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PubMed1983

Effects of heroin, methadone, LAAM and cyclazocine on acquisition and performance of response sequences in monkeys.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levels. Sequence completions produced food on a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). At high doses, each drug tested produced essentially the same effect. In all three components, response rate was substantially decreased and percent errors increased. At lower doses, however, their effects differed. Heroin and methadone produced dose-dependent sporadic periods of pausing, but had little or no effect on the accuracy of responding. LAAM also produced sporadic periods of pausing, but its effects on accuracy were variable. In contrast, cyclazocine produced no such pauses in responding but rather decreased the local rates of correct responding in a dose-related manner. These same doses of cyclazocine increased percent errors in the learning component, but not in the faded learning or performance components. The results are generally consistent with the view that putative mu opioid agonists do not affect the accuracy of a discrimination in monkeys except at those doses which produce a substantial decrease in the overall rate of responding.

Animals↗

PubMed2006

No effects of enhanced central norepinephrine on finger-sequence learning and attention.

RATIONALE: When paired with training, substances that increase monoaminergic transmission in the brain support motor and language learning in healthy subjects and in rehabilitation after brain lesions. OBJECTIVES: To test the hypotheses that enhancement of central norepinephrine by the selective norepinephrine reuptake inhibitor reboxetine (1) improves skilled motor performance, (2) promotes skilled motor learning, and (3) does not exert these effects by modulation of attention. METHODS: In a double blind, placebo-controlled, crossover study in healthy, adult subjects (n=16), finger-sequence performance and learning was measured after the stimulation of the central noradrenergic system with a single dose (8 mg) of reboxetine and placebo. Effects on attention were assessed by the standardized continuous performance test "CPT-M". RESULTS: No differential effects of reboxetine or placebo on finger-sequence performance, learning and parameters of attention were found. CONCLUSION: Selective stimulation of the central noradrenergic system did not promote skilled motor learning or performance as assessed by finger-sequences. The plasticity-enhancing effect of reboxetine, documented in other studies, appears to be dependent on specific neurophysiological and neuropsychological characteristics of the task, and cannot be generalized to other behavioral paradigms.

Adrenergic Uptake Inhibitors↗

PubMed1996

Memory abilities in children with Williams syndrome.

Williams syndrome (WS) is a rare genetic condition characterised by intellectual disability, typical facial dysmorphology and several medical anomalies. A specific neuropsychological profile with a dissociation between language (relatively preserved) and visuo-spatial abilities (more seriously impaired) has been hypothesised in these children. Memory abilities of these patients have not been adequately investigated, although they may substantially contribute to better understanding their neuropsychological profile. The present study aimed at investigating verbal and spatial memory in patients with WS (N = 16). Their performance was compared with that of normally developing children on tasks of verbal and spatial span and immediate and delayed recall of verbal and visuo-perceptual materials. Memory abilities of WS children appear to be characterised by defective visuo-spatial memory, both in the short-term and long-term domain, and a dissociation between normal short- but deficient long-term verbal learning. Results are interpreted by supporting the thesis that intellectual disability reflects the defective functioning of a complex system in which some cognitive competencies may be disrupted more than others (Detterman, 1987; Vicari, Albertini and Caltagirone, 1992).

Child↗

PubMed2004

Are multi-layer backpropagation networks catastrophically amnesic?

Connectionist models with a backpropagation learning rule are known to have a serious problem. Such models exhibit catastrophic interference (or forgetting) with sequential training. Having learned a set of patterns, if the model is trained on another set of patterns, its performance on the first set can dramatically deteriorate very rapidly. The present study reconsiders this issue with four simulations. The model learned arithmetic facts sequentially, but the interference was only modest with random (hence approximately orthogonal) inputs. Essentially the same result was obtained when the inputs are made less orthogonal by adding irrelevant elements. Reducing the number of hidden units did not have major effects. This study suggests that the interference problem has been somewhat overstated.

Algorithms↗

PubMed2001

Anticipating incoming events: an impaired cognitive process in schizophrenia.

Intentions are central to guiding actions to their completion because they generate expectations which precede the realization of a task. This ability to manage time was investigated by using a cognitive task which involves several highly integrated processes: sequential learning, explicit processing, and working memory. In this task, participants are required to explicitly learn a repeating color sequence before receiving an instruction to give an anticipatory motor response concerning the next element. Two types of sequences (temporal and spatial) and three experimental conditions were tested in both a group of normal participants and a group of schizophrenic patients. Schizophrenics were included because their condition is known to alter conscious executive function. Our results showed that schizophrenic patients have a strong deficit in performing anticipation tasks. Although they learned the sequences almost normally, their anticipatory ability was reduced in comparison to normal participants in all the tested conditions. These results expand the notion of a working memory deficit in schizophrenia and bear strong implications for understanding executive disorders observed in such patients.

Adult↗

PubMed1988

Teaching an amnesic a complex cognitive skill.

G.P., a Korsakoff's amnesic, was able to learn an algorithm for squaring two-digit numbers mentally over a 7-day period at a rate comparable to that of age-matched controls. He failed to show normal positive transfer to specific problems or to specific numbers used in components of the task. He also exhibited slight improvement in simple naming speed, forward digit span, simple multiplication speed, but no apparent improvement for the recall of repeated supraspan digit strings. He was unable to state the algorithm he had learned to square two-digit numbers, though he could implement it successfully. The results suggest that the compilation of a skill may involve two dissociable components: composition and proceduralization, with the former, but not the latter, occurring at normal rates for Korsakoff's amnesics.

Aged↗

PubMed2004

Serial order of conditional stimuli as a discriminative cue for Pavlovian conditioning.

The serial order in which events occur can be a signal for different outcomes and therefore might be a determinant of how an animal should respond. In this report, we propose a novel design for studying serial order learning in Pavlovian conditioning. In both Experiments 1a and 1b, hungry rats were trained with successively presented pairs of auditory and visual stimuli (e.g., A --> B) using four different stimuli (A-D). Four orders were paired with food (A --> B, B --> C, C --> D, D --> A) while the reversals were extinguished (B --> A, C --> B, D --> C, A --> D). An analysis of responding from the second element of each pair showed that the rats discriminated trial types that preceded food from those that did not. A replication of the effect using a completely counterbalanced design is described in Experiment 1b. These results suggest that rats can use the serial or temporal order of two sequentially presented non-overlapping elements as the basis for discrimination. Two associative accounts are suggested as possible mechanisms for solving the discrimination.

Animals↗

PubMed1996

Self-instructional intervention for teaching generalized problem-solving within a functional task sequence.

Effects of an intervention that combined self-instruction with multiple exemplar training on the generalized problem solving of five high school students with severe mental retardation were examined. Innovative features of the intervention included (a) preteaching self-instruction to proficiency with one exemplar before introducing multiple exemplars and (b) embedding problem situations within a functional task sequence. Findings indicated that all students learned to perform five trained problem responses and five generalized responses while self-instructing. The self-instructional intervention appeared to decrease training time required to self-instruct as well as to decrease variability with which participants verbalized their self-instructions.

Adolescent↗

PubMed1992

Cognitive flexibility and mental programming after closed head injuries and anterior or posterior cerebral excisions.

Cognitive inflexibility and deficient mental programming are specifically related to frontal lobe lesions. The aim was to demonstrate that closed head injury (CHI) patients with brain lesions verified by computed tomography have such cognitive deficits, and are inferior in these respects to patients with posterior cerebral excisions mainly for tumours. This hypothesis was confirmed using a Category Identification and Sorting test as well as a measure of mental programming in a Spatial Learning task. Furthermore, CHI patients who had non-frontal parenchymal lesions were inferior by these measures to patients with posterior excisions. This result suggests that diffuse axonal lesion in CHI causes the deficits similar to those following frontal lobe excision.

Adolescent↗

PubMed1999

Learning versus performance impairments following regional administration of MK-801 into nucleus accumbens and dorsomedial striatum.

To further ascertain the relative contributions of nucleus accumbens (NAC) and dorsomedial striatum (DS) to cognitive behaviors, the comparative effects in rats of MK-801 microinjections into these regions on a multiple schedule of repeated learning (RL) and performance (P) were examined. The RL component required learning of a new three-member response sequence during each experimental session, while the P component required rote performance of a pre-learned response, thus permitting a more precise delineation of treatment-related cognitive vs. non-cognitive changes. MK-801 decreased overall accuracy in both the RL and P components of the schedule in both brain regions, indicating that in neither NAC nor DS are NMDA receptors exclusively involved in mediating acquisition processes. Decreases in overall accuracy were primarily due to increased perseverative errors which may have been the result of excessively accelerated responding, a type of motoric alteration. MK-801 administered into NAC also resulted in an additional increase in skipping errors at the 2.5 micrograms dose, a finding which could be consistent with disrupted learning resulting from an inability to encode spatial relationships. Collectively these findings suggest that NAC and DS mediate some behavioral functions in common, but that additional cognitive-related spatial processes are mediated by NAC.

