María Ángeles Jurado

Impact of the COMT Val108/158 Met and DAT genotypes on prefrontal function in healthy subjects.

Two limiting factors of dopamine activity are the catechol-o-methyltransferase (COMT) and the dopamine transporter (DAT), which terminate dopamine activity by degradation and uptake, respectively. Genetic variants of COMT and DAT have been related to the enzymatic activity and protein availability, respectively. The Met allele of the COMT Val108/158 Met polymorphism has been associated to lower enzymatic activity and the 9-repeat allele of the DAT 40 base-pair (bp) variable number of tandem repeat (VNTR) polymorphism has been related to lower protein availability. Genotypes for COMT and DAT were determined in a sample of 75 healthy subjects, who underwent functional magnetic resonance imaging (fMRI) while performing an N-back task. To further assess the effects of the genotypes on cognition, subjects were administered the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test (CPT). Analysis of fMRI data revealed an additive effect of these two genes on brain activation in an N-back task, with subjects homozygous for the Val and the 9-repeat alleles showing the highest activation for the same level of performance. Moreover, the Val allele was related to higher number of perseverative errors on the WCST and with a higher number of commission errors on the CPT. The 10-repeat allele was associated with faster reaction times but also with a higher number of commission errors. Our results support a role of the COMT Val108/158 Met and the DAT 40 bp VNTR in both brain activation and cognition.

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.

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.

Reward processing in obesity, substance addiction and non-substance addiction

Similarities and differences between obesity and addiction are a prominent topic of ongoing research. We conducted an activation likelihood estimation meta‐analysis on 87 studies in order to map the functional magnetic resonance imaging (fMRI) response to reward in participants with obesity, substance addiction and non‐substance (or behavioural) addiction, and to identify commonalities and differences between them. Our study confirms the existence of alterations during reward processing in obesity, non‐substance addiction and substance addiction. Specifically, participants with obesity or with addictions differed from controls in several brain regions including prefrontal areas, subcortical structures and sensory areas. Additionally, participants with obesity and substance addictions exhibited similar blood‐oxygen‐level‐dependent fMRI hyperactivity in the amygdala and striatum when processing either general rewarding stimuli or the problematic stimuli (food and drug‐related stimuli, respectively). We propose that these similarities may be associated with an enhanced focus on reward – especially with regard to food or drug‐related stimuli – in obesity and substance addiction. Ultimately, this enhancement of reward processes may facilitate the presence of compulsive‐like behaviour in some individuals or under some specific circumstances. We hope that increasing knowledge about the neurobehavioural correlates of obesity and addictions will lead to practical strategies that target the high prevalence of these central public health challenges.

Frontal cortical thinning and subcortical volume reductions in early adulthood obesity

Obesity depends on homeostatic and hedonic food intake behavior, mediated by brain plasticity changes in cortical and subcortical structures. The aim of this study was to investigate cortical thickness and subcortical volumes of regions related to food intake behavior in a healthy young adult sample with obesity. Thirty-seven volunteers, 19 with obesity (age=33.7±5.7 (20-39) years body-mass index (BMI)=36.08±5.92 (30.10-49.69)kg/m(2)) and 18 controls (age=32.3±5.9 (21-40) years; BMI=22.54±1.94 (19.53-24.97)kg/m(2)) participated in the study. Patients with neuropsychiatric or biomedical disorders were excluded. We used FreeSurfer software to analyze structural magnetic resonance images (MRI) and obtain global brain measures, cortical thickness and subcortical volume estimations. Finally, correlation analyses were performed for brain structure data and obesity measures. There were no between-group differences in age, gender, intelligence or education. Results showed cortical thickness reductions in obesity in the left superior frontal and right medial orbitofrontal cortex. In addition, the obesity group had lower ventral diencephalon and brainstem volumes than controls, while there were no differences in any other subcortical structure. There were no statistically significant correlations between brain structure and obesity measures. Overall, our work provides evidence of the structural brain characteristics associated with metabolically normal obesity. We found reductions in cortical thickness, ventral diencephalon and brainstem volumes in areas that have been implicated in food intake behavior.

Dopamine Genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and Executive Function: Their Interaction with Obesity

Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42) if their body mass index (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The ‘DRD2/ANKK1-TaqIA A1-allele status’ had a significant effect on almost all the executive variables, but no significant ‘DRD4 7R-allele status’ effects were observed for any of the executive variables analyzed. There was a significant ‘group’ x ‘DRD2/ANKK1-TaqIA A1-allele status’ interaction effect on LN and ‘group’ x ‘DRD4 7R-allele status’ interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions.

Functional connectivity in obesity during reward processing

Obesity is a health problem that has become a major focus of attention in recent years. There is growing evidence of an association between obesity and differences in reward processing. However, it is not known at present whether these differences are linked exclusively to food, or whether they can be detected in other rewarding stimuli. We compared responses to food, rewarding non-food and neutral pictures in 18 young adults with obesity and 19 normal-weight subjects using independent component analysis. Both groups modulated task-related activity in a plausible way. However, in response to both food and non-food rewarding stimuli, participants with obesity showed weaker connectivity in a network involving activation of frontal and occipital areas and deactivation of the posterior part of the default mode network. In addition, obesity was related with weaker activation of the default mode network and deactivation of frontal and occipital areas while viewing neutral stimuli. Together, our findings suggest that obesity is related to a different allocation of cognitive resources in a fronto-occipital network and in the default mode network.

White matter fractional anisotropy is related to processing speed in metabolic syndrome patients: a case-control study

BackgroundMetabolic Syndrome (MetSd) is a cluster of vascular risk factors that may influence cerebrovascular pathology during aging. Recently, microstructural white matter (WM) changes detected by diffusion tensor imaging (DTI) and processing speed deficits have been reported in MetSd patients. We aimed to test the relationship between WM alteration and cognitive impairment in these patients.MethodsThe sample comprised 38 subjects (19 patients aged between 50 and 80 years old, and 19 controls). All patients fulfilled National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria for MetSd. Speed of information processing was measured by the Symbol Digit Modalities Test (SDMT) and reaction time (RT) on the Continuous Performance Test (CPT-II) and the Grooved Pegboard Test (GPT). DTI images were acquired in a 3 Tesla Siemens Trio scanner. Voxelwise statistical analysis of the fractional anisotropy (FA) data was performed using the Tract-Based Spatial Statistics part of the FMRIB Software Library. A correlation analysis was performed between processing speed variables and FA values.ResultsThere was a larger proportion of slow subjects (percentile below 25th) in the patient group (Chi2 = 7.125 p = 0.008). FA values correlated positively with SDMT in anterior and posterior parts of the corpus callosum, and RT CPT-II correlated negatively with FA values in the anterior corpus callosum (p < 0.05 corrected) in the patient group.ConclusionWe found significant correlations between WM alterations and cognitive impairment in MetSd patients, especially in the frontal lobe. These findings highlight the importance of MetSd prevention and control due to its association with structural and functional damage in the central nervous system.