Memory traces of duration and location in the right intraparietal sulcus.

Time and space form an integral part of every human experience, and for the neuronal representation of these perceptual dimensions, previous studies point to the involvement of the right-hemispheric intraparietal sulcus and structures in the medial temporal lobe. Here we used multi-voxel pattern analysis (MVPA) to investigate long-term memory traces for temporal and spatial stimulus features in those areas. Participants were trained on four images associated with short versus long durations and with left versus right locations. Our results demonstrate stable representations of both temporal and spatial information in the right posterior intraparietal sulcus. Building upon previous findings of stable neuronal codes for directly perceived durations and locations, these results show that the reactivation of long-term memory traces for temporal and spatial features can be decoded from neuronal activation patterns in the right parietal cortex.

The influence of travel time on perceived traveled distance varies by spatiotemporal scale.

The influence of travel time on perceived traveled distance has often been studied, but the results are inconsistent regarding the relationship between the two magnitudes. We argue that this is due to differences in the lengths of investigated travel distances and hypothesize that the influence of travel time differs for rather short compared to rather long traveled distances. We tested this hypothesis in a virtual environment presented on a desktop as well as through a head-mounted display. Our results show that, for longer distances, more travel time leads to longer perceived distance, while we do not find an influence of travel time on shorter distances. The presentation through an HMD vs. desktop only influenced distance judgments in the short distance condition. These results are in line with the idea that the influence of travel time varies by the length of the traveled distance, and provide insights on the question of how distance perception in path integration studies is affected by travel time, thereby resolving inconsistencies reported in previous studies.

Validating virtual reality for time perception research: Virtual reality changes expectations about the duration of physical processes, but not the sense of time.

Immersive virtual reality (VR) provides a versatile method for investigating human time perception, because it allows the manipulation and control of relevant variables (e.g., the speed of environmental changes) that cannot be modified in the real world. However, an important premise for interpreting the results of VR studies, namely that the method itself does not affect time perception, has received little attention. Here we tested this assumption by comparing timing performance in a real environment and a VR scenario. Participants performed two timing tasks, requiring the production of intervals defined either by numerical values ("eight seconds") or by a physical process ("the time it takes for a bottle to run out when turned over"). We found that the experience of immersive VR exclusively altered judgments about the duration of physical processes, whereas judgments about the duration of abstract time units were unaffected. These results demonstrate that effects of VR on timing performance are not driven by changes in time perception itself, but rather by altered expectations regarding the duration of physical processes. The present study validates the use of VR in time perception research and strengthens the interpretation of changed timing behaviour induced by manipulations within VR.

Cross-dimensional interference between time and distance during spatial navigation is mediated by speed representations in intraparietal sulcus and area hMT.

When navigating a straight path, perceived travel time and perceived traveled distance are linked via movement speed. Behavioral studies have revealed systematic interferences between the perception of travel time and distance, but the role of neuronal representations of movement speed for these effects has not been addressed to date. Using a combined fMRI-behavioral paradigm, we investigate the neuronal representations that underlie cross-dimensional interferences between travel time and traveled distance. Participants underwent fMRI while experiencing visual forward movements for either a short or a long duration, and covering either a short or a long distance. At the behavioral level, we found bi-directional interference effects between time and distance perception, which was correlated with greater representational similarity in speed-sensitive brain regions. The strength of the distance-on-time effect scaled with representational similarity in the left human middle temporal complex (hMT+), and the strength of the time-on-distance effect scaled with representational similarity in the right intraparietal sulcus (IPS). In accordance with the idea that the interference is mediated by the perception of speed, distance-on-time and time-on-distance effects were of opposing directions. Increases in traveled distance led to increases in perceived travel time, while increases in travel time led to decreases in perceived traveled distance. Together, these findings support the view that cross-dimensional interference effects between travel time and traveled distance are mediated by neuronal representations of movement speed.

Temporal context effects are associated with cognitive status in advanced age.

The perception of temporal intervals changes during the life-span, and especially older adults demonstrate specific impairments of timing abilities. Recently, we demonstrated that timing performance and cognitive status are correlated in older adults, suggesting that timing tasks can serve as a behavioral marker for the development of dementia. Easy-to-administer and retest-capable timing tasks therefore have potential as diagnostic tools for tracking cognitive decline. However, before being tested in a clinical cohort study, a further validation and specification of the original findings is warranted. Here we introduce several modifications of the original task and investigated the effects of temporal context on time perception in older adults (> 65 years) with low versus high scores in the Montreal Cognitive Assessment survey (MoCA) and a test of memory functioning. In line with our previous work, we found that temporal context effects were more pronounced with increasing memory deficits, but also that these effects are stronger for realistic compared to abstract visual stimuli. Furthermore, we show that two distinct temporal contexts influence timing behavior in separate experimental blocks, as well as in a mixed block in which both contexts are presented together. These results replicate and extend our previous findings. They demonstrate the stability of the effect for different stimulus material and show that timing tasks can reveal valuable information about the cognitive status of older adults. In the future, these findings could serve as a basis for the development of a diagnostic tool for pathological cognitive decline at an early, pre-clinical stage.

