海洛因依赖者环境线索诱发心理生理反应

目的：了解海洛因依赖者对吸毒相关环境线索诱发反应。方法：对来自自愿戒毒机构的36例刚完成生理脱毒（康复早期）的海洛因依赖者和劳教戒毒机构112例康复期满1年的海洛因依赖者观看吸毒相关视频同时给予海洛因模拟物及吸毒用具刺激,于暴露前后自评渴求程度、情绪以及戒断症状反应;用生物反馈仪自动记录暴露前后的生理反应。结果：环境线索暴露后海洛因依赖者心理渴求、害怕／焦虑、抑郁／悲伤、戒断症状、心率、皮肤导电和肌电增高（P〈0．05）,中性／放松／自然降低（P〈0．05）。自愿戒毒机构康复早期海洛因依赖者环境诱发心率增高,比康复期满一年以上者更明显（P〈0．05）,其余与康复期长短无显著关系。结论：海洛因依赖者戒断康复期的延长并不会使渴求和环境诱发心理生理反应减弱或消褪。     

美沙酮合并心理干预对海洛因依赖者的影响

目的:评估心理干预对美沙酮维持治疗患者的应对方式、压力感受和自我效能状况的影响。方法:将美沙酮维持治疗门诊的海洛因依赖者分为研究组(n=71)和对照组(n=55)。研究组给予为期3个月的心理干预。两组在入组时,1个月后以及3个月后评定应对方式问卷(SCSQ)、压力感受量表(PSS)、自我效能量表(SES),并进行评分比较。结果:与入组时相比,研究组干预后1个月、3个月应对方式、压力感受、自我效能评分的差异均有统计学意义(P<0.01)。干预后1个月两组间积极应对方式、压力感受评分差异有统计学意义(P<0.05),消极应对方式、自我效能评分差异无统计学意义(P>0.05);干预后3个月两组间积极应对方式、消极应对方式、压力感受、自我效能评分差异均有统计学意义(P<0.05)。两组维持治疗率差异有统计学意义(P<0.01)。结论:心理干预有利于改善海洛因依赖者的应对方式和自我效能,提高美沙酮维持治疗率。     

性别对海洛因相关环境线索诱发心理生理反应的影响

目的 了解康复期海洛因依赖者对吸毒相关环境线索的心理生理反应的性别差异.方法 采用自身配对设计,173例男性和235例女性康复期海洛因依赖者观看吸毒相关视频的同时给予海洛因模拟物及吸毒用具刺激,用生物反馈仪记录诱发前、中、后的心理生理反应.结果 环境线索诱发使男女海洛因依赖者的皮温随时间变化而不同,其中诱发中与诱发后阶段比较差异有统计学意义(P＜0.05);环境线索诱发导致女性诱发中阶段的呼吸频率和诱发后阶段的皮温均低于男性(P＜0.01).结论 环境线索诱发对男女性的呼吸频率和皮温指标反应具有不同影响,且性别对皮温的影响随时间阶段的变化而不同.     

Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment

BACKGROUND: Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment (MMT). METHODS: We included 238 MMT patients according to their response to treatment and methadone dosing, along with 217 subjects without substance dependence. All were genotyped for polymorphisms of the dopamine D(1), D(2), micro-opioid and delta-opioid receptor genes. Results: The polymorphisms of the micro-opioid (118A>G), delta-opioid (921T>C), dopamine D(1) (DdeI) and D(2) (TaqI A) receptor genes were not associated with response to MMT and methadone dosing, whereas an association was found with the dopamine D(2) receptor (DRD2) 957C>T polymorphism. The 957CC carriers were more frequently non-responders to treatment (OR=2.4; p=0.02) and presented a fourfold shorter period of negative urine screening (p=0.02). No significant differences in allele frequencies were observed between the MMT patients and the control group, suggesting no association of the analyzed polymorphisms with opioid dependence. CONCLUSIONS: These results suggest that DRD2 genotype may contribute to the understanding of the interindividual variability to the response to MMT.     

Differential regional effects of methadone maintenance compared to heroin dependence on mu-opioid receptor desensitization in rat brain

Methadone maintenance therapy has been the mainstay of treatment for heroin addiction since the 1970s. Recent studies indicate that methadone is of greater relative intrinsic efficacy than the active metabolites of heroin at mu-opioid receptors and that the extent of mu-opioid receptor desensitization is dependent upon agonist efficacy. Regional differences have been found for mu-opioid receptor desensitization with chronic heroin self-administration, and a similar paradigm was employed to compare regional differences between the effects of heroin and methadone. Rats were trained to self-administer heroin i.v., and the dose available was increased incrementally to a terminal value of 6 mg/kg for each infusion. Half of these rats were allowed to continue to self-administer heroin, while dependence was maintained in the others by hourly infusions of 3 mg/kg of methadone. A separate group of animals was kept on a low dose of heroin. Activation of G-proteins by the high efficacy agonist DAMGO was decreased to a greater extent in animals treated chronically with methadone compared with those allowed to self-administer heroin in amygdala, periaqueductal gray, and subicular nucleus. Activation of G-proteins by the partial agonist endomorphin was decreased in striatum, thalamus, and amygdala in rats from all drug treatment groups, but to a greater extent in the striatum in methadone treated rats compared with the heroin groups. Elucidating the mechanisms by which methadone induces differential desensitization of mu-opioid receptors across brain regions compared with heroin could provide insights to improve the pharmacotherapy of heroin addiction.     

FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects

Olfactory function is affected by aging and deficits often result in decreasing quality of life, health and safety. The present study investigated the cortical substrate of olfactory deficits related to aging with functional Magnetic Resonance Imaging (fMRI), with a retronasal olfactory stimulation protocol using flavored aqueous solutions presented to the mouth. Activation was found in young subjects in the piriform/amygdalar region and in the orbitofrontal cortex and in other areas previously found activated in neuroimaging studies using odorized air, including insula and cerebellum. Activation was seen in similar areas in old subjects but the degree of activation was significantly lower in regions receiving primary olfactory projections (piriform cortex, entorhinal cortex, and amygdala). This result supports the hypothesis of dysfunction and/or degeneration in areas critical to olfactory processing as a major cause of olfactory deficits in the older population.     

Psychoneuroendocrine effects of methadone maintenance

A variety of neuroendocrine and psychiatric dysfunctions have been demonstrated in humans maintained on opiates, but both have not previously been examined in the same population. We performed a series of neuroendocrine challenge tests in men participating in a methadone maintenance clinic and in normal controls. Psychiatric diagnoses were made with DSM-III Criteria, using the Diagnostic Interview Schedule, and subjects also completed the Symptom Checklist. Our results in the methadone group suggest (a) near-maximal stimulation of prolactin secretion, with a blunted prolactin response to insulin hypoglycemia, (b) mild suppression of cortisol levels, but an exaggerated cortisol response to stimulation, (c) a delayed and inhibited insulin response to food ingestion with resulting mild hyperglycemia, (d) low body weight, but elevated calorie ingestion, and (e) inability to concentrate urine when dehydrated, which was partially corrected by administration of arginine vasopressin. Phobic disorder was associated with a lower prolactin response to both inhibitory and stimulatory challenges. Depression did not appear to be related to the increased cortisol response to stimulation. These results suggest several potentially fruitful areas for future investigation, including the prolactin system and anxiety disorders, nutrient ingestion and metabolism, and posterior pituitary function.     

FMRI study relevant to the Mozart effect: brain areas involved in spatial-temporal reasoning.

Behavioral studies, motivated by columnar cortical model predictions, have given evidence for music causally enhancing spatial-temporal reasoning. A wide range of behavioral experiments showed that listening to a Mozart Sonata (K.448) gave subsequent enhancements. An EEG coherence study gave evidence for a carryover from that Mozart Sonata listening condition to the subsequent spatial-temporal task in specific cortical regions. Here we present fMRI studies comparing cortical blood flow activation by the Mozart Sonata vs. other music. In addition to expected temporal cortex activation, we report dramatic statistically significant differences in activation by the Mozart Sonata (in comparison to Beethoven's Fur Elise and 1930s piano music) in dorsolateral pre-frontal cortex, occipital cortex and cerebellum, all expected to be important for spatial-temporal reasoning. It would be of great interest to explicitly test this expectation. We propose an fMRI study comparing (subject by subject) brain areas activated in music listening conditions and in spatial-temporal tasks.     

The effect of hunger state on hypothalamic functional connectivity in response to food cues

The neural underpinnings of the integration of internal and external cues that reflect nutritional status are poorly understood in humans. The hypothalamus is a key integrative area involved in short‐ and long‐term energy intake regulation. Hence, we examined the effect of hunger state on the hypothalamus network using functional magnetic resonance imaging. In a multicenter study, participants performed a food cue viewing task either fasted or sated on two separate days. We evaluated hypothalamic functional connectivity (FC) using psychophysiological interactions during high versus low caloric food cue viewing in 107 adults (divided into four groups based on age and body mass index [BMI]; age range 24–76 years; BMI range 19.5–41.5 kg/m²). In the sated compared to the fasted condition, the hypothalamus showed significantly higher FC with the bilateral caudate, the left insula and parts of the left inferior frontal cortex. Interestingly, we observed a significant interaction between hunger state and BMI group in the dorsolateral prefrontal cortex (DLPFC). Participants with normal weight compared to overweight and obesity showed higher FC between the hypothalamus and DLPFC in the fasted condition. The current study showed that task‐based FC of the hypothalamus can be modulated by internal (hunger state) and external cues (i.e., food cues with varying caloric content) with a general enhanced communication in the sated state and obesity‐associated differences in hypothalamus to DLPFC communication. This could potentially promote overeating in persons with obesity.     

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance

BACKGROUND: Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. METHODS: Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). RESULTS: Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. CONCLUSIONS: In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.     

