Altered functional connectivity in binge eating disorder and bulimia nervosa: A resting-state fMRI study.

INTRODUCTION: The etiology of bulimic-type eating (BTE) disorders such as binge eating disorder (BED) and bulimia nervosa (BN) is still largely unknown. Brain networks subserving the processing of rewards, emotions, and cognitive control seem to play a crucial role in the development and maintenance of eating disorders. Therefore, further investigations into the neurobiological underpinnings are needed to discern abnormal connectivity patterns in BTE disorders. METHODS: The present study aimed to investigate functional as well as seed-based connectivity within well-defined brain networks. Twenty-seven individuals with BED, 29 individuals with BN, 28 overweight, and 30 normal-weight control participants matched by age, gender, and education underwent resting-state functional magnetic resonance imaging. Functional connectivity was assessed by spatial group independent component analysis and a seed-based correlation approach by examining the default mode network (DMN), salience network (SN), and executive network (EN). RESULTS: Group comparisons revealed that BTE disorder patients exhibit aberrant functional connectivity in the dorsal anterior cingulate cortex (dACC) within the SN, as well as in the medial prefrontal cortex within the DMN. Furthermore, BED and BN groups differed from each other in functional connectivity within each network. Seed-based correlational analysis revealed stronger synchronous dACC-retrosplenial cortex activity in the BN group. CONCLUSION: Our findings demonstrate abnormalities in brain networks involved in salience attribution, self-referential processing, and cognitive control in bulimic-type eating disorders. Together with our observation of functional connectivity differences between BED and BN, this study offers a differentiated account of both similarities and differences regarding brain connectivity in BED and BN.

Blunted emotion-modulated startle reflex in anorexia nervosa.

OBJECTIVE: Patients with anorexia nervosa (AN) often show difficulties in the perception, expression, and regulation of emotions and a strong avoidance of aversive feelings. According to psychobiological models, dietary restraint and accompanying weight loss may serve as a maladaptive mechanism of emotion regulation by attenuating aversive emotional states in AN, thereby contributing to the maintenance of the disorder. METHOD: Twenty-seven women with AN and 26 age-matched healthy women were shown short film-clips to elicit fear, sadness, amusement, and neutral emotional states. Eyeblink startle response was measured by electromyography in reaction to startle-eliciting acoustic stimuli presented 12 times binaurally during each film-clip. RESULTS: As compared to healthy controls, patients with AN showed a blunted startle response to the fear- but not to the sadness-eliciting stimulus. DISCUSSION: The findings support the assumption that underweight is associated with attenuated emotional reactivity to fear-eliciting material in AN. This is in line with the hypothesis that starvation and low body weight constitute a maladaptive mechanism of emotion regulation in AN, contributing to the maintenance of the disorder.

Emotional responses to receiving peer feedback on opinions in borderline personality disorder.

Although emotional reactivity to social rejection has been examined in patients with borderline personality disorder (BPD) in several studies, the effects of other aspects of social feedback, such as evaluation of one's opinions that concern self-esteem, have not been addressed yet. The objective of this study was to examine emotional responses of BPD patients after exchanging personal opinions in a new, ecologically valid virtual peer interaction paradigm ("chatroom paradigm"). In this paradigm, 21 BPD patients and 21 healthy controls received peer feedback on their own statements and rated the intensity of their own emotional responses (happiness, sadness, anger, and shame) and the self or other affirmation in response to agreement, disagreement, and neutral statements. Across all social feedback conditions, BPD patients reported more intense negative emotions and less happiness than healthy controls. While healthy controls showed a "positivity bias" for any type of social feedback, the emotional responses of BPD patients' corresponded to the valence of the feedback; that is, they were happiest after positive than after neutral feedback and least happy after negative feedback. Disagreement resulted in more intense anger and less other affirmation in both groups but only BPD patients also experienced higher shame in this condition. This is the first study to assess emotional responses to social feedback in an ecologically valid chatroom paradigm. Our findings underline that more negative emotional reactions in everyday interactions play a central part in interpersonal difficulties of patients with BPD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Neural signature of behavioural inhibition in women with bulimia nervosa.

BACKGROUND: Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. METHODS: Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. RESULTS: We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). LIMITATIONS: The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. CONCLUSION: Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.