Synthesis of Arylidene-ß-lactams via exo-Selective Matsuda-Heck Arylation of Methylene-ß-lactams.

exo-Methylene-ß-lactams were synthesized in two steps from commercially available 3-bromo-2-(bromomethyl)propionic acid and reacted with arene diazonium salts in a Heck-type arylation in the presence of catalytic amounts of Pd(OAc)2 under ligand-free conditions. The products, arylidene-ß-lactams, were obtained in high yields as single isomers. The ß-hydride elimination step of the Pd-catalyzed coupling reaction proceeds with high exo-regioselectivity and E-stereoselectivity. With aryl iodides, triflates, or bromides, the coupling products were isolated only in low yields, due to extensive decomposition of the starting material at elevated temperatures. This underlines that arene diazonium salts can be superior arylating reagents in Heck-type reactions and yield coupling products in synthetically useful yields and selectivities when conventional conditions fail.

Negative errors in time reproduction tasks.

In time reproduction tasks, the reaction time of motor responses is intrinsically linked to the measure of perceptual timing. Decisions are based on a continuous comparison between elapsed time and a memory trace of the to-be-reproduced interval. Here, we investigate the possibility that negative reproduction errors can be explained by the tendency to prefer earlier over later response times, or whether the whole range of possible response times is shifted. In experiment 1, we directly compared point reproduction (participants indicate the exact time point of equality) and range reproduction (participants bracket an interval containing this time point). In experiment 2, participants indicated, in three separate tasks, the exact time point at which the reproduction phase was equal to the standard duration (point reproduction), the earliest (start reproduction), or the latest moment (stop reproduction) at which the exact time point of equality might have been reached. The results demonstrate that the bias towards earlier responses not only affects reproduction of the exact time point of equality. Rather, even if the decision threshold is changed in favor of late responses, they exhibit a continuous shift towards negative errors that increases with the length of the standard duration. The findings are discussed in the context of the hypothesis that systematic errors in time reproduction tasks reflect a dimension-unspecific tendency towards earlier responses caused by the psychophysical method rather than by a time-specific perceptual distortion.

Memory Image Completion: Establishing a task to behaviorally assess pattern completion in humans.

For memory retrieval, pattern completion is a crucial process that restores memories from partial or degraded cues. Neurocognitive aging models suggest that the aged memory system is biased toward pattern completion, resulting in a behavioral preference for retrieval over encoding of memories. Here, we built on our previously developed behavioral recognition memory paradigm-the Memory Image Completion (MIC) task-a task to specifically target pattern completion. First, we used the original design with concurrent eye-tracking in order to rule out perceptual confounds that could interact with recognition performance. Second, we developed parallel versions of the task to accommodate test settings in clinical environments or longitudinal studies. The results show that older adults have a deficit in pattern completion ability with a concurrent bias toward pattern completion. Importantly, eye-tracking data during encoding could not account for age-related performance differences. At retrieval, spatial viewing patterns for both age groups were more driven by stimulus identity than by response choice, but compared to young adults, older adults' fixation patterns overlapped more between stimuli that they (wrongly) thought had the same identity. This supports the observation that older adults choose responses perceived as similar to a learned stimulus, indicating a bias toward pattern completion. Additionally, two shorter versions of the task yielded comparable results, and no general learning effects were observed for repeated testing. Together, we present evidence that the MIC is a reliable behavioral task that targets pattern completion, that is easily and repeatedly applicable, and that is made freely available online.

On the (a)symmetry between the perception of time and space in large-scale environments.

Cross-dimensional interference between spatial and temporal processing is well documented in humans, but the direction of these interactions remains unclear. The theory of metaphoric structuring states that space is the dominant concept influencing time perception, whereas time has little effect upon the perception of space. In contrast, theories proposing a common neuronal mechanism representing magnitudes argue for a symmetric interaction between space and time perception. Here, we investigated space-time interactions in realistic, large-scale virtual environments. Our results demonstrate a symmetric relationship between the perception of temporal intervals in the supra-second range and room size (experiment 1), but an asymmetric relationship between the perception of travel time and traveled distance (experiment 2). While the perception of time was influenced by the size of virtual rooms and by the distance traveled within these rooms, time itself affected only the perception of room size, but had no influence on the perception of traveled distance. These results are discussed in the context of recent evidence from rodent studies suggesting that subsets of hippocampal place and entorhinal grid cells can simultaneously code for space and time, providing a potential neuronal basis for the interactions between these domains.

