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T H Rammsayer

Publications and source records attributed to T H Rammsayer.

15 recordsLinked to original sources

Unimpaired negative but enhanced positive priming in Parkinson's disease: evidence from an identity and a location priming task.

Mechanisms of selective attention are frequently reported to be impaired in Parkinson's disease (PD). Fundamental to selective attention is attending to relevant information and, concurrently, ignoring irrelevant information. Both processes can be assessed by positive priming (PP) and negative priming (NP) tasks, respectively. Unlike previous studies, in the present experiment, two separate identity- and location-based priming tasks were applied to 48 PD patients and 48 sex- and age-matched healthy controls. Results indicated that identity and location PP were reliably enhanced in PD patients compared to controls. Both groups showed significant location NP of almost identical magnitude but no identity NP. However, there was evidence for a positive functional relationship between severity of bradykinesia and identity NP. Furthermore, with increasing depression scores, location NP was enhanced in PD patients but not in controls. These findings suggest that disturbed selective attention associated with PD is due to changed mechanisms mediating attention to relevant information rather than due to mechanisms involved in inhibition of irrelevant information.

Aged↗

Effects of noradrenergic activity on temporal information processing in humans.

Temporal processing of durations in the range of seconds or more is mediated by working-memory mechanisms whereas processing of brief durations in the range of milliseconds appears to be beyond cognitive control and modulated by dopaminergic activity in the basal ganglia. In the present study, the effects of the selective noradrenaline reuptake inhibitor reboxetine on temporal information processing were evaluated. In a double-blind crossover design, either placebo or 2 or 4 mg of reboxetine were administered to 24 healthy male volunteers. Performance on temporal discrimination of longer durations, as indicated by 75%-difference thresholds in relation to a 1,000-ms standard interval, was significantly improved by 2 mg of reboxetine as compared to placebo, whereas the improvement observed with the 4-mg dose just failed to reach statistical significance. There was, however, no effect of reboxetine on temporal discrimination of extremely brief durations, as indicated by threshold values in relation to a 50-ms standard interval. Findings provided additional evidence for the notion that temporal processing of durations in the range of seconds is based on working-memory processes including aspects of directed attention. In timing of brief durations in the range of milliseconds, however, noradrenergic activity did not seem to play a critical role.

Adrenergic Uptake Inhibitors↗

Dopamine-antagonistic, anticholinergic, and GABAergic effects on declarative and procedural memory functions.

Declarative and procedural memory functions are related to dissociable neuroanatomic substrates. In the present study differential effects of pharmacologically induced changes in dopaminergic, GABAergic, and cholinergic activity in the brain on declarative (object and face recognition, immediate and delayed word recall) and procedural memory processes (compensatory tracking) were investigated. In a double-blind design, either 3 mg of haloperidol, 11 mg of midazolam, 1 mg of scopolamine, or placebo were administered to 80 healthy volunteers randomly assigned to one of the four drug conditions. Although all three drugs produced a detrimental effect on immediate and delayed word recall, recall performance was substantially more impaired by the benzodiazepine midazolam than by either haloperidol or scopolamine. While recognition of faces was affected by neither of the drugs, performance on object recognition was significantly decreased by midazolam as compared to placebo. Procedural learning was markedly impaired by all drugs but, again, the observed effect was most pronounced with midazolam. Additional analyses of measures of subjective activation, cortical arousal, and psychomotor performance argued against the assumption that the observed memory-impairing effects were secondary to drug-induced sedation. The overall pattern of results revealed that memory processes are much more susceptible to changes in GABAergic than in dopaminergic or cholinergic neurotransmitter activity. Furthermore, the present findings point to the conclusion that the modulating effects of dopaminergic, GABAergic, and cholinergic neurotransmitter systems on declarative and procedural memory functions are less specific than suggested by neuropsychological studies in patients.

Acetylcholine↗

Neuropharmacological evidence for different timing mechanisms in humans.

Temporal processing of intervals in the range of seconds or more is cognitively mediated, whereas processing of brief durations below 500 msec appears to be based on brain mechanisms outside cognitive control. To elucidate the critical role of various neurotransmitters in timing processes in humans, the effects of 3 mg of haloperidol, a dopamine receptor antagonist, 11 mg of the benzodiazepine midazolam, and 1 mg of scopolamine, a cholinergic receptor antagonist, were compared in a placebo-controlled double-blind experiment. In addition, changes in cortical arousal, semantic memory, and cognitive and motor skill acquisition were assessed. Temporal processing of long durations was significantly impaired by haloperiodol and midazolam, whereas processing of extremely brief intervals was only affected by haloperidol. The overall pattern of results supports the notion that temporal processing of longer intervals is mediated by working-memory functions and, therefore, any pharmacological treatment, irrespective of the neurotransmitter system involved, that produces a deterioration of working memory, may interfere with temporal processing of longer intervals. Temporal processing of intervals in the range of milliseconds appears to depend on the effective level of dopaminergic activity in the basal ganglia.