ACTH, cortisol and beta-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans

Normal responses to metyrapone were observed in most steady-state methadone maintained treatment patients. These preliminary studies suggest that in recently detoxified methadone maintained treatment patients, there may be an exaggerated response of the hypothalamic-pituitary-adrenal axis to metyrapone.     

Politics on the brain: an FMRI investigation

We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation also was associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks-one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge-cooperate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.     

A cross-linguistic FMRI study of spectral and temporal cues underlying phonological processing

It remains a matter of controversy precisely what kind of neural mechanisms underlie functional asymmetries in speech processing. Whereas some studies support speech-specific circuits, others suggest that lateralization is dictated by relative computational demands of complex auditory signals in the spectral or time domains. To examine how the brain processes linguistically relevant spectral and temporal information, a functional magnetic resonance imaging study was conducted using Thai speech, in which spectral processing associated with lexical tones and temporal processing associated with vowel length can be differentiated. Ten Thai and 10 Chinese subjects were asked to perform discrimination judgments of pitch and timing patterns presented in the same auditory stimuli under two different conditions: speech (Thai) and nonspeech (hums). In the speech condition, tasks required judging Thai tones (T) and vowel length (VL); in the nonspeech condition, homologous pitch contours (P) and duration patterns (D). A remaining task required listening passively to nonspeech hums (L). Only the Thai group showed activation in the left inferior prefrontal cortex in speech minus nonspeech contrasts for spectral (T vs. P) and temporal (VL vs. D) cues. Thai and Chinese groups, however, exhibited similar fronto-parietal activation patterns in nonspeech hums minus passive listening contrasts for spectral (P vs. L) and temporal (D vs. L) cues. It appears that lower level specialization for acoustic cues in the spectral and temporal domains cannot be generalized to abstract higher order levels of phonological processing. Regardless of the neural mechanisms underlying low-level auditory processing, our findings clearly indicate that hemispheric specialization is sensitive to language-specific factors.     

Lateralized response of chicks to magnetic cues

Previous research has shown that the ability to orient with the use of directional cues from the geomagnetic field is lateralized in three avian species: orientation is possible when the birds are restricted to use of their right eye, but not when they have to use their left eye. This has been interpreted as possible lateralization of the perception mechanisms for magnetic cues in favour of the right eye. Recent discovery of magnetic compass orientation in domestic chicks, a species in which lateralization has been well studied, has made available a model system in which to explore these lateralized processes more fully. Hence we tested chicks monocularly in the same test conditions as used previously to demonstrate the chick's use of a magnetic compass. In a magnetic field with North shifted by 90 degrees , chicks using their right eye oriented according to magnetic cues, whereas chicks using the left eye did not, but continued to prefer the original direction. Analysis of the times taken to respond indicated longer latencies in the chicks using their left eye, suggesting a possible conflict between cues. The different behaviour of the chicks using their left eye might not be a matter of a right eye-left hemisphere specialization for detecting magnetic directions, but of hemispheric specialization for attending to specific types of cues.     

The influence of gender and emotional valence of visual cues on FMRI activation in humans

Emotional neuroscience maps neurocircuits associated with the processing of affective stimuli. To assess gender differences in brain activation elicited by affective stimuli, we used pictures from the International Affective Picture System in a functional magnetic resonance imaging (fMRI) study. Ten male and ten female age-matched healthy volunteers were included and viewed affectively negative versus positive pictures, which were presented in an event related design. There was a significant interaction between valence of emotional stimuli and gender in the sublenticular extended amygdala (SLEA) and the rostral anterior cingulate. fMRI activation in these regions was stronger for negative compared to positive cues in women. In men fMRI activation was independent of stimulus valence. These results suggest to take gender differences into account when emotional paradigms are tested in functional brain imaging.     

Analysis and use of FMRI response delays

In this study, we implemented a new method for measuring the temporal delay of functional magnetic resonance imaging (fMRI) responses and then estimated the statistical distribution of response delays evoked by visual stimuli (checkered annuli) within and across voxels in human visual cortex. We assessed delay variability among different cortical sites and between parenchyma and blood vessels. Overall, 81% of all responsive voxels showed activation in phase with the stimulus while the remaining voxels showed antiphase, suppressive responses. Mean delays for activated and suppressed voxels were not significantly different (P < 0.001). Cortical flat maps showed that the pattern of activated and suppressed voxels was dynamically induced and depended on stimulus size. Mean delays for blood vessels were 0.7-2.4 sec longer than for parenchyma (P < 0.01). However, both parenchyma and blood vessels produced responses with long delays. We developed a model to identify and quantify different components contributing to variability in the empirical delay measurements. Within-voxel changes in delay over time were fully accounted for by the effects of empirically measured fMRI noise with virtually no measurable variability associated with the stimulus-induced response itself. Across voxels, as much as 47% of the delay variance was also the result of fMRI noise, with the remaining variance reflecting fixed differences in response delay among brain sites. In all cases, the contribution of fMRI noise to the delay variance depended on the noise power at the stimulus frequency. White noise models significantly underestimated the fMRI noise effects.