慢性应激性抑郁发生中大鼠眶额叶多巴胺D1受体对谷氨酸及其NMDA受体的调节

本文旨在探讨慢性应激性抑郁发生过程中眶额叶多巴胺D1受体对谷氨酸(glutamic acid, Glu)及其N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体的NR2B亚基的影响。实验通过建立慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS)抑郁模型, 结合眶额叶微量注射多巴胺D1受体激动剂SKF38393和多巴胺D1受体拮抗剂SCH23390, 运用糖水偏爱测试、悬尾实验和敞箱实验等方法检测动物的行为表现, 采用高效液相色谱法(high-performance liquid chromatography, HPLC)和蛋白质免疫印迹法(Western blot, WB)来检测眶额叶内谷氨酸、多巴胺含量及NR2B和多巴胺D1受体的表达。结果显示, 与对照组相比, CUMS组大鼠表现出明显的抑郁样行为变化, 且眶额叶多巴胺含量降低, 其D1型受体表达降低, 谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调; 注射SKF38393后可明显改善应激引起的抑郁样行为, 且眶额叶谷氨酸含量显著下降, NMDA受体的NR2B亚基表达也有所降低; 正常大鼠注射多巴胺D1受体拮抗剂SCH23390, 大鼠表现出和CUMS模型组相似的抑郁样行为, 且眶额叶谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调。以上结果表明, 慢性不可预见性应激可能使眶额叶多巴胺释放减少, 从而使谷氨酸过量释放, NMDA受体过度激活, 导致抑郁发生。多巴胺抗抑郁作用是通过D1型受体抑制谷氨酸及其NMDA受体NR2B亚基表达来实现。     

Cognitive deficits in relation to personality type and hypothalamic-pituitary-adrenal (HPA) axis dysfunction in women with stress-related exhaustion

Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26-53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.     

The role of the ventral and dorsal pathways in reading Chinese characters and English words

Previous literature in alphabetic languages suggests that the occipital-temporal region (the ventral pathway) is specialized for automatic parallel word recognition, whereas the parietal region (the dorsal pathway) is specialized for serial letter-by-letter reading ( [Cohen et al., 2008] and [Ho et al., 2002] ). However, few studies have directly examined the role of the ventral and dorsal pathways in Chinese reading compared to English reading. To investigate this issue, we adopted the degraded word processing paradigm used by Cohen et al. (2008) and compared brain regions involved in the processing of degraded Chinese characters and English words during lexical decision, using functional magnetic resonance imaging (fMRI). The degraded characters/words were created by inserting blank spaces between radicals of Chinese characters or syllables of English polysyllabic words. Generally, the current study replicated the effects of Cohen et al. (2008), showing that in Chinese – like in alphabetic languages – character spacing modulates both ventral (bilateral cuneus, left middle occipital gyrus) and dorsal (left superior parietal lobule and middle frontal gyrus) pathways. In addition, the current study showed greater activation in bilateral cuneus and right lingual gyrus for Chinese versus English when comparing spaced to normal stimuli, suggesting that Chinese character recognition relies more on ventral visual-spatial processing than English word recognition. Interestingly, bilateral cuneus showed monotonic patterns in response to increasing spacing, while the rest of the regions of interest showed non-monotonic patterns, indicating different profiles for these regions in visual-spatial processing.     

Magnitude and chronometry of neural mechanisms of emotion regulation in subtypes of aggressive children

Emotion regulation is a key social skill and children who fail to master it are at risk for clinical disorders. Specific styles of emotion regulation have been associated with particular patterns of prefrontal activation. We investigated whether anxious aggressive children would reveal a different pattern of cortical activation than non-anxious aggressive children and normally-developing children. We examined the magnitude and timing of source activation underlying the N2—an ERP associated with inhibitory control—during a go/nogo task with a negative emotion induction component (loss of earned points). We estimated cortical activation for two regions of interest—a ventral prefrontal and a dorsomedial prefrontal region—for three 100-ms windows over the range of the N2 (200–500 ms). Anxious aggressive children showed high ventral prefrontal activation in the early window; non-anxious aggressive children showed high ventral prefrontal activation in the late window, but only for the duration of the emotion induction; and normally-developing children showed low ventral prefrontal activation throughout. There were no group differences in dorsomedial prefrontal activation. These results suggest that anxious aggressive children recruit ventral prefrontal activation quickly and indiscriminately, possibly giving rise to their rigid, threat-oriented approach to conflict. The late ventral prefrontal activation seen for non-anxious aggressive children may underlie a more delayed, situation-specific, but ineffective response to frustration.     

