Associations between Early Life Nutrient Intakes and Brain Maturation Show Developmental Dynamics from Infancy to Toddlerhood: A Neuroimaging Observation Study.

BACKGROUND: Myelin imaging has increasingly been applied to study the impact of nutrition on brain development in recent years. Although individual dynamics for nutrient intakes and myelin trajectories previously have been investigated across childhood, the longitudinal interaction between both remains unclear in typically developed children. OBJECTIVES: The objective of this work was to explore the developmental dynamics of nutrient-myelin interactions from infancy to early childhood using myelin imaging as a marker for brain maturation. METHODS: Brain neuroimaging (1 scan per child) and dietary nutrient intake data were analyzed for 88 nutrients from 293 children (127 female, 62% White) from a longitudinal cohort study in the United States. A sliding window approach was used to investigate correlations between nutrient intakes and brain myelination over a continuous set of age windows. Image processing techniques (Sobel-filter vertical edge detection) were applied to determine age windows with unique association profiles, providing novel insight into how these relationships change with child age. RESULTS: We identified 3 nutrient-myelin windows covering the age range of 1-5 y: window 1 from 6 to 20 mo with 60% positive nutrient correlations, window 2 from 20 to 30 mo with 20% positive correlations, and window 3 from 30 to 60 mo with 37% positive correlations. The windows are aligned with reported myelin and white matter dynamics that change in the first 5 y from fast and steep (window 1) to continued but slower growth (window 3), with window 2 possibly representing the inflection period. CONCLUSIONS: To our knowledge, this is the first study in typically developing children demonstrating the developmental dynamics between early life nutrient intakes and brain maturation in toddlerhood. The knowledge can be applied for identifying targeted and brain-stage-appropriate nutritional interventions for this critical stage of brain development.

Asymmetry and Structure of the Fronto-Parietal Networks Underlie Visuomotor Processing in Humans.

Research in both humans and monkeys has shown that even simple hand movements require cortical control beyond primary sensorimotor areas. An extensive functional neuroimaging literature demonstrates the key role that cortical fronto-parietal regions play for movements such as reaching and reach-to-grasp. However, no study so far has examined the specific white matter connections linking the fronto-parietal regions, namely the 3 parallel pathways of the superior longitudinal fasciculus (SLF). The aim of the current study was to explore how selective fronto-parietal connections are for different kinds of hand movement in 30 right-handed subjects by correlating diffusion imaging tractography and kinematic data. We showed that a common network, consisting of bilateral SLF II and SLF III, was involved in both reaching and reach-to-grasp movements. Larger SLF II and SLF III in the right hemisphere were associated with faster speed of visuomotor processing, while the left SLF II and SLF III played a role in the initial movement trajectory control. Furthermore, the right SLF II was involved in the closing grip phase necessary for efficient grasping of the object. We demonstrated for the first time that individual differences in asymmetry and structure of the fronto-parietal networks were associated with visuomotor processing in humans.

The role of the frontal aslant tract and premotor connections in visually guided hand movements.

Functional neuroimaging and brain lesion studies demonstrate that secondary motor areas of the frontal lobe play a crucial role in the cortical control of hand movements. However, no study so far has examined frontal white matter connections of the secondary motor network, namely the frontal aslant tract, connecting the supplementary motor complex and the posterior inferior frontal regions, and the U-shaped dorsal and ventral premotor fibers running through the middle frontal gyrus. The aim of the current study is to explore the involvement of the short frontal lobe connections in reaching and reach-to-grasp movements in 32 right-handed healthy subjects by correlating tractography data based on spherical deconvolution approach with kinematical data. We showed that individual differences in the microstructure of the bilateral frontal aslant tract, bilateral ventral and left dorsal premotor tracts were associated with kinematic features of hand actions. Furthermore, bilateral ventral premotor connections were also involved in the closing grip phase necessary for determining efficient and stable grasping of the target object. This work suggests for the first time that hand kinematics and visuomotor processing are associated with the anatomy of the short frontal lobe connections.

Frontal networks in adults with autism spectrum disorder.

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

Age-Related Differences and Heritability of the Perisylvian Language Networks.

Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and their lateralization remains stable throughout adolescence and early adulthood. Conversely, the posterior segment shows right lateralization in childhood but becomes progressively bilateral during adolescence, driven by a reduction in volume in the right hemisphere. Analysis of the twin sample showed that genetic and shared environmental factors influence the anatomy of those segments that lateralize earlier, whereas specific environmental effects drive the variability in the volume of the posterior segment that continues to change in adolescence and adulthood. Our results suggest that the age-related differences in the lateralization of the language perisylvian pathways are related to the relative contribution of genetic and environmental effects specific to each segment. SIGNIFICANCE STATEMENT: Our study shows that, by early childhood, frontotemporal (long segment) and frontoparietal (anterior segment) connections of the arcuate fasciculus are left and right lateralized, respectively, and remain lateralized throughout adolescence and early adulthood. In contrast, temporoparietal (posterior segment) connections are right lateralized in childhood, but become progressively bilateral during adolescence. Preliminary twin analysis suggested that lateralization of the arcuate fasciculus is a heterogeneous process that depends on the interplay between genetic and environment factors specific to each segment. Tracts that exhibit higher age effects later in life (i.e., posterior segment) appear to be influenced more by specific environmental factors.

Child and adolescent health in Europe: Towards meeting the 2030 agenda.

Background: Childhood and adolescence are critical stages for a healthy life. To support countries in promoting health and development and improving health care for this age group, the WHO Regional Office for Europe developed the European strategy for child and adolescent health 2015-2020, which was adopted by all countries. This paper reports progress in the strategy's implementation until 2020. Methods: A survey was sent to all ministries of health of the 53 Member States of the WHO European Region. Responses were received from 45 Member States. Results are presented in this paper. Results: The European Region made overall progress in recent years, but increasing levels of overweight and obesity among children, adolescent mental health and low breastfeeding rates are recognized as key national challenges. Although forty-one countries adopted a national child and adolescent health strategy, only eight countries involve children in their review, development and implementation stages. Two-thirds of countries have a strategy for health-promoting schools and a school curriculum for health education. One-third of countries do not have legislation against marketing of unhealthy foods and beverages to children. Most countries reported routine assessment for developmental difficulties in children, but less than a quarter collected and reported data on children who are developmentally on track. There are major gaps in data collection for migrant children. Hospitalization rates for young children vary five-fold across the region, indicating over-hospitalization and access problems in some countries. Only ten countries allow minors access to health care without parental consent based on their maturity and only eleven countries allow school nurses to dispense contraceptives to adolescents without a doctor's prescription. Conclusions: This paper shows the progress in child and adolescent health made by countries in Europe until 2020 and key areas where additional work is needed to move the 2030 agenda forward. The survey was undertaken before the COVID-19 pandemic and the war in Ukraine. Both will likely exacerbate many of the observed problems and potentially reverse some gains reported. A renewed commitment is needed.

Exploring the ventral white matter language network in bimodal and unimodal bilinguals.

We used diffusion magnetic resonance imaging tractography to investigate the effect of language modality on the anatomy of the ventral white matter language network by comparing unimodal (Italian/English) and bimodal bilinguals (Italian/Italian Sign Language). We extracted the diffusion tractography measures of the Inferior Longitudinal fasciculus (ILF), Uncinate fasciculus (UF) and Inferior Fronto-Occipital fasciculus (IFOF) and we correlated them with the degree of bilingualism and the individual performance in fluency tasks. For both groups of bilinguals, the microstructural properties of the right ILF were correlated with individual level of proficiency in L2, confirming the involvement of this tract in bilingualism. In addition, we found that the degree of left lateralization of the ILF predicted the performance in semantic fluency in L1. The microstructural properties of the right UF correlated with performance in phonological fluency in L1, only for bimodal bilinguals. Overall, the pattern shows both similarities and differences between the two groups of bilinguals.

Corticospinal excitability and conductivity are related to the anatomy of the corticospinal tract.

Probing the brain structure-function relationship is at the heart of modern neuroscientific explorations, enabled by recent advances in brain mapping techniques. This study aimed to explore the anatomical blueprint of corticospinal excitability and shed light on the structure-function relationship within the human motor system. Using diffusion magnetic resonance imaging tractography, based on the spherical deconvolution approach, and transcranial magnetic stimulation (TMS), we show that anatomical inter-individual variability of the corticospinal tract (CST) modulates the corticospinal excitability and conductivity. Our findings show for the first time the relationship between increased corticospinal excitability and conductivity in individuals with a bigger CST (i.e., number of streamlines), as well as increased corticospinal microstructural organization (i.e., fractional anisotropy). These findings can have important implications for the understanding of the neuroanatomical basis of TMS as well as the study of the human motor system in both health and disease.

