Higher fresh fruit intake relates to larger grey matter volumes in areas involved in dementia and depression: A UK Biobank study.

The benefits of consuming fruits and vegetables are widely accepted. While previous studies suggest a protective role of fruits and vegetables against a variety of diseases such as dementia and depression, the biological mechanisms/effects remain unclear. Here we investigated the effect of fruit and vegetable consumption on brain structure. Particularly on grey matter (GM) and white matter (WM) volumes, regional GM volumes and subcortical volumes. Cross-sectional imaging data from UK Biobank cohort was used. A total of 9925 participants (Mean age 62.4 ± 7.5 years, 51.1 % men) were included in the present analysis. Measures included fruit and vegetable intake, other dietary patterns and a number of selected lifestyle factors and clinical data. Brain volumes were derived from structural brain magnetic resonance imaging. General linear model was used to study the associations between brain volumes and fruit/vegetable intakes. After adjusting for selected confounding factors, salad/raw vegetable intake showed a positive association with total white matter volume, fresh fruit intake showed a negative association with total grey matter (GM) volume. Regional GM analyses showed that higher fresh fruit intake was associated with larger GM volume in the left hippocampus, right temporal occipital fusiform cortex, left postcentral gyrus, right precentral gyrus, and right juxtapositional lobule cortex. We conclude that fruit and vegetable consumption seems to specifically modulate brain volumes. In particular, fresh fruit intake may have a protective role in specific cortical areas such as the hippocampus, areas robustly involved in the pathophysiology of dementia and depression.

From Virtual Reality to Regenerative Virtual Therapy: Some Insights from a Systematic Review Exploring Inner Body Perception in Anorexia and Bulimia Nervosa.

Despite advances in our understanding of the behavioral and molecular factors that underlie the onset and maintenance of Eating Disorders (EDs), it is still necessary to optimize treatment strategies and establish their efficacy. In this context, over the past 25 years, Virtual Reality (VR) has provided creative treatments for a variety of ED symptoms, including body dissatisfaction, craving, and negative emotions. Recently, different researchers suggested that EDs may reflect a broader impairment in multisensory body integration, and a particular VR technique-VR body swapping-has been used to repair it, but with limited clinical results. In this paper, we use the results of a systematic review employing PRISMA guidelines that explore inner body perception in EDs (21 studies included), with the ultimate goal to analyze the features of multisensory impairment associated with this clinical condition and provide possible solutions. Deficits in interoception, proprioception, and vestibular signals were observed across Anorexia and Bulimia Nervosa, suggesting that: (a) alteration of inner body perception might be a crucial feature of EDs, even if further research is needed and; (b) VR, to be effective with these patients, has to simulate/modify both the external and the internal body. Following this outcome, we introduce a new therapeutic approach-Regenerative Virtual Therapy-that integrates VR with different technologies and clinical strategies to regenerate a faulty bodily experience by stimulating the multisensory brain mechanisms and promoting self-regenerative processes within the brain itself.

Phonological working memory is adversely affected in adults with anorexia nervosa: a systematic literature review.

PURPOSE: Cognitive restraint has potentiating and deleterious effects on working memory (WM) in anorexia nervosa (AN). Conflicting evidence may be due to heterogeneity of tasks examining different WM components (e.g., verbal/auditory versus visuospatial), and differences in adolescent versus adult AN. Additionally, differential cognitive profiles of restricting versus binge/purging subtypes, comorbid psychiatric disorders and psychotropic medication use may confound findings. METHODS: To address these conflicts, 25 studies, published between 2016 and 2021, investigating WM in children, adolescents and adults with AN were systematically reviewed using PRISMA guidelines. RESULTS: In 71% of WM tasks, no difference in performance between AN patients and age-matched controls was reported, while 29% of WM tasks showed worse performance. Adults with AN displayed deficits in 44% of the verbal/auditory tasks, while performance remained unaffected in 86% of visuospatial tasks. CONCLUSION: Examining age groups and WM subsystems separately revealed novel findings of differentially affected WM components in AN. Comorbidities and psychotropic medications were common among AN participants and should be regarded as critical confounding factors for WM measures. Future studies examining different components of WM, acknowledging these confounding factors, may reveal specific deficits in AN to aid treatment improvement strategies. LEVEL OF EVIDENCE: I, systematic review.

