A framework to improve the alignment of individual cytoarchitectonic maps of the Julich-Brain atlas using cortical folding landmarks.

The segregation of the cortical mantle into cytoarchitectonic areas provides a structural basis for the specialization of different brain regions. In vivo neuroimaging experiments can be linked to this postmortem cytoarchitectonic parcellation via Julich-Brain. This atlas embeds probabilistic maps that account for inter-individual variability in the localization of cytoarchitectonic areas in the reference spaces targeted by spatial normalization. We built a framework to improve the alignment of architectural areas across brains using cortical folding landmarks. This framework, initially designed for in vivo imaging, was adapted to postmortem histological data. We applied this to the first 14 brains used to establish the Julich-Brain atlas to infer a refined atlas with more focal probabilistic maps. The improvement achieved is significant in the primary regions and some of the associative areas. This framework also provides a tool for exploring the relationship between cortical folding patterns and cytoarchitectonic areas in different cortical regions to establish new landmarks in the remainder of the cortex.

What do brain endocasts tell us? A comparative analysis of the accuracy of sulcal identification by experts and perspectives in palaeoanthropology.

Palaeoneurology is a complex field as the object of study, the brain, does not fossilize. Studies rely therefore on the (brain) endocranial cast (often named endocast), the only available and reliable proxy for brain shape, size and details of surface. However, researchers debate whether or not specific marks found on endocasts correspond reliably to particular sulci and/or gyri of the brain that were imprinted in the braincase. The aim of this study is to measure the accuracy of sulcal identification through an experiment that reproduces the conditions that palaeoneurologists face when working with hominin endocasts. We asked 14 experts to manually identify well-known foldings in a proxy endocast that was obtained from an MRI of an actual in vivo Homo sapiens head. We observe clear differences in the results when comparing the non-corrected labels (the original labels proposed by each expert) with the corrected labels. This result illustrates that trying to reconstruct a sulcus following the very general known shape/position in the literature or from a mean specimen may induce a bias when looking at an endocast and trying to follow the marks observed there. We also observe that the identification of sulci appears to be better in the lower part of the endocast compared to the upper part. The results concerning specific anatomical traits have implications for highly debated topics in palaeoanthropology. Endocranial description of fossil specimens should in the future consider the variation in position and shape of sulci in addition to using models of mean brain shape. Moreover, it is clear from this study that researchers can perceive sulcal imprints with reasonably high accuracy, but their correct identification and labelling remains a challenge, particularly when dealing with extinct species for which we lack direct knowledge of the brain.

Exploring the emergence of morphological asymmetries around the brain's Sylvian fissure: a longitudinal study of shape variability in preterm infants.

Brain folding patterns vary within the human species, but some folding properties are common across individuals, including the Sylvian fissure's inter-hemispheric asymmetry. Contrarily to the other brain folds (sulci), the Sylvian fissure develops through the process of opercularization, with the frontal, parietal, and temporal lobes growing over the insular lobe. Its asymmetry may be related to the leftward functional lateralization for language processing, but the time course of these asymmetries' development is still poorly understood. In this study, we investigated refined shape features of the Sylvian fissure and their longitudinal development in 71 infants born extremely preterm (mean gestational age at birth: 26.5 weeks) and imaged once before and once at term-equivalent age (TEA). We additionally assessed asymmetrical sulcal patterns at TEA in the perisylvian and inferior frontal regions, neighbor to the Sylvian fissure. While reproducing renowned strong asymmetries in the Sylvian fissure, we captured an early encoding of its main asymmetrical shape features, and we observed global asymmetrical shape features representative of a more pronounced opercularization in the left hemisphere, contrasting with the previously reported right hemisphere advance in sulcation around birth. This added novel insights about the processes governing early-life brain folding mechanisms, potentially linked to the development of language-related capacities.

Disentangling the variability of the superficial white matter organization using regional-tractogram-based population stratification.

