We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions and obtaining pairwise connectivity. First, we studied age-associations in interregional connectivity and their relationship with the length of the connections. Aging was associated with less connectivity in the long-range connections of fronto-parietal and fronto-occipital systems and with higher connectivity of the short-range connections within frontal, parietal, and occipital lobes. We also used the graph theory to measure functional integration and segregation. The pattern of the overall age-related correlations presented positive correlations of average minimum path length (r = 0.380, p = 0.008) and of global clustering coefficients (r = 0.454, p < 0.001), leading to less integrated and more segregated global networks. Main correlations in clustering coefficients were located in the frontal and parietal lobes. Higher clustering coefficients of some areas were related to lower performance in verbal and visual memory functions. In conclusion, we found that older participants showed lower connectivity of long-range connections together with higher functional segregation of these same connections, which appeared to indicate a more local clustering of information processing. Higher local clustering in older participants was negatively related to memory performance.
Graph-theoretical analyses of functional networks obtained with resting-state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty-six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting-state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long-range connections as well as increased local interconnectedness manifested as higher measures of clustering, small-worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker.
Ageing entails cognitive and motor decline as well as brain changes such as loss of gray (GM) and white matter (WM) integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode Network (DMN) relates to cognitive function and has been postulated to be a hallmark of ageing. However, the relationship between age-related connectivity changes and other neuroimaging-based measures in ageing is fragmentarily investigated. In a sample of 116 healthy elders we aimed to study the relationship between antero-posterior DMN connectivity and measures of WM integrity, GM integrity and cerebral blood flow (CBF), assessed with an arterial spin labeling sequence. First, we replicated previous findings demonstrating DMN connectivity decreases in ageing and an association between antero-posterior DMN connectivity and memory scores. The results showed that the functional connectivity between posterior midline structures and the medial prefrontal cortex was related to measures of WM and GM integrity but not to CBF. Gray and WM correlates of anterio-posterior DMN connectivity included, but were not limited to, DMN areas and cingulum bundle. These results resembled patterns of age-related vulnerability which was studied by comparing the correlates of antero-posterior DMN with age-effect maps. These age-effect maps were obtained after performing an independent analysis with a second sample including both young and old subjects. We argue that antero-posterior connectivity might be a sensitive measure of brain ageing over the brain. By using a comprehensive approach, the results provide valuable knowledge that may shed further light on DMN connectivity dysfunctions in ageing.
Abstract Signal-intensity contrast of T1-weighted magnetic resonance imaging scans has been associated with tissue integrity and reported as a sign of neurodegenerative changes in diseases such as Alzheimers disease. After severe traumatic brain injury (TBI), progressive structural changes occur in white (WM) and gray matter (GM). In the current study, we assessed the signal-intensity contrast of GM and WM in patients with diffuse TBI in the chronic stage to (1) characterize the regional pattern of WM/GM changes in intensity contrast associated with traumatic axonal injury, (2) evaluate possible associations between this measure and diffusion tensor image (DTI)/fractional anisotropy (FA) for detecting WM damage, and (3) investigate the correlates of both measures with cognitive outcomes. Structural T1 scans were processed with FreeSurfer software to identify the boundary and calculate the WM/GM contrast maps. DTIs were processed with the FMRIB software library to obtain FA maps. The WM/GM contrast in TBI patients showed a pattern of reduction in almost all of the brain, except the visual and motor primary regions. Global FA values obtained from DTI correlated with the intensity contrast of all associative cerebral regions. WM/GM contrast correlated with memory functions, whereas FA global values correlated with tests measuring memory and mental processing speed. In conclusion, tissue-contrast intensity is a very sensitive measure for detecting structural brain damage in chronic, severe and diffuse TBI, but is less sensitive than FA for reflecting neuropsychological sequelae, such as impaired mental processing speed.
The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of the brain substrates of cognitive outcome after traumatic axonal injury. This knowledge may contribute to improve clinical management and rehabilitation programs.
The aim of this study was to determine the effects of an omega-3 (n-3) polyunsaturated fatty acid (PUFA)-enriched diet on animal fat depots and lipid oxidation in the blood and meat of broiler chickens. Abdominal fat pad (AFP), sartorius muscle and liver histology were used to assess the effect of the dietary fat on animal lipid depots. A total of 60 female broilers (14 days old) was randomly divided into two groups which received a diet containing 10 % of tallow (S diet), rich in saturated fatty acids or 10 % of a blend of fish oil and linseed oil (N3 diet), rich in n-3 PUFA from 14 to 50 days of life. Both absolute and relative weights of AFP in N3 animals were lower than in the S group (P < 0.05). These results paralleled with a lower adipocyte mean area (P < 0.001) obtained in N3-fed animals, leading to a higher number of fat cells per unit of surface measured (383.4 adipocytes/mm(2) vs. 273.7 adipocytes/mm(2)). Similarly, fat content and the intramuscular fat-occupied area of muscle were lower in N3 (P < 0.0001) than in the S-fed birds. Neither macroscopic nor microscopic differences were observed in the liver. The inclusion of dietary n-3 PUFA increased meat and erythrocyte oxidation susceptibility; however, the erythrocytes from the S group were less resistant to osmotic changes. Results indicate that feeding an n-3 PUFA diet influences fat distribution and the oxidative status of broiler chickens.
