Double dissociation of dopamine genes and timing in humans.

University of Pennsylvania, Philadelphia, PA 19104-6241, USA.
Journal of Cognitive Neuroscience (Impact Factor: 4.69). 10/2011; 23(10):2811-21. DOI: 10.1162/jocn.2011.21626
Source: PubMed

ABSTRACT 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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The capacity to synchronize movements to the beat in music is a complex, and apparently uniquely human characteristic. Synchronizing movements to the beat requires beat perception, which entails prediction of future beats in rhythmic sequences of temporal intervals. Absolute timing mechanisms, where patterns of temporal intervals are encoded as a series of absolute durations, cannot fully explain beat perception. Beat perception seems better accounted for by relative timing mechanisms, where temporal intervals of a pattern are coded relative to a periodic beat interval. Evidence from behavioral, neuroimaging, brain stimulation and neuronal cell recording studies suggests a functional dissociation between the neural substrates of absolute and relative timing. This chapter reviews current findings on relative timing in the context of rhythm and beat perception.
    Advances in Experimental Medicine and Biology 01/2014; 829:325-38. DOI:10.1007/978-1-4939-1782-2_17 · 1.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Posttraumatic Stress Disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. The majority of individuals with PTSD often have comorbid psychiatric conditions such as major depression, generalized anxiety disorder, and substance use disorders, and are at increased risk for suicide. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. One promising target for modulation is Tropomyosin Receptor Kinase B (TrkB), the receptor for Brain-Derived Neurotrophic Factor (BDNF), a signaling pathway important for neuronal plasticity, survival, and growth. The following discusses how genetic and environmental alterations to this signaling pathway may contribute to anatomical and functional changes in the hippocampus, amygdala, anterior cingulate cortex, ventromedial prefrontal cortex, and the nucleus accumbens. Changes in these brain regions may in turn contribute to the predisposition to or maintenance of some of the clinical manifestations of PTSD, including intrusive memories, hyperarousal, increased fear, and emotional numbing.
    10/2013; 2013(S4). DOI:10.4172/2167-1044.S4-006
  • 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


Available from