Long-Term Neurodevelopmental Outcomes after Moderate and Late Preterm Birth: A Systematic Review.

OBJECTIVE: To systematically review and perform meta-analyses on the long-term neurodevelopmental outcomes of adults born moderate and late preterm (MLPT) in relation to cognitive functioning and psychiatric disorders. STUDY DESIGN: A search was conducted to identify any studies that involved prematurity in adulthood. From these studies, reports that included a group of MLPT adults and included description of cognitive and/or mental health domains (including specific long-term outcomes) were selected. RESULTS: In total, 155 publications were identified, but only 16 papers met the inclusion criteria. A small effect size (g = 0.38) was found in MLPT to demonstrate poorer intellectual performance compared with those born at term. Moreover, MLPT adults exhibited greater odds for any psychiatric (OR 1.14), substance use (OR 1.16), mood (OR 1.06), and psychotic disorders (OR 1.40). CONCLUSIONS: Despite inconsistency due to the methodologic differences between the selected studies, MLPT showed minor long-term effects into adulthood. However, more studies are needed, because prematurity seems to confer some vulnerability to biological and environmental factors that enhance susceptibility to adverse neurodevelopment outcomes.

The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group.

BACKGROUND: In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. AIM: To examine the neurobiology of transgender persons in a large sample. METHODS: Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. OUTCOMES: Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS: Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. CLINICAL TRANSLATION: The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. STRENGTHS AND LIMITATIONS: While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION: Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. Mueller SC, Guillamon A, Zubiaurre-Elorza L, et al. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med 2021;18:1122-1129.

Spanish adaptation and validation of the Social Attribution Task-Multiple choice (SAT-MC) versions I and II for children and adolescents.

Social cognition is progressively acquired from childhood to early adulthood. Nevertheless there is a shortage of social cognition scales with normative data for Spanish children and adolescents. Social Attribution Task-Multiple Choice (SAT-MC) and its alternate version SAT-MC-II are social cognition instruments that measure mentalization skills in adults with psychosis. This study aimed to report psycho- metric characteristics and normative data of the Spanish version of SAT-MC and SAT-MC-II in a sample of minors.

Auditory structural connectivity in preterm and healthy term infants during the first postnatal year.

Assessing language development in the first postnatal year is difficult, as receptive and expressive skills are rudimentary. Although outward manifestations of change are limited, the auditory language system is thought to undergo critical development at this age, as the foundations are laid for the rapid onset of spoken language in the second and third years. We recruited 11 infants, 7 healthy controls (gestational age = 40.69 ± 0.56; range from 40 to 41.43) and preterm babies (gestational age = 28.04 ± 0.95; range from 27.43 to 29.43) who underwent a Magnetic Resonance Imaging study during the first postnatal year (age at scan = 194.18 ± 97.98). We assessed white matter tracts using diffusion-weighted magnetic resonance imaging with probabilistic tractography. Fractional anisotropy was found to be largely mature even at one month, although there was a little further increase during the first postnatal year in both the acoustic radiation and the direct brainstem-Heschl's pathway.

Adult-like processing of naturalistic sounds in auditory cortex by 3- and 9-month old infants.

Functional neuroimaging has been used to show that the developing auditory cortex of very young human infants responds, in some way, to sound. However, impoverished stimuli and uncontrolled designs have made it difficult to attribute brain responses to specific auditory features, and thus made it difficult to assess the maturity of feature tuning in auditory cortex. To address this, we used functional magnetic resonance imaging (fMRI) to measure the brain activity evoked by naturalistic sounds (a series of sung lullabies) in two groups of infants (3 and 9 months) and adults. We developed a novel analysis method - inter-subject regression (ISR) - to quantify the similarity of cortical responses between infants and adults, and to decompose components of the response due to different auditory features. We found that the temporal pattern of activity in infant auditory cortex shared similarity with adults. Some of this shared response could be attributed to simple acoustic features, such as frequency, pitch, envelope, but other parts were not, suggesting that even more complex adult-like features are represented in auditory cortex in early infancy.

Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function.

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system. Hum Brain Mapp 38:4594-4612, 2017. © 2017 Wiley Periodicals, Inc.

Using Functional Magnetic Resonance Imaging to Detect Preserved Function in a Preterm Infant with Brain Injury.

We studied developmental plasticity using functional magnetic resonance imaging (fMRI) in a preterm infant with brain injury on structural MRI. fMRI showed preserved brain function and subsequent neurodevelopment was within the normal range. Multimodal neuroimaging including fMRI can improve understanding of neural plasticity after preterm birth and brain injury.

Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals.