Large-scale longitudinal multi-site MRI brain morphometry studies are becoming increasingly crucial to characterize both normal and clinical population groups using fully automated segmentation tools. The test-retest reproducibility of morphometry data acquired across multiple scanning sessions, and for different MR vendors, is an important reliability indicator since it defines the sensitivity of a protocol to detect longitudinal effects in a consortium. There is very limited knowledge about how across-session reliability of morphometry estimates might be affected by different 3T MRI systems. Moreover, there is a need for optimal acquisition and analysis protocols in order to reduce sample sizes. A recent study has shown that the longitudinal FreeSurfer segmentation offers improved within session test-retest reproducibility relative to the cross-sectional segmentation at one 3T site using a nonstandard multi-echo MPRAGE sequence. In this study we implement a multi-site 3T MRI morphometry protocol based on vendor provided T1 structural sequences from different vendors (3D MPRAGE on Siemens and Philips, 3D IR-SPGR on GE) implemented in 8 sites located in 4 European countries. The protocols used mild acceleration factors (1.5-2) when possible. We acquired across-session test-retest structural data of a group of healthy elderly subjects (5 subjects per site) and compared the across-session reproducibility of two full-brain automated segmentation methods based on either longitudinal or cross-sectional FreeSurfer processing. The segmentations include cortical thickness, intracranial, ventricle and subcortical volumes. Reproducibility is evaluated as absolute changes relative to the mean (%), Dice coefficient for volume overlap and intraclass correlation coefficients across two sessions. We found that this acquisition and analysis protocol gives comparable reproducibility results to previous studies that used longer acquisitions without acceleration. We also show that the longitudinal processing is systematically more reliable across sites regardless of MRI system differences. The reproducibility errors of the longitudinal segmentations are on average approximately half of those obtained with the cross sectional analysis for all volume segmentations and for entorhinal cortical thickness. No significant differences in reliability are found between the segmentation methods for the other cortical thickness estimates. The average of two MPRAGE volumes acquired within each test-retest session did not systematically improve the across-session reproducibility of morphometry estimates. Our results extend those from previous studies that showed improved reliability of the longitudinal analysis at single sites and/or with non-standard acquisition methods. The multi-site acquisition and analysis protocol presented here is promising for clinical applications since it allows for smaller sample sizes per MRI site or shorter trials in studies evaluating the role of potential biomarkers to predict disease progression or treatment effects.
Quantification and description of patients recently infected by HIV can provide an accurate estimate of the dynamics of HIV transmission. Between 2006 and 2008 in Catalonia, we estimated the prevalence of recent HIV infection among newly diagnosed cases, described the epidemiological characteristics of the infection according to whether it was recent, long-standing or advanced, and identified factors associated with recent infection.
Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls.
Brain regions simultaneously activated during any cognitive process are functionally connected, forming large-scale networks. These functional networks can be examined during active conditions [i.e., task-functional magnetic resonance imaging (fMRI)] and also in passive states (resting-fMRI), where the default mode network (DMN) is the most widely investigated system. The role of the DMN remains unclear, although it is known to be responsible for the shift between resting and focused attention processing. There is also some evidence for its malleability in relation to previous experience. Here we investigated brain connectivity patterns in 16 healthy young subjects by using an n-back task with increasing levels of memory load within the fMRI context. Prior to this working memory (WM) task, participants were trained outside fMRI with a shortened test version. Immediately after, they underwent a resting-state fMRI acquisition followed by the full fMRI n-back test. We observed that the degree of intrinsic correlation within DMN and WM networks was maximal during the most demanding n-back condition (3-back). Furthermore, individuals showing a stronger negative correlation between the two networks under both conditions exhibited better behavioural performance. Interestingly, and despite the fact that we considered eight different resting-state fMRI networks previously identified in humans, only the connectivity within the posteromedial parts of the DMN (precuneus) prior to the fMRI n-back task predicted WM execution. Our results using a data-driven probabilistic approach for fMRI analysis provide the first evidence of a direct relationship between behavioural performance and the degree of negative correlation between the DMN and WM networks. They further suggest that in the context of expectancy for an imminent cognitive challenge, higher resting-state activity in the posteromedial parietal cortex may be related to increased attentional preparatory resources.
Establishing the relationship between cerebrospinal fluid (CSF) ß-amyloid 1-42 (Aß) and cortical thickness (CTh) would represent a major step forward in the understanding of the Alzheimers disease (AD) process. We studied this relationship in a group of healthy control subjects and subjects with subjective memory complaints with preserved cognitive function at neuropsychological testing.
