The functional neuroanatomy of the evolving parent–infant relationship

Infant survival and the development of secure and cooperative relationships are central to the future of the species. In humans, this relies heavily on the evolving early parent–infant social and affective relationship. While much is known about the behavioural and psychological components of this relationship, relatively little is known about the underlying functional neuroanatomy. Affective and social neuroscience has helped to describe the main adult brain networks involved, but has so far engaged very little with developmental findings. In this review, we seek to highlight future avenues for research by providing a coherent framework for describing the parent–infant relationship over the first 18 months. We provide an outline of the evolving nature of the relationship, starting with basic orienting and recognition processes, and culminating in the infant's attainment of higher socio-emotional and cognitive capacities. Key social and affective interactions, such as communication, cooperative play and the establishment of specific attachments propel the development of the parent–infant relationship. We summarise our current knowledge of the developing infant brain in terms of structure and function, and how these relate to the emergent abilities necessary for the formation of a secure and cooperative relationship with parents or other caregivers. Important roles have been found for brain regions including the orbitofrontal, cingulate, and insular cortices in parent–infant interactions, but it has become clear that much more information is needed about the developmental time course and connectivity of these regions.     

Elevated tauopathy and alpha-synuclein pathology in postmortem Parkinson's disease brains with and without dementia

Parkinson's disease (PD), a progressive neurodegenerative disease, results in abnormal accumulation of insoluble alpha-synuclein (α-Syn) in dopaminergic neurons. Here we examined tauopathic changes and the α-Syn/p-GSK-3β/proteasome pathway in postmortem striata and inferior frontal gyri (IFG) from patients with PD and PD with dementia (PDD). In both PD and PDD, α-Syn levels were high, especially the insoluble form of this protein; in PDD, insoluble α-Syn levels were persistently higher than PD across both brain regions. Levels of p-GSK-3β phosphorylated at Tyr 216, which hyperphosphorylates Tau to produce toxic pathological forms of p-Tau, were higher in striata of both PD and PDD compared to controls, but were unaltered in IFG. While proteasomal activity was unchanged in striatum of PD and PDD, such activity was diminished in the IFG of both PD and PDD. A decrease in 19S subunit of the proteasomes was seen in IFG of PDD, while lower levels of 20S subunits were seen in striatum and IFG of both PD and PDD patients. Parkin levels were similar in PD and PDD, suggesting lack of involvement of this protein. Most interestingly, tauopathic changes were noted only in striatum of PD and PDD, with increased hyperphosphorylation seen at Ser262 and Ser396/404; increases in Ser202 levels were seen only in PD but not in PDD striatum. We were unable to detect any tauopathy in IFG in either PD or PDD despite increased levels of α-Syn, and decreased proteasomal activity, and is probably due to lack of increase in p-GSK-3β in IFG. Unlike Alzheimer's disease where tauopathy is more globally observed in diverse brain regions, our data demonstrates restricted expression of tauopathy in brains of PD and PDD, probably limited to dopaminergic neurons of the nigrostriatal region.     

Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor

The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-induced salivary cortisol increases. Furthermore, metabolic glucose rate in these regions was inversely coupled with changes in glucose metabolic rate in other areas, known to be involved in HPA axis regulation such as the amygdala/hippocampal region. In contrast, metabolic glucose rate in areas more lateral to the mPFC was positively associated with saliva cortisol. Subjective ratings on task stressfulness, task controllability and self-reported dispositional mood states also showed positive and negative associations with the glucose metabolic rate in prefrontal regions. These findings suggest that in humans, the PFC is activated in response to psychosocial stress and distinct prefrontal metabolic glucose patterns are linked to endocrine stress measures as well as subjective ratings on task stressfulness, controllability as well as dispositional mood states.     

