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At least 523 records · Page 29Linked to original sources
PubMed2026

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans↗
PubMed2000

Similarities in the development of place and cue navigation by rats in a swimming pool.

The development of place and cue spatial navigation was evaluated in 18-, 19-, and 20-day-old males in the Morris water task (MWT). Past work has suggested that place and cue learning develop at different rates, suggesting that the two aspects of spatial navigation have different neural substrates. In the present study, a new training methodology was used in which animals received spaced training trials, drying and warming in between trials to maintain body temperature, and two probe trial-dependent measures to evaluate spatial memory performance. All ages of rats had lower latencies on the cue task than on the place task. Nevertheless, 18-day-old rats did not learn either task as measured by acquisition latencies and probe trial-dependent measures. The 19- and 20-day-old rats learned both the place and cue tasks as measured by acquisition latency and direct swims to the correct platform location on the probe trial, and both 19- and 20-day-old rats demonstrated a strong spatial bias to the former platform location on the place probe trial but not on the cue probe trial. The finding that developmental onset of place and cue spatial navigation is rapid and complete by day 19 is discussed in relation to contemporary theories of spatial navigation.

Aging↗
PubMed2006

The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue-elicited heroin craving in Chinese.

Heroin dependence is resulted from the interaction between multiple genetic and environmental factors. Subjective craving is considered to be a central phenomenon, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers. Dopamine pathway has been implicated in the cue-elicited craving for a variety of addictive substances. The objective of this study was to test the hypothesis that heroin addicts carrying specific variants in dopamine-related genes would have higher levels of craving following exposure to a heroin-related cue. Craving induced by a series of exposure to heroin-related cue was assessed in a cohort of Chinese heroin abuser (n = 420) recruited from natural abstinence center at Shanghai. Significantly stronger cue-elicited heroin craving was found in individuals carrying D2 dopamine receptor gene (DRD2) TaqI RFLP A1 allele than the non-carriers (P < 0.001). Furthermore, we did not observed significant association of cue-elicited craving with the nine-repeat allelic variants in dopamine transporter gene (DAT) SLC6A3 and with the dinucleotide repeat polymorphism (DRP) 148bp allele in D5 dopamine receptor gene (DRD5). The results of our study suggest that human dopamine pathway be involved in cue-induced heroin craving, and indicate a potential genetic risk factor for persistent heroin behavior and relapse.

Adolescent↗
PubMed2002

Cue reactivity as a predictor of outcome with bulimia nervosa.

The present study sought to evaluate specific hypotheses concerning the relation between cue reactivity and outcome among women with bulimia nervosa. Participants were 135 women aged between 17 and 45 years with a current, primary diagnosis of bulimia nervosa who participated in a randomized clinical trial evaluating the additive efficacy of exposure and nonexposure-based behavior therapy, to a core of cognitive behavior therapy (CBT). Physiological, self-report, and behavioral measures of cue reactivity to individualized high-risk binge foods were obtained at pretreatment and posttreatment. Primary, secondary, and tertiary outcome measures are reported for posttreatment and six-month follow-up. Self-report measures of cue reactivity at posttreatment were significantly positively associated with symptomatology at posttreatment. Cue reactivity at posttreatment was significantly positively associated with symptomatology at 6-month follow-up. However, cue reactivity at posttreatment did not contribute to the prediction of outcome at follow-up over and above posttreatment outcome. The notion that pretreatment cue reactivity may predict which treatment modality will be most beneficial (exposure or nonexposure-based treatment), as measured by reductions in symptomatology at posttreatment could not be supported. Implications for future research are discussed.

Adolescent↗
PubMed2001

Changes in cue reactivity following treatment for bulimia nervosa.

OBJECTIVE: To examine changes in cue reactivity following cognitive-behavior therapy (CBT) for bulimia nervosa and to evaluate whether changes are associated with treatment modality or treatment outcome. METHOD: Subjects were 135 women (17-45 years old) with a current, primary diagnosis of bulimia nervosa. They were participants in a randomized clinical trial examining the additive efficacy of exposure and nonexposure-based behavior therapy to a core of CBT. Physiological, self-report, and behavioral measures of cue reactivity to individualized high-risk binge foods were obtained at pretreatment and posttreatment. Primary, secondary, and tertiary outcome measures are reported for posttreatment. RESULTS: Bulimic patients experienced significant changes in cue reactivity following treatment. With the exception of salivary reactivity, patients experienced less reactivity at posttreatment. Changes in cue reactivity were not related to treatment modality, but were related to positive treatment outcome for self-report measures of cue reactivity. DISCUSSION: Favorable treatment outcome among bulimic women is associated with low cue reactivity on self-report measures at posttreatment.

