Age effect on the default mode network,inner thoughts,and cognitive abilities

Age-related effects on the default mode network (DMN) connectivity as measured at rest using functional magnetic resonance imaging (fMRI) are now well described. Little is known however about the relationships between these changes and age-related effects on cognition or on the unconstrained thoughts which occur during the resting-state scan, called inner experience. Brain resting-state activity, inner experience, and cognitive ability measurements were obtained in 70 participants aged 19–80 years. The anterior-posterior disruption of DMN activity with age reported in previous studies was recovered here. A significant effect of age was also found on cognitive abilities but not on inner experience. Finally, age-related changes in DMN connectivity were found to correlate with cognitive abilities, and more specifically with autobiographical memory performance. These findings provide new information to fuel the debate on the role of the brain default mode and more specifically on the effect of age-related changes in resting-state activity as measured with fMRI.     

Combining spatial and temporal information to explore resting-state networks changes in abstinent heroin-dependent individuals

Majority of previous heroin fMRI studies focused on abnormal brain function in heroin-dependent individuals. However, few fMRI studies focused on the resting-state abnormalities in heroin-dependent individuals and assessed the relationship between the resting-state functional connectivity changes and duration of heroin use. In the present study, discrete cosine transform (DCT) was employed to explore spatial distribution of low frequency BOLD oscillations in heroin-dependent individuals and healthy subjects during resting-state; meanwhile resting-state functional connectivity analysis was used to investigate the temporal signatures of overlapping brain regions obtained in DCT analysis among these two groups. Main finding of the present study is that the default mode network (DMN) and rostral anterior cingulate cortex (rACC) network of heroin-dependent individuals were changed compared with healthy subjects. More importantly, these changes negatively correlated with duration of heroin use. These resting-state functional abnormalites in heroin-dependent individuals provided evidence for abnormal functional organization in heroin-dependent individuals, such as functional impairments in decision-making and inhibitory control.     

Gray matter deficits and resting-state abnormalities in abstinent heroin-dependent individuals

Previous neuroimaging studies have demonstrated both structural and functional damages in heroin-dependent individuals. However, few studies investigated gray matter deficits and abnormal resting-state networks together in heroin-dependent individuals. In the present study, voxel-based morphometry (VBM) was used to identify brain regions with gray matter density reduction. Resting-state fMRI connectivity analysis was employed to assess potential functional abnormalities during resting-state. All clinical significances were investigated by examining their association with duration of heroin use. Compared with healthy subjects, heroin-dependent individuals showed significant reduction in gray matter density in the right dorsolateral prefrontal cortex (DLPFC) and a decrease in resting-state functional connectivity between the right DLPFC and left inferior parietal lobe (IPL). The gray matter density of the right DLPFC and its resting-state functional connectivity with the left IPL both showed significantly negative correlation with duration of heroin use, which were likely to be related to the functional impairments in decision-making and cognitive control exhibited by heroin-dependent individuals. Our findings demonstrated that long heroin dependence impairs the right DLPFC in heroin-dependent individuals, including structural deficits and resting-state functional impairments.     

慢性失眠患者大脑蓝斑的异常静息态功能连接

目的:利用功能连接方法观察慢性失眠患者静息态下蓝斑的异常功能连接。方法:采集49例慢性失眠患者以及47例性别年龄和受教育程度相匹配的健康对照组的功能磁共振图像,以蓝斑为感兴趣区域,与全脑其他体素进行功能连接分析,得到两组之间功能连接的差异脑区,再对异常连接脑区的功能连接值与临床量表分数做相关分析。结果:与对照组相比,慢性失眠患者蓝斑与右楔前叶皮质、右后扣带回皮质、左颞中回皮质、左距状沟周围皮质、右眶部额上回皮质之间的功能连接增强（P<0.05, FDR校正）,并且蓝斑与左颞中回皮质之间功能连接值与抑郁自评量表呈正相关（P=0.021）。结论:慢性失眠患者蓝斑与多个脑区（主要是默认模式网络）出现的异常功能连接,可能有助于更好地理解慢性失眠的神经生物学机制,可能为失眠的高度唤醒假说提供新的影像学证据。     

