Eva M. Palacios

A Role for the Default Mode Network in the Bases of Disorders of Consciousness

Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity. Nevertheless, the integrity of the structural architecture supporting this network and its relation with the exhibited functional disconnections are very poorly understood. We investigated the structural connectivity and white matter integrity of the DMN in patients with disorders of consciousness of varying clinical severity.

Long-term declarative memory deficits in diffuse TBI: Correlations with cortical thickness, white matter integrity and hippocampal volume

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.

Resting-State Functional Magnetic Resonance Imaging Activity and Connectivity and Cognitive Outcome in Traumatic Brain Injury

IMPORTANCE 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. OBJECTIVE To study functional magnetic resonance imaging abnormalities in signal amplitude and brain connectivity at rest and their relationship to cognitive outcome in patients with chronic and severe traumatic axonal injury. DESIGN Observational study. SETTING University of Barcelona and Hospital Clinic de Barcelona, Barcelona, and Institut Guttmann-Neurorehabilitation Hospital, Badalona, Spain. PARTICIPANTS Twenty patients with traumatic brain injury (TBI) were studied, along with 17 matched healthy volunteers. INTERVENTIONS Resting-state functional magnetic resonance imaging and diffusion tensor imaging data were acquired. After exploring group differences in amplitude of low-frequency fluctuations (ALFF), we studied functional connectivity within the default mode network (DMN) by means of independent component analysis, followed by a dual regression approach and seed-based connectivity analyses. Finally, we performed probabilistic tractography between the frontal and posterior nodes of the DMN. MAIN OUTCOMES AND MEASURES Signal amplitude and functional connectivity during the resting state, tractography related to DMN, and the association between signal amplitudes and cognitive outcome. RESULTS Patients had greater ALFF in frontal regions, which was correlated with cognitive performance. Within the DMN, patients showed increased connectivity in the frontal lobes. Seed-based connectivity analyses revealed augmented connectivity within surrounding areas of the frontal and left parietal nodes of the DMN. Fractional anisotropy of the cingulate tract was correlated with increased connectivity of the frontal node of the DMN in patients with TBI. CONCLUSIONS AND RELEVANCE Increased ALFF is related to better cognitive performance in chronic TBI. The loss of structural connectivity produced by damage to the cingulum tract explained the compensatory increases in functional connectivity within the frontal node of the DMN.

Diffusion tensor imaging differences relate to memory deficits in diffuse traumatic brain injury

BackgroundMemory is one of the most impaired functions after traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to determine the structural basis of memory deficit. We correlated fractional anisotropy (FA) of the fasciculi connecting the main cerebral regions that are involved in declarative and working memory functions.MethodsFifteen patients with severe and diffuse TBI and sixteen healthy controls matched by age and years of education were scanned. The neuropsychological assessment included: Letter-number sequencing test (LNS), 2-back task, digit span (forwards and backwards) and the Rivermead profilet. DTI was analyzed by a tract-based spatial statics (TBSS) approach.ResultsWhole brain DTI analysis showed a global decrease in FA values that correlated with the 2-back d-prime index, but not with the Rivermead profile. ROI analysis revealed positive correlations between working memory performance assessed by 2-back d-prime and superior longitudinal fasciculi, corpus callosum, arcuate fasciculi and fornix. Declarative memory assessed by the Rivermead profile scores correlated with the fornix and the corpus callosum.ConclusionsDiffuse TBI is associated with a general decrease of white matter integrity. Nevertheless deficits in specific memory domains are related to different patterns of white matter damage.

White matter integrity related to functional working memory networks in traumatic brain injury

Objective: This study explores the functional and structural patterns of connectivity underlying working memory impairment after severe traumatic axonal injury. Methods: We performed an fMRI n-back task and acquired diffusion tensor images (DTI) in a group of 19 chronic-stage patients with severe traumatic brain injury (TBI) and evidence of traumatic axonal injury and 19 matched healthy controls. We performed image analyses with FSL software and fMRI data were analyzed using probabilistic independent component analysis. Fractional anisotropy (FA) maps from DTI images were analyzed with FMRIBs Diffusion Toolbox. Results: We identified working memory and default mode networks. Global FA values correlated with both networks and FA whole-brain analysis revealed correlations in several tracts associated with the functional activation. Furthermore, working memory performance in the patient group correlated with the functional activation patterns and with the FA values of the associative fasciculi. Conclusion: Combining structural and functional neuroimaging data, we were able to describe structural white matter changes related to functional network alterations and to lower performance in working memory in chronic TBI.

Changes in whole-brain functional networks and memory performance in aging

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.

