Initial evidence of abnormal brain plasticity in anorexia nervosa: an ultra-high field study.

Anorexia Nervosa has been associated with white matter abnormalities implicating subcortical abnormal myelination. Extending these findings to intracortical myelin has been challenging but ultra-high field neuroimaging offers new methodological opportunities. To test the integrity of intracortical myelin in AN we used 7 T neuroimaging to acquire T1-weighted images optimized for intracortical myelin from seven females with AN (age range: 18-33) and 11 healthy females (age range: 23-32). Intracortical T1 values (inverse index of myelin concentration) were extracted from 148 cortical regions at ten depth-levels across the cortical ribbon. Across all cortical regions, these levels were averaged to generate estimates of total intracortical myelin concentration and were clustered using principal component analyses into two clusters; the outer cluster comprised T1 values across depth-levels ranging from the CSF boundary to the middle of the cortical regions and the inner cluster comprised T1 values across depth-levels ranging from the middle of the cortical regions to the gray/white matter boundary. Individuals with AN exhibited higher T1 values (i.e., decreased intracortical myelin concentration) in all three metrics. It remains to be established if these abnormalities result from undernutrition or specific lipid nutritional imbalances, or are trait markers; and whether they may contribute to neurobiological deficits seen in AN.

Prospective Associations Between Driven Exercise and Other Eating Disorder Behaviors in Adolescence: A Longitudinal Cohort Study.

PURPOSE: Dysfunctional exercise is a common, debilitating symptom across eating disorders (ED). We examined the cross-sectional and longitudinal associations between experiences of exercise and ED behaviors and cognitions in an adolescent, population-based sample. METHODS: Adolescents (n = 4,054) self-reported whether they exercised to control shape and weight (exercise for weight loss [EWL]), and, if so, whether they exercised even when injured, and whether exercise interfered with life functioning (driven exercise) at age 14 years, allowing delineation of three exercise-based groups: no-EWL, EWL, and driven exercise. Participants also reported ED cognitions at age 14 years along with other ED behaviors (fasting, purging, binge eating) at ages 14 and 16 years. Sex-stratified regression approaches were employed to examine relationships between these exercise categories at age 14 and ED behaviors and cognitions at ages 14 and 16. RESULTS: Cross-sectionally, those in the driven exercise group, compared to the no-EWL group, consistently reported higher levels of ED cognitions and behaviors, with those in the EWL group also reporting higher levels of some ED cognitions and behaviors relative to the no-EWL group. Those in the EWL and driven exercise groups at age 14 also demonstrated a higher prospective likelihood of fasting (boys and girls) and purging (girls only) at age 16, relative to those in the no-EWL group at age 14. DISCUSSION: Results inform our understanding of EWL and driven exercise and the developmental timing of ED behaviors in adolescence and point toward the potential utility of targeted prevention for young people who report EWL.

Neurophysiological, Oculomotor, and Computational Modeling of Impaired Reading Ability in Schizophrenia.

Schizophrenia (Sz) is associated with deficits in fluent reading ability that compromise functional outcomes. Here, we utilize a combined eye-tracking, neurophysiological, and computational modeling approach to analyze underlying visual and oculomotor processes. Subjects included 26 Sz patients (SzP) and 26 healthy controls. Eye-tracking and electroencephalography data were acquired continuously during the reading of passages from the Gray Oral Reading Tests reading battery, permitting between-group evaluation of both oculomotor activity and fixation-related potentials (FRP). Schizophrenia patients showed a marked increase in time required per word (d = 1.3, P < .0001), reflecting both a moderate increase in fixation duration (d = .7, P = .026) and a large increase in the total saccade number (d = 1.6, P < .0001). Simulation models that incorporated alterations in both lower-level visual and oculomotor function as well as higher-level lexical processing performed better than models that assumed either deficit-type alone. In neurophysiological analyses, amplitude of the fixation-related P1 potential (P1f) was significantly reduced in SzP (d = .66, P = .013), reflecting reduced phase reset of ongoing theta-alpha band activity (d = .74, P = .019). In turn, P1f deficits significantly predicted increased saccade number both across groups (P = .017) and within SzP alone (P = .042). Computational and neurophysiological methods provide increasingly important approaches for investigating sensory contributions to impaired cognition during naturalistic processing in Sz. Here, we demonstrate deficits in reading rate that reflect both sensory/oculomotor- and semantic-level impairments and that manifest, respectively, as alterations in saccade number and fixation duration. Impaired P1f generation reflects impaired fixation-related reset of ongoing brain rhythms and suggests inefficient information processing within the early visual system as a basis for oculomotor dyscontrol during fluent reading in Sz.

Emotional instability as a trait risk factor for eating disorder behaviors in adolescents: Sex differences in a large-scale prospective study.

BACKGROUND: Temperament and personality traits, including negative emotionality/neuroticism, may represent risk factors for eating disorders. Further, risk factors may differ by sex. We examined longitudinal temperament/personality pathways of risk for purging and binge eating in youth stratified by sex using data from a large-scale prospective study. METHODS: Temperament, borderline personality features, sensation seeking, 'big five' personality factors, and depressive symptoms were measured at five time points from early childhood to adolescence in 5812 adolescents (3215 females; 2597 males) in the Avon Longitudinal Study of Parents and Children. We conducted univariate analyses with these predictors of binge eating and purging at 14 and 16 years for total and sex-stratified samples. We used structural equation modeling (SEM) to fit data to a path analysis model of hypothesized associations. RESULTS: Of the total sample, 12.54% engaged in binge eating and 7.05% in purging by 16 years. Prevalence was much greater and increased dramatically for females from 14 years (7.50% binge eating; 2.40% purging) to 16 years (15.80% binge eating; 9.50% purging). For both sexes, borderline personality, depressive symptoms and lower emotional stability predicted eating disorder behaviors; sensation seeking and conscientiousness were also significant predictors for females. SEM identified an 'emotional instability' pathway for females from early childhood into adolescence (RMSEA = 0.025, TLI = 0.937 and CFI = 0.970). CONCLUSIONS: Binge eating and purging are common in female and male adolescents. Early temperament/personality factors related to difficulty regulating emotions were predictive of later adolescent eating disorder behaviors. Results have important clinical implications for eating disorder prevention and intervention.

Glucose elicits cephalic-phase insulin release in mice by activating KATP channels in taste cells.

The taste of sugar elicits cephalic-phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647, or a nonmetabolizable sugar analog. The only taste stimuli that elicited CPIR were glucose and the glucose-containing saccharides (sucrose, maltose, Polycose). When we mixed an α-glucosidase inhibitor (acarbose) with the latter three saccharides, the mice no longer exhibited CPIR. This revealed that the carbohydrates were hydrolyzed in the mouth, and that the liberated glucose triggered CPIR. We also found that increasing the intensity or duration of oral glucose stimulation caused a corresponding increase in CPIR magnitude. To identify the components of the glucose-specific taste-signaling pathway, we examined the necessity of Calhm1, P2X2+P2X3, SGLT1, and Sur1. Among these proteins, only Sur1 was necessary for CPIR. Sur1 was not necessary, however, for taste-mediated attraction to sugars. Given that Sur1 is a subunit of the ATP-sensitive K+ channel (KATP) channel and that this channel functions as a part of a glucose-sensing pathway in pancreatic ß-cells, we asked whether the KATP channel serves an analogous role in taste cells. We discovered that oral stimulation with drugs known to increase (glyburide) or decrease (diazoxide) KATP signaling produced corresponding changes in glucose-stimulated CPIR. We propose that the KATP channel is part of a novel signaling pathway in taste cells that mediates glucose-induced CPIR.