Each variation of the cortical folding pattern implies a particular rearrangement of the geometry of the fibers of the underlying white matter. While this rearrangement only impacts the ends of the long pathways, it may affect most of the trajectory of the short bundles. Therefore, mapping the short fibers of the human brain using diffusion-based tractography requires a dedicated strategy to overcome the variability of the folding patterns. In this paper, we propose a fiber-based stratification strategy splitting the population into homogeneous groups for disentangling the superficial white matter bundle organization. This strategy introduces a new refined fiber distance which includes angular considerations for inferring fine-grained atlases of the short bundles surrounding a specific sulcus and a subtractogram distance that quantifies the similitude between fiber sets of two different subjects. The stratification splits the population into groups with similar regional fiber organization using manifold learning. We first successfully test the hypothesis that the main source of variability of the regional fiber organization is the variability of the regional folding pattern. Then, in each group, we proceed with the automatic identification of the most stable bundles, at a higher granularity level than what can be achieved with the non-stratified whole population, enabling the disentanglement of the very variable configuration of the short fibers. Finally, the method searches for bundle correspondence across groups to build a population level atlas. As a proof of concept, the atlas refinement achieved by this strategy is illustrated for the fibers that surround the central sulcus and the superior temporal sulcus using the HCP dataset.

Shape variability of the central sulcus in the developing brain: A longitudinal descriptive and predictive study in preterm infants.

Despite growing evidence of links between sulcation and function in the adult brain, the folding dynamics, occurring mostly before normal-term-birth, is vastly unknown. Looking into the development of cortical sulci in infants can give us keys to address fundamental questions: what is the sulcal shape variability in the developing brain? When are the shape features encoded? How are these morphological parameters related to further functional development? In this study, we aimed to investigate the shape variability of the developing central sulcus, which is the frontier between the primary somatosensory and motor cortices. We studied a cohort of 71 extremely preterm infants scanned twice using MRI - once around 30 weeks post-menstrual age (w PMA) and once at term-equivalent age, around 40w PMA -, in order to quantify the sulcus's shape variability using manifold learning, regardless of age-group or hemisphere. We then used these shape descriptors to evaluate the sulcus's variability at both ages and to assess hemispheric and age-group specificities. This led us to propose a description of ten shape features capturing the variability in the central sulcus of preterm infants. Our results suggested that most of these features (8/10) are encoded as early as 30w PMA. We unprecedentedly observed hemispheric asymmetries at both ages, and the one captured at term-equivalent age seems to correspond with the asymmetry pattern previously reported in adults. We further trained classifiers in order to explore the predictive value of these shape features on manual performance at 5 years of age (handedness and fine motor outcome). The central sulcus's shape alone showed a limited but relevant predictive capacity in both cases. The study of sulcal shape features during early neurodevelopment may participate to a better comprehension of the complex links between morphological and functional organization of the developing brain.

Automatic recognition of specific local cortical folding patterns.

The study of local cortical folding patterns showed links with psychiatric illnesses as well as cognitive functions. Despite the tools now available to visualize cortical folds in 3D, manually classifying local sulcal patterns is a time-consuming and tedious task. In fact, 3D visualization of folds helps experts to identify different sulcal patterns but fold variability is so high that the distinction between these patterns sometimes requires the definition of complex criteria, making manual classification difficult and not reliable. However, the assessment of the impact of these patterns on the functional organization of the cortex could benefit from the study of large databases, especially when studying rare patterns. In this paper, several algorithms for the automatic classification of fold patterns are proposed to allow morphological studies to be extended and confirmed on such large databases. Three methods are proposed, the first based on a Support Vector Machine (SVM) classifier, the second on the Scoring by Non-local Image Patch Estimator (SNIPE) approach and the third based on a 3D Convolution Neural Network (CNN). These methods are generic enough to be applicable to a wide range of folding patterns. They are tested on two types of patterns for which there is currently no method to automatically identify them: the Anterior Cingulate Cortex (ACC) patterns and the Power Button Sign (PBS). The two ACC patterns are almost equally present whereas PBS is a particularly rare pattern in the general population. The three models proposed achieve balanced accuracies of approximately 80% for ACC patterns classification and 60% for PBS classification. The CNN-based model is more interesting for the classification of ACC patterns thanks to its rapid execution. However, SVM and SNIPE-based models are more effective in managing unbalanced problems such as PBS recognition.

Network analysis of whole-brain fMRI dynamics: A new framework based on dynamic communicability.

