Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

Cerebellar network alterations in adult attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults. METHODS: We applied diffusion-weighted spherical deconvolution tractography to dissect the cerebellar peduncles of male adults with ADHD (including those who did or did not respond to methylphenidate, based on at least 30% symptom improvement at 2 months) and controls. We investigated differences in tract metrics between controls and the whole ADHD sample and between controls and treatment-response groups using sensitivity analyses. Finally, we analyzed the association between the tract metrics and cliniconeuropsychological profiles. RESULTS: We included 60 participants with ADHD (including 42 treatment responders and 18 nonresponders) and 20 control participants. In the whole ADHD sample, MCP fractional anisotropy (FA; t 78 = 3.24, p = 0.002) and hindrance modulated orientational anisotropy (HMOA; t 78 = 3.01, p = 0.004) were reduced, and radial diffusivity (RD) in the right ICP was increased (t 78 = -2.84, p = 0.006), compared with controls. Although case-control differences in MCP FA and HMOA, which reflect white-matter microstructural organization, were driven by both treatment response groups, only responders significantly differed from controls in right ICP RD, which relates to myelination (t 60 = 3.14, p = 0.003). Hindrance modulated orientational anisotropy of the MCP was significantly positively associated with hyperactivity measures. LIMITATIONS: This study included only male adults with ADHD. Further research needs to investigate potential sex- and development-related differences. CONCLUSION: These results support the role of the cerebellar networks, especially of the MCP, in adult ADHD pathophysiology and should encourage further investigation. CLINICAL TRIAL REGISTRATION: NCT03709940.

Temporal Diffusion Ratio (TDR) for imaging restricted diffusion: Optimisation and pre-clinical demonstration.

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell'Acqua et al., proc. ISMRM 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation. Hence, it has a potential for informing on pore sizes, in particular the presence of large axon diameters or other cellular structures. TDR employs the signal from two dMRI acquisitions obtained with the same, large, b-value but with different diffusion gradient waveforms. TDR is advantageous as it employs standard acquisition sequences, does not make any assumptions on the underlying tissue structure and does not require any model fitting, avoiding issues related to model degeneracy. This work for the first time introduces and optimises the TDR method in simulation for a range of different tissues and scanner constraints and validates it in a pre-clinical demonstration. We consider both substrates containing cylinders and spherical structures, representing cell soma in tissue. Our results show that contrasting an acquisition with short gradient duration, short diffusion time and high gradient strength with an acquisition with long gradient duration, long diffusion time and low gradient strength, maximises the TDR contrast for a wide range of pore configurations. Additionally, in the presence of Rician noise, computing TDR from a subset (50% or fewer) of the acquired diffusion gradients rather than the entire shell as proposed originally further improves the contrast. In the last part of the work the results are demonstrated experimentally on rat spinal cord. In line with simulations, the experimental data shows that optimised TDR improves the contrast compared to non-optimised TDR. Furthermore, we find a strong correlation between TDR and histology measurements of axon diameter. In conclusion, we find that TDR has great potential and is a very promising alternative (or potentially complement) to model-based approaches for informing on pore sizes and restricted diffusion in general.

Comparing the test-retest reliability of resting-state functional magnetic resonance imaging metrics across single band and multiband acquisitions in the context of healthy aging.

The identification of meaningful functional magnetic resonance imaging (fMRI) biomarkers requires measures that reliably capture brain performance across different subjects and over multiple scanning sessions. Recent developments in fMRI acquisition, such as the introduction of multiband (MB) protocols and in-plane acceleration, allow for increased scanning speed and improved temporal resolution. However, they may also lead to reduced temporal signal to noise ratio and increased signal leakage between simultaneously excited slices. These methods have been adopted in several scanning modalities including diffusion weighted imaging and fMRI. To our knowledge, no study has formally compared the reliability of the same resting-state fMRI (rs-fMRI) metrics (amplitude of low-frequency fluctuations; seed-to-voxel and region of interest [ROI]-to-ROI connectivity) across conventional single-band fMRI and different MB acquisitions, with and without in-plane acceleration, across three sessions. In this study, 24 healthy older adults were scanned over three visits, on weeks 0, 1, and 4, and, on each occasion, underwent a conventional single band rs-fMRI scan and three different rs-fMRI scans with MB factors 4 and 6, with and without in-plane acceleration. Across all three rs-fMRI metrics, the reliability scores were highest with MB factor 4 with no in-plane acceleration for cortical areas and with conventional single band for subcortical areas. Recommendations for future research studies are discussed.

Tissue optimization strategies for high-quality ex vivo diffusion imaging.

Ex vivo diffusion imaging can be used to study healthy and pathological tissue microstructure in the rodent brain with high resolution, providing a link between in vivo MRI and ex vivo microscopy techniques. Major challenges for the successful acquisition of ex vivo diffusion imaging data however are changes in the relaxivity and diffusivity of brain tissue following perfusion fixation. In this study we address this question by examining the combined effects of tissue preparation factors that influence signal-to-noise ratio (SNR) and consequently image quality, including fixative concentration, contrast agent concentration and tissue rehydration time. We present an optimization strategy combining these factors to manipulate the T 1 and T 2 of fixed tissue and maximize SNR efficiency. We apply this strategy in the rat brain, for a diffusion-weighted spin echo protocol with TE = 27 ms on a 9.4 T scanner with a 39 mm volume coil and 660 mT/m 114 mm gradient insert. We used a reduced fixative concentration of 2% paraformaldehyde (PFA), rehydration time more than 20 days, 15 mM Gd-DTPA in perfusate and TR 250 ms. This resulted in a doubling of SNR and an increase in SNR per unit time of 135% in cortical grey matter and 88% in white matter compared with 4% PFA and no contrast agent. This improved SNR efficiency enabled the acquisition of excellent-quality high-resolution (78 µ m isotropic voxel size) diffusion data with b = 4000 s/mm 2 , 30 diffusion directions and a field of view of 40 × 13 × 18 mm3 in less than 4 days. It was also possible to achieve comparable data quality for a standard resolution (150 µ m) diffusion dataset in 2 1 4 h. In conclusion, the tissue optimization strategy presented here may be used to improve SNR, increase spatial resolution and/or allow faster acquisitions in preclinical ex vivo diffusion MRI experiments.

Processing of social and monetary rewards in autism spectrum disorders.

BACKGROUND: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. AIMS: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. METHOD: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). RESULTS: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. CONCLUSIONS: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Mapping acute neuroinflammation in vivo with diffusion-MRI in rats given a systemic lipopolysaccharide challenge.

It is becoming increasingly apparent that neuroinflammation plays a critical role in an array of neurological and psychiatric disorders. Recent studies have demonstrated the potential of diffusion MRI (dMRI) to characterize changes in microglial density and morphology associated with neuroinflammation, but these were conducted mostly ex vivo and/or in extreme, non-physiological animal models. Here, we build upon these studies by investigating the utility of well-established dMRI methods to detect neuroinflammation in vivo in a more clinically relevant animal model of sickness behavior. We show that diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) indicate widespread increases in diffusivity in the brains of rats given a systemic lipopolysaccharide challenge (n = 20) vs. vehicle-treated controls (n = 12). These diffusivity changes correlated with histologically measured changes in microglial morphology, confirming the sensitivity of dMRI to neuroinflammatory processes. This study marks a further step towards establishing a noninvasive indicator of neuroinflammation, which would greatly facilitate early diagnosis and treatment monitoring in various neurological and psychiatric diseases.

Differences in Frontal Network Anatomy Across Primate Species.

The frontal lobe is central to distinctive aspects of human cognition and behavior. Some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. The discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. In this study, we used a novel tractography approach to demonstrate that frontal lobe networks, extending within and beyond the frontal lobes, occupy 66% of total brain white matter in humans and 48% in three monkey species: vervets (Chlorocebus aethiops), rhesus macaque (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis), all male. The simian-human differences in proportional frontal tract volume were significant for projection, commissural, and both intralobar and interlobar association tracts. Among the long association tracts, the greatest difference was found for tracts involved in motor planning, auditory memory, top-down control of sensory information, and visuospatial attention, with no significant differences in frontal limbic tracts important for emotional processing and social behaviour. In addition, we found that a nonfrontal tract, the anterior commissure, had a smaller volume fraction in humans, suggesting that the disproportionally large volume of human frontal lobe connections is accompanied by a reduction in the proportion of some nonfrontal connections. These findings support a hypothesis of an overall rearrangement of brain connections during human evolution.SIGNIFICANCE STATEMENT Tractography is a unique tool to map white matter connections in the brains of different species, including humans. This study shows that humans have a greater proportion of frontal lobe connections compared with monkeys, when normalized by total brain white matter volume. In particular, tracts associated with language and higher cognitive functions are disproportionally larger in humans compared with monkeys, whereas other tracts associated with emotional processing are either the same or disproportionally smaller. This supports the hypothesis that the emergence of higher cognitive functions in humans is associated with increased extended frontal connectivity, allowing human brains more efficient cross talk between frontal and other high-order associative areas of the temporal, parietal, and occipital lobes.

Atypical measures of diffusion at the gray-white matter boundary in autism spectrum disorder in adulthood.

Autism spectrum disorder (ASD) is a highly complex neurodevelopmental condition that is accompanied by neuroanatomical differences on the macroscopic and microscopic level. Findings from histological, genetic, and more recently in vivo neuroimaging studies converge in suggesting that neuroanatomical abnormalities, specifically around the gray-white matter (GWM) boundary, represent a crucial feature of ASD. However, no research has yet characterized the GWM boundary in ASD based on measures of diffusion. Here, we registered diffusion tensor imaging data to the structural T1-weighted images of 92 adults with ASD and 92 matched neurotypical controls in order to examine between-group differences and group-by-sex interactions in fractional anisotropy and mean diffusivity sampled at the GWM boundary, and at different sampling depths within the superficial white and into the gray matter. As hypothesized, we observed atypical diffusion at and around the GWM boundary in ASD, with between-group differences and group-by-sex interactions depending on tissue class and sampling depth. Furthermore, we identified that altered diffusion at the GWM boundary partially (i.e., ~50%) overlapped with atypical gray-white matter tissue contrast in ASD. Our study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.

Generalized Richardson-Lucy (GRL) for analyzing multi-shell diffusion MRI data.

Spherical deconvolution is a widely used approach to quantify the fiber orientation distribution (FOD) from diffusion MRI data of the brain. The damped Richardson-Lucy (dRL) is an algorithm developed to perform robust spherical deconvolution on single-shell diffusion MRI data while suppressing spurious FOD peaks due to noise or partial volume effects. Due to recent progress in acquisition hardware and scanning protocols, it is becoming increasingly common to acquire multi-shell diffusion MRI data, which allows for the modelling of multiple tissue types beyond white matter. While the dRL algorithm could, in theory, be directly applied to multi-shell data, it is not optimised to exploit its information content to model the signal from multiple tissue types. In this work, we introduce a new framework based on dRL - dubbed generalized Richardson-Lucy (GRL) - that uses multi-shell data in combination with user-chosen tissue models to disentangle partial volume effects and increase the accuracy in FOD estimation. Further, GRL estimates signal fraction maps associated to each user-selected model, which can be used during fiber tractography to dissect and terminate the tracking without need for additional structural data. The optimal weighting of multi-shell data in the fit and the robustness to noise and to partial volume effects of GRL was studied with synthetic data. Subsequently, we investigated the performance of GRL in comparison to dRL and to multi-shell constrained spherical deconvolution (MSCSD) on a high-resolution diffusion MRI dataset from the Human Connectome Project and on an MRI dataset acquired at 3T on a clinical scanner. In line with previous studies, we described the signal of the cerebrospinal-fluid and of the grey matter with isotropic diffusion models, whereas four diffusion models were considered to describe the white matter. With a third dataset including small diffusion weightings, we studied the feasibility of including intra-voxel incoherent motion effects due to blood pseudo-diffusion in the modelling. Further, the reliability of GRL was demonstrated with a test-retest scan of a subject acquired at 3T. Results of simulations show that GRL can robustly disentangle different tissue types at SNR above 20 with respect to the non-weighted image, and that it improves the angular accuracy of the FOD estimation as compared to dRL. On real data, GRL provides signal fraction maps that are physiologically plausible and consistent with those obtained with MSCSD, with correlation coefficients between the two methods up to 0.96. When considering IVIM effects, a high blood pseudo-diffusion fraction is observed in the medial temporal lobe and in the sagittal sinus. In comparison to dRL and MSCSD, GRL provided sharper FODs and less spurious peaks in presence of partial volume effects, but the FOD reconstructions are also highly dependent on the chosen modelling of white matter. When performing fiber tractography, GRL allows to terminate fiber tractography using the signal fraction maps, which results in a better tract termination at the grey-white matter interface or at the outer cortical surface. In terms of inter-scan reliability, GRL performed similarly to or better than compared methods. In conclusion, GRL offers a new modular and flexible framework to perform spherical deconvolution of multi-shell data.

Modelling white matter with spherical deconvolution: How and why?

Since the realization that diffusion MRI can probe the microstructural organization and orientation of biological tissue in vivo and non-invasively, a multitude of diffusion imaging methods have been developed and applied to study the living human brain. Diffusion tensor imaging was the first model to be widely adopted in clinical and neuroscience research, but it was also clear from the beginning that it suffered from limitations when mapping complex configurations, such as crossing fibres. In this review, we highlight the main steps that have led the field of diffusion imaging to move from the tensor model to the adoption of diffusion and fibre orientation density functions as a more effective way to describe the complexity of white matter organization within each brain voxel. Among several techniques, spherical deconvolution has emerged today as one of the main approaches to model multiple fibre orientations and for tractography applications. Here we illustrate the main concepts and the reasoning behind this technique, as well as the latest developments in the field. The final part of this review provides practical guidelines and recommendations on how to set up processing and acquisition protocols suitable for spherical deconvolution.

Frontoparietal Tracts Linked to Lateralized Hand Preference and Manual Specialization.

Humans show a preference for using the right hand over the left for tasks and activities of everyday life. While experimental work in non-human primates has identified the neural systems responsible for reaching and grasping, the neural basis of lateralized motor behavior in humans remains elusive. The advent of diffusion imaging tractography for studying connectional anatomy in the living human brain provides the possibility of understanding the relationship between hemispheric asymmetry, hand preference, and manual specialization. In this study, diffusion tractography was used to demonstrate an interaction between hand preference and the asymmetry of frontoparietal tracts, specifically the dorsal branch of the superior longitudinal fasciculus, responsible for visuospatial integration and motor planning. This is in contrast to the corticospinal tract and the superior cerebellar peduncle, for which asymmetry was not related to hand preference. Asymmetry of the dorsal frontoparietal tract was also highly correlated with the degree of lateralization in tasks requiring visuospatial integration and fine motor control. These results suggest a common anatomical substrate for hand preference and lateralized manual specialization in frontoparietal tracts important for visuomotor processing.

Connectomic correlates of response to treatment in first-episode psychosis.

Connectomic approaches using diffusion tensor imaging have contributed to our understanding of brain changes in psychosis, and could provide further insights into the neural mechanisms underlying response to antipsychotic treatment. We here studied the brain network organization in patients at their first episode of psychosis, evaluating whether connectome-based descriptions of brain networks predict response to treatment, and whether they change after treatment. Seventy-six patients with a first episode of psychosis and 74 healthy controls were included. Thirty-three patients were classified as responders after 12 weeks of antipsychotic treatment. Baseline brain structural networks were built using whole-brain diffusion tensor imaging tractography, and analysed using graph analysis and network-based statistics to explore baseline characteristics of patients who subsequently responded to treatment. A subgroup of 43 patients was rescanned at the 12-week follow-up, to study connectomic changes over time in relation to treatment response. At baseline, those subjects who subsequently responded to treatment, compared to those that did not, showed higher global efficiency in their structural connectomes, a network configuration that theoretically facilitates the flow of information. We did not find specific connectomic changes related to treatment response after 12 weeks of treatment. Our data suggest that patients who have an efficiently-wired connectome at first onset of psychosis show a better subsequent response to antipsychotics. However, response is not accompanied by specific structural changes over time detectable with this method.

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.

Functional segregation and integration within fronto-parietal networks.

Experimental data on monkeys and functional studies in humans support the existence of a complex fronto-parietal system activating for cognitive and motor tasks, which may be anatomically supported by the superior longitudinal fasciculus (SLF). Advanced tractography methods have recently allowed the separation of the three branches of the SLF but are not suitable for their functional investigation. In order to gather comprehensive information about the functional organisation of these fronto-parietal connections, we used an innovative method, which combined tractography of the SLF in the largest dataset so far (129 participants) with 14 meta-analyses of functional magnetic resonance imaging (fMRI) studies. We found that frontal and parietal functions can be clustered into a dorsal spatial/motor network associated with the SLF I, and a ventral non-spatial/motor network associated with the SLF III. Further, all the investigated functions activated a middle network mostly associated with the SLF II. Our findings suggest that dorsal and ventral fronto-parietal networks are segregated but also share regions of activation, which may support flexible response properties or conscious processing. In sum, our novel combined approach provided novel findings on the functional organisation of fronto-parietal networks, and may be successfully applied to other brain 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.

Reinforcement of the Brain's Rich-Club Architecture Following Early Neurodevelopmental Disruption Caused by Very Preterm Birth.

The second half of pregnancy is a crucial period for the development of structural brain connectivity, and an abrupt interruption of the typical processes of development during this phase caused by the very preterm birth (<33 weeks of gestation) is likely to result in long-lasting consequences. We used structural and diffusion imaging data to reconstruct the brain structural connectome in very preterm-born adults. We assessed its rich-club organization and modularity as 2 characteristics reflecting the capacity to support global and local information exchange, respectively. Our results suggest that the establishment of global connectivity patterns is prioritized over peripheral connectivity following early neurodevelopmental disruption. The very preterm brain exhibited a stronger rich-club architecture than the control brain, despite possessing a relative paucity of white matter resources. Using a simulated lesion approach, we also investigated whether putative structural reorganization takes place in the very preterm brain in order to compensate for its anatomical constraints. We found that connections between the basal ganglia and (pre-) motor regions, as well as connections between subcortical regions, assumed an altered role in the structural connectivity of the very preterm brain, and that such alterations had functional implications for information flow, rule learning, and verbal IQ.

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study.

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI.

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.