Bàrbara Segura

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Cognitive impairment and resting‐state network connectivity in Parkinson's disease

The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinsons disease (PD) using resting‐state functional MRI. Sixty‐five nondemented PD patients and 36 matched healthy controls were included. Thirty‐four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in attention/executive, visuospatial/visuoperceptual (VS/VP) and memory functions. A data‐driven approach using independent component analysis (ICA) was used to identify the default‐mode network (DMN), the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual‐regression approach controlling for gray matter atrophy. Additional seed‐based analyses using a priori defined regions of interest were used to characterize local changes in intranetwork and internetwork connectivity. Structural group comparisons through voxel‐based morphometry and cortical thickness were additionally performed to assess associated gray matter atrophy. ICA results revealed reduced connectivity between the DAN and right frontoinsular regions in MCI patients, associated with worse performance in attention/executive functions. The DMN displayed increased connectivity with medial and lateral occipito‐parietal regions in MCI patients, associated with worse VS/VP performance, and with occipital reductions in cortical thickness. In line with data‐driven results, seed‐based analyses mainly revealed reduced within‐DAN, within‐DMN and DAN‐FPN connectivity, as well as loss of normal DAN‐DMN anticorrelation in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD. Hum Brain Mapp, 36:199–212, 2015.

Functional brain networks and cognitive deficits in Parkinson's disease

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 Parkinsons 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. Hum Brain Mapp 35:4620–4634, 2014.

Alterations of the salience network in obesity: A resting‐state fMRI study

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. Hum Brain Mapp 34:2786–2797, 2013.

Microstructural white matter changes in metabolic syndrome A diffusion tensor imaging study

Background: Although metabolic syndrome is associated with cardiovascular disease and stroke, limited information is available on specific brain damage in patients with this syndrome. We investigated the relationship of the syndrome with white matter (WM) alteration using a voxel-based approach with diffusion tensor imaging (DTI). Methods: We compared fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measurements of DTI in 19 patients with metabolic syndrome aged between 50 and 80 years and 19 age-matched controls without any vascular risk factors for the syndrome. Results: Patients with metabolic syndrome showed an anterior–posterior pattern of deterioration in WM with reduced FA and increased ADC values compared with controls. WM changes were not related to any isolated vascular risk factor. Conclusion: Although the mechanism of this damage is not clear, the results indicate microstructural white matter alterations in patients with metabolic syndrome, mainly involving the frontal lobe.

Neural Responses to Visual Food Cues: Insights from Functional Magnetic Resonance Imaging

The aim of this paper is to describe the patterns of functional magnetic resonance imaging activation produced by visual food stimuli in healthy participants, as well as in those with anorexia nervosa, bulimia nervosa, binge eating disorder and obesity. We conducted a systematic review of studies published in the last decade on normal and abnormal eating. This review suggested the existence of neural differences in response to the sight of food between healthy individuals, those with an eating disorder and obese subjects. Differences were identified in two brain circuits: (i) limbic and paralimbic areas associated with salience and reward processes and (ii) prefrontal areas supporting cognitive control processes.

Structural correlates of facial emotion recognition deficits in Parkinson's disease patients.

The ability to recognize facial emotion expressions, especially negative ones, is described to be impaired in Parkinsons disease (PD) patients. Previous neuroimaging work evaluating the neural substrate of facial emotion recognition (FER) in healthy and pathological subjects has mostly focused on functional changes. This study was designed to evaluate gray matter (GM) and white matter (WM) correlates of FER in a large sample of PD. Thirty-nine PD patients and 23 healthy controls (HC) were tested with the Ekman 60 test for FER and with magnetic resonance imaging. Effects of associated depressive symptoms were taken into account. In accordance with previous studies, PD patients performed significantly worse in recognizing sadness, anger and disgust. In PD patients, voxel-based morphometry analysis revealed areas of positive correlation between individual emotion recognition and GM volume: in the right orbitofrontal cortex, amygdala and postcentral gyrus and sadness identification; in the right occipital fusiform gyrus, ventral striatum and subgenual cortex and anger identification, and in the anterior cingulate cortex (ACC) and disgust identification. WM analysis through diffusion tensor imaging revealed significant positive correlations between fractional anisotropy levels in the frontal portion of the right inferior fronto-occipital fasciculus and the performance in the identification of sadness. These findings shed light on the structural neural bases of the deficits presented by PD patients in this skill.

Morphometric Correlation of Impulsivity in Medial Prefrontal Cortex

Impulsivity is a complex behaviour composed of different domains encompassing behavioural dis-inhibition, risky decision-making and delay discounting abnormalities. To investigate regional brain correlates between levels of individual impulsivity and grey matter volume, we performed voxel-based morphometric correlation analysis in 34 young, healthy subjects using impulsivity scores measured with Barratt Impulsivity Scale-11 and computerized Kirby’s delay discounting task. The VBM analysis showed that impulsivity appears to be reliant on a network of cortical (medial prefrontal cortex and dorsolateral prefrontal cortex) and subcortical (ventral striatum) structures emphasizing the importance of brain networks associated with reward related decision-making in daily life as morphological biomarkers for impulsivity in a normal healthy population. While our results in healthy volunteers may not directly extend to pathological conditions, they provide an insight into the mechanisms of impulsive behaviour in patients with abnormalities in prefrontal/frontal-striatal connections, such as in drug abuse, pathological gambling, ADHD and Parkinson’s disease.

Progression of cortical thinning in early Parkinson's disease.

The aim of this study was to investigate the progression of cortical thinning and gray‐matter (GM) volume loss in early Parkinsons disease (PD). MRI and neuropsychological assessment were obtained at baseline and follow‐up (mean ± standard deviation = 35.50 ± 1.88 months) in a group of 16 early‐PD patients (H & Y stage ≤II and disease duration ≤5 years) and 15 healthy controls matched for age, gender, and years of education. FreeSurfer software was used for the analysis of cortical thickness as well as for cortical and subcortical volumetric analyses. Voxel‐based morphometry analysis was performed using SPM8. Compared to controls, PD patients showed greater regional cortical thinning in bilateral frontotemporal regions as well as greater over‐time total GM loss and amygdalar volume reduction. PD patients and controls presented similar over‐time changes in cognitive functioning. In early‐PD patients, global GM loss, amygdalar atrophy, and cortical thinning in frontotemporal regions are specifically associated with the PD‐degenerative process.

Mental slowness and executive dysfunctions in patients with metabolic syndrome

Metabolic Syndrome is a cluster of vascular risk factors which has been related to dementia and cognitive decline. The aim of this study was to describe the neuropsychological profile of metabolic syndrome patients. An extensive neuropsychological protocol was administered to 55 patients and 35 controls assessing memory, executive, visuoperceptual and visuoconstructive functions, language and speed of processing. There were differences between groups in speed of processing and some executive functions after controlling for the influences of education and gender. The results suggest that metabolic syndrome may be a prodromal state of vascular cognitive impairment.