Comparison of Fasting Glucose with Post-Load Glucose Values and Glycated Hemoglobin for Prediction of Type 2 Diabetes: The Isfahan Diabetes Prevention Study

OBJECTIVES: The aim of this study was to compare the ability of fasting plasma glucose (FPG), post-load plasma glucose values and glycated hemoglobin (HbA1c) to predict progression to diabetes in non-diabetic first-degree relatives (FDR) of patients with type 2 diabetes. METHODS: A total of 701 non-diabetic FDR of diabetic patients aged 20-70 years surveyed in 2003 to 2005 were followed until 2008 for the onset of type 2 diabetes mellitus. At baseline and at follow-ups, participants underwent a standard 75 g 2-hour oral glucose tolerance test (OGTT). Prediction of progression to type 2 diabetes was assessed by using area under the receiver-operating characteristic (ROC) curves based upon measurement of FPG, post-load glucose values and HbA1c. RESULTS: The incidence of type 2 diabetes was 33.9 per 1000 person-years in men and 48.6 in women. The incidence rates were 4.6, 50.7, and 99.7 per 1000 person-years in FDR with normal glucose tolerance, impaired fasting glucose and impaired glucose tolerance respectively. FPG value was a better predictor of progression to diabetes than any post-load glucose values or HbA1c. The areas under the ROC curves were 0.811 for fasting, 0.752 for 1/2-hour, 0.782 for 1-hour and 0.756 for 2-hour glucose vs. 0.634 for HbA1c (p < 0.001). CONCLUSIONS: FPG had more discriminatory power to distinguish between individuals at risk for diabetes and those who were not at risk than post-load glucose values during OGTT or HbA1c. Our findings support the American Diabetes Association recommendation of using FPG concentration to diagnose diabetes.     

泸天化(集团)公司员工糖尿病的现况调查

目的：了解化工行业人群糖尿病的患病率及其分布特征。方法：采用WHO（1985）诊断标准和美国糖尿病协会1997年公布的糖尿病诊断标准，对泸天化（公司20岁以上的全体人员6387人，进行问卷调查、体格检查及血液生化指标测定，计算患病率并进行统计分析。结果：糖尿病（DM）、糖耐量减低（IGT）、空腹血糖不良（IFG）的患病率分别为3．33％、3．91％、0．31％，标化患病率分别为3．39％、3．74％、0．25％（用1990年全国人口统计数据标化）。DM、IGT的标化患病率女性高于男性；DM、IGT、IFG患病率随年龄的增大、文化程度的降低而升高；餐饮服务人员、行政干部的DM、IGT和IFG患病率与职业有关；DM、IGT和IFG人群的血压、体重指数、腰臀围比值等均值都显著高于正常人群。结论：泸天化（集团）公司员工DM的患病率高于全国平均水平。     

拜糖苹和二甲双胍干预糖稳态受损病例的结果研究

目的:观察拜糖苹和二甲双胍对糖稳态受损包括糖耐量减低(IGT)和空腹血糖异常(IFG)病例的影响,为不同类型糖稳态受损病例提供更合理的预防糖尿病的方案.方法:按1999年WHO诊断标准判断的糖稳态受损病例69例,经卫生宣教,自主选择干预方案,其中饮食运动组15例,二甲双胍组28例,拜糖苹组26例.观察时间6个月,干预前后分别测空腹血糖(FPG),餐后2h血糖(2HPG),总胆固醇(TC),甘油三酯(TG).结果:饮食运动组经干预6个月,检测指标均有不同程度下降,但无统计学意义(P>0.05);两治疗组FPG及2hPG与治疗前比较有明显下降(P<0.01),对FPG控制两组无明显区别,对2hPG的控制拜糖苹组优于二甲双胍组(P<0.01),两治疗组TC、TG与治疗前对比明显下降(P<0.05).结论:在饮食运动基础上,对IFG病例建议选用二甲双胍,对IGT病例建议选用拜糖苹预防糖尿病的发生.     