INTRODUCTION: Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatments are used to masculinize or feminize the bodies of female-to-male (FtMs) or male-to-female (MtFs) transsexuals, respectively. AIM: A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs. METHODS: This study investigated 15 female-to-male (FtMs) and 14 male-to-female (MtFs) transsexuals prior and during at least six months of cross-sex hormone therapy treatment. Brain MRI imaging was performed in a 3-Tesla TIM-TRIO Siemens scanner. T1-weighted images were analyzed with FreeSurfer software to obtain CTh as well as subcortical volumetric values. MAIN OUTCOME MEASURES: Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy. RESULTS: After testosterone treatment, FtMs showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs, after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles. CONCLUSIONS: Testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system.

Cortical thickness in untreated transsexuals.

Sex differences in cortical thickness (CTh) have been extensively investigated but as yet there are no reports on CTh in transsexuals. Our aim was to determine whether the CTh pattern in transsexuals before hormonal treatment follows their biological sex or their gender identity. We performed brain magnetic resonance imaging on 94 subjects: 24 untreated female-to-male transsexuals (FtMs), 18 untreated male-to-female transsexuals (MtFs), and 29 male and 23 female controls in a 3-T TIM-TRIO Siemens scanner. T1-weighted images were analyzed to obtain CTh and volumetric subcortical measurements with FreeSurfer software. CTh maps showed control females have thicker cortex than control males in the frontal and parietal regions. In contrast, males have greater right putamen volume. FtMs had a similar CTh to control females and greater CTh than males in the parietal and temporal cortices. FtMs had larger right putamen than females but did not differ from males. MtFs did not differ in CTh from female controls but had greater CTh than control males in the orbitofrontal, insular, and medial occipital regions. In conclusion, FtMs showed evidence of subcortical gray matter masculinization, while MtFs showed evidence of CTh feminization. In both types of transsexuals, the differences with respect to their biological sex are located in the right hemisphere.

Determinants of quality of life in Spanish transsexuals attending a gender unit before genital sex reassignment surgery.

PURPOSE: To evaluate the self-reported perceived quality of life (QoL) in transsexuals attending a Spanish gender identity unit before genital sex reassignment surgery, and to identify possible determinants that likely contribute to their QoL. METHODS: A sample of 119 male-to-female (MF) and 74 female-to-male (FM) transsexuals were included in the study. The WHOQOL-BREF scale was used to evaluate self-reported QoL. Possible determinants included age, sex, education, employment, partnership status, undergoing cross-sex hormonal therapy, receiving at least one non-genital sex reassignment surgery, and family support (assessed with the family APGAR questionnaire). RESULTS: Mean scores of all QoL domains ranged from 55.44 to 63.51. Linear regression analyses revealed that undergoing cross-sex hormonal treatment, having family support, and having an occupation were associated with a better QoL for all transsexuals. FM transsexuals have higher social domain QoL scores than MF transsexuals. The model accounts for 20.6 % of the variance in the physical, 32.5 % in the psychological, 21.9 % in the social, and 20.1 % in the environment domains, and 22.9 % in the global QoL factor. CONCLUSIONS: Cross-sex hormonal treatment, family support, and working or studying are linked to a better self-reported QoL in transsexuals. Healthcare providers should consider these factors when planning interventions to promote the health-related QoL of transsexuals.

Enhancement of phonemic verbal fluency in multilingual young adults by transcranial random noise stimulation.

Several studies have analyzed the effects of transcranial direct current stimulation on verbal fluency tasks in non-clinical populations. Nevertheless, the reported effects on verbal fluency are inconsistent. In addition, the effect of other techniques such as transcranial random noise stimulation (tRNS) on verbal fluency enhancement has yet to be studied in healthy multilingual populations. This study aims to explore the effects of tRNS on verbal fluency in healthy multilingual individuals. Fifty healthy multilingual (Spanish, English and Basque) adults were randomly assigned to a tRNS or sham group. Electrodes were placed on the left dorsolateral prefrontal cortex and left inferior frontal gyrus. All participants performed phonemic and semantic verbal fluency tasks before, during (online assessment) and immediately after (offline assessment) stimulation in three different languages. The results showed significantly better performance by participants who received tRNS in the phonemic verbal fluency tasks in Spanish (in the online and offline assessment) and English (in the offline assessment). No differences between conditions were found in Basque nor semantic verbal fluency. These findings suggests that tRNS on the left prefrontal cortex could help improve phonemic, yet not semantic, fluency in healthy multilingual adults.

Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis.

Long-term persistent symptoms of COVID-19 affect 30-80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities. The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286). Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model. The results showed an overall medium-high effect size (g = -.68, p = .02) with a 95% CI (-1.05 to -.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p < .001; I2 = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls. Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear.

