Altered small-world brain functional networks and duration of heroin use in male abstinent heroin-dependent individuals

Although previous studies reported addiction-related alteration in resting-state brain connectivity, it is unclear whether these resting-state connectivity alterations were associated with chronic heroin use. In the current study, graph theory analysis (GTA) was applied to detect abnormal topological properties in heroin-dependent individuals. Several statistical parameters, such as degree (D), clustering coefficient (C) and shortest absolute path length (L), were included to test whether or not there was significant correlation between these parameters and the duration of heroin use. Our results demonstrated abnormal topological properties in several brain regions among our heroin-dependent subjects. Some of these regions are key areas of drug addiction-related circuits (control, reward, motivation/drive and memory), while others are involved in stress regulation. In addition, the duration of heroin use was positively correlated with the parameter D in the right parahippocampal gyrus, left putamen and bilateral cerebellum, but negatively correlated with the parameter L in the same regions. Our findings suggested that there is abnormal functional organization in heroin-dependent individuals and that the duration of heroin use is a critical factor leading to the altered brain connectivity.     

Changes in resting connectivity with age: a simultaneous electroencephalogram and functional magnetic resonance imaging investigation

Resting fluctuations in the blood oxygenation level-dependent signal have attracted considerable interest for their sensitivity to pathological brain processes. However, these analyses are susceptible to confound by nonneural physiological factors such as vasculature, breathing, and head movement which is a concern when investigating elderly or pathological groups. Here, we used simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG/fMRI) to constrain the analysis of resting state networks (RSNs) and identify aging differences. Four of 26 RSNs showed fMRI and EEG/fMRI group differences; anterior default-mode network, left frontal-parietal network, bilateral middle frontal, and postcentral gyri. Seven RSNs showed only EEG/fMRI differences suggesting the combination of these 2 methods might be more sensitive to age-related neural changes than fMRI alone. Five RSNs showed only fMRI differences and might reflect nonneural group differences. Activity within some EEG/fMRI RSNs was better explained by neuropsychological measures (Mini Mental State Examination and Stroop) than age. These results support previous studies suggesting that age-related changes in specific RSNs are neural in origin, and show that changes in some RSNs relate better to elderly cognition than age.     

Changes in brain activity patterns in aging: The novelty oddball

A decrease in the frontal lobes' efficiency is supposed to play a role in age-related changes in cognitive function. If frontal lobes are involved in the maintenance of working memory, the elderly may require increased frontal activity because of more rapid memory decay. This is consistent with the fact that the P3 component of the eventrelated potential (ERP) has a more frontal orientation with increasing age. However, frontally distributed P3s are also observed in young people when novel stimuli are unexpectedly presented in an oddball paradigm. Young and old subjects were run in an auditory novelty oddball in which ERPs were recorded from 30 scalp sites. The young adults' P3s showed either a posterior (targets) or more frontally oriented (novels) scalp focus. The elderly were less accurate in their memory for the novel stimuli, and their P3s showed anterior and posterior foci to both targets and novels. The young adults' target P3s changed over time from a frontal to a posterior focus, whereas the old adults' did not. These results are consistent with decreased ability of the elderly to maintain the templates needed for stimulus categorization.     

Extracting biomarkers of autism from MEG resting-state functional connectivity networks

The present study is a preliminary attempt to use graph theory for deriving distinct features of resting-state functional networks in young adults with autism spectrum disorder (ASD). Networks modeled neuromagnetic signal interactions between sensors using three alternative interdependence measures: (a) a non-linear measure of generalized synchronization (robust interdependence measure [RIM]), (b) mutual information (MI), and (c) partial directed coherence (PDC). To summarize the information contained in each network model we employed well-established global graph measures (average strength, assortativity, clustering, and efficiency) as well as graph measures (average strength of edges) tailored to specific hypotheses concerning the spatial distribution of abnormalities in connectivity among individuals with ASD. Graph measures then served as features in leave-one-out classification analyses contrasting control and ASD participants. We found that combinations of regionally constrained graph measures, derived from RIM, performed best, discriminating between the two groups with 93.75% accuracy. Network visualization revealed that ASD participants displayed significantly reduced interdependence strength, both within bilateral frontal and temporal sensors, as well as between temporal sensors and the remaining recording sites, in agreement with previous studies of functional connectivity in this disorder.     

