Mapping the subcortical connectome using in vivo diffusion MRI: Feasibility and reliability

Tractography combined with regions of interest (ROIs) has been used to non-invasively study the structural connectivity of the cortex as well as to assess the reliability of these connections. However, the subcortical connectome (subcortex to subcortex) has not been comprehensively examined, in part due to the difficulty of performing tractography in this complex and compact region. In this study, we performed an in vivo investigation using tractography to assess the feasibility and reliability of mapping known connections between structures of the subcortex using the test-retest dataset from the Human Connectome Project (HCP). We further validated our observations using a separate unrelated subjects dataset from the HCP. Quantitative assessment was performed by computing tract densities and spatial overlap of identified connections between subcortical ROIs. Further, known connections between structures of the basal ganglia and thalamus were identified and visually inspected, comparing tractography reconstructed trajectories with descriptions from tract-tracing studies. Our observations demonstrate both the feasibility and reliability of using a data-driven tractography-based approach to map the subcortical connectome in vivo

Effects of MP2RAGE B\u3csub\u3e1\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e sensitivity on inter-site T\u3csub\u3e1\u3c/sub\u3e reproducibility and hippocampal morphometry at 7T

Most neuroanatomical studies are based on T -weighted MR images, whose intensity profiles are not solely determined by the tissue\u27s longitudinal relaxation times (T ), but also affected by varying non-T contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameter choices – e.g., to emphasize intracortical myelin-dependent contrast variations – can substantially impact image quality and cortical analyses through remnants of B -related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal morphometry. The latter remained unexplored initially, but can provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B inhomogeneities have a considerably variable effect on cortical T estimates, as well as on hippocampal morphometry depending on the MP2RAGE setup. While T differed substantially across datasets initially, we show the inter-site T comparability improves after correcting for the spatially varying B field using a separately acquired Sa2RAGE B map. Finally, removal of B residuals affects hippocampal volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid). Taken together, we show that the choice of MP2RAGE parameters can impact T comparability across sites and present evidence that hippocampal segmentation results are modulated by B inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols, as well as (2) acquisition of a B map to correct MP2RAGE data for potential B variations to allow comparison across datasets. 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 + + + + + + + +

The role of the temporal pole in temporal lobe epilepsy: A diffusion kurtosis imaging study

This study aimed to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) and its temporopolar cortex in temporal lobe epilepsy (TLE) patients. DKI quantitative maps were obtained from fourteen lesional TLE and ten non-lesional TLE patients, along with twenty-three healthy controls. Data collected included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with disease duration. To characterize temporopolar cortex microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Patients were separated according to the temporal lobe ipsilateral to seizure onset and their AFQ results were used as input for statistical analyses. Significant differences were observed between lesional TLE and controls, towards the most temporopolar segment of ILF and Unc proximal to the TP within the ipsilateral temporal lobe in left TLE patients for MK, RK, AWF and MD. No significant changes were observed with DKI maps in the non-lesional TLE group. DKI measurements correlated with disease duration, mostly towards the temporopolar segments of the WM bundles. Stronger differences in MK, RK and AWF within the temporopolar cortex were observed in the lesional TLE and noticeable differences (except for MD) in non-lesional TLE groups compared to controls. This study demonstrates that DKI has potential to detect subtle microstructural alterations within the temporopolar segments of the ILF and Unc and the connected temporopolar cortex in TLE patients including non-lesional TLE subjects. This could aid our understanding of the extrahippocampal areas, more specifically the temporal pole role in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes

Neurodegenerative and functional signatures of the cerebellar cortex in m.3243A \u3e G patients

Mutations of the mitochondrial DNA are an important cause of inherited diseases that can severely affect the tissue\u27s homeostasis and integrity. The m.3243A \u3e G mutation is the most commonly observed across mitochondrial disorders and is linked to multisystemic complications, including cognitive deficits. In line with in vitro experiments demonstrating the m.3243A \u3e G\u27s negative impact on neuronal energy production and integrity, m.3243A \u3e G patients show cerebral grey matter tissue changes. However, its impact on the most neuron dense, and therefore energy-consuming brain structure - the cerebellum - remains elusive. In this work, we used high-resolution structural and functional data acquired using 7 T MRI to characterize the neurodegenerative and functional signatures of the cerebellar cortex in m.3243A \u3e G patients. Our results reveal altered tissue integrity within distinct clusters across the cerebellar cortex, apparent by their significantly reduced volume and longitudinal relaxation rate compared with healthy controls, indicating macroscopic atrophy and microstructural pathology. Spatial characterization reveals that these changes occur especially in regions related to the frontoparietal brain network that is involved in information processing and selective attention. In addition, based on resting-state functional MRI data, these clusters exhibit reduced functional connectivity to frontal and parietal cortical regions, especially in patients characterized by (i) a severe disease phenotype and (ii) reduced information-processing speed and attention control. Combined with our previous work, these results provide insight into the neuropathological changes and a solid base to guide longitudinal studies aimed to track disease progression