Neuroimaging techniques such as MRI have been widely used to explore the associations between brain areas. Structural connectivity (SC) captures the anatomical pathways across the brain and functional connectivity (FC) measures the correlation between the activity of brain regions. These connectivity measures have been much studied using network theory in order to uncover the distributed organization of brain structures, in particular FC for task-specific brain communication. However, the application of network theory to study FC matrices is often "static" despite the dynamic nature of time series obtained from fMRI. The present study aims to overcome this limitation by introducing a network-oriented analysis applied to whole-brain effective connectivity (EC) useful to interpret the brain dynamics. Technically, we tune a multivariate Ornstein-Uhlenbeck (MOU) process to reproduce the statistics of the whole-brain resting-state fMRI signals, which provides estimates for MOU-EC as well as input properties (similar to local excitabilities). The network analysis is then based on the Green function (or network impulse response) that describes the interactions between nodes across time for the estimated dynamics. This model-based approach provides time-dependent graph-like descriptor, named communicability, that characterize the roles that either nodes or connections play in the propagation of activity within the network. They can be used at both global and local levels, and also enables the comparison of estimates from real data with surrogates (e.g. random network or ring lattice). In contrast to classical graph approaches to study SC or FC, our framework stresses the importance of taking the temporal aspect of fMRI signals into account. Our results show a merging of functional communities over time, moving from segregated to global integration of the network activity. Our formalism sets a solid ground for the analysis and interpretation of fMRI data, including task-evoked activity.

Measurement of Sylvian Fissure asymmetry and occipital bending in humans and Pan troglodytes.

The evolution of human-specific lateralised functions such as language has been linked to the development of structural asymmetries in the brain. Here we applied state of the art image analysis techniques to measure Sylvian Fissure (SF) asymmetry and Occipital Bending (OB) in 3D Magnetic Resonance (MR) images of the brain obtained in-vivo for 30 humans and 30 chimpanzees (Pan troglodytes). SF morphology differed between species, with the human SF terminating more superiorly in right inferior parietal lobe, an asymmetry that was on average absent in chimpanzees (F (1,52) = 5.963, p = 0.018). Irrespective of morphology, Total SF Length was, as previously reported, leftward in humans but not in chimpanzees, although the difference did not reach significance between species. However, when only brains possessing comparable bilateral SF bifurcation morphology were compared, humans showed previously reported "Typical" left-lateralised Anterior-Horizontal (AH-SF) and right-lateralised Vertical (V-SF) SF asymmetries. In contrast, chimpanzees lacked both asymmetries, and this approached being a significant difference between-species in the AH-SF segment (F (1, 34) = 3.680, p = 0.064). On average in humans the left occipital lobe crossed the midline toward the right (Rightward OB) which was significantly different from the chimpanzee cohort that showed no average OB (Independent-Samples Mann-Whitney U Test, p = 0.012). Furthermore, OB was related to SF asymmetry in humans, such that the more rightward V-SF and leftward AH-SF, the more rightward the OB. This "Default" pattern of SF and OB asymmetries was found in 41.7% of human individuals with bilateral SF bifurcation but none of the chimpanzees. To our knowledge, this is the first study highlighting that a pattern of SF and OB asymmetry distinguishes the human from the chimpanzee brain, and suggests this may be associated with a unique trajectory of brain development and functional abilities in humans.

"Plis de passage" Deserve a Role in Models of the Cortical Folding Process.

Cortical folding is a hallmark of brain topography whose variability across individuals remains a puzzle. In this paper, we call for an effort to improve our understanding of the pli de passage phenomenon, namely annectant gyri buried in the depth of the main sulci. We suggest that plis de passage could become an interesting benchmark for models of the cortical folding process. As an illustration, we speculate on the link between modern biological models of cortical folding and the development of the Pli de Passage Frontal Moyen (PPFM) in the middle of the central sulcus. For this purpose, we have detected nine interrupted central sulci in the Human Connectome Project dataset, which are used to explore the organization of the hand sensorimotor areas in this rare configuration of the PPFM.

The chaotic morphology of the left superior temporal sulcus is genetically constrained.

The asymmetry of the superior temporal sulcus (STS) has been identified as a species-specific feature of the human brain. The so-called superior temporal asymmetrical pit (STAP) area is observed from the last trimester of gestation onwards and is far less pronounced in the chimpanzee brain. This asymmetry is associated with more frequent sulcal interruptions, named plis de passage (PPs), leading to the irregular morphology of the left sulcus. In this paper, we aimed to characterize the variability, asymmetry, and heritability of these interruptions in the STS in comparison with the other main sulci. We developed an automated method to extract PPs across the cortex based on a highly reproducible grid of sulcal pits across individuals, which we applied to a subset of Human Connectome Project (HCP) subjects (N = 820). We report that only a few PPs across the cortex are genetically constrained, namely in the collateral, postcentral and superior temporal sulci and the calcarine fissure. Moreover, some PPs occur more often in one hemisphere than the other, namely in the precentral, postcentral, intraparietal sulci, as well as in both inferior and superior temporal sulci. Most importantly, we found that only the interruptions within the STAP region are both asymmetric and genetically constrained. Because this morphological pattern is located in an area of the left hemisphere related to speech, our results suggest structural constraints on the architecture of the linguistic network.