An fMRI investigation of a novel analogue to the Trail-Making Test

The Trail-Making Test (TMT) is a widely used neuropsychological measure that assesses visuomotor abilities and cognitive flexibility. For the TMT-A condition participants are required to locate and connect numbers (i.e. 1-2-3…) while in the TMT-B condition participants perform the set-shifting task of locating and connecting numbers and letters (i.e. 1-A-2-B…). The TMT-B condition has shown impairments in many clinical populations, particularly schizophrenia patients, but the neurobiological underpinning of the task can be difficult to discern given pragmatic obstacles in adapting the task for neuroimaging. In a behavioural testing experiment we demonstrated a close correspondence between performance on the standard TMT and a novel, computer programmed adaptation of the TMT (pcTMT). The pcTMT was designed for functional magnetic resonance imaging (fMRI) administration and neuroimaging data for this task were obtained in. A whole brain analysis revealed significantly greater activation during the pcTMT-B relative to the pcTMT-A in right inferior/middle frontal cortices, right precentral gyrus, left angular gyrus/left middle temporal gyrus. These results identify the regions that most likely underlie cognitive flexibility during the TMT and are candidate regions underlying the impairment of groups with poor set-shifting abilities.     

Conscious Vision for Action Versus Unconscious Vision for Action?

David Milner and Melvyn Goodale’s dissociation hypothesis is commonly taken to state that there are two functionally specialized cortical streams of visual processing originating in striate (V1) cortex: a dorsal, action‐related “unconscious” stream and a ventral, perception‐related “conscious” stream. As Milner and Goodale acknowledge, findings from blindsight studies suggest a more sophisticated picture that replaces the distinction between unconscious vision for action and conscious vision for perception with a tripartite division between unconscious vision for action, conscious vision for perception, and unconscious vision for perception. The combination excluded by the tripartite division is the possibility of conscious vision for action. But are there good grounds for concluding that there is no conscious vision for action? There is now overwhelming evidence that illusions and perceived size can have a significant effect on action ( Bruno & Franz, 2009 ; Dassonville & Bala, 2004 ; Franz & Gegenfurtner, 2008 ; McIntosh & Lashley, 2008 ). There is also suggestive evidence that any sophisticated visual behavior requires collaboration between the two visual streams at every stage of the process ( Schenk & McIntosh, 2010 ). I nonetheless want to make a case for the tripartite division between unconscious vision for action, conscious vision for perception, and unconscious vision for perception. My aim here is not to refute the evidence showing that conscious vision can affect action but rather to argue (a) that we cannot gain cognitive access to action‐guiding dorsal stream representations, and (b) that these representations do not correlate with phenomenal consciousness. This vindicates the semi‐conservative view that the dissociation hypothesis is best understood as a tripartite division.     

经颅直流电刺激在抑郁症治疗中的应用

已有的神经影像学研究成果揭示, 抑郁症发作的重要原因之一是大脑前额叶皮层结构和功能受损。经颅直流电刺激(tDCS)作为一种无创脑刺激, 选取前额叶皮层作为刺激区域, 通过调节皮层兴奋性来治疗抑郁症, 能够有效缓解抑郁症状和改善受损的认知功能, 疗效明显且持久稳定。针对tDCS在抑郁症治疗研究中的问题, 未来可从有效性、个体差异以及预防干预等六个方面进一步研究, 以期tDCS作为一种具有潜力的治疗手段, 在临床上有更为广泛地应用。     

Frontal cortex functioning in the infant broader autism phenotype

Atypical attention has been proposed as a marker of the broader autism phenotype. In the present study we investigated this and the related process of inhibitory control at the youngest possible age through the study of infant siblings of children with an autism spectrum disorder (Sibs-ASD). Both attention and inhibition have been related to the frontal cortex of the brain. Nine- to ten-month-old Sibs-ASD and low-risk control infants completed the Freeze-Frame task, in which infants are encouraged to inhibit looks to peripherally presented distractors whilst looking at a central animation. The attractiveness of the central stimulus is varied in order to investigate the selectivity of infants’ responses. In line with previous studies, it was found that a subset of Sibs-ASD infants had difficulty disengaging attention from a central stimulus in order to orient to a peripheral stimulus. The Sibs-ASD group also showed less Selective Inhibition than controls. However, Sibs-ASD infants did demonstrate Selective Inhibitory Learning. These results provide preliminary evidence for atypical frontal cortex functioning in the infant broader autism phenotype.     

Developmental changes in dopamine neurotransmission in adolescence: Behavioral implications and issues in assessment

Adolescence is characterized by increased risk-taking, novelty-seeking, and locomotor activity, all of which suggest a heightened appetitive drive. The neurotransmitter dopamine is typically associated with behavioral activation and heightened forms of appetitive behavior in mammalian species, and this pattern of activation has been described in terms of a neurobehavioral system that underlies incentive-motivated behavior. Adolescence may be a time of elevated activity within this system. This review provides a summary of changes within cortical and subcortical dopaminergic systems that may account for changes in cognition and affect that characterize adolescent behavior. Because there is a dearth of information regarding neurochemical changes in human adolescents, models for assessing links between neurochemical activity and behavior in human adolescents will be described using molecular genetic techniques. Furthermore, we will suggest how these techniques can be combined with other methods such as pharmacology to measure the impact of dopamine activity on behavior and how this relation changes through the lifespan.