Axonal integrity predicts cortical reorganisation following cervical injury

Traumatic spinal cord injury (SCI) leads to disruption of axonal architecture and macroscopic tissue loss with impaired information flow between the brain and spinal cord-the presumed basis of ensuing clinical impairment

The correlation between white-matter microstructure and the complexity of spontaneous brain activity: A difussion tensor imaging-MEG study

The advent of new signal processing methods, such as non-linear analysis techniques, represents a new perspective which adds further value to brain signals' analysis. Particularly, Lempel–Ziv's Complexity (LZC) has proven to be useful in exploring the complexity of the brain electromagnetic activity. However, an important problem is the lack of knowledge about the physiological determinants of these measures. Although acorrelation between complexity and connectivity has been proposed, this hypothesis was never tested in vivo. Thus, the correlation between the microstructure of the anatomic connectivity and the functional complexity of the brain needs to be inspected. In this study we analyzed the correlation between LZC and fractional anisotropy (FA), a scalar quantity derived from diffusion tensors that is particularly useful as an estimate of the functional integrity of myelinated axonal fibers, in a group of sixteen healthy adults (all female, mean age 65.56 ± 6.06 years, intervals 58–82). Our results showed a positive correlation between FA and LZC scores in regions including clusters in the splenium of the corpus callosum, cingulum, parahipocampal regions and the sagittal stratum. This study supports the notion of a positive correlation between the functional complexity of the brain and the microstructure of its anatomical connectivity. Our investigation proved that a combination of neuroanatomical and neurophysiological techniques may shed some light on the underlying physiological determinants of brain's oscillation

Structure of the motor descending pathways correlates with the temporal kinematics of hand movements

Simple Summary: How hand motor behavior relates to the microstructure of the underlying subcortical white matter pathways is yet to be fully understood. Here we consider two well-known examples of our everyday motor repertoire, reaching and reach-to-grasp, by looking at their temporal unfolding and at the microstructure of descending projection pathways, conveying motor information from the motor cortices towards the more ventral regions of the nervous system. We combine three-dimensional kinematics, describing the temporal profile of hand movements, with diffusion imaging tractography, exploring the microstructure of specific segments of the projection pathways (internal capsule, corticospinal and hand motor tracts). The results indicate that the level of anisotropy characterizing these white matter tracts can influence the temporal unfolding of reaching and reach-to-grasp movements. Abstract: 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

Neuropoboljšavanje i ranjivost u adolescenciji

The very definition, scope, and practical implications of the concept of vulnerability are among the most debated questions in the field of vulnerability research. However, a consensus seems to exist regarding children and adolescents: they are generally considered vulnerable and in need of special protection due to their physical and psychological immaturity, lack of knowledge and life experience, and overall dependency on adults. The special status of this population is safeguarded in numerous legal and ethics documents. In this paper, we discuss the commercial use of transcranial direct current stimulation (tDCS), as a method that have potential to affect functioning of the brain tissue with electrical currents, but also a variety of digital methods used to influence the brain. tDCS is openly advertised, affordable and accessible, even to minors. However, changes that tDCS and similar methods could induce in developing brain tissue and consequently their interference with the normal neurodevelopmental processes could have far-reaching health ramifications and thus represent new sources of vulnerability that slip under the radar of formalized legal and ethics documents. This article discusses changes in the adolescent brain during development and address whether adolescents who would wish to use these neuroenhancement procedures should be considered vulnerable and on what grounds.Sama definicija, opseg i praktične implikacije koncepta ranjivosti su među najčešće raspravljanim pitanjima u području istraživanja ranjivosti. Zbog njihove fizičke i psihološke nezrelosti, nedostatka znanja i životnog iskustva te sveukupne ovisnosti o odraslima, postoji konsenzus da se djeca i adolescenti općenito smatraju ranjivima, te da ih je potrebno zaštititi. Poseban status ove populacije potvrđen je i u brojnim zakonskim i etičkim dokumentima. U radu raspravljamo o komercijalnoj upotrebi transkranijalne stimulacije istosmjernom strujom (tDCS) kao metode koja, djelujući s električnom strujom, može utjecati na funkcioniranje moždanog tkiva. Također govorimo i o ostalim digitalnim metodama koje se koriste za djelovanje na mozak. tDSC se otvoreno oglašava, pristupačan je cijenom i dostupan, čak i maloljetnicima. No, promjene koje bi tDCS i slične metode mogle potaknuti u razvoju moždanog tkiva i posljedično njihovu interferenciju s normalnim neurorazvojnim procesima mogle bi imati dalekosežne zdravstvene posljedice i tako predstavljati nove izvore ranjivosti koji nisu obuhvaćeni u formalnim pravnim i etičkim dokumentima. U ovom se članku raspravlja o promjenama u adolescentskom mozgu tijekom razvoja i pitanjem trebaju li se adolescenti koji žele koristiti ove postupke za neuropoboljšanje smatrati ranjivima i na temelju čega