Longitudinal assessment of default-mode brain function in aging

Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49–79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.     

Object working memory and visuospatial processing: functional neuroanatomy analyzed by event-related fMRI

We report an event-related functional magnetic-resonance-imaging (fMRI) experiment that investigates the relationship of transient visual object memory, visuospatial orienting, and object recognition. Delayed object matching and visuospatial orienting involved a highly overlapping network of brain areas. Common areas were the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA)/SMA complex, the precentral gyri, and the horizontal and descending branches of the intraparietal sulcus (IPS). Selective delay activation was observed anterior to the FEF and in the ascending part of the IPS. Right dorsolateral prefrontal cortex was involved in goal-directed visual search, but showed no delay activity.     

海洛因成瘾者停用海洛因后的脑功能情况-静息状态下fMRI研究

目的：探讨海洛因成瘾者停止用药后静息状态下脑功能的变化情况。方法：对海洛因成瘾者在停止使用海洛因3天（10人），1个月（10人）以及2个月（14人）时分别在静息状态下进行功能磁共振检测。并与正常对照进行比较。结果：成瘾者停用海洛因3天时出现额叶内侧，扣带回。颞上回等异常，停用1个月，额叶脑功能异常加重，海马功能出现异常，停用2个月，脑功能逐步恢复。结论：脑区的变化可能反映出海洛因成瘾者停药后渴求和复发可能性先增加。再下降的变化过程。额叶和海马发生变化时有时间上的关联性。本研究结果一方面为成瘾的动机假说提供了新的支持，另一方面提出海洛因依赖者在停药1个月左右复发的风险最大。     

Neural recruitment and connectivity during emotional memory retrieval across the adult life span

Although research has identified age-related changes in neural recruitment during emotional memory encoding, it is unclear whether these differences extend to retrieval. In this study, participants engaged in a recognition task during a functional magnetic resonance imaging scan. They viewed neutral titles and indicated whether each title had been presented with an image during the study phase. Neural activity and connectivity during retrieval of titles associated with positive and negative images were compared with age (treated as a continuous variable) included as a regressor of interest. Aging was associated with increased prefrontal activation for retrieval of positive and negative memories, but this pattern was more widespread for negative memories. Aging also was associated with greater negative connectivity between a left hippocampal seed region and multiple regions of prefrontal cortex, but this effect of age occurred during negative retrieval only. These findings demonstrate that age-related changes in prefrontal recruitment and connectivity during retrieval depend on memory valence. The use of a life span approach also emphasized both continuities and discontinuities in recruitment and connectivity across the adult life span, highlighting the insights to be gained from using a full life span sample.     

Non-coding RNA regulation of synaptic plasticity and memory: Implications for aging

Advancing age is associated with the loss of cognitive ability and vulnerability to debilitating mental diseases. Although much is known about the development of cognitive processes in the brain, the study of the molecular mechanisms governing memory decline with aging is still in its infancy. Recently, it has become apparent that most of the human genome is transcribed into non-coding RNAs (ncRNAs) rather than protein-coding mRNAs. Multiple types of ncRNAs are enriched in the central nervous system, and this large group of molecules may regulate the molecular complexity of the brain, its neurons, and synapses. Here, we review the current knowledge on the role of ncRNAs in synaptic plasticity, learning, and memory in the broader context of the aging brain and associated memory loss. We also discuss future directions to study the role of ncRNAs in the aging process.     

EEG-based functional networks in schizophrenia

Schizophrenia is often considered as a dysconnection syndrome in which, abnormal interactions between large-scale functional brain networks result in cognitive and perceptual deficits. In this article we apply the graph theoretic measures to brain functional networks based on the resting EEGs of fourteen schizophrenic patients in comparison with those of fourteen matched control subjects. The networks were extracted from common-average-referenced EEG time-series through partial and unpartial cross-correlation methods. Unpartial correlation detects functional connectivity based on direct and/or indirect links, while partial correlation allows one to ignore indirect links. We quantified the network properties with the graph metrics, including mall-worldness, vulnerability, modularity, assortativity, and synchronizability. The schizophrenic patients showed method-specific and frequency-specific changes especially pronounced for modularity, assortativity, and synchronizability measures. However, the differences between schizophrenia patients and normal controls in terms of graph theory metrics were stronger for the unpartial correlation method.     

A simultaneous ERP/fMRI investigation of the P300 aging effect

One of the most reliable psychophysiological markers of aging is a linear decrease in the amplitude of the P300 potential, accompanied by a more frontal topographical orientation, but the precise neural origins of these differences have yet to be explored. We acquired simultaneous electroencephalogram (EEG)/functional magnetic resonance imaging (fMRI) recordings from 14 older and 15 younger adults who performed a 3-stimulus visual oddball task designed to elicit P3a and P3b components. As in previous reports, older adults had significantly reduced P3a/P3b amplitudes over parietal electrodes but larger amplitudes over frontal scalp with no between-group differences in accuracy or reaction time. Electroencephalogram/functional magnetic resonance imaging fusion revealed that the P3a age effects were driven by increased activation of left inferior frontal and cingulate cortex and decreased activation of inferior parietal cortex in the older group. P3b differences were driven by increased activation of left temporal regions, right hippocampus, and right dorsolateral prefrontal cortex in the older group. Our results support the proposal that the age-related P300 anterior shift arises from an increased reliance on prefrontal structures to support target and distractor processing.     

Aging and the neural correlates of source memory: over-recruitment and functional reorganization

Behavioral evidence suggests that memory for context (i.e., source memory) is more vulnerable to age-related decline than item memory. It is not clear, however, whether this pattern reflects a specific age-related deficit in context memory or a more general effect of task difficulty. In the present study, we used event-related functional magnetic resonance imaging (fMRI) with healthy younger and older adults to dissociate the effects of age, task (item vs. source memory), and task difficulty (1 vs. 2 study presentations) on patterns of blood oxygen level-dependent (BOLD) signal changes during memory retrieval. Behavioral performance was similar in both age groups, but was sensitive to task and difficulty (item > source; easy > difficult). Data-driven multivariate analyses revealed age differences consistent with age-related overrecruitment of frontoparietal regions during difficult task conditions, and age-related functional reorganization in bilateral frontal and right-lateralized posterior regions that were sensitive to difficulty in younger adults, but to task (i.e., context demand) in older adults. These findings support the hypothesis of a specific context memory deficit in older adults.     

Memory load and the cognitive pupillary response in aging

The effect of memory load on the cognitive pupillary response among 16 young adults and 16 older adults was investigated. Mean pupil dilation and reaction time were measured during a Sternberg memory-search task, which involved six levels of memory load. A classic interaction pattern was obtained in which the reaction times of the elderly participants increased more as a function of memory load than the reaction times of the young participants. In the encoding phase of the experiment, mean dilation increased with memory load. No age differences were observed here. In the search phase of the experiment, however, mean pupil dilation was considerably greater in the young than in the elderly participants. Moreover, mean dilation of the older participants was not sensitive to memory load, whereas mean dilation increased as a function of memory load in the young participants. The results suggest that the usefulness of the pupillary response as a correlate of subtle fluctuations in memory load diminishes with old age.     

Local brain atrophy accounts for functional activity differences in normal aging

Functional brain imaging studies of normal aging typically show age-related under- and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under- and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under- as well as overrecruitment.     

Structural and functional bases of visuospatial associative memory in older adults

Impaired visuospatial associative memory may be one of the earliest changes predicting cognitive impairment and Alzheimer’s disease. We explored the relationship between performance on a visuospatial associative memory task (the Placing Test) and brain structure and function in cognitively healthy older adults. First, we performed a voxel-based morphometry correlational analysis on structural magnetic resonance imaging (MRI) data from 144 healthy older adults with their scores on the Placing Test. Second, we carried out a functional MRI study on another group of 28 healthy older adults who performed a similar task during functional MRI. Decreased performance on the Placing Test was associated with increased atrophy in medial-temporal regions. Functional activation of the same regions—controlling for the effect of atrophy—occurred during successful performance of the same task. The colocalization of structural and functional MRI correspondents of visuospatial associative test performance within medial-temporal regions validates multimodal imaging in describing behaviorally relevant variability in the aging brain and suggests that the Placing Test has the potential for detecting early cognitive changes occurring in preclinical phases of Alzheimer's disease.     

