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PubMed2006

Imaging alcohol cue exposure in alcohol dependence using a PET 15O-H2O paradigm: results from a pilot study.

Craving is a commonly used term to describe an intense desire for a substance or behaviour; however, its underlying neurobiology is not fully characterized. We have successfully used a cue exposure paradigm with functional neuro-imaging (H2 15O PET; PET, positron emission tomography) in abstinent opiate addicts. This study showed that salient cue exposure results in activation in the left anterior cingulate/mediofrontal cortex and elicited craving correlated with activity in the left orbitofrontal cortex. We therefore aimed to replicate this study in alcohol dependence to see if a similar pattern of neural activation occurred. We recruited six abstinent alcohol-dependent and six non-dependent subjects who each underwent a 12-run PET scan using H2 15O to measure changes in regional blood flow during exposure to an alcoholic drink or its visually matched non-alcoholic drink. Physiological data and subjective ratings were also recorded. Statistical parametric mapping (SPM99) was used to analyse the PET images. Compared with control subjects, abstinent alcohol-dependent subjects rated their alcohol craving higher at baseline and throughout the study, but there was no significant change in the scores in response to the cues in either group. SPM analysis across all subjects showed significant activation in the occipital cortex in response to the alcohol cue as compared with the neutral one. Analysis of the same regions that were activated in the opiate study, revealed significant increases in signal activation in the left medial prefrontal area, but only in abstinent alcohol-dependent subjects. In conclusion, in abstinent alcohol dependence we suggest that a simple cue exposure paradigm is not sufficiently powerful in functional imaging studies to determine the underlying neurobiology of subjective craving. Comparisons with the finding in opiate dependence suggest a shared region, the anterior cingulate/left medial prefrontal cortex is involved in the cue response in dependent subjects but not controls.

Adult↗
PubMed1995

Inertial, substratal and landmark cue control of hippocampal CA1 place cell activity.

Hippocampal 'place cells' discharge when a rat occupies a location that is fixed in relation to environmental landmarks. A principal goal of this study was to determine whether hippocampal place cell activity could be influenced by inertial cues. Water-deprived rats were trained in a square-walled open field in a dark room. The behavioral task required alternating visits to water reservoirs in the centre and in the four corners of the arena. The rat and arena were rotated in total darkness through +/-90, 180 or 270 degrees C. The next water reward was then presented in the corner at the same position relative to the outside room as before the rotation. A cue card was later illuminated in this corner as a visual cue for the extra-arena (room) reference frame. Fifteen out of 97 recorded hippocampal CA1 complex spike cells had spatially selective discharges in non-central parts of the arena. After arena rotations, the firing fields of three units shifted between corners of the arena to maintain a fixed orientation relative to the room. This indicates that the hippocampus updated its representation of the position and heading direction of the rat using vestibular-derived inputs concerning rotation angle. Other spatially selective discharges were guided to landmark cues (cue card or position of the reward: two units) or arena-locked 'substratal' cues (eight units). In six cells, place cell activity suddenly ceased or appeared following rotations. These results provide evidence for contributions of inertial as well as substratal and landmark information to hippocampal spatial representations.

Animals↗
PubMed2005

Contextual cues associated with nicotine administration increase arc mRNA expression in corticolimbic areas of the rat brain.

Conditioned responses to cues associated with the administration of drugs of misuse are an impediment to continued abstinence for drug-free addicted individuals. In order to study the neuroanatomical and cellular response of the brain to cues associated with nicotine administration, we conditioned Sprague-Dawley rats to receive an ascending dose regimen of nicotine over 14 days in two distinct non-home cage environments and assessed expression of the early response gene arc in corticolimbic areas in response to the nicotine-associated context. All of the rats received the same dose regimen of nicotine. Three days after the last training day, the rats were exposed to the test environment. The rats that had previously received nicotine exhibited increased motor activity compared with the rats that had received saline in the test environment. After 45 min in the test environment, brains were taken for Northern blotting and in situ hybridization analysis, which revealed an increase in levels of activity-regulated, dendritically localized mRNA for arc in a variety of brain regions (medial and lateral prefrontal cortices, cingulate cortex, primary sensory cortex, sensorimotor cortex, ventral striatum and amygdala). Plasma corticosterone levels were not different between the groups, suggesting that exposure to nicotine cues is insufficient to activate the hypothalamo-pituitary-adrenal axis. Given that Arc plays a direct role in neuronal plasticity and memory consolidation, its induction by nicotine-associated cues in brain regions critical for cognitive and emotional processing suggests that rats may be learning that these cues are no longer necessarily predictive of nicotine administration. Further work will be needed in order to assess the role of arc expression in the extinction of conditioned responses to drug-paired cues.

Animals↗
PubMed2006

Selective excitotoxic lesions of the hippocampus and basolateral amygdala have dissociable effects on appetitive cue and place conditioning based on path integration in a novel Y-maze procedure.

The hippocampus and amygdala are thought to be functionally distinct components of different learning and memory systems. This functional dissociation has been particularly apparent in pavlovian fear conditioning, where the integrity of the hippocampus is necessary for contextual conditioning, and of the amygdala for discrete cue conditioning. Their respective roles in appetitive conditioning, however, remain equivocal mainly due to the lack of agreement concerning the operational definition of a 'context'. The present study used a novel procedure to measure appetitive conditioning to spatial context or to a discrete cue. Following selective excitotoxic lesions of the hippocampus (HPC) or basolateral amygdala (BLA), rats were initially trained to acquire discrete CS-sucrose conditioning in a Y-maze apparatus with three topographically identical chambers, the chambers discriminated only on the basis of path integration. The same group of animals then underwent 'place/contextual conditioning' where the CS presented in a chamber assigned as the positive chamber was paired with sucrose, but the same CS presented in either of the other two chambers was not. Thus, spatial context was the only cue that the animal could use to retrieve the value of the CS. HPC lesions impaired the acquisition of conditioned place preference but facilitated the acquisition of cue conditioning, while BLA lesions had the opposite effect, retarding the acquisition of cue conditioning but leaving the acquisition of conditioned place preference intact. Here we provide strong support for the notion that the HPC and BLA subserve complementary and competing roles in appetitive cue and contextual conditioning.

Amygdala↗
PubMed2006

The contribution of monocular depth cues to scene perception by pigeons.

The contributions of different monocular depth cues to performance of a scene perception task were investigated in 4 pigeons. They discriminated the sequential depth ordering of three geometric objects in computer-rendered scenes. The orderings of these objects were specified by the combined presence or absence of the pictorial cues of relative density, occlusion, and relative size. In Phase 1, the pigeons learned the task as a direct function of the number of cues present. The three monocular cues contributed equally to the discrimination. Phase 2 established that differential shading on the objects provided an additional discriminative cue. These results suggest that the pigeon visual system is sensitive to many of the same monocular depth cues that are known to be used by humans. The theoretical implications for a comparative psychology of picture processing are considered.

Animals↗
PubMed2006

Environmental cues, alcohol seeking, and consumption in baboons: effects of response requirement and duration of alcohol abstinence.

BACKGROUND: Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions. METHODS: Alcohol drinking was established in 4 baboons. A sequence of lights and tones was presented during daily 3-hour sessions. First, cues were presented alone and no programmed contingencies were in effect. Second, cues were paired with 3 linked components consisting of different behavioral contingencies leading to and concluding with access to alcohol for self-administration in the last component (i.e., a chained schedule of alcohol reinforcement). Third, the effects of withholding alcohol access (i.e., forced abstinence) and increasing the number of lever responses required per drink were evaluated. RESULTS: Cues paired with a chained schedule of alcohol reinforcement engendered behaviors that brought baboons into contact with alcohol-related cues and occasioned operant responding that facilitated access to alcohol (alcohol seeking) during components that preceded alcohol access. Increasing the response requirement for each drink decreased the number of drinks and volume of alcohol consumed, but did not alter alcohol seeking. On the first session after 14 days of alcohol abstinence, latency to complete the operant requirement that produced alcohol access was decreased while both alcohol self-administration and volume of alcohol consumed were increased. CONCLUSIONS: Alcohol self-administration and consumption were sensitive to increases in response requirement and duration of alcohol abstinence, while seeking was only enhanced by duration of alcohol abstinence. This animal model may be useful to further examine the interactions between environmental cues and behaviors associated with seeking and consumption of alcohol and to evaluate the efficacy of potential alcohol treatment drugs on these behaviors.

Alcohol Drinking↗
PubMed2002

Contribution of spectral cues to human sound localization.

The contribution of spectral cues to human sound localization was investigated by removing cues in 1/2-, 1- or 2-octave bands in the frequency range above 4 kHz. Localization responses were given by placing an acoustic pointer at the same apparent position as a virtual target. The pointer was generated by filtering a 100-ms harmonic complex with equalized head-related transfer functions (HRTFs). Listeners controlled the pointer via a hand-held stick that rotated about a fixed point. In the baseline condition, the target, a 200-ms noise burst, was filtered with the same HRTFs as the pointer. In other conditions, the spectral information within a certain frequency band was removed by replacing the directional transfer function within this band with the average transfer of this band. Analysis of the data showed that removing cues in 1/2-octave bands did not affect localization, whereas for the 2-octave band correct localization was virtually impossible. The results obtained for the 1-octave bands indicate that up-down cues are located mainly in the 6-12-kHz band, and front-back cues in the 8-16-kHz band. The interindividual spread in response patterns suggests that different listeners use different localization cues. The response patterns in the median plane can be predicted using a model based on spectral comparison of directional transfer functions for target and response directions.

Adult↗
PubMed2004

Masker-first advantage for cues in informational masking.

The detectability of a pure-tone signal may be reduced by adding a small number of randomly drawn masker tones remote from the signal frequency, an effect attributed to informational masking. A pretrial cue consisting of either the upcoming signal or masker releases informational masking, but a pretrial cue of the signal-plus-masker stimulus does not. In these experiments the relative potency of pre- and posttrial cues in releasing informational masking was examined. In separate conditions the masker-alone and signal-plus-masker stimuli were cues. The results indicated a masker-first advantage, i.e., sensitivity was superior when a masker cue preceded a yes/no trial interval compared to (a) when a signal-plus-masker preceded the trial, and (b) when either cue type followed the yes/no trial interval. A masker-first advantage was also obtained when the results from a two-interval forced-choice same/different task were examined. In contrast, a masker-first advantage was not obtained when the frequency of the signal to be detected was random. For detection tasks using random multi-tone maskers there may be differences in processing efficiency depending on the order in which stimuli are presented. The "masker-first advantage" may depend, in part, on observers maintaining their attention at the signal frequency.

Acoustic Stimulation↗
PubMed2004

Relative contributions of temporal and place pitch cues to fundamental frequency discrimination in cochlear implantees.

The effect of the filter bank on fundamental frequency (F0) discrimination was examined in four Nucleus CI24 cochlear implant subjects for synthetic stylized vowel-like stimuli. The four tested filter banks differed in cutoff frequencies, amount of overlap between filters, and shape of the filters. To assess the effects of temporal pitch cues on F0 discrimination, temporal fluctuations were removed above 10 Hz in one condition and above 200 Hz in another. Results indicate that F0 discrimination based upon place pitch cues is possible, but just-noticeable differences exceed 1 octave or more depending on the filter bank used. Increasing the frequency resolution in the F0 range improves the F0 discrimination based upon place pitch cues. The results of F0 discrimination based upon place pitch agree with a model that compares the centroids of the electrical excitation pattern. The addition of temporal fluctuations up to 200 Hz significantly improves F0 discrimination. Just-noticeable differences using both place and temporal pitch cues range from 6% to 60%. Filter banks that do not resolve the higher harmonics provided the best temporal pitch cues, because temporal pitch cues are clearest when the fluctuation on all channels is at F0 and preferably in phase.

Adult↗
PubMed2005

Effects of cochlear hearing loss on perceptual grouping cues in competing-vowel perception.

This study compared how normal-hearing listeners (NH) and listeners with moderate to moderately severe cochlear hearing loss (HI) use and combine information within and across frequency regions in the perceptual separation of competing vowels with fundamental frequency differences (deltaF0) ranging from 0 to 9 semitones. Following the procedure of Culling and Darwin [J. Acoust. Soc. Am. 93, 3454-3467 (1993)], eight NH listeners and eight HI listeners identified competing vowels with either a consistent or inconsistent harmonic structure. Vowels were amplified to assure audibility for HI listeners. The contribution of frequency region depended on the value of deltaF0 between the competing vowels. When deltaF0 was small, both groups of listeners effectively utilized deltaF0 cues in the low-frequency region. In contrast, HI listeners derived significantly less benefit than NH listeners from deltaF0 cues conveyed by the high-frequency region at small deltaF0's. At larger deltaF0's, both groups combined deltaF0 cues from the low and high formant-frequency regions. Cochlear impairment appears to negatively impact the ability to use F0 cues for within-formant grouping in the high-frequency region. However, cochlear loss does not appear to disrupt the ability to use within-formant F0 cues in the low-frequency region or to group F0 cues across formant regions.

Acoustic Stimulation↗
PubMed2006

Temporal and spectral cues in Mandarin tone recognition.

This study evaluates the relative contributions of envelope and fine structure cues in both temporal and spectral domains to Mandarin tone recognition in quiet and in noise. Four sets of stimuli were created. Noise-excited vocoder speech was used to evaluate the temporal envelope. Frequency modulation was then added to evaluate the temporal fine structure. Whispered speech was used to evaluate the spectral envelope. Finally, equal-amplitude harmonics were used to evaluate the spectral fine structure. Results showed that normal-hearing listeners achieved nearly perfect tone recognition with either spectral or temporal fine structure in quiet, but only 70%-80% correct with the envelope cues. With the temporal envelope, 32 spectral bands were needed to achieve performance similar to that obtained with the original stimuli, but only four bands were necessary with the additional temporal fine structure. Envelope cues were more susceptible to noise than fine structure cues, with the envelope cues producing significantly lower performance in noise. These findings suggest that tonal pattern recognition is a robust process that can make use of both spectral and temporal cues. Unlike speech recognition, the fine structure is more important than the envelope for tone recognition in both temporal and spectral domains, particularly in noise.

Acoustic Stimulation↗
PubMed1979

Auditory lateralization in monkeys: an examination of two cues serving directional hearing.

In assigning binaural ongoing time differences (phase) as the cue for localization of low frequencies, and binaural intensity differences as the cue for localization of high frequencies, the duplex theory has successfully accounted for human directional hearing of tones. Sensitivity of monkeys to these cues was examined in two experiments. The dependencies on frequency of interaural intensity difference thresholds (lateralization experiment I) and time difference thresholds (lateralization experiment II) were determined behaviorally on three monkeys (M. nemestrina). The range of frequencies was from 125 Hz to 8 kHz in experiment I and from 250 Hz to 2 kHz in experiment II. The results indicate that the duplex theory is applicable to monkeys. However, monkeys are less sensitive than man to both binaural cues. The shortest time disparity monkeys discriminate is 42 microseconds at 1.5 kHz and the smallest intensity difference is 3.5 dB at 500 Hz. Good agreement between the present findings and localization measurements [C. H. Brown et al., J. Acoust. Soc. Am. 63, 1484-1492 (1978)] suggests: (a) that monkeys utilize time disparity cues through higher frequencies than man; and (b) that inaccurate localization by monkeys at high frequencies reflects decreasing sensitivity to interaural intensity cues.

Acoustic Stimulation↗
PubMed1992

The use of static and dynamic vowel cues by multichannel cochlear implant users.