基于独立成分分析和时间相关分析的脑功能连通研究方法

目的：利用静息状态功能磁共振成像（functional magnetic resonance imaging，fMRI）技术，提出联合独立成分分析（independent component analysis，ICA）和时间相关分析的人脑功能连通性研究方法。方法：首先采用空间ICA定位任务激活的脑区；然后选择一个激活区作为感兴趣区域（region of interest，ROI），采用时间相关分析方法检测静息状态大脑特定皮层的功能连通性，并通过检测人脑运动皮层的功能连通性验证方法的有效性。结果：大脑运动皮层功能连通网络包括初级运动区、辅助运动区、初级感觉皮层、背侧前运动区和后顶骨体觉区。实验结果表明，静息状态下。时间相关分析检测到的运动皮层的功能连通网络与已知的解剖连通相一致。结论：利用静息fMRI。结合空间ICA和时间相关分析方法。检测了静息时人脑运动皮层的功能连通网络。为脑区间功能连通的研究提供了一种简便的、无损的、有效的研究方法。     

基于独立成分分析和时间相关分析的脑功能连通研究方法[英文]

目的:利用静息状态功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,提出联合独立成分分析(independent component analysis,ICA)和时间相关分析的人脑功能连通性研究方法。方法:首先采用空间ICA定位任务激活的脑区;然后选择一个激活区作为感兴趣区域(region of interest,ROI),采用时间相关分析方法检测静息状态大脑特定皮层的功能连通性,并通过检测人脑运动皮层的功能连通性验证方法的有效性。结果:大脑运动皮层功能连通网络包括初级运动区、辅助运动区、初级感觉皮层、背侧前运动区和后顶骨体觉区。实验结果表明,静息状态下,时间相关分析检测到的运动皮层的功能连通网络与已知的解剖连通相一致。结论:利用静息fMRI,结合空间ICA和时间相关分析方法,检测了静息时人脑运动皮层的功能连通网络,为脑区间功能连通的研究提供了一种简便的、无损的、有效的研究方法。     

Detecting Functional Connectivity in fMRI Using PCA and Regression Analysis

A fMRI connectivity analysis approach combining principal component analysis (PCA) and regression analysis is proposed to detect functional connectivity between the brain regions. By first using PCA to identify clusters within the vectors of fMRI time series, more energy and information features in the signal can be maintained than using averaged values from brain regions of interest. Then, regression analysis can be applied to the extracted principal components in order to further investigate functional connectivity. Finally, t-test is applied and the patterns with t-values lager than a threshold are considered as functional connectivity mappings. The validity and reliability of the presented method were demonstrated with both simulated data and human fMRI data obtained during behavioral task and resting state. Compared to the conventional functional connectivity methods such as average signal based correlation analysis, independent component analysis (ICA) and PCA, the proposed method achieves competitive performance with greater accuracy and true positive rate (TPR). Furthermore, the ‘default mode’ and motor network results of resting-state fMRI data indicate that using PCA may improve upon application of existing regression analysis methods in study of human brain functional connectivity.     

Dopamine and frontostriatal networks in cognitive aging

Recent studies have linked dopamine to differences in behavior and brain activity in normal individuals. We explored these relationships in older and younger adults by investigating how functional connectivity between the striatum and prefrontal cortex is related to caudate dopamine and verbal working memory task performance. We studied 12 young and 18 older participants with functional magnetic resonance imaging (fMRI) during this task, and used positron emission tomography with the tracer 6-[¹⁸F]-fluoro-L-m-tyrosine (FMT) to assess dopamine synthesis capacity. Younger adults had a greater extent of frontal caudate functional connectivity during the load-dependent delay period of the working memory task than the older participants. Across all subjects, the extent of this functional connectivity was negatively correlated with dopamine synthesis capacity, such that participants with the greatest connectivity had the lowest caudate 6-[¹⁸F]-fluoro-L-m-tyrosine (FMT) signal. Additionally, the extent of functional connectivity was positively correlated with working memory performance. Overall these data suggest interdependencies exist between frontostriatal functional connectivity, dopamine, and working memory performance and that this system is functioning suboptimally in normal aging.     

