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The effects of sequence structure and reward schedule on serial reaction time learning in the monkey.

This research tests the hypothesis that sequence learning performance in non-human primates will be modulated both by the structure of the sequences to be learned and by the schedule of reward applied during learning. Sequence learning in humans has been extensively explored with serial reaction time (SRT) protocols where learning is revealed by reduced reaction times for stimuli presented in repeating sequences vs. stimuli presented in random series. The SRT protocol has been used to demonstrate that different types of sequential structure may be learned under different awareness conditions. Here, we consider surface and abstract structure of sensorimotor sequences such that sequences ABCBAC and DEFEDF (where A to F correspond to spatial locations on a touch sensitive screen) have different serial order or surface structure, but share the same abstract structure 123213, and are thus considered isomorphic. In four experiments, we manipulated the type of sequential structure to be learned, and the schedule of reward in spatial sequence learning tasks. Both of the two monkeys tested demonstrated significant SRT learning for serial order or surface structure, while they failed to learn and transfer abstract structure. Their learning performance was also modulated by the schedule of reward. These results are in support of our hypothesis and are discussed in the context of existing models of sensorimotor sequence learning.

Animals↗

Ordinal position learning and remote anticipation.

Rats were runway trained on each of two 3-trial series of reward outcomes. The series are labeled XNY and ZNN, for which X represents a trial that was rewarded with Noyes pellets and N represents a trial that ended with no reward. Units of distinctively flavored breakfast cereals served as reward on trials labeled Y and Z. One group (Floor) had each series occur with a correlated runway floor, either smooth and black or rough and white. For a second group (Memory), the floor cue was uncorrelated with series. Animals in both groups learned to approach the goal rapidly on the 1st trials of the 2 series and slowly on the 2nd trials, but only Group Floor learned to differentiate the 3rd trials of the series. These results recommend a view of serial learning that emphasizes the role played by information about the ordinal position of series items.

Animals↗

Non-spatial learning following posterior parietal or hippocampal lesions.

Posterior parietal, hippocampal, or sham-lesioned rats were tested for the acquisition of a non-monotonic serial learning task. The performance of control rats and those with a posterior parietal lesion was similar, while those with hippocampal damage demonstrated a working memory deficit. The results are integrated with contemporary conceptualizations of hippocampal and posterior parietal cortex involvement in learning and memory for non-spatial tasks.

Analysis of Variance↗

Effector dependent sequence learning in the serial RT task.

At least five earlier studies could not find effector-dependent learning in the keying version of the serial reaction time (RT) task. Experiment 1 examined whether effector-dependent learning occurs when participants practice the serial RT task with three fingers of one hand for about 1,300 sequence repetitions instead of the more common 50-100 repetitions. The results confirm that, following extended practice, sequence learning produces an effector-dependent component. Specifically, an unpracticed hand executed a practiced sequence slower than a practiced hand. However, Experiment 2 showed that effector-dependent sequence learning develops only when fingers of one hand are used, suggesting that effector-dependent sequence learning involves adjustment to the mechanical interactions between the fingers of one hand. In addition, when sequences had been practiced with one hand, mirror versions of the practiced sequences in both experiments showed moderate transfer. But when practiced with two hands no transfer to a mirrored version of the sequence was observed. This suggests that only practice with one hand produces a representation that facilitates the execution of mirror sequences. Generally, the same results were found in more or less aware participants, congruent with the idea that the effector-dependent representation and the representation allowing transfer to mirror sequences are implicit.

Adult↗

Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel monkeys before and after neurotoxic MDMA administration.

