures of neuropsychological abilities such as executive functions, visuoperceptual and linguistic skills are often impaired. Preterm children with PVL have a similar profile, with lower IQ scores and poorer executive functions, mental calculation and visuoperceptual skills than controls. Cerebral structural gray matter (GM) abnormalities that might contribute to the poor performance of preterm samples are localized in the frontal, parietal, temporal and occipital lobes. The cerebellum and deep gray matter structures such as the caudate nuclei, the thalami and the hippocampus are also altered. Over the past few years, magnetic resonance imaging and neuropathological studies have shown that, in addition to the classical WM injury seen in preterm samples with PVL, cortical and subcortical GM injury may also contribute to the impaired cognitive performance.La prematuridad es definida por la Organización Mundial de la Salud (OMS, 1977) como el parto que ocurre antes de las 37 semanas de gestación. La alteración de la sustancia blanca (SB) es la principal característica de daño cerebral y la leucomalacia periventricular (LPV) es el hallazgo patológico más común en estudios de resonancia magnética Los niños nacidos prematuros comparados con los niños nacidos a término presentan un cociente de inteligencia (CI) con puntuaciones menores pero dentro de la normalidad. Las funciones neuropsicológicas específicas más afectadas son las ejecutivas, visuo-perceptivas y lingüísticas. Los niños prematuros con LPV, también muestran puntuaciones más bajas en el CI, en las funciones ejecutivas, en el cálculo mental y en las capacidades visuoperceptivas. Las alteraciones cerebrales estructurales de sustancia gris (SG) que pueden contribuir a una peor ejecución cognitiva en estas muestras de prematuros implican regiones en los lóbulos cerebrales temporal, parietal, frontal y occipital. Además, el cerebelo y diversos núcleos grises subcorticales tales como el núcleo caudado, el tálamo y el hipocampo están también afectados. En los últimos años, los estudios de resonancia magnética y neuropatológicos, están demostrando que además de la alteración clásica de SB, los niños prematuros con LPV presentan daño en la SG tanto cortical como subcortical a los cuales se les atribuye una implicación directa en la peor ejecución cognitiva

Alteraciones neuropsicológicas y daño cerebral en la infancia y adolescencia asociados al nacimiento prematuro

Prematurity is defined by the World Health Organization (WHO, 1977) as a delivery occurring before 37 completed weeks of gestation. White matter (WM) abnormalities and periventricular leukomalacia (PVL) are the most prominent pathologies in the preterm neonate. Compared with their term-peers, children born preterm have lower intelligence quotient (IQ) scores, although within the normal range. Moreover, domain-specific measures of neuropsychological abilities such as executive functions, visuoperceptual and linguistic skills are often impaired. Preterm children with PVL have a similar profile, with lower IQ scores and poorer executive functions, mental calculation and visuoperceptual skills than controls. Cerebral structural gray matter (GM) abnormalities that might contribute to the poor performance of preterm samples are localized in the frontal, parietal, temporal and occipital lobes. The cerebellum and deep gray matter structures such as the caudate nuclei, the thalami and the hippocampus are also altered. Over the past few years, magnetic resonance imaging and neuropathological studies have shown that, in addition to the classical WM injury seen in preterm samples with PVL, cortical and subcortical GM injury may also contribute to the impaired cognitive performance.  La prematuridad es definida por la Organización Mundial de la Salud (OMS, 1977) como el parto que ocurre antes de las 37 semanas de gestación. La alteración de la sustancia blanca (SB) es la principal característica de daño cerebral y la leucomalacia periventricular (LPV) es el hallazgo patológico más común en estudios de resonancia magnética Los niños nacidos prematuros comparados con los niños nacidos a término presentan un cociente de inteligencia (CI) con puntuaciones menores pero dentro de la normalidad. Las funciones neuropsicológicas específicas más afectadas son las ejecutivas visuo-perceptivas y lingüísticas. Los niños prematuros con LPV, también muestran puntuaciones más bajas en el CI, en las funciones ejecutivas, en el cálculo mental y en las capacidades visuoperceptivas. Las alteraciones cerebrales estructurales de sustancia gris (SG) que pueden contribuir a una peor ejecución cognitiva en estas muestras de prematuros implican regiones en los lóbulos cerebrales temporal, parietal, frontal y occipital. Además, el cerebelo y diversos núcleos grises subcorticales tales como el núcleo caudado, el tálamo y el hipocampo están también afectados. En los últimos años, los estudios de resonancia magnética y neuropatológicos, están demostrando que además de la alteración clásica de SB, los niños prematuros con LPV presentan daño en la SG tanto cortical como subcortical a los cuales se les atribuye una implicación directa en la peor ejecución cognitiva

Brainstem Shape is Affected by Clinical Course in the Neonatal Intensive Care Unit