Adult↗

Effects of body core temperature and brain dopamine activity on timing processes in humans.

In a placebo-controlled study, the effects of experimentally induced increase in body core temperature and of the dopamine antagonist haloperidol on judgments of an apparent second, a speeded-tapping task, and temporal discrimination of intervals in the range of milliseconds and seconds were investigated in 40 healthy male subjects. A 0.7 degree C-increase in body core temperature due to 3-h exposure to an ambient temperature of 52 degrees C did not cause any statistically significant changes in timing tasks. Unlike heat exposure, 3 mg of haloperidol caused a pronounced impairment of performance on the temporal discrimination of intervals in the range of milliseconds and seconds (P < 0.01 and P < 0.001, respectively) as well as speeded tapping (P < 0.05). For temporal discrimination of intervals in the range of seconds, a significant interaction between ambient temperature and haloperidol could be established (P < 0.05) indicating that haloperidol caused a significant performance decrement only in subjects exposed to an ambient temperature of 28 degrees C but not in those exposed to 52 degrees C. The overall pattern of results suggests that temporal processing of intervals in the range of milliseconds can be considered a function of dopaminergic activity in the basal ganglia while temporal processing of longer intervals appears to be cognitively mediated. Furthermore, the hypothesis that timing processes in humans are modulated by changes in body core temperature could not be established.

Adult↗

Are there dissociable roles of the mesostriatal and mesolimbocortical dopamine systems on temporal information processing in humans?

There is some experimental evidence suggesting that temporal processing of brief duration in the range of milliseconds is based on dopamine (DA)-dependent neural counting mechanisms, whereas processing of longer duration is cognitively mediated. To further elucidate the critical role of DA receptors of the D2 receptor family for temporal information processing in humans, the effects of the 3 mg of haloperidol, 300 mg of sulpiride, and 150 mg of remoxipride were studied in a placebo-controlled double-blind experiment. In addition, concomitant changes in cortical arousal as well as speed of information processing and motor execution were measured. Temporal processing of brief duration was significantly impaired by haloperidol (p < 0.01) but not by sulpiride and remoxipride, whereas processing of longer duration was adversely affected by haloperidol (p < 0.001) as well as remoxipride (p < 0.01) as compared to placebo. The pattern of results in combination with the different pharmacological profiles of the dopaminergic drugs applied in the present study suggests that temporal processing of brief duration is mediated by D2 receptor activity in the mesostriatal system and, thus, point to the basal ganglia as a neuroanatomical structure possibly involved in timing of brief duration. On the other hand, deteriorating effects of D2 receptor blockers on processing of longer duration appear to be due to DA-induced impairment of memory functions which may be mediated by the mesolimbocortical DA system.

Adult↗

Temporal discrimination as a function of marker duration.

In a series of three experiments, the effect of marker duration on temporal discrimination was evaluated with empty auditory intervals bounded by markers ranging from 3 to 300 msec or presented as a gap within a continuous tone. As a measure of performance, difference thresholds in relation to a base duration of 50 msec were computed. Performance on temporal discrimination was significantly better with markers ranging from 3 to 150 msec than with markers ranging from 225 to 300 msec or under the gap condition. However, within each range of marker duration (3-150 msec; 225-300 msec or gap) performance did not differ significantly. A fourth experiment provided evidence that the effect of marker duration cannot be explained in terms of marker-induced masking. A good approximation of the relationship between marker duration and temporal discrimination performance in the present experiments is a smooth step function, which can account for 99.3% of the variance of mean discrimination performance. Thus, the findings of the present study point to the conclusion that two different mechanisms are used in the processing of temporal information, depending on the duration of the auditory markers. The tradeoff point for the hypothetical shift from one timing mechanism to the other may be found at a marker duration of approximately 200 msec.

Adult↗

A cognitive-neuroscience approach for elucidation of mechanisms underlying temporal information processing.

