Dynamic functional connectivity in anorexia nervosa: alterations in states of low connectivity and state transitions.

BACKGROUND: The onset of anorexia nervosa (AN) frequently occurs during adolescence and is associated with preoccupation with body weight and shape and extreme underweight. Altered resting state functional connectivity in the brain has been described in individuals with AN, but only from a static perspective. The current study investigated the temporal dynamics of functional connectivity in adolescents with AN and how it relates to clinical features. METHOD: 99 female patients acutely ill with AN and 99 pairwise age-matched female healthy control (HC) participants were included in the study. Using resting-state functional MRI data and an established sliding-window analytic approach, we identified dynamic resting-state functional connectivity states and extracted dynamic indices such as dwell time (the duration spent in a state), fraction time (the proportion of the total time occupied by a state), and number of transitions (number of switches) from one state to another, to test for group differences. RESULTS: Individuals with AN had relatively reduced fraction time in a mildly connected state with pronounced connectivity within the default mode network (DMN) and an overall reduced number of transitions between states. CONCLUSIONS: These findings revealed by a dynamic, but not static analytic approach might hint towards a more "rigid" connectivity, a phenomenon commonly observed in internalizing mental disorders, and in AN possibly related to a reduction in energetic costs as a result of nutritional deprivation.

Dynamic Changes in Local Brain Connectivity and Activity: A Longitudinal Study in Adolescent Anorexia Nervosa.

BACKGROUND: Resting-state functional connectivity analysis has been used to study disruptions in neural circuitries underlying eating disorder symptoms. Research has shown resting-state functional connectivity to be altered during the acute phase of anorexia nervosa (AN), but little is known about the biological mechanisms underlying neural changes associated with weight restoration. The goal of the current study was to investigate longitudinal changes in regional homogeneity (ReHo) among neighboring voxels, degree centrality (DC) (a voxelwise whole brain correlation coefficient), voxel-mirrored homotopic connectivity (VMHC) (measuring the synchronization between hemispheres), and the fractional amplitude of low-frequency fluctuations associated with weight gain during AN treatment. METHODS: Resting-state functional connectivity data were acquired and analyzed from a sample of 174 female volunteers: 87 underweight patients with AN that were scanned before treatment and again after at least 12% body mass index increase, as well as 87 age-matched healthy control participants. RESULTS: Longitudinal changes in ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations were observed in most regions identified to differ between patients with AN before treatment and healthy control participants. However, the degree of normalization varied for each parameter, ranging from 9% of all clusters in DC to 66% in VMHC. Longitudinal changes in ReHo and VMHC showed a linear association weight gain. CONCLUSIONS: Resting-state functional magnetic resonance imaging measures, including ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations, show varying degrees of recovery after short-term weight restoration. Although only some of these changes were related to weight gain, our results provide an overall positive message, suggesting that weight restoration is associated with changes in functional brain measures that point toward normalization.

Mouse-cursor trajectories reveal reduced contextual influence on decision conflict during delay discounting in anorexia nervosa.

OBJECTIVE: The capacity of individuals with anorexia nervosa (AN) to forgo immediate food rewards in their long-term pursuit of thinness is thought to reflect elevated self-control and/or abnormal reward sensitivity. Prior research attempted to capture an increased tendency to delay gratification in AN using delay-discounting tasks that assess how rapidly the subjective value of rewards decreases as a function of time until receipt. However, significant effects were mostly subtle or absent. Here, we tested whether the process leading to such decisions might be altered in AN. METHOD: We recorded mouse-cursor movement trajectories leading to the final choice in a computerized delay-discounting task (238 trials) in 55 acutely underweight females with AN and pairwise age-matched female healthy controls (HC). We tested for group differences in deviations from a direct choice path, a measure of conflict strength in decision making, and whether group moderated the effect of several predictors of conflict strength (e.g., choice difficulty, consistency). We also explored reaction times and changes in trajectory directions (X-flips). RESULTS: No group differences in delay-discounting parameters or movement trajectories were detected. However, the effect of the aforementioned predictors on deviations (and to a lesser extent reaction times) was reduced in AN. DISCUSSION: These findings suggest that while delay discounting and conflict strength in decision making are generally unaltered in AN, conflict strength was more stable across different decisions in the disorder. This might enable individuals with AN to pursue (maladaptive) long-term body-weight goals, because particularly conflicting choices may not be experienced as such. PUBLIC SIGNIFICANCE: The deviations from a direct path of mouse-cursor movements during a computerized delay-discounting task varied less in people with anorexia nervosa. Assuming such deviations measure decision conflict, we speculate that this increased stability might help people with anorexia nervosa achieve their long-term weight goals, as for them the struggle with the decision to eat high-calorie meals when hungry will be milder, so they would be more likely to skip them.

Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN. METHODS: Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n = 147). RESULTS: In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected. CONCLUSIONS: A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.

Increased Habit Frequency in the Daily Lives of Patients with Acute Anorexia Nervosa.

Strict eating routines and frequent rigid behavior patterns are commonly observed in patients with anorexia nervosa (AN). A recent theory proposes that while these behaviors may have been reinforced initially, they later become habitual. To date, however, research has been overly focused on eating-disorder (ED)-related habits. Over the course of seven days, we applied an ecological momentary assessment (EMA) to investigate the habit frequency and strength of ED-specific (food intake) and ED-unspecific (hygiene) habits in the daily lives of a sample of n = 57 AN and n = 57 healthy controls (HC). The results of the hierarchical models revealed that habits were significantly more likely in patients compared with HC for both categories, independently. Furthermore, a lower body mass index (BMI) was associated with increased habit frequency in AN. Our study strengthens the habit theory of AN by showing the relevance of habits beyond ED-specific behavioral domains. This also supports the development of innovative therapeutic interventions targeting habitual behavior in EDs.

Real-life self-control conflicts in anorexia nervosa: An ecological momentary assessment investigation.

BACKGROUND: Individuals with anorexia nervosa (AN) are often thought to show heightened self-control and increased ability to inhibit desires. In addition to inhibitory self-control, antecedent-focused strategies (e.g., cognitive reconstrual-the re-evaluation of tempting situations) might contribute to disorder maintenance and enable disorder-typical, maladaptive behaviors. METHODS: Over a period of 14 days, 40 acutely underweight young female patients with anorexia nervosa (AN) and 40 healthy control (HC) participants reported their affect and behavior in self-control situations via ecological momentary assessment during inpatient treatment (AN) and everyday life (HC). Data were analyzed via hierarchical analyses (linear and logistic modeling). RESULTS: Conflict strength had a significantly lower impact on self-control success in AN compared to HC. While AN and HC did not generally differ in the number or strength of self-control conflicts or in the percentage of self-control success, AN reported self-controlled behavior to be less dependent on conflict strength. CONCLUSIONS: While patients with AN were not generally more successful at self-control, they appeared to resolve self-control conflicts more effectively. These findings suggest that the magnitude of self-control conflicts has comparatively little impact on individuals with AN, possibly due to the use of antecedent-focused strategies. If confirmed, cognitive-behavioral therapy might focus on and help patients to exploit these alternative self-control strategies in the battle against their illness.

Combining day treatment and outpatient treatment for eating disorders: findings from a naturalistic setting.

BACKGROUND: Day treatment programs for individuals with eating disorders (ED) have been the subject of research and are promoted as an alternative to inpatient treatment due to their therapeutic and economic advantages, but have not regularly been implemented in regular care. PURPOSE: We investigated the long-term effectiveness of a transdiagnostic combined eating disorder treatment program which consisted of an 8-week day treatment phase followed by an average of 19 sessions of outpatient treatment over an average of 39 weeks in a naturalistic setting. METHODS: We accepted 148 patients with different diagnoses of eating disorders into our combined treatment program. We assessed weight, behavioral eating disorder symptoms and eating disorder related cognitions and attitudes at the beginning and the end of the day treatment phase and after 6, 12 and 26 months. RESULTS: Over the course of the 8-week day treatment phase, patients with initial binge eating, purging and/or fasting behavior reduced these symptoms by 91%, 90% and, 86%. Patients who were underweight at baseline gained on average 1.05 BMI points (d = 0.76). In addition, eating disorder related cognitions and attitudes of all patients significantly improved with large effect sizes (d = 1.12). On average, all improvements remained stable during the follow-up period. CONCLUSIONS: Our findings add to the existing studies on day treatment and support previously found encouraging effects of treatment programs that combine day treatment and consecutive outpatient treatment for eating disorders. LEVEL OF EVIDENCE: Level III, longitudinal cohort study.