Primatologist: A modular segmentation pipeline for macaque brain morphometry.

Because they bridge the genetic gap between rodents and humans, non-human primates (NHPs) play a major role in therapy development and evaluation for neurological disorders. However, translational research success from NHPs to patients requires an accurate phenotyping of the models. In patients, magnetic resonance imaging (MRI) combined with automated segmentation methods has offered the unique opportunity to assess in vivo brain morphological changes. Meanwhile, specific challenges caused by brain size and high field contrasts make existing algorithms hard to use routinely in NHPs. To tackle this issue, we propose a complete pipeline, Primatologist, for multi-region segmentation. Tissue segmentation is based on a modular statistical model that includes random field regularization, bias correction and denoising and is optimized by expectation-maximization. To deal with the broad variety of structures with different relaxing times at 7 T, images are segmented into 17 anatomical classes, including subcortical regions. Pre-processing steps insure a good initialization of the parameters and thus the robustness of the pipeline. It is validated on 10 T2-weighted MRIs of healthy macaque brains. Classification scores are compared with those of a non-linear atlas registration, and the impact of each module on classification scores is thoroughly evaluated.

A study of cortical morphology in children with fetal alcohol spectrum disorders.

Prenatal alcohol exposure is responsible for a broad range of brain structural malformations, which can be studied using magnetic resonance imaging (MRI). Advanced MRI methods have emerged to characterize brain abnormalities, but the teratogenic effects of alcohol on cortical morphology have received little attention to date. Twenty-four 9-year-old children with fetal alcohol spectrum disorders (9 with fetal alcohol syndrome, 15 heavy exposed nonsyndromal children) and 16 age-matched controls were studied to assess the effect of alcohol consumption during pregnancy on cortical morphology. An automated method was applied to 3D T1-weighted images to assess cortical gyrification using global and regional sulcal indices and two region-based morphological measurements, mean sulcal depth and fold opening. Increasing levels of alcohol exposure were related to reduced cortical folding complexity, even among children with normal brain size, indicating a reduction of buried cortical surface. Fold opening was the strongest anatomical correlate of prenatal alcohol intake, indicating a widening of sulci in all regions that were examined. These data identify cortical morphology as a suitable marker for further investigation of brain damage associated with prenatal alcohol exposure.

A bipolar taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients.

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (N=34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bipolar distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex; complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (N=228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.

The effect of handedness on the shape of the central sulcus.

Sinistrals differ from dextrals in the size of certain cortical folds. For instance, handedness has an impact on central sulcus surface area: the sulcus is larger in the dominant left hemisphere of dextrals and vice versa for sinistrals. However, the impact of handedness on the shape of the central sulcus is largely unexplored. In this paper, we propose first an original strategy based on manifold learning to quantify the shape of the central sulcus. Using this approach we show that the "hand knob", a major landmark of the hand motor representation, is sited more dorsally in the left hemisphere in dextrals than in sinistrals. Sinistrals forced to write with their non-preferred right hand display a pattern of central sulcus size asymmetry which is typical of dextrals, yet forced dextrality does not shift the handedness-specific location of the "hand knob". Hence, cortical morphology in adults holds an accumulated record of both innate biases and early developmental experience. Characterizing normal variation of cortical morphology provides a means of systematically correlating behavior with cortical development.

Role of hippocampal CA1 atrophy in memory encoding deficits in amnestic Mild Cognitive Impairment.

Identifying the specific substrates of memory deficits in early Alzheimer's disease would help to develop clinically-relevant therapies. The present study assesses the relationships between encoding versus retrieval deficits in patients with amnestic Mild Cognitive Impairment (aMCI) and atrophy specifically within the hippocampus and throughout the white matter. Twenty-two aMCI patients underwent T1-weighted MRI scans and neuropsychological testing. Grey matter and white matter segments obtained from the MRI images were each entered in correlation analyses, assessed only in the hippocampus for grey matter segments, with encoding and retrieval memory performances. For the grey matter segments, the resulting spmT correlation maps were then superimposed onto a 3D surface view of the hippocampus to identify the relative involvement of the different subfields, a method already used and validated elsewhere. Memory encoding deficits specifically correlated with CA1 subfield atrophy, while no relationship was found with white matter atrophy. In contrast, retrieval deficits were weakly related to hippocampal atrophy and did not involve a particular subfield, while they strongly correlated with loss of white matter, specifically in medial parietal and frontal areas. In aMCI patients, encoding impairment appears specifically related to atrophy of the CA1 hippocampal subfield, consistent with the predominance of encoding deficits and CA1 atrophy in aMCI. In contrast, episodic retrieval deficits seem to be underlain by more distributed tissue losses, consistent with a disruption of a hippocampo-parieto-frontal network.

