Uncertainty analysis for wheelchair propulsion dynamics

Nefiracetam is undergoing preclinical and clinical tests as a cognition-enhancing drug in Alzheimer's disease (AD). Nicotinic cholinergic receptors are lost in AD, and nicotinic as well as muscarinic cholinergic receptors are involved in the modulation of eyeblink conditioning. Experiments were carried out using young rabbits to examine the effect of nefiracetam on cholinergic antagonists to nicotinic (mecamylamine) and muscarinic (scopolamine) receptors. Rabbits were tested for 15 days in the 750 ms delay eyeblink classical conditioning paradigm in paired and explicitly unpaired conditions. Nefiracetam at a dose of 15 mg/kg significantly ameliorated the effects of 0.5 mg/kg mecamylamine, and nefiracetam at a dose of 10 mg/kg significantly ameliorated the effect of 1.5 mg/kg scopolamine. The vehicle alone and nefiracetam alone groups performed similarly to the groups treated with mecamylamine or scopolamine and nefiracetam. Reversal by nefiracetam of a nicotinic as well as a muscarinic cholinergic antagonist indicates that the drug may affect deficits specific to AD.     

Delay classical conditioning in young and older rabbits: Initial acquisition and retention at 12 and 18 months.

Classical conditioning of the nictitating membrane-eyeblink response in young (age 7 mo) and older (age 36 mo) New Zealand white rabbits in a delay paradigm with 400-msec CS–unconditioned stimulus/stimuli (UCS) interval was examined for initial acquisition and retention. Older animals required significantly more acquisition trials to reach learning criterion. Age differences in acquisition were temporary. Older rabbits responded at a level comparable to that of young rabbits such that total performance over the 630 trials of acquisition was not different. Rabbits in the explicitly unpaired control groups exhibited no age differences in unconditioned response (UCR) amplitude or latency measures. 12- and 18-mo retests demonstrated no significant age effects on retention. Patterns of retention differed between age groups. Older rabbits required fewer trials to obtain the learning criterion at each phase of testing. Younger rabbits maintained a stable performance throughout training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related deficits in retention of the classically conditioned nictitating membrane response in rabbits.

Young and aged rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS) for 18 consecutive days. Rabbits were then returned to their home cages for a 90-day period in which they received no further conditioning, but they were handled daily. On Day 91 they underwent retention testing during which the CS alone was presented 20 times. This was immediately followed by reacquisition in which the CS and UCS were again paired for 100 trials. Reacquisition was repeated on the following day. As in previous studies, aged rabbits acquired the conditioned response (CR) more slowly than young rabbits; however, by the end of acquisition, both groups reached similar asymptotic levels. Retention of the CR was significantly lower for aged than young rabbits. Reacquisition was also retarded in aged vs young rabbits. Nonassociative factors, such as sensitivity to the stimuli or general health, could not account for these differences. Data are discussed in terms of using retention of the conditioned eyeblink response as a model system for studying age-related memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebellar stimulation as an unconditioned stimulus in classical conditioning.

Implanted rabbits with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone CS, produced learning comparable to that seen with peripheral unconditioned stimulus/stimuli (UCS). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS–UCS trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS–UCS preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal dynamics of the rabbit's nictitating membrane response in serial compound conditioned stimuli.

Two experiments, with 88 female albino rabbits, investigated conditioning of the nictitating membrane response to a reinforced serial compound stimulus. The serial compound was composed of a 400-msec CS (CSA), a trace interval of at least 2 sec, and a brief 2nd CS (CSB) prior to the UCS. The CSB duration was either 150, 250, or 400 msec in Exp I, and the CSB duration in Exp II was 400 msec. Exp I compared serial compound training to an "uncoupled" condition, which contained intermixed CSA–UCS trials and CSB–UCS trials. Exp II compared serial compound training with uncoupled training, 2nd-order conditioning (CSA–CSB/CSB–UCS), trace conditioning (CSA–UCS), and generalization testing that entailed CSB–UCS training and unreinforced tests with CSA. The serial compound, uncoupled, and 2nd-order conditioning procedures all produced high levels of responding during CSA, but only the reinforced serial compound procedure yielded an appreciable likelihood of CR initiation during the trace interval between CSA and CSB. The CRs during the trace interval were temporally distinct from the CRs during CSA and did not appear to be belated CRs to CSA itself. Results are discussed in connection with stimulus selection phenomena, for example, overshadowing and potentiation of toxicosis conditioning. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulation at a site of auditory-somatosensory convergence in the medial geniculate nucleus is an effective unconditioned stimulus for fear conditioning.

