慢性海洛因成瘾者的冲动性和行为抑制缺陷脑机制

In recent years, the deficit of inhibition has become an important reason for explaining addiction. Response inhibition resembles the compulsive drug seeking behavior and it is the basement of addiction inhibition deficits. However, there were no enough evidence for the relationship between addiction and response inhibition deficits and the results of the neuro mechanisms studies remains unclear. Few studies has focused on the exploring the heroin users. Among those paradigms for study response inhibition deficits, stop signal is a very suitable model for the representation of compulsive drug seeking, but only a few researches has worked on this paradigm. In this study, we selected about 100 heroin abusers and had behaviour and neuro imaging scannings for investigating the response inhibition deficits. The behaviour researches found: first, the chronic heroin users had longer reaction time than control group and this reaction time were not affected by stop signals in heroin users. Second, heroin users had less waiting time than control group and they were more impulsive but less flexibility. Their erro monitoring and flexibale adjustment ability decreased. Third, the SSRT of heroin users was significantly longer than control group. These results suggested that the inhibition of heroin users were impaired. Further investigation showed that the SSRT of heroin users had positive correlation of four factor scores of ASI and the macro correlation coefficient was factor three of drug use. This correlation suggested that drug use was the main reason of inhibition deficits. fMRI results mainly focused on the ANOVA analysis for group difference. First, there was no intensity difference in M1 and SMA brain areas between the two groups. Second, heroin users had less activation in right dorsalateral prefrontal cortex, right inferior prefrontal cortex and anterior cingulated cortex, while in bilateral striatum and amygdala, heroin users had more activation than control group. The right prefrontal cortex was indentified as the main inhibition brain area. The anterior cingulated cortex has relationship with erro monitoring and amygdale was an important brain area for impulsivity and emotion control. The network of these brain areas was envovled in impulsivity and inhibition and it was suggested the mainly damaged network for heroin users’ disinhibition. We also investigated the gray matter changes of heroin users and found that chonic heroin use made their gray matter density decreased in prefrontal cortex (including bilateral dorsalateral prefrontal cortex, obital frontal cortex, inferior prefrontal cortex) and anterior cingulated cortex. The gray matter density in these brain regions had negative correlation with drug use duration. In conclusion, we indentified the disinhibition of heroin users and its neuro mechanism. Their compulsivity brain areas had more activation than control group and their inhibition brain areas had less activation than normal control. On the other side, the biological mechanism of this activation changes was the gray matter density decrease in these brain areas.

顿悟中的蔡格尼克效应：左右脑在解题失败与提示信息加工时的活动差异

Zeigarnik effect refers to the enhanced memory performance for unfinished tasks and studies on insight using hemi-visual field presentation technology also find that after failing to solve an problem, hints to the problem are more effective received and lead to insight experience when presented to the left-visual field (Right hemisphere) than presented to the right-visual field, especial when the hints appeared with a delay. Thus, it seems that right hemisphere may play an important role in preserving information of unsolved problems and processing related cues. To further examine the finding above, we introduce an Chinese character chunking task to investigate the brain activities during the stage of failure to resolve problems and of hint presentation using Event-Related Potentials (ERP) and functional MRI technology. Our FMRI results found that bilateral BA10 showed more activation when seeing hints for unsolved problems and we proposed that it may reflect the processes of information to failure problems, howerver, there was no hemispheric difference. The ERP results after the effort to the problems showed that unsolved problems elicited a more positive P150 over the right frontal cortex while solved problems demonstrated a left hemispheric advantage of P150. When hints present, P2 amplitudes of hints were modulated by the status of problem only in the right hemisphere but not in the left hemisphere. Our results confirmed the hypothesis that failure to solve problems would trigger the perseverance processes in right hemisphere, which would make right hemisphere more sensitive to related information of failure problems.

