Increased graymatter may represent a presymptomatic stage of the OSA disease process where its severity is characterized by reactive and adaptive brain mechanisms, such as cerebral edema, reactive gliosis, neuronal branching, and increased -amyloid deposition. Later in the disease progression, graymatteratrophy could represent predominantly neuronal damage due to chronic OSA and lead to cognitive decline. Both adaptive and maladaptive effects on the brain have consistently been described for processes that follow cycles of airway obstructions and reoxygenation (36). Our sample had low levels of symptoms, namely sleepiness, mood and cognitive deficits, which reflect that most subjects were in a presymptomatic stage of OSA that may be characterized by more adaptive brain responses and thus, increased graymatter. Obviously, these hypotheses must be confirmed.
91 disease pathology with an atypical presentation may be responsible 92 for lvPPA ( Josephs et al., 2008 ; Mesulam et al., 2008 ; Rabinovici et al.,
93 2008b ; Rohrer et al., 2012 , 2013 ).
94 PPA syndromes can be quite heterogeneous in terms of disease dura- 95 tion and symptom progression. A better understanding of anatomical 96 disease progression could signiﬁcantly help predict the time course of 97 the disease, the symptoms that may arise in these patients and could 98 also have a major impact on caregiver education and support. Further- 99 more, tracking the disease over time could shed light on the possible 100 mechanisms involved in the spreading of the disease. In this frame- 101 work, the characterization of the pattern of atrophy progression rep- 102 resents a major challenge in the study of PPA patients. To date, only a 103 few studies have investigated the progression of graymatteratrophy 104 over time in a single variant of PPA, such as svPPA ( Brambati et al.,
mainly focused on brain function aspects (ie, glucose metabolism using FDG-PET, and functional connectivity based on blood oxygen level-dependent signal) rather than brain structure.
Here we aim to investigate the neural correlates of the language-related abilities in a specific population of patients with disorders of consciousness who had recovered these abilities (ie, MCS+) in comparison with another population of MCS patients who had not (ie, MCS-). To do so, we examined the regional and global brain metabolism and the metabolic functional connectivity differences in patients in MCS- versus MCS+ by means of FDG-PET, as well as structural differences between these subcategories by means of graymatter volume atrophy quantification (ie, voxel- based morphometry [VBM]). In line with previous studies, we expect that MCS + patients exhibit higher glucose metabolism and less graymatteratrophy compared with MCS- patients, in particular in consciousness and language-related areas.
confounding factors, by a sex and age match between patients and healthy volunteers. Nevertheless, it could be argued that additional factors, such as comorbid conditions (7) or socio- cultural level (35), could potentially contribute to brain atro- phy. This point needs to be addressed in future studies in the field. Furthermore, the current study was designed to pro- vide a snapshot of the impact of CA on brain graymatter volumes, and the timing of neuroimaging acquisitions was decided to obtain the best balance between clinical relevance and study feasibility. Several points must be highlighted that justify the level standardization and consistency in the timing of MRI of the current study: 1) to avoid confounding fac- tors, all patient MRI assessments were conducted at least 2 days (4 ± 2 d) after a complete withdrawal of sedative drugs therapies and under normothermic conditions, 2) to guar- antee patients management according to standard of care recommendations, patients transfer to the imaging centers was exclusively performed after achievement of clinical sta- bility, and 3) to specifically address the impact of cortical and subcortical graymatteratrophy induced by CA, we focused the MRI assessment during the consistent acute period that follows early brain edema development. Future longitudinal neuroimaging studies will need to focus on repeated brain scan acquisitions after CA, aiming to disentangle the dynamic structural signatures of brain injury in this setting and ulti- mately identify the best timing to use such neuroimaging bio- markers for neuroprognostication.
The T1 scans were spatially normalized and segmented into three tissue classes (i.e., graymatter, white matter, and cere- brospinal fluid) with SPM5 (statistical parametric mapping) soft- ware (Wellcome Department of Cognitive Neurology, London, UK, www.fil.ion.ucl.ac.uk/spm) implemented in Matlab version 7.4 (Mathworks, Inc., Natick, MA, USA) using a specific template based on the T1-weighted scans (55 MR scans of typically develop- ing children aged 5–12 years acquired with the same MRI scanner and including children’s images acquired in the present study). A factorial VBM analysis ( Ashburner and Friston, 2000 ) comparing the two groups of children was performed using SPM5 software on normalized, modulated, and 8 mm FWHM Gaussian-smoothed GM volumes. This analysis included a total brain volume cor- rection for each subject, brain volume values being included as a global calculation in the SPM model. The results reported thereafter were obtained for p values corresponding to p < 0.001 uncorrected with clusters with a minimum of 80 voxels. VBM analysis was performed using two-sample t -tests contrasting the two groups including age as covariate.