The architecture of cancellous bone in the hindlimb of moa (Aves: Dinornithiformes), with implications for stance and gait

The extinct, flightless moa of New Zealand included some of the largest birds to have existed and possessed many distinguishing pelvic and hindlimb osteological features. These features may have influenced stance and gait in moa compared with extant birds. One means of assessing locomotor biomechanics, particularly for extinct species, is quantitative analysis of the architecture of cancellous bone, since this architecture is adapted to suit its mechanical environment with high sensitivity. This study investigated the three-dimensional architecture of cancellous bone in the femur, tibiotarsus and fibula of three moa species: Dinornis robustus, Pachyornis elephantopus and Megalapteryx didinus. Using computed tomographic X-ray scanning and previously developed fabric analysis techniques, the spatial variation in cancellous bone fabric patterns in moa was found to be largely comparable with that previously reported for extant birds, particularly large species. Moa hence likely used postures and kinematics similar to those employed by large extant bird species, but this interpretation is tentative on account of relatively small sample sizes. A point of major difference between moa and extant birds concerns the diaphyses; cancellous bone invades the medullary cavity in both groups, but the invasion is far more extensive in moa. Combined with previous assessments of cortical geometry, this further paints a picture of at least some moa species possessing very robust limb bones, for which a convincing explanation remains to be determine

Miocene waterfowl and other birds from central Otago, New Zealand

Copyright © The Natural History Museum 2007Abundant fossil bird bones from the lower Bannockburn Formation, Manuherikia Group, an Early-Middle Miocene lacustrine deposit, 16–19 Ma, from Otago in New Zealand, reveal the “St Bathans Fauna” (new name), a first Tertiary avifauna of land and freshwater birds from New Zealand. At least 23 species of birds are represented by bones, and probable moa, Aves: Dinornithiformes, by eggshell. Anatids dominate the fauna with four genera and five species described as new: a sixth and largest anatid species is represented by just one bone. This is the most diverse Early-Middle Miocene duck fauna known worldwide. Among ducks, two species of dendrochenines are most numerous in the fauna, but a tadornine is common as well. A diving petrel (Pelecanoididae: Pelecanoides) is described, so extending the geological range of this genus worldwide from the Pliocene to the Middle Miocene, at least. The remaining 16 taxa are left undescribed but include: a large species of gull (Laridae); two small waders (Charadriiformes, genus indet.), the size of Charadrius bicinctus and Calidris ruficollis, respectively; a gruiform represented by one specimen similar to Aptornis; abundant rail (Rallidae) bones, including a common flightless rail and a rarer slightly larger taxon, about the size of Gallirallus philippensis; an ?eagle (Accipitridae); a pigeon (Columbidae); three parrots (Psittacidae); an owlet nightjar (Aegothelidae: Aegotheles sp.); a swiftlet (Apodidae: Collocalia sp.); and three passerine taxa, of which the largest is a member of the Cracticidae. The absence of some waterbirds, such as anserines (including swans), grebes (Podicipedidae) and shags (Phalacrocoracidae), among the abundant bones, indicates their probable absence from New Zealand in the Early-Middle Miocene.T. H. Worthy, A. J. D. Tennyson, C. Jones, J. A. McNamara and B. J. Dougla

Meta-analysis of variation suggests that embracing variability improves both replicability and generalizability in preclinical research

The replicability of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets replicability has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that cannot be replicated. An alternative approach is to, instead, deliberately introduce heterogeneity, known as "heterogenization" of experimental design. Here, we explore a novel perspective in the heterogenization program in a meta-analysis of variability in observed phenotypic outcomes in both control and experimental animal models of ischemic stroke. First, by quantifying interindividual variability across control groups, we illustrate that the amount of heterogeneity in disease state (infarct volume) differs according to methodological approach, for example, in disease induction methods and disease models. We argue that such methods may improve replicability by creating diverse and representative distribution of baseline disease state in the reference group, against which treatment efficacy is assessed. Second, we illustrate how meta-analysis can be used to simultaneously assess efficacy and stability (i.e., mean effect and among-individual variability). We identify treatments that have efficacy and are generalizable to the population level (i.e., low interindividual variability), as well as those where there is high interindividual variability in response; for these, latter treatments translation to a clinical setting may require nuance. We argue that by embracing rather than seeking to minimize variability in phenotypic outcomes, we can motivate the shift toward heterogenization and improve both the replicability and generalizability of preclinical research