条件反射性免疫抑制及其脑机制的c-fos研究

To explore the neural mechanisms underlying conditioned immunomodulation, this study employed the classical taste aversion (CTA) behavioral paradigm to establish the conditioned humoral and cellular immunosuppression (CIS) in Wistar rats, by paring saccharin (CS) with intraperitoneal (i.p.) injection of an immunosuppressive drug cyclophophamide (UCS). C-fos immunohistochemistry method was used to observe the changes of the neuronal activities in the rat brain during the acquisition, expression and extinction of the conditioned immunosuppression (CIS). The followings are the main results: 1. Five days after one trial of CS-UCS paring, reexposure to CS alone significantly decreased the level of the anti-ovalbumin (OVA) IgG in the peripheral serum. Two trials of CS-UCS paring and three reexposures to CS not only resulted in further suppression of the primary immune response, but also reduced the numbers of peripheral lymphocytes and white blood cells. This finding indicates that CS can induce suppression of the immune function, and the magnitude of the effects is dependent on the intensity of training. 2. On day 5 following two trials of CS-UCS pairing, CS suppressed the spleen lymphocytes responsiveness to mitogens ConA, PHA and PWM, and decreased the numbers of peripheral lymphocytes and white blood cells. On day 15, only PHA induced lymphocyte proliferation was suppressed by CS. On day 30, presentation of CS did not have any effect on these immune parameters. These results suggest that the conditioned suppression of the cellular immune function can retain 5-15 days, and extinct after 30 days. 3. CTA was easily induced by one or two CS-UCS parings, and remained robust even after 30 days. These data demonstrate that CIS can be dissociated from CTA, and they may be mediated by different neural mechanisms. 4. Immunohistochemistry assays revealed a broad pattern of c-fos expression throughout the rat brain following the CS-UCS pairing and reexposure to CS, suggesting that many brain regions are involved in CIS. Some brain areas including the solitary tract nucleus (Sol), lateral parabrachial nucleus (LPB) and insular cortex (IC), showed high level c-fos expressions in response to both CS and UCS, suggesting that they may be involved in the transmission and integration of the CS and UCS signals in the brain. There were dense c-FOS positive neurons in the paraverntricular nucleus (PVN) and supraoptic nucleus (SO) of hypothalamus, subfornical organ (SFO) and area postrema (AP) etc. after two trials of CS-UCS paring and after the reexposure to CS 5 days later, but not in the first training and after the extinction of CIS (30 days later). The results reflect that these nuclei may have an important role in CIS expression, and may also response to the immunosuppression of UCS. The conditioned training and reexposure to CS 5 days later induced high level c-fos expression in the cingulate cortex (Cg), central amygdaloid nucleus (Ce), intermediate part of lateral septal nucleus (LSI) and ventrolateral parabrachial nucleus (VLPB) etc. But c-fos induction was not apparent when presenting CS 30 days later. These brain regions are mainly involved in CIS, and may be critical structures in the acquisition and expression of CIS. Some brain regions, including the frontal cortex (Fr), ventral orbital cortex (VO), IC, perirhinal cortex (PRh), LPB and the medial part of solitary nucleus (SolM), showed robust c-FOS expression following the conditioning training and reexposure to CS both on day 5 and day 30, suggesting that they are critically involved in CTA.

情绪应激对大鼠体液免疫功能的影响及其机制

This study was undertaken to investigate the effect of emotional stress on humoral immunoactivity and to examine whether the sympathetic nervous system was involved in the immunomodulation. In the present study, two types of emotional stressors were used. One was footshock apparatus used to cause the rats which were given footshock before, emotional stressed; the other was an empty water bottle used to cause the rats which were trained to drink water at two set times each day, emotional stressed. The effect of emotional stress on the primary immune function (anti-ovallum antibody level and spleen index), the endocrine response (corticosterone level, epinephrine and norepinephrine level), the behavioral changes (freezing, defecation, grooming and attacking behavior) were investigated. The main results were: 1. Two types of emotional stress significantly increased the level of plasma corticosterone, norepinephrine and epinephrine, as well as freezing, defecation and attacking behavior. 2. Two types of emotional stress significantly decreased the level of anti-ovallum antibody. A negative correlation between catecholamine level (epinephrine and norepinephrine) and antibody level or spleen index was found. 3. β-adrenergic receptor antagonist propranolol could reverse the immunomodulation induced by emotional stress. 4. After two types of emotional stress, c-fos expression was observed in the following brain areas or nucleus; arcuate nucleus, anterior commissure nucleus, diffuse part of dorsalmedial nucleus hypothalamus, lateral dorsal nucleus thalamus, medial nucleus amygdala, solitary nucleus, frontal cortex and cingulum. These brain areas and nucleus are involved in the central modulation of the autonomic nervous system. Taken together, these findings demonstrate that emotional stress can suppress humoral immunity and the activation of the sympathetic nervous system is involved in the humoral immunomodulation induced by emotional stress.

汉字形音义加工时间进程的事件相关电位（ERP）研究

The time-courses of orthographic, phonological and semantic processing of Chinese characters were investigated systematically with multi-channel event-related potentials (ERPs). New evidences concerning whether phonology or semantics is processed first and whether phonology mediates semantic access were obtained, supporting and developing the new concept of repetition, overlapping, and alternating processing in Chinese character recognition. Statistic parameter mapping based on physiological double dissociation has been developed. Seven experiments were conducted: I) deciding which type of structure, left-right or non-left-right, the character displayed on the screen was; 2) deciding whether or not there was a vowel/a/in the pronunciation of the character; 3) deciding which classification, natural object or non-natural object, the character was; 4) deciding which color, red or green, the character was; 5) deciding which color, red or green, the non-character was; 6) fixing on the non-character; 7) fixing on the crosslet. The main results are: 1. N240 and P240:N240 and P240 localized at occipital and prefrontal respectively were found in experiments 1, 2, 3, and 4, but not in experiments 5, 6, or 7. The difference between the former 4 and the latter 3 experiments was only their stimuli: the former's were true Chinese characters while the latter's were non-characters or crosslet. Thus Chinese characters were related to these two components, which reflected unique processing of Chinese characters peaking at about 240 msec. 2. Basic visual feature analysis: In comparison with experiment 7 there was a common cognitive process in experiments 1, 2, 4, and 6 - basic visual feature analysis. The corresponding ERP amplitude increase in most sites started from about 60 msec. 3. Orthography: The ERP differences located at the main processing area of orthography (occipital) between experiments 1, 2, 3, 4 and experiment 5 started from about 130 msec. This was the category difference between Chinese characters and non-characters, which revealed that orthographic processing started from about 130 msec. The ERP differences between the experiments 1, 2, 3 and the experiment 4 occurred in 210-250, 230-240, and 190-250 msec respectively, suggesting orthography was processed again. These were the differences between language and non-language tasks, which revealed a higher level processing than that in the above mentioned 130 msec. All the phenomena imply that the orthographic processing does not finished in one time of processing; the second time of processing is not a simple repetition, but a higher level one. 4. Phonology: The ERPs of experiment 2 (phonological task) were significantly stronger than those of experiment 3 (semantic task) at the main processing areas of phonology (temporal and left prefrontal) starting from about 270 msec, which revealed phonologic processing. The ERP differences at left frontal between experiment 2 and experiment 1 (orthographic task) started from about 250 msec. When comparing phonological task with experiment 4 (character color decision), the ERP differences at left temporal and prefrontal started from about 220 msec. Thus phonological processing may start before 220 msec. 5. Semantic: The ERPs of experiment 3 (semantic task) were significantly stronger than those of experiment 2 (phonological task) at the main processing areas of semantics (parietal and occipital) starting from about 290 msec, which revealed semantic processing. The ERP differences at these areas between experiment 3 and experiment 4 (character color decision) started from about 270 msec. The ERP differences between experiment 3 and experiment 1 (orthographic task) started from about 260 msec. Thus semantic processing may start before 260 msec. 6. Overlapping of phonological and semantic processing: From about 270 to 350 msec, the ERPs of experiment 2 (phonological task) were significantly larger than those of experiment 3 (semantic task) at the main processing areas of phonology (temporal and left prefrontal); while from about 290-360 msec, the ERPs of experiment 3 were significantly larger than those of experiment 2 at the main processing areas of semantics (frontal, parietal, and occipital). Thus phonological processing may start earlier than semantic and their time-courses may alternate, which reveals parallel processing. 7. Semantic processing needs part phonology: When experiment 1 (orthographic task) served as baseline, the ERPs of experiment 2 and 3 (phonological and semantic tasks) significantly increased at the main processing areas of phonology (left temporal and frontal) starting from about 250 msec. The ERPs of experiment 3, besides, increased significantly at the main processing areas of semantics (parietal and frontal) starting from about 260 msec. When experiment 4 (character color decision) served as baseline, the ERPs of experiment 2 and 3 significantly increased at phonological areas (left temporal and frontal) starting from about 220 msec. The ERPs of experiment 3, similarly, increased significantly at semantic areas (parietal and frontal) starting from about270 msec. Hence, before semantic processing, a part of phonological information may be required. The conclusion could be got from above results in the present experimental conditions: 1. The basic visual feature processing starts from about 60 msec; 2. Orthographic processing starts from about 130 msec, and repeats at about 240 msec. The second processing is not simple repetition of the first one, but a higher level processing; 3. Phonological processing begins earlier than semantic, and their time-courses overlap; 4. Before semantic processing, a part of phonological information may be required; 5. The repetition, overlapping, and alternating of the orthographic, phonological and semantic processing of Chinese characters could exist in cognition. Thus the problem of whether phonology mediates semantics access is not a simple, but a complicated issue.