Orphanet Journal of Rare Diseases 2006, 1:22 http://www.OJRD.com/content/1/1/22
despite total bowel rest. Onset most often occurs within the first days of life. Microvillous atrophy, first described in 1978 , was the first clinical entity identified on a morphological basis as being responsible for the so-called protracted or intractable diarrhea syndrome. The diagno- sis is based on typical morphological abnormalities detected through a combination of light and electron microscopic (EM) analyses of small bowel biopsies [8- 14]. Standard histology reveals a variable degree of villous atrophy without marked crypt hyperplasia, in addition to abnormal periodic-acid schiff (PAS) positive secretory granules accumulating in the apical cytoplasm of mature enterocytes and an altered (atrophic after PAS staining) enterocyte brush border membrane. These findings are completed by EM with the detection of atrophic or com- pletely absent microvilli on mature enterocytes (see below) along with so-called microvillous inclusions (vac- uoles lined by microvilli) and the finding of large PAS positive granules in immature enterocytes.
Psychoeducation, University of Montreal, Montreal, QC, Canada, 5 Department of Psychology and Pediatrics, University of Montreal, Montreal, QC, Canada, 6 School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland
Numerous studies have shown differences in the functioning in the areas of the frontal- limbic circuitry between depressed patients and controls. However, current knowledge on frontal-limbic neural substrates of individual differences in mood states in everyday life in healthy individuals is scarce. The present study investigates anatomical, resting-state, and functional neural correlates of daily mood states in healthy individuals. We expected to observe associations between mood and the frontal-limbic circuitry and the default- mode network (DMN). A total of 42 healthy adults (19 men, 23 women; 34 ± 1.2 years) regularly followed for behavior and psychosocial functioning since age of 6, underwent a functional magnetic resonance imaging scan, and completed a daily diary of mood states and related cognitions for 5 consecutive days. Results showed that individuals with smaller left hippocampal graymatter volumes experienced more negative mood and rumination in their daily life. Greater resting-state functional connectivity (rsFC) within the DMN, namely between posterior cingulate cortex (PCC) and medial prefrontal cortex regions as well as between PCC and precuneus, was associated with both greater negative and positive mood states in daily life. These rsFC results could be indicative of the role of the DMN regional functioning in emotional arousal, irrespective of valence. Lastly, greater daily positive mood was associated with greater activation in response to negative emotional stimuli in the precentral gyri, previously linked to emotional interference on cognitive control. Altogether, present findings might reflect neural mechanisms underlying daily affect and cognition among healthy individuals.
Morphological studies of anatomical structures play an important role in neu- roimaging. For example in the analysis of the circuits connecting sub-cortical areas to the cortical surface one would like to study together graymatter sur- faces and white matter tracts (ber bundles). To the best of our knowledge, there is no generic method to study these objects together.
The aim of our study is to compare typically achieving school- children of the same age with different levels of expertise in numerical cognition. For this comparison, we used the Voxel- Based Morphometry (VBM) method (i.e., an analysis that allows the detection of volumetric brain variations between two groups of subjects and their localizations after separating gray and white matter from brain anatomical MRI images, see Ashburner and Friston, 2000 ). We searched for possible neuroanatomical dif- ferences between the numerical cognition performances of two groups of 10-year-old schoolchildren, only differing in their numerical transcoding proficiency (i.e., the representation of numerical magnitude, the core of number processing, and its link to numerical symbols). We used two standardized subtests (i.e., number line task and visual estimation of quantities task) from the ZAREKI-R, a mathematical cognition battery ( Von Aster and Dellatolas, 2006 ) that allows assessment of the transcoding proficiency of the children. These two subtests address the rep- resentation of numerical magnitude and its link to numerical symbols: the transcoding processing from the symbolic system to the analog system (number line task) and the transcoding pro- cessing from the analog system to the symbolic system (visual estimation of quantities task). According to developmental mat- uration data ( Gogtay et al., 2004 ), one would expect that the higher level group would present a loss of GM in some brain areas due to a more advanced maturation in agreement with a “synap- tic pruning” phenomenon (i.e., a fundamental neural plasticity mechanism that may underlie selective behavioral specialization, see Edelman, 1993 ). Alternatively, from an experience-dependent structural changes perspective, one would expect that better per- formance would depend on an increase in GM. For the first time, our study seeks to contribute to a better understanding of this important open issue regarding the intertwined relation- ships between maturation, experience, and learning in typical developing children.
