Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder - study protocol for a randomized clinical trial.

BACKGROUND: Anhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated. METHODS: This is a randomized, controlled, double-blind, single-dose, single-center parallel-group clinical trial to assess the effects of a single dose of amisulpride (100 mg) on blood-oxygenation-level-dependent (BOLD) responses during reward- and motivation-related processing in healthy subjects (n = 60) and MDD patients (n = 60). Using functional magnetic resonance imaging (fMRI), BOLD responses are assessed during the monetary incentive delay (MID) task (primary outcome). Exploratory outcomes include BOLD responses and behavioral measures during the MID task, instrumental learning task, effort-based decision-making task, social incentive delay task, and probabilistic reward task as well as changes in resting state functional connectivity and cerebral blood flow. DISCUSSION: This study broadly covers all aspects of reward- and motivation-related processing as categorized by the National Institute of Mental Health Research Domain Criteria and is thereby an important step towards precision psychiatry. Results regarding the immediate effects of a dopaminergic drug on deficits in reward- and motivation-related processing not only have the potential to significantly broaden our understanding of underlying neurobiological processes but might eventually also pave the way for new treatment options. TRIAL REGISTRATION: ClinicalTrials.gov NCT05347199. April 12, 2022.

Processing of Action and Sound Verbs in Context: An FMRI Study.

Recent theories propose a flexible recruitment of sensory and motor brain regions during conceptual processing depending on context and task. The present functional magnetic resonance imaging study investigated the influence of context and task on conceptual processing of action and sound verbs. Participants first performed an explicit semantic context decision task, in which action and sound verbs were presented together with a context noun. The same verbs were repeatedly presented in a subsequent implicit lexical decision task together with new action and sound verbs. Thereafter, motor and acoustic localizer tasks were administered to identify brain regions involved in perception and action. During the explicit task, we found differential activations to action and sound verbs near corresponding sensorimotor brain regions. During the implicit lexical decision task, differences between action and sound verbs were absent. However, feature-specific repetition effects were observed near corresponding sensorimotor brain regions. The present results suggest flexible conceptual representations depending on context and task. Feature-specific effects were observed only near, but not within corresponding sensorimotor brain regions, as defined by the localizer tasks. Our results therefore only provide limited evidence in favor of grounded cognition theories assuming a close link between the conceptual and the sensorimotor systems.

Brain Activation During Conceptual Processing of Action and Sound Verbs.

Grounded cognition approaches to conceptual representations postulate a close link between conceptual knowledge and the sensorimotor brain systems. The present fMRI study tested, whether a feature-specific representation of concepts, as previously demonstrated for nouns, can also be found for action- and sound-related verbs. Participants were presented with action- and soundrelated verbs along with pseudoverbs while performing a lexical decision task. Sound-related verbs activated auditory areas in the temporal cortex, whereas action-related verbs activated brain regions in the superior frontal gyrus and the cerebellum, albeit only at a more liberal threshold. This differential brain activation during conceptual verb processing partially overlapped with or was adjacent to brain regions activated during the functional localizers probing sound perception or action execution. Activity in brain areas involved in the processing of action information was parametrically modulated by ratings of action relevance. Comparisons of action- and sound-related verbs with pseudoverbs revealed activation for both verb categories in auditory and motor areas. In contrast to proposals of strong grounded cognition approaches, our study did not demonstrate a considerable overlap of activations for action- and sound-related verbs and for the corresponding functional localizer tasks. However, in line with weaker variants of grounded cognition theories, the differential activation pattern for action- and sound-related verbs was near corresponding sensorimotor brain regions depending on conceptual feature relevance. Possibly, action-sound coupling resulted in a mutual activation of the motor and the auditory system for both action- and sound-related verbs, thereby reducing the effect sizes for the differential contrasts.

Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition.

Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.