Adolescent↗
PubMed2005

Impact of internal versus external cueing on driving performance in people with Parkinson's disease.

Numerous aspects of driving performance seem compromised in people with Parkinson's disease (PD). Measures of cognitive impairment consistently correlate with poor driving simulator performance in this population; however, the effects of specific cognitive difficulties on discrete aspects of driving behavior have not been investigated thoroughly. Previous studies have demonstrated that people with PD exhibit difficulties internally cueing cognitive processes. This study examined the impact of impaired internal cueing on specific driving behaviors. A simulator measured the driving behavior of 18 current drivers in the mild-to-moderate stages of PD and 18 matched controls. Participants navigated through different driving conditions where the opportunity to use internal and external cues was manipulated. People with PD exhibited difficulties using internal cues to regulate driving behavior around traffic signals and curves. Instead of using internal cues, participants with PD were more reliant on external cues to regulate driving behavior. They were also less able to adapt their driving behavior to suit driving conditions. Because all participants with PD were current drivers in the mild-to-moderate stages of the disease, findings challenge the widely-held assumption that cognitive difficulties only impact on driving performance in the moderate-to-severe stages of PD.

Accidents, Traffic↗
PubMed2001

Semantic cueing effects on word retrieval in aphasic patients with lexical retrieval deficit.

We examined lexical access in word production, focusing on lexical retrieval deficit in aphasic patients. These patients were asked to name one picture at a time and we investigated how semantic cueing affected their ability to retrieve the word. When the subjects experienced a retrieval failure, they were presented with one type of cue, and then they tried to name the target picture again. Four types of cues were used: phonological, semantic related, semantic category member, and baseline cue. Both phonological and semantically related cues improved performance. In contrast, category member cues had no effects on releasing the retrieval block. These results can be explained by an interactive activation model in word production (Dell & O'Seaghdha, 1991).

Adult↗
PubMed2002

Proximal versus distal cue utilization in spatial navigation: the role of visual acuity?

Proximal versus distal cue use in the Morris water maze is a widely accepted strategy for the dissociation of various problems affecting spatial navigation in rats such as aging, head trauma, lesions, and pharmacological or hormonal agents. Of the limited number of ontogenetic rat studies conducted, the majority have approached the problem of preweanling spatial navigation through a similar proximal-distal dissociation. An implicit assumption among all of these studies has been that the animal's visual system is sufficient to permit robust spatial navigation. We challenged this assumption and have addressed the role of visual acuity in spatial navigation in the preweanling Fischer 344-N rat by training animals to locate a visible (proximal) or hidden (distal) platform using double or null extramaze cues within the testing environment. All pups demonstrated improved performance across training, but animals presented with a visible platform, regardless of extramaze cues, simultaneously reached asymptotic performance levels; animals presented with a hidden platform, dependent upon location of extramaze cues, differentially reached asymptotic performance levels. Probe trial performance, defined by quadrant time and platform crossings, revealed that distal-double-cue pups demonstrated spatial navigational ability superior to that of the remaining groups. These results suggest that a pup's ability to spatially navigate a hidden platform is dependent on not only its response repertoire and task parameters, but also its visual acuity, as determined by the extramaze cue location within the testing environment. The standard hidden versus visible platform dissociation may not be a satisfactory strategy for the control of potential sensory deficits.

Aging↗
PubMed1996

Auditory cues and inhibition of return: the importance of oculomotor activation.

We studied the effects of eccentric auditory cues to clarify the conditions that evoke inhibition of return (IOR). We found that auditory cues positioned 12 degrees to the left or right of midline failed to produce IOR whereas visual cues produced IOR under the same experimental conditions. The eccentric auditory cues elicited automatic orienting as evidenced by more rapid detection of cued than uncued visual targets at short stimulus onset asynchrony. Yet these same cues did not produce IOR unless observers were required to saccade to the cue and back to center before generating a manual detection response. Thus, under the conditions examined herein automatic orienting was not sufficient to evoke IOR, but oculomotor activation appeared to be essential. The functional significance of IOR and the question of modality-specific orienting processes are considered.

Adolescent↗
PubMed1993

Central alpha-2 adrenoceptors are responsible for a clonidine-induced cue in a rat drug discrimination paradigm.

Clonidine produces an interoceptive discriminative stimulus or "cue" in rat drug discrimination studies. This cue may be mediated by its alpha-2 adrenoceptor agonist properties and/or its affinity for the non-adrenoceptor imidazoline preferring receptor. Six rats were trained to respond differentially after receiving clonidine (0.02 mg kg-1, IP) or a saline vehicle. The alpha-2 adrenoceptor agonists clonidine, UK14, 304 and rilmenidine, which bind to the imidazoline preferring receptor, and guanabenz which does not, dose-dependently substituted for (i.e. > 80% total responding was clonidine associated) the clonidine-induced cue in doses up to 0.02, 0.16, 1.25 and 0.32 mg kg-1, respectively. Furthermore, the cue was blocked when clonidine was given in combination with 30-min pretreatments of the highly selective alpha-2 adrenoceptor antagonists RX811059 (2.5 mg kg-1) and fluparoxan (3 mg kg-1). Since the clonidine-induced cue was substituted for by guanabenz, which does not act at the imidazoline-preferring receptor, and antagonised by RX811059 and fluparoxan it appears to be mediated by alpha-2 adrenoceptors. Moreover, abolition of the clonidine-induced cue did not occur with the peripherally acting alpha-2 adrenoceptor antagonist L659, 066 suggesting it involves central as opposed to peripheral sites.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Hand deviations away from visual cues: indirect evidence for inhibition.

Previous research has demonstrated that when a stimulus is to be ignored, the path of motion towards a target (saccade or manual reach) deviates away from the to-be-ignored stimulus. Path deviations in saccade and reaching tasks have, however, been observed in very different situations. In the saccade tasks subjects initially attended to a cue, then disengaged attention while saccading to a target. By contrast, in the selective reaching tasks attention was continuously withdrawn from the to-be-ignored stimulus, as this was irrelevant throughout the experiment. In the two experiments reported here, cues similar to those studied in saccade tasks are examined with selective reaching procedures. Experiment 1 shows that when a coloured light-emitting diode cue, upon which subjects engage and then subsequently disengage attention, is close to the responding hand, the hand deviates away from the cue. Experiment 2 confirms this cue avoidance by showing that, compared with central fixation alone, the hand veers away from a central cue. These results confirm that the path deviations observed in saccades can also be obtained in manual reaching movements. Such findings support the notion that eye and hand movements are both affected by inhibitory mechanisms of attention.

Acoustic Stimulation↗
PubMed1997

The removal of binocular cues disrupts the calibration of grasping in patients with visual form agnosia.

The present study tested the idea that the visuomotor systems mediating prehension do not have independent access to pictorial cues processed by perceptual mechanisms. Individuals with visual form agnosia, whose perceptual systems are compromised but who have intact visuomotor control, were examined to determine whether they could use pictorial scene cues to calibrate manual prehension when binocular information was removed. The removal of binocular cues produced considerable disruptions in size-constancy of grip aperture, which, combined with earlier observations in normal subjects, suggests that binocular cues are of primary importance in calibration of grasping. In the absence of binocular vision, normal subjects can use pictorial information, information that is severely compromised in individuals with visual form agnosia, to compute the distance (and thus the size) of the goal object. Thus, individuals with visual form agnosia must rely on a retinal image that remains uncalibrated, leading to inaccurate calibrations of grip aperture. The fact that these individuals scaled their grasp much less accurately under the monocular viewing condition, despite showing normal binocular grasping, suggests that pictorial cues to depth, which are presumably processed by mechanisms mediating our perception of objects and events in the world, can be accessed by visuomotor mechanisms only indirectly. These results, together with others, suggest that the visuomotor system 'prefers' to use binocular information and uses pictorial cues only as a last resort.

Adult↗
PubMed2003

Reinstatement of ethanol-seeking behavior by drug cues following single versus multiple ethanol intoxication in the rat: effects of naltrexone.