Attentional Lapses of Adults with Attention Deficit Hyperactivity Disorder in Tasks of Sustained Attention.

Adults with attention deficit hyperactivity disorder (ADHD) show attentional dysfunction such as distractibility and mind-wandering, especially in lengthy tasks. However, fundamentals of dysfunction are ambiguous and relationships of neuropsychological test parameters with self-report measures of ADHD symptoms are marginal. We hypothesize that basic deficits in sustaining attention explain more complex attentional dysfunction in persons with ADHD and relate to ADHD symptoms. Attentional function was analyzed by computing ex-Gaussian parameters for 3 time Blocks in a 20 min test of sustained alertness. Changes in performance across these blocks were analyzed by comparing adult persons with ADHD (n = 24) with healthy matched controls (n = 24) and correlated with neuropsychological measures of selective and divided attention as well as self-report measures of ADHD symptoms. We found a significantly steeper increase in the number of slow responses (ex-Gaussian parameter τ) in persons with ADHD with time on task in basic sustained alertness. They also performed significantly worse in tasks of sustained selective and divided attention. However, after controlling for an increase in τ during the alertness task, significant differences between groups disappeared for divided and partly selective attention. Increases in τ in the sustained alertness task correlated significantly with self-report measures of ADHD symptoms. Our results provide evidence that very basic deficits in sustaining attention in adults with ADHD are related to infrequent slow responses (=attentional lapses), with changes over time being relevant for more complex attentional function and experienced ADHD symptoms in everyday life.

Neural signature of food reward processing in bulimic-type eating disorders.

Clinical observations and similarities to addiction suggest heightened reward sensitivity to food in patients with bulimic-type eating (BTE) disorders. Therefore, we investigated the expectation and receipt of food reward compared with monetary reward in patients with BTE. Fifty-six patients with BTE (27 patients with binge eating disorder and 29 with bulimia nervosa) and 55 matched healthy control participants underwent event-related functional magnetic resonance imaging while performing both food and monetary incentive delay tasks. BTE patients exhibited reduced brain activation in the posterior cingulate cortex during the expectation of food and increased activity in the medial orbitofrontal cortex, anterior medial prefrontal cortex and posterior cingulate cortex during the receipt of food reward. These findings were relevant to food because we found no significant group differences related to monetary reward. In the patients, higher brain activity in the medial orbitofrontal cortex during the receipt of food reward was related to higher levels of trait food craving and external eating. BTE patients exhibited increased hedonic processing during the receipt of food reward. These findings corroborate the notion that an altered responsiveness of the reward network to food stimuli is associated with BTE.

Brain effects of computer-assisted cognitive remediation therapy in anorexia nervosa: A pilot fMRI study.

Poor cognitive-behavioral flexibility is considered a trait marker in anorexia nervosa (AN) that can be improved by cognitive remediation therapy (CRT). The present pilot study aimed at identifying changes in brain function potentially associated with CRT in AN. Data was obtained from a randomized, controlled trial. Twenty-four patients were assessed before and after 30 sessions of either CRT or a non-specific neurocognitive therapy. Voxel-wise analysis of whole brain functional magnetic resonance imaging was applied. Brain activation was measured during response inhibition and task switching. Although results did not reach significance, we found tentative support for CRT-related increases in brain activation in the dorsal putamen during task switching and in the dorsolateral prefrontal, sensorimotor and temporal cortex during response inhibition. These pilot findings provide viable pathways for future research on brain changes underlying CRT in AN.

Intraindividual variability in inhibitory function in adults with ADHD--an ex-Gaussian approach.

OBJECTIVE: Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses. METHODS: Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education. RESULTS: We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors. CONCLUSIONS: Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological testing in aADHD.

Training cognitive flexibility in patients with anorexia nervosa: a pilot randomized controlled trial of cognitive remediation therapy.

OBJECTIVE: Inefficient cognitive flexibility is considered a neurocognitive trait marker involved in the development and maintenance of anorexia nervosa (AN). Cognitive Remediation Therapy (CRT) is a specific treatment targeting this cognitive style. The aim of this study was to investigate the feasibility and efficacy (by estimating the effect size) of specifically tailored CRT for AN, compared to non-specific cognitive training. METHOD: A prospective, randomized controlled, superiority pilot trial was conducted. Forty women with AN receiving treatment as usual (TAU) were randomized to receive either CRT or non-specific neurocognitive therapy (NNT) as an add-on. Both conditions comprised 30 sessions of computer-assisted (21 sessions) and face-to-face (9 sessions) training over a 3-week period. CRT focused specifically on cognitive flexibility. NNT was comprised of tasks designed to improve attention and memory. The primary outcome was performance on a neuropsychological post-treatment assessment of cognitive set-shifting. RESULTS: Data available from 25 treatment completers were analyzed. Participants in the CRT condition outperformed participants in the NNT condition in cognitive set-shifting at the end of the treatment (p = 0.027; between-groups effect size d = 0.62). Participants in both conditions showed high treatment acceptance. DISCUSSION: This study confirms the feasibility of CRT for AN, and provides a first estimate of the effect size that can be achieved using CRT for AN. Furthermore, the present findings corroborate that neurocognitive training for AN should be tailored to the specific cognitive inefficiencies of this patient group.

Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder.

OBJECTIVE: Patients with borderline personality disorder are characterized by emotional hyperarousal with increased stress levels, anger proneness, and hostile, impulsive behaviors. They tend to ascribe anger to ambiguous facial expressions and exhibit enhanced and prolonged reactions in response to threatening social cues, associated with enhanced and prolonged amygdala responses. Because the intranasal administration of the neuropeptide oxytocin has been shown to improve facial recognition and to shift attention away from negative social information, the authors investigated whether borderline patients would benefit from oxytocin administration. METHOD: In a randomized placebo-controlled double-blind group design, 40 nonmedicated, adult female patients with a current DSM-IV diagnosis of borderline personality disorder (two patients were excluded based on hormonal analyses) and 41 healthy women, matched on age, education, and IQ, took part in an emotion classification task 45 minutes after intranasal administration of 26 IU of oxytocin or placebo. Dependent variables were latencies and number or initial reflexive eye movements measured by eye tracking, manual response latencies, and blood-oxygen-level-dependent responses of the amygdala to angry and fearful compared with happy facial expressions. RESULTS: Borderline patients exhibited more and faster initial fixation changes to the eyes of angry faces combined with increased amygdala activation in response to angry faces compared with the control group. These abnormal behavioral and neural patterns were normalized after oxytocin administration. CONCLUSIONS: Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing. Oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression.

Event-related potentials during recognition of semantic and pictorial food stimuli in patients with anorexia nervosa and healthy controls with varying internal states of hunger.

OBJECTIVE: To elucidate maladaptive central processing of food cues during recognition tasks in anorexia nervosa (AN), while considering influences of nutritional preload and presentation modality (word versus picture). METHODS: Event-related potentials to food-related word and pictorial stimuli were assessed during recognition tasks in 16 patients with AN, 16 control participants with food intake before the study, and 16 control participants with a fasting period before the study. RESULTS: Patients with AN showed a P3b amplitude reduction especially at the midline parietal site compared with satiated controls (5.7 [standard deviation = 3.3] versus 8.7 [3.1] µV, p < .03). Subtle recognition deficits in patients with AN were indicated by smaller "old/new" effects compared with satiated (p = .049) and fasting controls (p < .003) for pictorial stimuli. Hunger-modulated enhanced old/new effects for food pictures compared with neutral pictorial stimuli could be observed in fasting controls only (2.7 [2.6] versus 0.8 [2.2] µV, p < .01). CONCLUSIONS: The presented data provide evidence for a midline parietal P3b amplitude reduction in patients with AN, which might point to reduced network activation in AN even during satiety. Observed subtle recognition deficits either represent a stable trait characteristic or a "scar" effect of chronic starvation that may play a role in the development and/or persistence of the disorder.

Grey matter abnormalities within cortico-limbic-striatal circuits in acute and weight-restored anorexia nervosa patients.

Functional disturbances within cortico-striatal control systems have been implicated in the psychobiology (i.e. impaired cognitive-behavioral flexibility, perfectionist personality) of anorexia nervosa. The aim of the present study was to investigate the morphometry of brain regions within cortico-striatal networks in acute anorexia nervosa (AN) as well as long-term weight-restored anorexia nervosa (AN-WR) patients. A total of 39 participants: 12 AN, 13 AN-WR patients, and 14 healthy controls (HC) underwent high-resolution, T1-weighted magnetic resonance imaging (MRI), a cognitive-behavioral flexibility task, and a psychometric assessment. Group differences in local grey matter volume (GMV) were analyzed using whole brain voxel-based morphometry (VBM) and brain-atlas based automatic volumetry computation (IBASPM). Individual differences in total GMV were considered as a covariate in all analyses. In the regional brain morphometry, AN patients, as compared to HC, showed decreased GMVs (VBM and volumetry) in the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and in subcortical regions (amygdala, putamen: VBM only). AN-WR compared to HC showed decreased GMV (VBM and volumetry) in the ACC and SMA, whereas GMV of the subcortical region showed no differences. The findings of the study suggest that structural abnormalities of the ACC and SMA were independent of the disease stage, whereas subcortical limbic-striatal changes were state dependent.

Response inhibition or salience detection in the right ventrolateral prefrontal cortex?

This study addresses the question of whether frontal activation in response-inhibition tasks is specifically associated with the suppression of a motor response. An alternative model suggests a role in the detection of behaviorally relevant or salient events. For this purpose, we used functional MRI with an auditory go/no-go paradigm. This paradigm allowed the disentangling of inhibition-related from salience-related effects, which were associated with different frontal regions. Importantly, the right ventrolateral prefrontal cortex consistently showed sensitivity for salience but not for inhibition requirements. This reflects a more general salience-detection mechanism, which is not specific for response-inhibition tasks.

Temporal variability and spatial diffusion of the N2 event-related potential in high-functioning patients with schizophrenia.

Recent theories of schizophrenia have proposed a fundamental instability of information processing on a neurophysiological level, which can be measured as an increase in latency variability of event-related potentials (ERPs). If this reflects a fundamental deficit of the schizophrenic illness, it should also occur in high-functioning patients. These patients have also been observed to show a more diffuse activation pattern in neuroimaging studies, which is thought to reflect compensatory processes to maintain task performance. In the present study we investigated temporal variability and spatial diffusion of the visual N2 component in a group of high-functioning patients with preserved cognitive performance. 28 patients with schizophrenia and 28 control participants matched for gender, age and education participated in the study. Subjects performed a visual Go/Nogo task, while event-related potentials were obtained. Trial-to-trial latency variability was calculated with a Wavelet-based method. Patients with schizophrenia showed a robust increase in N2 latency variability at electrodes Fz and Cz in all task conditions. Regarding spatial distribution healthy participants showed a focused fronto-central N2 peak. In contrast, patients with schizophrenia showed a more diffuse pattern and additional negative peaks over lateral electrodes in the Nogo condition. These results clearly show that even in high-functioning patients with schizophrenia a higher temporal variability of ERPs can be observed. This provides support for temporal instability of information processing as a fundamental deficit associated with schizophrenia. The more diffuse scalp distribution might reflect processes that compensate for this instability when cognitive control is required.

Development of brain synchronisation within school-age--individual analysis of resting (α) coherence in a longitudinal data set.

OBJECTIVE: Given evidence that synchronisation of neuronal activity may be a correlate of cognition, we examined EEG coherence as function of age and inter-electrode distance in healthy children and adolescents in order to elucidate basic information for a better understanding of developmental disorders associated with deficits in cognitive functions. METHODS: Based on a 64-channel eyes closed resting EEG we combined local and global coherence measures in order to reduce volume conduction and reference effects. We used a two point longitudinal design in order to analyze intraindividual change during school-age (n=40; 6-18 years). Coherence was analyzed within individually adjusted frequency bands and around iPF (= individual alpha peak frequency). RESULTS: Both local and global resting coherence was largest in the alpha range and particularly around iPF. Local synchronisation was larger in the left compared with the right hemisphere. Controlling for increases in iPF, synchronisation increased with age, with global changes being most pronounced in the alpha range. Moreover age-related changes suggest an earlier development in girls. CONCLUSIONS: Our data provides evidence that both local and global functional integration increases during normal development within school-age. SIGNIFICANCE: This general pattern - combined with more specific effects of sex and frequency - may help to specify deviations in developmental disorders.

Individual analysis of EEG background-activity within school age: impact of age and sex within a longitudinal data set.

