Joe J. Simon

Neurocircuit function in eating disorders

OBJECTIVE Eating disorders are serious psychosomatic disorders with high morbidity and lifetime mortality. Inadequate response to current therapeutic interventions constitutes a challenging clinical problem. A better understanding of the underlying neurobiological mechanisms could improve psychotherapeutic and drug treatment strategies. METHOD A review highlighting the current state of brain imaging in eating disorders related to the anxiety and pathological fear learning model of anorexia nervosa (AN) and the impulsivity model of binge eating in bulimia nervosa (BN). RESULTS Available neuroimaging studies in patients with acute AN primarily suggest a hyper-responsive emotional and fear network to food, but not necessarily to eating disorder-unrelated, salient stimuli. Furthermore, patients with AN show decreased activation in the ventral fronto-striatal circuits during the performance of a cognitive flexibility task. Results in patients with BN primarily suggest a hypo-responsive reward system to food stimuli, especially to taste reward. Additionally, patients with BN exhibit impaired brain activation in the inhibitory control network during the performance of general response-inhibition tasks. DISCUSSION Anxiety and pathological fear learning may lead to conditioned neural stimulus-response patterns to food stimuli and increased cognitive rigidity, which could account for the phobic avoidance of food intake in patients with acute AN. However, further neurobiological studies are required to investigate pathological fear learning in patients with AN. Patients with BN may binge eat to compensate for a hypo-responsive reward system. The impaired brain activation in the inhibitory control network may facilitate the loss of control over food intake in patients with BN.

The Negative Symptoms of Schizophrenia: Category or Continuum?

Negative symptoms have been considered to be specific to schizophrenia or a subtype of schizophrenia: the deficit syndrome. In other words, these symptoms have been considered to be categorically different from other forms of human behavior and experience, whether they occur in healthy persons or patients with other psychiatric disorders. In this paper, we advocate a dimensional approach to negative symptoms, which is supported by two main arguments. First, enduring negative symptoms can even be observed in a variety of psychiatric disorders and they are not specific to schizophrenia. Second, we review evidence that negative symptoms show a continuous distribution from apparently healthy subjects to those with a fully developed clinical syndrome. Although the evidence does not allow for a definite decision concerning the dimensional distribution of negative symptoms, it certainly justifies exploring a dimensional approach with respect to its clinical and scientific utility. Understanding negative symptoms as a variation of normal mental processes will strengthen the development of neurocognitive models and treatment approaches.

The impact of cognitive impairment and impulsivity on relapse of alcohol‐dependent patients: implications for psychotherapeutic treatment

Recent models of the development of addiction propose a transition from a pleasure‐driven to a heavily automatized behaviour, marked by a loss of cognitive control. This study investigated the deficits in different components of cognitive functions including behavioural inhibition in response to alcohol‐related stimuli in alcohol‐dependent patients (ADP) and healthy controls (HC). The aims of the study were to identify which particular cognitive functions are impaired in ADP. Furthermore, we analysed the association between cognitive deficits and relapse rates and the reversibility of cognitive deficits under abstinence in a 6‐month follow‐up period. Ninety‐four recently detoxified ADP and 71 HC completed the cognitive tasks as well as questionnaire measures assessing drinking behaviour and personality traits. Compared with HC, ADP showed poorer performance in response initiation, response inhibition, complex‐sustained attention and executive functions. Impairment in response inhibition was a significant predictor for relapse, yet the strongest predictor was the interaction between the number of previous detoxifications and response‐inhibition deficits. The results of a moderation analysis showed that patients with many previous detoxifications and large deficits in response inhibition showed the highest relapse risk. These findings indicate that interventions should take into account inhibitory deficits especially in ADP with a high number of previous detoxifications.

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.

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.

Is binge drinking in young adults associated with an alcohol-specific impairment of response inhibition?