Genetics of anorexia nervosa: An overview of genome-wide association studies and emerging biological links.

Anorexia nervosa (AN) is a complex disorder with a strong genetic component. Comorbidities are frequent and there is substantial overlap with other disorders. The lack of understanding of the molecular and neuroanatomical causes has made it difficult to develop effective treatments and it is often difficult to treat in clinical practice. Recent advances in genetics have changed our understanding of polygenic diseases, increasing the possibility of understanding better how molecular pathways are intertwined. This review synthetizes the current state of genetic research providing an overview of genome-wide association studies (GWAS) findings in AN as well as overlap with other disorders, traits, pathways, and imaging results. This paper also discusses the different putative global pathways that are contributing to the disease including the evidence for metabolic and psychiatric origin of the disease.

Brain and Cognitive Development in Adolescents with Anorexia Nervosa: A Systematic Review of fMRI Studies.

Anorexia nervosa (AN) is an eating disorder often occurring in adolescence. AN has one of the highest mortality rates amongst psychiatric illnesses and is associated with medical complications and high risk for psychiatric comorbidities, persisting after treatment. Remission rates range from 23% to 33%. Moreover, weight recovery does not necessarily reflect cognitive recovery. This issue is of particular interest in adolescence, characterized by progressive changes in brain structure and functional circuitries, and fast cognitive development. We reviewed existing literature on fMRI studies in adolescents diagnosed with AN, following PRISMA guidelines. Eligible studies had to: (1) be written in English; (2) include only adolescent participants; and (3) use block-design fMRI. We propose a pathogenic model based on normal and AN-related neural and cognitive maturation during adolescence. We propose that underweight and delayed puberty-caused by genetic, environmental, and neurobehavioral factors-can affect brain and cognitive development and lead to impaired cognitive flexibility, which in turn sustains the perpetuation of aberrant behaviors in a vicious cycle. Moreover, greater punishment sensitivity causes a shift toward punishment-based learning, leading to greater anxiety and ultimately to excessive reappraisal over emotions. Treatments combining physiological and neurobehavioral rationales must be adopted to improve outcomes and prevent relapses.

Altered thalamo­cortical and occipital­parietal­ temporal­frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies

Background: Anorexia nervosa and bulimia nervosa are complex mental disorders, and their etiology is still not fully understood. This paper reviews the literature on diffusion tensor imaging studies in patients with anorexia nervosa and bulimia nervosa to explore the usefulness of white matter microstructural analysis in understanding the pathophysiology of eating disorders. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify diffusion tensor imaging studies that compared patients with an eating disorder to control groups. We searched relevant databases for studies published from database inception to August 2018, using combinations of select keywords. We categorized white matter tracts according to their 3 main classes: projection (i.e., thalamo­cortical), association (i.e., occipital­parietal­temporal­frontal) and commissural (e.g., corpus callosum). Results: We included 19 papers that investigated a total of 427 participants with current or previous eating disorders and 444 controls. Overall, the studies used different diffusion tensor imaging approaches and showed widespread white matter abnormalities in patients with eating disorders. Despite differences among the studies, patients with anorexia nervosa showed mainly white matter microstructural abnormalities of thalamo­cortical tracts (i.e., corona radiata, thalamic radiations) and occipital­parietal­temporal­frontal tracts (i.e., left superior longitudinal and inferior fronto-occipital fasciculi). It was less clear whether white matter alterations persist after recovery from anorexia nervosa. Available data on bulimia nervosa were partially similar to those for anorexia nervosa. Limitations: Study sample composition and diffusion tensor imaging analysis techniques were heterogeneous. The number of studies on bulimia nervosa was too limited to be conclusive. Conclusion: White matter microstructure appears to be affected in anorexia nervosa, and these alterations may play a role in the pathophysiology of this eating disorder. Although we found white matter alterations in bulimia nervosa that were similar to those in anorexia nervosa, white matter changes in bulimia nervosa remain poorly investigated, and these findings were less conclusive. Further studies with longitudinal designs and multi-approach analyses are needed to better understand the role of white matter changes in eating disorders.

Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa.

Atypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naïve adolescent patients with atypical AN, and 24 healthy controls. Psychological traits related to the ED and depressive symptoms have been assessed using the Eating Disorders Examination Questionnaire (EDE-Q) and the Montgomery-Åsberg Depression Rating Scale self-reported (MADRS-S) respectively. Reduced connectivity was found in patients in brain areas involved in face-processing and social cognition, such as the left putamen, the left occipital fusiform gyrus, and specific cerebellar lobules. The connectivity was, on the other hand, increased in patients compared with controls from the right inferior temporal gyrus to the superior parietal lobule and superior lateral occipital cortex. These areas are involved in multimodal stimuli integration, social rejection and anxiety. Patients scored higher on the EDE-Q and MADRS-S questionnaires, and the MADRS-S correlated with connectivity from the right inferior temporal gyrus to the superior parietal lobule in patients. Our findings point toward a role for an altered development of socio-emotional skills in the pathogenesis of atypical AN. Nonetheless, longitudinal studies will be needed to assess whether these connectivity alterations might be a neural marker of the pathology.

Altered cerebellar-insular-parietal-cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network-based statistic analysis.

To date, few functional magnetic resonance imaging (fMRI) studies have explored resting-state functional connectivity (RSFC) in long-lasting anorexia nervosa (AN) patients via graph analysis. The aim of the present study is to investigate, via a graph approach (i.e., the network-based statistic), RSFC in a sample of adolescents at the earliest stages of AN (i.e., AN duration less than 6 months). Resting-state fMRI data was obtained from 15 treatment-naive female adolescents with AN restrictive type (AN-r) in its earliest stages and 15 age-matched healthy female controls. A network-based statistic analysis was used to isolate networks of interconnected nodes that differ between the two groups. Group comparison showed a decreased connectivity in a sub-network of connections encompassing the left and right rostral ACC, left paracentral lobule, left cerebellum (10th sub-division), left posterior insula, left medial fronto-orbital gyrus, and right superior occipital gyrus in AN patients. Results were not associated to alterations in intranodal or global connectivity. No sub-networks with an increased connectivity were identified in AN patients. Our findings suggest that RSFC may be specifically affected at the earliest stages of AN. Considering that the altered sub-network comprises areas mainly involved in somatosensory and interoceptive information and processing and in emotional processes, it could sustain abnormal integration of somatosensory and homeostatic signals, which may explain body image disturbances in AN. Further studies with larger samples and longitudinal designs are needed to confirm our findings and better understand the role and consequences of such functional alterations in AN.

What Is the Role of the Placebo Effect for Pain Relief in Neurorehabilitation? Clinical Implications From the Italian Consensus Conference on Pain in Neurorehabilitation.

BACKGROUND: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. METHODS: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. RESULTS: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. CLINICAL IMPLICATIONS: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy.

Locked to a wrong body: Eating disorders as the outcome of a primary disturbance in multisensory body integration.

In his recent paper "Distorted body representations in anorexia nervosa" Gadsby (2017) discussed empirical evidence regarding anorexic patients' distorted body representations. In particular, he interpreted them using the O'Shaughnessy's long-term body image (LTB) hypothesis (O'Shaughnessy, 1998): individuals with anorexia nervosa (AN) have a distorted LTB that tracks changes in the spatial content of the body and supplies this distorted content to other body representations. Even if we agree on the involvement of body memory in the distorted body representation, an open issue not fully addressed in the paper is: why AN patients do not update their LTBs to reflect their true dimensions? Our correspondence tries to answer to this question using a new neuropsychological and neurobiological theory: the Allocentric Lock Theory - ALT.

Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.

OBJECTIVE: Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients. METHOD: We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated. RESULTS: Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups. DISCUSSION: The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN.

White matter abnormalities in treatment-naive adolescents at the earliest stages of Anorexia Nervosa: A diffusion tensor imaging study.