Temporal processing of durations in the range of seconds or more is cognitively mediated, whereas processing of brief durations below 100 ms appears to be based on brain mechanisms beyond cognitive control. In a series of experiments, applying a single-behavior-multiple-brain-systems strategy, activity of various neurotransmitter systems was pharmacologically changed and effects on temporal information processing were studied. In addition, concomitant changes in different psychological functions, such as cortical arousal, speed of information processing, and memory were measured. This experimental strategy proved to be highly efficient for elucidating mechanisms underlying temporal information processing in humans. Temporal processing of durations in the range of seconds was markedly impaired by pharmacologic agents which induced deterioration of memory functions. On the other hand, temporal processing of brief durations below 100 ms was shown to be largely independent of pharmacologically induced impairment of cognitive functioning, but may rather depend on D2 receptor activity in the basal ganglia.

Administration, Oral↗

Effects of practice and signal energy on duration discrimination of brief auditory intervals.

In Experiment 1, the proposition that duration discrimination of filled auditory intervals is based on temporal information rather than on energy-dependent cues was tested in 64 naive subjects. The subjects were presented with two auditory stimuli at different levels of intensity within one trial, and had to decide which of the two was longer in duration. An adaptive psychophysical procedure was used. As a measure of performance, difference threshold estimates in relation to a 50-msec standard interval were computed. Duration discrimination showed no effect of energy values, indicating that the subjects' discrimination was independent of stimulus intensity. The goal of Experiments 2A and 2B was to investigate the effects of practice on duration discrimination which, in addition, may provide an indirect test for the potential use of energy-dependent cues. Effects of practice on duration discrimination of filled (Experiment 2A) and empty (Experiment 2B) intervals were studied in 6 subjects in each case, over 20 testing sessions. An adaptive psychophysical procedure that was similar to the one used in Experiment 1 was applied. Neither short-term effects of practice based on the first five testing sessions, nor long-term effects of practice based on the means of 4 consecutive weeks, could be demonstrated. The results of the present study suggest that duration discrimination of brief auditory intervals is based on temporal information and not on stimulus energy. Furthermore, implications for the notion of a very basic biological timing mechanism underlying temporal processing of brief auditory intervals in the range of milliseconds are discussed.

Acoustic Stimulation↗

Aging and temporal discrimination of brief auditory intervals.

In a duration-discrimination experiment, young adults (mean age = 25.1), middle-aged adults (mean age = 45.5), and older adults (mean age = 64.6) were presented with two very brief auditorily marked intervals per trial, and their task was to decide which of the two was longer in duration. An adaptive psychophysical procedure was used to determine difference thresholds in relation to a constant standard interval of 50 ms. It was found that duration-discrimination performance was unaffected by age; all three age groups yielded a difference threshold of approximately 17 ms. It was concluded that the ability to discriminate durations of very brief auditory intervals appears to be based on an underlying timing mechanism that does not slow down with advancing adult age.

Adult↗

On dopaminergic modulation of temporal information processing.

Temporal processing of durations in the range of seconds or more (i.e. time estimation) is cognitively mediated, whereas processing of brief durations in the range of milliseconds (i.e. time perception) appears to be beyond cognitive control and based on neural counting mechanisms. Although there is some evidence from animal and human studies suggesting that the internal timing mechanism underlying time perception is modulated by the effective level of brain dopamine, the findings are not conclusive. Therefore, the effects of pharmacologically induced changes in D2 receptor activity on temporal information processing were evaluated. In a double-blind design, either 3 mg of haloperidol, 150 mg of remoxipride, or placebo were administered in a single oral dose. Performance on time estimation was significantly impaired by both haloperidol and remoxipride as compared with placebo. Both drugs obviously affected cognitive mechanisms underlying temporal processing of durations in the range of seconds. On the other hand, only haloperidol produced a significant decrease in performance on time perception as compared with placebo and remoxipride, whereas the remoxipride and placebo groups did not differ significantly. The differential effects of haloperidol and remoxipride on performance on time perception suggest that D2 receptor activity in the basal ganglia may play a critical role in timing of brief durations in the range of milliseconds.

Acoustic Stimulation↗

Pharmacologic properties of the internal clock underlying time perception in humans.

