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PubMed2005

Reinstatement of conditioned fear in humans is context dependent and impaired in amnesia.

A contextual reinstatement procedure was developed to assess the contributions of environmental cues and hippocampal function in the recovery of conditioned fear following extinction in humans. Experiment 1 showed context specificity in the recovery of extinguished skin conductance responses after presentations of an auditory unconditioned stimulus. Experiment 2 demonstrated that fear recovery did not generalize to an explicitly unpaired conditioned stimulus. Experiment 3 replicated the context dependency of fear recovery with a shock as an unconditioned stimulus. Two amnesic patients failed to recover fear responses following reinstatement in the same context, despite showing initial fear acquisition. These results extend the known functions of the human hippocampus and highlight the importance of environmental contexts in regulating the expression of latent fear associations.

Acoustic Stimulation↗
PubMed1990

Methods of measuring tooth hypersensitivity.

Thermal, tactile, osmotic, and electrical stimuli, as well as exposure to air, can each elicit a painful response in individuals with hypersensitive teeth, and thus provide the basis for the different methods used to measure dentinal hypersensitivity. Tactile methods range from simple use of a sharp dental explorer to devices that can quantify the probing or scratching pressure exerted generally along the cementoenamel junction. Thermal methods involve flow of air or metal probes applied in different ways. Electrical stimulus is more complex and generally consists of progressive elevation of the magnitude of the stimulus until a sense of prepain rather than pain is felt. More than one method is usually needed in order to assess dentinal hypersensitivity, which has been estimated to affect one in every seven patients that visit a dental office.

Dentin Sensitivity↗
PubMed1994

Cross-modal compatibility effects with visual-spatial and auditory-verbal stimulus and response sets.

Within the visual-spatial and auditory-verbal modalities, reaction times to a stimulus have been shown to be faster if salient features of the stimulus and response sets correspond than if they do not. Accounts that attribute such stimulus-response compatibility effects to general translation processes predict that similar effects should occur for cross-modal stimulus and response sets. To test this prediction, three experiments were conducted examining four-choice reactions with (1) visual spatial-location stimuli assigned to speech responses, (2) speech stimuli assigned to keypress responses, and (3) symbolic visual stimuli assigned to speech responses. In all the experiments, responses were faster when correspondence between salient features of the stimulus and response sets was maintained, demonstrating that similar principles of translation operate both within and across modalities.

Auditory Perception↗
PubMed1987

Experimental analysis of syntax training in Broca's aphasia: a generalization and social validation study.

A multiple baseline design across responses was used to examine the effect of syntax training on the sentence production of 4 individuals with chronic Broca's aphasia. Subjects were trained to produce five exemplars of five sentence types from Helm's Elicited Language Program for Syntax Stimulation (Helm-Estabrooks, 1981). Generalization and maintenance of trained sentence types to novel exemplars and novel stimulus conditions served as dependent measures. In addition, five naïve judges rated subjects' responses before and following the treatment in terms of their "adequacy." Generalization to novel exemplars was demonstrated sequentially by 3 subjects (i.e., following the teaching of all five forms), and the remaining subject demonstrated generalization for three of five sentence types trained. Maintenance was variable across subjects and sentence types. Generalization across stimulus conditions was limited for all subjects. Adequacy judgments revealed improved communication skills for wh-questions but limited changes in the perceived adequacy of subjects' declarative responses. These findings indicate that the effects of syntax training procedures are limited to those grammatical constructions taught, that generalization of learned forms to novel stimulus conditions is not an automatic consequence of acquisition, and that the effect of such training on the adequacy of subjects' responses may be limited.

Adult↗
PubMed1994

Discriminative stimulus properties of the benzodiazepine receptor inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM).

The purpose of this study was to determine whether rats could be trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor inverse agonist DMCM from saline in a conditioned taste aversion paradigm. On a drug trial, water-deprived rats were injected with DMCM (0.55-0.6 mg/kg IP), allowed access to a 0.25% saccharin solution for 30 min, and then injected with LiCl. On non-drug trials, saline injections bracketed the drinking period. Conditioned controls were treated similarly with DMCM and saline on drug and non-drug trials, but received injections of saline instead of LiCl. At the completion of training, CMCM produced a 69% reduction of saccharin consumption on drug trials, compared with 23% for conditioned controls. The stimulus properties of DMCM were then measured by its ability to reduce the preference for saccharin over water in a two-bottle choice test. DMCM reduced saccharin preference in rats that received discrimination training from 68% to 19%, but did not alter saccharin preference in conditioned controls. Other compounds with varying activity at BZ receptors were evaluated for their ability to substitute for the discriminative stimulus effects of DMCM. Two BZ receptor inverse agonists, beta-CCE (10-18 mg/kg) and FG 7142 (3.2-18 mg/kg), substituted completely for DMCM. Partial substitution for DMCM was shown by the BZ receptor antagonist CGS 8216 (3.2-10 mg/kg) and the non-BZ convulsant pentylenetetrazol (10-20 mg/kg). The BZ receptor agonists chlordiazepoxide (0.32-5.0 mg/kg), diazepam (0.32-10 mg/kg), and alprazolam (0.1-3.2 mg/kg) and the BZ receptor antagonist flumazenil (1.0-32 mg/kg) failed to substitute for the DMCM stimulus. Pretreatment with flumazenil (1.0 mg/kg) blocked the stimulus effects of the training dose of DMCM and produced a shift to the right of the DMCM generalization curve. The pattern of compounds that substituted for the DMCM stimulus and the blockade of that stimulus by flumazenil indicate that the stimulus properties of DMCM are associated with its effects as a BZ receptor inverse agonist.

Animals↗
PubMed1982

Electrical stimulation of tooth pulp in humans. I. Relationships among physical stimulus intensities, psychological magnitude estimates and cerebral evoked potentials.

Brief electrical pulses were applied to the pulp of individual pre-molar teeth of 14 healthy, adult volunteers via wire electrodes implanted and sealed in dentine. The sensation threshold was estimated in each individual by the Two-Alternative Forced-Choice Staircase (2AFCS) method. Seven, 5 or 4 stimulus intensities were employed which were equally spaced in a logarithmic scale between 10 microA above threshold and 500 microA. Magnitude estimates of the subjective intensity of the sensation produced by individual dental excitations were obtained. Cerebral tooth pulp-evoked potentials were simultaneously recorded in 11 subjects. The growth of psychological sensory magnitude with increasing strength of electrical stimulus conformed to the general psychophysical power law. Individual power function exponents varied from 0.204 to 0.907 with a mean of 0.475 and a standard deviation of 0.190. The amplitude of TPEPs, measured between components N135 and P293, also was a power function of stimulus intensity. The exponents of individual TPEP amplitude-intensity functions ranged from 0.055 to 0.362 with a mean of 0.144 and a standard deviation of 0.100. These last exponents were substantially smaller than those describing the growth of psychological magnitude estimates. Neither magnitude estimation nor TPEP amplitude-intensity functions displayed abrupt changes in slope which might accompany transition from one operating sensory mechanism to another and/or changes in qualities of subjective sensations from 'innocuous' to 'uncomfortable' to 'painful.' The result of our psychophysical and electrophysiologic experiments indicate that: (1) albeit highly specialized both morphologically and functionally, human tooth pulp has certain fundamental properties in common with other sensory systems and (2) late midline TPEP components may provide measures of central events that, within a range of stimulus intensities, are associated with the perception of pain, but should not be looked upon as specific indicators of pain processes.

Adult↗
PubMed1995

Lead-induced changes in muscarinic cholinergic sensitivity.

This study was undertaken to determine whether the biochemical changes in cholinergic systems produced by lead exposure result in corresponding changes in cholinergic sensitivity in vivo. Rats chronically exposed from weaning to 0, 50 or 150 ppm lead (Pb) acetate in drinking water were trained to discriminate the stimulus properties of a dose of 1.75 mg/kg of the muscarinic cholinergic agonist, arecoline, from saline, using standard operant food reinforced drug discrimination procedures. Following acquisition of the discrimination, various doses of arecoline, another muscarinic agonist, oxotremorine, a nicotinic agonist, nicotine, and the GABAA modulator, pentobarbital, were substituted for the arecoline training dose, and the ability of various doses of the muscarinic antagonist, atropine, to antagonize the discriminative stimulus properties of the 1.75 mg/kg dose of arecoline were examined. Arecoline and oxotremorine produced dose-related increases in drug lever responding, while pentobarbital produced a partial generalization that was not dose-related. Arecoline's stimulus properties were substantially antagonized by atropine. Pb exposure significantly increased sensitivity to oxotremorine but not to arecoline, and attenuated the ability of some doses of atropine to antagonize the stimulus properties of arecoline. These findings demonstrate altered cholinergic sensitivity in response to environmentally relevant levels of lead in blood, and raise the possibility of cholinergic system disturbances in the behavioral manifestations produced by lead exposure.

