Katharina Schmack

Ventral Striatal Activation During Reward Anticipation Correlates with Impulsivity in Alcoholics

BACKGROUND Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects. METHODS Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence. Impulsivity was assessed with the Barratt Impulsiveness Scale-Version 10 (BIS-10). RESULTS Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy control subjects. Low activation of the ventral striatum and anterior cingulate during gain anticipation was correlated with high impulsivity only in alcoholics, not in control subjects. CONCLUSIONS This study suggests that reduced ventral striatal recruitment during anticipation of conventional rewards in alcoholics may be related to their increased impulsivity and indicate possibilities for enhanced treatment approaches in alcohol dependence.

Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram

Major Depressive Disorder (MDD) involves deficits in the reward system. While neuroimaging studies have focused on affective stimulus processing, few investigations have directly addressed deficits in the anticipation of incentives. We examined neural responses during gain and loss anticipation in patients with MDD before and after treatment with a selective serotonin reuptake inhibitor (SSRI). Fifteen adults with MDD and 15 healthy participants, matched for age, verbal IQ and smoking habits, were investigated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay task. Patients were scanned drug-free and after 6 weeks of open-label treatment with escitalopram; controls were scanned twice at corresponding time points. We compared the blood oxygenation level dependent (BOLD) response during the anticipation of gain and loss with a neutral condition. A repeated measures ANOVA was calculated to identify effects of group (MDD vs. controls), time (first vs. second scan) and group-by-time interaction. Severity of depression was measured with the Hamilton Rating Scale of Depression and the Beck Depression Inventory. MDD patients showed significantly less ventral striatal activation during anticipation of gain and loss compared with controls before, but not after, treatment. There was a significant group-by-time interaction during anticipation of loss in the left ventral striatum due to a signal increase in patients after treatment. Ventral striatal hyporesponsiveness was associated with the severity of depression and in particular anhedonic symptoms. These findings suggest that MDD patients show ventral striatal hyporesponsiveness during incentive cue processing, which normalizes after successful treatment.

Reward Feedback Alterations in Unmedicated Schizophrenia Patients: Relevance for Delusions

BACKGROUND Increased attribution of incentive salience to neutral or aversive stimuli might be associated with dysfunction of neuronal processing of positive and negative reinforcement and contribute to the formation of delusions in schizophrenia. METHODS Fifteen unmedicated patients with schizophrenia (8 drug-naive and 7 drug-free for at least 3 months) and 15 age- and gender-matched healthy control participants underwent functional magnetic resonance imaging to investigate neural responses to feedback of (successful vs. unsuccessful) monetary gain or avoidance of loss. Functional connectivity was assessed between the medial prefrontal cortex (MPFC) and ventral striatum (VS), brain areas known to be activated by feedback of reward and loss. RESULTS Responses to negative outcome in reward trials (omission of expected reward) were exaggerated in the MPFC of patients with schizophrenia. In contrast, schizophrenia patients showed reduced neural responses to successful versus unsuccessful avoidance of loss in the VS. Increased severity of delusions in schizophrenia patients was associated with a decrease in MPFC activation elicited by successful versus unsuccessful avoidance of loss. Functional connectivity between the MPFC and the VS was reduced in patients with schizophrenia compared with healthy control subjects. CONCLUSIONS These findings demonstrate a differential impairment of-and reduced connectivity between--VS and MPFC during processing of reward and loss-avoidance in drug-free patients with schizophrenia. Moreover, our results provide a link between the formation of delusions and the neural processing of aversive outcomes.