Diffusion and Functional MRI of the Brain Following Sports-Related Impacts and Concussion

Concussion is a prevalent injury associated with contact sports, however the underlying brain changes associated with concussion remain poorly understood. Therefore it is critical to (a) understand the complex sequelae that underlie concussion, (b) when or if the brain recovers, and (c) if there are brain changes associated with contact sports in general. Advanced imaging techniques may be sensitive to changes that persist beyond relatively prompt symptom recovery and clearance to return to play. Resting state functional MRI (RS-fMRI) and diffusion tensor imaging (DTI) data was acquired on the 3T at Robarts Research Institute from healthy and concussed athletes from three separate cohorts. Healthy male hockey players were compared to longitudinal data acquired from concussed peers participating in Bantam-level hockey at 24-72 hours and 3 months after the injury. There were alterations in diffusion measures along multiple tracts with the largest significant decreases located along the superior longitudinal fasciculus at both times post-concussion. DTI tractography was used to relate diffusion changes with acute changes in functional connectivity. At 3 months post-concussion, network and regional connectivity analysis revealed compensatory functional hyperconnectivity patterns based on correlations with clinical symptoms and diffusion data. Longitudinal imaging data was acquired from concussed female rugby players post-concussion (at 24-72 hours, 3 and 6 months after injury) and compared to non-concussed teammates throughout the in- and off-season. Using a data-driven linked independent component analysis we observed acute disruptions in diffusion metrics inferiorly along the brainstem that recovered by 3 months post-concussion. However, we also observed long-lasting signatures that reflect co-varying alterations in brain microstructure and functional connectivity that related to the number of self-reported concussions. Based on these findings it appears that concussion initiates both acute and persistent changes to central white matter structures with subtle changes in functional connectivity. Given these findings, we acquired data from varsity-level female swimmers and rowers that were also scanned during the in- and off-season in order to directly compare with healthy rugby players and rule out the effects of high-level competitive exercise. We used accelerometers to quantify head rotational accelerations in a subset of the rowers and rugby players to confirm the number and magnitude of subclinical impacts. We quantified DTI alterations along major white matter tracts in contact compared to non-contact athletes that were in the opposite direction of our concussion findings. Diffusion changes within the genu and splenium of the corpus callosum were related to a history of concussion. Fluctuations in brainstem diffusion parameters between the in- and off-season as well as functional hyperconnectivity patterns within the default mode and medial visual networks were observed in contact athletes only. Together, these studies suggest that concussions result in an acute set of symptoms and microstructural brain changes. Despite quick resolution of symptoms, evidence of persistent axonal disruption exists at 3 and 6 months post-concussion and well-beyond symptomatic recovery. While functional hyperconnectivity may be one mechanism that allows the brain to function despite these disruptions, concussion may also compromise neuroprotective microstructural changes that protect the young, healthy brain throughout years of contact play. It remains to be seen if the brain changes associated with contact play and concussions are directly related to later risks of neurodegenerative processes

Examining the development of brain structure in utero with fetal MRI, acquired as part of the Developing Human Connectome Project

