Many species, including humans, show both accurate timing-appropriate time estimation in the seconds to minutes range-and -time estimation error varies linearly with estimated duration. Behavioral paradigms aimed at investigating interval timing are expected to evaluate these dissociable characteristics of timing. However, when evaluating interval timing in models of neuropsychiatric disease, researchers are confronted with a lack of adequate studies about the parent (background) strains, since accuracy and scalar timing have only been demonstrated for the C57Bl/6 strain of mice (Buhusi et al., 2009). We used a peak-interval procedure with three intervals-a protocol in which other species, including humans, demonstrate accurate, scalar timing-to evaluate timing accuracy and scalar timing in three strains of mice frequently used in genetic and behavioral studies: 129, Swiss-Webster, and C57Bl/6. C57Bl/6 mice showed accurate, scalar timing, while 129 and Swiss-Webster mice showed departures from accuracy and/or scalar timing. Results suggest that the genetic background / strain of the mouse is a critical variable for studies investigating interval timing in genetically-engineered mice. Our study validates the PI procedure with multiple intervals as a proper technique, and the C57Bl/6 strain as the most suitable genetic background to date for behavioral investigations of interval timing in genetically engineered mice modeling human disorders. In contrast, studies using mice in 129, Swiss-Webster, or mixed-background strains should be interpreted with caution, and thorough investigations of accuracy and scalar timing should be conducted before a less studied strain of mouse is considered for use in timing studies.

We examined the influence of emotional arousal and valence on estimating time intervals. A reproduction task was used in which images from the International Affective Picture System served as the stimuli to be timed. Experiment 1 assessed the effects of positive and negative valence at a moderate arousal level and Experiment 2 replicated Experiment 1 with the addition of a high arousal condition. Overestimation increased as a function of arousal during encoding of times regardless of valence. For images presented during reproduction, overestimation occurred at the moderate arousal level for positive and negative valence but underestimation occurred in the negative valence high arousal condition. The overestimation of time intervals produced by emotional arousal during encoding and during reproduction suggests that emotional stimuli affect temporal information processing in a qualitatively different way during different phases of temporal information processing.

This study investigated the ability of individuals with Parkinson's disease (PD) to synthesize temporal information across the senses, namely audition and vision. Auditory signals (A) are perceived as lasting longer than visual signals (V) when they are compared together, since attentsion is captured and sustained more easily than for visual information. We used the audiovisual illusion to probe for disturbances in brain networks that govern the resolution of time in two intersensory conditions that putatively differ in their attention demands. PD patients and controls judged the relative duration of successively presented pairs of unimodal (AA, VV) and crossmodal (VA, AV) signals whilst undergoing fMRI. There were four main findings. First, underestimation of time was exaggerated in PD when timing depended on controlled attention (AV), whereas subtle deficits were found when audition dominated and attention was more easily sustained (VA). Second, group differences in regional activation were observed only for the AV-unimodal comparison, where the PD group failed to modulate basal ganglia, anterior insula, and inferior cerebellum activity in accord with the timing condition. Third, the intersensory timing conditions were dissociated by patterns of abnormal functional connectivity. When intersensory timing emphasized controlled attention, patients showed weakened connectivity of the cortico-thalamus-basal ganglia (CTBG) circuit and the anterior insula with widespread cortical regions, yet enhanced cerebellar connectivity. When audition dominated intersensory timing, patients showed enhanced connectivity of CTBG elements, the anterior insula, and the cerebellum with the caudate tail and frontal cortex. Fourth, abnormal connectivity measures showed excellent sensitivity and specificity in accurately classifying subjects. The results demonstrate that intersensory timing deficits in PD were well characterized by context-dependent patterns of functional connectivity within a presumed core timing system (CTBG) and a ventral attention hub (anterior insula), and enhanced cerebellar connectivity irrespective of the hypothesized attention demands of timing.

