Double Dissociation of Dopamine Genes and Timing in Humans

University of Pennsylvania, Philadelphia, PA 19104-6241, USA.
Journal of Cognitive Neuroscience (Impact Factor: 4.09). 10/2011; 23(10):2811-21. DOI: 10.1162/jocn.2011.21626
Source: PubMed


A number of lines of evidence implicate dopamine in timing [Rammsayer, T. H. Neuropharmacological approaches to human timing. In S. Grondin (Ed.), Psychology of time (pp. 295-320). Bingley, UK: Emerald, 2008; Meck, W. H. Neuropharmacology of timing and time perception. Brain Research, Cognitive Brain Research, 3, 227-242, 1996]. Two human genetic polymorphisms are known to modulate dopaminergic activity. DRD2/ANKK1-Taq1a is a D(2) receptor polymorphism associated with decreased D(2) density in the striatum [Jönsson, E. G., Nothen, M. M., Grunhage, F., Farde, L., Nakashima, Y., Propping, P., et al. Polymorphisms in the dopamine D(2) receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Molecular Psychiatry, 4, 290-296, 1999]; COMT Val158Met is a functional polymorphism associated with increased activity of the COMT enzyme such that catabolism of synaptic dopamine is greater in pFC [Meyer-Lindenberg, A., Kohn, P. D., Kolachana, B., Kippenhan, S., McInerney-Leo, A., Nussbaum, R., et al. Midbrain dopamine and prefrontal function in humans: Interaction and modulation by COMT genotype. Nature Neuroscience, 8, 594-596, 2005]. To investigate the role of dopamine in timing, we genotyped 65 individuals for DRD2/ANKK1-Taq1a, COMT Val158Met, and a third polymorphism, BDNF Val66Met, a functional polymorphism affecting the expression of brain-derived neurotrophic factor [Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257-269, 2003]. Subjects were tested on a temporal discrimination task with sub- and supra-second intervals (500- and 2000-msec standards) as well as a spontaneous motor tempo task. We found a double dissociation for temporal discrimination: the DRD2/ANKK1-Taq1a polymorphism (A1+ allele) was associated with significantly greater variability for the 500-msec duration only, whereas the COMT Val158Met polymorphism (Val/Val homozygotes) was associated with significantly greater variability for the 2000-msec duration only. No differences were detected for the BDNF Vall66Met variant. Additionally, the DRD2/ANKK1-Taq1a polymorphism was associated with a significantly slower preferred motor tempo. These data provide a potential biological basis for the distinctions between sub- and supra-second timing and suggest that BG are integral for the former whereas pFC is implicated in the latter.

1 Follower
30 Reads
  • Source
    • "The addition of the defection lever effectively mixes a bi-peak procedure with a delay of gratification procedure, in which the smaller sooner option is available throughout the delay (Reynolds et al., 2002). We then used this hybrid procedure to measure the effects of a selective 5-HT reuptake inhibitor (fluoxetine) and indirect DA agonists (cocaine and methamphetamine) on both interval timing and intertemporal choice because of their known impact on time perception and prediction (Ardayfio et al., 2008; Barr et al., 2004; Coull et al., 2011; Daw et al., 2002; Sysoeva et al., 2010; Wiener et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of our study was to characterize the relationship between intertemporal choice and interval timing, including determining how drugs that modulate brain serotonin and dopamine levels influence these two processes. In Experiment 1, rats were tested on a standard 40-s peak-interval procedure following administration of fluoxetine (3, 5, or 8mg/kg) or vehicle to assess basic effects on interval timing. In Experiment 2, rats were tested in a novel behavioral paradigm intended to simultaneously examine interval timing and impulsivity. Rats performed a variant of the bi-peak procedure using 10-s and 40-s target durations with an additional "defection" lever that provided the possibility of a small, immediate reward. Timing functions remained relatively intact, and 'patience' across subjects correlated with peak times, indicating a negative relationship between 'patience' and clock speed. We next examined the effects of fluoxetine (5mg/kg), cocaine (15mg/kg), or methamphetamine (1mg/kg) on task performance. Fluoxetine reduced impulsivity as measured by defection time without corresponding changes in clock speed. In contrast, cocaine and methamphetamine both increased impulsivity and clock speed. Thus, variations in timing may mediate intertemporal choice via dopaminergic inputs. However, a separate, serotonergic system can affect intertemporal choice without affecting interval timing directly. This article is part of a Special Issue entitled: Associative and Temporal Learning.
    Behavioural processes 10/2014; 101:123-134. DOI:10.1016/j.beproc.2013.09.013 · 1.57 Impact Factor
  • Source
    • "Specifically, the PSE was more negative for (1) carriers of the SS genotype of the 5-HTT gene (associated with lower 5-HT reuptake) than for carriers of the SL and LL variants, (2) carriers of the low-expression variant of monoamine oxidase A (MAOA, associated with lower 5-HT breakdown) than for carriers of the high-expression variant, and (3) carriers of the TT genotype of the 5-HT2a receptor (associated with higher receptor density) than for CC-carriers. In contrast, differences in time perception were not related to differences in the genes encoding components of the DA system, although more recent genetic studies have shown DA receptors, transporter, and enzyme systems to be important for interval timing.87–89 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Time perception is fundamental and heavily researched, but the field faces a number of obstacles to theoretical progress. In this advanced review, we focus on three pieces of “bad news” for time perception research: temporal perception is highly labile across changes in experimental context and task; there are pronounced individual differences not just in overall performance but in the use of different timing strategies and the effect of key variables; and laboratory studies typically bear little relation to timing in the “real world”. We describe recent examples of these issues and in each case offer some “good news” by showing how new research is addressing these challenges to provide rich insights into the neural and information-processing bases of timing and time perception.
    Wiley interdisciplinary reviews. Cognitive science 07/2014; 5:429-446. DOI:10.1002/wcs.1298 · 0.79 Impact Factor
  • Source
    • "People are moving away from the use of Braille, due to high cost and dimensions of Braille books, as well as the existing range of alternative technologies to read and communicate beyond the written word. But Braille is the only path that allows interaction reader / text because by the touch of text messages go straight to the reader [2]. "
    Conference Paper: Single Braille cell
    [Show abstract] [Hide abstract]
    ABSTRACT: Blind people face several problems related to access information. A Braille language symbol is a technique to solve this problem. A set of points which when nerve endings felt by the finger lets to form a character. With the exponential growth in technological era, the need arose to bring the users a Braille computer. For this, electromechanical devices were created, called Braille displays, allowing users to make use of Braille on their own computers. However, access to this kind of devices is difficult, because the embedded technology turn it expensive. The current Braille displays have commonly something between 8 and 80 cells and the market trend is to rise this number. A cell is nothing more than the set of points that make up a Braille character, commonly a piezo Braille cell. Another alarming factor is the absence of specific software adapted to users' needs by using accessibility standards. In this context, this work aims to contribute to digital access of Braille, by developing an integrated solution of hardware and software. The proposed system is based on the concept of one Braille cell, since Braille reading is done character by character. In this scenario, was also developed a specific software interface which also communicates with hardware solution. The software makes use of the accessibility standards imposed by the U.S. consortium for the visually impaired, formed by large companies, such as IBM and Microsoft. The proposed system is been evaluated by blind voluntaries with different knowledge of Braille and computer experience. The preliminary results show the efficiency of the system proposed.
    5th IEEE Biosignals and Biorobotics conference (BRC 2014); 05/2014
Show more


30 Reads
Available from