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Dimensional psychiatry
(2014)
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
We used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects' individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.
Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.
One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.
Background
Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country.
Methods
The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program.
The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG).
Discussion
An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers.
Trial registration
DRKS, DRKS00020373. Registered on 15 April 2020