The functional connectivity in the motor loop of human basal ganglia

Basal ganglia interact in a complex way which is still not completely understood. The model generally used to explain basal ganglia interactions is based on experimental data in animals, but its validation in humans has been hampered by methodological restrictions. The time-relationship (partial correlation) of the fluctuations of the blood-oxygen-level-dependent signals recorded in the main basal ganglia was used here (32 healthy volunteers; 18–72 years of age; 16 males and 16 females) to test whether the interaction of the main basal ganglia in humans follows the pattern of functional connectivity in animals. Data showed that most basal ganglia have a functional connectivity which is compatible with that of the established closed-loop model. The strength of the connectivity of some basal ganglia changed with finger motion, suggesting that the functional interactions between basal ganglia are quickly restructured by the motor tasks. The present study with the motor cortico-BG loop centers supports the circling dynamic of the basal ganglia model in humans, showing that motor tasks may change the functional connectivity of these centers.     

Altered functional connectivity of basal ganglia circuitry in dental phobia

Recent symptom provocation studies that compared patients suffering from dental phobia with healthy controls identified hyperactivation of basal ganglia structures, but none have assessed striatal functional connectivity. We reanalyzed data from a previous functional magnetic resonance imaging study on dental phobia. Patients (20 men, 25 women) and healthy controls (18 men, 23 women) had been exposed to pictures showing dental treatment, and neutral contents. We conducted connectivity analyses via psychophysiological interactions (PPIs). Relative to non-phobic controls, the patients showed decreased connectivity between prefrontal and basal ganglia regions. Moreover, the clinical group was characterized by increased internal basal ganglia connectivity, which was more pronounced in female compared with male patients. This study provides first evidence for an altered information flow within a fronto-striatal network in dentophobic individuals during visual symptom provocation, which can be considered a neuromarker of this disorder.     

The functional connectivity of intralaminar thalamic nuclei in the human basal ganglia

Projections of the centromedian‐parafasicularis neurons of the intralaminar thalamus are major inputs of the striatum. Their functional role in the activity of human basal ganglia (BG) is not well known. The aim of this work was to study the functional connectivity of intralaminar thalamic nuclei with other BG by using the correlations of the BOLD signal recorded during “resting” and a motor task. Intralaminar nuclei showed a marked functional connectivity with all the tested BG, which was observed during “resting” and did not change with the motor task. As regards the intralaminar nuclei, BG connectivity was much lower for the medial dorsal nucleus (a thalamic nucleus bordering the intralaminar nuclei) and for the default mode network (although intralaminar nuclei showed a negative correlation with the default mode network). After the “regression” of intralaminar nuclei activity (partial correlation), the functional connectivity of the caudate and putamen nuclei with other BG decreased (but not with the primary sensorimotor cortex). Present data provide evidence that intralaminar nuclei are not only critical for striatal activity but also for the global performance of human BG, an action involving subcortical BG loops more than cortico‐subcortical loops. The high correlation found between BG suggest that, similarly to that reported in other brain centers, the very‐slow frequency fluctuations are relevant for the functional activity of these centers. Hum Brain Mapp 36:1335–1347, 2015. © 2014 Wiley Periodicals, Inc .     

Increased neural connectivity between the hypothalamus and cortical resting-state functional networks in chronic migraine

Journal of Neurology - The findings of resting-state functional MRI studies have suggested that abnormal functional integration between interconnected cortical networks characterises the brain of...     

长期海洛因成瘾者前额叶功能连接的静息态fMRI研究

目的 利用静息态fMRI探讨长期海洛因成瘾者前额叶功能连接的变化情况.方法 13例长期海洛因成瘾者和14例正常者接受静息态fMRI检查,对数据进行相关的预处理后,以前额叶为种子点与全脑每个体素进行相关分析,比较海洛因成瘾组与正常对照组前额叶功能连接的变化情况.结果 以左侧前额叶为种子点进行功能连接分析,海洛因成瘾组左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显低于正常对照组:以右侧前额叶为种子点进行功能连接分析,海洛因成瘾组右侧前额叶与左侧眶额叶、左侧额中回功能连接明显低于正常对照组.结论 长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,前额叶可能参与了海洛因成瘾的维持与戒断后复吸.

