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The ventral tegmental area is required for the behavioral and nucleus accumbens neuronal firing responses to incentive cues.

Reward-predictive cues exert powerful control over behavioral choice and may be a critical factor in drug addiction. Reward-seeking elicited by predictive cues is facilitated by the release of dopamine in the nucleus accumbens (NAc), yet the contribution of dopamine to the specific NAc firing patterns that underlie goal-directed behavior has remained elusive. We present evidence that subpopulations of NAc neurons that respond to predictive cues require the dopaminergic projection from the ventral tegmental area (VTA) to promote reward-seeking behavior. Rats trained to perform an operant response to a cue to obtain a sucrose reward were implanted with both multiunit recording electrodes in the NAc and microinjection cannulas in the VTA. Both the behavioral response to cues and the cue-evoked firing of NAc neurons were blocked by injection of the GABA(B) agonist baclofen into the VTA. An additional group of rats was trained on the same task and then implanted with microinjection cannulas in the NAc. Like VTA baclofen injection, injection of dopamine receptor antagonists into the NAc profoundly reduced cue-elicited reward seeking. Together, these results support the conclusion that both the behavioral response to the cue and the specific NAc neuronal firing that promotes the response depend on dopamine release within the NAc. Our findings suggest a neural mechanism by which the dopamine-dependent firing of NAc neurons mediates goal-directed behavior.

Animals↗

Cue reactivity in adolescents: measurement of separate approach and avoidance reactions.

OBJECTIVE: There were two specific goals for the current study: (1) to demonstrate that adolescents display drug-specific cue reactivity to alcohol and cigarette visual cues that varies based on drug-use history and (2) to test the unique contribution of adolescents' avoidance reactions to alcohol and cigarette cues, independent of approach/craving reaction. METHOD: Adolescents (N = 143; age 13-20 years; 58 males) with varied substance-use histories were recruited from school and community sites. Adolescents were presented with a series of alcohol, cigarette, and nondrug comparison visual cues and reported their approach/craving and avoidance reactions. They also completed individual difference measures related to their alcohol and cigarette use and experiences. RESULTS: When adolescents were grouped according to their current alcohol or cigarette use (no use, low use, high use), increased use of alcohol or cigarettes was associated with stronger reactions (increased approach, decreased avoidance) to cues for that substance but not to nondrug control cues. Simultaneous regression analyses demonstrated that after controlling for approach/craving reactions, avoidance cue reactions predicted unique and/or incremental variance in measures of alcohol and cigarette usage, recent change in patterns of use, alcohol expectancies, alcohol restraint and parental alcohol problems. CONCLUSIONS: Adolescents displayed robust alcohol and cigarette cue-specific reactions that varied systematically with their current use of these drugs. Across numerous clinically relevant individual difference variables, predictive power was greatly enhanced through the inclusion of both avoidance and approach reactions.

Adolescent↗

Priming or executive control? Associative priming of cue encoding increases "switch costs" in the explicit task-cuing procedure.

The explicit task-cuing procedure involves presenting a cue that indicates which task to perform on a target. Responses are typically faster when tasks repeat than when they alternate, and this difference is often interpreted as a measure of the time required for executive control processes to change task set. This article suggests that the difference reflects priming of cue encoding when successive cues are identical or associatively related. Subjects responded to task repetitions more quickly when the cue on the current trial was associatively related to the cue on the previous trial (e.g., day --> night) than when the cues were unrelated (e.g., verb --> night). Models applied to the time course function--generated by manipulating the interval between the onsets of the cue and the target--showed that the facilitation was due to cue encoding, a process that does not require online executive control.

Attention↗

Sensory mediation of stimulus-driven attentional capture in multiple-cue displays.

Three location-cuing experiments were conducted in order to examine the stimulus-driven control of attentional capture in multiple-cue displays. These displays consisted of one to four simultaneously presented direct location cues. The results indicated that direct location cuing can produce cue effects that are mediated, in part, by nonattentional processing that occurs simultaneously at multiple locations. When single cues were presented in isolation, however, the resulting cue effect appeared to be due to a combination of sensory processing and attentional capture by the cue. This suggests that the faster responses produced by direct cues may be associated with two different components: an attention-related component that can be modulated by goal-driven factors and a nonattentional component that occurs in parallel at multiple direct-cue locations and is minimally affected by goal-driven factors.

Attention↗

Spectral tilt as a cue to word segmentation in infancy and adulthood.

Across a variety of tasks, adults respond differently to syllables with multiple stress cues than to syllables with only one cue to stress. This series of experiments was designed to explore how infants and adults use partial stress as a cue to word boundaries. In the first experiment, 9-month-old infants treated syllables with only one cue to stress (spectral tilt) as a strong cue to word boundaries. The second experiment shows that whereas adults treat syllables with multiple cues to stress as word onsets, they do not consider syllables marked only by spectral tilt to be strong indicators of word boundaries. Thethird experiment shows that 1-year-old infants are more adultlike than 9-month-olds in their use of stress cues. Taken together, these results suggest a rapid development of stress cue knowledge in infancy, perhaps due to infants' experience with word segmentation.

Adult↗

Cue set size effects: sampling activated associates or cross-target interference?

Previous findings indicate that test cues linked to more associates (more knowledge) produce lower levels of recall than cues with fewer associates. One hypothesis attributes this effect to cross-target interference arising during retrieval on the assumption that cues with more associates are more likely to be indirectly connected to studied words other than the target. Another attributes the effect to sampling associates of the cue on the assumption that the probability of sampling the target declines as more associates are activated. Findings from four experiments showed that recall varied with cue set size, and, more importantly, that cue set size affected recall independently of the interference produced by cross-target connections. These results were interpreted as supporting a model that attributes cue set size effects to sampling processes associated with the intersection of the test cue and its associates with the target and its associates.

Adult↗

Event-related potentials and cue-reactivity in alcoholism.

BACKGROUND: Relapse is a major problem in the treatment of addictive behaviors. Conditioning models of alcohol addiction suggest that stimuli associated with previous drug use (cues) may initiate relapse in a definite group of alcoholics. Event-related potentials (ERPs) might be useful to reveal the brain functional substrates of cue-reactivity. METHODS: In a preliminary investigation, 11 alcohol-dependent patients who did not take part in the electrophysiological study completed a structured interview to rate 80 words as to the degree of relatedness to alcohol. Based on these results, cue-reactivity for 15 alcohol-related and 15 unrelated word cues, each repeated eight times, was investigated in 19 alcohol-dependent men (44.2 +/- 8.5 years) and 19 healthy control men (42.5 +/- 12.5 years). RESULTS: A cue-reactivity that consisted of significantly higher amplitudes in the ERPs after alcohol-related words compared with unrelated words was found in alcohol-dependent patients, but not in controls, at the electrode location Pz [F(1,36) = 5.2,p < 0.05]. CONCLUSIONS: Consistent with the hypothesis, only alcohol-dependent patients were characterized by signs of increased cerebral activity associated with alcohol-related compared with unrelated cues. Therefore, the results support the concept of cue-reactivity in alcoholism based on a neurobiological measurement. Future investigations will show whether this cue-reactivity can be applied to assess the risk of relapse in individual alcohol-dependent patients.

Adult↗

[Facilitating and inhibiting effects of the orientation of attention using peripheral cues].

The attentional field resulting from the presentation of peripheral cues; which were either informative or non informative about the position of the imperative stimulus, was studied. Different time intervals between cue and stimulus (120, 300, 600 ms) were used. The results showed facilitation of the response with the informative cue and inhibition with the non informative cue. This happened for the longest cue-stimulus intervals and when the position of the cue and the position of the stimulus were congruent. Also order of cue presentation (i.e., either informative followed by the non informative cue or vice versa) proved important in producing facilitatory and inhibitory effects.

Attention↗

Detection of conspecific alarm cues by juvenile salmonids under neutral and weakly acidic conditions: laboratory and field tests.

A variety of fishes possess damage-released chemical alarm cues, which play a critical role in the detection and avoidance of potential predation threats. Recently, we have demonstrated that the ability of fathead minnows ( Pimephales promelas) and finescale dace ( Phoxinus neogaeus) to detect and respond to conspecific alarm cues is significantly reduced under weakly acidic conditions (pH 6.0). Rainbow trout ( Oncorhynchus mykiss) and brook charr ( Salvelinus fontinalis) possess an analogous alarm cue system. However, it is unknown if the trout alarm cue system is likewise affected by relatively small changes in pH. In addition, previous studies have not verified this phenomenon under natural conditions. We conducted laboratory and field trials to examine the potential effects of acute exposure to weakly acidic (pH 6.0) conditions on the detection and response of conspecific alarm cues by juvenile trout. Our laboratory results demonstrate that while juvenile rainbow trout exhibit significant increases in antipredator behaviour under normal pH conditions (pH 7.0-7.2), they do not respond to the presence of conspecific chemical alarm cues (i.e. response is not different from controls) under weakly acidic conditions. Similarly, a wild strain of brook charr in their natural streams near Sudbury, Ontario, failed to detect conspecific alarm cues in a weakly acidic stream (mean pH 6.11) while they responded to these cues in a neutral stream (mean pH of 6.88). This is the first demonstration that relatively small changes in ambient pH can influence alarm responses under natural conditions. These data suggest significant, sub-lethal effects of acid precipitation on natural waterways.

Acid Rain↗

Virtual reality cue reactivity assessment: a case study in a teen smoker.

Cigarette smoking in adolescents is a major public health problem. To address the increasing need for efficacious assessment and treatment methods, we developed and tested a novel virtual reality cue reactivity assessment system. A case study of a controlled virtual reality cue reactivity trial with a 17-year-old adolescent cigarette smoker is presented. During the trial, the participant was exposed to virtual reality (VR) smoking cues and VR neutral cues and assessments of subjective craving and skin conductance response (SCR) were recorded. Upon exposure to VR smoking cues, craving increased. A novel methodology for collecting and analyzing SCR in VR was developed and explored to expand the role of physiological variables in VR research. SCR data indicated specific reactions to smoking cue stimuli, with the subject experiencing increased reactivity to smoking cues (i.e., cigarettes) compared to food or drinks. Based on this case study, further research using VR cue reactivity assessment in adolescent smokers is warranted. The impact of VR in drug research and future applications in research are also discussed.

Adolescent↗

Rightward attentional bias and left hemisphere dominance in a cue-target light detection task in a callosotomy patient.

Six normal subjects and a callosotomized man with a prefrontal lesion, mostly on the right side, were tested in a reaction time (RT) task involving a key-pressing response to an extrafoveal light target preceded by an extrafoveal light cue. Cues and targets were presented along the horizontal meridian at 4 degrees and 12 degrees on the right and left of fixation. Fixation was maintained throughout each trial. The cue signalled the occurrence of the target within a time window extending from 200 to 4000 misec from the cue, but did not predict target location. Normal controls responded faster to medial than to lateral targets in both fields, but showed no between-field difference, and their RT was not affected by cue location. Furthermore, they showed the so-called 'ipsilateral inhibition' or 'inhibition of return' effect, their RT being longer when cues and targets occurred in the same field than when they occurred in opposite fields. The RT of the callosotomized subject showed a left-right gradient for both cue location and target location, being longest for the leftmost location and shortest for the right locations. In addition, he showed a significant advantage for the right hand regardless of cue and target location, as well as a consistent ipsilateral inhibition in the left field, whereas in the right field there was ipsilateral inhibition only at the two longest stimulus onset asynchronies. These results suggest that, at least under these experimental conditions, there was a rightward orientational bias which reflected the taking over of the control of performance by the left hemisphere. This attentional bias was reminiscent of that seen in patients with hemi-inattention from right hemisphere damage, although the callosotomized patient showed no sign of such hemi-inattention in routine clinical tests. On the basis of several considerations the rightward bias could be attributed to the callosal interhemispheric disconnection rather than to the right prefrontal lesion.

Adult↗

Mechanism of ubiquitin recognition by the CUE domain of Vps9p.

Coupling of ubiquitin conjugation to ER degradation (CUE) domains are approximately 50 amino acid monoubiquitin binding motifs found in proteins of trafficking and ubiquitination pathways. The 2.3 A structure of the Vps9p-CUE domain is a dimeric domain-swapped variant of the ubiquitin binding UBA domain. The 1.7 A structure of the CUE:ubiquitin complex shows that one CUE dimer binds one ubiquitin molecule. The bound CUE dimer is kinked relative to the unbound CUE dimer and wraps around ubiquitin. The CUE monomer contains two ubiquitin binding surfaces on opposite faces of the molecule that cannot bind simultaneously to a single ubiquitin molecule. Dimerization of the CUE domain allows both surfaces to contact a single ubiquitin molecule, providing a mechanism for high-affinity binding to monoubiquitin.

Carrier Proteins↗

Left and right occipital cortices differ in their response to spatial cueing.

We investigated cue and target-related laterality effects with event-related fMRI. Both left and right occipital areas responded maximally when both cue and target were presented in the contralateral visual hemifield (VF), and minimally when cue and target were presented in the ipsilateral VF. However, whereas signal increases in right ventromedial and lateral occipital cortex were intermediate in those trials in which the cue appeared in the VF contralateral to the target (invalid cue trials), signal strength in left occipital cortex was almost identical for valid and invalid cues, i.e., high for RVF cues, and low for LVF cues, independent of the VF of the target. These data support theories which postulate a greater ability of the right hemisphere for bilateral processing. However, these laterality effects were observed earlier in the visual pathway than previously thought, leading to the question whether the hemispheric differences observed in occipital cortex are generated in the activated areas or are the effect of reentrant processes from more anterior areas, potentially in parietal cortex.

Adult↗

Avoidance of conspecific injury-released chemical cues by free-ranging Gammarus lacustris (Crustacea:Amphipoda).

Behavioral responses to chemical cues have been demonstrated for a range of aquatic animals. Injury-released chemical alarm cues from conspecifics are released when a prey's predator is actively foraging. Detection of these cues elicits antipredator behaviors that reduce the probability of predation. Amphipod crustaceans in the genus Gammarus are widespread denizens of ponds and streams. Antipredator responses by Gammarus to conspecific alarm cues, and subsequent reduction of predation risk, are known from experiments in the laboratory. Here, we verify laboratory findings by demonstrating an avoidance response to alarm cues using a field population of G. lacustris. We used small traps baited with sponge blocks containing either water (control) or injury-released cues from Gammarus. We repeated the experiment twice. In both experiments, significantly fewer Gammarus were captured in traps with alarm cue sponges than in traps with water sponges. Predatory leeches Dina parva were attracted to Gammarus traps in the first experiment but not the second experiment. In the second experiment, we measured the individual weight of captured amphipods. Two size classes were present; small (1-5 mg) and large (35-108 mg). Both sizes contributed to the avoidance response. Within the large size class, small individuals were significantly less responsive to the alarm cue than large individuals, implying that small adult Gammarus may have different cost/benefit decision criteria for risk assessment than large Gammarus.

Animal Communication↗

Are chemical alarm cues conserved within salmonid fishes?

A wide diversity of fishes possess chemical alarm signalling systems. However, it is not known whether the specific chemicals that act as alarm signals are conserved within most taxonomic groups. In this study we tested whether cross-species responses to chemical alarm signals occurred within salmonid fishes. In separate laboratory experiments, we exposed brook charr (Salvelinus fontinalis), brown trout (Salmo trutta), and rainbow trout (Oncorhynchus mykiss) to chemical alarm signals from each of the three salmonid species and from swordtails (Xiphophorus helleri). In each case, the test species responded with appropriate antipredator behavior to all three salmonids alarm cues, but did not react to swordtail cues. These data suggest that chemical alarm cues are partially conserved within the Family Salmonidae. For each species tested, the intensity of the response was stronger to conspecific alarm cues, than to heterospecific alarm cues, indicating that salmonids could distinguish between chemical cues of conspecifics versus heterospecifics. These results suggest that the chemical(s) that act as the alarm cues may be: 1) identical and that there may be other chemical(s) that allow the test fish to distinguish between conspecifics and heterospecifics, or 2) that the cues that act as signals are not identical, but are similar enough to be recognized.

Animal Communication↗

Hippocampal place fields are altered by the removal of single visual cues in a distance-dependent manner.

Hippocampal CA3 cells were recorded in male Long-Evans rats that explored a square recording chamber. Three of the 4 chamber walls held a rectangular cue card, each of different size. Rotating the set of cue cards rotated the location of the place fields. Place fields were common close to the walls of the recording chamber, particularly the walls with cues. When single cues were removed, the spatial information content decreased but returned to baseline levels when the cue was replaced. When a cue near a place field was removed, the place field firing rate and area decreased; when a distant cue was removed, firing rate and area increased. Thus, removing single visual cues predictably and reversibly altered hippocampal place fields. Together, the results suggest that hippocampal neurons may optimize the encoding of visual information and are consistent with a distance-encoding hypothesis of CA3 network function.

Animals↗

Subjective and physiological responses to smoking cues in smokers with schizophrenia.

The prevalence of smoking is high among people with schizophrenia. Although several research groups are developing smoking treatments for these smokers, abstinence rates to date have been modest. Methodological tools such as cue exposure are useful in clinical research with smokers in general, but the value of these paradigms with smokers with schizophrenia has yet to be established. The aim of the present study was to determine the subjective and physiological effects of exposure to in vivo smoking cues in smokers with schizophrenia. A total of 25 heavy smokers with schizophrenia or schizoaffective disorder were assessed while nonabstinent and after 2-hr smoking abstinence. Urge to smoke, mood, nicotine withdrawal symptoms, heart rate, and blood pressure were measured during a precue relaxation period, after exposure to neutral cues, and after exposure to smoking cues. Results indicate that both exposure to smoking cues and brief abstinence increased urge levels, nicotine withdrawal symptom levels, and negative affect. Abstinence did not amplify the effects of cues on urges or other cue reactivity measures. These results indicate that smoking cue reactivity laboratory models may be useful for investigating potential smoking treatments for, or neurobiological contributions to, smoking behavior in smokers with schizophrenia.

Blood Pressure↗

Attention cueing aids auditory intensity resolution.

Intensity resolution of pure tones in a one-interval forced-choice paradigm was measured for experienced musicians under fixed- and uncertain-frequency conditions, and under uncertain-frequency conditions with informative cues as to target frequency. The uncertain frequency effect for intensity resolution, when present, was reduced or removed by frequency cueing, both with auditory stimulus cues and with visually presented information cues. Also, intensity resolution performance improved over the course of the experiment, both for fixed- and for uncertain-frequency conditions, as had been found previously. Analysis of the individual data indicated that across-experiment learning was unrelated to the ability to use the auditory stimulus cue, and that multiple-band learning was incompatible with the use of the visual information cue. The results are consistent with the idea that the single-band listening observed in fixed-frequency conditions was induced in most listeners by the auditory stimulus cue, but that some listeners chose to use the visual information cue to single-band listen while others ignored it and used multiple-band listening in that condition.

Adult↗