Multichannel cochlear implant users vary greatly in their word-recognition abilities. This study examined whether their word recognition was related to the use of either highly dynamic or relatively steady-state vowel cues contained in /bVb/ and /wVb/ syllables. Nine conditions were created containing different combinations of formant transition, steady-state, and duration cues. Because processor strategies differ, the ability to perceive static and dynamic information may depend on the type of cochlear implant used. Ten Nucleus and ten Ineraid subjects participated, along with 12 normal-hearing control subjects. Vowel identification did not differ between implanted groups, but both were significantly poorer at identifying vowels than the normal-hearing group. Vowel identification was best when at least two kinds of cues were available. Using only one type of cue, performance was better with excised vowels containing steady-state formants than in "vowelless" syllables, where the center vocalic portion was deleted and transitions were joined. In the latter syllable type, Nucleus subjects identified vowels significantly better when /b/ was the initial consonant; the other two groups were not affected by specific consonantal context. Cochlear implant subjects' word-recognition was positively correlated with the use of dynamic vowel cues, but not with steady-state cues.

Adult↗
PubMed2005

Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination.

The zolpidem discriminative cue is mediated by GABA(A)-alpha1 receptors, whereas the chlordiazepoxide cue may be mediated via non-alpha1 GABA(A) receptors because compounds with selective affinity for GABA(A)-alpha1 receptors fully generalize to the former cue. We predicted that L-838,417 [7-tert-butyl-3-(2,5-difluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine], a partial agonist at non-alpha1 GABA(A) receptors and an antagonist at GABA(A)-alpha1 receptors, would generalize to the chlordiazepoxide but not the zolpidem-discriminative cue. SL651498 [6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyridol[3,4-b]indol-1-one] is a full agonist at GABA(A)-alpha2 receptors, with lower efficacy at GABA(A)-alpha3 receptors and least efficacy at GABA(A)-alpha1 and GABA(A)-alpha5 receptors. Because SL651498 has efficacy at GABA(A)-alpha1 receptors, we anticipated that it would generalize to both discriminative cues. Rats were trained to discriminate either zolpidem (3 mg/kg) or chlordiazepoxide (5 mg/kg) from vehicle using a two-lever operant procedure. The generalization profiles of L-838,417 and SL651498 were compared with nonselective full agonists, GABA(A)-alpha1-selective ligands zolpidem and CL218,872 [3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo[4,3-b]pyridazine], the nonselective partial agonist bretazenil, and the novel anxioselective drug ocinaplon. A nonselective partial agonist was included because L-838,417 and SL651498 are partial agonists at some GABA(A) receptors, and this property may influence their generalization profiles. All nonselective full agonists and ocinaplon fully generalized to both cues. CL218,872 and zolpidem generalized to zolpidem only, whereas L-838,417 fully generalized to chlordiazepoxide only. SL651498 fully generalized to chlordiazepoxide and occasioned significant zolpidem-appropriate responding. Bretazenil was similar to SL651498. In conclusion, at this training dose, the chlordiazepoxide-discriminative stimulus is mediated primarily via non-alpha1 GABA(A) receptors and the generalization profiles of the ligands tested seem to correspond with their in vitro profiles at GABA(A) receptor subtypes.

Animals↗
PubMed2004

Internal models and contextual cues: encoding serial order and direction of movement.

During reaching, the brain may rely on internal models to transform desired sensory outcomes into motor commands. This transformation depends on both the state of the limb and the cues that can identify the context of the movement. How are contextual cues and information about state of the limb combined in the computations of internal models? We considered a reaching task where forces on the hand depended on both the direction of movement (state of the limb) and order of that movement in a predefined sequence (contextual cue). When the cue was available, the motor system formed an internal model that used both serial order and target direction to program motor commands. Assuming that the internal model was formed by a population code through a combination of unknown basis elements, the sensitivity of the bases with respect to state of the limb and contextual cue should dictate how error in one type of movement affected all other movement types. Using a state-space theory, we estimated this generalization function and identified the adaptive system from trial-by-trial changes in performance. The results implied that the basis elements were tuned to direction of movement but output of each basis at its preferred direction was multiplicatively modulated by a weak tuning with respect to the contextual cue. Activity fields that multiplicatively encode diverse sources of information may serve as a general mechanism for a single network to produce context-dependent motor output.

Cues↗
PubMed2003

Cue-evoked firing of nucleus accumbens neurons encodes motivational significance during a discriminative stimulus task.