对代谢综合征人群中单纯IFG的干预研究

目的为探讨对代谢综合征的积极干预意义。方法从仙河地区健康查体职工中筛选出983例代谢综合征患者,将其中血糖异常的675例进行分组,通过OGTT试验分出单纯IFG组、IFG＋IGT组和糖尿病组（有明确糖尿病病史者不进行OGTT试验）,对单纯IFG组117例进行干预研究,分为生活方式干预组、生活方式加二甲双胍干预组和对照组,研究干预治疗后这部分病人的转归情况。结果生活方式干预和生活方式干预并加服二甲双胍对这部分病人转归有积极的意义。结论研究表明代谢综合征病人应该一经诊断即进行生活方式干预和二甲双胍等药物治疗,生活方式干预并加服二甲双胍有更明确的干预效果。     

Effects of changes in obesity and exercise on the development of diabetes and return to normal fasting plasma glucose levels at one-year follow-up in middle-aged subjects with impaired fasting glucose

Objectives  Borderline diabetes, a precursory condition of diabetes, is an important issue in the prevention of diabetes. The aim of the present study was to clarify the effects of one-year changes in obesity and exercise on the development of diabetes or return to normal fasting plasma glucose (FPG) levels among middle-aged people with impaired fasting glucose (IFG) at baseline. Methods  Among those who attended a basic health examination in 1997, we selected 1,620 subjects who showed impaired fasting glucose (FPG of 110 mg/dl or higher) and had complete data on height, weight and exercise. At the one-year follow-up (in 1998), 1,099 of those subjects attended a health examination; FPG, height, weight and exercise were evaluated for 731 subjects. Subjects were classified into the following three groups, on the basis of changes in FPG during the year between the two examinations: developing diabetes (DM), remaining IFG, and returning to normal (WNL). Results  Among those who were initially obese, there was a significant difference in the proportions of DM, IFG and WNL between those with and without improvement in obesity in the year preceding the follow-up (p<0.05). Those with improvement in obesity showed a significantly higher tendency to return to WNL than those without improvement in obesity. Multiple logistic regression analysis showed that those with improvement in obesity had a significantly higher odds ratio (2.17) to return to WNL (p=0.015). Among those who were initially not obese, there was no significant association between changes in obesity and developing DM or returning to WNL. No significant association was observed between changes in exercise and developing DM or returning to WNL. Conclusion  The present findings suggest that, among obese IFG subjects, improvement in obesity is associated with returning to normal plasma glucose. Weight control may be important for the normalization of borderline diabetes.     

A non-elaborative mental stance and decoupling of executive and pain-related cortices predicts low pain sensitivity in Zen meditators

Concepts originating from ancient Eastern texts are now being explored scientifically, leading to new insights into mind/brain function. Meditative practice, often viewed as an emotion regulation strategy, has been associated with pain reduction, low pain sensitivity, chronic pain improvement, and thickness of pain-related cortices. Zen meditation is unlike previously studied emotion regulation techniques; more akin to ‘no appraisal’ than ‘reappraisal’. This implies the cognitive evaluation of pain may be involved in the pain-related effects observed in meditators. Using functional magnetic resonance imaging and a thermal pain paradigm we show that practitioners of Zen, compared to controls, reduce activity in executive, evaluative and emotion areas during pain (prefrontal cortex, amygdala, hippocampus). Meditators with the most experience showed the largest activation reductions. Simultaneously, meditators more robustly activated primary pain processing regions (anterior cingulate cortex, thalamus, insula). Importantly, the lower pain sensitivity in meditators was strongly predicted by reductions in functional connectivity between executive and pain-related cortices. Results suggest a functional decoupling of the cognitive-evaluative and sensory-discriminative dimensions of pain, possibly allowing practitioners to view painful stimuli more neutrally. The activation pattern is remarkably consistent with the mindset described in Zen and the notion of mindfulness. Our findings contrast and challenge current concepts of pain and emotion regulation and cognitive control; commonly thought to manifest through increased activation of frontal executive areas. We suggest it is possible to self-regulate in a more ‘passive’ manner, by reducing higher-order evaluative processes, as demonstrated here by the disengagement of anterior brain systems in meditators.