Non-stimulated regions in early visual cortex encode the contents of conscious visual perception.

Predictions shape our perception. The theory of predictive processing poses that our brains make sense of incoming sensory input by generating predictions, which are sent back from higher to lower levels of the processing hierarchy. These predictions are based on our internal model of the world and enable inferences about the hidden causes of the sensory input data. It has been proposed that conscious perception corresponds to the currently most probable internal model of the world. Accordingly, predictions influencing conscious perception should be fed back from higher to lower levels of the processing hierarchy. Here, we used functional magnetic resonance imaging and multivoxel pattern analysis to show that non-stimulated regions of early visual areas contain information about the conscious perception of an ambiguous visual stimulus. These results indicate that early sensory cortices in the human brain receive predictive feedback signals that reflect the current contents of conscious perception.

STEP.De study-a multicentre cluster-randomised effectiveness trial of exercise therapy for patients with depressive symptoms in healthcare services: study protocol.

INTRODUCTION: Although exercise therapy has widely been shown to be an efficacious treatment modality for depression, evidence for its effectiveness and cost efficiency is lacking. The Sport/Exercise Therapy for Depression study is a multicentre cluster-randomised effectiveness trial that aims to compare the effectiveness and cost efficiency of exercise therapy and psychotherapy as antidepressant treatment. METHODS AND ANALYSIS: 480 patients (aged 18-65) with an International Classification of Diseases diagnosis associated with depressive symptoms are recruited. Up to 30 clusters (psychotherapists) are randomly assigned to allocate patients to either an exercise or a psychotherapy treatment as usual in a 2:1 ratio. The primary outcome (depressive symptoms) and the secondary outcomes (work and social adjustment, quality of life) will be assessed at six measurement time points (t0: baseline, t1: 8 weeks after treatment initiation, t2: 16 weeks after treatment initiation, t3/4/5: 2, 6, 12 months after treatment). Linear regression analyses will be used for the primary endpoint data analysis. For the secondary endpoints, mixed linear and logistic regression models with fixed and random factors will be added. For the cost efficiency analysis, expenditures in the 12 months before and after the intervention and the outcome difference will be compared between groups in a multilevel model. Recruitment start date was 1 July 2018 and the planned recruitment end date is 31 December 2020. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee of the University of Potsdam (No. 17/2018) and the Freie Universität Berlin (No. 206/2018) and registered in the ISRCTN registry. Informed written consent will be obtained from all participants. The study will be reported in accordance with the Consolidated Standards of Reporting Trials and the Recommendations for Interventional Trials statements. The results will be published in peer-reviewed academic journals and disseminated to the public. TRIAL REGISTRATION NUMBER: ISRCTN28972230.

Differentiating aversive conditioning in bistable perception: Avoidance of a percept vs. salience of a stimulus.

Alternating conscious visual perception of bistable stimuli is influenced by several factors. In order to understand the effect of negative valence, we tested the effect of two types of aversive conditioning on dominance durations in binocular rivalry. Participants received either aversive classical conditioning of the stimuli shown alone between rivalry blocks, or aversive percept conditioning of one of the two possible perceptual choices during rivalry. Both groups showed successful aversive conditioning according to skin conductance responses and affective valence ratings. However, while classical conditioning led to an immediate but short-lived increase in dominance durations of the conditioned stimulus, percept conditioning yielded no significant immediate effect but tended to decrease durations of the conditioned percept during extinction. These results show dissociable effects of value learning on perceptual inference in situations of perceptual conflict, depending on whether learning relates to the decision between conflicting perceptual choices or the sensory stimuli per se.

Combined fMRI- and eye movement-based decoding of bistable plaid motion perception.

The phenomenon of bistable perception, in which perception alternates spontaneously despite constant sensory stimulation, has been particularly useful in probing the neural bases of conscious perception. The study of such bistability requires access to the observer's perceptual dynamics, which is usually achieved via active report. This report, however, constitutes a confounding factor in the study of conscious perception and can also be biased in the context of certain experimental manipulations. One approach to circumvent these problems is to track perceptual alternations using signals from the eyes or the brain instead of observers' reports. Here we aimed to optimize such decoding of perceptual alternations by combining eye and brain signals. Eye-tracking and functional magnetic resonance imaging (fMRI) was performed in twenty participants while they viewed a bistable visual plaid motion stimulus and reported perceptual alternations. Multivoxel pattern analysis (MVPA) for fMRI was combined with eye-tracking in a Support vector machine to decode participants' perceptual time courses from fMRI and eye-movement signals. While both measures individually already yielded high decoding accuracies (on average 86% and 88% correct, respectively) classification based on the two measures together further improved the accuracy (91% correct). These findings show that leveraging on both fMRI and eye movement data may pave the way for optimized no-report paradigms through improved decodability of bistable motion perception and hence for a better understanding of the neural correlates of consciousness.

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

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.

fMRI-based decoding of reward effects in binocular rivalry.

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.

Probing the influence of unconscious fear-conditioned visual stimuli on eye movements.

Efficient threat detection from the environment is critical for survival. Accordingly, fear-conditioned stimuli receive prioritized processing and capture overt and covert attention. However, it is unknown whether eye movements are influenced by unconscious fear-conditioned stimuli. We performed a classical fear-conditioning procedure and subsequently recorded participants' eye movements while they were exposed to fear-conditioned stimuli that were rendered invisible using interocular suppression. Chance-level performance in a forced-choice-task demonstrated unawareness of the stimuli. Differential skin conductance responses and a change in participants' fearfulness ratings of the stimuli indicated the effectiveness of conditioning. However, eye movements were not biased towards the fear-conditioned stimulus. Preliminary evidence suggests a relation between the strength of conditioning and the saccadic bias to the fear-conditioned stimulus. Our findings provide no strong evidence for a saccadic bias towards unconscious fear-conditioned stimuli but tentative evidence suggests that such an effect may depend on the strength of the conditioned response.

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.

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.

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.

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.

Exploring preoperational features in chronic depression.

BACKGROUND: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) by James McCullough is the first psychotherapeutical approach specifically designed for chronic depression. Whereas its efficacy has recently been studied, empirical investigations on the underlying etiopathological hypotheses are missing. McCullough postulates that chronically depressed patients - particularly those with early onset - think preoperationally. This term was coined by J. Piaget and includes egocentrism in the views of self and others and incapacity for authentic interpersonal empathy. In accordance, empirical studies indicate a deficit in theory of mind (ToM) in depressed individuals. METHODS: Sixteen patients with early onset chronic depression were compared to sixteen matched healthy controls using three measurements: 1) the Movie for the Assessment of Social Cognition (MASC) as a new video-based theory of mind test, 2) self-rated questionnaires on empathy (Interpersonal Reactivity Index (IRI), and a scale assessing individual competence in relationships), and 3) a structured evaluation by the patients' therapists. RESULTS: The groups did not differ in their theory of mind performance on any aspect assessed by the used test. However, patients rated their empathy in daily life as significantly inferior to healthy controls. In addition, the therapists assigned a considerable amount of preoperational behavior to their patients. No meaningful correlations between these three types of measurements were found. LIMITATIONS: Small sample size, no structural assessment of possible psychopathology in the control group, control group was not rated by clinicians concerning preoperational behaviors. CONCLUSIONS: Lack of empathy exists in the daily life of early onset chronically depressed patients according to their own and their therapists' evaluation. However, a video-based test failed to pick up deficits in their theory of mind capacities. Further research is needed to investigate theory of mind deficits using real life interpersonal interactions demanding the patient's personal involvement.

Patterns of response to repetitive transcranial magnetic stimulation (rTMS) in major depression: replication study in drug-free patients.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to moderate therapeutic effects in major depression, but mechanism of action and its clinical relevance have not been clarified yet. Previous trials have reported patterns of symptomatology predicting response to rTMS. As most patients also received concomitant antidepressant medication these response patterns may rather refer to combined treatment than rTMS alone. Thus, this study aims to replicate previous findings and explore patterns of response in drug-free patients. METHODS: In the Munich-Berlin Predictor Study data of 79 patients from two open clinical trials evaluating effects of high-frequency rTMS of the left dorsolateral prefrontal cortex were pooled. Previous models predicting the response to rTMS [Fregni, F., Marcolin, M.A., Myczkowski, M., Amiaz, R., Hasey, G., Rumi, D.O., Rosa, M., Rigonatti, S.P., Camprodon, J., Walpoth, M., Heaslip, J., Grunhaus, L., Hausmann, A., Pascual-Leone, A., 2006. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 9, 641-654; Brakemeier, E.L., Luborzewski, A., Danker-Hopfe, H., Kathmann, N., Bajbouj, M., 2007. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J. Psychiatr. Res. 41, 395-403.] were systematically tested and new explorative regression analyses were conducted. RESULTS: Of the 79 patients, 34.2% showed an antidepressant response. Previous models could not be validated. Explorative regression analysis revealed a significant model with therapy resistance, HAMD items 1 (depressed mood), and 2 (feelings of guilt) as negative and retardation as positive predictors. LIMITATIONS: No controlled study; specific statistical issues; sample size; differences concerning patient population and stimulation parameters between study sites. CONCLUSIONS: In sum, this study does not confirm clinical valid and robust patterns being predictive for a response to rTMS in depression. The only exception is a high level of therapy resistance being associated with poor outcome. Future predictor studies should focus on large and homogenous samples of rTMS multicenter trials and include neurobiological variables.