Structure of the Motor Descending Pathways Correlates with the Temporal Kinematics of Hand Movements.

The projection system, a complex organization of ascending and descending white matter pathways, is the principal system for conveying sensory and motor information, connecting frontal and sensorimotor regions with ventral regions of the central nervous system. The corticospinal tract (CST), one of the principal projection pathways, carries distal movement-related information from the cortex to the spinal cord, and whether its microstructure is linked to the kinematics of hand movements is still an open question. The aim of the present study was to explore how microstructure of descending branches of the projection system, namely the hand motor tract (HMT), the corticospinal tract (CST) and its sector within the internal capsule (IC), can relate to the temporal profile of reaching and reach-to-grasp movements. Projection pathways of 31 healthy subjects were virtually dissected by means of diffusion tractography and the kinematics of reaching and reach-to-grasp movements were also analyzed. A positive association between Hindrance Modulated Orientation Anisotropy (HMOA) and kinematics was observed, suggesting that anisotropy of the considered tract can influence the temporal unfolding of motor performance. We highlight, for the first time, that hand kinematics and the visuomotor transformation processes underlying reaching and reach-to-grasp movements relate to the microstructure of specific projection fibers subserving these movements.

Handedness and White Matter Networks.

The development and persistence of laterality is a key feature of human motor behavior, with the asymmetry of hand use being the most prominent. The idea that asymmetrical functions of the hands reflect asymmetries in terms of structural and functional brain organization has been tested many times. However, despite advances in laterality research and increased understanding of this population-level bias, the neural basis of handedness remains elusive. Recent developments in diffusion magnetic resonance imaging enabled the exploration of lateralized motor behavior also in terms of white matter and connectional neuroanatomy. Despite incomplete and partly inconsistent evidence, structural connectivity of both intrahemispheric and interhemispheric white matter seems to differ between left and right-handers. Handedness was related to asymmetry of intrahemispheric pathways important for visuomotor and visuospatial processing (superior longitudinal fasciculus), but not to projection tracts supporting motor execution (corticospinal tract). Moreover, the interindividual variability of the main commissural pathway corpus callosum seems to be associated with handedness. The review highlights the importance of exploring new avenues for the study of handedness and presents the latest state of knowledge that can be used to guide future neuroscientific and genetic research.

Neuroanatomical Correlates of Binge-Eating Behavior: At the Roots of Unstoppable Eating.

Binge-eating refers to episodes of uncontrolled eating accompanied by a perceived loss of control, which can be common in the general population. Given the profound negative consequences of persistent binge-eating such as weight and eating disorders, it is vital to determine what makes someone more vulnerable than others to engage in such a conduct. A total of 42 normal-weight individuals (21 with binge-eating episodes and 21 without binge-eating episodes) underwent a structural magnetic resonance imaging measurement and Voxel-based morphometry (VBM) was used to assess between-group differences in terms of gray matter volume (GMV), together with self-report impulsivity and binge-eating measures. The results showed binge-eating individuals as characterized by higher trait impulsivity and greater regional GMV in the left middle frontal gyrus: however, the GMV in this region appeared to be positively correlated only with measures of binge-eating but not with trait impulsivity measures. These findings provide novel insights on the neurobiological roots of BE in normal-weight individuals and highlight how this behavior can be associated with brain morphometric changes within prefrontal regions also in a non-clinical population. Overall, this study provides a further characterization of the neural correlates of binge-eating and novel insights into the treatment of its more severe pathological forms.

Cross-talk connections underlying dorsal and ventral stream integration during hand actions.

According to the dual-stream theory, the processing of visual information is divided into a ventral pathway mediating object recognition, and a dorsal pathway supporting visuomotor control. Increasing evidence suggests that these streams are not independent, but where this dorsal-ventral stream integration occurs remains unknown. We explored the candidate white matter pathways linking dorsal and ventral visual streams in 30 right-handed participants performing object-oriented hand movements of varying complexity (reaching, grasping and lifting), using advanced diffusion imaging tractography based on the spherical deconvolution and kinematical analysis. We provided for the first time a direct evidence of cross-communication between dorsal and ventral visual streams in humans, through vertical occipital fasciculus and temporo-parietal fibers of the arcuate fasciculus during on-line control of grasping and lifting actions. We showed that individual differences in the microstructure of these cross-talk connections were associated with the variability of the arm deceleration, the grip opening and the grasp accuracy. This study suggests that hand kinematics, in skilled hand actions where high degree of online control is required, is related to the anatomy of the cross-talk networks between dorsal and ventral streams, bringing important insights to the dual-stream theory and the sensorimotor organization of hand actions.