Interval timing is crucial for decision-making and motor control and is impaired in many neuropsychiatric disorders, including schizophrenia - a neurodevelopmental disorder with a strong genetic component. Several gene mutations, polymorphisms or rare copy number variants have been associated with schizophrenia. L1 cell adhesion molecules (L1CAMs) are involved in neurodevelopmental processes, and in synaptic function and plasticity in the adult brain. Mice deficient in the Close Homolog to L1 (CHL1) adhesion molecule show alterations of hippocampal and thalamo-cortical neuroanatomy as well as deficits in sensorimotor gating and exploratory behavior. We analyzed interval timing and attentional control of temporal and spatial information in male CHL1 deficient (KO) mice and wild type (WT) controls. In a 20-s peak-interval timing procedure (standard and reversed), KO mice showed a maintained leftward shift of the response function relative to WT, indicative of a deficit in memory encoding/decoding. In trials with 2, 5, or 10-s gaps, KO mice shifted their peak times less than WT controls at longer gap durations, suggesting a decreased (attentional) effect of interruptions. In the spatial-temporal task, KO mice made more working and reference memory errors than controls, suggestive of impaired use of spatial and/or temporal information. When the duration spent on the central platform of the maze was manipulated, WT mice showed fewer spatial errors at the trained duration than at shorter or longer durations, indicative of discrimination based upon spatial-temporal integration. In contrast, performance was similar at all tested durations in KO mice, indicative of control by spatial cues, but not by temporal cues. These results suggest that CHL1 KO mice selectively attend to the more relevant cues of the task, and fail to integrate more complex spatial-temporal information, possibly as a result of reduced memory capacity related to hippocampal impairment, and altered temporal-integration mechanisms possibly due to thalamo-cortical anomalies.

Discriminative fear conditioning requires learning to dissociate between safety cues and cues that predict negative outcomes yet little is known about what processes contribute to discriminative fear learning. According to attentional models of time perception, processes that distract from timing result in temporal underestimation. If discriminative fear learning only requires learning what cues predict what outcomes, and threatening stimuli distract attention from timing, then better discriminative fear learning should predict greater temporal distortion on threat trials. Alternatively, if discriminative fear learning also reflects a more accurate perceptual experience of time in threatening contexts, discriminative fear learning scores would predict less temporal distortion on threat trials, as time is perceived more veridically. Healthy young adults completed discriminative fear conditioning in which they learned to associate one stimulus (CS+) with aversive electrical stimulation and another stimulus (CS-) with non-aversive tactile stimulation and then an ordinal comparison timing task during which CSs were presented as task-irrelevant distractors Consistent with predictions, we found an overall temporal underestimation bias on CS+ relative to CS- trials. Differential skin conductance responses to the CS+ versus the CS- during conditioning served as a physiological index of discriminative fear conditioning and this measure predicted the magnitude of the underestimation bias, such that individuals exhibiting greater discriminative fear conditioning showed less underestimation on CS+ versus CS- trials. These results are discussed with respect to the nature of discriminative fear learning and the relationship between temporal distortions and maladaptive threat processing in anxiety.

Despite considerable interest in impulsive choice as a predictor of a variety of maladaptive behaviors, the mechanisms that drive choice behavior are still poorly understood. The present study sought to examine the influence of one understudied variable, reward magnitude contrast, on choice and timing behavior as changes in magnitude commonly occur within choice procedures. In addition, assessments of indirect effects on choice behavior through magnitude-timing interactions were assessed by measuring timing within the choice task. Rats were exposed to choice procedures composed of different pairs of magnitudes of rewards for either the smaller-sooner (SS) or larger-later (LL) option. In Phase 2, the magnitude of reward either increased or decreased by 1 pellet in different groups (LL increase = 1v1→1v2; SS decrease = 2v2 → 1v2; SS increase = 1v2 → 2v2), followed by a return to baseline in Phase 3. Choice behavior was affected by the initial magnitudes experienced in the task, demonstrating a strong anchor effect. The nature of the change in magnitude affected choice behavior as well. Timing behavior was also affected by the reward contrast manipulation albeit to a lesser degree and the timing and choice effects were correlated. The results suggest that models of choice behavior should incorporate reinforcement history, reward contrast elements, and magnitude-timing interactions, but that direct effects of reward contrast on choice should be given more weight than the indirect reward-timing interactions. A better understanding of the factors that contribute to choice behavior could supply key insights into this important individual differences variable.

The Striatal Beat Frequency (SBF) model of interval timing uses many neural oscillators, presumably located in the frontal cortex (FC), to produce beats at a specific criterion time Tc. The coincidence detection produces the beats in the basal ganglia spiny neurons by comparing the current state of the FC neural oscillators against the long-term memory values stored at reinforcement time Tc. The neurobiologically realistic SBF model has been previously used for producing precise and scalar timing in the presence of noise. Here we simplified the SBF model to gain insight into the problem of resource allocation in interval timing networks. Specifically, we used a noise-free SBF model to explore the lower limits of the number of neural oscillators required for producing accurate timing. Using abstract sine-wave neural oscillators in the SBF-sin model, we found that the lower limit of the number of oscillators needed is proportional to the criterion time Tc and the frequency span (fmax - fmin) of the FC neural oscillators. Using biophysically realistic Morris-Lecar model neurons in the SBF-ML model, the lower bound increased by one to two orders of magnitude compared to the SBF-sin model.