RATIONALE: Establishing functional deficits as a result of neurotoxic dosing regimens of MDMA has been difficult. However, moderate success has been achieved when sensitive animal models and drug challenge have been used together. OBJECTIVE: The present study used a repeated-acquisition technique and dose-effect determinations before, during and after neurotoxic MDMA exposure to characterize the effects of serotonergic drugs on learning, and to determine if MDMA-induced serotonin (5-HT) neurotoxicity is associated with learning deficits as measured by changes in response rate or the percentage of errors. METHOD: The effects of various serotonergic drugs were characterized in six squirrel monkeys responding under a repeated-acquisition procedure before and after neurotoxic dose regimens of MDMA. Specifically, cumulative dose-effect curves for m-CPP (0.032-1 mg/kg), fenfluramine (0.1-3.2 mg/kg) and triazolam (0.0032-0.1 mg/kg) were obtained prior to MDMA administration, with the latter drug serving as a non-5-HT control. RESULTS: In general, all of the drugs tested decreased overall response rate as the cumulative dose increased, whereas only triazolam markedly increased the percentage of errors. MDMA treatment produced significant (80-99%) decreases in brain 5-HT and 5-HIAA axonal markers, but did not lead to changes in either dependent measure of responding or shifts in the dose-effect curves obtained during pharmacological challenges with m-CPP, fenfluramine or triazolam. CONCLUSIONS: Taken together, these results demonstrate that serotonergic drugs can disrupt learning in monkeys, but indicate that MDMA-induced 5-HT neurotoxicity does not lead to disruptions in this particular type of serial learning task.

Animals↗

Relationship between memory strategies and motor symptoms in Parkinson's disease.

Patients with Parkinson's disease(PD) show a serious decrease in performance on tasks which lack explicit guidelines and which necessitate the subject to develop his or her own strategy. Using the California Verbal Learning Task(CVLT) we have found evidence that this phenomenon becomes also manifest in learning and memory. The goal of the present study on PD was to investigate whether or not there is an intrinsic relationship between PD-specific deviant learning characteristics and the severity of motor symptomatology. The results show, as expected, a significant correlation between the severity of bradykinetic/hypokinetic symptoms and the serial clustering gradient of the CVLT: the more bradykinetic PD patients (n = 48) were, the more they were dependent on the externally guided serial learning strategy. The findings are discussed in the context of our hypothesis that the actual deficit in patients with PD is a deficient processing of ambiguous internal cues.

Cluster Analysis↗

Striatal dopamine and learning strategy-an (123)I-FP-CIT SPECT study.

UNLABELLED: Patients with Parkinson's disease (PD) have difficulty in processing learning tasks that lack external guidelines and, consequently, necessitate the subjects to generate their own problem-solving strategy. While the contribution of striatal dopaminergic deficiency to PD-specific motor symptoms is well established, its role in the PD-characteristic deviant learning style remains unclear. The aim of this study was to assess the relation between striatal dopamine activity as revealed by single photon emission computed tomography (SPECT) with (123)I-FP-CIT, a ligand for the dopamine transporter (DaT), and type of learning strategy, as identified by the California Verbal Learning Task (CVLT) in 19 patients with probable PD. The results showed a robust inverse correlation between striatal dopamine DaT binding and the externally guided, serial learning strategy: the lower the DaT in caudate nucleus as well as in putamen, the more the patient group appeared to rely on externally structured learning. Additionally, a significant positive correlation was found between caudatal DaT activity and the internally generated, semantic learning strategy. Unlike these strategic learning characteristics, IQ equivalent and recall total score appeared to vary independently from striatal DaT availability. CONCLUSION: our findings provide direct evidence that striatal dopaminergic activity is specifically involved in the regulation of strategic learning processes.

Adult↗

Coding of hierarchical versus linear pattern structure in rats and humans.

In 3 experiments, rats and humans learned serial patterns composed of 24, 30, or 36 items. Patterns had a 2-, 3-, or 4-level hierarchical rule structure. In Experiments 1 and 2, patterns had either perfect hierarchical structure or 2 modified chunks that violated hierarchical structure, thus producing linear structure (i.e., nonhierarchical structure). For both rats and humans, pattern structure predicted pattern learning difficulty and also the nature and relative frequency of errors. Both treated chunks that were inconsistent with hierarchical structure as violation chunks, that is, they made errors that reflected their "tendency to regularize the perception of an irregular pattern" (F. Restle & B. L. Burnside, 1972). The results support the view that rats can abstract and encode a representation of multilevel hierarchical structure in serial patterns in much the same way as humans do in analogous tasks.

Animals↗

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↗

Tissue plasminogen activator administration does not result in clinically relevant neuropsychological dysfunction in patients with myocardial ischemia.

