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PubMed1994

The effects of lesions to the fornix and dorsomedial thalamus on concurrent discrimination learning by rats.

Rats with lesions in either the fornix or the thalamic nucleus medialis dorsalis were unimpaired on the acquisition of two object discrimination tasks. The same animals were then tested on a concurrent learning task in which various object discriminations were presented at different rates during the same session. This arrangement was primarily designed to minimise any response bias effects. Animals were able to acquire the various concurrent tasks, even when only one trial per day was given for a particular discrimination. It was found that fornix lesions had little or no effect and only produced a mild impairment when the rate of stimulus presentation resembled that used in typical concurrent tasks. Lesions of medialis dorsalis produced a more general, but again mild, deficit. In a final task, the animals were trained to discriminate between two stimuli composed of common elements arranged in different spatial combinations. Fornix lesions impaired acquisition of this spatial configural discrimination, while lesions of medialis dorsalis had a variable effect. The results indicate that fornix lesions can spare concurrent discrimination learning, and that any deficits may be related to interference effects associated with common elements in the stimuli. Lesions in medialis dorsalis appear to affect the initial learning of reward-based performance rules.

Animals↗
PubMed2001

Involvement of the dorsal anterior cingulate cortex in temporal behavioral sequencing: subregional analysis of the medial prefrontal cortex in rat.

We recently demonstrated that rats with dorsal anterior cingulate (ACd) cortical lesions were disrupted in the acquisition of a temporal Go/No-Go alternation task, suggesting either an involvement of this medial prefrontal subregion in sequencing temporally ordered behaviors or alternatively in more general response selection processes 'Gisquet-Verrier et al., Psychobiology 28 (2000) 248'. In the present study, the effects of ACd lesions were investigated in two different training situations. Both tasks involved response selection but only one of the two tasks required behavioral sequencing. In experiment 1, rats with ACd lesions were normally able to select Go and No-Go responses, when selection processes were based on a tone/light conditional rule that does not require temporal patterning. In experiment 2, ACd-lesioned rats were disrupted during the acquisition of a spatial alternation task that relies on temporal patterning. These results provide further evidence of ACd involvement in behavioral sequencing, regardless of the nature (spatial or non-spatial) of chained responses. A comparison of ACd lesions-induced effects with those obtained with lesions to the adjacent prelimbic-infralimbic area 'Delatour & Gisquet-Verrier, Behav. Neurosci. 110 (1996) 1282; Delatour & Gisquet-Verrier, Behav. Neurosci. 113 (1999) 941' reveals a double dissociation of these two regions that reflects a functional regionalization of the medial prefrontal cortex in the rat.

Animals↗
PubMed1989

Dissociation of item and order memory following parietal cortex lesions in the rat.

Rats with parietal cortex lesions were tested for both item and order memory for a list of spatial events in a probe recognition procedure. Rats with parietal cortex lesions were impaired for all events within the item memory task but had good memory for the early events within the order memory task. These data suggest a dissociation of function between item and order memory for parietal cortex damaged animals. In conjunction with previous findings with rats with medial prefrontal cortex lesions, these data suggest that item and order memory can be coded and represented independently.

Animals↗
PubMed1989

Further studies of hippocampal representation during odor discrimination learning.

The contribution of hippocampal and nonhippocampal memory processing to simultaneous-cue odor discrimination learning was assessed. In this task, rats with hippocampal system damage consequent to fornix lesions (fornix rats) were severely and persistently impaired in discrimination learning, acquisition of learning set, and concurrent discrimination, although they occasionally solved some problems at a normal rate. By using those problems on which fornix rats succeeded, to permit comparisons of performance strategies with normal rats, differences between groups were shown on response latency measures and on probe trials involving the novel pairing of familiar odors. Normal rats had a bimodal distribution of response latencies, and their latency depended on where the S+ was presented. Fornix rats had short response latencies and responded equally quickly wherever the S+ was presented. Furthermore, when the representation of familiar S+ and S- odor pairs was challenged in probe trials, normal rats responded appropriately to the correct stimulus, whereas fornix rats behaved as if presented with a new odor pair. These data provide support for the view that the hippocampus participates in the representation of relations among odor (and other) stimuli and among other experiences and that it permits the flexible use of these representations in new contexts. In contrast, memory processing outside the hippocampal system can represent only the significance of individual stimuli and can be revealed only in a repetition of the original learning event.

Animals↗
PubMed2000

A double dissociation between the rat hippocampus and medial caudoputamen in processing two forms of knowledge.