Post-mortem chemical excitability of the iris should not be used for forensic death time diagnosis.

Post-mortem chemical excitability of the iris is one of the non-temperature-based methods in forensic diagnosis of the time since death. Although several authors reported on their findings, using different measurement methods, currently used time limits are based on a single dissertation which has recently been doubted to be applicable for forensic purpose. We investigated changes in pupil-iris ratio after application of acetylcholine (n = 79) or tropicamide (n = 58) and in controls at upper and lower time limits that are suggested in the current literature, using a digital photography-based measurement method with excellent reliability. We observed "positive," "negative," and "paradox" reactions in both intervention and control conditions at all investigated post-mortem time points, suggesting spontaneous changes in pupil size to be causative for the finding. According to our observations, post-mortem chemical excitability of the iris should not be used in forensic death time estimation, as results may cause false conclusions regarding the correct time point of death and might therefore be strongly misleading.

Space, time, and numbers in the right posterior parietal cortex: Differences between response code associations and congruency effects.

The mental representations of space, time, and number magnitude are inherently linked. The right posterior parietal cortex (PPC) has been suggested to contain a general magnitude system that underlies the overlap between various perceptual dimensions. However, comparative studies including spatial, temporal, and numerical dimensions are missing. In a unified paradigm, we compared the impact of right PPC inhibition on associations with spatial response codes (i.e., Simon, SNARC, and STARC effects) and on congruency effects between space, time, and numbers. Prolonged cortical inhibition was induced by continuous theta-burst stimulation (cTBS), a protocol for transcranial magnetic stimulation (TMS), at the right intraparietal sulcus (IPS). Our results show that congruency effects, but not response code associations, are affected by right PPC inhibition, indicating different neuronal mechanisms underlying these effects. Furthermore, the results demonstrate that interactions between space and time perception are reflected in congruency effects, but not in an association between time and spatial response codes. Taken together, these results implicate that the congruency between purely perceptual dimensions is processed in PPC areas along the IPS, while the congruency between percepts and behavioral responses is independent of this region.

Systematic Underreproduction of Time Is Independent of Judgment Certainty.

We recently proposed that systematic underreproduction of time is caused by a general judgment bias towards earlier responses, instead of reflecting a genuine misperception of temporal intervals. Here we tested whether this bias can be explained by the uncertainty associated with temporal judgments. We applied transcranial magnetic stimulation (TMS) to inhibit neuronal processes in the right posterior parietal cortex (PPC) and tested its effects on time discrimination and reproduction tasks. The results show increased certainty for discriminative time judgments after PPC inhibition. They suggest that the right PPC plays an inhibitory role for time perception, possibly by mediating the multisensory integration between temporal stimuli and other quantities. Importantly, this increased judgment certainty had no influence on the degree of temporal underreproduction. We conclude that the systematic underreproduction of time is not caused by uncertainty for temporal judgments.

Psychophysics and the anisotropy of time.

In psychophysics, experimental control over the presented stimuli is an important prerequisite. Due to the anisotropy of time, this prerequisite is not given in psychophysical experiments on time perception. Many important factors (e.g., the direction of perceived time flow) cannot be manipulated in timing experiments. The anisotropy of time is a peculiarity, which distinguishes the time dimension from other perceptual qualities. Here I summarize the anisotropy-related differences between the perception of time and the perception of other qualities. It is discussed to what extent these differences might affect results and interpretations in psychophysical experiments. In conclusion, I argue for a 'view from nowhen' on the psychophysical study of time perception.

Suzuki-Miyaura coupling of halophenols and phenol boronic acids: systematic investigation of positional isomer effects and conclusions for the synthesis of phytoalexins from pyrinae.

The Suzuki-Miyaura couplings of o-, m-, and p-halophenols with o-, m-, and p-phenol boronic acids were investigated for all combinations under standardized conditions, using Pd/C as a heterogeneous catalyst and water as a solvent. In the case of iodophenols, conventional heating was used, while for bromophenols significantly better results could be obtained using microwave irradiation. This systematic study revealed that 2,4'-biphenol is particularly difficult to access, irrespective of the starting materials used, but that these difficulties can be overcome by using different additives. The conclusions drawn from this investigation allowed us to identify conditions for the protecting group-free or minimized total synthesis of biaryl-type phytoalexins. These compounds possess antibacterial activity and are produced by fruit trees as a response to microbial infection.