Few studies have examined white matter (WM) integrity in long-lasting Anorexia Nervosa (AN) patients using Diffusion Tensor Imaging (DTI). In this paper, we investigated WM integrity at the earliest stages of AN (i.e. less than 6 months duration). Fourteen treatment-naive female adolescents with AN restrictive type (AN-r) in its earliest stages and 15 age-matched healthy females received brain MRI. Fractional Anisotropy (FA), Axial Diffusivity (AD), Radial diffusivity (RD), and Mean Diffusivity (MD) maps were computed from DTI data using Tract-Based Spatial Statistics analysis. AN-r patients showed FA decreases compared to controls (pFWE < 0.05) mainly in left anterior and superior corona radiata and left superior longitudinal fasciculus. AN-r patients also showed decreased AD in superior longitudinal fasciculus bilaterally and left superior and anterior corona radiata, (pFWE < 0.05). No significant differences were found in RD and MD values between the two groups. FA and AD integrity appears to be specifically affected at the earliest stages of AN. Alterations in the microstructural properties of the above mentioned tracts, also involved in cognitive control and visual perception and processing, may be early mechanisms of vulnerability/resilience of WM in AN and sustain the key symptoms of AN, such as impaired cognitive flexibility and body image distortion.

Correction: Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.

[This corrects the article DOI: 10.1371/journal.pone.0172129.].

Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.

Few studies have used diffusion tensor imaging (DTI) to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED), and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs) through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA) and mean, radial and axial diffusivities (MD, RD and AD, respectively). Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.

A systematic review of resting-state functional-MRI studies in anorexia nervosa: Evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration.

This paper systematically reviews the literature pertaining to the use of resting-state functional magnetic resonance imaging (rsfMRI) in anorexia nervosa (AN), classifying studies on the basis of different analysis approaches. We followed PRISMA guidelines. Fifteen papers were included, investigating a total of 294 participants with current or past AN and 285 controls. The studies used seed-based, whole-brain independent component analysis (ICA), network-of-interest ICA based and graph analysis approaches. The studies showed relatively consistent overlap in results, yet little overlap in their analytical approach and/or a-priori assumptions. Functional connectivity alterations were mainly found in the corticolimbic circuitry, involved in cognitive control and visual and homeostatic integration. Some overlapping findings were found in brain areas putatively important in AN, such as the insula. These results suggest altered functional connectivity in networks/areas linked to the main symptom domains of AN, such as impaired cognitive control and body image disturbances. These preliminary evidences suggest that more targeted treatments need to be developed that focus on these two symptom domains. Further studies with multi-approach analyses and longitudinal designs are needed to better understand the complexity of AN.

A Novel Technique for Improving Bodily Experience in a Non-operable Super-Super Obesity Case.

INTRODUCTION: The available clinical guidelines for super-super obese patients (i.e., with body mass index (BMI) > 60 kg/m(2)) that are not suitable for bariatric surgery mandate a palliative multidisciplinary treatment (i.e., production and maintenance of weight loss) provided in a center of excellence. However, the modality and the impact of this approach are still controversial. Moreover, it is not able to address the high level of body dissatisfaction and body distortions that are common among these patients. CLINICAL PRESENTATION: We report the case of a non-operable super-super obesity - a 37 year old woman with a BMI of 62 kg/m(2) - receiving a specialized treatment for her obstructive sleep apnea. She entered a multidisciplinary program that promoted healthy behaviors, including physical activities and psychological intervention. To improve body dissatisfaction, which was linked to a significant multisensory impairment of body perception, she also entered a virtual reality (VR) body-swapping illusion protocol. At the end of the current investigation, the patient continued her multidisciplinary program, reporting an increase in the motivation for undertaking healthy behavior and a decrease in the anxiety feelings associated with her clinical condition. CONCLUSION: This case provides preliminary evidence that both body dissatisfaction and body-size distortions of non-operable super-super obesity patients could be addressed by a VR body-swapping protocol, which is important because the palliative multidisciplinary treatment recommended for these patients is not able to address them. Interestingly, the use of a VR body-swapping illusion protocol seems to be able to improve not only the experience of the body in these patients but their motivation for change, too.