Abstract：

Objective To explore the changes of functional connectivity of the prefrontal cortex in chronic heroin addicts under resting-state functional MRI (fMRI). Methods Resting fMRI examination was performed on 13 chronic heroin addicts and 14 healthy volunteers. After pre-processing the resting-state fMRI data, the prefrontal cortex was selected as the seed region, with which a whole-brain voxel temporal correlation in Iow frequency fMRI fluctuations was analyzed and the changes of functional connectivity of the prefrontal lobe in both chronic heroin addicts and healthy volunteers were calculated with SPM5 software. Results Compared with that in the control group, the functional connectivity between the left prefrontal cortex and the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus, right precuneus in the heroin addiction group was significantly decreased. The functional connectivity between the right prefrontal cortex and the left orbital frontal cortex, left middle frontal gyrus in thc heroin addiction group was also significantly decreased as compared with that in the control group. Conclusion Functional connectivity of prefrontal cortex in chronic heroin addicts decreases, indicating that the prefrontal cortex may be involved in the maintenance of heroin addiction and relapse after withdrawal.     

The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD

We examined the effect of a single dose of methylphenidate (MPH) on whole brain functional connectivity, assessed using resting state functional MRI (rsfMRI), in young people with ADHD. 16 young people with ADHD participated in two rsfMRI scans in a randomized, placebo-controlled study with an acute dose of MPH (20 mg). 15 typically developing controls also performed the task under placebo conditions. The network-based statistic (NBS) was used to identify differential connectivity patterns between the MPH and placebo conditions in the ADHD group. Mean connectivity of the resulting sub-network was examined in the ADHD and control groups. Resting state functional connectivity (RSFC) analysis revealed significantly reduced connectivity under MPH compared to placebo in young people with ADHD. Findings were robust across a range of thresholds. No sub-networks of increased connectivity were found at any threshold. Mean connectivity of the identified sub-network was significantly higher in ADHD individuals in the placebo condition compared to controls, however there was no difference between MPH condition and controls. We demonstrated a significant MPH-related reduction in RSFC in a large, robust network primarily involving occipital, temporal and cerebellar regions, and visual, executive and default mode networks. These findings suggest that MPH is ‘normalising’ a higher RSFC in young people with ADHD. This study is a novel addition to the understanding of treatment effects on the brain in ADHD.     

Cognition and resting-state functional connectivity in schizophrenia

Individuals with schizophrenia consistently display deficits in a multitude of cognitive domains, but the neurobiological source of these cognitive impairments remains unclear. By analyzing the functional connectivity of resting-state functional magnetic resonance imaging (rs-fcMRI) data in clinical populations like schizophrenia, research groups have begun elucidating abnormalities in the intrinsic communication between specific brain regions, and assessing relationships between these abnormalities and cognitive performance in schizophrenia. Here we review studies that have reported analysis of these brain–behavior relationships. Through this systematic review we found that patients with schizophrenia display abnormalities within and between regions comprising (1) the cortico-cerebellar-striatal-thalamic loop and (2) task-positive and task-negative cortical networks. Importantly, we did not observe unique relationships between specific functional connectivity abnormalities and distinct cognitive domains, suggesting that the observed functional systems may underlie mechanisms that are shared across cognitive abilities, the disturbance of which could contribute to the “generalized” cognitive deficit found in schizophrenia. We also note several areas of methodological change that we believe will strengthen this literature.     

部分性发作癫痫患者静息状态功能磁共振默认模式网络的功能连接改变

目的 应用静息状态功能磁共振成像(fMRI)探讨部分性发作癫痫患者静息状态下的脑功能改变.方法 对60例部分性发作癫痫患者(患者组)和60名性别、年龄和教育程度匹配的健康对照者(对照组),使用3.0T磁共振采集两组的静息状态下fMRI数据,采用功能连接方法分析计算脑区的默认模式网络的功能连接,利用SPM5软件分析比较患者组和对照组脑功能的差异.结果 患者组的默认模式网络的功能连接主要包括左侧楔前叶/后扣带回和角回、扣带回;对照组的功能连接主要包括左侧楔前叶/后扣带回和右侧角回,双侧内侧额叶和颞叶;患者组的左侧顶下小叶[坐标值(x,y,z):-57,-39,48;t=4.90,P＜0.01]、左侧缘上回[坐标值(x,y,z):-63,- 48,33;t=4.25,P＜0.01]、左侧海马旁回[坐标值(x,y,z):-30,-6,-21;t =4.05,P＜0.01]、左侧颞上回[坐标值(x,y,z):-48,-39,6;t=3.72,P＜0.01],左侧钩回[坐标值(x,y,z):-24,6,- 36;=4.56,P＜0.01]及右侧钩回[坐标值(x,y,z):33,-15,- 36;t=4.00,P＜0.01]的默认模式网络功能连接较对照组降低;未发现功能连接升高的脑区.结论 部分性发作癫痫患者静息状态下脑区的功能连接改变,可能是部分性发作癫痫潜在的病理生理机制.静息状态fMRI能发现常规MRI正常的癫痫患者的广泛脑功能异常,是一种无创的研究癫痫患者脑功能的有效方法.     