Interrelations between the perception of time and space in large-scale environments.

Interactions between perceived temporal and spatial properties of external stimuli (e.g. duration and size) suggest common neural mechanisms underlying the perception of time and space. This conclusion, however, lacks support from studies in large-scale environments, showing that judgements on travelled distances and associated travel times are independent from each other. Here, we used a different approach to test whether the perception of travelled distances is influenced by the perception of time. Unlike previous studies, in which temporal and spatial judgements were related to the same experience of walking, we assessed time and distance perception in analogous, but separate versions of estimation and production tasks. In estimation tasks, participants estimated the duration of a presented sound (time) or the length of a travelled distance (space), and in production tasks, participants terminated a sound after a numerically specified duration (time) or covered a numerically specified distance (space). The results show systematic overestimation of time and underestimation of travelled distance, and the latter reflecting previously reported misperceptions of visual distance. Time and distance judgements were related within individuals for production, but not for estimation tasks. These results suggest that temporal information might constitute a probabilistic cue for path integration.

Virtual patients: the influence of case design and teamwork on students' perception and knowledge - a pilot study.

BACKGROUND: Virtual patient (VP) cases are an effective teaching method, although little is known about how to design and implement them for maximum effectiveness. The aim of this study was to explore the effect of case design and teamwork on students' learning outcome. METHODS: One hundred forty-six undergraduate medical students participated in a mandatory medical computer science course consisting of five seminars. At the end of each seminar, they worked on one VP case, either in teams of two or individually. Each student filled out an introductory and a final survey and a feedback sheet after completing each case. Additionally, there was a surprise multiple choice (MC) test after the last seminar with three questions regarding each case. RESULTS: Students with more clinical experience and students who had worked in a team performed significantly better on MC questions. Students with less clinical experience more frequently used information which had been positioned less prominently on the case material. Certain aspects of case design were rated more positively by students who had an interest in e-learning. In general, students preferred to work on cases for less than 15 minutes. CONCLUSIONS: Clinically more advanced students and students working with a partner seem to benefit most from short VP cases with prominently presented information.

Differences between sub-second and supra-second durations for the assessment of timing deficits in amnestic mild cognitive impairment.

Previous studies have often reported timing deficits in older adults with different degrees of cognitive decline, however, the exact nature of impairments in time perception is still to be elucidated. In particular, it is unclear if the deficits are more pronounced for short or long intervals, consistent with notions that different cognitive processes and neuroanatomical areas are involved in the processing of durations of different ranges. The present study aims to further investigate timing abilities in amnestic mild cognitive impairment (aMCI) patients and age-matched controls. Participants were asked to decide whether an acoustic event occurred within the first or the second half of a reference duration. The results revealed a bias towards larger PSE values and reduced precision in aMCI patients compared to healthy controls. Further analyses showed that the bias towards larger PSE values correlated with memory performance, especially when sub-second durations were tested. Overall, the results demonstrate that memory deficits in aMCI patients coincide with changes in time perception in the sub-second interval range.

Age-related changes in time perception: Effects of immersive virtual reality and spatial location of stimuli.

The perception of time is subject to various environmental influences and exhibits changes across the lifespan. Studies on time perception have often been conducted using abstract stimuli and artificial scenarios, and recent claims for more naturalistic paradigms and realistic stimuli pose the question as to whether immersive virtual reality set-ups differently affect the timing abilities of older versus younger adults. Here, we tested the hypotheses that naturalistic 3D stimuli presented in immersive virtual reality (as opposed to abstract 2D stimuli presented on a computer screen) and the spatial location of those stimuli (left vs. right) affect the perceived time point of their occurrence. Our results demonstrate that a naturalistic presentation of stimuli leads to a bias towards earlier time points in younger, but not older participants. Furthermore, this bias was associated with lower scores of memory capacity. Contrary to our hypothesis that right-sided stimuli are perceived as later than left-sided stimuli, no spatial influences on temporal processing were observed. These results show that older and younger adults are differently affected by an increase in the realism and the immersiveness of experimental paradigms, and highlight the importance of task design in studies on human time perception.

2,2'-Biphenols via protecting group-free thermal or microwave-accelerated Suzuki-Miyaura coupling in water.

User-friendly protocols for the protecting group-free synthesis of 2,2'-biphenols via Suzuki-Miyaura coupling of o-halophenols and o-boronophenol are presented. The reactions proceed in water in the presence of simple additives such as K2CO3, KOH, KF, or TBAF and with commercially available Pd/C as precatalyst. Expensive or laboriously synthesized ligands or other additives are not required. In the case of bromophenols, efficient rate acceleration and short reaction times were accomplished by microwave irradiation.