Single-dose Levodopa Administration and Aging Independently Disrupt Time Production

We tested the hypothesis that age-related time production deficits are dopamine-mediated. The experiment was conducted double-blind, and with random assignment of 32 healthy aged and 32 healthy young participants to either inert placebo or levodopa (200 mg) groups. The procedure included training participants to produce two target time intervals (6 and 17 sec) in separate blocks, drug/placebo administration, a 1-hr delay, and then delayed free-recall time production retesting without feedback. Participants also performed a speeded choice reaction time (RT) task, as a control for potential dopaminergic and aging effects on attention and psychomotor speed. Results indicate that during retesting, aged participants show duration-dependent timing errors that are larger than those shown by the young participants. Levodopa administration yielded lengthened time production of both target intervals. The aging and levodopa effects did not interact. Also, aging slowed RT and increased RT variability, but levodopa had no effect on the RT. These results suggest that at this dosage and under these specific conditions, timing is dopamine-mediated but the effect of aging on time production is not. Moreover, the levodopa timing effect cannot be attributed to the effects of dopaminergic function on psychomotor speed

Time perception and its neuropsychological correlates in patients with schizophrenia and in healthy volunteers

Disordered time perception has been reported in schizophrenia. We investigated time perception dysfunction and its neuropsychological correlates in patients with schizophrenia. Participants comprised 38 patients and 38 age- and sex-matched healthy volunteers who were compared in an auditory temporal bisection paradigm using two interval ranges (a 400/800 ins condition and a 1000/2000 ms condition). In the temporal bisection, subjects were required to categorise a probe duration as short or long, based upon the similarity with two reference durations. All subjects also completed a battery of neuropsychological tests measuring sustained attention, short- and long-term memory and executive function. In the 400/800 ins condition, patients judged durations significantly shorter than did control subjects. Patients also exhibited decreased temporal sensitivity in both conditions. We found in both groups a negative association between temporal sensitivity and sustained attention for the 400/800 ms condition, and between temporal sensitivity and long-term memory for the 1000/200 ms condition. In patients, short-term memory performance was negatively associated with duration judgement in both conditions, while executive dysfunction was correlated to a general performance deficit in the 400/800 ms condition. These findings suggest the possibility that time perception abnormalities in schizophrenia are part of neuropsychological dysfunction and are likely to adversely impact upon activity of daily living. (c) 2008 Elsevier Ireland Ltd. All rights reserved

Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds

Dorsal hippocampal involvement in conditioned-response timing and maintenance of temporal information in the absence of the CS

Involvement of the dorsal hippocampus (DHPC) in conditioned-response timing and maintaining temporal information across time gaps was examined in an appetitive Pavlovian conditioning task, in which rats with sham and DHPC lesions were first conditioned to a 15-s visual cue. After acquisition, the subjects received a series of non-reinforced test trials, on which the visual cue was extended (45 s) and gaps of different duration, 0.5, 2.5, and 7.5 s, interrupted the early portion of the cue. Dorsal hippocampal-lesioned subjects underestimated the target duration of 15 s and showed broader response distributions than the control subjects on the no-gap trials in the first few blocks of test, but the accuracy and precision of their timing reached the level of that of the control subjects by the last block. On the gap trials, the DHPC-lesioned subjects showed greater rightward shifts in response distributions than the control subjects. We discussed these lesion effects in terms of temporal versus non-temporal processing (response inhibition, generalisation decrement, and inhibitory conditioning)

Neurobehavioral Mechanisms of Temporal Processing Deficits in Parkinson's Disease

Parkinson's disease (PD) disrupts temporal processing, but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping, potential working memory (WM) and executive problems could also disrupt timing.The present study addressed these issues by testing controls and PD volunteers 'on' and 'off' DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes, we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping, the encoding and decision phases emphasized WM and executive processes, respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction. Unlike studies of timed movement, our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second, for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex, lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus, posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD, but was sometimes characterized by abnormal temporal dynamics (e.g., lagged, prolonged) that were not due to longer response times. Finally, DA therapy did not alleviate timing deficits.Our findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity

Computational models of interval timing

In recent years great progress has been made in the computational modeling of interval timing. A wide range of models capturing different aspects of interval timing now exist. These models can be seen as constituting four, sometimes overlapping, general classes of models: pacemaker–accumulator models, multiple–oscillator models, memory–trace models, and drift–diffusion (or random-process) models. We suggest that computational models should be judged based on their performance on a number of criteria — namely, the scalar property, their ability to reproduce retrospective and prospective timing effects, and their sensitivity to attentional and neurochemical manipulations. Future challenges will involve building integrated models and sharing model code to allow direct comparisons against a battery of empirical data

Penelope Delta, recently discovered writer

The aim of this article is to present a Greek writer, Penelope Delta. This writer has recently come up in the field of the studies of the Greek literature and, although there are neither many translations of her works in foreign languages nor many theses or dissertations, she was chosen for the great interest for her works. Her books have been read by many generations, so she is considered a classical writer of Modern Greek Literature. The way she uses the Greek language, the unique characters of her heroes that make any child or adolescent identified with them, the understood organization of her material are only a few of the main characteristics and advantages of her texts. It is also of high importance the fact that her books can be read by adults, as they can provide human values, such as love, hope, enjoyment of life, the educational significance of playing, the innocence of the infancy, the adventurous adolescence, even the unemployment, the value of work and justice. Thus, the educative importance of her texts was the main reason for writing this articl

Penelope Delta, recently discovered writer

The aim of this article is to present a Greek writer, Penelope Delta. This writer has recently come up in the field of the studies of the Greek literature and, although there are neither many translations of her works in foreign languages nor many theses or dissertations, she was chosen for the great interest for her works. Her books have been read by many generations, so she is considered a classical writer of Modern Greek Literature. The way she uses the Greek language, the unique characters of her heroes that make any child or adolescent identified with them, the understood organization of her material are only a few of the main characteristics and advantages of her texts. It is also of high importance the fact that her books can be read by adults, as they can provide human values, such as love, hope, enjoyment of life, the educational significance of playing, the innocence of the infancy, the adventurous adolescence, even the unemployment, the value of work and justice. Thus, the educative importance of her texts was the main reason for writing this articl

Galen on pharmacology: His scientific way of thinking and contribution to the pharmacology of Cyprus

The article provides an overview of Galen's work on pharmacology taking into account the mindset and the general attitude towards medicine in the ancient era. Pharmacology was considered one of the three fields of medical science (surgery and dietology were the other two). The ancient people used a great many natural substances of vegetable or animal origin in order to produce many kinds of drugs for healing or alleviating the pain of the human body in a natural way. The evidence of the use of this kind of medical material in the ancient literature is evident, from the epic poems, tragedies and comedies to the medical literature, especially the texts of Galen, one of the most significant ancient medical writers, pharmacologists, and researchers. Galen's scientific way of thinking and the careful attention he paid to pharmacological concepts and methods of healing are illustrated by his observations concerning the inefficacy, errors and failure of pharmacological terms of his era. The aim of this article is to provide information about the medical material (materia medica) of Cyprus, which are found in many passages of Galen's works and try to explain the real origin of these substances. It is known that Galen had traveled to many places of the ancient world in order to explore the substances used or provided for pharmaceutical manufacturing, and one of his destinations was Cyprus. The author represents all these possible cases of the chronological determination of Galen's journey to Cyprus and the reasons for his visit which was to gather information concerning medical substances of vegetarian and animal origin and minerals (especially, copper). The research work and information about the use and utility of many minerals in pharmaceutical manufacturing were of great importance for the development of ancient Greek pharmacology. The author points out the importance of the references to the names of many ancient Cypriot doctors in Galen's texts for a researcher of today in order to complete the image of ancient medicine and pharmacology. © Athina Malapani