Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction

Clinical practice: The care of children with Down syndrome

Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available

Aberrant Function of Learning and Cognitive Control Networks Underlie Inefficient Cognitive Flexibility in Anorexia Nervosa: A Cross-Sectional fMRI Study

Objectives People with Anorexia Nervosa exhibit difficulties flexibly adjusting behaviour in response to environmental changes. This has previously been attributed to problematic behavioural shifting, characterised by a decrease in fronto-striatal activity. Additionally, alterations of instrumental learning, which relies on fronto-striatal networks, may contribute to the observation of inflexible behaviour. The authors sought to investigate the neural correlates of cognitive flexibility and learning in Anorexia Nervosa. Method Thirty-two adult females with Anorexia Nervosa and thirty-two age-matched female control participants completed the Wisconsin Card Sorting Task whilst undergoing functional magnetic resonance imaging. Event-related analysis permitted the comparison of cognitive shift trials against those requiring maintenance of rule-sets and allowed assessment of trials representing learning. Results Although both groups performed similarly, we found significant interactions in the left middle frontal gyrus, precuneus and superior parietal lobule whereby blood-oxygenated-level dependent response was higher in Anorexia Nervosa patients during shifting but lower when maintaining rule-sets, as compared to healthy controls. During learning, posterior cingulate cortex activity in healthy controls decreased whilst increasing in the Anorexia Nervosa group, whereas the right precuneus exhibited the opposite pattern. Furthermore, learning was associated with lower blood-oxygenated-level dependent response in the caudate body, as compared to healthy controls. Conclusions People with Anorexia Nervosa display widespread changes in executive function. Whilst cognitive flexibility appears to be associated with aberrant functioning of the fronto-parietal control network that mediates between internally and externally directed cognition, fronto-striatal alterations, particularly within the caudate body, were associated with instrumental learning. Together, this shows how perseverative tendencies could be a substrate of multiple high-order processes that may contribute to the maintenance of Anorexia Nervosa

Auditory Function in the Tc1 Mouse Model of Down Syndrome Suggests a Limited Region of Human Chromosome 21 Involved in Otitis Media

Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K+ currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca2+ activated K+ current (IK,f), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active

Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction