Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong(EX-HN1), Yintang(EX-HN3), Neiguan(PC6), Taixi(KI3), Fenglong(ST40), and Taichong(LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.     

An abnormal resting-state functional brain network indicates progression towards Alzheimer＇s disease

Brain structure and cognitive function change in the temporal lobe,hippocampus,and prefrontal cortex of patients with mild cognitive impairment and Alzheimer’s disease,and brain network-connection strength,network efficiency,and nodal attributes are abnormal.However,existing research has only analyzed the differences between these patients and normal controls.In this study,we constructed brain networks using resting-state functional MRI data that was extracted from four populations(normal controls,patients with early mild cognitive impairment,patients with late mild cognitive impairment,and patients with Alzheimer’s disease)using the Alzheimer’s Disease Neuroimaging Initiative data set.The aim was to analyze the characteristics of resting-state functional neural networks,and to observe mild cognitive impairment at different stages before the transformation to Alzheimer’s disease.Results showed that as cognitive deficits increased across the four groups,the shortest path in the resting-state functional network gradually increased,while clustering coefficients gradually decreased.This evidence indicates that dementia is associated with a decline of brain network efficiency.In addition,the changes in functional networks revealed the progressive deterioration of network function across brain regions from healthy elderly adults to those with mild cognitive impairment and Alzheimer’s disease.The alterations of node attributes in brain regions may reflect the cognitive functions in brain regions,and we speculate that early impairments in memory,hearing,and language function can eventually lead to diffuse brain injury and other cognitive impairments.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

Resting-state connectivity in the default mode network and insula during experimental low back pain简

Functional magnetic resonance imaging studies have shown that the insular cortex has a significant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the default mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy subjects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the importance of the interaction between these regions in pain processing.     

Functional magnetic resonance imaging evaluation of visual cortex activation in patients with anterior visual pathway lesions

The aim of this study was to examine the secondary visual cortex functional disorder in patients with glaucoma and large pituitary adenoma by functional magnetic resonance imaging, and to determine the correlation between visual field defect and primary visual cortex activation. Results showed that single eye stimulation resulted in bilateral visual cortex activation in patients with glaucoma or large pituitary adenoma. Compared with the normal control group, the extent and intensity of visual cortex activation was decreased after left and right eye stimulation, and functional magnetic resonance imaging revealed a correlation between visual field defects and visual cortex activation in patients with glaucoma and large pituitary adenoma. These functional magnetic resonance imaging data suggest that anterior optic pathway lesions can cause secondary functional disorder of the visual cortex, and that visual defects are correlated with visual cortex activation.     

Neural bases of reappraisal regulatory effect on negative emotion in high reappraisers

Previous studies have reported that individual differences in reappraisal use are associated with particular patterns of neural activity. We hypothesized that if ’high reappraisers’ (individuals who use reappraisal well in a behavioral experiment) completed two training sessions, they would exhibit more reliable patterns of neural activity related to cognitive reappraisal. In the present study, 13 high reappraisers were selected from 27 healthy volunteers through an initial behavioral experiment (first training) followed by a functional MRI experiment (second training). Emotional images selected from the International Affective Picture System were used for both the behavioral and functional MRI sessions of the experiment. The behavioral results revealed that reappraisal reduced subjective unpleasantness. The functional MRI results revealed that the cognitive reappraisal used by high reappraisers decreased the activation of emotion-responsive regions, including the amygdala, insula, and cingulate gyrus, and increased the activation of regulation-related regions, including the inferior prefrontal cortex, orbital prefrontal cortex, and dorsal medial prefrontal cortex. These findings suggest the involvement of inferior orbital and dorsal medial prefrontal cortex in constructing reappraisal strategies that modulate activity in emotion-processing systems.     

Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe (MTL), right hippocampus, parahippocampal cortex (PHC) and amygdala. Further, there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.     

Preoperative functional MRI localization of language areas in Chinese patients with brain tumors Validation with intraoperative electrocortical mapping

Ten Chinese patients with brain tumors involving language regions were selected.Preoperative functional MRI was performed to locate Broca’s or Wernicke’s area,and the cortex that was essential for language function was determined by electrocortical mapping.A site-by-site comparison between functional MRI and electrocortical mapping was performed with the aid of a neuronavigation device.Results showed that the sensitivity and specificity of preoperative functional MRI were 80.0% and 85.0% in Broca’s area and 66.6% and 85.2% in Wernicke’s area,respectively.These experimental findings indicate that functional MRI is an accurate,reliable technique with which to identify the location of Wernicke’s area or Broca’s area in patients with brain tumors.     

Advances in longitudinal studies of amnestic mild cognitive impairment and Alzheimer＇s disease based on multi-modal MRI techniques

Amnestic mild cognitive impairment （aMCI） is a prodromal stage of Alzheimer＇s disease （AD）, and 75%-80% of aMCI patients finally develop AD. So, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI （sMRI）, functional MRI （fMRI）, and diffusion tensor imaging （DTI） respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques （e.g., sMRI, fMRI, and DTI） can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.     

