Ana Narberhaus

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.

Patterns of cerebral white matter damage and cognitive impairment in adolescents born very preterm.

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age ± S.D.: 14.4 ± 1.6 years) born before 32 weeks of gestational age and 43 term‐born adolescents (14.5 ± 2.1 years). Individual voxel‐based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole‐brain white matter volume (r = 0.32; P = 0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.

Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity

Using optimized voxel-based morphometry (VBM), we compared the relationship between hippocampal and thalamic gray matter loss and memory impairment in 22 adolescents with history of prematurity (HP) and 22 normal controls. We observed significant differences between groups in verbal learning and verbal recognition, but not in visual memory. VBM analysis showed significant left hippocampal and bilateral thalamic reductions in HP subjects. Using stereological methods, we also observed a reduction in hippocampal volume, with left posterior predominance. We found correlations between left hippocampal gray matter reductions (assessed by VBM) and verbal memory (learning and percentage of memory loss) in the premature group. The stereological analysis showed a correlation between verbal learning and the left posterior hippocampus. Our results suggest that left hippocampal tissue loss may be responsible for memory impairment and is probably related to the learning disabilities that HP subjects present during schooling.

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.

White matter volume and concentration reductions in adolescents with history of very preterm birth: a voxel-based morphometry study.

Very preterm birth (VPTB) is an important risk factor for white matter (WM) damage. We used voxel-based morphometry (VBM) to examine regional WM brain abnormalities in 50 adolescents with antecedents of very preterm birth (VPTB) without evidence of WM damage on T2-weighted MRI. This group was compared with a group of 50 subjects born at term and matched for age, handedness and socio-cultural status. We also examined the relationship between WM changes and gestational age (GA) and weight (GW) at birth in VPTB subjects. Both modulated and unmodulated VBM analyses showed significant abnormalities in several WM brain regions in the VPTB group, involving all the cerebral lobes. However, density analyses (unmodulated data) mainly identified periventricular damage and the involvement of the longitudinal fascicles while volume analyses (modulated data) detected WM decreases in regions distant from the ventricular system, located at the origin and end of the long fascicles. A significant correlation was found between WM decreases and both GA and GW in various brain regions: the lower the GA and GW, the lower the WM integrity. This study supports the current view that widespread white matter impairment is associated with immature birth.

Corpus Callosum and Prefrontal Functions in Adolescents with History of Very Preterm Birth.

Very preterm (VPT) birth can account for thinning of the corpus callosum and poorer cognitive performance. Research findings about preterm and VPT adolescents usually describe a small posterior corpus callosum, although our research group has also found reductions of the anterior part, specifically the genu. The aim of the present study was to investigate the functional implications of this concrete reduction. Fifty-two VPT adolescents were compared with 52 adolescents born at term; there were no significant differences in age and gender, and socioeconomic status was similar between the groups. All participants underwent a magnetic resonance imaging (MRI) study and assessment of prefrontal functioning and vocabulary. The VPT group showed significant reductions of the genu, isthmus and splenium, as well as a significantly worse performance on category verbal fluency, executive functions, everyday memory and vocabulary. Although several parts of the corpus callosum correlated with some prefrontal functions, the genu was the part which principally explained these correlations. The subtest Vocabulary only correlated with the splenium. The relationship between genu and prefrontal functions and between splenium and vocabulary may be due to the fact that these parts of the corpus callosum connect prefrontal and posterior parietal cortex, respectively. The work presented here provides evidence of specific associations between reductions in the anterior corpus callosum (genu) and lower prefrontal functioning in VPT adolescents.

Gestational Age at Preterm Birth in Relation to Corpus Callosum and General Cognitive Outcome in Adolescents

Prematurity is associated with corpus callosum abnormalities and low general cognitive functioning. The present study explores the specific relationship between gestational age, corpus callosum, and intelligence quotient (IQ) in a sample of preterm-born adolescents. Sixty-four adolescents born at a gestational age of 36 weeks or less were divided into 4 groups attending to their gestational age (GA) (group 1, ≤ 27; group 2, 28-30; group 3, 31-33; group 4, 34-36). These individuals were compared with 53 adolescents born at term and of similar age, gender, and sociocultural status. Individuals born at a gestational age of 27 or less (group 1) presented a generalized corpus callosum reduction in the posterior part (posterior midbody, isthmus, and splenium) as well as in the anterior part (anterior midbody and genu), a reduced total white-matter volume, and a low Full-Scale IQ. Group 2 (GA between 28 and 30) also showed a low IQ, but corpus callosum reduction was only found in the splenium, without total white-matter volume reductions. Group 3 (GA between 31 and 33) did not present differences in corpus callosum size or a reduced total white- matter volume, but they showed a low Full-Scale IQ. Group 4 (GA between 34 and 36) did not show a smaller corpus callosum or a lower general cognitive performance. Specific significant correlations were found between corpus callosum subregions and gestational age. These results suggest the importance of gestational age in prematurity in relation to brain structural and functional outcome. Premature babies born at a gestational age of 27 weeks or less are the target group for long-term corpus callosum and white-matter anomalies and for a low IQ.

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.

Hippocampal functional magnetic resonance imaging during a face-name learning task in adolescents with antecedents of prematurity.

Functional magnetic resonance imaging (fMRI) was used to map hippocampal activation during a declarative memory task in a sample of 14 adolescents with antecedents of prematurity (AP). The sample with AP was matched by age, sex and handedness with 14 full-term controls with no history of neurological or psychiatric illness. The target task consisted in learning 16 novel face-name pairs, and the control task involved the examination of two repeated face-name pairs. Stereological methods were also used to quantify hippocampal volumes. In both groups, we observed increased activation in the learning condition compared to the control task in the right fusiform gyrus and the left inferior occipital gyrus, but only premature subjects activated the hippocampus. Group comparison of the activation versus control conditions showed that prematures had greater activity in the right hippocampus than controls during the encoding of the word-face association. Volumetric analyses showed a significant left hippocampal volume loss in adolescents with AP. In addition, we found a significant positive correlation in the premature group between right hippocampal activation and face-name recognition. Functional MRI data also correlated with structural MRI data: right hippocampal activation correlated positively with right hippocampal volume. Our findings are consistent with previous studies of brain plasticity after focal lesions. Left hippocampal tissue loss may be related to an increase in contralateral brain activity, probably reflecting a compensatory mechanism. Our data also suggest that this plasticity is not enough to achieve normal performance.

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.