Browsing Multiple Subjects When the Atlas Adaptation Cannot Be Achieved via a Warping Strategy.

Brain mapping studies often need to identify brain structures or functional circuits into a set of individual brains. To this end, multiple atlases have been published to represent such structures based on different modalities, subject sets, and techniques. The mainstream approach to exploit these atlases consists in spatially deforming each individual data onto a given atlas using dense deformation fields, which supposes the existence of a continuous mapping between atlases and individuals. However, this continuity is not always verified, and this "iconic" approach has limits. We present in this study an alternative, complementary, "structural" approach, which consists in extracting structures from the individual data, and comparing them without deformation. A "structural atlas" is thus a collection of annotated individual data with a common structure nomenclature. It may be used to characterize structure shape variability across individuals or species, or to train machine learning systems. This study exhibits Anatomist, a powerful structural 3D visualization software dedicated to building, exploring, and editing structural atlases involving a large number of subjects. It has been developed primarily to decipher the cortical folding variability; cortical sulci vary enormously in both size and shape, and some may be missing or have various topologies, which makes iconic approaches inefficient to study them. We, therefore, had to build structural atlases for cortical sulci, and use them to train sulci identification algorithms. Anatomist can display multiple subject data in multiple views, supports all kinds of neuroimaging data, including compound structural object graphs, handles arbitrary coordinate transformation chains between data, and has multiple display features. It is designed as a programming library in both C++ and Python languages, and may be extended or used to build dedicated custom applications. Its generic design makes all the display and structural aspects used to explore the variability of the cortical folding pattern work in other applications, for instance, to browse axonal fiber bundles, deep nuclei, functional activations, or other kinds of cortical parcellations. Multimodal, multi-individual, or inter-species display is supported, and adaptations to large scale screen walls have been developed. These very original features make it a unique viewer for structural atlas browsing.

Neural entrainment to speech and nonspeech in dyslexia: Conceptual replication and extension of previous investigations.

Whether phonological deficits in developmental dyslexia are associated with impaired neural sampling of auditory information is still under debate. Previous findings suggested that dyslexic participants showed atypical neural entrainment to slow and/or fast temporal modulations in speech, which might affect prosodic/syllabic and phonemic processing respectively. However, the large methodological variations across these studies do not allow us to draw clear conclusions on the nature of the entrainment deficit in dyslexia. Using magnetoencephalography, we measured neural entrainment to nonspeech and speech in both groups. We first aimed to conceptually replicate previous studies on auditory entrainment in dyslexia, using the same measurement methods as in previous studies, and also using new measurement methods (cross-correlation analyses) to better characterize the synchronization between stimulus and brain response. We failed to observe any of the significant group differences that had previously been reported in delta, theta and gamma frequency bands, whether using speech or nonspeech stimuli. However, when analyzing amplitude cross-correlations between noise stimuli and brain responses, we found that control participants showed larger responses than dyslexic participants in the delta range in the right hemisphere and in the gamma range in the left hemisphere. Overall, our results are weakly consistent with the hypothesis that dyslexic individuals show an atypical entrainment to temporal modulations. Our attempt at replicating previously published results highlights the multiple weaknesses of this research area, particularly low statistical power due to small sample size, and the lack of methodological standards inducing considerable heterogeneity of measurement and analysis methods across studies.

Influence of prefrontal target region on the efficacy of repetitive transcranial magnetic stimulation in patients with medication-resistant depression: a [(18)F]-fluorodeoxyglucose PET and MRI study.

