A detailed analysis of anatomical plausibility of crossed and uncrossed streamline rendition of the dentato-rubro-thalamic tract (DRT(T)) in a commercial stereotactic planning system

Background An increasing number of neurosurgeons use display of the dentato-rubro-thalamic tract (DRT) based on diffusion weighted imaging (dMRI) as basis for their routine planning of stimulation or lesioning approaches in stereotactic tremor surgery. An evaluation of the anatomical validity of the display of the DRT with respect to modern stereotactic planning systems and across different tracking environments has not been performed. Methods Distinct dMRI and anatomical magnetic resonance imaging (MRI) data of high and low quality from 9 subjects were used. Six subjects had repeated MRI scans and therefore entered the analysis twice. Standardized DICOM structure templates for volume of interest definition were applied in native space for all investigations. For tracking BrainLab Elements (BrainLab, Munich, Germany), two tensor deterministic tracking (FT2), MRtrix IFOD2 (https://www.mrtrix.org), and a global tracking (GT) approach were used to compare the display of the uncrossed (DRTu) and crossed (DRTx) fiber structure after transformation into MNI space. The resulting streamlines were investigated for congruence, reproducibility, anatomical validity, and penetration of anatomical way point structures. Results In general, the DRTu can be depicted with good quality (as judged by waypoints). FT2 (surgical) and GT (neuroscientific) show high congruence. While GT shows partly reproducible results for DRTx, the crossed pathway cannot be reliably reconstructed with the other (iFOD2 and FT2) algorithms. Conclusion Since a direct anatomical comparison is difficult in the individual subjects, we chose a comparison with two research tracking environments as the best possible “ground truth.” FT2 is useful especially because of its manual editing possibilities of cutting erroneous fibers on the single subject level. An uncertainty of 2 mm as mean displacement of DRTu is expectable and should be respected when using this approach for surgical planning. Tractographic renditions of the DRTx on the single subject level seem to be still illusive.

Uncal apex movement and positioning in Alzheimer's Disease

Alzheimer’s Disease (AD) patients have consistently shown declines in declarative memory, consolidation, and in many other cognitive areas. These changes are associated with atrophy and volumetric declines in medial temporal lobe structures, such as the hippocampus. Hippocampal atrophy has been associated with AD. However, the influence of AD atrophy on the position of the uncal apex—an anatomical landmark for the hippocampus—has not been longitudinally examined. The current study’s objective is to investigate changes in the position of the uncal apex of AD patients over the course of two years. The current study draws upon the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data set (adni.loni.usc.edu). For each participant, I obtained demographic data, anatomical MRI images in native space, hippocampal segmentations from the subcortical stream of FreeSurfer (v.5.3.0), and linear transforms to MNI space. Using uncal apex y-positions transformed in MNI space, I found that the uncal apex fell in a more posterior position in AD patients relative to control and that over time, the uncal apex migrates toward a more anterior position in both groups. These results suggest that part of the neuroimaging examinations that are done on AD patients should examine uncal apex positions as a biomarker of early AD progression. Future directions and limitations are discussed

Decoding the Information Structure Underlying the Neural Representation of Concepts

The nature of the neural code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. Three main types of information have been proposed as candidates for the neural representations of lexical concepts: taxonomic (i.e., information about category membership and inter-category relations), distributional (i.e., information about patterns of word co-occurrence in natural language use), and experiential (i.e., information about sensory-motor, affective, and other features of phenomenal experience engaged during concept acquisition). In two experiments, we investigated the extent to which these three types of information are encoded in the neural activation patterns associated with hundreds of English nouns from a wide variety of conceptual categories. Participants made familiarity judgments on the meaning of written nouns while undergoing functional MRI. A high-resolution, whole-brain activation map was generated for each noun in each participant′s native space. These word-specific activation maps were used to evaluate different representational spaces corresponding to the three types of information described above. In both studies, we found a striking advantage for experience-based models in most brain areas previously associated with concept representation. Partial correlation analyses revealed that only experiential information successfully predicted concept similarity structure when inter-model correlations were taken into account. This pattern of results was found independently for object concepts and event concepts. Our findings indicate that the neural representation of conceptual knowledge primarily encodes information about features of experience, and that - to the extent that it is represented in the brain - taxonomic and distributional information may rely on such an experience-based code.

