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Biomedical subjects

R M Church

Publications and source records attributed to R M Church.

At least 19 recordsLinked to original sources

Comparison of variance and covariance patterns in parallel and serial theories of timing.

Parallel and serial timing processes are analyzed for their account of the dynamics of intertrial responding in the peak procedure. A strictly serial model, such as the behavioral theory of timing (Killeen & Fetterman, 1988), does not fit the dynamic correlation pattern in the location and duration of the middle high-rate responding portion of peak trials. In contrast, the parallel scalar expectancy theory model, with a sample for memory and threshold, does fit this pattern. A modification of the serial model is presented that also accommodates the within-trial covariance pattern. The modification, which is formally equivalent to a model for human tapping (Wing & Kristofferson, 1973), entails the addition of concurrent processes operating in parallel with serial timing.

Animals

Categorical time production: evidence for discrete timing in motor control.

Subjects performed a repetitive manual tapping task, attempting to match a given rate of auditory stimulus pulses, first with the pulses audible (synchronization) and then with the pulses turned off (continuation). In different sessions, the interstimulus interval (ISI) was selected from the range 175 to 825 msec in steps of 25 msec, with different ISI values presented in a random order. Across this range of ISI conditions, interresponse intervals (IRIs) exhibited alternating positive bias (too slow) and negative bias (too fast). We interpret this pattern of bias in terms of a discrete, or categorical, timing mechanism in motor timing. Categorical time production can be viewed as extending our conception of the timekeeper in Wing's (Wing & Kristofferson, 1973a, 1973b) two-process model of motor timing and may be related to the system of multiple clocks proposed by Kristofferson (1980) to explain a categorical pattern of variability measures in duration discrimination.

Adult

Representation of time.

Memory representation for time was studied in two settings. First, an analysis of timing in a laboratory analog of a foraging situation revealed that departure times from a patchy resource followed a Weber Law-like property implied by scalar timing. A trial-by-trial analysis was then pursued in a similar but more structured experimental paradigm, the Peak procedure. Study of covariance structures in the data implicated scalar variance in the memory for time as well as in the decision process, but the correlation pattern ruled out multiple access to memory within a trial.

Animals

Alternative representations of time, number, and rate.

Three facts of time perception are described based upon a temporal generalization task for rats (the peak procedure) in which food reinforcement is delivered on half the trials following the first lever-press response after some fixed interval after signal onset. (1) The mean response rate as a function of time is a smooth, slightly asymmetric, function with a maximum near the time of reinforcement; (2) the response rate on individual trials is characterized by an abrupt change from a state of low responding to a state of high responding and finally another state of low responding (break-run-break pattern); and (3) the mean response rate in 12-s and 20-s peak procedures is similar when plotted against time relative to the time of reinforcement (superposition). An information-processing version of scalar timing theory is described and compared to an alternative connectionist version of scalar timing theory that involves multiple oscillators and an autoassociation network. Psychological, mathematical and biological descriptions of the two versions are described and some possible extensions of the connectionist version are proposed to deal with perception of number, rate, and spatial orientation.

Animals

Attention and the frontal cortex as examined by simultaneous temporal processing.

The brain mechanisms involved in attention and memory were examined by testing rats in temporal discriminations designed to emphasize these cognitive processes. Normal rats were able to time each of two stimuli whether they were presented alone or together. Rats with lesions of the frontal cortex (FC) or nucleus basalis magnocellularis (NBM) were able to time each stimulus when it was presented alone, but not when it was presented together with another stimulus. Rather, these rats timed only the intruding stimulus and ignored the other, demonstrating a failure of divided attention. Rats with lesions of the fimbria-fornix (FF) or medial septal area (MSA) performed the divided attention task normally, but failed to remember the duration of a stimulus that had been terminated temporarily earlier in the trial, demonstrating a failure of working memory. These results provide another informative dissociation between the functions of the frontal and hippocampal systems, emphasizing frontal involvement in attention, and hippocampal involvement in working memory.

Animals

Separation of hippocampal and amygdaloid involvement in temporal memory dysfunctions.

The role of the hippocampus and the amygdala in timing and in the memory of previously timed events was investigated in rats. Two testing procedures used the peak time (the time at which the maximum response rate occurred) to identify the time at which the rat expected reinforcement. Amygdala (AMG) lesions had no effect on the remembered time of reinforcement or on the ability to remember the duration of a previous stimulus. Fimbria-fornix (FF) lesions had two effects: these rats remembered the time of reinforcement as occurring earlier than it really did, and could not remember the duration of a previous stimulus even after a gap of only 0.5 s. This behavior pattern endured throughout testing in spite of reinforcement contingencies designed to eliminate it. Atropine, 0.45 mg/kg, caused control rats to forget the duration of a previous stimulus, while haloperidol, 0.15 mg/kg, did not. Taken together, these data indicate that the hippocampus, but not the amygdala, has an important role in the memory for time. They suggest that alterations in temporal processes may be intimately involved in the amnesic syndrome seen following damage to temporal lobe structures.

Amygdala

Cholinergic modulation of the content of temporal memory.

The pharmacological effects of anticholinesterases (physostigmine and neostigmine) and cholinergic receptor blockers (atropine and methylatropine) on the content of temporal memory in the rat were studied with the use of a 20-s peak-interval procedure with auditory signals. Physostigmine administered ip decreased the variability of the temporal discrimination and shifted peak times permanently leftward on the time scale in a dose-dependent fashion (0.01, 0.03, & 0.09 mg/kg). Neostigmine (0.03 mg/kg) did not produce any of these effects. Atropine administered ip increased the variability of the temporal discrimination and shifted peak times permanently rightward on the time scale in a dose-dependent fashion (0.05, 0.15, & 0.45 mg/kg). Methylatropine (0.15 mg/kg) did not produce any of these effects. Application of a scalar timing model indicated that physostigmine decreased the remembered times of reinforcement and increased sensitivity to time, whereas atropine increased the remembered times of reinforcement and decreased sensitivity to time. These results suggest that the effective level of brain acetylcholine sets the communication speed for the translation of durations measured by the internal clock into values stored in temporal memory.

Animals

Nutrients that modify the speed of internal clock and memory storage processes.

Two experiments assessed the effects of nutrients on timing behavior by rats. The nutrients were laced with saccharin and given to rats as a snack before training on a 20-s peak-interval procedure. The primary component of the snacks for four groups of 10 rats was lecithin (phosphatidylcholine), protein (casein), carbohydrate (sucrose), or a nonnutrient (saccharin). The primary measure of behavior was the time of the rat's highest response rate during a trial (peak time), which represented the interval during which the rat maximally expected food. With a lecithin snack, peak time was gradually shifted over sessions to a shorter time, remained shifted to the left of the normal function with additional testing, and then remained at the shorter time on two sessions after the snack was discontinued; with the protein snack, peak time was abruptly shifted to a shorter time, returned to normal with additional testing, and then rebounded to a longer time when the snack was discontinued; with a carbohydrate, snack peak time was abruptly shifted to a longer time, returned to normal with additional testing, and then rebounded to a shorter time when the snack was discontinued. The behavioral patterns produced by the nutrients were interpreted in terms of precursor effects on central neurotransmitter synthesis and release, psychological stages of an information-processing model, and mathematical parameters of a scalar timing theory.

Animals

Pharmacy practice in the Indian Health Service.