Performance on temporal discrimination of time intervals in the range of milliseconds is interpreted by the assumption of an internal clock; the higher the clock rate the better the temporal resolution of the internal clock will be, which is equivalent to more accuracy in timing of brief intervals. Although there is some evidence from animal and human studies suggesting that the clock rate depends on the effective level of brain dopamine (DA), the findings are not conclusive. Therefore, an alternative interpretation of the pharmacologic properties of the internal clock has been introduced. According to this interpretation, the internal timing mechanism can be seen as a biological rhythm that is susceptible to chronomutagenic agents, i.e., pharmacologic compounds that are able to produce an alteration in the period of a biological rhythm. To elucidate the pharmacologic properties of the internal timing mechanism, in a double-blind study either 1750 mg of the DA antagonist alpha-methyl-p-tyrosine (AMPT), 0.65 g/kg ethanol which possesses chronomutagenic effects, or placebo were applied to 80 male subjects. As measures of performance, difference threshold estimates in relation to a 50- and a 1,000-ms standard interval and respective response latencies were computed. Furthermore, urinary levels of DA, DOPAC, and HVA were quantified by HPLC analysis. Although AMPT treatment resulted in a pronounced reduction of more than 50% for DA, DOPAC, and HVA, temporal discrimination was not affected. On the other hand, ethanol induced a significant impairment in performance on temporal discrimination in the range of milliseconds as compared to placebo. Neither temporal discrimination in the range of seconds nor response latencies were affected by the drugs applied in this experiment. Our findings suggest that the internal timing mechanism underlying temporal discrimination of intervals in the range of milliseconds is independent of the effective level of brain DA. More likely, pharmacologically induced changes in clock rate appear to depend on the chronomutagenic effects of the drug applied. Furthermore, the absence of ethanol-induced changes in performance on temporal discrimination of longer intervals in the range of seconds supports the assumption of two distinct timing mechanisms underlying temporal discrimination in the millisecond and second range.

3,4-Dihydroxyphenylacetic Acid↗

Duration discrimination of filled and empty auditory intervals: cognitive and perceptual factors.

Adult subjects were presented with two auditory stimuli per trial, and their task was to decide which of the two was longer in duration. An adaptive psychophysical procedure was used. In Experiments 1, 2, and 4, the base duration was 50 msec, whereas in Experiment 3, the base duration was 1 sec. In Experiments 1, 2, and 4, it was found that filled intervals (continuous tones) were discriminated more accurately than empty intervals (with onset and offset marked by clicks). It was concluded that this difference was perceptual rather than cognitive in nature, since performance on filled and empty intervals was not affected by increasing cognitive load in a dual-task procedure (Experiment 2) but was affected by backward masking (Experiment 4). In contrast, the results of Experiment 3 showed that duration discrimination of filled auditory intervals of longer duration was cognitively influenced, since performance was impaired by increasing cognitive load. Implications for notions of perceptual processing and timing mechanism underlying differences in duration discrimination with filled and empty intervals are discussed.

Adult↗

Effects of cold on human information processing: application of a reaction time paradigm.

Only a very few studies on the effects of cold on human information processing appear to exist. Therefore, the present experiment was designed to study the effects of the experimentally induced lowering of body core temperature on information processing, while applying a reaction time paradigm. Thirty healthy male volunteers performed a stimulus evaluation-response selection reaction time task after exposure to ambient temperatures of either 28 or 5 degrees C. A 0.5 degree C-decrease in body core temperature resulted in a significant increase in both reaction and movement time indicating a general deteriorating effect of lowering of body core temperature on information processing. Mean reaction times were 538 ms and 549 ms for the control and the cold group, respectively (p < .05). The respective mean movement times were 298 ms and 269 ms (p < .001). Speed of stimulus evaluation was not sensitive to decreases in body core temperature. However, response complexity and body core temperature showed a significant interaction in their effect on movement time (p < .05), indicating that lowering of body core temperature is more likely to affect response-related stages of central information processing rather than stimulus evaluation. Furthermore, movement time appeared to be more sensitive to cold-induced effects on information processing as compared to reaction time. Additional correlational analyses suggest that the observed effects can be considered as independent of changes in skin temperature and experienced levels of thermal discomfort. Taken together, the results indicate that lowering of body core temperature differentially affects various stages of information processing.

Adult↗

Effects of pharmacologically induced changes in NMDA-receptor activity on long-term memory in humans.

In a double-blind crossover design, either 30 mg of the noncompetitive NMDA-receptor antagonist memantine or a placebo was administered to 40 healthy male volunteers. Twenty line drawings of objects and 20 photographs of unfamiliar faces were presented on a computer screen. After a retention interval of 80 min, the participants' task was to select the original objects and faces from a set of 80 items. Results were analyzed applying a signal-detection-theory approach. Recognition performance for objects was significantly impaired under memantine as compared to placebo, whereas performance on face recognition was not affected. Findings support the notion of differential effects of NMDA-receptor antagonists on memory functions in humans.

Adult↗