The nucleus accumbens (NAc) has long been thought of as a limbic-motor interface. Despite behavioral and anatomical evidence in favor of this idea, little is known about how NAc neurons encode information about motivationally relevant environmental cues and use this information to affect motor action. We therefore investigated the firing of these neurons during the performance of a discriminative stimulus (DS) task using simultaneous multiple single-unit recordings in rats. In this task, two stimuli are randomly presented to the animal: a DS, which signals the availability of a sucrose reward contingent on an operant response, and a similar but nonrewarded stimulus (NS). Subpopulations of NAc neurons increased or decreased their firing in association with several distinct components of the task. In this paper, we investigate cue- and operant-responsive neurons. Neurons excited and inhibited by cues showed larger firing changes in response to the DS than the NS and larger changes when the animal made an operant response to the cue than when the animal failed to respond. Excitations during operant responding were not modulated by the information contained by the cue, whereas inhibitions during operant responding were somewhat larger if the operant response occurred during the DS and somewhat smaller if they occurred in the absence of a cue. These results are consistent with the hypothesis that the firing of subpopulations of NAc neurons encode both the predictive value of environmental stimuli and the specific motor behaviors required to respond to them.

Animals↗
PubMedDate not supplied

Acoustic and electrical pattern analysis of consonant perceptual cues used by cochlear implant users.

It is hypothesized that for postlingually deafened adult cochlear implant (CI) users, a significant source of their perceptual performance variability is attributable to differences in their ability to discriminate the basic perceptual cues that are important in speech recognition. Previous research on 'electric hearing' has identified consistent perceptual cues for vowel recognition. However, the results on consonant perception by CI users are less clear. The primary purpose of this study is to present a quantitative method of evaluating potential 'electric cues' used by CI users in consonant identification. Since the actual input signals to the auditory periphery of CI users are electric in nature, we elected to measure the CI electric discharge patterns in addition to the original acoustic waveforms. The characteristics of the electric discharge patterns in response to intervocalic consonants were quantified and correlated with the dimensions of CI patients' perceptual spaces, which were computed from multidimensional scaling analyses of their consonant confusion matrices. The results agree with most, but not all, commonly accepted acoustic cues used by normal-hearing listeners. The correlation findings also suggest that CI users employ different sets of 'electric cues' in perceiving consonants that differ in their manner of articulation. Specifically, spectral and temporal cues associated with slowly changing formant structures and transitions, and features associated with frication and high-frequency noise, are all highly correlated with the perceptual dimensions of all CI users. However, rapidly changing formant transitions, such as those present in stop consonants, did not appear to play a significant role in consonant recognition by more poorly performing CI subjects. The perceptual results were consistent with our physical findings that the SPEAK coding strategy partially degraded the rapidly changing formant transitions.

Acoustic Stimulation↗
PubMed2005

Different effects of exogenous cues in a visual detection and discrimination task: delayed attention withdrawal and/or speeded motor inhibition?

Several studies examining spatial attention have found a discrepancy regarding the effects of exogenous cues on reaction times in visual detection and discrimination tasks. Namely, across a wide range of cue-target intervals, responses are slower for targets at cued than at uncued locations (inhibition of return) in detection tasks, whereas responses are faster for targets at cued than at uncued locations (facilitation) in discrimination tasks. Two hypotheses were proposed to account for this discrepancy. First, attention may dwell much longer on the exogenously cued location in discrimination tasks because stimuli have to be identified (i.e., the delayed attention withdrawal hypothesis). Secondly, due to increased motor preparation in detection tasks, cue-induced motor inhibition may rise much faster in these tasks than in discrimination tasks (i.e., the speeded motor inhibition hypothesis). We examined to what extent these hypotheses can account for effects of exogenous cues in a detection and discrimination task on the extrastriate P1 component, and the onset of motor activation, as indexed by the lateralized readiness potential. Some support was found for the delayed attention withdrawal hypothesis, as task-dependent cueing effects were found on the P1 component. Other aspects of our data, however, indicate that motor inhibition is also involved. Based on these findings, we propose that effects of exogenous cues in detection and discrimination tasks are determined by the interplay between two mechanisms, of which the time courses of activation may be modulated by the specific setting.

Adult↗