White matter (WM) damage has been reported in Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. Voxel-based tract based spatial-statistics (TBSS) was used to obtain whole-brain maps of main WM bundles for fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA) and mean diffusivity (MD). FA reductions were evidenced among AD patients with posterior predominance. A-MCI patients displayed reduced mean FA in these critical regions, compared to healthy elders. MD increases were widespread in both groups of patients. Interestingly, a-MCI patients exhibited DR increases in overlapping areas of FA shrinkages in AD, whereas DA increases were only observed in AD. Gray matter atrophy explained most DTI differences, except those regarding MD in both groups as well as DR increases in posterior associative pathways among a-MCI cases. FA values were the only DTI measure significantly related to memory performance among patients. Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy. Notably however, specific DR signal increases in posterior parts of the inferior fronto-occipital and longitudinal fasciculi may reflect early WM compromise in preclinical dementia, which is independent of atrophy. Finally, global measures of integrity, particularly orientation coherence (FA) of diffusion, appear to be more closely related to the cognitive profile of our patients than indexes reflecting water movement parallel (DA) and perpendicular (DR) to the primary diffusion direction.
Studies in asymptomatic granulin gene (GRN) mutation carriers are essential to improve our understanding of the pattern and timing of early morphologic brain changes in frontotemporal lobar degeneration. The main objectives of this study were to assess the effect of age in cortical thickness changes (CTh) in preclinical GRN mutation carriers and to study the relationship of CTh with cognitive performance in GRN mutation carriers. We calculated CTh maps in 13 asymptomatic carriers of the c.709-1G>A GRN mutation and 13 age- and sex-matched healthy subjects. Asymptomatic GRN mutation carriers presented different patterns of age-related cortical thinning in the right superior temporal and middle temporal gyri and the banks of the superior temporal sulcus bilaterally when compared with controls. Cortical thickness was correlated with neuropsychological test scores: Trail Making Tests A and B, and the Boston Naming Test. Distinctive age-related cortical thinning in asymptomatic GRN mutation carriers in lateral temporal cortices suggests an early and disease-specific effect in these areas.
In a previous functional MRI (fMRI) study, we found that patients with Parkinsons disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time.
In recent years, several theories have been proposed in attempts to identify the neural mechanisms underlying successful cognitive aging. Old subjects show increased neural activity during the performance of tasks, mainly in prefrontal areas, which is interpreted as a compensatory mechanism linked to functional brain efficiency. Moreover, resting-state studies have concluded that elders show disconnection or disruption of large-scale functional networks. We used functional MRI during resting-state and a verbal n-back task with different levels of memory load in a cohort of young and old healthy adults to identify patterns of networks associated with working memory and brain default mode. We found that the disruption of resting-state networks in the elderly coexists with task-related overactivations of certain brain areas and with reorganizations within these functional networks. Moreover, elders who were able to activate additional areas and to recruit a more bilateral frontal pattern within the task-related network achieved successful performance on the task. We concluded that the balanced and plastic reorganization of brain networks underlies successful cognitive aging. This observation allows the integration of several theories that have been proposed to date regarding the aging brain.
Obesity is a major health problem in modern societies. It has been related to abnormal functional organization of brain networks believed to process homeostatic (internal) and/or salience (external) information. This study used resting-state functional magnetic resonance imaging analysis to delineate possible functional changes in brain networks related to obesity. A group of 18 healthy adult participants with obesity were compared with a group of 16 lean participants while performing a resting-state task, with the data being evaluated by independent component analysis. Participants also completed a neuropsychological assessment. Results showed that the functional connectivity strength of the putamen nucleus in the salience network was increased in the obese group. We speculate that this abnormal activation may contribute to overeating through an imbalance between autonomic processing and reward processing of food stimuli. A correlation was also observed in obesity between activation of the putamen nucleus in the salience network and mental slowness, which is consistent with the notion that basal ganglia circuits modulate rapid processing of information.
We investigated structural brain damage in subjects who had suffered severe and diffuse traumatic brain injury (TBI), and examined its relationship with declarative memory impairment. Cortical thickness, diffusion tensor imaging (DTI), and volumetric and shape data of the hippocampus were assessed in a group of 26 adults with severe TBI in the chronic stage and 22 healthy matched controls. Declarative memory was evaluated by Reys Auditory Verbal Learning Test (RAVLT). TBI patients performed significantly worse than controls on all RAVLT measures. The group comparison for cortical thickness and DTI revealed a pattern of widespread atrophy in TBI patients. In the TBI group DTI measures correlated with cortical thickness in the prefrontal and parietal regions, including the precuneus. Declarative memory correlated with both cortical thickness and DTI measures. However, although hippocampal volume was significantly decreased in TBI patients, no correlations were found. Multiple regression analysis of all the structural measures revealed that decreases in Fractional anisotropy (FA) and thinning of the left parietal region were the best predictors of memory impairment. In conclusion, cortical thickness reductions in the left hemisphere and a lack of white matter integrity are the main contributors to long-term impairment in declarative memory among patients suffering from severe and diffuse TBI. In this study the hippocampus did not make a significant contribution to memory dysfunctions, suggesting that damage to this structure is compensated for by other regions, with the definitive sequelae being mainly explained by alterations in cortico-subcortical connectivity.
Verbal fluency relies on the coordinated activity between left frontal and temporal areas. Patients with Parkinsons disease (PD) present phonemic and semantic fluency deficits. Recent studies suggest that transcranial direct current stimulation (tDCS) enhances adaptative patterns of brain activity between functionally connected areas.
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