RATIONALE: A positive relationship exists between chronic ethanol intoxication experiences and the severity of neural hyperactivity and withdrawal seizures. An important possibility is that withdrawal reactions also influence the motivation to obtain and consume ethanol. OBJECTIVES: To test this hypothesis, the effects of ethanol-cues on the recovery of extinguished ethanol-seeking and the reversal of this effect by naltrexone, were determined in non-dependent rats and in rats subjected to single versus repeated ethanol intoxications. METHODS: Rats were trained to self-administer and discriminate between 10% ethanol and water. Instrumental responding then was extinguished and the effects of exposure to ethanol and water cues were determined. Subsequently, rats were divided into three groups and exposed to control vapor (CTRL), to 12-day ethanol vapor prior to withdrawal (SW), or to three cycles of 3-day intoxication experiences (MW), respectively. Following intoxication, reacquisition and breaking point for ethanol self-administration and cues-induced reinstatement of drug-seeking were investigated. RESULTS: Ethanol cues significantly reinstated responding in the pre- and post-dependence test, but no significant differences between groups was observed. However, the ability of naltrexone to attenuate the response-reinstatement was significantly reduced in MW rats. Moreover, in the progressive ratio schedule, the breaking points for ethanol were significantly increased in the MW animals. CONCLUSIONS: The results suggest that repeated intoxication did not enhance cue-induced reinstatement of ethanol-seeking. However, naltrexone effects on cues-induced "relapse" appear to be attenuated in MW rats.

Alcoholic Intoxication↗
PubMed2004

Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics.

RATIONALE: Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and maintenance of drug-seeking behavior. OBJECTIVES: Alcohol-associated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a motivational response that triggers relapse in alcohol-dependent patients. METHODS: We used functional magnetic resonance imaging and visual alcohol-associated and control cues to assess brain activation in ten abstinent alcoholics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded. RESULTS: Alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently relapsed during the observation period. A multiple regression analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning. CONCLUSIONS: This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motivational value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of relapse.

Adult↗
PubMed2004

Event-related potentials indicate motivational relevance of cocaine cues in abstinent cocaine addicts.

RATIONALE: Motivational drive and its underlying affect-related states are the core mechanisms that precede the seeking and taking of drugs in substance dependence. OBJECTIVE: The present study aimed to investigate the motivational relevance of cocaine cues and whether or not an appetitive emotional system is involved employing event-related potential (ERP) measurements. METHODS: Cocaine-addicted subjects and healthy controls were exposed to neutral and cocaine-related pictures whilst ERPs were recorded simultaneously over frontal, parietal and midline sites. RESULTS: Patients exhibited ERP amplitude discrepancies between neutral and cocaine-related pictures for N300, late slow positive wave (LSPW) and sustained slow positive wave (SSPW), whilst this effect was absent in control subjects. Differences in neutral and cocaine cue-evoked ERP waves were also found at left frontal sites for LSPW and SSPW in the patient group only. No group-specific cue-evoked ERP amplitudes were observed at parietal and midline sites. CONCLUSION: The findings confirm the assumption that cocaine cues induce motivational relevance in cocaine-dependent individuals. It is possible that exposure to cocaine cues triggers an appetitive emotional system since left frontal sites are assumed to be involved in processing positive emotional-laden stimuli. The present study provides evidence that the sensitivity of ERP correlates for cocaine cues may be an indicator of motivational and emotional processes in drug-dependent individuals.

Adult↗
PubMed2005

Alcohol-induced impulsivity in rats: an effect of cue salience?