Ces deux résultats prennent part chacun à un problème plus large.
Pour le premier, on l'a dit, il s'agit de la classication des variétés NK non kähleriennes homogènes en dimension 6. On apporte en même temps la réponse à une vieille conjecture de Gray et Wolf  : toutes les variétés strictement NK (i.e. qui ne peuvent pas être décomposées en un produit d'une variété kählerienne par une variété NK), homogènes sont des espaces 3-symétriques. Ces derniers sont dénis par Gray  comme des espaces homogènes G/H où le groupe G est muni d'un automorphisme d'ordre 3 dont H est l'ensemble des points xes. Cette conguration est moins singulière qu'il paraît. En eet on montre que les espaces localement 3-symétriques sont des variétés presque hermitiennes telles que la torsion et la courbure de la connexion intrinsèque sont parallèles, un cas particulier de variété localement homogène. Pour une G-structure générale, R. Cleyton et A. Swann ,  construisent une situation très générale où cela arrive en considérant des G-variétés telles que la représentation de G sur l'espace tangent est irréductible et la torsion intrinsèque est une 3-forme. La dernière condition est vériée par dénition par les variétés NK. Dès lors, un thème secondaire de cette thèse est le lien entre les géométries spéciales et les espaces homogènes.
The multimodal nature of our study highlights the importance of neuroimaging in both the diagnosis and characterization of PCA. In the present study, both MRI and PET results show a consistent epicenter of brain damage in PCA patients in bilateral parietal, occipital and pos- terior temporal regions. Nonetheless, our PET results revealed a more extended hypometabolism in associative regions in comparison to the GM atrophy pattern showed by our MRI results, although the PET analyses included a lower sample size. This could suggest that PET is a more sensitive neuroimaging tool in comparison to MRI in the detection of brain damage in PCA patients. This is in accordance with the French guidelines, which recommend the use of PET in addition to morpho- logical MRI to detect characteristic metabolism changes in posterior associative cortices in atypical presentations of AD ( Haute Autorité de Santé (HAS), 2011 ). The clinical utility of PET was also highlighted in a previous meta-analysis in which it achieved the highest area under the receiver operating curve (0.96) for the diagnosis of AD, in comparison to CSF biomarkers and MRI GM atrophy, with a sensitivity of 90% and a specificity of 89% ( Bloudek et al., 2011 ). Furthermore, the present multimodal approach was able to detect subtle anatomo-functional diﬀerences among patients presenting with the same cognitive profile, namely the temporal involvement in PCA-tAD and the frontal in- volvement in PCA-nonAD.
In this paper, we provide a systematic framework utilizing a com- mon data-set allowing a variety of techniques designed to measure change in brain, ventricles and hippocampi to be evaluated and com- pared. Despite the differences in techniques, challenge participants from around the world produced consistent and repeatable measures of change, particularly for the ventricle and the brain. Hippocampal measures are more variable, likely due to the differing de ﬁnitions of the structure. We demonstrate that, in general, direct measures of change are associated with smaller variances than indirect measures; and that the statistical model previously designed to analyse multiple time-point whole brain atrophy is also able to model rates of hippocam- pal atrophy and ventricular expansion accurately, and thus to provide estimates of within and between subject variability in rates of change. Our results suggest that sample size estimates based on ventricular ex- pansion rates are more consistent than those from whole brain atrophy, and both are markedly more stable than those derived from hippocam- pal atrophy measures. By providing comparisons between techniques based on sample size, our aim is not to determine which techniques should or should not be used for any given trial – noting that factors other than sample size alone need to be taken into account when choos- ing an imaging technique – but to provide the clinical trials community with robust sample size estimates for trials based on contemporary techniques; and in the absence of a ground truth, to provide the imaging community with a means of comparison. To this end the MIRIAD dataset – in both a blinded (challenge) and unblinded (ordered) form – will remain publicly available at http://www.ucl.ac.uk/drc/ research/miriad-scan-database for the community to continue to evaluate their methods. The statistical analysis as it was performed in the challenge will also be available so that new submissions can be evaluated using the same methods.
