White matter differences between healthy young ApoE4 carriers and non-carriers identified with tractography and support vector machines.

The apolipoprotein E4 (ApoE4) is an established risk factor for Alzheimer's disease (AD). Previous work has shown that this allele is associated with functional (fMRI) changes as well structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess the diffusion characteristics and the white matter (WM) tracts of healthy young (20-38 years) ApoE4 carriers and non-carriers. No significant differences in diffusion indices were found between young carriers (ApoE4+) and non-carriers (ApoE4-). There were also no significant differences between the groups in terms of normalised GM or WM volume. A feature selection algorithm (ReliefF) was used to select the most salient voxels from the diffusion data for subsequent classification with support vector machines (SVMs). SVMs were capable of classifying ApoE4 carrier and non-carrier groups with an extremely high level of accuracy. The top 500 voxels selected by ReliefF were then used as seeds for tractography which identified a WM network that included regions of the parietal lobe, the cingulum bundle and the dorsolateral frontal lobe. There was a non-significant decrease in volume of this WM network in the ApoE4 carrier group. Our results indicate that there are subtle WM differences between healthy young ApoE4 carriers and non-carriers and that the WM network identified may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age

Reduced hippocampal volume in healthy young ApoE4 carriers: an MRI study.

The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20-38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4-), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Using Support Vector Machines with Multiple Indices of Diffusion for Automated Classification of Mild Cognitive Impairment

Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical

Sexual Dimorphism in Healthy Aging and Mild Cognitive Impairment: A DTI Study

Previous PET and MRI studies have indicated that the degree to which pathology translates into clinical symptoms is strongly dependent on sex with women more likely to express pathology as a diagnosis of AD, whereas men are more resistant to clinical symptoms in the face of the same degree of pathology. Here we use DTI to investigate the difference between male and female white matter tracts in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). Differences between control and MCI participants were found in fractional anisotropy (FA), radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD). A significant main effect of sex was also reported for FA, MD and DR indices, with male control and male MCI participants having significantly more microstructural damage than their female counterparts. There was no sex by diagnosis interaction. Male MCIs also had significantly less normalised grey matter (GM) volume than female MCIs. However, in terms of absolute brain volume, male controls had significantly more brain volume than female controls. Normalised GM and WM volumes were found to decrease significantly with age with no age by sex interaction. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women

Tactile Hypersensitivity and GABA Concentration in the Sensorimotor Cortex of Adults with Autism

International audienceSensory hypersensitivity is frequently encountered in autism spectrum disorder (ASD). Gamma-aminobutyric acid (GABA) has been hypothesized to play a role in tactile hypersensitivity. The aim of the present study was twofold. First, as a study showed that children with ASD have decreased GABA concentrations in the sensorimotor cortex, we aimed at determining whether the GABA reduction remained in adults with ASD. For this purpose, we used magnetic resonance spectroscopy to measure GABA concentration in the sensorimotor cortex of neurotypical adults (n = 19) and ASD adults (n = 18). Second, we aimed at characterizing correlations between GABA concentration and tactile hypersensitivity in ASD. GABA concentration in the sensorimotor cortex of adults with ASD was lower than in neurotypical adults (decrease by 17%). Interestingly, GABA concentrations were positively correlated with self-reported tactile hypersensitivity in adults with ASD (r = 0.50, P = 0.01), but not in neurotypical adults. In addition, GABA concentrations were negatively correlated with the intra-individual variation during threshold measurement, both in neurotypical adults (r = −0.47, P = 0.04) and in adults with ASD (r = −0.59, P = 0.01). In other words, in both groups, the higher the GABA level, the more precise the tactile sensation. These results highlight the key role of GABA in tactile sensitivity, and suggest that atypical GABA modulation contributes to tactile hypersensitivity in ASD. We discuss the hypothesis that hypersensitivity in ASD could be due to suboptimal predictions about sensations. Autism Research 2019. Lay Summary: People with autism spectrum disorder (ASD) often experience tactile hypersensitivity. Here, our goal was to highlight a link between tactile hypersensitivity and the concentration of gamma-aminobutyric acid (GABA) (an inhibitory neurotransmitter) in the brain of adults with ASD. Indeed, self-reported hypersensitivity correlated with reduced GABA levels in brain areas processing touch. Our study suggests that this neurotransmitter may play a key role in tactile hypersensitivity in autism

