Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

Context: In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied.

Objective: To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients.

Ventral striatal activation during reward processing in subjects with ultra-high risk for schizophrenia.

Background: Early dysfunction of the brain reward system in schizophrenia might be already recognized in the prodromal phase of this illness. We used functional magnetic resonance imaging to assess the blood oxygen level-dependent response in the ventral striatum (VS) of subjects with ultra-high risk for psychosis during the presentation of reward-indicating and loss-indicating stimuli.

Methods: Thirteen prodromal patients (mean age: 25.

Decreased Verbal Learning but not Recognition Performance in Alcohol-dependent Individuals During Early Abstinence.

Objective: Alcoholism ultimately leads to impairment of memory and other cognitive functions. This can interfere with treatment, if cognitively impaired alcohol-dependent individuals have difficulties recalling and implementing skills acquired during therapy. We investigate if alcohol-dependent individuals without clinically apparent withdrawal symptoms may still be impaired in higher-order cognitive functions.

Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram.

Major Depressive Disorder (MDD) involves deficits in the reward system. While neuroimaging studies have focused on affective stimulus processing, few investigations have directly addressed deficits in the anticipation of incentives. We examined neural responses during gain and loss anticipation in patients with MDD before and after treatment with a selective serotonin reuptake inhibitor (SSRI).

Reward processing in male adults with childhood ADHD--a comparison between drug-naïve and methylphenidate-treated subjects.

Rationale: Dysfunctional reward processing has been proposed as a main deficit in attention-deficit/hyperactivity disorder (ADHD), which could be modulated by treatment with methylphenidate (MPH).

Objectives: We examined differences in reward processing in adulthood (independent of actual ADHD) depending on MPH treatment during childhood.

Methods: Eleven males with childhood ADHD treated with MPH, 12 drug-naïve males with childhood ADHD, and 12 controls matched by age, handedness, and smoking behavior were studied drug-free using functional magnetic resonance imaging.

Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence.

Objective: Alcohol-dependent patients in early abstinence show an impairment of cognitive functions which can be seen in poor implementation of newly learned skills for avoiding relapse. Executive dysfunction may persist during abstinence in alcohol-dependent persons, thus mitigating long-term abstinence. This study assessed visual memory function and choice of organizational strategies in alcoholics, as these are major factors necessary to implement ongoing behavior changes which are required for maintaining abstinence.

Childhood methylphenidate treatment of ADHD and response to affective stimuli.

Neural correlates of emotional dysregulation in attention-deficit/hyperactivity disorder (ADHD) and persisting influence of Methylphenidate (MPH) still remain insufficiently understood. Decreased activation in the subgenual cingulate and the ventral striatum were found during the perception of positive and negative affective pictures in drug-naïve males with ADHD during childhood (n=10). Males with ADHD during childhood treated with MPH (n=10) did not show any significant differences compared to healthy controls (n=10).

Prefrontal cortex fails to learn from reward prediction errors in alcohol dependence.

Patients suffering from addiction persist in consuming substances of abuse, despite negative consequences or absence of positive consequences. One potential explanation is that these patients are impaired at flexibly adapting their behavior to changes in reward contingencies. A key aspect of adaptive decision-making involves updating the value of behavioral options.

Switching schizophrenia patients from typical neuroleptics to aripiprazole: effects on working memory dependent functional activation.

Background: Deficits in working memory (WM) are a core symptom of schizophrenia patients and have been linked to dysfunctional prefrontal activation, which might be caused by a mesocortical hypodopaminergic state. Aripiprazole--a partial dopamine antagonist--is a novel antipsychotic, which increases frontal dopamine concentrations in preclinical studies. However, little is known about specific medication effects on the modulation of frontal activation during WM performance.

Altered representation of expected value in the orbitofrontal cortex in mania.

Objective: Increased responsiveness to appetitive and reduced responsiveness to aversive anticipatory cues may be associated with dysfunction of the brain reward system in mania. Here we studied neural correlates of gain and loss expectation in mania using functional magnetic resonance imaging (fMRI).

Method: Fifteen manic patients and 26 matched healthy control individuals performed a monetary incentive delay task, during which subjects anticipated to win or lose a varying amount of money.

Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics.

Background: Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects.

Methods: Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence.

5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls.

Rationale: In major depression, prefrontal regulation of limbic brain areas may be a key mechanism that is impaired during the processing of affective information. This prefrontal-limbic interaction has been shown to be modulated by serotonin (5-HTT) genotype, indicating a higher risk for major depressive disorder (MDD) with increasing number of 5-HTT low-expression alleles.

