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Altres ajuts: La Marató de TV3 (20142910) Altres ajuts: Acord transformatiu CRUE-CSIC Background: Huntington's disease is a neurodegenerative disorder characterized by clinical alterations in the motor, behavioral, and cognitive domains. However, the structure and disruptions to large-scale brain cognitive networks have not yet been established. Objective: We aimed to profile changes in large-scale cognitive networks in premanifest and symptomatic patients with Huntington's disease. Methods: We prospectively recruited premanifest and symptomatic Huntington's disease mutation carriers as well as healthy controls. Clinical and sociodemographic data were obtained from all participants, and resting-state functional connectivity data, using both time-averaged and dynamic functional connectivity, was acquired from whole-brain and cognitively oriented brain parcellations. Results: A total of 64 gene mutation carriers and 23 healthy controls were included; 21 patients with Huntington's disease were classified as premanifest and 43 as symptomatic Huntington's disease. Compared with healthy controls, patients with Huntington's disease showed decreased network connectivity within the posterior hubs of the default-mode network and the medial prefrontal cortex, changes that correlated with cognitive (t = 2.25, P = 0.01) and disease burden scores (t = −2.42, P = 0.009). The salience network showed decreased functional connectivity between insular and supramarginal cortices and also correlated with cognitive (t = 2.11, P = 0.02) and disease burden scores (t = −2.35, P = 0.01). Dynamic analyses showed that network variability was decreased for default-central executive networks, a feature already present in premanifest mutation carriers (dynamic factor 8, P = 0.02). Conclusions: Huntington's disease shows an early and widespread disruption of large-scale cognitive networks. Importantly, these changes are related to cognitive and disease burden scores, and novel dynamic functional analyses uncovered subtler network changes even in the premanifest stages.

Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD-MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level-1 Movement Disorders Society-Task Force Criteria. Voxel-based morphometry, functional connectivity and graph theoretical measures were obtained on a 3-Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD-MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.

We observed atypical astrocytic pTDP-43 pathology in astroglial predominant tauopathy.

BackgroundMinor hallucinations and well-structured hallucinations are considered in the severity continuum of the psychotic spectrum associated with Parkinson's disease. Although their chronological relationship is largely unknown, the spatial patterns of brain atrophy in these 2 forms of hallucinations partially overlap, suggesting they share similar pathophysiological processes. Functional connectivity studies show that disruption of functional networks involved in perception and attention could be relevant in the emergence of well-structured hallucinations. However, functional neuroimaging studies in patients with isolated minor hallucinations are lacking. The objectives of this study were to explore the structural and functional changes underlying minor hallucinations. MethodsWe compared patients with (n=18) and without (n=14) minor hallucinations using a multimodal structural (gray-matter volume voxel-based morphometry) and functional (seed-to-whole-brain resting-state functional MRI) neuroimaging study. ResultsCoincident with previously described structural changes in well-structured hallucinations in Parkinson's disease, patients with minor hallucinations exhibited gray-matter atrophy with significant voxel-wise differences in visuoperceptual processing areas and core regions of the default mode network. Functional connectivity changes consisted of altered connectivity within the default mode network, reduced negative correlation with task-positive network, and aberrant connectivity between posterior regions of the default mode network and visual-processing areas. These changes are in accordance with the attentional networks hypothesis proposed for well-structured hallucinations. ConclusionsAlthough longitudinal studies are needed to assess the potential role of minor hallucinations as an early clinical biomarker of progression to well-structured hallucinations, the present findings show that the 2 phenomena share similar structural and functional brain correlates. (c) 2018 International Parkinson and Movement Disorder Society