RATIONALE: There is a common assumption that alcohol produces impulsive behaviors, thereby increasing the preference for immediate over delayed rewards. An alternative explanation, provided by alcohol myopia theory, is that alcohol alters attentional processes such that intoxicated individuals respond exclusively to the most salient cues in their environment. OBJECTIVES: We tested these two hypotheses in rats using standard (impulsivity) and modified (cue salience) versions of the delayed reinforcement task. METHODS: In the impulsivity paradigm, rats were trained to choose between a small immediate reward (2 sucrose pellets) and a large delayed reward (12 sucrose pellets after 10 s) in a T-maze. In the cue salience paradigm, a light in one arm predicted either the small or the large reward, but the arm paired with the light varied across trials. In separate experiments, we examined how changes in delay to the large reward, alcohol administration, or alcohol combined with either a serotonin agonist [para-chloroamphetamine (pCA) at doses of 0.1, 0.4, 0.7, and 1.0 mg/kg, s.c.)] or a dopamine antagonist [cis-(Z)-flupenthixol dihydrochloride (alpha-flupenthixol) at doses of 0.0125, 0.025, 0.05, and 0.1 mg/kg, i.p.] affected performance in each task. RESULTS: Increasing the delay to the large reward increased impulsivity in both paradigms, but it had no effect on responding to a salient cue. Alcohol (0.6, 0.9, 1.2, and 1.8 g/kg, i.p.) increased the choice of the immediate reward and increased the choice of the lit arm, regardless of whether it signaled the small or the large reward. pCA selectively reduced alcohol-induced impulsivity, whereas alpha-flupenthixol selectively reduced responding to a salient cue. CONCLUSIONS: Rats, like humans, are influenced by cue salience when intoxicated. Although this alcohol myopia effect could explain alcohol-induced impulsivity, the two processes are probably distinct because they are mediated by dissociable pharmacological mechanisms.

Animals↗
PubMed2006

Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese.

RATIONALE: Subjective craving, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers, is considered to be a central phenomenon in addiction. Dopamine pathway has been implicated in the mechanism underlying the cue-elicited craving for a variety of addictive substances. OBJECTIVES: The objective of this study was to test the hypothesis that heroin addicts carrying D4 dopamine receptor gene (DRD4) variable number tandem repeat (VNTR) long type allele would have higher craving after exposure to a heroin-related cue. MATERIALS AND METHODS: Craving was induced by a series of exposure to neutral and heroin-related cue and were assessed in a cohort of Chinese heroin abusers (n=420) recruited from the Voluntary Drug Dependence Treatment Center at Shanghai. RESULTS: Significantly stronger cue-elicited heroin craving was found in individuals carrying DRD4 VNTR long type allele than the non-carriers (F=31.040, p<0.001). As for baseline craving and mean change in craving responding to neutral stimuli, no significance was found (1.06+/-0.34 vs 1.07+/-0.36, F=0.067, p=0.797 and 0.42+/-0.34 vs 0.45+/-0.37, F=0.277, p=0.599, respectively). CONCLUSIONS: The results of our study suggest that DRD4 VNTR polymorphism contributes to cue-elicited craving in heroin dependence, indicating DRD4 VNTR represents one of potential genetic risk factors for cue-induced craving.

Adolescent↗
PubMed2000

Smoking-related cues elicit craving in tobacco "chippers": a replication and validation of the two-factor structure of the Questionnaire of Smoking Urges.

RATIONALE: The reliability and validity of the Questionnaire of Smoking Urges (QSU), a multi-factorial measure of cravings to smoke cigarettes has recently been called into question. OBJECTIVE: In the first phase of the present study, the reliability of the two-factor structure of QSU was examined. The new and original factor structures were then used to investigate the effects of 2 h of abstinence from smoking, and exposure to smoking-related cues, in a subset of the same sample of regular smokers. The present study also investigated the effects of smoking-related cues on QSU measures in tobacco "chippers" (occasional non-dependent smokers). METHODS: The factor structure of the QSU was investigated with a factor analysis of responses to the 32 QSU items produced by a sample of 271 regular smokers. A subset of these data was used to assess the influence of abstinence and cues on QSU factor scores. The final study used a sample of 32 tobacco chippers to assess the effect of smoking-related cues on their QSU factor scores. RESULTS: The results revealed a two-factor structure almost identical to that published by Tiffany and Drobes. In the second experiment, a brief period of abstinence significantly elevated factor 1 scores, but not factor 2 scores, compared to the non-abstinent condition. Exposure to smoking-related cues significantly elevated factor 2 scores and also tended to elevate factor 1 scores. In experiment 3, exposure to smoking-related cues significantly elevated factor 1 scores, but not factor 2 scores, in tobacco chippers. CONCLUSION: The QSU is a psychometrically sound instrument for the assessment of urges to smoke, which shows good construct validity. The two factors of the QSU show differential discriminative properties.

Adolescent↗