Rats with hippocampus, medial caudoputamen (CPU), lateral CPU, or control lesions were trained on declarative and procedural knowledge variants of a novel rodent sequential learning task. Medial CPU lesions impaired rats' ability to learn the procedure of running through a sequence of open maze arms but did not disrupt their capacity to explicitly generate (i.e.. "declare") maze arm sequences. Hippocampus lesions produced the opposite set of results. Rats with lateral CPU lesions were not impaired on either version of the task. Transfer tests indicated that control rats predominantly used egocentric cues to solve the procedural task and allocentric spatial cues to solve the declarative task. These findings suggest a double dissociation between the medial CPU and hippocampus in processing egocentric-procedural and allocentric-declarative sequential information, respectively.

Animals↗
PubMed1982

Some cognitive effects of frontal-lobe lesions in man.

The study of patients undergoing unilateral frontal-lobe excisions for the relief of focal epilepsy has revealed specific cognitive disorders that appear against a background of normal functioning on many intellectual, perceptual and memory tasks. Lesions that invade the frontal eye field cause subtle impairments of voluntary oculomotor control, which reveal themselves as an inability to suppress an initial glance at a potentially distracting stimulus. After frontal lobectomy in either hemisphere, deficits are found quite consistently on motor-differentiation tasks (Konorski 1972) in which the subject must learn to produce different responses to different, randomly presented, environmental signals. More directly related to the concept of planning are those sequential tasks in which the subject is free to choose his own order of responding, but must not make the same response twice. Here the left frontal lobe plays the major role, a finding consistent with the notion of left-hemisphere dominance for the programming of voluntary actions. In contrast, the right frontal lobe appears to be more critically involved in monitoring the temporal sequence of externally ordered events, although the verbal or non-verbal nature of the stimuli remains a relevant factor.

Adult↗
PubMedDate not supplied

Learning of sensory sequences in cerebellar patients.

A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for age, sex, handedness, musicality, and level of education were tested. Auditory and visual sensory sequences were presented out of different sensory pattern categories (tones with different acoustic frequencies and durations, visual stimuli with different spatial locations and colors, sequential vision of irregular shapes) and different ranges of inter-cue time intervals (fast and slow). Motor requirements were small, with vocal responses and no time restrictions. Perception of visual and acoustic stimuli was generally preserved in patients and controls. The number of errors was significantly higher in the faster tempo of sequence presentation in learning of sequences of tones of different frequencies and in learning of sequences of visual stimuli of different spatial locations and different colors. No difference in tempo between the groups was shown. The total number of errors between the two groups was identical in the sequence conditions. No major disturbances in acquisition or discrimination of various sensory sequences were observed in the group of cerebellar patients. Sequence learning may be impaired only in tasks with significant motor demands.

Acoustic Stimulation↗
PubMed1999

Reversing the phonological similarity effect.

The phonological similarity effect--poor retention of order for lists of similar-sounding items--is a benchmark finding in the short-term memory literature. In our first two experiments, we show that the effect actually reverses following relatively brief periods of distraction, yielding better order retention for similar than for dissimilar lists, provided that different items are used on every trial. In Experiment 3, the same items were used on every trial and similar lists produced poorer performance across all three retention intervals. The results are interpreted from a general discrimination framework: Items are viewed as occupying positions in a multidimensional space defined by list and within-list dimensions.

Adult↗
PubMed1982

Intravenous diazepam in humans: effects on acquisition and performance of response chains.

A technique based upon an individual-subject design was used to investigate the effects of intravenous diazepam on the acquisition and performance of response chains in humans. In each of two conditions subjects were required to emit a different sequence of ten responses in a predetermined order on three levers. The conditions alternated within each session under a multiple schedule. In the performance condition the sequence of responses was the same each session. The second condition was a repeated-acquisition task. In this condition subjects were required to learn a different sequence of responses each session. Diazepam produced dose-dependent decreases in the overall rate of responding in each subject under both conditions. In two of the three subjects tested, errors were increased in the learning condition at doses lower than those required to disrupt accuracy in the performance condition. In one subject, accuracy in both the learning and performance conditions was equisensitive to the disruptive effects of diazepam. These data are consistent with the effects of the benzodiazepines in analogous animal procedures. Furthermore, the data suggest that the behavioral effects of intravenous diazepam may exhibit marked variations across subjects at clinically relevant doses (5-10 mg).