Animals↗

PubMed2005

Impaired procedural learning in obsessive-compulsive disorder and Parkinson's disease, but not in major depressive disorder.

The striatum has been consistently implicated in the pathophysiology of obsessive-compulsive disorder (OCD), yet, studies assessing the performance of OCD patients in procedural learning tasks, assumed to rely on the intact functioning of the striatum, have yielded inconsistent results. Recently, Rauch et al. [Rauch SL, Savage CR, Alpert NM, Dougherty D, Kendrick A, Curran T, et al. Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning. J Neuropsychiatry Clin Neurosci 1997;9:568-73] have obtained evidence suggesting that seemingly intact performance of OCD patients in such tasks may be achieved by recruiting systems which in normal subjects are reserved for explicit or declarative, rather than implicit or procedural, processing. The present study assessed procedural learning in OCD patients using a card betting task in which explicit processing impairs, rather than assists, acquisition. In addition, we tested a group of Parkinson's disease (PD) patients, in order to better establish the dependence of the task on procedural learning, and a group of major depressive disorder (MDD) patients, in order to test the possibility that impaired learning in the card betting task may be a result of concurrent depression. The majority of OCD (15/18) and PD patients (14/16) did not acquire the task, whereas MDD patients acquired the task similarly to normal control subjects. These results demonstrate that OCD patients are impaired on a procedural learning task in which explicit processing impairs acquisition. Two different interpretations are suggested: that the striatal system is dysfunctional in OCD, or that inappropriate explicit processing in OCD interferes with the functioning of the striatal system.

Adult↗

PubMed2001

Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine.

The abuse of psychostimulants, such as methamphetamine (METH), can cause long-lasting deficits in the dopamine (DA) innervation of the striatum. Although the consequences of large DA depletions on basal ganglia function have been well characterized, less is known about the alterations associated with smaller depletions, such as those produced by high doses of METH. The purpose of this study was to assess the long-term consequences of METH-induced DA depletion on basal ganglia function. Three weeks after rats were given multiple administrations of METH (5-10 mg/kg, four times at 2-h intervals), dose-related decreases in DA tissue content in striatum and tyrosine hydroxylase mRNA in the substantia nigra pars compacta were observed. In situ hybridization histochemistry revealed a selective decrease in preprotachykinin mRNA in striatum, predominantly at the highest dose of METH, and no change in striatal preprodynorphin, preproenkephalin, or neurotensin/neuromedin N mRNAs. Cytochrome oxidase activity was significantly elevated in the entopeduncular nucleus and substantia nigra pars reticulata of METH-treated rats, but not in the striatum, globus pallidus, or subthalamic nucleus, consistent with a selective decrease in striatonigral, but not striatopallidal, neuron function. Additionally, rats treated with a neurotoxic regimen of METH were impaired on a radial maze sequential learning task when tested 3 weeks following METH administration. These data indicate that exposure to a neurotoxic regimen of METH results in long-term changes in striatonigral, but not striatopallidal neuron function and, consequently, altered basal ganglia function.

Animals↗

PubMed1996

Acquisition of prototype-based information about social groups in adulthood.

Two experiments examined adult age differences in the ability to acquire prototype-based information about a fictitious social group. Young and older adults were presented with 60 descriptions of people who varied in their similarity to a prototypical group member along 12 (Experiment 1) or 10 (Experiment 2) feature dimensions. The prototype represented either an arbitrary combination of features or a coherent set of features based on evaluative content. Younger adults generally performed better than the older adults in learning the arbitrary prototype, whereas age differences were absent or in favor of the older adults when the prototype consisted of evaluatively consistent features. The authors argue that the results can be explained by the age-related variations in the reliance on automatic processing mechanisms and the congruence of these processes with the demands of the task across prototype conditions.

Adolescent↗

PubMed1996

Anticipatory saccades in sequential procedural learning in monkeys.

1. In a preceding paper we examined the short-term and long-term processes of learning of sequential procedures in monkeys. We now report that the pattern of eye movements changed along with the long-term learning. 2. The monkey's task was to press five consecutive pairs of target buttons (indicated by illumination) in the correct order for every pair, which the monkey had to find by trial and error (2 x 5 task). The whole sequence was called the "hyperset"; each pair was called the "set." 3. Initially, the saccade toward the correct target occurred after illumination of the targets (visually guided saccade). After sufficient learning, the saccade tended to occur before the target illumination (anticipatory saccade). This was true only for the hyperset that had been learned. 4. The likelihood of anticipatory saccade increased gradually over 20-30 days of practice of the particular hyperset. The time course was similar to how the hand learned (button press latency). 5. The monkeys were required to use the same hand for each hyperset throughout learning, except when we asked them to use the opposite hand. The nearly perfect performance due to the extensive practice was then deteriorated by the use of the opposite hand. We found, in addition, that anticipatory saccades became much less frequent. This finding suggests that critical for the skilled performance was the combination of the eyes and the side of the hand that was used for the practice of a given sequence.