Animals↗
PubMed1991

Inverse agonist properties of the FG 7142 discriminative stimulus.

A two-lever, food-motivated discrimination was established between the benzodiazepine receptor partial inverse agonist FG 7142 (5.0 mg/kg) and its vehicle. The FG 7142 discriminative stimulus was pharmacologically characterized by testing trained rats with a variety of benzodiazepine receptor ligands. Administration of the inverse agonist DMCM (0.15-0.30 mg/kg) dose-dependently mimicked the FG 7142 stimulus. In contrast, the benzodiazepine receptor agonist chlordiazepoxide, partial agonist ZK 91 296, mixed agonist/antagonist CGS 9896 and antagonist RO 15-1788 blocked the FG 7142 cue. These results indicate that the FG 7142 discriminative stimulus is based on its inverse agonist activity. The generalization of FG 7142 to the anxiogenic/convulsant compound pentylenetetrazole (PTZ), but not to the anorectic agent norfenfluramine, indicates that the anxiogenic properties of FG 7142, rather than its anorectic actions, may underlie the FG 7142 discriminative stimulus.

Animals↗
PubMed1994

Removal of the amygdala plus subjacent cortex disrupts the retention of both intramodal and crossmodal associative memories in monkeys.

Naive rhesus monkeys (Macaca mulatta) were trained preoperatively in an automated test apparatus on an auditory-visual (crossmodal) conditional task or on a visual-visual (intramodal) conditional task that involved learning a fixed set of stimulus-stimulus associations or paired associates. After having learned their respective tasks, each monkey received bilateral removal of the amygdala plus subjacent cortex. The 2 experimental groups showed equally poor retention of the stimulus-stimulus associations and subsequently relearned their respective crossmodal and intramodal associations at the same rate. These data argue against the idea that the amygdala is specialized for crossmodal associations. Instead, the data indicate that the amygdala or its underlying cortex, or both, play a more generalized role in stimulus-stimulus associative memory.

Amygdala↗
PubMed1969

The bisection of a brightness interval by pigeons.

Pigeons were trained on a discrete trials, successive discrimination procedure, in which the stimuli were two luminance values on the center key. Behavior was maintained by 25% reinforcement of correct responses on two side-keys. During occasional test trials the luminance of the center key was maintained at one of a number of values, intermediate to those of the two training stimuli, and a function relating the relative frequency of responses on the two side keys to stimulus intensity was obtained. The intersection of this function with the 50% line provided an estimate of the bisection point. Since no bisection point occurred below the geometric mean of the interval, the results were not consistent with a logarithmic scale of brightness but fitted the general mean theorem with an exponent of 0.24. With continued testing, the performance of individual subjects oscillated in an irregular manner about the mean bisection point. The relative stability of the test behavior and the absence of context effects indicated that the method was suitable as a general procedure for measuring stimulus distances.

Journal Article↗
PubMed2002

Learning to discriminate simple sinusoidal gratings is task specific.

Learning transfer effects of a modified spatial frequency discrimination task with simple sinusoidal gratings on various untrained test tasks, testing performance in relative position, local width and global size discrimination, have been investigated. Six subjects were exposed to grating stimuli of varying spatial frequency and size but constant relative position while they had to respond only to spatial frequency. In the course of 7 consecutive days all subjects showed significant reduction of spatial frequency discrimination thresholds. Comparison of discrimination thresholds for the untrained test tasks, taken before and after the learning epoch, reveals complete learning transfer to spatial frequency discrimination with gratings of constant size and variable relative position, but complete lack of transfer when grating spatial frequency is shifted about one octave lower. Further, there is improvement of relative position discrimination and width discrimination of single luminance bars, which is not very specific for the learnt spatial frequency. Although size variation was part of the learning procedure, discrimination of global stimulus size did not improve. Generally, the observed scheme of learning transfer reveals that there is learning only for stimulus attributes that are behaviorally relevant in the learning task. The differential scheme of improvement and code usage in the test tasks strongly indicates involvement of higher stages capable of independent access to different coding domains, as well as attentionally guided attribute selection and suppression. Supported by other recent findings, it is suggested that discrimination learning can be understood as a higher level process of gradual refinement of code selection out of a rich code base provided by lower level stages.

