Structural and Functional Changes in Subcortical Vascular Mild Cognitive Impairment: A Combined Voxel-Based Morphometry and Resting-State fMRI Study

The present study aimed to investigate changes in structural gray matter (GM) volume and functional amplitude of spontaneous low-frequency oscillations (LFO) and functional connectivity density in patients with subcortical vascular mild cognitive impairment (svMCI). Structural MRI and resting-sate functional MRI data were collected from 26 svMCI patients and 28 age- and gender-matched healthy controls. Structurally, widespread GM atrophy was found in the svMCI patients that resided primarily in frontal (e.g., the superior and middle frontal gyri and medial prefrontal cortex) and temporal (the superior and inferior temporal gyri) brain regions as well as several subcortical brain sites (e.g., the thalamus and the caudate). Functionally, svMCI-related changes were predominantly found in the default mode network (DMN). Compared with the healthy controls, the svMCI patients exhibited decreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontal cortex), whereas increased LFO amplitudes in the posterior part of the DMN (e.g., the posterior cingulate/precuneus). As for functional connectivity density, the DMN regions (e.g., the posterior cingulate/precuneus, the medial prefrontal cortex and the middle temporal gyrus) consistently exhibited decreased functional connectivity. Finally, the overall patterns of functional alterations in LFO amplitudes and functional connectivity density remained little changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GM volume changes. Together, our results indicate that svMCI patients exhibit widespread abnormalities in both structural GM volume and functional intrinsic brain activity, which have important implications in understanding the pathophysiological mechanism of svMCI.     

Imaging the default mode network in aging and dementia

Although in the last decade brain activation in healthy aging and dementia was mainly studied using task-activation fMRI, there is increasing interest in task-induced decreases in brain activity, termed deactivations. These deactivations occur in the so-called default mode network (DMN). In parallel a growing number of studies focused on spontaneous, ongoing ‘baseline’ activity in the DMN. These resting state fMRI studies explored the functional connectivity in the DMN. Here we review whether normal aging and dementia affect task-induced deactivation and functional connectivity in the DMN. The majority of studies show a decreased DMN functional connectivity and task-induced DMN deactivations along a continuum from normal aging to mild cognitive impairment and to Alzheimer's disease (AD). Even subjects at risk for developing AD, either in terms of having amyloid plaques or carrying the APOE4 allele, showed disruptions in the DMN. While fMRI is a useful tool for detecting changes in DMN functional connectivity and deactivation, more work needs to be conducted to conclude whether these measures will become useful as a clinical diagnostic tool in AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Selective Vulnerability Related to Aging in Large-Scale Resting Brain Networks

Normal aging is associated with cognitive decline. Evidence indicates that large-scale brain networks are affected by aging; however, it has not been established whether aging has equivalent effects on specific large-scale networks. In the present study, 40 healthy subjects including 22 older (aged 60–80 years) and 18 younger (aged 22–33 years) adults underwent resting-state functional MRI scanning. Four canonical resting-state networks, including the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN) and salience network, were extracted, and the functional connectivities in these canonical networks were compared between the younger and older groups. We found distinct, disruptive alterations present in the large-scale aging-related resting brain networks: the ECN was affected the most, followed by the DAN. However, the DMN and salience networks showed limited functional connectivity disruption. The visual network served as a control and was similarly preserved in both groups. Our findings suggest that the aged brain is characterized by selective vulnerability in large-scale brain networks. These results could help improve our understanding of the mechanism of degeneration in the aging brain. Additional work is warranted to determine whether selective alterations in the intrinsic networks are related to impairments in behavioral performance.     

Intrinsic Brain Network Abnormalities in Migraines without Aura Revealed in Resting-State fMRI

Background

Previous studies have defined low-frequency, spatially consistent intrinsic connectivity networks (ICN) in resting functional magnetic resonance imaging (fMRI) data which reflect functional interactions among distinct brain areas. We sought to explore whether and how repeated migraine attacks influence intrinsic brain connectivity, as well as how activity in these networks correlates with clinical indicators of migraine.

