A Neglected Topic in Neuroscience: Replicability of fMRI Results With Specific Reference to ANOREXIA NERVOSA.

Functional magnetic resonance imaging (fMRI) studies report impaired functional correlates of cognition and emotion in mental disorders. The validity of preexisting studies needs to be confirmed through replication studies, which there is a lack of. So far, most replication studies have been conducted on non-patients (NP) and primarily investigated cognitive and motor tasks. To fill this gap, we conducted the first fMRI replication study to investigate brain function using disease-related food stimuli in patients with anorexia nervosa (AN). Using fMRI, we investigated 31 AN patients and 27 NP for increased amygdala and reduced midcingulate activation when viewing food and non-food stimuli, as reported by the original study (11AN, 11NP; Joos et al., 2011). Similar to the previous study, we observed in the within group comparisons (food>non-food) a frontoinsular activation for both groups. Although in AN the recorded activation clustered more prominently and extended into the cingulate cortex. In the between-group comparisons, the increased amygdala and reduced midcingulate activation could not be replicated. Instead, AN showed a higher activation of the cingulate cortices, the pre-/postcentral gyrus and the inferior parietal lobe. Unlike in the initial study, no significant differences between NP>AN could be observed. The inconsistency of results and the non-replication of the study could have several reasons, such as high inter-individual variance of functional correlates of emotion processing, as well as intra-individual variances and the smaller group size of the initial study. These results underline the importance of replication for assessing the reliability and validity of results from fMRI research.

Insular Cell Integrity Markers Linked to Weight Concern in Anorexia Nervosa-An MR-Spectroscopy Study.

OBJECTIVE: An insular involvement in the pathogenesis of anorexia nervosa (AN) has been suggested in many structural and functional neuroimaging studies. This magnetic resonance spectroscopy (MRS) study is the first to investigate metabolic signals in the anterior insular cortex in patients with AN and recovered individuals (REC). METHOD: The MR spectra of 32 adult women with AN, 21 REC subjects and 33 healthy controls (HC) were quantified for absolute N-acetylaspartate (NAA), glutamate + glutamine (Glx), total choline, myo-inositol, creatine concentrations (mM/L). After adjusting the metabolite concentrations for age and partial gray/white matter volume, group differences were tested using one-way multivariate analyses of variance (MANOVA). Post-hoc analyses of variance were applied to identify those metabolites that showed significant group effects. Correlations were tested for associations with psychometric measures (eating disorder examination), duration of illness, and body mass index. RESULTS: The MANOVA exhibited a significant group effect. The NAA signal was reduced in the AN group compared to the HC group. The REC and the HC groups did not differ in metabolite concentrations. In the AN group, lower NAA and Glx signals were related to increased weight concern. DISCUSSION: We interpret the decreased NAA availability in the anterior insula as a signal of impaired neuronal integrity or density. The association of weight concern, which is a core feature of AN, with decreased NAA and Glx indicates that disturbances of glutamatergic neurotransmission might be related to core psychopathology in AN. The absence of significant metabolic differences between the REC and HC subjects suggests that metabolic alterations in AN represent a state rather than a trait phenomenon.

White Matter Abnormalities in the Corpus Callosum in Acute and Recovered Anorexia Nervosa Patients-A Diffusion Tensor Imaging Study.

Objective: Severe malnutrition in patients with anorexia nervosa (AN) as well as possible trait-related aberrations lead to pronounced structural brain changes whose reversibility after recovery is currently unclear. Previous diffusion tensor imaging (DTI) studies investigating white matter (WM) microstructure alterations in AN are inconsistent. Methods: In this so far largest DTI study in adults, we investigated 33 AN patients, 20 recovered (REC), and 33 healthy women. DTI data were processed using the "DTI and Fiber tools," and the Computational Anatomy Toolbox. WM integrity, both in terms of fractional anisotropy (FA) and mean diffusivity (MD), was assessed. Results: We found a significant FA decrease in the corpus callosum (body) and an MD decrease in the posterior thalamic radiation in the AN group. The REC group displayed FA decrease in the corpus callosum in comparison to HC, whereas there were no MD differences between the REC and HC groups. Conclusion: Despite prolonged restoration of weight in the REC group, no significant regeneration of WM integrity in terms of FA could be observed. Transient changes in MD likely represent a reversible consequence of the acute state of starvation or result from dehydration. Reduction of FA either may be due to WM damage resulting from malnutrition or may be considered a pre-morbid marker.

Altered cortical folding and reduced sulcal depth in adults with anorexia nervosa.