It is currently unknown whether the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) depends on specific characteristics of the stimulated frontal area, such as metabolic changes. We investigated the effect of high-frequency rTMS, administered over the most hypometabolic prefrontal area in depressed patients in a two-site, double-blind, randomized placebo-controlled add-on study. Forty-eight patients with medication-resistant major depression underwent magnetic resonance imaging and [(18)F]-fluorodeoxyglucose positron emission tomography (PET) in order to determine a target area for rTMS. After randomization to PET-guided (n = 16), standard (n = 18), or sham rTMS (n = 14) conditions, the patients received 10 sessions of 10-Hz rTMS (1600 pulses/session) at 90% motor threshold. Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores did not differ between PET-guided, standard and sham groups at 2-wk end-point. Exploratory comparison of left PET-guided (n = 9), right PET-guided, standard, and sham rTMS revealed significant effects. The highest improvement in MADRS scores was observed with left PET-guided (60 + or - 31%), significantly superior to sham (30 + or - 37%, p = 0.01) and right-guided (31 + or - 33%, p = 0.02) stimulation. Comparison between left PET-guided and standard rTMS (49 + or - 28%) was not significant (p = 0.12). Comparison between stimulation over dorsolateral prefrontal cortex (BA 9-46), stimulation of other areas, and sham rTMS was statistically significant. Stimulation over BA 9-46 region (n = 15) was superior to sham rTMS (p = 0.02). The results do not support the general hypothesis of increased antidepressant effects of high-frequency rTMS with prefrontal hypometabolism-related PET guidance. Nonetheless, whether metabolism and anatomy characteristics of left frontal area underneath the coil might account for an increase or speeding up of rTMS effects needs further investigation.

Automatic labeling of cortical sulci using patch- or CNN-based segmentation techniques combined with bottom-up geometric constraints.

The extreme variability of the folding pattern of the human cortex makes the recognition of cortical sulci, both automatic and manual, particularly challenging. Reliable identification of the human cortical sulci in its entirety, is extremely difficult and is practiced by only a few experts. Moreover, these sulci correspond to more than a hundred different structures, which makes manual labeling long and fastidious and therefore limits access to large labeled databases to train machine learning. Here, we seek to improve the current model proposed in the Morphologist toolbox, a widely used sulcus recognition toolbox included in the BrainVISA package. Two novel approaches are proposed: patch-based multi-atlas segmentation (MAS) techniques and convolutional neural network (CNN)-based approaches. Both are currently applied for anatomical segmentations because they embed much better representations of inter-subject variability than approaches based on a single template atlas. However, these methods typically focus on voxel-wise labeling, disregarding certain geometrical and topological properties of interest for sulcus morphometry. Therefore, we propose to refine these approaches with domain specific bottom-up geometric constraints provided by the Morphologist toolbox. These constraints are utilized to provide a single sulcus label to each topologically elementary fold, the building blocks of the pattern recognition problem. To eliminate the shortcomings associated with the Morphologist's pre-segmentation into elementary folds, we complement this regularization scheme using a top-down perspective which triggers an additional cleavage of the elementary folds when required. All the newly proposed models outperform the current Morphologist model, the most efficient being a CNN U-Net-based approach which carries out sulcus recognition within a few seconds.

Neocortical morphometry in Huntington's disease: Indication of the coexistence of abnormal neurodevelopmental and neurodegenerative processes.

Huntington's disease (HD) is an inherited, autosomal dominant disorder that is characteristically thought of as a degenerative disorder. Despite cellular and molecular grounds suggesting HD could also impact normal development, there has been scarce systems-level data obtained from in vivo human studies supporting this hypothesis. Sulcus-specific morphometry analysis may help disentangle the contribution of coexisting neurodegenerative and neurodevelopmental processes, but such an approach has never been used in HD. Here, we investigated cortical sulcal depth, related to degenerative process, as well as cortical sulcal length, related to developmental process, in early-stage HD and age-matched healthy controls. This morphometric analysis revealed significant differences in the HD participants compared with the healthy controls bilaterally in the central and intra-parietal sulcus, but also in the left intermediate frontal sulcus and calcarine fissure. As the primary visual cortex is not connected to the striatum, the latter result adds to the increasing in vivo evidence for primary cortical degeneration in HD. Those sulcal measures that differed between HD and healthy populations were mainly atrophy-related, showing shallower sulci in HD. Conversely, the sulcal morphometry also revealed a crucial difference in the imprint of the Sylvian fissure that could not be related to loss of grey matter volume: an absence of asymmetry in the length of this fissure in HD. Strong asymmetry in that cortical region is typically observed in healthy development. As the formation of the Sylvian fissure appears early in utero, and marked asymmetry is specifically found in this area of the neocortex in newborns, this novel finding likely indicates the foetal timing of a disease-specific, genetic interplay with neurodevelopment.