resulted in a positive and predictable outcome. 3 This underlines the need for further understanding of SCI, particularly contusion injuries following burst fracture, which show a high prevalence. 5 Both this prevalence and the severity of the injury highly vary, depending on the vertebral level of the injury and the type of vertebral fracture involved. 1,2,5 While this latter may be relatively well known today, the contribution of the geometrical variations in the human spinal cord and canal along the spine in SCI mechanisms is yet to be studied exten- sively. The geometrical parameters of particular interest are the spinal canal cross-sectional area, the amount of cerebrospinal fluid (CSF), and the white matter (WM)/ graymatter (GM) proportion, since they are recognized to vary significantly along the spine. 6–9
12. Koedam ELGE, Lehmann M, van der Flier WM, Scheltens P, Pijnenburg YAL, Fox N, et al. Visual assessment of posterior atrophy development of a MRI rating scale. Eur Radi- ol. déc 2011;21(12):2618‑25.
13. From the Imaging Cognitive Impairment Network (ICINET), Wahlund L-O, Westman E, van Westen D, Wallin A, Shams S, et al. Imaging biomarkers of dementia: recommended visual rating scales with teaching cases. Insights Imaging. févr 2017;8(1):79‑90.
Functional connectivity Graph analysis
A B S T R A C T
This study investigated the functional brain connectome architecture in patients with Posterior Cortical Atrophy (PCA). Eighteen PCA patients and 29 age- and sex- matched healthy controls were consecutively recruited in a specialized referral center. Participants underwent neurologic examination, cerebrospinal ﬂuid (CSF) ex- amination for Alzheimer's disease (AD) biomarkers, cognitive assessment, and brain MRI. For a smaller subset of participants, FDG-PET examination was available. We assessed topological brain network properties and re- gional functional connectivity as well as intra- and inter-hemispheric connectivity, using graph analysis and connectomics. Supplementary analyses were performed to explore the association between the CSF AD proﬁle and the connectome status, and taking into account hypometabolic, atrophic, and spared regions (nodes). PCA patients showed di ﬀuse functional connectome alterations at both global and regional level, as well as a con- nectivity breakdown between the posterior brain nodes. They had a widespread loss of both intra- and inter- hemispheric connections, exceeding the structural damage, and including the frontal connections. In PCA, connectome alterations were identi ﬁed in all the brain nodes irrespectively of their structural and metabolic classi ﬁcation and were associated with a connectivity breakdown between damaged and spared areas. Taken together, these ﬁndings suggest the potentially high sensitivity of graph-analysis and connectomic in capturing the progression and maybe early signs of neurodegeneration in PCA patients.
F IG . 3. Deletion of myostatin gene prevents the muscle atrophy
caused by dexamethasone treatment. WT and KO mice were injected
for 4 d with dexamethasone (5 mg/kg 䡠d, black box) or saline (white
box). Tibialis anterior (A), gastrocnemius (B), and soleus (C) masses
Treatment with synthetic GCs is associated with skeletal muscle atrophy and/or a so-called steroid myopathy. This deleterious condition affects many patients suffering from respiratory diseases, autoimmune diseases, or cancers. Re- cently, several teams have shown that the mTORC1 inhibitor REDD1 was strongly induced by DEX administration in skel- etal muscle tissue (24, 39, 48). Thus, one objective of this study was to determine the role of REDD1 on DEX-induced skeletal muscle atrophy. We used relatively low doses of DEX and short treatment durations compared with those usually given in rodent studies [e.g., Baehr et al. (2), 3 mg/kg for 14 days; Gilson et al. (18), 5 mg/kg for 4 days; Proserpio et al. (33), 2
Results: Imagery explorations showed the atrophy of the right rectus femoris combined with fatty degeneration but this exam did not allow determining the actual etiology. Therefore, a precise diagnosis was not allowed, even if the EMG confirmed the presence of important signs of specific and isolated denervation only in the right rectus femoris. The isokinetic test, performed in the classical sitting position, highlighted symmetrical performances for flexors of the knee and a moderately decrease in the right concentric quadriceps torque (-10%). A complementary isokinetic assessment, in a lying supine position, demonstrated a more marked deficit of this right quadriceps (higher than -30%).