Objective: Functional magnetic resonance imaging was used to assess neural response to uncued unpleasant affective pictures in 21 unmedicated patients with MDD compared to 21 matched healthy controls, taking into account genetic influences of the 5-HTT (SCL6A4) high- and low-expression genotype.

A model comparison of COMT effects on central processing of affective stimuli.

The number of studies on imaging genetics has risen considerably over the last few years, and haplotypes are being increasingly applied as a model to increase the explained variance in functional brain activation. Haplotypes, however, are not always the preferable approach. While such highly complex models have a greater capacity for fitting data, they might also lead to over-fitting.

Reward feedback alterations in unmedicated schizophrenia patients: relevance for delusions.

Background: Increased attribution of incentive salience to neutral or aversive stimuli might be associated with dysfunction of neuronal processing of positive and negative reinforcement and contribute to the formation of delusions in schizophrenia.

Methods: Fifteen unmedicated patients with schizophrenia (8 drug-naive and 7 drug-free for at least 3 months) and 15 age- and gender-matched healthy control participants underwent functional magnetic resonance imaging to investigate neural responses to feedback of (successful vs. unsuccessful) monetary gain or avoidance of loss.

A preliminary study of increased amygdala activation to positive affective stimuli in mania.

Objectives: The present study in hypomanic and manic patients explored how amygdala responses to affective stimuli depend on the valence of the stimuli presented.

Methods: We compared 10 patients with 10 matched healthy control subjects. We measured blood oxygen level-dependent (BOLD) responses in the amygdala while subjects passively viewed photographs taken from the International Affective Picture System.

Dopamine in amygdala gates limbic processing of aversive stimuli in humans.

Dopamine is released under stress and modulates processing of aversive stimuli. We found that dopamine storage capacity in human amygdala, measured with 6-[(18)F]fluoro-L-DOPA positron emission tomography, was positively correlated with functional magnetic resonance imaging blood oxygen level-dependent signal changes in amygdala and dorsal anterior cingulate cortex that were evoked by aversive stimuli. Furthermore, functional connectivity between these two regions was inversely related to trait anxiety.

Identifying the neural circuitry of alcohol craving and relapse vulnerability.

With no further intervention, relapse rates in detoxified alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of alcohol and to alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified alcoholics.

Dorsal striatal-midbrain connectivity in humans predicts how reinforcements are used to guide decisions.

It has been suggested that the target areas of dopaminergic midbrain neurons, the dorsal (DS) and ventral striatum (VS), are differently involved in reinforcement learning especially as actor and critic. Whereas the critic learns to predict rewards, the actor maintains action values to guide future decisions. The different midbrain connections to the DS and the VS seem to play a critical role in this functional distinction.

Novelty seeking modulates medial prefrontal activity during the anticipation of emotional stimuli.

In a functional magnetic resonance imaging experiment, expectancy cues signaling emotional stimuli were used to study the personality trait of novelty seeking. BOLD responses to emotional expectancy were positively correlated with novelty-seeking scores in the medial prefrontal cortex. This correlation was strongest for the sub-dimension of exploratory excitability.

Catechol-O-methyltransferase val158met genotype influences neural processing of reward anticipation.

Reward processing depends critically on dopaminergic neurotransmission in the ventral striatum. The common polymorphism val(158)met of catechol-O-methyltransferase (COMT) accounts for significant interindividual variations in dopamine (DA) degradation, although the direct effect of COMT on striatal DA might be limited. Using fMRI we assessed the influence of COMT val(158)met genotype on brain activations elicited by the anticipation of monetary gains and losses in forty-four healthy volunteers.

Amygdala volume associated with alcohol abuse relapse and craving.

Objective: Amygdala volume has been associated with drug craving in cocaine addicts, and amygdala volume reduction is observed in some alcohol-dependent subjects. This study sought an association in alcohol-dependent subjects between volumes of reward-related brain regions, alcohol craving, and the risk of relapse.

Method: Besides alcohol craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification.

Switching schizophrenia patients from typical neuroleptics to olanzapine: effects on BOLD response during attention and working memory.

Dysfunctional activation of the dorsolateral prefrontal cortex (DLPFC) during working memory (WM) in schizophrenia patients has repeatedly been observed, however little is known about specific medication effects on the modulation of DLPFC activation. We measured activation of DLPFC during a WM task in a longitudinal fMRI study in ten schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to olanzapine (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points.