The medial division of the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN) are necessary for conditioning to an auditory conditioned stimulus/stimuli (CS), receive both auditory and somatosensory input, and project to the amygdala, which is involved in production of fear conditioned responses (CRs). If CS–unconditioned stimulus (UCS) convergence in the MGm-PIN is critical for fear conditioning, then microstimulation of this area should serve as an effective UCS during classical conditioning, in place of standard footshock. Guinea pigs underwent conditioning (40–60 trials) using a tone as the CS and medial geniculate complex microstimulation as the UCS. Conditioning bradycardia developed when the UCS electrodes were in the PIN. However, microstimulation was not an effective UCS for conditioning in other parts of the medial geniculate or for sensitization training in the PIN or elsewhere. Learning curves were similar to those found previously for footshock UCS. Thus, the PIN can be a locus of functional CS–UCS convergence for fear conditioning to acoustic stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Topography of sexually conditioned behavior in male Japanese quail (Coturnix japonica) depends on the CS–US interval.

The interval between exposure to a CS to male quail and access to a female (the unconditioned stimulus [UCS]) was varied from 0.5 to 20 min using a Pavlovian delayed conditioning procedure. Increasing the CS–UCS interval altered the spatial distribution of sexual conditioned behavior. With a short CS–UCS interval (1 min), conditioning resulted in the Ss remaining close to the CS and increasing their locomotor behavior near the CS. With a long CS–UCS interval (20 min), the Ss approached the CS to some degree, but their locomotor behavior was increased in areas farther removed from the CS. Results are interpreted within the context of a behavior systems approach to the study of learning and indicate that the typical finding of an inverse relation between conditioned responding and the CS–UCS interval may be an artifact of the use of a limited range or behavioral measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluative conditioning in the picture–picture paradigm with random assignment of conditioned stimuli to unconditioned stimuli.

Human participants were allocated to 1 of 3 groups. In the conditioning group, each conditioned stimulus (CS)–unconditioned stimulus (UCS) pair was presented 7 times during the acquisition phase. Participants who were assigned to the extinction group saw 5 additional presentations of each CS in isolation after the 7 presentations of each CS–UCS pair. In the latent inhibition group, the CS-only trials were presented before the CS–UCS trials. Overall, a significant evaluative conditioning effect was observed. This effect cannot be dismissed on the basis of the arguments developed by A. P. Field and G. C. L. Davey (see records 1997-42912-009, 1998-11983-008, and 1999-10526-006), and the results thus provide strong evidence for the associative nature of evaluative conditioning. The results are also in line with other findings, which showed that evaluative conditioning is resistant to extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Training to criterion in eyeblink classical conditioning in Alzheimer's disease, Down's syndrome with Alzheimer's disease, and healthy elderly.

The cholinergic antagonist scopolamine delays acquisition of eyeblink classical conditioning (EBCC) in rabbits and humans, but scopolamine-treated organisms eventually acquire conditioned responses (CRs). Patients with probable Alzheimer's disease (AD) and older adults with Down's syndrome (DS/AD) have disrupted cholinergic systems and perform EBCC very poorly. It was hypothesized that patients with probable AD and DS/AD, like scopolamine-injected organisms, would acquire CRs if given sufficient training. Twelve probable AD patients, 12 DS/AD patients, and 6 healthy elderly control individuals participated in 5 daily 90-trial sessions of EBCC. Fifty-eight percent of the probable AD, 92% of the DS-AD, and 100% of the control participants achieved learning criterion. Probable AD, DS/AD, and control participants had statistically significant increases in the percentage of CRs produced over 5 EBCC sessions. The neural substrate for EBCC was not eliminated in probable AD or DS/AD patients, although the learning mechanism was disrupted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned opioid activity in the rat fetus.

Classical conditioning in the rat fetus (Embryonic Day 20) was investigated in 4 experiments. Reexposure to a CS (sucrose), after 3 pairings with an unconditioned stimulus (UCS; milk), reduced fetal facial wiping in a bioassay of perioral cutaneous responsiveness. Reduced responsiveness was evident only in Ss that received paired presentations of the CS and UCS and cannot be attributed to habituation, sensitization to the CS, or protracted effects of UCS exposure during conditioning trials. Fetuses attended to the chemosensory, not the tactile, qualities of the sucrose infusion during CS reexposure. Changes in fetal responsiveness resulted from conditioned activity in the endogenous opioid system, specifically at mu opioid receptors. These data confirm that the rat fetus is capable of exhibiting a conditioned opioid response in utero. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation or diminution of discrete motor unconditioned responses (rabbit eyeblink) to an aversive Pavlovian unconditioned stimulus by two associative processes: Conditioned fear and a conditioned diminution of unconditioned stimulus processing.

In 2 experiments using the rabbit conditioned eyeblink preparation, the conditions under which a Pavlovian conditioned stimulus/stimuli (CS) potentiates or diminishes the unconditioned response (UCR) were examined. Results indicate that, after discrimination training (CS+ vs CS–), the CS+ diminished UCR amplitude at the training interstimulus interval (ISI). When CS+ trials were segregated into trials on which a conditioned response (CR) did or did not occur, the CS+ diminished the UCR when it elicited a CR, but not when a CR failed to occur. When the CS-unconditioned stimulus (UCS) interval was lengthened to 10 sec, the CS+ reliably potentiated the eyeblink UCR on CR trials but did not potentiate responding on trials on which a CR was absent. Results are discussed in terms of the modulatory effects and temporal properties of conditioned fear and an associatively produced decrement in UCS processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Studies in early infant learning: Classical conditioning of the neonatal heart rate.

Three experiments demonstrated that human newborn heart rate level can be reliably modified through classical conditioning procedures. The theory of sensitization served as a frame of reference for Exps I and II, and drive reduction served for Exp III. In Exp I the delay, delay-trace, and control groups, with 10 2-day-old newborns in each, received 5 preconditioning trials of the CS alone, 16 conditioning trials with CS–UCS pairings differing for each group, and 5 extinction trials. Exp II was a replication of the 1st study and involved only the delay and delay-trace groups with 10 infants each. In both studies the delay group curves showed significant monophasic acceleratory responses during extinction. Results support the sensitization hypothesis (i.e., the CR occurring in the interstimulus interval was fashioned out of the response to the CS). In Exp III, the measure of conditioning was the response to the probe technique. 10 experimental Ss received preconditioning trials of nitrogen puff (UCS?) administered to the abdomen, followed by 10 CS–UCS? (500-Hz tone acetic acid) pairings with an interstimulus interval of 3 sec. 10 controls received the same design with a CS–UCS? interval of 40 sec. Analyses of the probe stimulus trials showed significant changes for the control group and none for the experimental group. The CS–UCS? pairings in the experimental group are interpreted as producing increased drive and adaptive damping of the heart rate response. Findings show that early learning may occur under a variety of conditions and that the results can be incorporated by different theories. (79 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response.