Adolescent social isolation influences cognitive function in adult rats

Adolescence is a critical period for neurodevelopment. Evidence from animal studies suggests that isolated rearing can exert negative effects on behavioral and brain development. The present study aimed to investigate the effects of adolescent social isolation on latent inhibition and brain-derived neurotrophic factor levels in the forebrain of adult rats. Male Wistar rats were randomly divided into adolescent isolation (isolated housing, 38-51 days of age) and social groups. Latent inhibition was tested at adulthood. Brain-derived neurotrophic factor levels were measured in the medial prefrontal cortex and nucleus accumbens by an enzyme-linked immunosorbent assay. Adolescent social isolation impaired latent inhibition and increased brain-derived neurotrophic factor levels in the medial prefrontal cortex of young adult rats. These data suggest that adolescent social isolation has a profound effect on cognitive function and neurotrophin levels in adult rats and may be used as an animal model of neurodevelopmental disorders.     

Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia

Schizophrenia is hypothesized to arise from disrupted brain connectivity. This "dysconnectivity hypothesis" has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex(PFC) and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging(DTI) and functional magnetic resonance imaging(f MRI), make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and f MRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefl y discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.     

The Glutamatergic Postrhinal Cortex–Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex(POR) and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatialmemory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.     

Promises and pitfalls of immune-based strategies for Huntington's disease

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease characterized by the selec-tive loss of neurons in the striatum and cortex, leading to progressive motor dysfunction, cognitive decline and behavioral symptoms. HD is caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin. Several studies have suggested that inflammation is an important feature of HD and it is already observed in the early stages of the disease. Recently, new molecules presenting anti-inflammatory and/or immunomodulatory have been investigated for HD. The objective of this review is to discuss the data obtained so far on the immune-based therapeutic strategies for HD.     

A network-based cognitive training induces cognitive improvements and neuroplastic changes in patients with relapsing-remitting multiple sclerosis: an exploratory case-control study

Cognitive impairments are commonly observed in patients with multiple sclerosis and are associated with lower levels of quality of life. No consensus has been reached on how to tackle effectively cognitive decline in this clinical population non-pharmacologically. This exploratory case-control study aims to investigate the effectiveness of a hypothesis-based cognitive training designed to target multiple domains by promoting the synchronous co-activation of different brain areas and thereby improve cognition and induce changes in functional connectivity in patients with relapsing-remitting multiple sclerosis. Forty-five patients(36 females and 9 males, mean age 44.62 ± 8.80 years) with clinically stable relapsing-remitting multiple sclerosis were assigned to either a standard cognitive training or to control groups(sham training and nonactive control). The standard training included twenty sessions of computerized exercises involving various cognitive functions supported by distinct brain networks. The sham training was a modified version of the standard training that comprised the same exercises and number of sessions but with increased processing speed load. The non-active control group received no cognitive training. All patients underwent comprehensive neuropsychological and magnetic resonance imaging assessments at baseline and after 5 weeks. Cognitive and resting-state magnetic resonance imaging data were analyzed using repeated measures models. At reassessment, the standard training group showed significant cognitive improvements compared to both control groups in memory tasks not specifically targeted by the training: the Buschke Selective Reminding Test and the Semantic Fluency test. The standard training group showed reductions in functional connectivity of the salience network, in the anterior cingulate cortex, associated with improvements on the Buschke Selective Reminding Test. No changes were observed in the sham training group. These findings suggest that multi-domain training that stimulates multiple brain areas synchronously may improve cognition in people with relapsing-remitting multiple sclerosis if sufficient time to process training material is allowed. The associated reduction in functional connectivity of the salience network suggests that training-induced neuroplastic functional reorganization may be the mechanism supporting performance gains. This study was approved by the Regional Ethics Committee of Yorkshire and Humber(approval No. 12/YH/0474) on November 20, 2013.     

Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients

A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.     

Pine pollen inhibits cell apoptosis-related protein expression in the cerebral cortex of mice with arsenic poisoning

Previous studies have demonstrated that pine pollen can inhibit cerebral cortical cell apoptosis in mice with arsenic poisoning.The present study sought to detect the influence of pine pollen on apoptosis-related proteins.Immunohistochemistry,western blotting and enzyme-linked immunosorbent assays were used to measure the levels of apoptosis-related proteins in the cerebral cortex of mice with arsenic poisoning.Results indicated that pine pollen suppressed cell apoptosis in the cerebral cortex of arsenic-poisoned mice by reducing Bax,Bcl-2 protein expression and increasing p53 protein expression.     

精神分裂症认知功能障碍的脑网络组研究(英文)

Impaired cognitive function,along with positive and negative symptoms,is a core clinical feature of schizophrenia.Earlier studies suggest that impaired cognitive functioning should be assessed from the perspective of brain networks.The recently developed brainnetome approach to evaluating brain networks-an approach that was initially developed by Chinese scientists-provides a new methodology for studying this issue.In this paper we first introduce the concept of brainnetome.We then review recent progress in developing a brainnetome of impaired cognitive function in people with schizophrenia.The models of the relevant brain networks considered were created using data obtained from functional and anatomical brain imaging technologies at different levels of analysis:networks centered on regions of interest,networks related to specific cognitive functions,whole brain networks,and the attributes of brain networks.Finally,we discuss the current challenges and potential new directions for research about brainnetome.