BACKGROUND: Recent evidence from animal models has demonstrated that tPA can be neurotoxic to the hippocampus and cerebellum. Since tPA is used in patients with myocardial infarction and has been approved for the treatment of acute ischemic stroke, we carried out a pilot study to investigate whether its administration could result in any clinically relevant neuropsychological dysfunction, with particular attention to those structures most involved in the animal model. PATIENT AND METHODS: Patients with acute myocardial infarction (AMI) who were subjected to thrombolysis with r-tPA and without evidence of prior or concomitant neurological-neuropsychological damage, were eligible. Controls consisted of patients with AMI not candidate for thrombolysis or patients with severe angina admitted to the intensive care unit. A detailed neurological and neuropsychological evaluation was performed, which included mood, visual and verbal memory, psychomotor speed processing and motor dexterity and visuomotor sequence learning. RESULTS: Ten patients and 13 controls were included. No significant differences between both groups were found, although all the subjects performed in the lower limits of the normal range on the Purdue pegboard test (motor dexterity) and digit-symbol test (psychomotor speed). There was no evidence of depression, as assessed by the Hamilton scale, that could have interfered with performance. Declarative memory (Rey auditory-verbal learning test) as well as visual memory (Rey-Osterrieth figure copy) and visuomotor sequence learning (serial reaction time task) were normal, without between-group differences. CONCLUSIONS: tPA administration at the usual doses did not result in detectable neuropsychological abnormalities in patients with myocardial ischemia.

Adult↗

The California Verbal Learning Test: psychometric characteristics and clinical application.

The California Verbal Learning Test (CVLT) is a popular clinical and research test that claims to measure key constructs in cognitive psychology such as repetition learning, serial position effects, semantic organization, intrusions, and proactive interference. The psychometric characteristics of the CVLT are reviewed and related to the test's clinical utility. The utility of the CVLT is shown to be limited by its poor standardization and inflated norms. Further, the validity is limited because the CVLT uses multiple trials whereas the constructs it purports to measure are based on single-trial paradigms. The review proposes modifications to the CVLT and guidelines for its clinical use. It concludes that if the limitations of the CVLT are recognized, it can still make a useful contribution to the clinical assessment of verbal learning and memory.

Adolescent↗

Effect of focal cerebellar lesions on procedural learning in the serial reaction time task.

Prior studies have shown that procedural learning is severely impaired in patients with diffuse cerebellar damage (cortical degeneration) as measured by the serial reaction time task (SRTT). We hypothesize that focal cerebellar lesions can also have lateralized effects on procedural learning. Our objective was to assess the effects of focal cerebellar lesions in procedural learning as measured by the SRTT. We studied 14 patients with single, unilateral vascular lesions in the territory of the posterior-inferior or superior cerebellar artery, who were compared with ten age- and sex-matched controls in a one-handed version of the SRTT. Patients with lesions at any other level of the brain or posterior fossa were excluded by cranial magnetic resonance imaging. Our results show that patients do not acquire procedural knowledge when performing the task with the hand ipsilateral to the lesion, but show normal learning with the contralateral hand. No correlation was found with the side, size, or vascular territory of the lesion. We conclude that procedural learning is impaired in hemispheric cerebellar lesions and involves only the hand ipsilateral to the lesion, which suggests a critical role for the cerebellum and/or crossed cerebellar-prefrontal connections in this type of learning.

Adult↗

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↗

Age-related norms for AVLT in a male patient population.

Sets forth norms for the AVLT memory test for male inpatients in a general hospital (N = 677), age range 19-81. Significant decreases were found for verbal recall, serial learning, and recognition. For younger men education and higher IQ favor maintenance of learning ability; a more complicated relationship is found for older men. Higher education level enhances recall, higher IQ enhances recognition, and, as in the younger group, learning and IQ are associated. Drop for learning is not uniform and temporarily increases significantly at age range 35-39. Discussion of the findings focuses on cognitive testing of the elderly.

Adult↗

The association between auditory memory span and speech rate in children from kindergarten to sixth grade.

This study reexamined the association between speech rate and memory span in children from kindergarten to sixth grade (N = 152) in order to potentially account for the inconsistencies within the published literature on this topic. Some of the inconsistencies in past research may reflect the different methods adopted in assessing speech rate. In particular, repeating word triples may itself involve memory demands, contaminating the correlation between speech rate and memory span in younger children. Analyses using composite speech rate and memory span measures showed that speech rate for word triples shared variance with memory span that was independent of speech rate for single words. Moreover, speech rate for word triples was largely redundant with age in explaining additional variation in memory span once the effects of speech rate for single words were controlled.

Child↗

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↗