The brainstem, critical for motor function, autonomic regulation, and many neurocognitive functions, undergoes rapid development from the third trimester. Accordingly, we hypothesized it would be vulnerable to insult during this period, and that a difficult clinical course in the neonatal intensive care unit (NICU) would affect development, and be reflected through atypical shape. Our study population consisted of 66 neonates - all inpatients from the NICU at Victoria Hospital, London Health Sciences Centre, ON, Canada, of which 45 entered the final analysis. The cohort varied in gestational age (GA) and ranged from neurologically healthy to severely brain-injured. Structural MRI was used to quantify brainstem shape at term-equivalent age. From these images, brainstems were semi-automatically segmented and co-registered across subjects. The anterior-posterior dimensions on a sagittal maximum intensity projection were used as the basis for shape comparison. Factor analysis was used to summarize variation in shape and in clinical course to determine three shape factors and three clinical factors, and their relationship assessed using correlation. A factor driven by low GA and associated complications correlated with alterations in the posterior medulla, while a factor driven by complications independent of GA correlated with alterations in the midbrain. Additionally, single clinical measures most representative of their respective clinical factor (days in NICU; days on ventilation) predicted the changes. Thus, different clinical courses in the NICU may have different effects on the shape of the brainstem, and may mediate some of the distinct neurodevelopmental profiles observed in premature and brain-injured neonates

Disruption to Functional Networks in Neonates With Perinatal Brain Injury Predicts Motor Skills at 8 Months

Objective: Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Methods: Infants ( Results: Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. Conclusion: fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies

CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment

[Abstract] Gender identity refers to the consciousness of being a man, a woman or other condition. Although it is generally congruent with the sex assigned at birth, for some people it is not. If the incongruity is distressing, it is defined as gender dysphoria (GD). Here, we measured whole-genome DNA methylation by the Illumina © Infinium Human Methylation 850k array and reported its correlation with cortical thickness (CTh) in 22 transgender men (TM) experiencing GD versus 25 cisgender men (CM) and 28 cisgender women (CW). With respect to the methylation analysis, TM vs. CW showed significant differences in 35 CpGs, while 2155 CpGs were found when TM vs. CM were compared. With respect to correlation analysis, TM showed differences in methylation of CBLL1 and DLG1 genes that correlated with global and left hemisphere CTh. Both genes were hypomethylated in TM compared to the cisgender groups. Early onset TM showed a positive correlation between CBLL1 and several cortical regions in the frontal (left caudal middle frontal), temporal (right inferior temporal, left fusiform) and parietal cortices (left supramarginal and right paracentral). This is the first study relating CBLL1 methylation with CTh in transgender persons and supports a neurodevelopmental hypothesis of gender identity.Ministerio de Ciencia, Innovación y Universidades; PGC2018-094919-B-C21 & PDI21-127547NB-C21 (A.G.), PGC2018-094919-B-C22 and PID2021-127547NB-C22 (R.F., E.P.).Xunta de Galicia; ED431B 2022/16 (E.P.)Special Research Fund (BOF) of Ghent University (IOP003- 18) (S.M.C. and G.T.S)

The Effects of Testosterone on the Brain of Transgender Men

[Abstract] Transgender men (TM) experience an incongruence between the female sex assigned when they were born and their self-perceived male identity. Some TM seek for a gender affirming hormone treatment (GAHT) to induce a somatic transition from female to male through continuous administration of testosterone. GAHT seems to be relatively safe. However, testosterone produces structural changes in the brain as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control of astrocyte water trafficking, thereby controlling brain volum

Cortical thickness and behavior abnormalities in children born preterm

Abstract Aim To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. Methods We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). Results We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas. Interpretation The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems

The Effects of Testosterone on the Brain of Transgender Men

Transgender men (TM) experience an incongruence between the female sex assigned when they were born and their self-perceived male identity. Some TM seek for a gender affirming hormone treatment (GAHT) to induce a somatic transition from female to male through continuous administration of testosterone. GAHT seems to be relatively safe. However, testosterone produces structural changes in the brain as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control of astrocyte water trafficking, thereby controlling brain volume

Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix intraventricular hemorrhage.

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term efects that GM-IVH have on hippocampal subfelds, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced signifcantly lower total hippocampal volumes bilaterally and hippocampal subfeld volumes compared to both low-risk preterm and full-term groups. Finally, signifcant positive correlations between memory and hippocampal subfeld volumes were only found in preterm participants together; memory and the right CA-feld correlation remained signifcant after Bonferroni correction was applied (p= .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifcally related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-feld volume and memory during childhood

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function

Background: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. Aims: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. Patients and methods: Thirty-three participants with dyskinetic CP (mean +/- SD age: 24.42 +/- 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. Results: White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum). Conclusion: The widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult