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Representation of serial order in monkeys (Cebus apella).

Cebus monkeys were trained on a five-item serial learning task, symbolized as ABCDE; the initial stages of training were on the shorter subseries AB, ABC, and ABCD. To assess the monkeys' knowledge of the sequential position of each item, pair-wise tests were given to 2 subjects after acquisition of the ABCD series and to 4 subjects after reaching criterion on the ABCDE series. In both tests, the monkeys performed at high levels on the interior pairs, which were BC for the ABCD series, and BC, BD, and CD for the ABCDE series. These results, as well as the orderly relations observed in the pair-wise tests between first-item response latency and first-item position and between second-item response latency and number of missing items, indicated that the monkeys had developed a well-organized internal representation of the four- and five-item series. Although pigeons are also capable of learning four-item and five-item series, they apparently do not develop a comparable representational structure. The disparity between the monkeys' and pigeons' representational competence for serial order is predictable from the difference in their capacities for associative transitivity.

Animals

The effect of cyclandelate in depressed and demented patients: a controlled study in psychogeriatric patients.

In a double-blind clinical trial the effects of the vasodilator drug cyclandelate (in a dose of 1200 mg daily) were studied in a group of patients with depressive illnesses or dementing conditions. The measures used before treatment and after six weeks' treatment were: clinical rating, psychometric tests (Paired Associate Learning Test, Digit Copying Test, Digit Substitution Test, and Serial Learning Test), cortical evoked potentials, the sedation threshold and the Gresham Questionnaire. In the depressive group there were no significant differences in the changes in scores at six weeks in three groups: those who received cyclandelate plus amitriptyline, those who received placebo plus amitriptyline, and those who received neither placebo nor cyclandelate. In the demented group there were significant changes in favour of the placebo on two measures (Digit Copying test, and one component of the auditory evoked response). The results do not support the previously reported views claiming, in a number of studies, a significant improvement in the performance of both demented and normal elderly subjects treated with cyclandelate. The significance of these findings is discussed.

Aged

A double-blind comparison of the effects of temazepam and triazolam on residual, daytime performance in elderly insomniacs.

Benzodiazepine hypnotic medications are widely prescribed for elderly patients, but there is a paucity of information available concerning the residual cognitive and psychomotor (the morning-after) effects of these drugs. We compared two commonly used hypnotics--temazepam and triazolam--in a double-blind, placebo-controlled, single-dose study with community-dwelling healthy elderly with a DSM-III-R diagnosis of primary insomnia. Forty-five subjects over the age of 65 (mean age 72.23, SD = 4.44) qualified for the study. Subjects were randomly assigned to one of five treatment groups (placebo, triazolam 0.125 mg., triazolam 0.25 mg., temazepam 15 mg., and temazepam 30 mg.). Neuropsychological testing was completed at baseline and 12-14 hours after the dosing. Patients were evaluated with a variety of tests that measured attention, concentration, motor speed, immediate memory, and learning of new information. Separate repeated measured analyses of variance were performed to assess the significant changes among the five treatment groups. We found improved performance or no change in all the measures for all medication groups except for impairment of performance on a serial learning task for both high-dose medication groups. The significance of these results and the need for further research in elderly insomniacs is discussed.

Aged

Serial spatial reversal learning in rats: comparison of instrumental and automaintenance procedures.

Serial reversals of a spatial discrimination were trained in rats under automaintenance conditions, in which food reward occurred regardless of responding. This automaintained reversal learning was compared to instrumental reversal learning in other rats trained under a similar procedure which required responding for reward. In the automaintenance (AU) procedure, rats received food after every retraction of a "positive" response lever (S+); retraction of a second, "neutral" lever (So) was not paired with food delivery. Responses to the S+ were elicited at fairly constant rates during daily 100-trial conditioning sessions. Responses to the So occurred early in each session but rapidly diminished across trials. When the valences of the levers were reversed, responding shifted to the new S+ and diminished on the new So. Criterion for reversal was defined as a discrimination ratio (DR) of at least 90% responding to the S+ in two consecutive 10-trial blocks. With repeated reversals, acquisition of criterion performance occurred with increasing rapidity, reaching an asymptote below that required for the original discrimination. A second group of rats was trained on a similar instrumental schedule, in which at least one response to the S+ was required for food delivery. Response rates in this instrumental (IN) group were approximately double those of the AU group. However, ratios of S+ to So response rates were similar to those of the AU group, and the serial reversal curves generated were qualitatively similar. Thus rats can show improvement across serial reversals of a spatial discrimination based entirely on pairings of stimulus events (automaintenance), in a manner similar to that observed in instrumental procedures, in which reward is contingent upon correct responding.

Animals

Behavioral deficits after intrahippocampal fetal septal grafts in rats with selective fimbria-fornix lesions.

Fetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, 10 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (AChE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to almost non-existent in all transplant groups. AChE-positivity in the dorsal hippocampus (DH) was not related to behavioral performance. However, the grafts often grew to a considerable size within the host brain and in many rats, especially those in Group FI.T, produced moderate to extreme damage of the host DH. There was a significant positive correlation between errors in the radial maze and graft-induced DH damage but no relationship between errors and graft size. The results indicate that, after partial lesions of the fimbria-fornix, intrahippocampal septal grafts survive well but are likely to damage recipient structures and result in behavioral impairments.

