Science posts

See science posts on page 19 below.

    • 1997
    • Tadao Arinami et al.
    • A Functional Polymorphism in the Promoter Region of the Dopamine D2 Receptor Gene Is Associated with Schizophrenia
    • An excess dopaminergic activity may be implicated in the etiology of schizophrenia. Our objective was to identify nucleotide variants in the 5′ region of the dopamine D2 receptor gene (DRD2) and to clarify their effects on schizophrenia. We identified two polymorphisms, the A-241G and −141C Ins/Del, by examination of 259 bp in the 5′-flanking region and 249 bp of exon 1 of DRD2. Reporter constructs containing the −141C Delallele cloned into a luciferase reporter plasmid drove 21% (Y-79 cells) and 43% (293 cells) expression compared with the −141C Ins allele. In a case-control study, the −141C Delallele frequency was significantly lower in 260 schizophrenic patients than in 312 controls (OR = 0.60, 95%CI 0.44–0.81, P < 0.001). No significant association was found between the A-241G polymorphism and in vitro luciferase activity, or in allele frequency between the patients versus controls. These findings show that the −141C Ins/Delmay b..
    • 2005
    • Sidney H VanNess et al.
    • The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density
    • Background A 40-bp variable number of tandem repeats (VNTR) polymorphism exists in the 15th exon of DAT1, the gene encoding the human dopamine transporter (DAT). Though the VNTR resides in a region encoding the 3' untranslated region (UTR) and does not alter the protein's amino acid sequence, the prevalent 10-repeat variant has shown both linkage and association to Attention Deficit Hyperactivity Disorder (ADHD). In this study, we examined the effects of the DAT1 VNTR on measures of in vitro DAT expression and pharmacology. A series of four DAT1 constructs, each containing the DAT1 coding region, but varying with respect to the downstream presence or content of the 3'UTR, were engineered and stably transfected into an HEK-293 variant using Flp-In integration, an enzyme-mediated, site-specific recombination technology. Results [3H] Win 35,428 saturation binding assays and DAT immunoblots revealed statistically significant differences in DAT expression attributable to DAT1 gen..
    • 2014
    • Markus Ullsperger et al.
    • Neurophysiology of Performance Monitoring and Adaptive Behavior
    • Successful goal-directed behavior requires not only correct action selection, planning, and execution but also the ability to flexibly adapt behavior when performance problems occur or the environment changes. A prerequisite for determining the necessity, type, and magnitude of adjustments is to continuously monitor the course and outcome of one's actions. Feedback-control loops correcting deviations from intended states constitute a basic functional principle of adaptation at all levels of the nervous system. Here, we review the neurophysiology of evaluating action course and outcome with respect to their valence, i.e., reward and punishment, and initiating short- and long-term adaptations, learning, and decisions. Based on studies in humans and other mammals, we outline the physiological principles of performance monitoring and subsequent cognitive, motivational, autonomic, and behavioral adaptation and link them to the underlying neuroanatomy, neurochemistry, psychological theorie..
    • 2009
    • Christian C. Luhmann et al.
    • Temporal Decision-Making: Insights from Cognitive Neuroscience
    • Decisions frequently have consequences that play out over time and these temporal factors can exert strong influences on behavior. For example, decision-makers exhibit delay discounting, behaving as though immediately consumable goods are more valuable than those available only after some delay. With the use of functional magnetic resonance imaging, we are now beginning to characterize the physiological bases of such behavior in humans and to link work on this topic from neuroscience, psychology, and economics. Here we review recent neurocognitive investigations of temporal decision-making and outline the theoretical picture that is beginning to take shape. Taken as a whole, this body of work illustrates the progress made in understanding temporal choice behavior. However, we also note several questions that remain unresolved and areas where future work is needed.
    • 2007
    • Juliana Yacubian et a.
    • Gene–gene interaction associated with neural reward sensitivity
    • Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual dif..
    • 2007
    • Leontien Diergaarde et al.
    • Impulsive Choice and Impulsive Action Predict Vulnerability to Distinct Stages of Nicotine Seeking in Rats
    • Background Although heavy smoking has been associated with impulsivity in humans, it is not clear whether poor impulse control represents a risk factor in the etiology of nicotine dependence. Methods To address this issue, rats were selected on the basis of individual differences in impulsivity in the delayed reward task (impulsive choice) and the 5-choice serial reaction time task (impulsive action). Subsequently, rats were subjected to a nicotine self-administration (SA) paradigm tailored to measure the motivational properties of nicotine and nicotine-associated stimuli. In separate groups, differences in electrically evoked dopamine release in slice preparations obtained from several mesolimbic brain regions were determined. Results Impulsive action was associated with an enhanced motivation to initiate and maintain nicotine SA. In contrast, impulsive choice predicted a diminished ability to inhibit nicotine seeking during abstinence and an enhanced vulnerability to rel..
    • 2008
    • Bianca C. Wittmann et al.
    • Striatal Activity Underlies Novelty-Based Choice in Humans
    • The desire to seek new and unfamiliar experiences is a fundamental behavioral tendency in humans and other species. In economic decision making, novelty seeking is often rational, insofar as uncertain options may prove valuable and advantageous in the long run. Here, we show that, even when the degree of perceptual familiarity of an option is unrelated to choice outcome, novelty nevertheless drives choice behavior. Using functional magnetic resonance imaging (fMRI), we show that this behavior is specifically associated with striatal activity, in a manner consistent with computational accounts of decision making under uncertainty. Furthermore, this activity predicts interindividual differences in susceptibility to novelty. These data indicate that the brain uses perceptual novelty to approximate choice uncertainty in decision making, which in certain contexts gives rise to a newly identified and quantifiable source of human irrationality.
    • 2006
    • Nico Bunzeck et al.
    • Absolute Coding of Stimulus Novelty in the Human Substantia Nigra/VTA
    • Novelty exploration can enhance hippocampal plasticity in animals through dopaminergic neuromodulation arising in the substantia nigra/ventral tegmental area (SN/VTA). This enhancement can outlast the exploration phase by several minutes. Currently, little is known about dopaminergic novelty processing and its relationship to hippocampal function in humans. In two functional magnetic resonance imaging (fMRI) studies, SN/VTA activations in humans were indeed driven by stimulus novelty rather than other forms of stimulus salience such as rareness, negative emotional valence, or targetness of familiar stimuli, whereas hippocampal responses were less selective. SN/VTA novelty responses were scaled according to absolute rather than relative novelty in a given context, unlike adaptive SN/VTA responses recently reported for reward outcome in animal studies. Finally, novelty enhanced learning and perirhinal/parahippocampal processing of familiar items presented in the same context. Thus, the..
    • 2010
    • Todd S. Braver et al.
    • Vive les differences! Individual variation in neural mechanisms of executive control
    • Investigations of individual differences have become increasingly important in the cognitive neuroscience of executive control. For instance, individual variation in lateral prefrontal cortex function (and that of associated regions) has recently been used to identify contributions of executive control processes to a number of domains, including working memory capacity, anxiety, reward/motivation, and emotion regulation. However, the origins of such individual differences remain poorly understood. Recent progress toward identifying the genetic and environmental sources of variation in neural traits, in combination with progress identifying the causal relationships between neural and cognitive processes, will be essential for developing a mechanistic understanding of executive control.
    • 2010
    • Cindy M. de Frias et al.
    • Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
    • The catechol O-methyltransferase (COMT) gene—encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)—contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic–phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic–phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, ..