The current status of pharmaceutical services in the Indian Health Service (IHS) is described. IHS is a nationwide program for providing health-care services to more than 960,000 American Indians and Alaska Natives who live on or near federal Indian reservations. Because IHS pharmacy practice revolves around the needs of the patient, pharmacists have close and frequent contact with patients and must have an acute sensitivity to and respect for the cultural values and beliefs of the patients. Ambulatory-care services are emphasized; pharmacists often provide primary care to patients and make frequent use of prescribing authority. All prescriptions are filled directly from the patient's permanent health record, and private patient consultation rooms are used extensively. In the inpatient setting, pharmacists obtain medication and related histories from newly admitted patients and provide patient counseling at the time of discharge. Pharmacists are also actively involved in facility-wide programs and committees (especially those that deal with quality assurance and facility accreditation) and serve as preceptors of pharmacy residents and students. In the future, IHS pharmacy practice will emphasize the expansion of patient-care activities and primary-care programs, effective use of prescribing authority, and the refinement of patient consultation services, services for the elderly, home health-care services, and inpatient clinical services.

Ambulatory Care

Nucleus basalis magnocellularis and medial septal area lesions differentially impair temporal memory.

Functional dissociations between the medial septal area (MSA) and the nucleus basalis magnocellularis (NBM) were examined using the concepts and experimental procedures developed by scalar timing theory. Rats were tested in variations of a signalled discrete-trial peak-interval schedule of reinforcement in which the response rate functions identified the time when the rats expected reinforcement. The variations assessed aspects of both reference and working memory for information obtained from prior trials and from the current trial. A double dissociation was found in reference memory. Rats with NBM lesions, like those with frontal cortex (FC) lesions, remembered the time of reinforcement as having occurred later than it actually did; rats with MSA lesions, like those with fimbria-fornix (FF) lesions, remembered the time of reinforcement as having occurred earlier than it did. A single dissociation was found in working memory. MSA lesions and FF lesions impaired working memory, while NBM and FC lesions had no effect on it. These data begin to identify the brain mechanisms underlying temporal memory; they indicate that the frontal and hippocampal systems are both involved, but in complementary ways; and they provide information that helps specify more clearly the functions of the frontal and hippocampal systems.

Animals

Arginine vasopressin innoculates against age-related increases in sodium-dependent high affinity choline uptake and discrepancies in the content of temporal memory.

Systemic injections of arginine vasopressin (AVP, 0.08 pressor units/kg i.p.) to mature rats (10-13 months) trained on a positively reinforced timing task prevented the age-related discrepancies in the content of temporal memory and the increases in sodium-dependent high affinity choline uptake (SDHCU) in the frontal cortex observed in control rats when the rats became aged (27-30 months). AVP administration had no effect on muscarinic receptor density as measured by [3H]quinuclidinyl benzilate (QNB) binding or on choline acetyltransferase (ChAT) levels in either the hippocampus or the frontal cortex.

Aging

Temporal integration in duration and number discrimination.

Temporal integration in duration and number discrimination by rats was investigated with the use of a psychophysical choice procedure. A response on one lever ("short" response) following a 1-s white-noise signal was followed by food reinforcement, and a response on the other lever ("long" response) following a 2-s white-noise signal was also followed by food reinforcement. Either response following a signal of one of five intermediate durations was unreinforced. This led to a psychophysical function in which the probability of a long response was related to signal duration in an ogival manner. On 2 test days, a white-noise signal with 5, 6, 7, 8, or 10 segments of either 0.5-s on and 0.5-s off or 1-s on and 1-s off was presented, and a choice response following these signals was unreinforced. The probability of a long response was the same function of a segmented signal and a continuous signal if each segment was considered equivalent to 200 ms. A quantitative fit of a scalar estimation theory suggested that the latencies to initiate temporal integration and to terminate the process are both about 200 ms, and that the same internal accumulation process can be used for counting and timing.

Animals

Hippocampus, time, and memory.