Effects of transcranial electrical stimulation techniques on foreign vocabulary learning.

Although the use of transcranial electrical stimulation (tES) techniques on healthy population has been linked to facilitating language learning, studies on their effects on foreign language learning processes are scarce and results remain unclear. The objective of this study was to analyze whether tES enhances foreign language learning processes. Sixty-four healthy native Spanish-speaking participants were randomly assigned to four groups (transcranial direct current, transcranial random noise, tDCS-tRNS stimulation, or sham). They completed two intervention sessions with a two-week gap in between. During the first session the participants received stimulation (1.5 mA) while learning new English words and then performed recall and recognition tasks. Learning was assessed at follow-up, two weeks later. No differences in learning between groups were observed in the first session (F(1,61)= .86; p = .36). At follow-up, significantly higher learning accuracy was observed after tRNS compared to sham (p = .037). These results suggest that tRNS could be helpful in improving the processes involved in foreign language vocabulary learning.

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

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.

Preterm birth and early life environmental factors: neuropsychological profiles at adolescence and young adulthood.

OBJECTIVES: To establish neuropsychological profiles after high- and low-risk preterm birth (i.e., with and without neonatal brain injury) during adolescence and young adulthood and to assess the potential role of early life environmental factors in cognition. STUDY DESIGN: Participants (N = 177; Mage = 20.11 years) of both sexes were evaluated when adolescent or in young adulthood. They were grouped according to their birth status: 30 high-risk preterm, 83 low-risk preterm and 64 born at full term. RESULTS: Significant differences were found in several cognitive domains between groups. Furthermore, familial socioeconomic status (SES) moderated the relation between the degree of maturity/immaturity at birth and cognition (F(5,171) = 11.94, p < 0.001, R2 = 0.26). DISCUSSION: The findings showed different neuropsychological profiles during adolescence and young adulthood, with the high-risk preterm sample evidencing lower cognitive values. In addition, higher scores in the familial SES score in this study seem to have a protective effect on cognition.

Thalamic changes in a preterm sample with periventricular leukomalacia: correlation with white-matter integrity and cognitive outcome at school age.

INTRODUCTION: Thalamic abnormalities have been well documented in preterms with periventricular leukomalacia (PVL), although their contribution to long-term cognitive dysfunctions has not been thoroughly investigated. RESULTS: Significant differences between groups were observed for global thalamic volume. Neuropsychological assessments showed that preterms with PVL scored within the normal range, although significantly below controls in the full intelligence quotient and the specific cognitive domains of processing speed and working memory. Correlations of several thalamic regions with Working Memory Index and FIQ were found in the PVL group. Moreover, thalamic atrophy correlated with white-matter (WM) damage indexes (fractional anisotropy and radial diffusivity) assessed by diffusion tensor imaging. DISCUSSION: The findings suggest that thalamic damage is a common correlate of WM microstructural alterations and might be involved in the cognitive deficits seen in premature infants with PVL at school age. METHODS: We analyzed the impact of PVL-associated thalamic injury on cognitive status at school age and its correlation with WM integrity as measured by magnetic resonance imaging techniques. Thalamic volume and shape of 21 preterm children with PVL were compared with those of 11 preterm children of similar gestational age and birth weight with no evidence of focal WM abnormality.

Anatomical correlates of category-selective visual regions have distinctive signatures of connectivity in neonates.

The ventral visual stream is shaped during development by innate proto-organization within the visual system, such as the strong input from the fovea to the fusiform face area. In adults, category-selective regions have distinct signatures of connectivity to brain regions beyond the visual system, likely reflecting cross-modal and motoric associations. We tested if this long-range connectivity is part of the innate proto-organization, or if it develops with postnatal experience, by using diffusion-weighted imaging to characterize the connectivity of anatomical correlates of category-selective regions in neonates (N = 445), 1-9 month old infants (N = 11), and adults (N = 14). Using the HCP data we identified face- and place- selective regions and a third intermediate region with a distinct profile of selectivity. Using linear classifiers, these regions were found to have distinctive connectivity at birth, to other regions in the visual system and to those outside of it. The results support an extended proto-organization that includes long-range connectivity that shapes, and is shaped by, experience-dependent development.

Voice, Body Cues and Facial Expression in Emotion Recognition of Spanish Children and Adolescents: The Validation of Bell-Lysaker Emotion Recognition Test.