Delusions and the Role of Beliefs in Perceptual Inference

Delusions are unfounded yet tenacious beliefs and a symptom of psychotic disorder. Varying degrees of delusional ideation are also found in the healthy population. Here, we empirically validated a neurocognitive model that explains both the formation and the persistence of delusional beliefs in terms of altered perceptual inference. In a combined behavioral and functional neuroimaging study in healthy participants, we used ambiguous visual stimulation to probe the relationship between delusion-proneness and the effect of learned predictions on perception. Delusional ideation was associated with less perceptual stability, but a stronger belief-induced bias on perception, paralleled by enhanced functional connectivity between frontal areas that encoded beliefs and sensory areas that encoded perception. These findings suggest that weakened lower-level predictions that result in perceptual instability are implicated in the emergence of delusional beliefs. In contrast, stronger higher-level predictions that sculpt perception into conformity with beliefs might contribute to the tenacious persistence of delusional beliefs.

Catechol-O-methyltransferase val158met genotype influences neural processing of reward anticipation

Reward processing depends critically on dopaminergic neurotransmission in the ventral striatum. The common polymorphism val(158)met of catechol-O-methyltransferase (COMT) accounts for significant interindividual variations in dopamine (DA) degradation, although the direct effect of COMT on striatal DA might be limited. Using fMRI we assessed the influence of COMT val(158)met genotype on brain activations elicited by the anticipation of monetary gains and losses in forty-four healthy volunteers. We found that the met(158) allele, which is presumably linked to higher synaptic DA levels, was associated with higher responses in ventral striatum to loss incentives. There was a linear relationship between the number of met(158) alleles and ventral striatal activity. Furthermore, we observed a similar gene-dose effect in the anterior temporal cortex, a region that has been linked to the coupling of sensory information with emotional contents. Temporal cortex also showed enhanced connectivity to the ventral striatum during the processing of incentive stimuli. Increased ventral striatal reactivity to loss incentives related to the met(158) allele might contribute to the observed association of the met(158) allele to higher loss aversion behaviour. Current evidence and our results are compatible with an interpretation that construes this effect of COMT genotype on striatal reactivity as a result of a cortico-striatal interaction.

Switching schizophrenia patients from typical neuroleptics to olanzapine: Effects on BOLD response during attention and working memory

Dysfunctional activation of the dorsolateral prefrontal cortex (DLPFC) during working memory (WM) in schizophrenia patients has repeatedly been observed, however little is known about specific medication effects on the modulation of DLPFC activation. We measured activation of DLPFC during a WM task in a longitudinal fMRI study in ten schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to olanzapine (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. We analyzed the fMRI data with SPM5 in a 2 x 2 x 2 design (group x session x task). Schizophrenia patients showed fewer correct responses compared to healthy controls at both time points. The fMRI data revealed a significant group by task interaction in the bilateral DLPFC and the right parietal cortex, indicating a reduced BOLD response in the patient group. After switching to olanzapine, schizophrenia patients displayed a significant increase in the BOLD response during the 0-back condition in the DLPFC. This study showed that switching patients from conventional neuroleptics to olanzapine did not significantly alter the frontal or parietal BOLD response during working memory task. However, medication status had influences on the activation during attentional task (0-back), emphasizing the importance of baseline selection in pharmacological fMRI studies.

Attentional modulation of reward processing in the human brain

Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes. Here, we sought to disentangle reward and attention‐related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants. During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention‐demanding task at two different levels of difficulty. In ventral striatum and ventral tegmental area, neural responses were modulated by reward anticipation irrespective of attentional demands, thus indicating attention‐independent processing of reward cues. By contrast, additive effects of reward and attention were observed in visual cortex. Critically, reward‐related activations in right anterior insula strongly depended on attention to the reward cue. Dynamic causal modelling revealed that the attentional modulation of reward processing in insular cortex was mediated by enhanced effective connectivity from ventral striatum to anterior insula. Our results provide evidence for distinct functional roles of the brain regions involved in the processing of reward‐indicating information: While subcortical structures signal the motivational salience of reward cues even when attention is fully engaged elsewhere, reward‐related responses in anterior insula depend on available attentional resources, likely reflecting the conscious evaluation of sensory information with respect to motivational value. Hum Brain Mapp 35:3036–3051, 2014.

