Temporal perception is fundamental to environmental adaptation in humans and other animals. To deal with timing and time perception, organisms have developed multiple systems that are active over a broad range of order of magnitude, the most important being circadian timing, interval timing and millisecond timing. The circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, and is driven by a selfsustaining oscillator with a period close to 24 h. Time estimation in the second-to-minutes range -known as interval timing -involves the interaction of the basal ganglia and the prefrontal cortex. In this work we tested the hypothesis that interval timing in mice is sensitive to circadian modulations. Animals were trained following the peak-interval (PI) procedure. Results show significant differences in the estimation of 24-second intervals at different times of day, with a higher accuracy in the group trained at night, which were maintained under constant dark (DD) conditions. Interval timing was also studied in animals under constant light (LL) conditions, which abolish circadian rhythmicity. Mice under LL conditions were unable to acquire temporal control in the peak interval procedure.Moreover, short time estimation in animals subjected to circadian desynchronizations (modeling jet lag-like situations) was also affected. Taken together, our results indicate that short-time estimation is modulated by the circadian clock.© 2010 Elsevier B.V. All rights reserved. Keywords:Circadian rhythms Interval timingBasal ganglia Suprachiasmatic nuclei IntroductionTiming and time perception are fundamental to survival and goal reaching in humans and other animals. Organisms have developed diverse mechanisms for timing across different scales, the most important being circadian timing, interval timing and millisecond timing . The circadian pacemaker -which is driven by a self-sustaining oscillator with a period close to 24 h -is located in the suprachiasmatic nuclei (SCN) of the hypothalamus (Dunlap et al., 2004), and the principal signal that adjusts its activity is the light-dark cycle (Morin and Allen, 2006;Golombek and Rosenstein, 2010). The molecular mechanism of the endogenous circadian clock is comprised by interlocked transcription-translation feedback loops (Reppert and Weaver, 2002). On the other hand, the perception of shorter durations in the seconds-to-minutes range, known as interval timing, is crucial to learning, memory, decision making and other cognitive

BackgroundAdults with bipolar disorder (BD) have cognitive impairments that affect face processing and social cognition. However, it remains unknown whether these deficits in euthymic BD have impaired brain markers of emotional processing.Methodology/Principal FindingsWe recruited twenty six participants, 13 controls subjects with an equal number of euthymic BD participants. We used an event-related potential (ERP) assessment of a dual valence task (DVT), in which faces (angry and happy), words (pleasant and unpleasant), and face-word simultaneous combinations are presented to test the effects of the stimulus type (face vs word) and valence (positive vs. negative). All participants received clinical, neuropsychological and social cognition evaluations. ERP analysis revealed that both groups showed N170 modulation of stimulus type effects (face > word). BD patients exhibited reduced and enhanced N170 to facial and semantic valence, respectively. The neural source estimation of N170 was a posterior section of the fusiform gyrus (FG), including the face fusiform area (FFA). Neural generators of N170 for faces (FG and FFA) were reduced in BD. In these patients, N170 modulation was associated with social cognition (theory of mind).Conclusions/SignificanceThis is the first report of euthymic BD exhibiting abnormal N170 emotional discrimination associated with theory of mind impairments.