Testosterone improves verbal learning and memory in postmenopausal women: Results from a pilot study

Objective

To explore the effects of testosterone on cognitive performance in healthy postmenopausal women.

Study design

Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47–60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison.

Main outcome measures

Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks.

Results

There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group (p < 0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p < 0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p < 0.02).

Conclusion

Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study.     

Estrogen therapy selectively enhances prefrontal cognitive processes: a randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women

OBJECTIVE: Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ET's influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. DESIGN: In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n = 26) or placebo transdermal patches (n = 26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. RESULTS: Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P = 0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P < 0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P < 0.001). CONCLUSIONS: Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep.     

Long term memory profile of disorders associated with dysregulation of the RAS-MAPK signaling cascade

In the present study we evaluated long term memory in twenty individuals with molecularly confirmed diagnosis of Noonan syndrome and LEOPARD syndrome, two disorders caused by mutations in genes coding transducers participating in the RAS-MAPK signaling cascade. The profile of explicit long term memory abilities was investigated using PROMEA, which includes a battery of tests specifically developed to assess memory and learning in verbal, visual and spatial domains. Ten individuals (50%) had impaired (≤5th percentile) or below average (≤15th percentile) performance on a delayed verbal free recall memory task, four (20%) on a delayed visual recognition memory task, and only one (5%) on a delayed spatial recognition memory task. Our data suggest that dysregulation of the RAS-MAPK cascade may be associated with a pattern of reduced verbal recall memory performance but relative sparing of visual and spatial recognition memory.     

首发未服药抑郁症静息态默认网络研究

目的:分析首发未治疗抑郁症患者静息态默认网络功能改变。方法:采用独立成分分析方法,对25例首发抑郁症患者与25名正常被试进行静息态功能磁共振数据处理,并依据空间最匹配原则对缺省模式网络的独立成分进行挑选,分析患者默认网络的改变。结果:与正常对照比较,抑郁症患者的默认网络呈现前部升高后部降低的模式:即背部额内侧回、腹部额内侧回和腹部前扣带回功能连接升高,楔前叶和后扣带回、角回功能连接减低。结论:静息态下抑郁症默认网络存在广泛的异常。     

基于功能连接的屈光参差性弱视视觉网络损伤研究

目的基于功能连接算法分析屈光参差性弱视和正常对照组的功能性磁共振成像(functional magnetic resonance imaging,fMRI)数据,通过对比弱视患者脑部自发活动的视觉网络功能连接异常,揭示其视觉损伤机制。方法在闭眼静息条件下采集21名弱视成年人和21名正常对照组的fMRI数据,进行去噪、校正等预处理后,计算初级视觉网络、高级视觉网络和视觉空间网络3个典型的视觉网络内和网络间的功能连接系数,并采用双样本t检验进行统计分析。结果屈光参差性弱视与正常对照组在初级视觉网络中差异无统计学意义,在高级视觉网络和视觉空间网络中差异具有统计学意义,并且它们网络之间的功能连接差异也无统计学意义。结论基于功能连接的静息态功能磁共振分析是有效的非侵入式脑区功能性连接异常研究方法,能够反映屈光参差性弱视不同视觉网络的自发脑部活动脑区异常表现,对于弱视致病机制模型研究和提出新的治疗方法都有重要启发。     