OBJECTIVES: Quantitative EEG can monitor changes in brain function during development and may help to understand developmental disorders. However, current EEG-databases are primarily based on standardized frequency bands which disregard age-related changes in alpha peak frequency (PF) and therefore complicate the interpretation of spectral estimates in the theta and alpha range. METHODS: We used a two point longitudinal design in order to analyze intraindividual changes in 40 healthy children and adolescents with age (T1: 6-18 years; interval approximately 4 years). Using a 64-channel eyes closed resting EEG we calculated absolute/relative power in individualized frequency bands (IFB: delta, theta, alpha1/2 and beta) based on PF. RESULTS: PF increased with age, with changes being larger for children than adolescents. Controlling for changes in PF, changes in absolute/relative alpha1/2 power and in absolute beta power were minor. Relative beta power, however, increased while absolute/relative delta and theta power decreased massively. Sex-differences in PF did not reach significance. However, boys exhibited larger changes during adolescence than girls for all absolute power measures except alpha. CONCLUSION: Normal EEG development during school-age is mainly based on an absolute decrease of slow frequency activity and increases of PF which may be interpreted in terms of a reorganization of the EEG towards a higher frequency oscillatory scale rather than a maturation of the theta-alpha1/2 band power sequence. Age-related changes differed between boys and girls suggesting a different developmental timing for the sexes. In future studies a combined analysis of PF and IFB may help to specify deviations in developmental disorders.

Motor impulsivity and the ventrolateral prefrontal cortex.

Functional magnetic resonance imaging in a Go/Nogo task was employed to investigate the relationship between trait impulsivity and brain activation during motor response inhibition. We found a positive correlation between motor impulsivity and activation of bilateral ventrolateral prefrontal cortex during successful inhibitions, which suggests stronger recruitment to maintain task performance.

Intra-individual variability in high-functioning patients with schizophrenia.

Intra-individual variability of reaction times (IIV) can be employed as a measure of the stability of information processing, which has been proposed to be fundamentally disturbed in schizophrenia. However, the theoretical and clinical significance of IIV is not clear, in part because it has previously been investigated in subject groups with generalized cognitive impairment. Therefore, the purpose of the study was to assess IIV in high-functioning patients with schizophrenia and relatively preserved cognitive performance. 28 high-functioning patients with schizophrenia and 28 controls performed a Go/Nogo task and a Continuous Performance Test. In contrast to average measures of task performance, IIV differentiated consistently and with large effect size between groups. Modelling with an Ex-Gaussian distribution revealed that patients have a higher proportion of slow responses reflected by an increased tau parameter. The tau parameter was correlated with work capability in the sample with schizophrenia. In conclusion, IIV is an easily obtained measure, which is highly sensitive to fundamental cognitive deficits not directly visible in a high-functioning patient group. The response pattern with more exceedingly slow reactions could reflect a core deficit in the stability of information processing. The relationship with work capability suggests investigation of IIV as a clinical measure.

A supramodal network for response inhibition.

Response inhibition is the capacity to suppress inappropriate actions and is considered to be a fundamental executive function. This study investigated whether the neural correlates of response inhibition are organized along supramodal or modality-specific principles. For this purpose, we used event-related functional magnetic resonance imaging in a go-nogo task with auditory and visual stimuli. Common activation relating to response inhibition across modalities was observed in a frontoparietal network including the ventrolateral prefrontal cortex. In contrast, there was no modality-specific activation related to response inhibition in the prefrontal cortex. These findings suggest that the neural correlates of response inhibition have a supramodal organization, which is consistent with its role as a core executive function.

Maintenance of real objects and their verbal designations in working memory.

The present study investigated the neural correlates of working memory maintenance for real objects in contrast to their verbal designations. For this purpose we employed a delayed match-to-sample task using functional magnetic resonance imaging. The conjunction of load effects for objects and for words revealed a common bilateral network with main foci in the ventrolateral prefrontal cortex and the intraparietal sulcus. Load effect for objects in comparison to load effect for words revealed stronger activation of bilateral precuneus, which suggests the use of mental imagery of objects and object features. The opposite comparison load words versus load objects showed premotor and auditory areas to be activated in association with phonological rehearsal. The bilateral common activation indicates overlapping codes for real-world objects and their verbal designations. Importantly, there is also a dissociation between maintenance of words and objects, which indicates that phonological rehearsal and mental imagery are employed to different degrees.