Amyloid burden quantification depends on PET and MR image processing methodology

Quantification of amyloid load with positron emission tomography can be useful to assess Alzheimer’s Disease in-vivo. However, quantification can be affected by the image processing methodology applied. This study’s goal was to address how amyloid quantification is influenced by different semi-automatic image processing pipelines. Images were analysed in their Native Space and Standard Space; non-rigid spatial transformation methods based on maximum a posteriori approaches and tissue probability maps (TPM) for regularisation were explored. Furthermore, grey matter tissue segmentations were defined before and after spatial normalisation, and also using a population-based template. Five quantification metrics were analysed: two intensity-based, two volumetric-based, and one multi-parametric feature. Intensity-related metrics were not substantially affected by spatial normalisation and did not significantly depend on the grey matter segmentation method, with an impact similar to that expected from test-retest studies (≤10%). Yet, volumetric and multi-parametric features were sensitive to the image processing methodology, with an overall variability up to 45%. Therefore, the analysis should be carried out in Native Space avoiding non-rigid spatial transformations. For analyses in Standard Space, spatial normalisation regularised by TPM is preferred. Volumetric-based measurements should be done in Native Space, while intensity-based metrics are more robust against differences in image processing pipelines.

Reproducing macaque lateral grasping and oculomotor networks using resting state functional connectivity and diffusion tractography

Cortico-cortical networks involved in motor control have been well defined in the macaque using a range of invasive techniques. The advent of neuroimaging has enabled non-invasive study of these large-scale functionally specialized networks in the human brain; however, assessing its accuracy in reproducing genuine anatomy is more challenging. We set out to assess the similarities and differences between connections of macaque motor control networks defined using axonal tracing and those reproduced using structural and functional connectivity techniques. We processed a cohort of macaques scanned in vivo that were made available by the open access PRIME-DE resource, to evaluate connectivity using diffusion imaging tractography and resting state functional connectivity (rs-FC). Sectors of the lateral grasping and exploratory oculomotor networks were defined anatomically on structural images, and connections were reproduced using different structural and functional approaches (probabilistic and deterministic whole-brain and seed-based tractography; group template and native space functional connectivity analysis). The results showed that parieto-frontal connections were best reproduced using both structural and functional connectivity techniques. Tractography showed lower sensitivity but better specificity in reproducing connections identified by tracer data. Functional connectivity analysis performed in native space had higher sensitivity but lower specificity and was better at identifying connections between intrasulcal ROIs than group-level analysis. Connections of AIP were most consistently reproduced, although those connected with prefrontal sectors were not identified. We finally compared diffusion MR modelling with histology based on an injection in AIP and speculate on anatomical bases for the observed false negatives. Our results highlight the utility of precise ex vivo techniques to support the accuracy of neuroimaging in reproducing connections, which is relevant also for human studies.

Convergence of cortical types and functional motifs in the mesiotemporal lobe

The parahippocampus-hippocampus complex in the mesiotemporal lobe (MTL) is implicated in many different cognitive processes, is compromised in numerous disorders, and exhibits a unique cytoarchitectural transition from six-layered isocortex to three-layered allocortex. Our study leveraged an ultra-high-resolution histological reconstruction of a human brain to (i) develop a continuous surface model of the MTL iso-to-allocortex transition and (ii) quantitatively characterise the region’s cytoarchitecture. We projected the model into the native space of in vivo functional magnetic resonance imaging of healthy adults to (iii) construct a generative model of its intrinsic circuitry and (iv) determine its relationship with distributed functional dynamics of macroscale isocortical fluctuations. We provide evidence that the most prominent axis of cytoarchitectural differentiation of the MTL follows infolding from iso-to-allocortex and is defined by depth-specific variations in neuron density. Intrinsic effective connectivity exhibited a more complex relationship to MTL geometry, varying across both iso-to-allocortical and anterior-posterior axes. Variation along the long axis of the MTL was associated with differentiation between transmodal and unimodal systems, with anterior regions linked to transmodal cortex. In contrast, the iso-to-allocortical gradient was associated with the multiple demand system, with isocortex linked to regions activated when task demands prohibit the use of prior knowledge. Our findings establish a novel model of the MTL, in which its broad influence on neural function emerges through the combination micro- and macro-scale structural features.