Acetylcholinesterase

The effect of R 58 735 (Sabeluzole) on memory functions in healthy elderly volunteers.

The effects of chronic treatment (5 mg b.i.d. for 2 days followed by 10 mg b.i.d. for 5 days) with R 58 735 on human memory functions were studied in healthy elderly (age greater than or equal to 50 years) volunteers in a double-blind placebo-controlled study. Serial learning of nonsense syllables was better under R 58 735, and relearning 1 week after termination of the treatment was superior to relearning of similar material initially learned under placebo. Free recall of nonsense syllables was significantly better when these were learned under active compound. Proactive inhibition induced by consecutive presentation of word lists was attenuated by R 58 735. Short-term memory functions, retrieval accuracy from semantic memory and unprepared reaction times were unchanged. R 58 735 ameliorated both learning and recall in conditions of age-related mild hypofunction in healthy volunteers. The compound seems to have had positive effects on encoding and consolidation of new material.

Cognition

Impaired verbal reasoning and constructional apraxia in subjects with right hemisphere damage.

In addition to causing visuospatial deficits, damage to the right cerebral hemisphere also impairs other cognitive abilities, including those requiring higher-order aspects of language. The present study used a standardized test battery to examine the relationship between visuospatial abilities and comprehension of narrative material in subjects having unilateral right hemisphere damage (RHD). In a series of 41 consecutively admitted RHD subjects, impairments in abstracting information from narrative passages were as prevalent and as severe in magnitude as constructional apraxia. Moreover, the extent of the visuospatial and linguistic impairments were highly correlated. Although age, educational levels, and degree of premorbid brain atrophy were all found to influence performance, analysis of a select subgroup of the population established that the covariation of visuospatial and verbal impairments is related to right hemisphere damage per se. Clinically, these findings may be of significance for understanding the pervasive cognitive impairments that are often evidenced by RHD patients.

Aged

Visual impairments in macaques following inferior temporal lesions are exacerbated selectively by additional damage to superior temporal sulcus.

The present study examined the behavioural effects of removing the inferior temporal cortex (area TE) either on its own or in combination with the adjacent fundus and upper bank of the superior temporal sulcus (area STP). Comparisons with preoperative behaviour showed that the addition of superior temporal sulcal damage led to an increase in visual components of the Klüver-Bucy syndrome, i.e. an increased tendency to touch and examine objects coupled with a decrease in emotional reactivity, but no excessive orality, changes in food preference, or coprophagia. No group differences were found in the learning of 3 pattern discriminations, but the animals with additional superior temporal sulcal lesions were more impaired than the others on 3 colour discriminations, successive reversals of an object discrimination, and a learning-set task. These findings indicate that STP provides an important route, independent of the route via TE, by which visual information can reach limbic structures to evoke affective responses and contribute to visual learning.

Amygdala

Differential effects of age and cerebral atrophy upon span of immediate recall and paired-associate learning in older patients suspected of dementia.

Seventy-eight patients suspected of dementia, 50 years of age or older and without evidence of focal cerebral lesion or systemic illness, were administered the Digit-Span Forward and Paired-Associate Learning subtests of the Wechsler Memory Scale. Computerized axial tomography, allowing a visualization and measurement of the lateral ventricles and cortical sulci, was employed to measure cerebral atrophy. Four groups were defined as follows: (1) age 50-69, without atrophy (N = 27), (2) age 50-69, with atrophy (N = 17), (3) age 70-89, without atrophy (N = 18), (4) age 70-89, with atrophy (N = 16). Results of analyses of variance indicate that Digit-Span is affected by cerebral atrophy but not by age, while Paired-Associate Learning is affected by both age and cerebral atrophy. No interaction effect between age and cerebral atrophy was found for either task. These results are discussed within the context of previous research, and implications for both models of memory and theories of the effects of cerebral atrophy in different ag groups are suggested.

Age Factors

The effects of excitotoxic lesions of the nucleus accumbens on a matching to position task.

The effects of bilateral ibotenic acid lesions of the nucleus accumbens in the rat were examined on a delayed matching to position task. The lesion induced a stable delay-dependent performance deficit suggestive of a short-term memory problem. Following analysis of the impaired performance on trials with long delays, using measures akin to signal detection indices, the deficit was interpreted as being largely due to the intrusion of a side-dependent response bias. Low-dose amphetamine (0.75 mg/kg) produced a similar disruption in the sham-operated rats, both in terms of accuracy impairment and degree of strategical bias. As well as mimicking the effects of low-dose amphetamine in sham-operated rats, the lesion also protected against the disruptive effects of the drug at low doses. Whilst exhibiting no performance deficit when the matching schedule lacked a delay component, the lesioned rats were very significantly impaired in switching their response strategies when exposed to a series of reversals. In addition, the lesioned rats were remarkably resistant to an extinction procedure. Both these findings indicate that the lesioned rats were unable to exhibit flexibility in their response patterns. These results, taken together with those of the delayed matching procedure, imply that one of the functions of the intact nucleus accumbens is to inhibit habitual responding under conditions of non-reward and low stimulus control, possibly via its connections to the dorsal striatal system.

Amphetamine