Regional Vulnerability of Hippocampal Subfields to Aging Measured by Structural and Diffusion MRI

In the past few years, there has been an increasing awareness of the regional vulnerability of the hippocampus to age‐related processes. However, to date, no studies have assessed the effects of age on different structural magnetic resonance parameters in the specific hippocampal subfields. In this study, we measured volume, mean diffusivity (MD) and fractional anisotropy (FA) in the presubiculum, subiculum, fimbria, cornu ammonis (CA) 1,2‐3,4‐DG and the whole hippocampus in fifty cognitively intact elder adults between 50 and 75 years of age (20 men, 30 women). Segmentation of hippocampal subfields was performed using FreeSurfer. Individual MD and FA images were coregistered to T1‐weighted volumes using FLIRT of FSL. Linear regression analyses were performed to assess the effects of age on the anatomical measures of each subfield. In addition, multiple regression analyses were also carried out to assess which of the anatomical measures that showed a correlation with age in the previous analyses, were the best age predictors in the hippocampus. In agreement with previous studies, our results showed a significant association between age and volume (P < 0.001) as well as MD (P < 0.001) in the whole hippocampus. Regarding the specific hippocampal subfields, we found that age had a significant negative effect on volume in CA2‐3 (P < 0.001) and CA4‐DG (P < 0.001). Importantly, we found a positive effect of age on MD in CA2‐3 (P < 0.001) and fimbria (P < 0.001) as well as a negative age effect on FA in the subiculum (P < 0.001). Multiple regression analyses revealed that the best overall predictors of age in the hippocampus were MD in the fimbria and volume of CA2‐3, which explained 73.8% of the age variance. These results indicate that age has an effect both on volume and diffusion tensor imaging measures in different subfields, suggesting they provide complementary information on age‐related processes in the hippocampus.

Neuroanatomical correlates of olfactory loss in normal aged subjects.

In non-demented older persons, smell dysfunction, measured premortem, has been associated with postmortem brain degeneration similar to that of Alzheimers disease. We hypothesized that distinct measures of gray and white matter integrity evaluated through magnetic resonance imaging (MRI) techniques could detect degenerative changes associated with age-related olfactory dysfunction. High-resolution T1-weighted images and diffusion-tensor images (DTI) of 30 clinically healthy subjects aged 51-77 were acquired with a 3-Tesla MRI scanner. Odor identification performance was assessed by means of the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT scores correlated with right amygdalar volume and bilateral perirhinal and entorhinal cortices gray matter volume. Olfactory performance also correlated with postcentral gyrus cortical thickness and with fractional anisotropy and mean diffusivity levels in the splenium of the corpus callosum and the superior longitudinal fasciculi. Our results suggest that age-related olfactory loss is accompanied by diffuse degenerative changes that might correspond to the preclinical stages of neurodegenerative processes.

Toward Precision and Reproducibility of Diffusion Tensor Imaging: A Multicenter Diffusion Phantom and Traveling Volunteer Study

BACKGROUND AND PURPOSE: Precision medicine is an approach to disease diagnosis, treatment, and prevention that relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of this study was to assess the intersite variability after harmonization of a high-angular-resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury multisite study. MATERIALS AND METHODS: Diffusion MR imaging was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology and from the brain of a traveling volunteer on thirteen 3T MR imaging scanners representing 3 major vendors (GE Healthcare, Philips Healthcare, and Siemens). Means of the DTI parameters and their coefficients of variation across scanners were calculated for each DTI metric and white matter tract. RESULTS: For the National Institute of Standards and Technology diffusion phantom, the coefficients of variation of the apparent diffusion coefficient across the 13 scanners was <3.8% for a range of diffusivities from 0.4 to 1.1 × 10−6 mm2/s. For the volunteer, the coefficients of variations across scanners of the 4 primary DTI metrics, each averaged over the entire white matter skeleton, were all <5%. In individual white matter tracts, large central pathways showed good reproducibility with the coefficients of variation consistently below 5%. However, smaller tracts showed more variability, with the coefficients of variation of some DTI metrics reaching 10%. CONCLUSIONS: The results suggest the feasibility of standardizing DTI across 3T scanners from different MR imaging vendors in a large-scale neuroimaging research study.

Inferior frontal and insular cortical thinning is related to dysfunctional brain activation/deactivation during working memory task in schizophrenic patients

Although working memory is known to be impaired in schizophrenia the anatomical and functional relationships underlying this deficit remain to be elucidated. A combined imaging approach involving functional and structural magnetic resonance techniques was used, applying independent component analysis and surface-based morphometry to 14 patients with schizophrenia and 14 healthy controls. Neurocognitive functioning was assessed by a neuropsychological test battery that measured executive function. It was hypothesized that working memory dysfunctional connectivity in schizophrenia is related to underlying anatomical abnormalities. Patients with schizophrenia showed cortical thinning in the left inferior frontal gyrus and insula, which explained 57% of blood oxygenation level-dependent signal magnitude in functional magnetic resonance imaging in the central executive network (lateral prefrontal and parietal cortex) over-activation and default mode network (anterior and posterior cingulate) deactivation. No structure-function relationship emerged in the healthy control group. The study provides evidence to suggest that dysfunctional activation/deactivation patterns in schizophrenia may be explained in terms of underlying gray matter deficits.