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.

Intact neural and behavioral correlates of emotion processing and regulation in weight-recovered anorexia nervosa: a combined fMRI and EMA study.

Altered emotion processing and regulation mechanisms play a key role in eating disorders. We recently reported increased fMRI responses in brain regions involved in emotion processing (amygdala, dorsolateral prefrontal cortex) in acutely underweight anorexia nervosa (AN) patients while passively viewing negatively valenced images. We also showed that patients' ability to downregulate activity elicited by positively valenced pictures in a brain region involved in reward processing (ventral striatum) was predictive of worse outcomes (increased rumination and negative affect). The current study tries to answer the question of whether these alterations are only state effects associated with undernutrition or whether they constitute a trait characteristic of the disorder that persists after recovery. Forty-one individuals that were weight-recovered from AN (recAN) and 41 age-matched healthy controls (HC) completed an established emotion regulation paradigm using negatively and positively valenced visual stimuli. We assessed behavioral (arousal) and fMRI measures (activity in the amygdala, ventral striatum, and dorsolateral prefrontal cortex) during emotion processing and regulation. Additionally, measures of disorder-relevant rumination and affect were collected several times daily for 2 weeks after scanning via ecological momentary assessment. In contrast to our previous findings in acute AN patients, recAN showed no significant alterations either on a behavioral or neural level. Further, there were no associations between fMRI responses and post-scan momentary measures of rumination and affect. Together, these results suggest that neural responses to emotionally valenced stimuli as well as relationships with everyday rumination and affect likely reflect state-related alterations in AN that improve following successful weight-recovery.

The costs of over-control in anorexia nervosa: evidence from fMRI and ecological momentary assessment.

A growing body of evidence suggests that a high level of self-control may, despite its positive effects, influence cognitive processing in an unfavorable manner. However, the affective costs of self-control have only rarely been investigated. Anorexia nervosa (AN) is an eating disorder that is often characterized by excessive self-control. Here, we used fMRI to explore whether over-control in AN may have negative affective consequences. 36 predominantly adolescent female AN patients and 36 age-matched healthy controls (HC) viewed negative and neutral pictures during two separate fMRI sessions before and after 10 min of rest. We tested whether abnormally elevated neural activity during the initial presentation in a brain region broadly implicated in top-down control, the dorsolateral prefrontal cortex (dlPFC), could predict subsequent activation in limbic areas relevant to bottom-up affective processing. Using ecological momentary assessment (EMA), we also tested for associations between the aforementioned neuroimaging markers and negative affective states in the two weeks following the experiment. fMRI data revealed that higher initial activation of the dlPFC in AN predicted increased amygdala reactivity during the second fMRI session, which in turn was related to increased self-reported tension during two weeks following the scan. These data suggest that over-control in AN patients may come at a cost including negative affective states on a short (minutes) as well as a longer time scale (days). This mechanism may significantly contribute to the persistence of AN.

Differential longitudinal changes of neuronal and glial damage markers in anorexia nervosa after partial weight restoration.

Atrophic brain changes in acute anorexia nervosa (AN) are often visible to the naked eye on computed tomography or magnetic resonance imaging scans, but it remains unclear what is driving these effects. In neurological diseases, neurofilament light (NF-L) and tau protein have been linked to axonal damage. Glial fibrillary acidic protein (GFAP) has been associated with astroglial injury. In an attempt to shed new light on factors potentially underlying past findings of structural brain alterations in AN, the current study investigated serum NF-L, tau protein, and GFAP levels longitudinally in AN patients undergoing weight restoration. Blood samples were obtained from 54 acutely underweight, predominantly adolescent female AN patients and 54 age-matched healthy control participants. AN patients were studied in the severely underweight state and again after short-term partial weight restoration. Group comparisons revealed higher levels of NF-L, tau protein, and GFAP in acutely underweight patients with AN compared to healthy control participants. Longitudinally, a decrease in NF-L and GFAP but not in tau protein levels was observed in AN patients upon short-term partial weight restoration. These results may be indicative of ongoing neuronal and astroglial injury during the underweight phase of AN. Normalization of NF-L and GFAP but not tau protein levels may indicate an only partial restoration of neuronal and astroglial integrity upon weight gain after initial AN-associated cell damage processes.

Intact value-based decision-making during intertemporal choice in women with remitted anorexia nervosa? An fMRI study

Background: Extreme restrictive food choice in anorexia nervosa is thought to reflect excessive self-control and/or abnormal reward sensitivity. Studies using intertemporal choice paradigms have suggested an increased capacity to delay reward in anorexia nervosa, and this may explain an unusual ability to resist immediate temptation and override hunger in the long-term pursuit of thinness. It remains unclear, however, whether altered delay discounting in anorexia nervosa constitutes a state effect of acute illness or a trait marker observable after recovery. Methods: We repeated the analysis from our previous fMRI investigation of intertemporal choice in acutely underweight patients with anorexia nervosa in a sample of weight-recovered women with anorexia nervosa (n = 36) and age-matched healthy controls (n = 36) who participated in the same study protocol. Follow-up analyses explored functional connectivity separately in both the weight-recovered/healthy controls sample and the acute/healthy controls sample. Results: In contrast to our previous findings in acutely underweight patients with anorexia nervosa, we found no differences between weight-recovered patients with anorexia nervosa and healthy controls at either behavioural or neural levels. New analysis of data from the acute/healthy controls sample sample revealed increased coupling between dorsal anterior cingulate cortex and posterior brain regions as a function of decision difficulty, supporting the hypothesis of altered neural efficiency in the underweight state. Limitations: This was a cross-sectional study, and the results may be task-specific. Conclusion: Although our results underlined previous demonstrations of divergent temporal reward discounting in acutely underweight patients with anorexia nervosa, we found no evidence of alteration in patients with weight-recovered anorexia nervosa. Together, these findings suggest that impaired valuebased decision-making may not constitute a defining trait variable or "scar" of the disorder.