Five experiments were conducted to determine the effects of hippocampal damage on timing and the memory for temporal events. In Experiments 1-3, rats were trained to discriminate between auditory signals that differed in both duration (2 or 8 s) and rate (2 or 16 cycles/s). Half of the rats were trained to discriminate duration, and half were trained to discriminate rate. After rats acquired the relevant discrimination, signals with intermediate durations and rates were presented to obtain psychophysical functions that related signal duration and/or rate to response choice. Rats then received either lesions of the fimbria-fornix or control operations. Postoperatively, the accuracy of duration and rate discriminations as measured by the difference limen (DL) was unaffected by the lesion, but the point of subjective equality (PSE) was shifted to a shorter duration and a slower rate by the lesion in Experiment 1. Both rats with lesions and rats with control operations showed cross-modal transfer of duration and rate from the auditory signals used in training to visual signals used in testing in Experiment 2. A 5-s delay was imposed between the end of a signal and the opportunity to respond in Experiment 3. The delay served as a retention interval for the rats trained in the rate discrimination, and the rats with fimbria-fornix lesions were selectively impaired by the addition of the delay as measured by an increase in the DL. The delay did not serve as a retention interval for rats trained in the duration discrimination because they were able to continue timing through the delay. A peak procedure was employed in Experiment 4. The maximum response rate of control rats was approximately at the time of scheduled reinforcement (20 s), but the maximum response rate of rats with fimbria-fornix lesions was reliably earlier than the time of scheduled reinforcement. When a 5-s gap was imposed in the signal, control rats summed the signal durations before and after the gap, whereas rats with fimbria-fornix lesions showed no retention of the signal duration prior to the gap. Experiment 5 continued the testing of the rats used in Experiments 1-4 and showed that rats with lesions had an impairment in a test of spatial working memory in an eight-arm radial maze. Taken together, these results demonstrate that a fimbria-fornix lesion interferes with temporal and spatial working memory, reduces the remembered time of reinforcement stored in reference memory, and has no effect on the animal's sensitivity to stimulus duration.

Animals

Properties of the internal clock.

Evidence has been cited for the following properties of the parts of the psychological process used for timing intervals: The pacemaker has a mean rate that can be varied by drugs, diet, and stress. The switch has a latency to operate and it can be operated in various modes, such as run, stop, and reset. The accumulator times up, in absolute, arithmetic units. Working memory can be reset on command or, after lesions have been created in the fimbria fornix, when there is a gap in a signal. The transformation from the accumulator to reference memory is done with a multiplicative constant that is affected by drugs, lesions, and individual differences. The comparator uses a ratio between the value in the accumulator (or working memory) and reference memory. Finally, there must be multiple switch-accumulator modules to handle simultaneous temporal processing; and the psychological timing process may be used on some occasions and not on others.

Animals

Simultaneous temporal processing.

Seven experiments assessed the ability of rats to process temporal information from two internal clocks simultaneously and independently. In the first six experiments a light stimulus signalled an overall interval between the beginning of a trial and the availability of food reinforcement (e.g., a 50-s fixed interval). During the overall interval a sound stimulus was used to signal shorter intervals that divided the overall interval into equal segments. When there was a fixed temporal relation between the final segment signal and the availability of reinforcement, there was a double-scallop pattern of responding throughout the segmented overall interval; the function relating response rate to time during segment intervals was similar to the function relating response rate to time in unsegmented overall intervals; a change in response rate occurred at the time that a normally presented segment signal was omitted. Taken together, the results indicate that rats timed the overall interval and the segment intervals simultaneously and independently without interference. In Experiment 7 a light stimulus was used on some trials, and a sound stimulus was used on other trials to signal a discrete-trial 50-s peak procedure. When these two signals were presented in compound, there was a leftward shift of the response function, which suggests that rats timed both signals simultaneously. For all of the experiments a scalar timing model with specific stimulus integration rules is used to explain the results. The stimulus integration rule used in the first six experiments, in which there were two signals for the same reinforcement, was to respond if both the segment and the overall interval had exceeded a response threshold. The stimulus integration rule used in Experiment 7, in which there were two signals for different reinforcements, was to respond if the response threshold for either interval had been exceeded.

Animals