In 2 experiments, 36 New Zealand albino rabbits received classical conditioning of the nictitating membrane response in a trace conditioning paradigm. In this paradigm, a 250-msec tone conditioned stimulus (CS) occurred, after which there was a 500-msec period of time in which no stimuli occurred (the trace interval), followed by a 100-msec air-puff unconditioned stimulus (UCS). In Exp I, lesions of the hippocampus or cingulate/retrosplenial cortex (CRC) disrupted acquisition of the long-latency or adaptive conditioned response (CR) relative to unoperated controls and Ss that received neocortical lesions that spared the CRC. When Ss with hippocampal or CRC lesions were switched to a standard delay paradigm in which the CS and UCS were contiguous in time, they acquired in about the same number of trials as naive Ss. In Exp II, multiple-unit activity in area CA1 of the hippocampus was examined during acquisition of the trace CR. Ss had a 500-msec trace interval (Group T-500), received explicitly unpaired presentations of the CS and UCS, or underwent conditioning with a 2-sec trace interval. Group T-500 acquired the CR in about 500 trials. Early in training, there was a substantial increase in neuronal activity in the hippocampus that began during the CS and persisted through the trace interval. Later in conditioning as CRs emerged, the activity shifted to later in the trace interval and formed a model of the amplitude–time course of the behavioral CR. (65 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of conditioned associations in Hermissenda: Additive effects of contiguity and the forward interstimulus interval.

Examined conditioned suppression of photokinesis (CSPK) by the marine mollusc in 3 experiments. In each experiment, groups of Ss received light (conditioned stimulus, CS) paired with high-speed orbital rotation (unconditioned stimulus, UCS), light and rotation explicitly unpaired, or no exposure to these stimuli. 24 hrs after training, all Ss were tested for CSPK in the presence of the light. 50 CS–UCS pairings resulted in a marginal CSPK, whereas 100 and 150 pairings produced strong CSPK. In Exp 2, delay between CS onset and UCS onset was varied between 1 and 10 s. The 10-s interstimulus interval (ISI) did not support conditioning, whereas 1-s and 2-s ISIs were effective. In Exp 3, CS–UCS pairings in which the CS preceded the onset of the UCS and ended with the offset of the UCS evoked stronger CSPK than either a CS that preceded the UCS and ended with its onset or a CS that was paired in simultaneous compound with the UCS. CS–UCS contiguity and the forward ISI act additively to establish the CS–UCS association. No differences were observed between groups that were untreated and that received the CS and UCS unpaired. Similarities are noted in the temporal characteristics of associative learning in these Ss and vertebrate species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of amygdala lesions on reflex facilitation and conditioned response acquisition during nictitating membrane response conditioning in rabbit.

Demonstrated that large lesions of the amygdala disrupt the maintenance of reflex facilitation of the unconditioned nictitating membrane (NM) response and slow the acquisition of conditioned NM responses in rabbits. Before behavioral training, the central nucleus of the amygdala and adjacent areas were lesioned electrolytically. In Exp 1, the lesioned animals exhibited no reflex facilitation of the unconditioned NM response at conditioned stimulus (CS)–unconditioned stimulus (UCS) intervals of 125–8,000 ms. In Exps 2 and 3, in which 1 CS–UCS interval (500 ms) was used, the lesions disrupted the maintenance of reflex facilitation but did not alter the facilitation exhibited in the 1st block of training. The lesions retarded the acquisition of conditioned NM responses when the 1,000-Hz tone CS intensity was 65 dB, but not when the intensity was 85 dB. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of US duration on classical conditioning of the rabbit's nictitating membrane response.

Attempted to distinguish the effects of UCS duration based on explicit pairings with the CS from the consequences of sheer exposure to the UCS in the rabbit nictitating membrane response. 228 albino rabbits received various proportions of CS (a 1,000-Hz tone) and UCS (a 60-Hz shock). Exp I revealed that there was an inverse relation between the overall level of CR acquisition and UCS durations of 50, l,500, and 6,000 msec. In addition, decrements in CR likelihood occurred within the daily sessions of 90 CS–UCS trials, and the magnitude of these within-session decrements was directly related to UCS duration. In Exp II, UCS duration of 50 and 6,000 msec were paired with the CS. When UCS exposure was equated, the UCS duration paired with the CS had a positive effect on CR likelihood. Conversely, in Exp III, the duration of interpolated UCSs had inverse effects on the rate of CR acquisition. In Exp IV, the opportunity for within-session decrements was eliminated by presenting only 1 CS–UCS trial per day, which resulted in a positive relation between CR likelihood and UCS duration. Results are discussed in terms of associative and performance hypotheses. (54 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance

Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention to peripheral targets. Rhesus monkeys and humans fixated a visual stimulus and responded to the onset of visual targets presented randomly in two visual field locations. The target was preceded by a valid cue (cue and target at the same location), an invalid cue (cue and target to opposite locations), a double cue (cues to both spatial locations, target to one), or, the cue was omitted (no-cue, target to either location). Reaction times (RTs) to the onset of the target were recorded. For monkeys, systemic injections of nicotine (0.003-0.012 mg/kg) or atropine (0.001-0.01 mg/kg), but not saline control injections, reduced mean RTs for all trials, indicating general behavioral stimulation. In addition, nicotine significantly reduced RTs for invalid trials but had little additional effect on those for valid, double, or no-cue trials. Virtually identical effects were observed for human chronic tobacco smokers in performing the same task following cigarette smoking. Injections of atropine in monkeys had no effect on RTs for valid or invalid trials but significantly slowed RTs in double-cue trials that did not require the orienting of attention. These results suggest that in both species, the nicotinic cholinergic system may play a role in automatic sensory orienting. In addition, the muscarinic system may play a role in alerting to visual stimuli in monkeys.     

Bridging temporal gaps between CS and US in autoshaping: Insertion of other stimuli before, during, and after CS.

In 4 experiments, female White Carneaux pigeons were exposed to key-light illuminations separated from food delivery by 12–60 sec. Approach to the key light did not develop on conventional trace-conditioning arrangements but occurred consistently whenever some auditory or visual stimulus filled the CS–UCS gap (serial conditioning) or was always present except during the gap. The CS approach was strong only when the stimulus present during the intertrial interval remained on until the termination of CS; if the stimulus ended at CS onset, conditioning did not occur. Although discriminability of CS–UCS gaps from intertrial periods seemed necessary for conditioning to occur in the absence of close CS–UCS contiguity, the outcome of the final experiment indicates that such discriminability was not sufficient for conditioning. Results are discussed in terms of possible 2nd-order conditioning effects and the changes in the associative strength of the "local context" existing when the CS appears, which may lead to superconditioning of CS. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of the associative and occasion-setting properties of contexts participating in a Pavlovian discrimination.

In 3 conditioned suppression experiments with 64 male Wistar rats, contextual control of performance to a conditioned stimulus (CS) was generated by alternating CS–unconditioned stimulus (UCS) pairings in Context A with CS presentations alone in Context B. Suppression to the CS during discrimination training and during tests of the CS in a 3rd context suggested that Contexts A and B had both acquired an ability to modulate performance. Whether the contexts modulated behavior through their direct associations with the UCS or through their abilities to occasion-set the CS–UCS relation was explored. There was no evidence of direct context–UCS associations in either context. Repeated extinction exposures to Context A following discrimination training did not affect its ability to modulate CS performance. Excitatory conditioning of Context B, however, abolished its ability to modulate. It is suggested that demonstrable context–UCS associations are not necessary for the contextual control of CS performance and that although the parallel is not perfect, contexts share several critical properties with stimuli that occasion-set CS–UCS relations. The possible role of configural conditioning is discussed. (54 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response.

16 6-mo-old and 15 36–60 mo old New Zealand albino rabbits underwent classical conditioning of the nictitating membrane response in either a delay conditioning (Exp I) or a trace conditioning (Exp II) paradigm. There was no difference between old and young Ss in the acquisition of the CR in the delay paradigm, nor were there any age-related differences in generalization to the tone CS or in sensitivity to the tone CS or eyeshock UCS. However, in the trace conditioning paradigm, old Ss acquired the CR significantly more slowly than young Ss. Because the same stimulus parameters and the same response were used in both experiments, it is unlikely that age-related differences in trace conditioning were due to stimulus sensitivity, motivation, or fatigue. Results are discussed in terms of how brain changes that accompany aging could differentially affect these 2 types of classical conditioning. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)