Background Apathy is the most prevalent and characteristic neuropsychiatric feature of Huntington's disease. Congruent with the main early pathological changes, apathy is primarily associated with subcortical damage in frontal-striatal circuits. However, little is known about its precise subserving mechanisms and the contribution of regions other than the basal ganglia. Objectives We aimed to define the neural correlates of apathy in Huntington's disease based on gray matter volume and PET/CT of 18 F-fluorodeoxyglucose metabolism. Methods We rated the severity of apathy in 40 mild Huntington's disease participants using the Problem Behaviors Assessment for Huntington's disease. Voxelwise regression analysis was performed, controlling for effects of potential confounders, and PET/CT results were corrected for the effects of gray matter atrophy. Results Apathy was strongly associated with decreased gray matter within a spatially distributed cortico-subcortical network, with major compromise of the bilateral amygdala and temporal cortex. PET metabolism was significantly decreased in frontotemporal and parietal regions. Metabolic uptake and gray matter values in the identified clusters showed significant correlations with multiple clinical measures. Conclusions Our findings indicate that apathy in Huntington's disease is not exclusively a consequence of basal ganglia and related frontal-executive alterations. It is subserved by a complex cortico-subcortical network where critical reward and emotional-related prefrontal, temporal, and limbic nodes contribute strongly to its severity. This highlights the contribution of damage in regions other than the basal ganglia to the clinical expression of Huntington's disease. © 2018 International Parkinson and Movement Disorder Society.

Background and purpose Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. Methods In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. Results No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. Conclusions In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

Behavioral symptoms and traits have been proposed as early markers in neurodegenerative diseases. The aim of this study was to evaluate social anxiety and autism in FMR1 premutation carriers using the Social Phobia Inventory (SPIN) and the Autism-Spectrum Quotient (AQ) questionnaires. Fifty-nine premutation carriers were compared with 50 controls. The SPIN test showed statistically significant differences between female but not male carriers. The AQ questionnaire found statistically significant differences between premutation carriers and controls in the total AQ as well as in the social skills and attention switching subdomains. A gender effect was only observed for the social skills subdomain. Spearman's correlation analysis revealed a moderately positive correlation with the total AQ scores as well as the social skills and communication subdomains. Our results show that fragile X-associated tremor/ataxia syndrome (FXTAS) patients have higher AQ scores. Moreover, this is the first study to find statistically significant differences between FXTAS and no-FXTAS premutation carriers in the communication and the imagination subdomains, suggesting that FXTAS patients present a broader autistic phenotype than premutation carriers without FXTAS. Based on our results, a wide range of behavioral/psychiatric traits should be included within the broader phenotypic presentation of individuals with the FMR1 premutation.

SummaryContext and objective Cushing's syndrome (CS) is caused by a glucocorticoid excess. This hypercortisolism can damage the prefrontal cortex, known to be important in decision-making. Our aim was to evaluate decision-making in CS and to explore cortical thickness. Subjects and methods Thirty-five patients with CS (27 cured, eight medically treated) and thirty-five matched controls were evaluated using Iowa gambling task (IGT) and 3 Tesla magnetic resonance imaging (MRI) to assess cortical thickness. The IGT evaluates decision-making, including strategy and learning during the test. Cortical thickness was determined on MRI using freesurfer software tools, including a whole-brain analysis. Results There were no differences between medically treated and cured CS patients. They presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (P

Keywords: Gerstmann-Straussler-Scheinker; progressive supanuclear palsy; corticobasal syndrome; frontotemporal dementia; MRI

SummaryBackground Proton magnetic resonance spectroscopy (1H-MRS) is a sensitive, noninvasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushing's syndrome (CS) is associated with negative effects on memory and hippocampal volumes, even after biochemical cure. Objective To investigate metabolites in the hippocampi of CS patients and controls, using 1H-MRS. Patients and methods Eighteen right-handed cured CS patients (age 44·8 ± 12·5 years, 12·6 ± 3·8 years of education) and 18 right-handed healthy controls, matched for age (40·0 ± 11·9) and years of education (14·4 ± 3·8), underwent 3-Tesla magnetic resonance imaging (3T MRI) and 1H-MRS including the head of each hippocampus. Concentrations of Glu (Glutamate), Glx (Glutamate + Glutamine), NAA (N-Acetyl-aspartate), total NAA (N-Acetyl-aspartate + N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Hippocampal volumes (mm3) were additionally calculated using an automated procedure (FreeSurfer). Results CS patients had lower NAA than controls in the left and right hippocampus (5·2 ± 1·0 vs 6·1 ± 0·7, P