Residual functional connectivity in the split-brain revealed with resting-state functional MRI

Split-brain patients present a unique opportunity to address controversies regarding subcortical contributions to interhemispheric coordination. We characterized residual functional connectivity in a complete commissurotomy patient by examining patterns of low-frequency BOLD functional MRI signal. Using independent components analysis and region-of-interest-based functional connectivity analyses, we demonstrate bilateral resting state networks in a patient lacking all major cerebral commissures. Compared with a control group, the patient's interhemispheric correlation scores fell within the normal range for two out of three regions examined. Thus, we provide evidence for bilateral resting state networks in a patient with complete commissurotomy. Such continued interhemispheric interaction suggests that, at least in part, cortical networks in the brain can be coordinated by subcortical mechanisms.     

Altered resting-state functional connectivity of the cerebellum in schizophrenia

Structural and functional abnormalities of the cerebellum in schizophrenia have been reported. Most previous studies investigating resting-state functional connectivity (rsFC) have relied on a priori restrictions on seed regions or specific networks, which may bias observations. In this study, we aimed to elicit the connectivity alterations of the cerebellum in schizophrenia in a hypothesis-free approach. Ninety-five schizophrenia patients and 93 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). A voxel-wise data-driven method, resting-state functional connectivity density (rsFCD), was used to investigate cerebellar connectivity changes in schizophrenia patients. Regions with altered rsFCD were chosen as seeds to perform seed-based resting-state functional connectivity (rsFC) analyses. We found that schizophrenia patients exhibited decreased rsFCD in the right hemispheric VI; moreover, this cerebellar region showed increased rsFC with the prefrontal cortex and subcortical nuclei and decreased rsFC with the visual cortex and sensorimotor cortex. In addition, some rsFC changes were associated with positive symptoms. These findings suggest that abnormalities of the cerebellar hub and cerebellar-subcortical-cortical loop may be the underlying mechanisms of schizophrenia.     

A spiking neural network based on the basal ganglia functional anatomy

We introduce a spiking neural network of the basal ganglia capable of learning stimulus–action associations. We model learning in the three major basal ganglia pathways, direct, indirect and hyperdirect, by spike time dependent learning and considering the amount of dopamine available (reward). Moreover, we allow to learn a cortico-thalamic pathway that bypasses the basal ganglia. As a result the system develops new functionalities for the different basal ganglia pathways: The direct pathway selects actions by disinhibiting the thalamus, the hyperdirect one suppresses alternatives and the indirect pathway learns to inhibit common mistakes. Numerical experiments show that the system is capable of learning sets of either deterministic or stochastic rules.     

精神分裂症患者基底节功能连接的静息态fMRI研究

目的通过功能磁共振(fMRI)技术,探讨精神分裂症患者静息状态下与基底节异常连接的脑区。方法采用3.0T功能磁共振成像技术检测15例精神分裂症患者与12例正常对照组在静息状态下的全脑功能活动。采用功能连接分析对比两组被试的基底节(双侧尾状核、壳核和苍白球共6个区域)与全脑功能连接的差异。结果与对照组相比,精神分裂症患者的内侧额上回、后扣带与尾状核的功能连接上升;左侧额上回、右侧前扣带与左侧苍白球功能连接上升;左内侧额上回与右侧苍白球功能连接上升;左侧额上回与左侧壳核功能连接上升。差异均有统计学意义。结论精神分裂症患者的基底节区域与默认网络的重要节点功能连接上升,提示基底节-默认网络环路出现异常,这可能与精神分裂症的病理机制有关。     

Subthreshold depression is associated with impaired resting-state functional connectivity of the cognitive control network

