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.

The neural basis of temporal processing is unclear. We addressed this important issue by performing two experiments in which repetitive transcranial magnetic stimulation (rTMS) was administered in different sessions to the left or right supramarginal gyrus (SMG) or vertex; in both tasks, two visual stimuli were presented serially and subjects were asked to judge if the second stimulus was longer than the first (standard) stimulus. rTMS was presented on 50% of trials. Consistent with a previous literature demonstrating the effect of auditory clicks on temporal judgment, rTMS was associated with a tendency to perceive the paired visual stimulus as longer in all conditions. Crucially, rTMS to the right SMG was associated with a significantly greater subjective prolongation of the associated visual stimulus in both experiments. These findings demonstrate that the right SMG is an important element of the neural system underlying temporal processing and, as discussed, have implications for neural and cognitive models of temporal perception and attention.