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Biomedical subjects

T N Tombaugh

Publications and source records attributed to T N Tombaugh.

At least 19 recordsLinked to original sources

Effects of age on the Rey-Osterrieth and Taylor complex figures: test-retest data using an intentional learning paradigm.

The degree to which the Rey-Osterrieth and Taylor complex figures provide equivalent measures of visual memory, and the effects of age on figure comparability were examined in two experiments. Both experiments employed a multiple-trial, intentional learning procedure wherein each figure was administered twice in a counterbalanced sequence to subjects aged 20 to 80 years. In Experiment 1, a constant 60-s exposure duration was used; in Experiment 2, a self-pacing procedure was employed where the exposure duration was individually determined. The results from both experiments showed that the Taylor figure was easier to learn than the Rey-Osterrieth figure, indicating that the two figures are not equivalent for testing memory. These results were supported by subjective judgements on the relative difficulty to learn and remember each figure. Finally, younger (20-59 years) subjects performed at a higher level than older (60-80 years) subjects on both figures. Recommendations and possible alternatives are suggested regarding the use of the figures in both constructional and visuo-spatial memory test-retest situations.

Adult

The mini-mental state examination: a comprehensive review.

OBJECTIVE: The purpose of this paper is to provide a comprehensive review of information accumulated over the past 26 years regarding the psychometric properties and utility of the Mini-Mental State Examination (MMSE). PARTICIPANTS: The reviewed studies assessed a wide variety of subjects, ranging from cognitively intact community residents to those with severe cognitive impairment associated with various types of dementing illnesses. MAIN OUTCOME MEASURES: The validity of the MMSE was compared against a variety of gold standards, including DSM-III-R and NINCDS-ADRDA criteria, clinical diagnoses, Activities of Daily Living measures, and other tests that putatively identify and measure cognitive impairment. RESULTS: Reliability and construct validity were judged to be satisfactory. Measures of criterion validity showed high levels of sensitivity for moderate-to-severe cognitive impairment and lower levels for mild degrees of impairment. Content analyses revealed the MMSE was highly verbal, and not all items were equally sensitive to cognitive impairment. Items measuring language were judged to be relatively easy and lacked utility for identifying mild language deficits. Overall, MMSE scores were affected by age, education, and cultural background, but not gender. CONCLUSIONS: In general, the MMSE fulfilled its original goal of providing a brief screening test that quantitatively assesses the severity of cognitive impairment and documents cognitive changes occurring over time. The MMSE should not, by itself, be used as a diagnostic tool to identify dementia. Suggestions for the clinical use of the MMSE are made.

Activities of Daily Living

Four studies comparing the Rey-Osterrieth and Taylor complex figures.

The ability of the Rey-Osterrieth (R-O) and Taylor complex figures to produce equivalent scores on both constructional and memory tasks was examined in four studies. While the two figures yielded equivalent copy scores, the Taylor figure produced significantly higher scores on memory tests. This latter relationship was observed with three different retention conditions (immediate, 20-min, and 1-month recall), two types of learning paradigms (incidental and intentional), and two scoring systems (itemized and clinical neuropsychological). The failure to obtain equivalent recall scores cautions against using the R-O and Taylor as companion figures to evaluate normal recovery and treatment effectiveness on mnemonic processes. The relative merits of using an intentional rather than an incidental procedure to administer the figures in test-retest situations are discussed.

Adult

Failure to replicate the dorsal bundle extinction effect: telencephalic norepinephrine depletion does not reliably increase resistance to extinction but does augment gustatory neophobia.

Depletion of telencephalic noradrenaline (Ne), caused by lesion of the dorsal tegmental bundle, has been reported to increase persistence of non-reinforced responding in various operant tasks. This has been referred to as the dorsal bundle extinction effect (DBEE). In an effort to reproduce this effect, rats receiving 6-hydroxydopamine lesions of the dorsal Ne bundle (DB-6-OHDA) were compared to controls during extinction of a continuous food rewarded (CRF) lever-press response. While the lesion group showed an increase in responding during initial extinction, no significant difference in resistance to extinction using a 2-min non-response criterion was obtained. Moreover, no differences in reinforced response rates were observed with CRF, fixed ratio (FR-15, FR-30, FR-60) or variable interval (VI-30, VI-60, VI-120 s) schedules of reinforcement. In order to test the hypothesis that the DBEE is dependent on time of behavioral testing after surgery, subsequent experiments were performed where rats began CRF operant training 5, 17, 31 or 110 days post-lesion. No differences in resistance to extinction were observed between lesion and control rats at any post-lesion interval. Neonatal treatment with 6-OHDA which permanently lesions forebrain Ne terminals also failed to prolong extinction. Finally, when both DB-6-OHDA and neonatal rats were given a choice between water and saccharin the lesioned animals exhibited a neophobic reaction whereby they drank significantly less saccharin. We conclude that while the DBEE is not a reliably reproducible phenomenon other effects of forebrain Ne lesions, such as neophobia, appear to be robust.

Afferent Pathways

Failure of pimozide to disrupt the acquisition of light-dark and spatial discrimination problems.

The effects of pimozide, a dopamine (DA) receptor blocker, on associative learning was examined using two appetitively motivated choice paradigms. In Experiment I, low to moderate doses of pimozide (0.125, 0.25 mg/kg) were not found to disrupt the acquisition of a two bar simultaneous discrimination task. However, with continued testing, progressive deficits in response accuracy were observed in rats pretreated with 0.25 mg/kg pimozide. When subsequently tested drug-free these animals demonstrated a rapid and marked improvement in performance. Experiment II used a spatial discrimination task (T-maze) requiring a natural response (running) with minimal response demands (short stem and arms). Rats pretreated with 0.25, 0.50, and 1.0 mg/kg pimozide showed comparable levels of acquisition and maintained discriminated performance relative to vehicle controls. Similar results were obtained when the reinforced (S+) and nonreinforced (S-) stimuli were reversed. Moreover, animals receiving 2.0 mg/kg pimozide and not rendered cataleptic also demonstrated acquisition of both the initial discrimination and its reversal. It was concluded that rats pretreated with pimozide are able to acquire the significance of environmental stimuli and direct their responding accordingly if they are motorically capable of emitting the required response.

Animals

Alteration of exploration and the response to food associated cues after treatment with pimozide.

A series of experiments assessed the effects of pimozide on spontaneous alternation in a Y- and 8-arm radial maze, and on approach to food or cues that had previously been associated with food. Mice treated with pimozide (0.2, 0.4 and 0.8 mg/kg) displayed a dose dependent reduction of alternation performance, without engendering a perseverative tendency and apparently without affecting the course of habituation. When food deprived mice entered an arm of the maze that was baited with a food pellet they consumed the food and remained in the vicinity of the food cup. Moreover, upon retesting in the non-drug state mice still exhibited a preference for cues that had been associated with food. It seems that although pimozide at the doses tested produced a haphazard pattern of exploration, the drug did not alter the rewarding value of secondary reinforcers. Contrary to an anhedonic hypothesis, it is suggested that higher doses of pimozide may actually increase, rather than decrease, the saliency of biologically significant stimuli.

Animals

Failure to obtain functional equivalence between dopamine receptor blockade and extinction: evidence supporting a sensory-motor conditioning hypothesis.

The effects of pimozide were tested in a discrete trial paradigm. Following 8 days of continuous reinforcement training with a retractable bar, subjects were divided into 3 groups: Vehicle-Extinction; Pimozide-Extinction and Pimozide-Reinforcement. Pimozide rats received 1 mg/kg of drug 4 hours prior to test. On each of 3 test days reinforcement continued to be delivered on a continuous reinforcement schedule for the Pimozide-Reinforcement Group whereas it was no longer delivered for the other two groups. Each test day was separated by 4 drug-free days. The Pimozide-Reinforcement Group showed the least response suppression, followed by the Vehicle-Extinction and Pimozide-Extinction Groups. These results do not support the anhedonic hypothesis that dopamine containing neurons mediate reward processes and were interpreted within a sensory-motor conditioning framework.

Animals

Avoidance performance, cue and response-choice discrimination after neuroleptic treatment.

The effects of pimozide on discriminated avoidance performance in a Y-maze were evaluated in mice. Relatively low doses of pimozide (0.4 mg/kg) retarded acquisition of an active avoidance response. The avoidance deficit induced by this dosage was largely eliminated among mice that had received either 1 or 2 previous avoidance training sessions, but was still evident in mice treated with a higher drug dosage (0.8 mg/kg). If mice were initially trained in the drug condition, the disruptive effects were still evident in a later test conducted in the absence of the drug treatment. In contrast to the avoidance deficits, pimozide did not disrupt the acquisition or the performance of a cue- or response-choice discrimination. That is, once a running response was initiated (on avoidance trials) pimozide treated animals appeared capable of appropriately directing the response. It is suggested that at the dosages used pimozide did not affect S-S learning or learning response-outcome contingencies, but rather hindered performance owing to deficits in response initiation processes. Moreover, within a task involving aversive motivation pimozide did not appear to reduce the reinforcement derived for correct responding.

Animals

Establishment of secondary reinforcement in sign tracking and place preference tests following pimozide treatment.

The effects of pimozide (1.0 mg/kg), a DA receptor blocker, on the capacity of environmental stimuli to acquire secondary reinforcing properties was investigated using two different paradigms. In the first experiment rats pretreated with either pimozide or its vehicle, were exposed to light-food pairings. When tested under drug-free extinction conditions, these animals approached the light cue significantly more frequently than did control animals who never had the cue associated with food during training. No differences in approach behavior were observed between the pimozide and vehicle groups that received the light-food pairings. The second experiment employed a place preference paradigm where animals were confined in distinctive compartments under reinforced (S+) or nonreinforced (S-) conditions. Pimozide and vehicle treated animals, when tested drug-free and given unrestricted access to both chambers under extinction conditions, spent comparable amounts of time in the S+ chamber relative to vehicle subjects that had never received food in either chamber. The results from these two studies indicate that an animal's ability to code relevant environmental information and to use this encoded information to guide and direct food seeking behavior is relatively independent of dopaminergic activity. The results also have significance for any theory which assumes that dopamine mediates reward processes.

Animals

Effects of pimozide on nordiscriminated and discriminated performance in the pigeon.

The effects of pimozide (0.06, 0.18, 0.30 mg/kg), a dopamine receptor blocker, on nondiscriminated and discriminated performance were assessed in pigeons using a Latin Square design. In Experiment 1 a dose-dependent decrease in responding was observed with a variable interval 3-min schedule of reinforcement. More detailed analyses showed that total response rate, running response rate, and post-reinforcement pause all showed the same dose-dependent relationship. In Experiment 2 a successive discrimination task was employed to determine if pimozide affects a previously learned association between environmental stimuli. Each pigeon was first trained on the discrimination and then injected with the same doses as in Experiment 1. Although pimozide reduced responding in a dose-related fashion, a corresponding decrease in accuracy of responding was not evident. It was concluded that pimozide has a general response debilitating effect and that dopaminergic neurons probably are not involved in subserving associative processes.

Animals

Use of a fixed consecutive number schedule of reinforcement to investigate the effects of pimozide on behavior controlled by internal and external stimuli.

The effects of the neuroleptic pimozide, a specific dopamine receptor blocker, on behavior maintained under different degrees of stimulus control was examined by using a fixed consecutive number (FCN) schedule of reinforcement with pigeons. This schedule requires that at least eight consecutive responses be made on one key (work key) before a response on a second key (reinforcement key) will be reinforced. For half the birds no change in external stimuli accompanied the eight response (FCN-8) while for the other half the color of the work key changed from white to red after the eight peck (FCN-SD). Both schedules resulted in equal rates of baseline responding. Four doses of pimozide (vehicle, 0.1, 0.3, 0.5 mg/kg) were administered in a Latin Square sequence after baseline responding was stable. Similar pimozide-induced decreases in responding were observed in both conditions. However, pimozide selectively altered response patterns under the FCN-8 condition. The failure of the FCN-SD procedure to display a similar effect demonstrated that the use of salient exteroceptive stimuli can modulate behavioral deficits induced by pimozide. This conclusion has important implications for theories hypothesizing that dopamine subserves reward processes.

Animals

Ethanol-Metrecal diets: I. effects of different levels of ethanol-derived kilocalories on consumption of diet, body weight and grams of ethanol ingested.

