Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement t

海洛因成瘾脑灰质密度和结构网络研究

Behavioral and functional imaging studies consistently show that heroin abuse leads to various cognitive impairments, while brain structural changes associated with heroin use remain poorly understood. In the current study, we used voxel-based morphology (VBM), a method sensitive to structural changes of the brain, to investigate the gray concentration in MRI structure images of heroin addicts. Results show that the concentration of the temporal cortex and frontal cortex of heroin users significantly decreased as compared to age/education matched normal controls. Further analysis revealed that this brain structure change was detectable only in the users who had used heroin more than 5 year, but not in the remaining users. These results converge to the abnormality of the brain structure in heroin users and this abnormality is clearly associated with duration of drug use. We then analyzed the large-scale brain structure network in the heroin addicts. As compared to the normal controls, there was significant difference in interregional correlation between the temporal cortex, hippocampus, thalamus, and frontal cortex. Importantly, two major indices of the small-world properties, Clustering coefficient(Cp) and shortest path length (Lp), which are thought to reflect the local specialty and global integrity, were marginal-significantly larger than the normal controls, especially for Lp. These results suggest that chronic use of heroin results in the reorganization of the brain system. Taken together, this thesis has provided compelling evidence for brain structure impairments in chronic heroin users and further characterized the large-scale brain structure network in the same population.

通过语言任务和功能磁共振成像研究人类小脑功能

Since the 19th century, people have long believed that the function of cerebellum was restricted to fine motor control and modulation. In the past two decades, however, more and more studies challenged this traditional view. While the neuroanatomy of the cerebellum from cellular to system level has been well documented, the functions of this neural organ remain poorly understood. This study, including three experiments, attempted to further the understanding of cerebellar functions from different viewpoints. Experiment One used the parametric design to control motor effects. The activation in cerebellum was found to be associated with the difficulty levels of a semantic discrimination task, suggesting the involvement of the cerebellum in higher level of language functions. Moreover, activation of the right posterior cerebellum was found to co-vary with that of the frontal cortex. Experiment Two adopted the cue-go paradigm and event-related design to exclude the effects of phonological and semantic factors in a mental writing task. The results showed that bilateral anterior cerebellum and cerebral motor regions were significantly activated during the task and the hemodynamic response of the cerebellum was similar to those of the cerebral motor cortex. These results suggest that the cerebellum participates in motor imagination during orthographic output. Experiment Three investigated the learning process of a verb generation task. While both lateral and vermis cerebellum were found to be activation in the task, each was correlated a separate set of frontal regions. More importantly, activations both in the cerebellum and frontal cortex decreased with the repetition of the task. These results indicate that the cerebellum and frontal cortex is jointly engaged in some functions; each serves as a part of a single functional system. Taken these findings together, the following conclusions can be drawn: 1.The cerebellum is not only involved in functions related to speech or articulation, but also participates in the higher cognitive functions of language. 2.The cerebellum participates in various functions by supporting the corresponding regions in cerebral cortex, but not directly executes the functions as an independent module. 3.The anterior part of cerebellum is related to motor functions, whereas the posterior part is involved in cognitive functions. 4.While the motor functions rely on the engagement of both sides of the cerebellar hemispheres, the higher cognitive functions mainly depend on the right cerebellum.

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.

空间及言语工作记忆任务的情绪效应：来自ERP/ fMRI的证据

In the present study, based on processing efficiency theory, we used the event-related potentials (ERP) and functional magnetic resonance image (fMRI) techniques to explore the underlying neutral mechanism of influences of negative emotion on three subsystems of working memory, phonological loop、 visuospatial sketh pad and the central executive. The modified DSMT (delayed matching-to-sample task) and n-back tasks were adopted and IAPS (International Affective Picture System) pictures were employed to induce the expected emotional state of subjects. The main results and conclusions obtained in the series of experiments are as the following: 1. In DSM tasks, we found P200 and P300 were reduced by negative emotion in both spatial and verbal tasks, however the increased negative slow wave were only observed in spatial tasks, not in verbal tasks. 2. In n-back tasks, the updating function of WM associated P300 was affected by negative emotion only in spatial tasks, not in verbal tasks. Current density analysis revealed strong current density in the fronto-parietal cortex only in the spatial tasks as well. 3. We adopted fMRI-block design and ROIs analysis, and found significant emotion and task effects in spatial WM-associated right superior parietal cortex; only emotion effect in verbal WM-associated Broca’s area; the interaction effect in attention-associated medial prefrontal area and bilateral inferior parietal cortex. These results implied the negative emotion mainly disturbed the spatial WM-related areas, and the attention control system play a key role in the interaction of spatial WM and negative emotion. 4. to further examine the effects of positive、negative and neutral emotion on tasks with different cognitive loads, the selective effect of emotion on the ERP components of spatial WM was only found in 2-back tasks, not in visual searching tasks. So, firstly the positive emotion as well as negative emotion selectively disturbed on spatial WM in light of the attention resource competition mechanism. Secondly, the selective influences based on the different WM systems, not the properties of spatial and verbal information. At last, the manner of the interaction of emotion and cognition is correlated with the cognitive load.

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.

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory

Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM. (C) 2009 Elsevier Inc. All rights reserved.