Subthreshold depression (StD) is a prevalent condition associated with social morbidity and increased service utilization, as well as a high risk of developing into a major depressive disorder (MDD). The lack of well-defined diagnostic criteria for StD has limited research on this disorder, with very few brain-imaging studies examining the neurobiology of StD. Yet, identifying the neural pathology of StD has the potential to elucidate risk factors and prognostic markers for major depression and is crucial for developing tailored treatments for patients at mild stages of depression. We investigated resting-state functional connectivity (rs-FC) of the cognitive control network (CCN), known to be dysregulated in MDD, using the bilateral dorsolateral prefrontal cortex (DLPFC) as a seed, focusing on two cohorts of StD subjects (young and middle aged) as well as matched controls. Irrespective of age, we found a significant rs-FC decrease in the CCN of the StD subjects, compared with matched controls, particularly between the DLPFC and the brain regions associated with the representation of self and other mental states (temporo-parietal junction (TPJ) and precuneus), as well as salience detection and orienting (insula). The functional connectivity between the DLPFC and the left TPJ was also associated with depressive symptom scores measured by the Center for Epidemiologic Studies Depression Scale. This finding may shed light on the neural pathology of StD, leading to better understanding of mild stages of depression, its diagnosis and the development of new treatments.     

Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia

Hippocampus has been implicated in participating in the pathophysiology of schizophrenia. However, the functional and anatomical connectivities between hippocampus and other regions are rarely concurrently investigated in schizophrenia. In the present study, both functional magnetic resonance imaging (fMRI) during rest and diffusion tensor imaging (DTI) were performed on 17 patients with paranoid schizophrenia and 14 healthy subjects. Resting-state functional connectivities of the bilateral hippocampi were separately analyzed by selecting the anterior hippocampus as region of interest. The fornix body was reconstructed by diffusion tensor tractography, and the integrity of this tract was evaluated using fractional anisotropy (FA). In patients with schizophrenia, the bilateral hippocampi showed reduced functional connectivities to some regions which have been reported to be involved in episodic memory, such as posterior cingulate cortex, extrastriate cortex, medial prefrontal cortex, and parahippocampus gyrus. We speculated that these reduced connectivity may reflect the disconnectivity within a neural network related to the anterior hippocampus in schizophrenia. Meanwhile the mean FA of the fornix body was significantly reduced in patients, indicating the damage in the hippocampal anatomical connectivity in schizophrenia. The concurrence of the functional disconnectivity and damaged anatomical connectivity between the hippocampus and other regions in schizophrenia suggest that the functional–anatomical relationship need to be further investigated.     

Age-related changes in resting-state functional connectivity in older adults

Age-related changes in the brain connectivity of healthy older adults have been widely studied in recent years, with some differences in the obtained results. Most of these studies showed decreases in general functional connectivity, but they also found increases in some particular regions and areas. Frequently, these studies compared young individuals with older subjects, but few studies compared different age groups only in older populations. The purpose of this study is to analyze whole-brain functional connectivity in healthy older adult groups and its network characteristics through functional segregation. A total of 114 individuals, 48 to 89 years old, were scanned using resting-state functional magnetic resonance imaging in a resting state paradigm and were divided into six different age groups( 60, 60–64, 65–69, 70–74, 75–79,≥ 80 years old). A partial correlation analysis, a pooled correlation analysis and a study of 3-cycle regions with prominent connectivity were conducted. Our results showed progressive diminution in the functional connectivity among different age groups and this was particularly pronounced between 75 and 79 years old.The oldest group(≥ 80 years old) showed a slight increase in functional connectivity compared to the other groups. This occurred possibly because of compensatory mechanism in brain functioning. This study provides information on the brain functional characteristics of every age group, with more specific information on the functional progressive decline, and supplies methodological tools to study functional connectivity characteristics. Approval for the study was obtained from the ethics committee of the Comisión de Bioética de la Universidad de Barcelona(approval No. PSI2012-38257) on June 5, 2012, and from the ethics committee of the Barcelona's Hospital Clínic(approval No. 2009-5306 and 2011-6604) on October 22, 2009 and April 7, 2011 respectively.     

Functional connectivity in a baseline resting-state network in autism

Brain activity in people with high-functioning autism has been shown to be atypical in a number of ways, including reduced synchronization across areas of activation measured by functional magnetic resonance imaging. This activation atypicality has been observed mostly during the performance of cognitive tasks. This study compares the resting-state network of 57 participants with autism and 57 control participants matched for age and intelligence quotient. The results indicate that both groups have a resting-state network that is very similar both in volume and in organization, but in autism this network is much more loosely connected. This functional underconnectivity was observed in the anterior-posterior connections. The results expand the theory of cortical underconnectivity in autism to the resting state of the brain.     

Changes in brain functional network connectivity after stroke简

Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.