Perceptual instability in schizophrenia: Probing predictive coding accounts of delusions with ambiguous stimuli

Background Delusions, a core symptom of schizophrenia, are thought to arise from an alteration in predictive coding mechanisms that underlie perceptual inference. Here, we aimed to empirically test the hypothesized link between delusions and perceptual inference. Method 28 patients with schizophrenia and 32 healthy controls matched for age and gender took part in a behavioral experiment that assessed the influence of stabilizing predictions on perception of an ambiguous visual stimulus. Results Participants with schizophrenia exhibited a weaker tendency towards percept stabilization during intermittent viewing of the ambiguous stimulus compared to healthy controls. The tendency towards percept stabilization in participants with schizophrenia correlated negatively with delusional ideation as measured with a validated questionnaire. Conclusion Our results indicate an association between a weakened effect of sensory predictions in perceptual inference and delusions in schizophrenia. We suggest that attenuated predictive signaling during perceptual inference in schizophrenia may yield the experience of aberrant salience, thereby providing the starting point for the formation of delusions.

Biased Recognition of Facial Affect in Patients with Major Depressive Disorder Reflects Clinical State

Cognitive theories of depression posit that perception is negatively biased in depressive disorder. Previous studies have provided empirical evidence for this notion, but left open the question whether the negative perceptual bias reflects a stable trait or the current depressive state. Here we investigated the stability of negatively biased perception over time. Emotion perception was examined in patients with major depressive disorder (MDD) and healthy control participants in two experiments. In the first experiment subjective biases in the recognition of facial emotional expressions were assessed. Participants were presented with faces that were morphed between sad and neutral and happy expressions and had to decide whether the face was sad or happy. The second experiment assessed automatic emotion processing by measuring the potency of emotional faces to gain access to awareness using interocular suppression. A follow-up investigation using the same tests was performed three months later. In the emotion recognition task, patients with major depression showed a shift in the criterion for the differentiation between sad and happy faces: In comparison to healthy controls, patients with MDD required a greater intensity of the happy expression to recognize a face as happy. After three months, this negative perceptual bias was reduced in comparison to the control group. The reduction in negative perceptual bias correlated with the reduction of depressive symptoms. In contrast to previous work, we found no evidence for preferential access to awareness of sad vs. happy faces. Taken together, our results indicate that MDD-related perceptual biases in emotion recognition reflect the current clinical state rather than a stable depressive trait.

A predictive coding account of bistable perception - a model-based fMRI study

In bistable vision, subjective perception wavers between two interpretations of a constant ambiguous stimulus. This dissociation between conscious perception and sensory stimulation has motivated various empirical studies on the neural correlates of bistable perception, but the neurocomputational mechanism behind endogenous perceptual transitions has remained elusive. Here, we recurred to a generic Bayesian framework of predictive coding and devised a model that casts endogenous perceptual transitions as a consequence of prediction errors emerging from residual evidence for the suppressed percept. Data simulations revealed close similarities between the model’s predictions and key temporal characteristics of perceptual bistability, indicating that the model was able to reproduce bistable perception. Fitting the predictive coding model to behavioural data from an fMRI-experiment on bistable perception, we found a correlation across participants between the model parameter encoding perceptual stabilization and the behaviourally measured frequency of perceptual transitions, corroborating that the model successfully accounted for participants’ perception. Formal model comparison with established models of bistable perception based on mutual inhibition and adaptation, noise or a combination of adaptation and noise was used for the validation of the predictive coding model against the established models. Most importantly, model-based analyses of the fMRI data revealed that prediction error time-courses derived from the predictive coding model correlated with neural signal time-courses in bilateral inferior frontal gyri and anterior insulae. Voxel-wise model selection indicated a superiority of the predictive coding model over conventional analysis approaches in explaining neural activity in these frontal areas, suggesting that frontal cortex encodes prediction errors that mediate endogenous perceptual transitions in bistable perception. Taken together, our current work provides a theoretical framework that allows for the analysis of behavioural and neural data using a predictive coding perspective on bistable perception. In this, our approach posits a crucial role of prediction error signalling for the resolution of perceptual ambiguities.