Differential Impact of Emotion on Semantic Processing of Abstract and Concrete Words: ERP and fMRI Evidence.

Emotional valence is known to influence word processing dependent upon concreteness. Whereas some studies point towards stronger effects of emotion on concrete words, others claim amplified emotion effects for abstract words. We investigated the interaction of emotion and concreteness by means of fMRI and EEG in a delayed lexical decision task. Behavioral data revealed a facilitating effect of high positive and negative valence on the correct processing of abstract, but not concrete words. EEG data yielded a particularly low amplitude response of the late positive component (LPC) following concrete neutral words. This presumably indicates enhanced allocation of processing resources to abstract and emotional words at late stages of word comprehension. In fMRI, interactions between concreteness and emotion were observed within the semantic processing network: the left inferior frontal gyrus (IFG) and the left middle temporal gyrus (MTG). Higher positive or negative valence appears to facilitate semantic retrieval and selection of abstract words. Surprisingly, a reversal of this effect occurred for concrete words. This points towards enhanced semantic control for emotional concrete words compared to neutral concrete words. Our findings suggest fine-tuned integration of emotional valence and concreteness. Specifically, at late processing stages, semantic control mechanisms seem to integrate emotional cues depending on the previous progress of semantic retrieval.

Abnormal Spontaneous Regional Brain Activity in Young Patients With Anorexia Nervosa.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies have repeatedly shown alterations in patients with anorexia nervosa (AN). These alterations might be driven by baseline signal characteristics such as the (fractional) amplitude of low frequency fluctuations (fALFF/ALFF), as well as regional signal consistency (ie, regional homogeneity [ReHo]) within circumscribed brain regions. Previous studies have also demonstrated gray matter (pseudo-) atrophy in underweight individuals with AN. Here we study fALFF/ALFF and ReHo in predominantly adolescent patients with AN, while taking gray matter changes into consideration. METHOD: Resting state fMRI data were acquired from a sample of 148 female volunteers: 74 underweight patients with AN and 74 age-matched female healthy controls (HC). RESULTS: Group differences for fALFF and ReHo measures were found in several AN-relevant brain regions, including networks related to cognitive control, habit formation, and the ventral visual stream. Furthermore, the magnitude of correlation between gray matter volume/thickness and fALFF and ReHo were reduced in AN compared to HC. CONCLUSION: Abnormal local resting state characteristics in AN-related brain-networks as well as reduced structure-function relationships may help to explain previously reported task-related and classical resting state neural alterations in underweight AN. Patients with AN may serve as a valuable population for investigating dynamic changes in the relationships between brain structure and function.

Processing and regulation of negative emotions in anorexia nervosa: An fMRI study.

Theoretical models and recent advances in the treatment of anorexia nervosa (AN) have increasingly focused on the role of alterations in the processing and regulation of emotions. To date, however, our understanding of these changes is still limited and reports of emotional dysregulation in AN have been based largely on self-report data, and there is a relative lack of objective experimental evidence or neurobiological data. The current functional magnetic resonance imaging (fMRI) study investigated the hemodynamic correlates of passive viewing and voluntary downregulation of negative emotions by means of the reappraisal strategy detachment in AN patients. Detachment is regarded as adaptive regulation strategy associated with a reduction in emotion-related amygdala activity and increased recruitment of prefrontal brain regions associated with cognitive control processes. Emotion regulation efficacy was assessed via behavioral arousal ratings and fMRI activation elicited by an established experimental paradigm including negative images. Participants were instructed to either simply view emotional pictures or detach themselves from feelings triggered by the stimuli. The sample consisted of 36 predominantly adolescent female AN patients and a pairwise age-matched healthy control group. Behavioral and neuroimaging data analyses indicated a reduction of arousal and amygdala activity during the regulation condition for both patients and controls. However, compared with controls, individuals with AN showed increased activation in the amygdala as well as in the right dorsolateral prefrontal cortex (dlPFC) during the passive viewing of aversive compared with neutral pictures. These results extend previous findings indicative of altered processing of salient emotional stimuli in AN, but do not point to a general deficit in the voluntary regulation of negative emotions. Increased dlPFC activation in AN during passive viewing of negative stimuli is in line with the hypothesis that the disorder may be characterized by excessive self-control. Taken together, the data seem to suggest that reappraisal via detachment may be an effective strategy to reduce negative arousal for individuals with AN.