Cognitive control of orofacial motor and vocal responses in the ventrolateral and dorsomedial human frontal cortex

International audienceIn the primate brain, a set of areas in the ventrolateral frontal (VLF) cortex and the dorsomedial frontal (DMF) cortex appear to control vocalizations. The basic role of this network in the human brain and how it may have evolved to enable complex speech remain unknown. In the present functional neuroimaging study of the human brain, a multidomain protocol was utilized to investigate the roles of the various areas that comprise the VLF-DMF network in learning rule-based cognitive selections between different types of motor actions: manual, orofacial, nonspeech vocal, and speech vocal actions. Ventrolateral area 44 (a key component of the Broca's language production region in the human brain) is involved in the cognitive selection of orofacial, as well as, speech and nonspeech vocal responses; and the midcingulate cortex is involved in the analysis of speech and nonspeech vocal feedback driving adaptation of these responses. By contrast, the cognitive selection of speech vocal information requires this former network and the additional recruitment of area 45 and the presupplementary motor area. We propose that the basic function expressed by the VLF-DMF network is to exert cognitive control of orofacial and vocal acts and, in the language dominant hemisphere of the human brain, has been adapted to serve higher speech function. These results pave the way to understand the potential changes that could have occurred in this network across primate evolution to enable speech production

Evaluation of markerless prospective motion correction for neuroanatomical MRI

International audienceHead-motion is a main cause of artifacts in MRI. The performance of a markerless optical system, which records the subject's face, estimates head-motion, and allows real-time repositioning of the FOV, is evaluated for neuroanatomical MRI. Sets of T1W/T2W-images were collected from 2 subjects instructed to perform different head-motion protocols during the acquisitions. The System performance is evaluated by comparing images with/without motion-correction. The optical system ensures good corrections of head-motions. However, the correction quality depends on the amplitude of the movement, its location in k-space and its nature. Residual effects of large amplitudes/amounts movements may persist on corrected images. Summary of main findings:-Good performance of prospective motion correction for anatomical brain MRI-Correction quality depends on the magnitude of the motion, its location in k-space and its nature-Optical system is more effective at correcting discontinuous than continuous large motions, especially for T2W-MR

Evaluation of markerless prospective motion correction for neuroanatomical MRI

International audienceHead-motion is a main cause of artifacts in MRI. The performance of a markerless optical system, which records the subject's face, estimates head-motion, and allows real-time repositioning of the FOV, is evaluated for neuroanatomical MRI. Sets of T1W/T2W-images were collected from 2 subjects instructed to perform different head-motion protocols during the acquisitions. The System performance is evaluated by comparing images with/without motion-correction. The optical system ensures good corrections of head-motions. However, the correction quality depends on the amplitude of the movement, its location in k-space and its nature. Residual effects of large amplitudes/amounts movements may persist on corrected images. Summary of main findings:-Good performance of prospective motion correction for anatomical brain MRI-Correction quality depends on the magnitude of the motion, its location in k-space and its nature-Optical system is more effective at correcting discontinuous than continuous large motions, especially for T2W-MR

Evaluation of markerless prospective motion correction for neuroanatomical MRI

International audienceHead-motion is a main cause of artifacts in MRI. The performance of a markerless optical system, which records the subject's face, estimates head-motion, and allows real-time repositioning of the FOV, is evaluated for neuroanatomical MRI. Sets of T1W/T2W-images were collected from 2 subjects instructed to perform different head-motion protocols during the acquisitions. The System performance is evaluated by comparing images with/without motion-correction. The optical system ensures good corrections of head-motions. However, the correction quality depends on the amplitude of the movement, its location in k-space and its nature. Residual effects of large amplitudes/amounts movements may persist on corrected images. Summary of main findings:-Good performance of prospective motion correction for anatomical brain MRI-Correction quality depends on the magnitude of the motion, its location in k-space and its nature-Optical system is more effective at correcting discontinuous than continuous large motions, especially for T2W-MR