The human brain is an incredibly complex organ, and the study of it traverses many scales across space and time. The development of the brain is a protracted process that begins embryonically but continues into adulthood. Although neural circuits have the capacity to adapt and are modulated throughout life, the major structural foundations are laid in utero during the fetal period, through a series of rapid but precisely timed, dynamic processes. These include neuronal proliferation, migration, differentiation, axonal pathfinding, and myelination, to name a few. The fetal origins of disease hypothesis proposed that a variety of non-communicable diseases emerging in childhood and adulthood could be traced back to a series of risk factors effecting neurodevelopment in utero (Barker 1995). Since this publication, many studies have shown that the structural scaffolding of the brain is vulnerable to external environmental influences and the perinatal developmental window is a crucial determinant of neurological health later in life. However, there remain many fundamental gaps in our understanding of it. The study of human brain development is riddled with biophysical, ethical, and technical challenges. The Developing Human Connectome Project (dHCP) was designed to tackle these specific challenges and produce high quality open-access perinatal MRI data, to enable researchers to investigate normal and abnormal neurodevelopment (Edwards et al., 2022). This thesis will focus on investigating the diffusion-weighted and anatomical (T2) imaging data acquired in the fetal period, between the second to third trimester (22 – 37 gestational weeks). The limitations of fetal MR data are ill-defined due to a lack of literature and therefore this thesis aims to explore the data through a series of critical and strategic analysis approaches that are mindful of the biophysical challenges associated with fetal imaging. A variety of analysis approaches are optimised to quantify structural brain development in utero, exploring avenues to relate the changes in MR signal to possible neurobiological correlates. In doing so, the work in this thesis aims to improve mechanistic understanding about how the human brain develops in utero, providing the clinical and medical imaging community with a normative reference point. To this aim, this thesis investigates fetal neurodevelopment with advanced in utero MRI methods, with a particular emphasis on diffusion MRI. Initially, the first chapter outlines a descriptive, average trajectory of diffusion metrics in different white matter fiber bundles across the second to third trimester. This work identified unique polynomial trajectories in diffusion metrics that characterise white matter development (Wilson et al., 2021). Guided by previous literature on the sensitivity of DWI to cellular processes, I formulated a hypothesis about the biophysical correlates of diffusion signal components that might underpin this trend in transitioning microstructure. This hypothesis accounted for the high sensitivity of the diffusion signal to a multitude of simultaneously occurring processes, such as the dissipating radial glial scaffold, commencement of pre-myelination and arborization of dendritic trees. In the next chapter, the methods were adapted to address this hypothesis by introducing another dimension, and charting changes in diffusion properties along developing fiber pathways. With this approach it was possible to identify compartment-specific microstructural maturation, refining the spatial and temporal specificity (Wilson et al., 2023). The results reveal that the dynamic fluctuations in the components of the diffusion signal correlate with observations from previous histological work. Overall, this work allowed me to consolidate my interpretation of the changing diffusion signal from the first chapter. It also serves to improve understanding about how diffusion signal properties are affected by processes in transient compartments of the fetal brain. The third chapter of this thesis addresses the hypothesis that cortical gyrification is influenced by both underlying fiber connectivity and cytoarchitecture. Using the same fetal imaging dataset, I analyse the tissue microstructural change underlying the formation of cortical folds. I investigate correlations between macrostructural surface features (curvature, sulcal depth) and tissue microstructural measures (diffusion tensor metrics, and multi-shell multi-tissue decomposition) in the subplate and cortical plate across gestational age, exploring this relationship both at the population level and within subjects. This study provides empirical evidence to support the hypotheses that microstructural properties in the subplate and cortical plate are altered with the development of sulci. The final chapter explores the data without anatomical priors, using a data-driven method to extract components that represent coordinated structural maturation. This analysis aims to examine if brain regions with coherent patterns of growth over the fetal period converge on neonatal functional networks. I extract spatially independent features from the anatomical imaging data and quantify the spatial overlap with pre-defined neonatal resting state networks. I hypothesised that coherent spatial patterns of anatomical development over the fetal period would map onto the functional networks observed in the neonatal period. Overall, this thesis provides new insight about the developmental contrast over the second to third trimester of human development, and the biophysical correlates affecting T2 and diffusion MR signal. The results highlight the utility of fetal MRI to research critical mechanisms of structural brain maturation in utero, including white matter development and cortical gyrification, bridging scales from neurobiological processes to whole brain macrostructure. their gendered constructions relating to women

White matter microstructural differences underlying beta oscillations during speech in adults who stutter

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen