Discriminative Stimulus Research Articles

Visual Field Reconstruction in Hemianopia Using fMRI Based Mapping Techniques.

PurposeA stroke that includes the primary visual cortex unilaterally leads to a loss of visual field (VF) representation in the hemifield contralateral to the damage. While behavioral procedures for measuring the VF, such as perimetry, may indicate that a patient cannot see in a particular area, detailed psychophysical testing often detects the ability to perform detection or discrimination of visual stimuli (“blindsight”). The aim of this study was to determine whether functional magnetic resonance imaging (fMRI) could be used to determine whether perimetrically blind regions of the VF were still represented in VF maps reconstructed on the basis of visually evoked neural activity.MethodsThirteen patients with hemianopia and nine control participants were scanned using 3T MRI while presented with visual stimulation. Two runs of a dynamic “wedge and ring” mapping stimulus, totaling approximately 10 min, were performed while participants fixated centrally. Two different analysis approaches were taken: the conventional population receptive field (pRF) analysis and micro-probing (MP). The latter is a variant of the former that makes fewer assumptions when modeling the visually evoked neural activity. Both methods were used to reconstruct the VF by projecting modeled activity back onto the VF. Following a normalization step, these “coverage maps” can be compared to the VF sensitivity plots obtained using perimetry.ResultsWhile both fMRI-based approaches revealed regions of neural activity within the perimetrically “blind” sections of the VF, the MP approach uncovered more voxels in the lesioned hemisphere in which a modest degree of visual sensitivity was retained. Furthermore, MP-based analysis indicated that both early (V1/V2) and extrastriate visual areas contributed equally to the retained sensitivity in both patients and controls.ConclusionIn hemianopic patients, fMRI-based approaches for reconstructing the VF can pick up activity in perimetrically blind regions of the VF. Such regions of the VF may be particularly amenable for rehabilitation to regain visual function. Compared to conventional pRF modeling, MP reveals more voxels with retained visual sensitivity, suggesting it is a more sensitive approach for VF reconstruction.

Auditory cortex plasticity in musicians

Abstract Background The objective of this study was to verify wether it was possible to observe greater plasticity of the auditory cortex and greater benefits in terms of auditory processing, better discrimination, attention and identification of rare stimuli, in musicians, verified through the performance of Long Latency Auditory Evoked Potential, P300, with and without competitive noise, in musicians compared to non-musician. Methods 20 individuals were divided into two groups: 8 in the musicians, and 12 in the control group. The P300 values were compared between the two groups and then between the results of the P300 with and without competitive noise, in both groups. Results When comparing the results without competitive noise, it appears that the average amplitude was higher in the group of musicians compared to the control group, in both ears. Latency was lower in the control group, only in the right ear. With competitive noise, in both groups, the average amplitude is lower, compared to the results of the P300 without competitive noise, both in the right ear and in the left ear, and this effect is more considerable in the group of musicians. Regarding latency, theaverage of the P300 with competitive noise, in both ears, with a greater increase in latency values, in the group of musicians. Conclusion Musicians show a greater cortical inhibition effect compared to non-musicians, demonstrating that the musician’s central auditory system shows greater activation, which can result in better performance in functions such as attention and discrimination, due to training by musical practice.

Digital Games and the Exercise of Attention

Digital games can be used to improve cognitive skills in schools, since they have rules, goals, challenges and propose actions that require the player’s attention, the use of problem-solving capacity, involving the planning of actions, keeping the goals and objectives in mind. Therefore, this article’s objective is to investigate indicators on the effects of the use of digital cognitive games in interventions carried out in small groups in the school context on the attention capacity. Therefore, a quasi-experimental study was conducted with 30 subjects, aged 7 to 11, which were divided into two groups, participant and control. Both were evaluated before and after the intervention through the application of a concentrated attention test. The results obtained indicated that the participant group had a significantly superior performance in relation to the quality of the attention because of less mistakes in the second application than the control group. The differences found in test variables that indicate the speed of discrimination of stimuli and attention more broadly were not significant.

Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats.

Kratom (Mitragyna speciosa Korth), a native medicinal plant of Southeast Asia, is proposed to exhibit potential therapeutic value as an opioid substitute. However, studies of its negative emotional states resulting from withdrawal particularly of its main psychoactive compound, mitragynine (MG), are limited. Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus. Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9days and withdrawal was precipitated on the tenth day using naloxone (1mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24h after the last dose of MG or morphine administration. Unlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points. These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder.

Tolerance of muzzle contact underpins the acquisition of foraging information in vervet monkeys (Chlorocebus pygerythrus).

Muzzle contact, where one animal brings its muzzle into close proximity to that of another, has often been hypothesized as a straightforward means of socially mediated food investigation. Using 2,707 observations of muzzle contact occurring across 3 troops of wild vervet monkeys (Chlorocebus pygerythrus), we tested this social learning hypothesis. We first explored the social structuring of muzzle contact by analyzing the characteristics of initiators and receivers. Similar to previous research, juveniles initiated contact at higher rates than adults, particularly toward adult females and animals with lower dominance rankings. The highest number of contacts occurred between kin compared to contacts between nonkin. However, on the whole, contacts occurred at low rates, even among kin dyads. We next determined whether muzzle contact was used as a means to learn socially, specifically by animals seeking foraging information. We found that initiators did not overwhelmingly target foragers, meaning animals do not appear to directly seek information about food during muzzle contact. However, animals that contacted foragers were more likely forage themselves in comparison to those that contacted nonforagers, suggesting that foragers do provide food information. These findings indicate that both kin and low-ranking animals serve as discriminative stimuli for social tolerance and that foraging animals serve as discriminative stimuli for food availability. We conclude that broad social tolerance, rather than the recipient's knowledge, is the most likely antecedent to muzzle contact and that animals engage in this behavior as a low-cost means of maintaining a baseline level of information about their environment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Linear Integration of Sensory Evidence over Space and Time Underlies Face Categorization.

Visual object recognition relies on elaborate sensory processes that transform retinal inputs to object representations, but it also requires decision-making processes that read out object representations and function over prolonged time scales. The computational properties of these decision-making processes remain underexplored for object recognition. Here, we study these computations by developing a stochastic multifeature face categorization task. Using quantitative models and tight control of spatiotemporal visual information, we demonstrate that human subjects (five males, eight females) categorize faces through an integration process that first linearly adds the evidence conferred by task-relevant features over space to create aggregated momentary evidence and then linearly integrates it over time with minimum information loss. Discrimination of stimuli along different category boundaries (e.g., identity or expression of a face) is implemented by adjusting feature weights of spatial integration. This linear but flexible integration process over space and time bridges past studies on simple perceptual decisions to complex object recognition behavior.SIGNIFICANCE STATEMENT Although simple perceptual decision-making such as discrimination of random dot motion has been successfully explained as accumulation of sensory evidence, we lack rigorous experimental paradigms to study the mechanisms underlying complex perceptual decision-making such as discrimination of naturalistic faces. We develop a stochastic multifeature face categorization task as a systematic approach to quantify the properties and potential limitations of the decision-making processes during object recognition. We show that human face categorization could be modeled as a linear integration of sensory evidence over space and time. Our framework to study object recognition as a spatiotemporal integration process is broadly applicable to other object categories and bridges past studies of object recognition and perceptual decision-making.

Nicotine-like discriminative and aversive effects of two α4β2-selective nicotine agonists, ispronicline and metanicotine.

An attempt to determine the receptor selective nature of some of nicotine's behavioral effects was undertaken through the evaluation of the ability of two nicotinic α4β2*-selective receptor agonists to produce nicotine-like effects and modify rates of responding in a discrimination assay and in an aversive stimulus assay. A group of eight rats was trained to discriminate the presence of 1 mg/kg nicotine base. Another group of 4-6 rats was trained to report the aversive effects of nicotine by selecting a lever that produced one food pellet over a second lever that produced two food pellets and an intravenous injection of nicotine. Ispronicline and metanicotine, two α4β2*-selective receptor agonists, increased selection of the nicotine-appropriate lever in a dose-related manner, up to a maximum of approximately 75%. The α4β2*-selective receptor antagonist, dihydro-beta-erythroidine blocked both the discriminative stimulus effects and the rate-suppressing effects of ispronicline, metanicotine, and small, but not large doses of nicotine. The nonselective antagonist, mecamylamine, antagonized the discriminative stimulus effects of each of the three nicotine agonists as well as the rate-decreasing effects of nicotine and metanicotine. Mecamylamine did not modify the rate-decreasing effects of ispronicline. Both ispronicline and metanicotine as well as nicotine were avoided in the drug + food vs. food choice situation. The receptor-selective nature of ispronicline and metanicotine was hereby confirmed in a behavioral assay, as were earlier reports that the discriminative stimulus effects of relatively small doses of nicotine are likely mediated by activity at the α4β2* nicotine receptor.

Rhythmic Modulation of Visual Perception by Continuous Rhythmic Auditory Stimulation.

At any given moment our sensory systems receive multiple, often rhythmic, inputs from the environment. Processing of temporally structured events in one sensory modality can guide both behavioral and neural processing of events in other sensory modalities, but whether this occurs remains unclear. Here, we used human electroencephalography (EEG) to test the cross-modal influences of a continuous auditory frequency-modulated (FM) sound on visual perception and visual cortical activity. We report systematic fluctuations in perceptual discrimination of brief visual stimuli in line with the phase of the FM-sound. We further show that this rhythmic modulation in visual perception is related to an accompanying rhythmic modulation of neural activity recorded over visual areas. Importantly, in our task, perceptual and neural visual modulations occurred without any abrupt and salient onsets in the energy of the auditory stimulation and without any rhythmic structure in the visual stimulus. As such, the results provide a critical validation for the existence and functional role of cross-modal entrainment and demonstrates its utility for organizing the perception of multisensory stimulation in the natural environment.SIGNIFICANCE STATEMENT Our sensory environment is filled with rhythmic structures that are often multi-sensory in nature. Here, we show that the alignment of neural activity to the phase of an auditory frequency-modulated (FM) sound has cross-modal consequences for vision: yielding systematic fluctuations in perceptual discrimination of brief visual stimuli that are mediated by accompanying rhythmic modulation of neural activity recorded over visual areas. These cross-modal effects on visual neural activity and perception occurred without any abrupt and salient onsets in the energy of the auditory stimulation and without any rhythmic structure in the visual stimulus. The current work shows that continuous auditory fluctuations in the natural environment can provide a pacing signal for neural activity and perception across the senses.

O-EV002. Auditory event-related potential changes over 6 months following acute organophosphate insecticide poisoning: A follow-up study

Introduction . Ingestion of organophosphate insecticides (OPIs) is a common method of self-harm and a major clinical problem is Asia. Apart from acute cholinergic effects, OPIs are also claimed to be associated with long-term neurobehavioural deficits. However, neurophysiological evidence for such long-term deficits is scarce in humans. We aimed to assess long-term changes in the pre-attentive (N1) and attentive (P3b) components of auditory event-related potentials (ERPs) following acute OPI self-poisoning. Methods . We recruited 203 patients (147 men) hospitalised following OPI ingestion (OP Group; all had significant red cell cholinesterase inhibition) and 50 patients (23 men) hospitalised with paracetamol overdose (Control Group) as a means of self harm. We recorded their EEG in an auditory oddball task and derived the averaged ERPs. The subjects underwent three testing sessions: on discharge from hospital (around 14 days post-ingestion), 6 weeks and 6 months post-ingestion. We compared the reaction time and ERP indices of the two groups at each time point, adjusting for sex, age, education and psychiatric comorbidities in multiple regression models. Results . After adjusting for covariates, OP Group had significantly slower reaction time than the Control Group on discharge (mean difference [SE] = 65[20] ms, p = 0.001) and at 6 weeks (mean difference [SE] = 45[20] ms, p = 0.024), but not at 6 months. Parietal (PZ) P3b amplitudes were significantly smaller in the OP group on discharge (mean difference [SE] = 2.23[0.84] V, p = 0.009) and at 6 months (mean difference [SE] = 3.34[1.43] V, p = 0.021). P3b latencies or frontal (FZ) N1 component did not show significant intergroup differences. Conclusion . Acute exposure to clinically significant doses of OPIs seem to cause impairment in behavioural and neurophysiological indices of stimulus discrimination, that outlast the cholinergic phase of intoxication. The behavioural impairment seems to disappear over months, but the underlying neurophysiological deficits of attentive processing seem to last even after 6 months post-exposure.

Design and evaluation of a touchscreen apparatus for operant research with pigeons.

We developed a touchscreen apparatus for pigeons and conducted a series of experiments that assessed its utility for free-operant procedures. The apparatus incorporated an on-board Windows computer, an electromechanical interface, an amplified speaker, and the touchscreen. We found that merely projecting a virtual key on the screen was insufficient; too many pecks missed the key. Adding a visual target in the center of the key and providing visual feedback for on-key pecks both failed to improve response accuracy. Accuracy was improved by imposing a timeout after off-key pecks or providing a physical boundary around the key. With the physical boundary, response accuracy was comparable to that obtained with conventional plastic keys, and response acquisition via autoshaping also was comparable. Mixing the color elements of the screen's pixels produced color stimuli, but the colors did not function as pure wavelengths of light in tests of stimulus generalization. Both colors and geometric shapes functioned as discriminative stimuli in multiple schedules with variable-interval and extinction components or rich and lean fixed-ratio components. In general, our touchscreen apparatus is a viable alternative to conventional pigeon chambers and increases the experimenter's options for visual stimuli, auditory stimuli, and the number and location of response keys.

Antinociceptive and Discriminative Stimulus Effects of Six Novel Psychoactive Opioid Substances in Male Rats.

Compounds with novel or fentanyl-like structures continue to appear on the illicit drug market and have been responsible for fatalities, yet there are limited preclinical pharmacological data available to evaluate the risk of these compounds to public health. The purpose of the present study was to examine acetyl fentanyl, butyryl fentanyl, 3,4-dichloro-N-[[1-(dimethylamino)cyclohexyl]methyl]benzamide (AH-7921), 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine (MT-45), 4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide (W-15), and 4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide (W-18) for their relative potency to reference opioids and their susceptibility to naltrexone antagonism using the 55oC warm-water, tail-withdrawal assay of antinociception and a morphine drug discrimination assay in male, Sprague-Dawley rats. In the antinociception assay, groups of 8 rats per drug were placed into restraining tubes, their tails were immersed into 40o or 55oC water, and the latency for tail withdrawal was measured with a cutoff time of 15 seconds. In the drug discrimination assay, rats (n = 11) were trained to discriminate between 3.2 mg/kg morphine and saline, subcutaneously, in a two-choice, drug discrimination procedure under a fixed ratio-5 schedule of sucrose pellet delivery. Morphine, fentanyl, and four of the synthetic opioids dose dependently produced antinociception and fully substituted for morphine in the drug discrimination assay with the following rank order of potency: fentanyl > butyryl fentanyl > acetyl fentanyl > AH-7921 > MT45 > morphine. All drugs that produced antinociception or morphine-like discriminative stimulus effects were blocked by naltrexone. W-15 and W-18 did not show antinociceptive or morphine-like discriminative stimulus effects at the doses tested supporting a lack of opioid activity for these two compounds. These findings suggest that butyryl fentanyl, acetyl fentanyl, AH-7941, and MT-45 have abuse liability like other opioid agonists. SIGNIFICANCE STATEMENT: As novel psychoactive substances appear on the illicit drug market, preclinical pharmacological testing is required to assist law enforcement, medical professionals, and legal regulators with decisions about potential public health risks. In this study, four synthetic opioids, acetyl fentanyl, butyryl fentanyl, AH-7921, and MT-45 produced effects similar to fentanyl and morphine and were blocked by naltrexone. These data suggest the four synthetic opioids possess similar abuse liability risks as typical opioid agonists.

Vigor Encoding in the Ventral Pallidum.

The ventral pallidum (VP) is the major downstream nucleus of the nucleus accumbens (NAc). Both VP and NAc neurons are responsive to reward-predictive stimuli and are critical drivers of reward-seeking behavior. The cue-evoked excitations and inhibitions of NAc neurons predict the vigor (latency and speed) of the cue-elicited locomotor approach response and encode the animal’s proximity to the movement target, but do not encode more specific movement features such as turn direction. VP neurons also encode certain vigor parameters, but it remains unknown whether they also encode more specific movement features, and whether such encoding could account for vigor encoding. To address these questions, we recorded the firing of neurons in the VP of freely moving male rats performing a discriminative stimulus (DS) task. Similar to NAc neurons, VP neurons’ cue-evoked excitations were correlated with the speed of the upcoming approach movement and the animal’s proximity to the movement target at cue onset. Unlike NAc neurons, VP neurons’ firing reflected the efficiency of the approach movement path but not the latency to initiate locomotion. VP cue-evoked excitations are unlikely to be directly influenced by NAc cue-evoked excitations because unilateral treatment of the NAc with a dopamine D1 receptor antagonist, a manipulation that reduces NAc neurons’ cue-evoked excitations, did not alter ipsilateral VP cue-evoked excitations. These observations suggest that the two structures receive simultaneous activation by inputs conveying similar but not identical information, and work in parallel to set the vigor of the behavioral response.

Assessment of the ‘timing’ function of schedule-induced behavior on fixed-interval performance.

It has been suggested that schedule-induced behaviors allow organisms to adapt better to temporal regularities of the environment. The main goal of the present study was to observe the effect of schedule-induced drinking (SID) on the performance in fixed-interval (FI) schedules. Rats were exposed to a FI 15-, 30-, or 60-s food reinforcement schedule, and only half of them had access to water in the experimental chamber. Rats with access to water developed SID, which occurred in the first part of the interval, regardless of the FI value, and was followed by an increase in lever pressing rate. There were no substantial differences in the quantitative measures of timing between groups that had or did not have access to water, except for the rats in the FI 15-s group with access to water, who showed longer postreinforcement pauses, possibly attributable to competition between SID and lever pressing. SID did not manifest the scalar property, contrary to lever pressing, but it is proposed that behaviors are displayed serially until the last behavior before the target operant response becomes a discriminative stimulus for that behavior. It is not assumed that the purpose of schedule-induced behaviors is to aid timing, but the development of behavioral patterns might determine the performance of organisms on temporal tasks. Additionally, in some cases competition between responses might exert more control on when the operant behavior occurs than timing. Timing seems to consist in the temporal organization of available behaviors that leads to a specific behavior occurring at a specified time, a single characteristic that typically had come to indicate accurate timing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

General Pavlovian-instrumental transfer tests reveal selective inhibition of the response type – whether Pavlovian or instrumental – performed during extinction

The present experiments examined whether extinction of a stimulus predicting food affects the ability of that stimulus to energize instrumental performance to obtain food. We first used a general Pavlovian instrumental transfer (PIT) paradigm in which rats were first given Pavlovian conditioning with a stimulus predicting one type of food outcome and were then trained to lever press for a different food outcome. We found that the Pavlovian stimulus enhanced performance of the lever press response and that this enhancement was preserved after extinction of that stimulus (Experiment 1) even when the context was manipulated to favor the expression of extinction (Experiment 2). Next, we assessed whether extinction influenced the excitatory effect of a stimulus when it was trained as a discriminative stimulus. Extinction of this stimulus alone had no effect on its ability to control instrumental performance; however, when extinguished with its associated lever press response, discriminative control was lost (Experiments 3 and 4). Finally, after instrumental and Pavlovian training, we extinguished a Pavlovian stimulus predicting one food outcome with a lever press response that delivered a different outcome. In a general PIT test, we found this extinction abolished the ability of the Pavlovian stimulus to elevate responding on a lever trained with a different outcome, revealing for the first time that extinction can abolish the general PIT effect. We conclude that extinction can produce an inhibitory association between the stimulus and the general response type, whether Pavlovian or instrumental, performed during the extinction training.

Knockout of the Serotonin Transporter in the Rat Mildly Modulates Decisional Anhedonia

Serotonin transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. While data exist on the effect of serotonin transporter gene knockout (5-HTT−/−) in rodents on consummatory and anticipatory anhedonia, with mixed outcomes, the effect on decisional anhedonia has not been investigated thus far. Here, we tested whether 5-HTT−/− contributes to decisional anhedonia. To this end, we established a novel touchscreen-based go/go task of visual decision-making. During the learning of stimulus discrimination, 5-HTT+/+ rats performed more optimal decision-making compared to 5-HTT−/− rats at the beginning, but this difference did not persist throughout the learning period. During stimulus generalization, the generalization curves were similar between both genotypes and did not alter as the learning progress. Interestingly, the response time in 5-HTT+/+ rats increased as the session increased in general, while 5-HTT−/− rats tended to decrease. The response time difference might indicate that 5-HTT−/− rats altered willingness to exert cognitive effort to the categorization of generalization stimuli. These results suggest that the effect of 5-HTT ablation on decisional anhedonia is mild and interacts with learning, explaining the discrepant findings on the link between 5-HTT gene and depression.

Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats.

Persistent susceptibility to cue-induced relapse is a cardinal feature of addiction. Discriminative stimuli (DSs) are one type of drug-associated cue that signal drug availability (DS+) or unavailability (DS-) and control drug seeking prior to relapse. We previously established a trial-based procedure in rats to isolate DSs from context, conditioned stimuli, and other drug-associated cues during cocaine self-administration and demonstrated DS-controlled cocaine seeking up to 300 abstinence days. The behavioral and neural mechanisms underlying trial-based DS-control of drug seeking have rarely been investigated. Here we show that following discrimination training in our trial-based procedure, the DS+ and DS- independently control the expression and suppression of cocaine seeking during abstinence. Using microinjections of GABAA + GABAB receptor agonists (muscimol + baclofen) in medial prefrontal cortex, we report that infralimbic, but not prelimbic, subregion of medial prefrontal cortex is critical to persistent DS-controlled relapse to cocaine seeking after prolonged abstinence, but not DS-guided discriminated cocaine seeking or DS-controlled cocaine self-admininstration. Finally, using ex vivo whole-cell recordings from pyramidal neurons in the medial prefrontal cortex, we demonstrate that the disruption of DS-controlled cocaine seeking following infralimbic cortexmicroinjections of muscimol+baclofen is likely a result of suppression of synaptic transmission in the region via a presynaptic mechanism of action.

Δ9-Tetrahydrocannabinol discrimination: Effects of route of administration in rats

Cannabis users typically smoke or vape cannabis or ingest it in edibles, whereas cannabinoids are typically administered via injection in rodent research. The present study examined the effects of route of administration (ROA) of Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Adult female and male Long Evans rats were trained to discriminate intraperitoneal (i.p.) THC from vehicle in a drug discrimination procedure. Following acquisition, dose-effect curves were determined with THC using i.p., oral (p.o.), and subcutaneous (s.c.) injection in both sexes and aerosol exposure in males only, followed by a time course with one dose for each ROA. Both sexes acquired THC discrimination in a similar number of sessions, although baseline response rates were significantly lower in females than males. THC fully substituted for the 3 mg/kg i.p. training dose across all ROA. While potencies were similar for ROA involving first-pass metabolism (i.p. and p.o.), THC potency was lower with s.c. administration. During the time course analysis, aerosol administration had the shortest latency to onset of discriminative stimulus effects and the shortest duration of effect, whereas s.c. administration had the longest duration. The results of this examination of the effects of ROA on an abuse-related effect of THC provide an empirical foundation to facilitate choice of ROA for mechanistic investigation of THC’s pharmacology. Further, animal models using translationally relevant ROA may facilitate more accurate predictions of their effects in humans.

Are the advantages of chess expertise on visuo-spatial working-memory capacity domain specific or domain general?

Chess experts have repeatedly demonstrated exceptional recall of chessboards, which is weakened by disruption of the chessboard. However, chess experts still perform better than novices when recalling such disrupted chessboards, suggesting a somewhat generalized expertise effect. In the current study, we examined the extent of this generalized expertise effect on early processing of visuo-spatial working memory (VSWM), by comparing 14 chess experts (Elo rating > 2000) and 15 novices on a change-detection paradigm using disrupted chessboards, where attention had to be selectively deployed to either visual or spatial features, or divided across both features. The paradigm differed in the stimuli used (domain-specific chess pieces vs. novel visual shapes) to evaluate domain-general effects of chess expertise. Both experts and novices had greater memory discriminability for chess stimuli than for the unfamiliar stimuli, suggesting a salience advantage for familiar stimuli. Experts, however, demonstrated better memory discriminability than novices not only for chess stimuli presented on these disrupted chessboards, but also for novel, domain-general stimuli, particularly when detecting spatial changes. This expertise advantage was greater for chessboards with supra-capacity set sizes. For set sizes within the working-memory capacity, the expertise advantage was driven by enhanced selective attention to spatial features by chess experts when compared to visual features. However, any expertise-related VSWM advantage disappeared in the absence of the 8 × 8 chessboard display, which implicates the chessboard display as an essential perceptual aspect facilitating the "expert memory effect" in chess, albeit one that might generalize beyond strictly domain-relevant stimuli.

Interactive effects of (±)-trans-U50488 and its stereoisomers with cannabinoids

The adverse effects of mu opioid agonists have spurred a renewed interest in using kappa opioid receptor (KOR) agonists as analgesics. KOR agonists also have potential for development as diuretics for the treatment of edema and hypertension. Here, we evaluated the discriminative stimulus, antinociceptive, and diuretic effects of the kappa agonist (±)-trans-U-50488 and its stereoisomers (−)-(1S,2S)-U-50488 or (+)-(1R,2R)-U-50488) alone and in combination with the cannabinoid agonist (−)-CP 55,940. To establish (±)-U-50488 as a discriminative stimulus, rats (n = 12) were trained to discriminate intraperitoneal (i.p.) administration of 5.6 mg/kg of (±)-trans-U-50488 from saline under a fixed-ratio 20 (FR-20) schedule of food reinforcement. Then, antinociception was assessed using two procedures: warm water tail withdrawal and von Frey paw withdrawal. Diuretic effects were assessed in separate rats (n = 6/group). Doses of (±)-U-50488 and (−)-U-50488 that served as discriminative stimuli produced significant increases in urine output, but at lower doses than those that produced antinociception. In contrast, (+)-U-50488 alone had no discriminative stimulus or diuretic effects at the doses tested, but did produce antinociception in the von Frey assay. When three cannabinoids and morphine were tested in the (±)-U-50488 discrimination procedure to determine the similarity of these drugs' discriminative stimulus effects to those for (±)-U-50488, the rank order similarity was (−)-CP 55,940 > (−)-trans-THC > (+)-WIN 55,212–2 ≥ morphine. (−)-CP 55,940 alone (0.056 mg/kg) partially substituted for the discriminative stimulus effects of (±)-U-50488 and produced significant diuretic and antinociceptive effects. (−)-CP 55,940 in combination with (±)-U-50488 also produced a two-fold leftward shift in the discriminative stimulus curve for (±)-U-50488, and near-additive antinociception with (±)-U-50488 and (+)-U-50488. Further, the diuretic effect of (−)-CP 55,940 was enhanced by a dose of (+)-U50488, which itself did not alter urine output. These data together indicate that a combination of cannabinoid and kappa opioid agonists can enhance diuresis, but may have limited potential for serving as opioid-sparing pharmacotherapeutics for treatment of pain.

Stimulus Contrast Affects Spatial Integration in the Lateral Geniculate Nucleus of Macaque Monkeys.

Gain-control mechanisms adjust neuronal responses to accommodate the wide range of stimulus conditions in the natural environment. Contrast gain control and extraclassical surround suppression are two manifestations of gain control that govern the responses of neurons in the early visual system. Understanding how these two forms of gain control interact has important implications for the detection and discrimination of stimuli across a range of contrast conditions. Here, we report that stimulus contrast affects spatial integration in the lateral geniculate nucleus of alert macaque monkeys (male and female), whereby neurons exhibit a reduction in the strength of extraclassical surround suppression and an expansion in the preferred stimulus size with low-contrast stimuli compared with high-contrast stimuli. Effects were greater for magnocellular neurons than for parvocellular neurons, indicating stream-specific interactions between stimulus contrast and stimulus size. Within the magnocellular pathway, contrast-dependent effects were comparable for ON-center and OFF-center neurons, despite ON neurons having larger receptive fields, less pronounced surround suppression, and more pronounced contrast gain control than OFF neurons. Together, these findings suggest that the parallel streams delivering visual information from retina to primary visual cortex, serve not only to broaden the range of signals delivered to cortex, but also to provide a substrate for differential interactions between stimulus contrast and stimulus size that may serve to improve stimulus detection and stimulus discrimination under pathway-specific lower and higher contrast conditions, respectively.SIGNIFICANCE STATEMENT Stimulus contrast is a salient feature of visual scenes. Here we examine the influence of stimulus contrast on spatial integration in the lateral geniculate nucleus (LGN). Our results demonstrate that increases in contrast generally increase extraclassical suppression and decrease the size of optimal stimuli, indicating a reduction in the extent of visual space from which LGN neurons integrate signals. Differences between magnocellular and parvocellular neurons are noteworthy and further demonstrate that the feedforward parallel pathways to cortex increase the range of information conveyed for downstream cortical processing, a range broadened by diversity in the ON and OFF pathways. These results have important implications for more complex visual processing that underly the detection and discrimination of stimuli under varying natural conditions.