Grey matter correlates of autistic traits in women with anorexia nervosa.

BACKGROUND: Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. METHODS: We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. RESULTS: Women with anorexia nervosa (n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group (n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. LIMITATIONS: We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. CONCLUSION: Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating anorexia nervosa.

Grey matter correlates of autistic traits in women with anorexia nervosa

Background: Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. Methods: We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. Results: Women with anorexia nervosa (n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group (n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. Limitations: We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. Conclusion: Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating ­anorexia nervosa.

A dry ligand-binding cavity in a solvated protein.

Ligands usually bind to proteins by displacing water from the binding site. The affinity and kinetics of binding therefore depend on the hydration characteristics of the site. Here, we show that the extreme case of a completely dehydrated free binding site is realized for the large nonpolar binding cavity in bovine beta-lactoglobulin. Because spatially delocalized water molecules may escape detection by x-ray diffraction, we use water (17)O and (2)H magnetic relaxation dispersion (MRD), (13)C NMR spectroscopy, molecular dynamics simulations, and free energy calculations to establish the absence of water from the binding cavity. Whereas carbon nanotubes of the same diameter are filled by a hydrogen-bonded water chain, the MRD data show that the binding pore in the apo protein is either empty or contains water molecules with subnanosecond residence times. However, the latter possibility is ruled out by the computed hydration free energies, so we conclude that the 315 A(3) binding pore is completely empty. The apo protein is thus poised for efficient binding of fatty acids and other nonpolar ligands. The qualitatively different hydration of the beta-lactoglobulin pore and carbon nanotubes is caused by subtle differences in water-wall interactions and water entropy.

Protein cold denaturation as seen from the solvent.

Unlike most ordered molecular systems, globular proteins exhibit a temperature of maximum stability, implying that the structure can be disrupted by cooling. This cold denaturation phenomenon is usually linked to the temperature-dependent hydrophobic driving force for protein folding. Yet, despite the key role played by protein-water interactions, hydration changes during cold denaturation have not been investigated experimentally. Here, we use water-(17)O spin relaxation to monitor the hydration dynamics of the proteins BPTI, ubiquitin, apomyoglobin, and beta-lactoglobulin in aqueous solution from room temperature down to -35 degrees C. To access this temperature range without ice formation, we contained the protein solution in nonperturbing picoliter emulsion droplets. Among the four proteins, only the destabilized apomyoglobin was observed to cold denature. Ubiquitin was found to be thermodynamically stable at least down to -32 degrees C, whereas beta-lactoglobulin is expected to be unstable below -5 degrees C but remains kinetically trapped in the native state. When destabilized by 4 M urea, beta-lactoglobulin cold denatures at 10 degrees C, as found previously by other methods. As seen from the solvent, the cold-denatured states of apomyoglobin in water and beta-lactoglobulin in 4 M urea are relatively compact and are better described as solvent-penetrated than as unfolded. This finding challenges the popular analogy between cold denaturation and the anomalous low-temperature increase in aqueous solubility of nonpolar molecules. Our results also suggest that the reported cold denaturation at -20 degrees C of ubiquitin encapsulated in reverse micelles is caused by the low water content rather than by the low temperature.

Processing of affective and emotionally neutral tactile stimuli in the insular cortex.

The insula is important for the processing of pleasant aspects of touch whereas its role in the processing of emotionally neutral touch has been less explored. Here, we used a network approach to investigate the insular processing of pleasant stroking touch and emotionally neutral vibratory touch, analysing functional magnetic resonance imaging data from 23 healthy adult participants. Vibration and skin stroking activated areas in the posterior, middle and anterior insula. Psychophysiological interaction analyses suggested that skin stroking increased functional connectivity between the posterior and ventral anterior insula. Vibration instead increased functional connectivity between the posterior and dorsal anterior insula, and induced a stronger decrease of the default mode network activity compared to stroking. These results confirmed findings from previous studies showing that the posterior insula processes affective touch information. We suggest that this is accomplished by relaying tactile information from the posterior insula to ventral anterior insula, an area tightly connected to the emotional parts of the brain. However, our results also suggested that the insula processes tactile information with less emotional valence. A central hub in this processing seemed to be the right dorsal anterior insula.

Abnormal brain processing of gentle touch in anorexia nervosa.

Body image disturbance is a core symptom in anorexia nervosa (AN). Recent research suggests that abnormalities in touch perception may contribute to the disease mechanisms in AN. Here, we used functional magnetic resonance imaging (fMRI) to study possible abnormalities in cortical processing of affective touch in AN. Gentle skin strokes were applied to the right forearm during fMRI scanning in women diagnosed with AN (n = 25) and in matched healthy controls (HC; n = 25). Blocks of skin stroking were alternated with blocks of static skin indentation. Participants provided ratings of the pleasantness of skin stroking stimulation. AN participants perceived skin stroking as significantly less pleasant than HC. We observed no group differences for the contrast between skin stroking and skin indentation in primary tactile regions. We did find, however, significantly less activity in the AN group in areas including left caudate nucleus. Also, we found less activity in the AN group in bilateral lateral occipital cortex for the main effect of skin stroking. Our results suggest that abnormal functioning of the dorsal striatum could affect evaluation of pleasant tactile stimuli, and that abnormal functioning of the lateral occipital cortex might be related to disturbed body image perception.

Posterior Superior Temporal Sulcus Responses Predict Perceived Pleasantness of Skin Stroking.

Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress-like skin stroking. We collected functional magnetic resonance imaging data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS) responses predicted healthy participant's perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment.

Biomolecular hydration: from water dynamics to hydrodynamics.

Thermally driven rotational and translational diffusion of proteins and other biomolecules is governed by frictional coupling to their solvent environment. Prediction of this coupling from biomolecular structures is a longstanding biophysical problem, which cannot be solved without knowledge of water dynamics in an interfacial region comparable to the dry protein in volume. Efficient algorithms have been developed for solving the hydrodynamic equations of motion for atomic-resolution biomolecular models, but experimental diffusion coefficients can be reproduced only by postulating hundreds of rigidly bound water molecules. This static picture of biomolecular hydration is fundamentally inconsistent with magnetic relaxation dispersion experiments and molecular dynamics simulations, which both reveal a highly dynamic interface where rotation and exchange of nearly all water molecules are several orders of magnitude faster than biomolecular diffusion. Here, we resolve this paradox by means of a dynamic hydration model that explicitly links protein hydrodynamics to hydration dynamics. With the aid of this model, bona fide structure-based predictions of global biomolecular dynamics become possible, as demonstrated here for a set of 16 proteins for which accurate experimental rotational diffusion coefficients are available.