The Neural Correlates of Grasping in Left-Handers: When Handedness Does Not Matter.

Neurophysiological studies showed that in macaques, grasp-related visuomotor transformations are supported by a circuit involving the anterior part of the intraparietal sulcus, the ventral and the dorsal region of the premotor area. In humans, a similar grasp-related circuit has been revealed by means of neuroimaging techniques. However, the majority of "human" studies considered movements performed by right-handers only, leaving open the question of whether the dynamics underlying motor control during grasping is simply reversed in left-handers with respect to right-handers or not. To address this question, a group of left-handed participants has been scanned with functional magnetic resonance imaging while performing a precision grasping task with the left or the right hand. Dynamic causal modeling was used to assess how brain regions of the two hemispheres contribute to grasping execution and whether the intra- and inter-hemispheric connectivity is modulated by the choice of the performing hand. Results showed enhanced inter-hemispheric connectivity between anterior intraparietal and dorsal premotor cortices during grasping execution with the left dominant hand (LDH) (e.g., right hemisphere) compared to the right (e.g., left hemisphere). These findings suggest that that the left hand, although dominant and theoretically more skilled in left handers, might need additional resources in terms of the visuomotor control and on-line monitoring to accomplish a precision grasping movement. The results are discussed in light of theories on the modulation of parieto-frontal networks during the execution of prehensile movements, providing novel evidence supporting the hypothesis of a handedness-independent specialization of the left hemisphere in visuomotor control.

Decoding social intentions in human prehensile actions: Insights from a combined kinematics-fMRI study.

Consistent evidence suggests that the way we reach and grasp an object is modulated not only by object properties (e.g., size, shape, texture, fragility and weight), but also by the types of intention driving the action, among which the intention to interact with another agent (i.e., social intention). Action observation studies ascribe the neural substrate of this 'intentional' component to the putative mirror neuron (pMNS) and the mentalizing (MS) systems. How social intentions are translated into executed actions, however, has yet to be addressed. We conducted a kinematic and a functional Magnetic Resonance Imaging (fMRI) study considering a reach-to-grasp movement performed towards the same object positioned at the same location but with different intentions: passing it to another person (social condition) or putting it on a concave base (individual condition). Kinematics showed that individual and social intentions are characterized by different profiles, with a slower movement at the level of both the reaching (i.e., arm movement) and the grasping (i.e., hand aperture) components. fMRI results showed that: (i) distinct voxel pattern activity for the social and the individual condition are present within the pMNS and the MS during action execution; (ii) decoding accuracies of regions belonging to the pMNS and the MS are correlated, suggesting that these two systems could interact for the generation of appropriate motor commands. Results are discussed in terms of motor simulation and inferential processes as part of a hierarchical generative model for action intention understanding and generation of appropriate motor commands.

Heritability of the limbic networks.

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum ('medial default-mode network'), the ventral cingulum and the fornix ('hippocampal-diencephalic-retrosplenial network') and the uncinate fasciculus ('temporo-amygdala-orbitofrontal network'). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.

Cognitive deficits from a cerebellar tumour: a historical case report from Luria's Laboratory.

In 1964 an original case report from A.R. Luria's Laboratory of Neuropsychology was published in Cortex, being one of the first to draw a link between cerebellum and cognition, by highlighting the manifestation of 'pseudo-frontal' symptoms resulting from a cerebellar tumour. The findings of Luria and his team seem more consistent with modern views about cerebellar interactions with the frontal lobe and its contributions to behaviour than the views prevalent at the time of publication. The paper was originally submitted in Russian, and translated into Italian for its publication by Cortex. However, Cortex did not preserve the original manuscript in Russian. With the passage of time, and available only to the Italian readership, this case report inevitably fell into obscurity. Hence, we present a translation in English based on the published Italian version of the manuscript and discuss it in the context of Luria's general thinking about information processing in the brain and our current understanding of cortico-cerebellar system. The publication of this article gives readers an opportunity to consider the substantial influence of Soviet neuropsychology on the field internationally under Luria's leadership in the 1960s. It also shows that time is the best judge of ones scientific endeavours, and what may seem implausible today might prove to be valid and worthy of exploration tomorrow.