Dopaminergic Modulation of Human Intertemporal Choice: A Diffusion Model Analysis Using the D2-Receptor Antagonist Haloperidol.

The neurotransmitter dopamine is implicated in diverse functions, including reward processing, reinforcement learning, and cognitive control. The tendency to discount future rewards over time has long been discussed in the context of potential dopaminergic modulation. Here we examined the effect of a single dose of the D2 receptor antagonist haloperidol (2 mg) on temporal discounting in healthy female and male human participants.

Region-specific effects of acute haloperidol in the human midbrain, striatum and cortex.

D2 autoreceptors provide an important regulatory mechanism of dopaminergic neurotransmission. However, D2 receptors are also expressed as heteroreceptors at postsynaptic membranes. The expression and the functional characteristics of both, D2 auto- and heteroreceptors, differ between brain regions.

Dopamine Enhances Item Novelty Detection via Hippocampal and Associative Recall via Left Lateral Prefrontal Cortex Mechanisms.

The involvement of fronto-striatal circuits in item and associative memory retrieval as well as in the stabilization of memories by retrieval practice suggests that both retrieval and re-encoding of stored memories might rely on dopaminergic mechanisms in humans. We tested these hypotheses in a placebo-controlled pharmacological fMRI study using 2 mg of the D2 antagonist haloperidol administered acutely before a cued associative recall task of previously encoded picture-word pairs in 53 healthy humans of both sexes. The cued associative recall was moreover repeated 3 d later outside the scanner without pharmacological intervention.

Dopamine is a double-edged sword: dopaminergic modulation enhances memory retrieval performance but impairs metacognition.

While memory encoding and consolidation processes have been linked with dopaminergic signaling for a long time, the role of dopamine in episodic memory retrieval remained mostly unexplored. Based on previous observations of striatal activity during memory retrieval, we used pharmacological functional magnetic resonance imaging to investigate the effects of dopamine on retrieval performance and metacognitive memory confidence in healthy humans. Dopaminergic modulation by the D2 antagonist haloperidol administered acutely during the retrieval phase improved recognition accuracy of previously learned pictures significantly and was associated with increased activity in the substantia nigra/ventral tegmental area, locus coeruleus, hippocampus, and amygdala during retrieval.

Enhanced transformation of incidentally learned knowledge into explicit memory by dopaminergic modulation.

During incidental learning statistical regularities are extracted from the environment without the intention to learn. Acquired implicit memory of these regularities can affect behavior in the absence of awareness. However, conscious insight in the underlying regularities can also develop during learning.

Differential Patterns of Dysconnectivity in Mirror Neuron and Mentalizing Networks in Schizophrenia.

Impairments of social cognition are well documented in patients with schizophrenia (SCZ), but the neural basis remains poorly understood. In light of evidence that suggests that the "mirror neuron system" (MNS) and the "mentalizing network" (MENT) are key substrates of intersubjectivity and joint action, it has been suggested that dysfunction of these neural networks may underlie social difficulties in SCZ patients. Additionally, MNS and MENT might be associated differently with positive vs negative symptoms, given prior social cognitive and symptom associations.

Multimodal connectivity of motor learning-related dorsal premotor cortex.

The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has been proposed as a technique that may also allow delineation of functional connectivity.

Goal- and retrieval-dependent activity in the striatum during memory recognition.

The striatum has been associated with successful memory retrieval but the precise functional link still remains unclear. One hypothesis is that striatal activity reflects an active evaluation process of the retrieval outcome dependent on the current behavioral goals rather than being a consequence of memory reactivation. We have recently shown that the striatum also correlates with confidence in memory recognition, which could reflect high subjective value ascribed to high certainty decisions.

Human pulvinar functional organization and connectivity.

The human pulvinar is the largest thalamic area in terms of size and cortical connectivity. Although much is known about regional pulvinar structural anatomy, relatively little is known about pulvinar functional anatomy in humans. Cooccurrence of experimentally induced brain activity is a traditional metric used to establish interregional brain connectivity and forms the foundation of functional neuroimaging connectivity analyses.

Evidence for an anterior-posterior differentiation in the human hippocampal formation revealed by meta-analytic parcellation of fMRI coordinate maps: focus on the subiculum.

Previous studies, predominantly in experimental animals, have suggested the presence of a differentiation of function across the hippocampal formation. In rodents, ventral regions are thought to be involved in emotional behavior while dorsal regions mediate cognitive or spatial processes. Using a combination of modeling the co-occurrence of significant activations across thousands of neuroimaging experiments and subsequent data-driven clustering of these data we were able to provide evidence of distinct subregions within a region corresponding to the human subiculum, a critical hub within the hippocampal formation.

Comparison of structural covariance with functional connectivity approaches exemplified by an investigation of the left anterior insula.

The anterior insula is a multifunctional region involved in various cognitive, perceptual and socio-emotional processes. In particular, a portion of the left anterior insula is closely associated with working memory processes in healthy participants and shows gray matter reduction in schizophrenia. To unravel the functional networks related to this left anterior insula region, we here combined resting state connectivity, meta-analytic-connectivity modeling (MACM) and structural covariance (SC) in addition to functional characterization based on BrainMap meta-data.

Meta-analytically informed network analysis of resting state FMRI reveals hyperconnectivity in an introspective socio-affective network in depression.

Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression.

Tackling the multifunctional nature of Broca's region meta-analytically: co-activation-based parcellation of area 44.

Cytoarchitectonic area 44 of Broca's region in the left inferior frontal gyrus is known to be involved in several functional domains including language, action and music processing. We investigated whether this functional heterogeneity is reflected in distinct modules within cytoarchitectonically defined left area 44 using meta-analytic connectivity-based parcellation (CBP). This method relies on identifying the whole-brain co-activation pattern for each area 44 voxel across a wide range of functional neuroimaging experiments and subsequently grouping the voxels into distinct clusters based on the similarity of their co-activation patterns.

Aberrant connectivity of areas for decoding degraded speech in patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are a hallmark of psychotic experience. Various mechanisms including misattribution of inner speech and imbalance between bottom-up and top-down factors in auditory perception potentially due to aberrant connectivity between frontal and temporo-parietal areas have been suggested to underlie AVH. Experimental evidence for disturbed connectivity of networks sustaining auditory-verbal processing is, however, sparse.

Resting state functional connectivity in patients with chronic hallucinations.

Auditory verbal hallucinations (AVH) are not only among the most common but also one of the most distressing symptoms of schizophrenia. Despite elaborate research, the underlying brain mechanisms are as yet elusive. Functional MRI studies have associated the experience of AVH with activation of bilateral language-related areas, in particular the right inferior frontal gyrus (rIFG) and the left superior temporal gyrus (lSTG).

Effects of prior information on decoding degraded speech: an fMRI study.

Expectations and prior knowledge are thought to support the perceptual analysis of incoming sensory stimuli, as proposed by the predictive-coding framework. The current fMRI study investigated the effect of prior information on brain activity during the decoding of degraded speech stimuli. When prior information enabled the comprehension of the degraded sentences, the left middle temporal gyrus and the left angular gyrus were activated, highlighting a role of these areas in meaning extraction.