Three experiments investigated the relationship between ethanol consumption and the percentage of ethanol-derived kilocalories contained in liquid diets. Rats were chronically maintained on diets where different concentrations of ethanol (10%, 12%, 14%) were added to Metrecal so that 41%, 49% and 57% of all kilocalories consumed were derived from ethanol. The ethanol-Metrecal diet served as the sole source of calories. Results demonstrated that rats can be maintained for extended time periods on diets where ethanol contributed approximately 50% of the daily kilocalories. Inspection of consummatory profiles revealed that an initial decrease occurred in volume of diet consumed when levels of ethanol were increased. This was followed by a gradual increase in the level of consumption until a new asymptotic level was established. Grams of ethanol/kg of body weight remained relatively constant over the range of ethanol concentrations employed. The results were discussed in respect to three factors controlling consummatory behavior--sensory stimuli, caloric intake and quantity of ethanol ingested.

Acoustic Stimulation

Ethanol-Metrecal diets: II. Failure to obtain impaired performance on a series of appetitively and aversively motivated tasks.

Rats were chronically maintained on ethanol-Metrecal diets where either 37%, 41%, 49% or 57% of the total kilocalories were derived from ethanol. In three experiments animals were tested on a series of problems (passive avoidance, shuttle avoidance, simultaneous and successive discrimination, and complex spatial maze learning) 6 to 8 weeks after the diet had been withdrawn. There was no evidence that chronic ethanol regimes impaired either learning or memory processes.

Alcohol Drinking

Application of contingent physical restraint to suppress stereotyped body rocking of profoundly mentally retarded persons.

The effectiveness of contingent restraint in reducing stereotyped body rocking of profoundly retarded subjects was investigated to determine (a) whether restraint reduced stereotyped body rocking and (b) the degree to which the effectiveness of restraint depended upon where in the behavioral sequence it was administered. Results showed that restraint, in comparison to no restraint, reduced the amount of body rocking. Also, restraint was judged to be generally more effective if it were applied when the subject was bent over in the middle of the response sequence rather than administered while the subject was sitting upright at the end of the response sequence. The results were interpreted in terms of response chaining and postural feedback. Implications for the utilization of physical restraint as a behavioral intervention were discussed.

Adolescent

Extinction and dopamine receptor blockade after intermittent reinforcement training: failure to observe functional equivalence.

Response decrements in an operant task produced by either extinction or by the dopamine receptor blocker pimozide were examined in three experiments which employed intermittent reinforcement schedules. In contrast to the congruency between these treatments previously observed following continuous reinforcement training, treatment with pimozide was markedly more effective than extinction in decreasing performance after training with variable interval, fixed interval, and fixed ratio reinforcement. The two treatments also produced substantially different patterns of responding. A shift from extinction to pimozide did not alter the progressive decline in response rate over days, but a shift from pimozide to extinction caused a pronounced increase of performance. These results indicate that the pimozide and extinction treatment did not produce functionally equivalent effects, and that the role of dopamine on reward processes should not be inferred from comparisons between pimozide and extinction.

Animals

Effects of pimozide on accuracy of performance and distribution of correct responding on a simultaneous discrimination task in the rat.

After training rats in a simultaneous discrimination problem, pimozide, a dopamine receptor blocker, was administered to determine whether accuracy of performance would be disrupted. Each animal received five doses of pimozide (vehicle, 0.05, 0.10, 0.30, and 0.60 mg/kg) delivered in a Latin Square sequence with five non-drug days between injections. Pimozide did not disrupt well established discrimination behavior at any of the doses even though a decrease in rate of responding was observed at the two higher doses. These results provide additional evidence that DA neutrons are not essential in the mediation of previously learned associations.

Animals

Effects of dopamine receptor blockade on alimentary behaviors: home cage food consumption, magazine training, operant acquisition, and performance.

Administration of the dopamine receptor blocker pimozide (1.0 mg/kg) disrupted the initiation, but not the maintenance, of home cage food consumption. Likewise, the number of pellets consumed during magazine training was decreased among pimozide-treated rats during the first, but not the second day of training. The acquisition of a bar-press response for food reinforcement (using a retractable bar) was severely retarded by pimozide. However, such an impairment was not evident if animals initially received 2 training days in the absence of the drug. Further, among rats trained to bar press to asymptote using a nonretractable bar, pimozide reduced the within and between days bar-press rate such that performance was indistinguishable from that of animals placed on extinction in the absence of the drug treatment. When transferred from the pimozide treatment to extinction in the absence of drug, the response rate increased to the level observed during the first session of either extinction or pimozide in the continuous reinforcement condition. The results are discussed in terms of sensory-motor and reinforcement consequences of dopamine receptor blockade.

Animals