影响吗啡动物行为效应的因素及其机制

Credible and stable animal behavioral models are necessary to research the mechanisms of addiction in vivo, especially to study the relationship between memory or stress and drug addiction, which has been one of the focuses in this field. So the object of this study was to observe the influences of several factors on the behavioral effects of morphine shown in the paradigms of conditioned place preference (CPP) and locomotor activity (LA), and to explore the effects of adrenalectomy on LA induced by morphine in rats. In addition, the cortexes of rats were examined, which were exposed to chronic administration of several doses of morphine with or without foot shock. Moreover, a new behavioral model was built to quantify the motivation of drug seeking. The results showed that CPP was more sensitive to low dose of morphine than to high dose. The period of experiment could be shortened by increasing the training times everyday, whereas in this way the dose of morphine should be low enough to avoid the impact between the near two exposures to morphine. Effects of chronic administration of morphine on LA in rats were dose- and time- dependent, which supplied evidence to choose parameters in other behavioral models. The results obtained by the simplified LA paradigm showed that hyperactivity of low dose of morphine following hypoactivity, and naloxone had no effects on LA but blocked the locomotion effects of morphine. Obvious effects of morphine on LA of rats might depend on a reasonable level of plasma corticosterone, which may determine individual vulnerability to drug addiction. Stress may also potentiate the vulnerability by aggravating damage to cortex of rats induced by drug dose-dependently, which is suggested by the results of histological examination. The result that frontal and temporal cortexes and hippocampus were injured suggests that there may be a close relationship between memory and drug addiction. It was showed that the new behavioral model on the basis of Morris water maze might be used to quantify the motivation of drug-craving.

Modeling of protein adsorption in membrane affinity chromatography

For the design of affinity membranes, protein adsorption in membrane affinity chromatography (MAC) was studied by frontal analysis. According to fast mass transfer, small thickness of affinity membranes and high affinity between the protein and the ligand, an ideal adsorption (IA) model was proposed for MAC and was used together with equilibrium-dispersive (E-D) model to describe the adsorption of bovine serum albumin (BSA) onto cellulose diacetate/polyethyleneimine (CA/PEI) blend membranes with and without Cu2+ chelating. E-D model was found to better describe the initial region of experimental breakthrough curves. The influence of axial dispersion was revealed and it showed the importance of design of the module to homogenously distribute feed solution. IA model was found to be better for the whole experimental breakthrough curve. According to it, the capacity of affinity membranes and the specificity of the interaction are of equal importance for the design of affinity membranes. An optimum feed concentration was also found in the operation of MAC. The discrepancy between experimental optimum feed concentrations and predicted ones from IA model may be due to the ignorance of some experimental effects such as axial dispersion.