Adult↗
PubMed1990

Memory for frequency in rats: role of the hippocampus and medial prefrontal cortex.

On a radial arm maze rats were tested for frequency memory of specific spatial locations, a task that presumably involves the coding of temporal information. On any trial during the study phase rats were allowed to visit three different spatial locations only once and one spatial location twice. During the test phase the rats were given a choice between a spatial location that had been visited once and spatial location that had been visited twice. The rats were reinforced for selecting the twice-visited spatial location. The number of spatial locations between a repetition (lag) was varied from one to three. After extensive training rats displayed memory for frequency only for a lag of three spatial locations, i.e., they displayed a repetition lag effect. Animals then received control, medial prefrontal cortex, or hippocampal lesions. Upon subsequent retests control rats continued to display frequency memory, but animals with medial prefrontal cortex or hippocampal lesions displayed a marked impairment. These data support the idea that both the hippocampus and medial prefrontal cortex code temporal order information.

Animals↗
PubMed2001

Endogenous plasma testosterone levels and commission errors in women: A preliminary report.

A correlation between elevated testosterone and aggressive behavior has been demonstrated in animals and to a lesser degree in humans, primarily in the context of dominance. Some aggression, namely non-premeditated aggression, is characterized by impaired impulse control. Real-world aggressive histories and self-reported impulsivity have correlated with commission errors (failures to withhold responses to nontarget stimuli) in versions of the continuous performance test (CPT). To begin exploring whether testosterone may play a role in aggression due more to a direct relationship with impaired impulse control, we related plasma total testosterone concentrations of 27 psychiatrically healthy women to commission errors in two variants of the CPT - with and without interstimulus distracters. Controlling for age and IQ, testosterone did not relate to rates of correct detections in either task, but correlated positively with commission errors in the distracter CPT variant. In light of the fact previous studies find commission errors on the CPT are associated with impulsivity, the results of this study support a positive relationship between testosterone and impulsivity.

Aggression↗
PubMedDate not supplied

Effects of cholinesterase inhibitors on a two-component chained schedule performance in rats.

The acetylcholinesterase (AChE) inhibitors physostigmine (PHY), tacrine (THA), and heptylphysostigmine (HEP) have been evaluated as potential therapeutics for treatment of Alzheimer's disease (AD) and as prophylactics against organophosphate (OP) poisoning. The above medical applications are based upon the neurochemical principles of elevation of transient levels of acetylcholine (ACh) in brain and reversible inhibition of AChE in blood and brain, respectively. The present study was undertaken to evaluate the effects of these drugs on performance of a two-component chained schedule of differential-reinforcement-of-high-rate (DRH) reward/differential-reinforcement-of-low-rate (DRL) nonreward contingencies, for water reinforcement in 2-h experimental sessions in rats. Both PHY (0.031-0.25 mg/kg, SC) and HEP (0.625-10.0 mg/kg, SC) decreased overall reinforcement rate and nonreinforced response in a dose-related and parallel manner, whereas THA (0.625-5.0 mg/kg) decreased the overall reinforcement rate in a dose-related manner, but did not significantly affect nonreinforced response. The least significant doses of PHY (0.625 mg/kg), THA (1.25 mg/kg), and HEP (1. 25 mg/kg) on the behavioral performance were associated with oral movements and/or muscle fasciculation. Moderate to high doses of these drugs (i.e., PHY >/= 0.624, THA >/= 1.25, and HEP >/= 1.25 mg/kg) produced behavioral suppression, which resulted mostly from the cessation of responding in the presence of cholinergic adverse events. The ED(50) values of the behavioral disruption (as documented by overall reinforcer loss) for PHY, THA, and HEP were 0. 081, 3.87, and 2.89 mg/kg, respectively, and the behavioral-deficit-free (BDF) doses were 0.031, 0.625, and 0.625 mg/kg, respectively. Preclinical data revealed that the BDF doses of both PHY and HEP have moderate inhibition of AChE, which leads to an efficacious elevation of ACh level in the brain, whereas the BDF dose of THA shows no significant AChE inhibition or elevation of brain ACh level; however, they all have cognition enhancing effects at their respective safety doses. The above data suggest that the BDF doses of PHY and HEP may have prophylactic efficacy against OP poisoning, whereas THA may not. The BDF doses of these three drugs are comparable to the maximum tolerated doses in clinical practice, suggesting that the present rat model may have potential value in predicting the clinical safety of AChE inhibitors developed for therapy of AD and prophylaxis against OP poisoning as well.

Animals↗