Task prioritization in aging: effects of sensory information on concurrent posture and memory performance

In older adults, cognitive resources play a key role in maintaining postural stability. In the present study, we evaluated whether increasing postural instability using sway referencing induces changes in resource allocation in dual-task performance leading older adults to prioritize the more age-salient posture task over a cognitive task. Young and older adults participated in the study which comprised two sessions. In the first session, three posture tasks (stable, sway reference visual, sway reference somatosensory) and a working memory task (n-back) were examined. In the second session, single- and dual-task performance of posture and memory were assessed. Postural stability improved with session. Participants were more unstable in the sway reference conditions, and pronounced age differences were observed in the somatosensory sway reference condition. In dual-task performance on the stable surface, older adults showed an almost 40% increase in instability compared to single-task. However, in the sway reference somatosensory condition, stability was the same in single- and dual-task performance, whereas pronounced (15%) costs emerged for cognition. These results show that during dual-tasking while standing on a stable surface, older adults have the flexibility to allow an increase in instability to accommodate cognitive task performance. However, when instability increases by means of compromising somatosensory information, levels of postural control are kept similar in single- and dual-task, by utilizing resources otherwise allocated to the cognitive task. This evidence emphasizes the flexible nature of resource allocation, developed over the life-span to compensate for age-related decline in sensorimotor and cognitive processing.     

Sex differences in prefrontal volume with aging and Alzheimer's disease

We used volumetric magnetic resonance imaging to examine sex differences in prefrontal tissue volumes of healthy aged and patients with Alzheimer’s disease (AD). Healthy subjects had greater total prefrontal volume than AD, and men had greater total prefrontal volume than women (ps ≤ 0.02). This was true for both gray and white matter volumes. There were no interactions between group and sex for total prefrontal volume. An exploratory analysis of each group suggested that sex differences in both gray and white matter in healthy aging are not sustained in AD.     

Choline chloride effects on memory in the elderly

Choline chloride (2 g QID) and placebo were administered to 10 subjects over age 60 in a placebo-drug-placebo design. Subjects first took placebo for 7 days, followed by choline for 21 days and finally took placebo for another 21 days. Memory tests were given at the end of both placebo periods and twice during choline administration. Choline did not significantly affect performance on a test of memory storage, a test of retrieval from memory or on the digit span test. In addition, a correlational analysis showed that the difference between memory performance during choline administration and during placebo administration was not significantly related to baseline memory performance. These results, together with results of previous studies indicate that choline is not an effective agent for improving memory in nondemented elderly patients.     

Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning

Objective: Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. Methods: To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Results: Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Conclusions: Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning.     

Figural memory performance and functional magnetic resonance imaging activity across the adult lifespan

We examined performance and functional magnetic resonance imaging activity in participants (n = 235) aged 17–81 years on a nonverbal recognition memory task, figural memory. Reaction time, error rate, and response bias measures indicated that the youngest and oldest participants were faster, made fewer errors, and showed a more conservative response bias than participants in the median age ranges. Encoding and Recognition phases activated a distributed bilateral network encompassing prefrontal, subcortical, lateral, and medial temporal and occipital regions. Activation during Encoding phase did not correlate with age. During Recognition, task-related activation for correctly identified targets (Hit-Targets) correlated linearly positively with age; nontask related activity correlated negative quadratically with age. During correctly identified distractors (Hit-Distractors) activity in task-related regions correlated positive linearly with age, nontask activity showed positive and negative quadratic relationships with age. Missed-Targets activity did not correlate with age. We concluded that figural memory performance and functional magnetic resonance imaging activity during Recognition but not Encoding was affected both by continued maturation of the brain in the early 20s and compensatory recruitment of additional brain regions during recognition memory in old age.