Abnormal approach-related motivation but spared reinforcement learning in MDD: Evidence from fronto-midline Theta oscillations and frontal Alpha asymmetry.

Major depression is characterized by abnormal reward processing and reinforcement learning (RL). This impairment might stem from deficient motivation processes, in addition to reduced reward sensitivity. In this study, we recorded 64-channel EEG in a large cohort of major depressive disorder (MDD) patients and matched healthy controls (HC) while they performed a standard RL task. Participants were asked to discover, by trial and error, several hidden stimulus-response associations having different reward probabilities, as enforced using evaluative feedback. We extracted induced fronto-midline Theta (FMT) power time-locked to the response and feedback as neurophysiological index of RL. Furthermore, we assessed approach-related motivation by measuring frontal alpha asymmetry concurrently. At the behavioral level, MDD patients and HCs showed comparable RL. At the EEG level, FMT power systematically varied as a function of reward probability, with opposing effects found at the response and feedback levels. Although this global pattern was spared in MDD, at the feedback level these patients showed however a steep FMT power decrease across trials when reward probability was low. Moreover, they showed impaired approach-related motivation during task execution, as reflected by frontal Alpha asymmetry. These results suggest a dissociation between (globally spared) RL and (impaired) approach motivation in MDD.

Modulatory effects of happy mood on performance monitoring: Insights from error-related brain potentials.

Goal-adaptive behavior requires the rapid detection of conflicts between actions and intentions or goals. Although many studies have focused in the past on the influence of negative affect on this cognitive control process (and more specifically, on error monitoring), little is known about the possible modulatory effects of positive affect on it. To address this question, we used a standard (positive) mood induction procedure (based on guided imagery) and asked participants to carry out a speeded go/no-go task while high-density electroencephalography was recorded concurrently. As a control condition, we used a group with neutral mood. Event-related potential results showed that the error-related negativity (ERN) component, reflecting early error detection within the dorsal anterior cingulate cortex, was not influenced by happy mood. In contrast, the subsequent error positivity (Pe) component, related to the appraisal of the motivational significance of errors, was reliably smaller in the happy than in the neutral mood group. Complementing source localization analyses showed that this effect was explained by decreased activation within the posterior cingulate and insular cortices. These results were obtained in the absence of group differences regarding behavioral performance and tonic arousal. These findings suggest that happy mood likely decreases and changes the motivational significance of worse-than-expected events (Pe), while leaving their earlier automatic detection (ERN) unaltered. We discuss these new results in terms of dynamic changes in the complex interplay of performance monitoring with motivation.

Spared internal but impaired external reward prediction error signals in major depressive disorder during reinforcement learning.

BACKGROUND: Major depressive disorder (MDD) creates debilitating effects on a wide range of cognitive functions, including reinforcement learning (RL). In this study, we sought to assess whether reward processing as such, or alternatively the complex interplay between motivation and reward might potentially account for the abnormal reward-based learning in MDD. METHODS: A total of 35 treatment resistant MDD patients and 44 age matched healthy controls (HCs) performed a standard probabilistic learning task. RL was titrated using behavioral, computational modeling and event-related brain potentials (ERPs) data. RESULTS: MDD patients showed comparable learning rate compared to HCs. However, they showed decreased lose-shift responses as well as blunted subjective evaluations of the reinforcers used during the task, relative to HCs. Moreover, MDD patients showed normal internal (at the level of error-related negativity, ERN) but abnormal external (at the level of feedback-related negativity, FRN) reward prediction error (RPE) signals during RL, selectively when additional efforts had to be made to establish learning. CONCLUSIONS: Collectively, these results lend support to the assumption that MDD does not impair reward processing per se during RL. Instead, it seems to alter the processing of the emotional value of (external) reinforcers during RL, when additional intrinsic motivational processes have to be engaged.

Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission?

Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.

What is in the feedback? Effect of induced happiness vs. sadness on probabilistic learning with vs. without exploration.

According to dominant neuropsychological theories of affect, emotions signal salience of events and in turn facilitate a wide spectrum of response options or action tendencies. Valence of an emotional experience is pivotal here, as it alters reward and punishment processing, as well as the balance between safety and risk taking, which can be translated into changes in the exploration-exploitation trade-off during reinforcement learning (RL). To test this idea, we compared the behavioral performance of three groups of participants that all completed a variant of a standard probabilistic learning task, but who differed regarding which mood state was actually induced and maintained (happy, sad or neutral). To foster a change from an exploration to an exploitation-based mode, we removed feedback information once learning was reliably established. Although changes in mood were successful, learning performance was balanced between the three groups. Critically, when focusing on exploitation-driven learning only, they did not differ either. Moreover, mood valence did not alter the learning rate or exploration per se, when titrated using complementing computational modeling. By comparing systematically these results to our previous study (Bakic et al., 2014), we found that arousal levels did differ between studies, which might account for limited modulatory effects of (positive) mood on RL in the present case. These results challenge the assumption that mood valence alone is enough to create strong shifts in the way exploitation or exploration is eventually carried out during (probabilistic) learning. In this context, we discuss the possibility that both valence and arousal are actually necessary components of the emotional mood state to yield changes in the use and exploration of incentives cues during RL.

Effects of positive mood on probabilistic learning: behavioral and electrophysiological correlates.

Whether positive mood can change reinforcement learning or not remains an open question. In this study, we used a probabilistic learning task and explored whether positive mood could alter the way positive versus negative feedback was used to guide learning. This process was characterized both at the behavioral and electro-encephalographic levels. Thirty two participants were randomly allocated either to a positive or a neutral (control) mood condition. Behavioral results showed that while learning performance was balanced between the two groups, participants in the positive mood group had a higher learning rate than participants in the neutral mood group. At the electrophysiological level, we found that positive mood increased the error-related negativity when the stimulus-response associations were deterministic, selectively (as opposed to random or probabilistic). However, it did not influence the feedback-related negativity. These new findings are discussed in terms of an enhanced internal reward prediction error signal after the induction of positive mood when the probability of getting a reward is high.