Gregor Wilbertz

Orbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder

Impulsivity symptoms of adult attention deficit hyperactivity disorder (ADHD) such as increased risk taking have been linked with impaired reward processing. Previous studies have focused on reward anticipation or on rewarded executive functioning tasks and have described a striatal hyporesponsiveness and orbitofrontal alterations in adult and adolescent ADHD. Passive reward delivery and its link to behavioral impulsivity are less well understood. To study this crucial aspect of reward processing we used functional magnetic resonance imaging (fMRI) combined with electrodermal assessment in male and female adult ADHD patients (N=28) and matched healthy control participants (N=28) during delivery of monetary and non-monetary rewards. Further, two behavioral tasks assessed risky decision making (game of dice task) and delay discounting. Results indicated that both groups activated ventral and dorsal striatum and the medial orbitofrontal cortex (mOFC) in response to high-incentive (i.e. monetary) rewards. A similar, albeit less strong activation pattern was found for low-incentive (i.e. non-monetary) rewards. Group differences emerged when comparing high and low incentive rewards directly: activation in the mOFC coded for the motivational change in reward delivery in healthy controls, but not ADHD patients. Additionally, this dysfunctional mOFC activity in patients correlated with risky decision making and delay discounting and was paralleled by physiological arousal. Together, these results suggest that the mOFC codes reward value and type in healthy individuals whereas this function is deficient in ADHD. The brain-behavior correlations suggest that this deficit might be related to behavioral impulsivity. Reward value processing difficulties in ADHD should be considered when assessing reward anticipation and emotional learning in research and applied settings.

A Comparison of Spatial Knowledge Acquisition with Maps and Mobile Maps

Abstract We investigated the effects of different modes of information provision on spatial knowledge acquisition in a large-scale environmental setting by comparing two groups of participants; those who had learned the environment from a map and those who had learned it using a mobile map. The experiment was conducted in an external urban environment and consisted of two phases; an initial learning phase, and a testing phase where participants were asked to provide orientation, Euclidean and route distance estimates. The results show that there are differences in the spatial knowledge acquired, and that mobile map users performed worse than map users on route distance estimation. Also, only mobile map users showed differences in configurational knowledge between different types of locations. We propose that mobile map users acquire a more fragmented and regionalised knowledge representation based on strong connections between locally clustered landmarks along the route. This can be attributed both to the piecemeal presentation of views during navigation and to increased requirements on users’ attention. We conclude by discussing the implications for learning with mobile navigation applications in urban environments.

Cognitive-Behavioral Therapy as Continuation Treatment to Sustain Response After Electroconvulsive Therapy in Depression: A Randomized Controlled Trial

BACKGROUND Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. METHODS In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. RESULTS Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. CONCLUSIONS These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients.

Neural and Psychophysiological Markers of Delay Aversion in Attention-Deficit Hyperactivity Disorder

Delay aversion (DAv) is thought to be a crucial factor in the manifestation of impulsive behaviors in patients with attention-deficit/hyperactivity disorder (ADHD). The imposition of delay is predicted to elicit negative emotional reactions in ADHD. The present study offers a multimodal approach to the investigation of DAv. Twelve adult patients with ADHD and 12 matched healthy controls were tested on a new task with several levels of anticipated delays during functional magnet resonance imaging (fMRI). Behavioral measures of delay discounting, DAv, and delay frustration were collected. Skin conductance and finger pulse rate were assessed. Results indicated a group difference in response to changes in delay in the right amygdala: For control participants activity decreased with longer delays, whereas activity tended to increase for ADHD patients. The degree of amygdala increase was correlated with the degree of behavioral DAv within the ADHD group. Patients also exhibited increased emotional arousal on physiological measures. These results support the notion of an exacerbated negative emotional state during the anticipation and processing of delay in ADHD.

Sensitivity to detect change and the correlation of clinical factors with the Hamilton Depression Rating Scale and the Beck Depression Inventory in depressed inpatients

Discrepancies between scores on the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI), as well as differences regarding their sensitivity to detect change, have been reported. This study investigates discrepancies and their potential prediction on the basis of demographic, personality, and clinical factors in depressed inpatients and analyzes the sensitivity to change. The HAMD and the BDI were administered to 105 inpatients with major depressive disorder randomized to 5 weeks of either interpersonal psychotherapy or clinical management. Personality was assessed with the NEO Five-Factor Inventory. Low extraversion and high neuroticism were associated with relatively higher endorsement of depressive symptoms on the BDI compared with the HAMD. The HAMD presented a greater reduction of symptom scores than the BDI. Patients with high BDI scores, high HAMD scores or both revealed the greatest change, possibly due to a statistical effect of regression to the mean. Restricted by sample size, analyses were not differentiated by treatment condition. Regression to the mean cannot be tested directly, but it might be considered as a possible explanation. The HAMD and the BDI should be regarded as two complementary rather than redundant or competing instruments as the discrepancy is associated with personality characteristics. Attributing large effect sizes solely to effective treatment and a sensitive measure may be misleading.