Emotion recognition has been traditionally measured trough the recognition of emotional expressions of static faces. Studies suggest that emotion recognition is progressively acquired from early stages in our infancy. However, the literature regarding other emotional domains such as voice or body movements is scarce. Additionally, the number of tools that integrate several domains is limited, especially in children and adolescents, and none of them tested in Spanish samples. Therefore, this study aimed to define the psychometric properties of the Bell-Lysaker Emotion Recognition Task (BLERT) and a new-designed alternate version providing normative data in Spanish children and adolescents (from 8 to 15 years old corresponding to 3th). Moreover, we aim to describe the emotional acquisition trajectory of children and adolescents with a tool that integrates voice, face expressions and body movements. For that purpose, BLERT was translated into Spanish (BLERT-SI) and an alternate version was created (BLERT-SII). A total of 545 children and adolescents from 8 to 15 year-old participated in the study (250 male/295 female). All participants fulfilled BLERT-SI and BLERT-SII within two weeks of difference. Order of presentation was counterbalanced. Results showed that BLERT-SI and SII have good internal consistency (α = .70 and 71 respectively). Test-retest reliability showed a moderate correlation (r = .45; p < .001). Percentages equivalences per age are provided. Age correlated with BLERT-SI (r = .31; p < .001) and BLERT-SII (r = .21; p < .001), showing a progressive acquisition and development of emotion recognition during this period. BLERT-SI and SII are useful tools when studying the follow-up of children and adolescents.

Comparing transcranial direct current stimulation and transcranial random noise stimulation over left dorsolateral prefrontal cortex and left inferior frontal gyrus: Effects on divergent and convergent thinking.

The essential role of creativity has been highlighted in several human knowledge areas. Regarding the neural underpinnings of creativity, there is evidence about the role of left dorsolateral prefrontal cortex (DLPFC) and left inferior frontal gyrus (IFG) on divergent thinking (DT) and convergent thinking (CT). Transcranial stimulation studies suggest that the left DLPFC is associated with both DT and CT, whereas left IFG is more related to DT. However, none of the previous studies have targeted both hubs simultaneously and compared transcranial direct current stimulation (tDCS) and random noise stimulation (tRNS). Additionally, given the relationship between cognitive flexibility and creativity, we included it in order to check if the improvement in creativity may be mediated by cognitive flexibility. In this double-blind, between-subjects study, 66 healthy participants were randomly assigned to one of three groups (N = 22) that received a transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), or sham for 20 min. The tDCS group received 1.5 mA with the anode over the left DLPFC and cathode over the left IFG. Locations in tRNS group were the same and they received 1.5 mA of high frequency tRNS (100-500 Hz). Divergent thinking was assessed before (baseline) and during stimulation with unusual uses (UU) and picture completion (PC) subtests from Torrance Creative thinking Test, whereas convergent thinking was evaluated with the remote association test (RAT). Stroop test was included to assess cognitive flexibility. ANCOVA results of performance under stimulation (controlling for baseline performance) showed that there were significant differences in PC (F = 3.35, p = 0.042, n p 2 = 0.10) but not in UU (F = 0.61, p = 0.546) and RAT (F = 2.65, p = 0.079) scores. Post-hoc analyses showed that tRNS group had significantly higher scores compared to sham (p = 0.004) in PC. More specifically, tRNS showed higher performance in fluency (p = 0.012) and originality (p = 0.021) dimensions of PC compared to sham. Regarding cognitive flexibility, we did not find any significant effect of any of the stimulation groups (F = 0.34, p = 0.711). Therefore, no further mediation analyses were performed. Finally, the group that received tDCS reported more adverse effects than sham group (F = 3.46, p = 0.035). Altogether, these results suggest that tRNS may have some advantages over tDCS in DT.

Gray matter volume decrements in preterm children with periventricular leukomalacia.

Periventricular leukomalacia (PVL) is the prototypic lesion in the encephalopathy of prematurity. Although PVL is identified by targeting cerebral white matter (WM), neuropathological and MRI studies document gray matter (GM) loss in cortical and subcortical structures. This study aimed to investigate the distribution of GM changes in children with a history of premature birth and PVL. Voxel-based morphometry was used to examine regional GM abnormalities in 22 children with a history of preterm birth and PVL. Preterms with PVL were compared with 22 terms and 14 preterms without PVL of similar GA and birth weight. GM and WM global volumetric volumes were found to decrease in comparison with both control groups. Regional GM volume abnormalities were also found: compared with their term peers, preterm children with PVL showed several regions of GM reduction. Moreover, PVL differed from preterms without PVL in the medial temporal lobe bilaterally, thalamus bilaterally, and caudate nuclei bilaterally. In addition, in our preterm sample with PVL, birth weight showed a statistical significant correlation with decreased GM regions. In conclusion, the voxel-based morphometry methodology revealed that PVL per se does involve GM reductions.