OBJECTIVE: Previous studies on anorexia nervosa (AN) focused on cortical volume and mainly reported grey matter reduction. They also investigated cortical surface parameters, for example, absolute mean curvature (AMC) providing information on cortical folding or sulcal depth (SD). For the first time, we also analysed cortical complexity using fractal dimension (FD) in AN. METHOD: In a cross-sectional study, we performed surface analyses (AMC, SD, and FD) on 34 women with AN, 24 recovered from AN (REC), and 41 healthy controls (HC). Structural MR data was processed using the Computational Anatomy Toolbox and statistically compared across groups on a vertex- and region-of-interest-wise level using statistical parametric mapping. RESULTS: We found a lower AMC and SD in AN, especially in temporal areas. FD was increased in the left precentral gyrus in AN. No differences of the parameters AMC, SD, or FD were evident between REC and HC participants. CONCLUSIONS: Alterations in AMC, SD, and FD in AN patients, but not between the REC and HC groups, suggest that these alterations are state related. The findings concur with other structural AN studies that suggest restitution with clinical recovery. The changes may be due to malnutrition, dehydration, osmotic dysregulation, or hormonal aberrations during the acute stage.

Neurobiological signature of intimacy in anorexia nervosa.

BACKGROUND: Intimacy and psychosexual development represent core problems of anorexia nervosa (AN). Experiential and neurobiological evidence however is scarce. MATERIAL AND METHODS: Thirty-one female AN patients were compared with 35 non-patients (NP) and 22 recovered participants (REC) by using functional magnetic resonance imaging. Participants viewed pictures of couples in intimate relationships and control stimuli. RESULTS: AN patients experienced intimate stimuli with lower valence and dominance. AN showed decreased activation of parietal cortices. NP decreased the prefrontal cortex response, which AN patients did not. REC participants did not differ from NP on a behavioural level, though with regard to the neural signature. DISCUSSION: Parietal cortices are related to processing of erotic themes, which seems to be deficient in AN. Dysfunction of prefrontal cortices likely mirrors dysfunctional control in AN. The neural signature does not seem to be state-related considering results of REC.

Recovery of cortical volume and thickness after remission from acute anorexia nervosa.

OBJECTIVE: Reduced grey (GM) and white matter (WM) volumes and increased cerebrospinal fluid (CSF) have been frequently reported in anorexia nervosa (AN), but studies focusing on cortical thickness (CT) are scarce and findings inconsistent. We conducted the first study in AN that analyzed both parameters in the same study to gain novel and comprehensive insight. METHOD: Voxel-based morphometry (VBM) analysis was performed on T1-weighted magnetic resonance images from 34 predominantly adult women with acute AN, 24 REC participants, and 41 healthy controls (HC). Global brain segment volumes (GM, WM, and CSF), regional GM volume, and cortical thickness measures were obtained from the same study sample. We further focused on recovery by including a REC group. RESULTS: The GM and WM volumes were decreased, and correspondingly, the CSF volume increased in the AN in comparison to the HC and REC groups. No significant volume differences between the REC and HC groups could be observed. AN patients showed reduced regional GM volumes in the right hippocampus and the left middle and right inferior frontal gyrus. Cortical thinning occurred in the AN group, which was particularly robust in fronto-parietal areas. The REC and HC groups failed to show any regional GM or cortical thickness differences. DISCUSSION: AN is accompanied by severe loss of brain volume and cortical thickness as assessed by complementary investigation tools. However, these changes seem to be largely reversible, which should be encouraging for therapists and patients. The underlying neurobiological mechanisms remain unclear and should be assessed in further studies.

Neural correlates of intimate picture stimuli in females.

Jacob et al. (2011) previously reported on intimate picture stimuli for emotion research in females in Psychiatry Research. Difficulties to engage in intimate relations constitute problems of many mental disorders, and intimacy must be differentiated from pure sex drive. Functional neuroimaging is an important tool to understand the pathophysiology of psychiatric disorders. We now studied cerebral activation in response to intimate stimuli in 35 healthy women. Comparison stimuli were taken from the International Affective Picture System. Neuroimaging revealed increased activation in bilateral occipitotemporal, parietal and anterior cingulate cortices extending to the orbitofrontal area. These data reflect cognitive, emotional and motivational compounds congruent with previous neuroimaging data of attachment and long term romantic relationships. Lateral prefrontal, posterior insular regions and the fusiform face area were more active during control images. Our data present a solid basis for use in psychiatric samples.