Mesolimbic confidence signals guide perceptual learning in the absence of external feedback

It is well established that learning can occur without external feedback, yet normative reinforcement learning theories have difficulties explaining such instances of learning. Here, we propose that human observers are capable of generating their own feedback signals by monitoring internal decision variables. We investigated this hypothesis in a visual perceptual learning task using fMRI and confidence reports as a measure for this monitoring process. Employing a novel computational model in which learning is guided by confidence-based reinforcement signals, we found that mesolimbic brain areas encoded both anticipation and prediction error of confidence—in remarkable similarity to previous findings for external reward-based feedback. We demonstrate that the model accounts for choice and confidence reports and show that the mesolimbic confidence prediction error modulation derived through the model predicts individual learning success. These results provide a mechanistic neurobiological explanation for learning without external feedback by augmenting reinforcement models with confidence-based feedback. DOI: http://dx.doi.org/10.7554/eLife.13388.001

Reinforcement of perceptual inference: reward and punishment alter conscious visual perception during binocular rivalry.

Perception is an inferential process, which becomes immediately evident when sensory information is conflicting or ambiguous and thus allows for more than one perceptual interpretation. Thinking the idea of perception as inference through to the end results in a blurring of boundaries between perception and action selection, as perceptual inference implies the construction of a percept as an active process. Here we therefore wondered whether perception shares a key characteristic of action selection, namely that it is shaped by reinforcement learning. In two behavioral experiments, we used binocular rivalry to examine whether perceptual inference can be influenced by the association of perceptual outcomes with reward or punishment, respectively, in analogy to instrumental conditioning. Binocular rivalry was evoked by two orthogonal grating stimuli presented to the two eyes, resulting in perceptual alternations between the two gratings. Perception was tracked indirectly and objectively through a target detection task, which allowed us to preclude potential reporting biases. Monetary reward or punishments were given repeatedly during perception of only one of the two rivaling stimuli. We found an increase in dominance durations for the percept associated with reward, relative to the non-rewarded percept. In contrast, punishment led to an increase of the non-punished compared to a relative decrease of the punished percept. Our results show that perception shares key characteristics with action selection, in that it is influenced by reward and punishment in opposite directions, thus narrowing the gap between the conceptually separated domains of perception and action selection. We conclude that perceptual inference is an adaptive process that is shaped by its consequences.

Neural response during anticipation of monetary loss is elevated in adult attention deficit hyperactivity disorder

Abstract Objectives: Risky behaviour seriously impacts the life of adult patients with attention deficit hyperactivity disorder (ADHD). Such behaviours have often been attributed to their exaggerated reward seeking, but dysfunctional anticipation of negative outcomes might also play a role. Methods: The present study compared adult patients with ADHD (n = 28) with matched healthy controls (n = 28) during anticipation of monetary losses versus gains while undergoing functional magnetic resonance imaging (fMRI) and skin conductance recording. Results: Skin conductance was higher during anticipation of losses compared to gains in both groups. Affective ratings of predictive cues did not differ between groups. ADHD patients showed increased activity in bilateral amygdalae, left anterior insula (region of interest analysis) and left temporal pole (whole brain analysis) compared to healthy controls during loss versus gain anticipation. In the ADHD group higher insula and temporal pole activations went along with more negative affective ratings. Conclusions: Neural correlates of loss anticipation are not blunted but rather increased in ADHD, possibly due to a life history of repeated failures and the respective environmental sanctions. Behavioural adaptations to such losses, however, might differentiate them from controls: future research should study whether negative affect might drive more risk seeking than risk avoidance.

Understanding Mobile Spatial Interaction in Urban Environments

In order to act in urban environments an individual accesses various types of knowledge, such as memories, spatial strategies and also information from the environment so as to develop plans and make decisions. This chapter will investigate the nature of spatial knowledge acquisition in an environmental setting by comparing performance in a task where the participants learnt the environment using spatial assistance either from a map or from a . It outlines the early results of an empirical experiment which evaluated participants’ spatial knowledge acquisition for orientation and distance estimation tasks in a large-scale urban environmental setting. The initial findings of the experiment highlight the fact that participants performed worse in distance estimation tasks than map participants and that their errors for complex routes were high. We will conclude by analysing the results of this experiment in terms of the specific types of knowledge afforded by mobile maps and the implications for spatial learning in urban environments.

fMRI-based decoding of reward effects in binocular rivalry

Abstract Binocular rivalry is a phenomenon where the simultaneous presentation of two different stimuli to the two eyes leads to alternating perception of the two stimuli. The temporary dominance of one stimulus over the other is influenced by several factors. Here, we studied the influence of reward on binocular rivalry dynamics and its neural representation in visual cortex. Orthogonal rotating grating stimuli were shown continuously, while monetary reward was given during the conscious perception of one stimulus but not the other. Periods of perceptual dominance were assessed both through participants’ subjective report and objectively using functional magnetic resonance imaging and multi-voxel pattern analysis. Results did not confirm previous evidence for an effect of reward on perceptual dominance durations. Exploratory post-hoc analyses indicated that knowledge regarding both the reward contingency and the subjective nature of perceptual alternations may have interfered with potential reward effects on perceptual phase durations, suggesting a moderating role of meta-cognitive awareness in reward-based perceptual inference. Future studies of top-down influences on bistable perception should carefully consider the methodological challenges related to meta-cognitive awareness.