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Author: Lorenz Deserno (38)


Feb
2018

Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks.

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Sep
2017

Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM) load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection.

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Dec
1969

Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence.

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Dec
1969

Instrumental learning and decision-making rely on two parallel systems: a goal-directed and a habitual system. In the past decade, several paradigms have been developed to study these systems in animals and humans by means of e.g.

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Aug
2017

Schizophrenia is a heterogeneous spectrum disorder often associated with detrimental negative symptoms. In recent years, computational approaches to psychiatry have attracted growing attention. Negative symptoms have shown some overlap with general cognitive impairments and were also linked to impaired motivational processing in brain circuits implementing reward prediction.

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Dec
2017

Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by a triad of movement disorder, neuropsychiatric symptoms and cognitive deficits. The striatum is particularly vulnerable to the effects of mutant huntingtin, and cell loss can already be found in presymptomatic stages. Since the striatum is well known for its role in reinforcement learning, we hypothesized to find altered behavioral and neural responses in HD patients in a probabilistic reinforcement learning task performed during functional magnetic resonance imaging.

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Oct
2016

Addicted individuals continue substance use despite the knowledge of harmful consequences and often report having no choice but to consume. Computational psychiatry accounts have linked this clinical observation to difficulties in making flexible and goal-directed decisions in dynamic environments via consideration of potential alternative choices. To probe this in alcohol-dependent patients (n = 43) versus healthy volunteers (n = 35), human participants performed an anticorrelated decision-making task during functional neuroimaging.

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Dec
1969

Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct ('direct'/'indirect') dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task - WPT) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [C]raclopride Positron Emission Tomography (PET), allowing for assessment of striatal DA release during learning, (2) Parkinson's disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington's disease (HD) patients, a disease that is associated with hyper-activation of the 'direct' pathway.

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Jan
2017

Adolescence is a critical maturation period for human cognitive control and executive function. In this study, a large sample of adolescents (n = 85) performed a reversal learning task during functional magnetic resonance imaging. We analyzed behavioral data using a reinforcement learning model to provide individually fitted parameters and imaging data with regard to reward prediction errors (PE).

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May
2017

Alcohol use disorder (AUD) and addiction in general is characterized by failures of choice resulting in repeated drug intake despite severe negative consequences. Behavioral change is hard to accomplish and relapse after detoxification is common and can be promoted by consumption of small amounts of alcohol as well as exposure to alcohol-associated cues or stress. While those environmental factors contributing to relapse have long been identified, the underlying psychological and neurobiological mechanism on which those factors act are to date incompletely understood.

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Aug
2017

The default mode network (DMN), a network centered around the cortical midline, shows deactivation during most cognitive tasks and pronounced resting-state connectivity, but is actively engaged in self-reference and social cognition. It is, however, yet unclear how information reaches the DMN during social cognitive processing. Here, we addressed this question using dynamic causal modeling (DCM) of functional magnetic resonance imaging (fMRI) data acquired during self-reference (SR) and reference to others (OR).

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Feb
2017

Despite its clinical relevance and the recent recognition as a diagnostic category in the DSM-5, binge eating disorder (BED) has rarely been investigated from a cognitive neuroscientific perspective targeting a more precise neurocognitive profiling of the disorder. BED patients suffer from a lack of behavioral control during recurrent binge eating episodes and thus fail to adapt their behavior in the face of negative consequences, eg, high risk for obesity. To examine impairments in flexible reward-based decision-making, we exposed BED patients (n=22) and matched healthy individuals (n=22) to a reward-guided decision-making task during functional resonance imaging (fMRI).

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Dec
1969

Generative models of neuroimaging data, such as dynamic causal models (DCMs), are commonly used for inferring effective connectivity from individual subject data. Recently introduced "generative embedding" approaches have used DCM-based connectivity parameters for supervised classification of individual patients or to find unknown subgroups in heterogeneous groups using unsupervised clustering methods.
We present a novel framework which combines DCMs with finite mixture models into a single hierarchical model.

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Mar
2016

Elevated striatal dopamine function is one of the best-established findings in schizophrenia. In this review, we discuss causes and consequences of this striata! dopamine alteration. We first summarize earlier findings regarding striatal reward processing and anticipation using functional neuroimaging.

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Aug
2016

Behavioral control is influenced not only by learning from the choices made and the rewards obtained but also by "what might have happened," that is, inference about unchosen options and their fictive outcomes. Substantial progress has been made in understanding the neural signatures of direct learning from choices that are actually made and their associated rewards via reward prediction errors (RPEs). However, electrophysiological correlates of abstract inference in decision-making are less clear.

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Dec
1969

Addiction shows familial aggregation and previous endophenotype research suggests that healthy relatives of addicted individuals share altered behavioral and cognitive characteristics with individuals suffering from addiction. In this study we asked whether impairments in behavioral control proposed for addiction, namely a shift from goal-directed, model-based toward habitual, model-free control, extends toward an unaffected sample (n = 20) of adult children of alcohol-dependent fathers as compared to a sample without any personal or family history of alcohol addiction (n = 17). Using a sequential decision-making task designed to investigate model-free and model-based control combined with a computational modeling analysis, we did not find any evidence for altered behavioral control in individuals with a positive family history of alcohol addiction.

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Jan
2016

A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis.

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Jul
2015

The striatum is known to play a key role in reinforcement learning, specifically in the encoding of teaching signals such as reward prediction errors (RPEs). It has been proposed that aberrant salience attribution is associated with impaired coding of RPE and heightened dopamine turnover in the striatum, and might be linked to the development of psychotic symptoms. However, the relationship of aberrant salience attribution, RPE coding, and dopamine synthesis capacity has not been directly investigated.

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Jul
2015

Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine.

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Jun
2015

In the present study, we explored possible alterations in the default mode network (DMN) and its functional connectivity in 41 schizophrenia patients and 42 age-matched healthy controls. Schizophrenia patients displayed reduced activation in the ventromedial prefrontal cortex, left superior temporal gyrus including auditory cortex and temporal pole. Psychophysiological interaction analysis revealed reduced connectivity between left superior temporal gyrus including auditory cortex and the left temporal pole in schizophrenia patients compared to healthy subjects.

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Mar
2015

It is suggested that acute stress shifts behavioral control from goal-directed, model-based toward habitual, model-free strategies. Recent findings indicate that interindividual differences in the cortisol stress response influence model-based decision-making. Although not yet investigated in humans, animal studies show that chronic stress also shifts decision-making toward more habitual behavior.

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Feb
2015

Dual system theories suggest that behavioral control is parsed between a deliberative "model-based" and a more reflexive "model-free" system. A balance of control exerted by these systems is thought to be related to dopamine neurotransmission. However, in the absence of direct measures of human dopamine, it remains unknown whether this reflects a quantitative relation with dopamine either in the striatum or other brain areas.

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Feb
2015

Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such 'hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse.

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Mar
2015

[(11)C]P943 is a novel, highly selective 5-HT1B PET radioligand. The aim of this study was to determine the test-retest reliability of [(11)C]P943 using two different modeling methods and to perform a power analysis with each quantification technique.
Seven healthy volunteers underwent two PET scans on the same day.

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Dec
1969

Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive.
Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns.

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Dec
2014

Impulsivity is a multidimensional construct that has been suggested as a vulnerability factor for several psychiatric disorders, especially addiction disorders. Poor response inhibition may constitute one facet of impulsivity. Trait impulsivity can be assessed by self-report questionnaires such as the widely used Barratt Impulsiveness Scale (BIS-11).

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Dec
1969

In experimental psychology different experiments have been developed to assess goal-directed as compared to habitual control over instrumental decisions. Similar to animal studies selective devaluation procedures have been used. More recently sequential decision-making tasks have been designed to assess the degree of goal-directed vs.

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Nov
2015

The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults.

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Dec
2013

Abnormalities in reinforcement learning are a key finding in schizophrenia and have been proposed to be linked to elevated levels of dopamine neurotransmission. Behavioral deficits in reinforcement learning and their neural correlates may contribute to the formation of clinical characteristics of schizophrenia. The ability to form predictions about future outcomes is fundamental for environmental interactions and depends on neuronal teaching signals, like reward prediction errors.

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Dec
1969

This proof-of-concept study examines the feasibility of defining subgroups in psychiatric spectrum disorders by generative embedding, using dynamical system models which infer neuronal circuit mechanisms from neuroimaging data. To this end, we re-analysed an fMRI dataset of 41 patients diagnosed with schizophrenia and 42 healthy controls performing a numerical n-back working-memory task. In our generative-embedding approach, we used parameter estimates from a dynamic causal model (DCM) of a visual-parietal-prefrontal network to define a model-based feature space for the subsequent application of supervised and unsupervised learning techniques.

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Jul
2014

Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes. Here, we sought to disentangle reward and attention-related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants. During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention-demanding task at two different levels of difficulty.

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Nov
2014

While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning.

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Apr
2014

Subjects with schizophrenia are impaired at reinforcement-driven reversal learning from as early as their first episode. The neurobiological basis of this deficit is unknown. We obtained behavioral and fMRI data in 24 unmedicated, primarily first episode, schizophrenia patients and 24 age-, IQ- and gender-matched healthy controls during a reversal learning task.

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Oct
2013

In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis.

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Sep
2012

Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown.
In a group of 16 healthy participants aged 22-61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K (in) (app); millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ.
Cognitive speed was associated with the magnitude of K (in) (app) in the prefrontal cortex (p < 0.

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Jun
2013

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subsample of 17 subjects also with positron emission tomography using 6-[(18) F]fluoro-L-DOPA to assess dopamine synthesis capacity.

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Jan
2012

The neural mechanisms behind cognitive deficits in schizophrenia still remain unclear. Functional neuroimaging studies on working memory (WM) yielded inconsistent results, suggesting task performance as a moderating variable of prefrontal activation. Beyond regional specific activation, disordered integration of brain regions was supposed as a critical pathophysiological mechanism of cognitive deficits in schizophrenia.

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