Background/Aims: Little is known about the association of binge drinking with impulsivity related to trait- or state-like aspects of behavior. The aim of the present study was therefore to investigate whether binge drinkers show an impairment of inhibitory control in comparison to non-binge drinkers when confronted with alcohol-associated or control stimuli, and whether this is reflected in self-reported impulsivity. Methods: A go/no-go task with pictures of alcoholic and nonalcoholic beverages as well as control stimuli was administered to binge drinkers and a gender-matched group of non-binge drinkers. All participants also completed the Barratt Impulsiveness Scale (BIS-11). Results: We found an alcohol-specific impairment of response inhibition for binge drinkers only, while the groups did not differ with regard to overall response inhibition to the experimental stimuli or self-reported impulsiveness (BIS-11). In addition, the number of commission errors in response to alcohol-associated stimuli was the only significant predictor of binge drinking. Conclusion: The findings of the present study suggest that when young adults have established binge drinking as a common drinking pattern, impairment of inhibition in response to alcoholic stimuli is the only significant predictor of binge drinking, but not general impulsive behavior. i 2014 S. Karger AG, Basel

Reward System Dysfunction as a Neural Substrate of Symptom Expression Across the General Population and Patients With Schizophrenia

Dysfunctional patterns of activation in brain reward networks have been suggested as a core element in the pathophysiology of schizophrenia. However, it remains unclear whether this dysfunction is specific to schizophrenia or can be continuously observed across persons with different levels of nonclinical and clinical symptom expression. Therefore, we sought to investigate whether the pattern of reward system dysfunction is consistent with a dimensional or categorical model of psychosis-like symptom expression. 23 patients with schizophrenia and 37 healthy control participants with varying levels of psychosis-like symptoms, separated into 3 groups of low, medium, and high symptom expression underwent event-related functional magnetic resonance imaging while performing a Cued Reinforcement Reaction Time task. We observed lower activation in the ventral striatum during the expectation of high vs no reward to be associated with higher symptom expression across all participants. No significant difference between patients with schizophrenia and healthy participants with high symptom expression was found. However, connectivity between the ventral striatum and the medial orbitofrontal cortex was specifically reduced in patients with schizophrenia. Dysfunctional local activation of the ventral striatum depends less on diagnostic category than on the degree of symptom expression, therefore showing a pattern consistent with a psychosis continuum. In contrast, aberrant connectivity in the reward system is specific to patients with schizophrenia, thereby supporting a categorical view. Thus, the results of the present study provide evidence for both continuous and discontinuous neural substrates of symptom expression across patients with schizophrenia and the general population.

Symptom dimensions are associated with reward processing in unmedicated persons at risk for psychosis

There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio- and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.

Impaired cross-talk between mesolimbic food reward processing and metabolic signaling predicts body mass index

The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food, which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food-related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum (VS) in participants with a broad BMI spectrum. The study differentiated between general (i.e., monetary) and food-related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m2) over a normal (20–25 kg/m2) and overweight (25–30 kg/m2) BMI, to class I (30–35 kg/m2) and class II (35–40 kg/m2) obesity. A total of 24 participants underwent functional magnetic resonance imaging while performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn “snack points” or “money coins,” which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the VS, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime). This relation was found to be mediated by impaired hormonal satiety signaling, i.e., increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling.

Neural dissociation of food- and money-related reward processing using an abstract incentive delay task

Food is an innate reward stimulus related to energy homeostasis and survival, whereas money is considered a more general reward stimulus that gains a rewarding value through learning experiences. Although the underlying neural processing for both modalities of reward has been investigated independently from one another, a more detailed investigation of neural similarities and/or differences between food and monetary reward is still missing. Here, we investigated the neural processing of food compared with monetary-related rewards in 27 healthy, normal-weight women using functional magnetic resonance imaging. We developed a task distinguishing between the anticipation and the receipt of either abstract food or monetary reward. Both tasks activated the ventral striatum during the expectation of a reward. Compared with money, greater food-related activations were observed in prefrontal, parietal and central midline structures during the anticipation and lateral orbitofrontal cortex (lOFC) during the receipt of food reward. Furthermore, during the receipt of food reward, brain activation in the secondary taste cortex was positively related to the body mass index. These results indicate that food-dependent activations encompass to a greater extent brain regions involved in self-control and self-reflection during the anticipation and phylogenetically older parts of the lOFC during the receipt of reward.