Delta EEG Activity in Left Orbitofrontal Cortex in Rats Related to Food Reward and Craving

眶额叶皮质与中脑边缘多巴胺奖赏系统有着复杂的相互纤维联系.先前的研究探讨了药物成瘾过程中眶额叶皮质的脑电活动.在本实验中,将探讨食物奖赏和渴求过程中该皮质的脑电活动.实验采用了两个环境:对照环境和食物刺激相关的环境.首先,训练大鼠在食物刺激相关的环境中吃巧克力花生豆,而后在该环境中设置两种不同的刺激方式:能看到和闻到但不能吃到(渴求实验),或者仍旧可以吃到巧克力花生豆(奖赏实验):同时进行左侧眶额叶皮质的脑电记录.结果发现,在食物刺激相关的环境中大鼠Delta频段(2-4Hz)的脑电活动与食物刺激显著相关,此外,与在对照环境中相比,其相对功率在食物渴求时下降而在食物奖赏时升高.本实验表明,食物相关的奖励可以改变大鼠眶额叶皮质的脑电活动,而且,Delta频段的脑电活动能够作为监测该奖励的一个指标.

A STUDY ON THE EFFECT OF LESIONS OF AREA-7 OF THE PARIETAL CORTEX ON THE SHORT-TERM VISUAL SPATIAL MEMORY OF RHESUS-MONKEYS (MACACA-MULATTA)

This research is focused on the contribution of area 7 to the short-term visual spatial memory. Three rhesus monkeys (Macaca mulatta) were trained in the direct delayed response task in which 5 delay intervals were used in each session. When each monkey reached the criterion of 90% correct responses in 5 successive sessions, two monkeys underwent a surgery while the other one received a sham operation as a control. In the first stage of the surgery, bilateral areas 7a, 7b and 7ip of the parietal cortex of two monkeys were precisely lesioned. After 7 days of recuperation, the monkeys were required to do the same task. The average percentage of correct responses in the lesioned animals decreased from 94.7% to 89.3% and 93.3% to 82.0% respectively (no significance, P > 0.05, n = 2). In addition, the monkeys' complex movements were mildly impaired. The lesioned monkeys were found to have difficulty picking up food from the wells. In the second stage, bilateral area 7m was lesioned. In the 5 postoperative sessions, the average percentage of correct responses in one monkey, with a relatively precise 7m lesion, decreased from 94.7% to 92.2% (no significance, P > 0.05), while the other monkey, with widely spread necrosis of lateral parietal cortex, showed an. obvious decline in performance, but still over the chance level. After 240 trials this monkey reattained the normal criterion. The results of this research suggest that the lesions of area 7 of the parietal cortex did not significantly affect the short-term visual spatial memory, which has been shown to be sensitive to lesions of the prefrontal cortex; they also support the notion of dissociation of spatial functions in the prefrontal and parietal cortices.

Dissociation of egocentric and allocentric spatial processing in prefrontal cortex

Monkeys with lesions of areas 9 and 46 performed three variants of the spatial delayed response (SDR) task. There were no impairments in allocentric spatial memory in which geometrical relationships between environmental cues were used to identify spatial location; thus, memory of a 3D environmental map is intact. In contrast, there were severe impairments in egocentric spatial memory guided by visual or tactile cues that monkeys can relate to their viewing perspective during testing. These results strongly suggest that dorsolateral prefrontal cortex selectively mediates spatial memory tasks that are solved by referencing the location of targets to the body's orientation. (C) 2003 Lippincott Williams Wilkins.

Age-related effects of bilateral frontal eye fields lesions on rapid eye movements during REM sleep in rhesus monkeys

Rapid eye movement (REM) is one of the most characteristic features of REM sleep, but the mechanisms underlying its regulation remain unclear. The present study aims to investigate whether the frontal eye field (FEF) is involved in the regulation of the r

EEG activities in the orbitofrontal cortex and dorsolateral prefrontal cortex during the development of morphine dependence, tolerance and withdrawal in rhesus monkeys

Investigating the activities of the prefrontal cortex (PFC) in the process of addiction is valuable for understanding the neural mechanism underlying the impairments of the PFC after drug abuse. However, limited data are obtained from primate animals and few studies analyze Electroencephalogram (EEG) in the gamma band, which plays an important role in cognitive functions. In addition, it is yet unclear whether drug abuse affects the orbitofrontal cortex (OFC) and dorsolateral PFC (DLPFC) - the two most important subregions of the PFC - in similar ways or not. The aim of this study is to address these issues. We recorded EEG in the OFC and DLPFC in three rhesus monkeys. All animals received a course of saline (NaCl 0.9%, 2 ml) injection (5 days) followed by 10 days of morphine injection (every 12 h), and then a further series of saline injection (7 days). A main finding in the present study was that morphine decreased EEG power in all frequency bands in a short period after injection in both the OFC and DLPFC in monkeys. And gamma power decreased not just in short period after morphine injection but lasted to 12 h after injection. Moreover, we found that although the changes in EEG activities in the OFC and DLPFC at 30-35 min after injection were similar, the DLPFC was more sensitive to the effect of morphine than the OFC. (c) 2005 Elsevier B.V. All rights reserved.

Neurochemical changes in brain induced by chronic morphine treatment: NMR studies in thalamus and somatosensory cortex of rats

To investigate the effects of chronic morphine treatment and its cessation on thalamus and the somatosensory cortex, an ex vivo high resolution (500 MHz) H-1 nuclear magnetic resonance spectroscopy (NMRS), in the present study, was applied to detect multi