Functional topography of the thalamocortical system in human

Various studies have indicated that the thalamus is involved in controlling both cortico-cortical information flow and cortical communication with the rest of the brain. Detailed anatomy and functional connectivity patterns of the thalamocortical system are essential to understanding the cortical organization and pathophysiology of a wide range of thalamus-related neurological and neuropsychiatric diseases. The current study used resting-state fMRI to investigate the topography of the human thalamocortical system from a functional perspective. The thalamus-related cortical networks were identified by performing independent component analysis on voxel-based thalamic functional connectivity maps across a large group of subjects. The resulting functional brain networks were very similar to well-established resting-state network maps. Using these brain network components in a spatial regression model with each thalamic voxel’s functional connectivity map, we localized the thalamic subdivisions related to each brain network. For instance, the medial dorsal nucleus was shown to be associated with the default mode, the bilateral executive, the medial visual networks; and the pulvinar nucleus was involved in both the dorsal attention and the visual networks. These results revealed that a single nucleus may have functional connections with multiple cortical regions or even multiple functional networks, and may be potentially related to the function of mediation or modulation of multiple cortical networks. This observed organization of thalamocortical system provided a reference for studying the functions of thalamic sub-regions. The importance of intrinsic connectivity-based mapping of the thalamocortical relationship is discussed, as well as the applicability of the approach for future studies.     

Preliminary data on the effect of culture on the assessment of Alzheimer's disease-related verbal memory impairment with the International Shopping List Test

The International Shopping List Test (ISLT) is a measure of verbal learning and memory, developed specifically for use in people from different cultural and linguistic backgrounds. In this report, we describe two studies that examined the ISLT's ability to detect memory impairment and memory decline in patients with mild Alzheimer's disease (AD) from a range of cultural and linguistic backgrounds. In Study 1, the performance of Australian-English-speaking adults with mild AD was compared with that of native Australian-English- and Korean-speaking patients with mild AD. Compared with controls, patients with AD from both language groups showed large but equivalent impairments in total recall, delayed recall, rate of learning, and primacy and retention-weighted recall (RWR) measures on the ISLT. In Study 2, the rate of deterioration in verbal memory over 1 year was examined in groups of native Canadian-English, French, and Korean speakers with mild AD using the total recall, delayed recall, and RWR measures. Rates of change on all three measures were equivalent across the language groups, although the magnitude of deterioration was most pronounced for the total recall and RWR measures. Taken together, these results suggest that the ISLT is valid and reliable for the assessment of verbal learning and memory impairment and decline in patients with mild AD from diverse language groups.     

Modulation of limbic-cerebellar functional connectivity enables alcoholics to recognize who is who

Chronic alcoholism is known to disrupt functions served by distributed brain systems, including limbic and frontocerebellar circuits involved in resting-state and task-activated networks subserving component processes of memory often affected in alcoholics. Using an fMRI paradigm, we investigated whether memory performance by alcoholics on a face–name association test previously observed to be problematic for alcoholics could be explained by desynchronous activity between nodes of these specific networks. While in the scanner, 18 alcoholics and 15 controls performed a face–name associative learning task with different levels of processing at encoding. This task was designed to activate the hippocampus, cerebellum, and frontal cortex. Alcoholics and controls were also scanned at rest. Twelve alcoholics and 12 controls were selected to be matched on face–name recognition performance. Task-related fMRI analysis indicated that alcoholics had preserved limbic activation but lower cerebellar activation (Crus II) than the controls in the face–name learning task. Crus II was, therefore, chosen as a seed for functional connectivity MRI analysis. At rest, the left hippocampus and left Crus II had positively synchronized activity in controls, while hippocampal and cerebellar activities were negatively synchronized in alcoholics. Task engagement resulted in hippocampal-cerebellar desynchronization in both groups. We speculate that atypical cerebello-hippocampal activity synchronization during rest in alcoholics was reset to the normal pattern of asynchrony by task engagement. Aberrations from the normal pattern of resting-state default mode synchrony could be interpreted as enabling preserved face–name associative memory in alcoholism.     