Adult↗
PubMed1999

Effects of dopamine and serotonin-releasing agents on methamphetamine discrimination and self-administration in rats.

To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.

Animals↗
PubMed2002

A PET study of stimulus- and task-induced semantic processing.

To investigate the neural correlates of semantic processing, previous functional imaging studies have used semantic decision and generation tasks. However, in addition to activating semantic associations these tasks also involve executive functions that are not specific to semantics. The study reported in this paper aims to dissociate brain activity due to stimulus-driven semantic associations and task-induced semantic and executive processing by using repetition and semantic decision on auditorily presented words in a cognitive conjunction design. The left posterior inferior temporal, inferior frontal (BA 44/45), and medial orbital gyri were activated by both tasks, suggesting a general role in stimulus-driven semantic and phonological processing. In addition, semantic decision increased activation in (i) left ventral inferior frontal cortex (BA 47), right cerebellum, and paracingulate, which have all previously been implicated in executive functions, and (ii) a ventral region in the left anterior temporal pole which is commonly affected in patients with semantic impairments. We attribute activation in this area to the effortful linkage of semantic features. Thus, our study replicated the functional dissociation between dorsal and ventral regions of the left inferior frontal cortex. Moreover, it also dissociated the semantic functions of the left posterior inferior temporal gyrus and anterior temporal pole: The posterior region subserves stimulus-driven activation of semantic associations and the left anterior region is involved in task-induced association of semantic information.

Adult↗
PubMed1993

Dopaminergic mediation of the stimulant generalization of nicotine.

1. Experiments were conducted to investigate if the psychostimulant cathinone, like d-amphetamine, would produce generalization of the discriminative stimulus effects of nicotine. 2. Rats were trained to discriminate either 0.8 mg/kg cathinone from its vehicle or 0.8 mg/kg nicotine from its vehicle and, subsequently, administered various doses of the other compound. 3. Results of Exp 1 indicate that animals trained to discriminate cathinone only partially generalize to the effects of 0.8-1.6 mg/kg nicotine. In contrast, animals trained to discriminate nicotine dose-responsively generalize to cathinone doses ranging from 0.1-1.2 mg/kg. 4. Exp 2 served to investigate the effects of the dopamine release inhibiting drug CGS 10746B upon the observed cathinone generalization in nicotine-trained rats. Pretreatment with this compound at doses of 20 and 30 mg/kg significantly attenuated cathinone generalization in these animals. 5. The results are discussed in light of the growing evidence that nicotinic receptors reside upon mesolimbic dopamine neurons and the possibility that the consequent increase in extracellular dopamine may produce the discriminative stimuli, as well as the reinforcing properties, of nicotine.

Alkaloids↗
PubMed2005

Prevalence of stereotypical responses to mistuned complex tones in the inferior colliculus.

The human auditory system has an exceptional ability to separate competing sounds, but the neural mechanisms that underlie this ability are not understood. Responses of inferior colliculus (IC) neurons to "mistuned" complex tones were measured to investigate possible neural mechanisms for spectral segregation. A mistuned tone is a harmonic complex tone in which the frequency of one component has been changed; that component may be heard as a separate sound source, suggesting that the mistuned tone engages the same mechanisms that contribute to the segregation of natural sounds. In this study, the harmonic tone consisted of eight harmonics of 250 Hz; in the mistuned tone, the frequency of the fourth harmonic was increased by 12% (120 Hz). The mistuned tone elicited a stereotypical discharge pattern, consisting of peaks separated by about 8 ms and a response envelope modulated with a period of 100 ms, which bore little resemblance to the discharge pattern elicited by the harmonic tone or to the stimulus waveform. Similar discharge patterns were elicited from many neurons with a range of characteristic frequencies, especially from neurons that exhibited short-latency sustained responses to pure tones. In contrast, transient and long-latency neurons usually did not exhibit the stereotypical discharge pattern. The discharge pattern was generally stable when the stimulus level or component phase was varied; the major effect of these manipulations was to shift the phase of the response envelope. Simulation of IC responses with a computational model suggested that off-frequency inhibition could produce discharge patterns with these characteristics.

Acoustic Stimulation↗