Animals↗

PubMed2003

Enhancement of brain activation during trial-and-error sequence learning in early PD.

BACKGROUND: Although the pathophysiology remains unknown, most nondemented patients with PD have difficulty with frontal tasks, including trial-and-error sequence learning. If given time, they can perform cognitive tasks of moderate difficulty as well as controls. However, it is not known how brain function is altered during this time period to preserve higher cortical function in the face of PD pathology. METHOD: To evaluate this phenomenon, the authors matched sequence learning between PD and control subjects for the last 30 seconds of a PET scan. Learning during the initial 50 seconds of PET was unconstrained. RESULTS: Learning indices were equivalent between groups during the last 30 seconds of the scan, whereas rates of acquisition, correct movements, and forgetting differed in the first 30 seconds. In normal controls sequence learning was associated with activations in the right prefrontal, premotor, parietal, rostral supplementary motor area, and precuneus regions. To achieve equal performance, the PD group activated greater volume within these same regions, and also their left sided cortical homologs and the lateral cerebellum bilaterally. CONCLUSIONS: Mildly affected patients with PD demonstrated only modest impairment of learning during the first 30 seconds of the task and performed equivalently with controls thereafter. However, the mechanism by which they achieved equiperformance involved considerable changes in brain function. The PD group had to activate four times as much neural tissue as the controls, including recruiting brain from homologous cortical regions and bilateral lateral cerebellum.

Aged↗

PubMed1995

Memory functioning in social drinkers: a study of event-related potentials.

Verbal memory functioning was assessed in light and heavy social drinkers by recording event-related potentials in subjects instructed to memorize lists of words using either repetition or elaborative learning strategies. Although overall performance did not differ significantly between light and heavy drinkers, heavy drinkers showed reduced within-list organization compared with light drinkers. There were statistically significant differences in the event-related potential indices of memory functioning elicited during complex elaborative processing which were consistent with decreased within-list organization in heavy drinkers.

Adult↗

PubMed2004

To act or not to act. Neural correlates of executive control of learned motor behavior.

Successful behavior requires contextual modulation of learned "programs", that is, the retrieval or nonretrieval (inhibition) of behavioral elements depending on situative context. Here we report neural correlates of these elementary aspects of behavior as identified with functional magnetic resonance imaging (fMRI). Inhibition of a "ready-to-go" behavioral program was represented in the brain by reduction of net synaptic activity in the cerebro-cerebellar pathway. The metabolic correlate of inhibition was a multifocal (premotor, primary sensorimotor, superior parietal, cingulate cortex, and cerebellum) decrease of the blood oxygenation level-dependent (BOLD) signal to below the resting state (negative BOLD) with a concomitant decrease of motor cortical excitability. The reverse was true for retrieval. We propose that contextual modulation of learned behavioral programs depends on an interplay of focal increases and decreases of neural activity and that the inhibitory changes are reflected by negative BOLD responses in an extended cerebro-cerebellar network of sensorimotor structures.

Adult↗

PubMed1994

Different effects of amphetamine on reinforced variations versus repetitions in spontaneously hypertensive rats (SHR).

The spontaneously hypertensive rat (SHR) may serve as an animal model of human attention deficit hyperactivity disorder (ADHD). We compared performances of SHRs and Wistar-Kyoto normotensive controls rats (WKY) in two experiments. When rewarded for varying sequences of responses across two manipulanda, the SHRs were more likely to vary than the WKYs. On the other hand, when rewarded for repetitions of a small number of sequences, the WKYs were more likely to learn to repeat. Both of these results confirm previous findings. Injecting 0.75 mg/kg d-amphetamine facilitated learning by SHRs to repeat the required sequences, with amphetamine-injected SHRs learning as rapidly as saline-injected, control WKYs. On the other hand, amphetamine tended to increase variability in both strains when high levels of variations were required for reward, and to decrease it in both strains when low levels of variability were required. Thus, amphetamine may have different effects on reinforced repetitions vs. reinforced variations.

Animals↗