Investigation of a functional quinine oxidoreductase (NQO2) polymorphism and cognitive decline

NAD(P)H dehydrogenase quinone 2 (NQO2) is a quinone reductase whose functions include the reduction of both oxidative stress during the redox cycle and neurotoxicity caused by the metabolism of catecholamines. We have investigated a functional non-synonymous exon 3 single nucleotide polymorphism (rs1143684) within the NQO2 gene for association with cognitive decline using a cohort of 722 community-dwelling older individuals aged 50 years and over. The volunteers had completed tests that measured fluid intelligence, processing speed, immediate/delayed verbal recall and semantic memory. We observed a nominal significant association between this polymorphism and the trajectory of delayed memory recall over time (p=0.029). No other associations were seen with the decline of other cognitive abilities.     

Motor brain regions are involved in the encoding of delayed intentions: a fMRI study.

In studies of prospective memory, recall of the content of delayed intentions is normally excellent, probably because they contain actions that have to be enacted at a later time. Action words encoded for later enactment are more accessible from memory than those encoded for later verbal report [Freeman, J.E., and Ellis, J.A. 2003a. The representation of delayed intentions: A prospective subject-performed task? Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 976-992.]. As this higher assessibility is lost when the intended actions have to be enacted during encoding, or when a motor interference task is introduced concurrent to intention encoding, Freeman and Ellis suggested that the advantage of to-be-enacted actions is due to additional preparatory motor operations during encoding. Accordingly, in a fMRI study with 10 healthy young participants, we investigated whether motor brain regions are differentially activated during verbal encoding of actions for later enactment with the right hand in contrast to verbal encoding of actions for later verbal report. We included an additional condition of verbal encoding of abstract verbs for later verbal report to investigate whether the semantic motor information inherent in action verbs in contrast to abstract verbs activates motor brain regions different from those involved in the verbal encoding of actions for later enactment. Differential activation for the verbal encoding of to-be-enacted actions in contrast to to-be-reported actions was found in brain regions known to be involved in covert motor preparation for hand movements, i.e. the postcentral gyrus, the precuneus, the dorsal and ventral premotor cortex, the posterior middle temporal gyrus and the inferior parietal lobule. There was no overlap between these brain regions and those differentially activated during the verbal encoding of actions in contrast to abstract verbs for later verbal report. Consequently, the results of this fMRI study suggest the presence of preparatory motor operations during the encoding of delayed intentions requiring a future motor response, which cannot be attributed to semantic information inherent to action verbs.     

The role of the frontal lobes in memory: evidence from unilateral frontal resections for relief of intractable epilepsy.

The current investigation explored processes associated with memory deficits in patients with frontal lobe dysfunction. Specifically, we examined deficits associated with the encoding, consolidation, and retrieval of information in memory in 53 patients who underwent either a unilateral frontal (N=13) or temporal (N=40) lobe resection for relief of intractable epilepsy. Post-surgical memory scores indicated that the frontal group and the temporal group did not differ in consolidation of information, as defined by the information forgotten between immediate and delayed recall. Instead, the temporal group evidenced significantly poorer recall of verbal information at both immediate and delayed recall. This effect was especially strong in the left temporal group for the recall of verbal information. Although no group differences were observed in the degree to which patients semantically organized information or made recency discriminations, the frontal group exhibited significantly weaker release from proactive interference than the temporal group, suggesting some impairment in encoding and retrieval processes associated with frontal lobe dysfunction.     

Material-specific memory in traumatic brain injury: differential effects during acquisition, recall, and retention

Material-specific memory refers to the ability to learn and recall new episodic information on the basis of the nature of the stimulus material (e.g., verbal vs. nonverbal-visuospatial). Structural equation modeling was used to analyze data from a sample of patients with traumatic brain injury to compare 3 models of memory functioning: material-specific, material-specific plus general, and general (non-material-specific). The models were examined separately for acquisition, delayed free recall, and retention aspects of memory. Results suggest that, at least in a population with traumatic brain injury, the acquisition of new information takes place in a material-specific memory fashion, delayed free recall involves both material-specific and general (non-material-specific) memory components, but retention relies primarily on general (non-material-specific) memory processes.