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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.

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.

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.

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.

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.

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.

Funding: This work was supported by a grant from the MIUR (N. 287713), the FP7: REWIRE project, by Progetto Strategico, Universitaà di Padova (N. 2010XPMFW4) to UC and by SIR grant (Scientific Independence of Young Researchers—N. RBSI141QKX) to LS. 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. Publisher PDF

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.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.

In the last decade, tractography methods based on diffusion imaging have been used to re-explore the anatomical basis of language and its disorders. This chapter is devoted to the harmonization of the findings from post-mortem dissection with more recent evidence emerging from diffusion tractography. We first focus on the anatomy and development of the arcuate fasciculus, its heterogeneity in the normal population, and possible functional and behavioral correlates of different patterns of lateralization. Other tracts relevant to language but located outside classical perisylvian regions will be also discussed. One outcome of this review will be to underlie the merits of the hodological (pathway-based) approach to neurology and psychiatry and its modern pursuit with diffusion tractography.

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.