Methods/Principal Findings

Resting-state fMRI data in twenty-three patients with migraines without aura (MwoA) and 23 age- and gender-matched healthy controls (HC) were analyzed using independent component analysis (ICA), in combination with a “dual-regression” technique to identify the group differences of three important pain-related networks [default mode network (DMN), bilateral central executive network (CEN), salience network (SN)] between the MwoA patients and HC. Compared with the HC, MwoA patients showed aberrant intrinsic connectivity within the bilateral CEN and SN, and greater connectivity between both the DMN and right CEN (rCEN) and the insula cortex - a critical region involving in pain processing. Furthermore, greater connectivity between both the DMN and rCEN and the insula correlated with duration of migraine.

Conclusions

Our findings may provide new insights into the characterization of migraine as a condition affecting brain activity in intrinsic connectivity networks. Moreover, the abnormalities may be the consequence of a persistent central neural system dysfunction, reflecting cumulative brain insults due to frequent ongoing migraine attacks.     

Task-induced deactivation from rest extends beyond the default mode brain network

Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized 'default-mode network' (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.     

Changes in Task-Related Functional Connectivity across Multiple Spatial Scales Are Related to Reading Performance

Reading requires the interaction of a distributed set of cortical areas whose distinct patterns give rise to a wide range of individual skill. However, the nature of these neural interactions and their relation to reading performance are still poorly understood. Functional connectivity analyses of fMRI data can be used to characterize the nature of interactivity of distributed brain networks, yet most previous studies have focused on connectivity during task-free (i.e., “resting state”) conditions. Here, we report new methods for assessing task-related functional connectivity using data-driven graph theoretical methods and describe how large-scale patterns of connectivity relate to individual variability in reading performance among children. We found that connectivity patterns of subjects performing a reading task could be decomposed hierarchically into multiple sub-networks, and we observed stronger long-range interaction between sub-networks in subjects with higher task accuracy. Additionally, we found a network of hub regions known to be critical to reading that displays increased short-range synchronization in higher accuracy subjects. These individual differences in task-related functional connectivity reveal that increased interaction between distant regions, coupled with selective local integration within key regions, is associated with better reading performance. Importantly, we show that task-related neuroimaging data contains far more information than usually extracted via standard univariate analyses – information that can meaningfully relate neural connectivity patterns to cognition and task.     

Deactivation of the default mode network as a marker of impaired consciousness: an fMRI study

Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation--a third main feature of the DMN--has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness.     

Functional Network Endophenotypes Unravel the Effects of Apolipoprotein E Epsilon 4 in Middle-Aged Adults

Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.     

Developing Neuroimaging Phenotypes of the Default Mode Network in PTSD: Integrating the Resting State,Working Memory,and Structural Connectivity

Complementary structural and functional neuroimaging techniques used to examine the Default Mode Network (DMN) could potentially improve assessments of psychiatric illness severity and provide added validity to the clinical diagnostic process. Recent neuroimaging research suggests that DMN processes may be disrupted in a number of stress-related psychiatric illnesses, such as posttraumatic stress disorder (PTSD).Although specific DMN functions remain under investigation, it is generally thought to be involved in introspection and self-processing. In healthy individuals it exhibits greatest activity during periods of rest, with less activity, observed as deactivation, during cognitive tasks, e.g., working memory. This network consists of the medial prefrontal cortex, posterior cingulate cortex/precuneus, lateral parietal cortices and medial temporal regions.Multiple functional and structural imaging approaches have been developed to study the DMN. These have unprecedented potential to further the understanding of the function and dysfunction of this network. Functional approaches, such as the evaluation of resting state connectivity and task-induced deactivation, have excellent potential to identify targeted neurocognitive and neuroaffective (functional) diagnostic markers and may indicate illness severity and prognosis with increased accuracy or specificity. Structural approaches, such as evaluation of morphometry and connectivity, may provide unique markers of etiology and long-term outcomes. Combined, functional and structural methods provide strong multimodal, complementary and synergistic approaches to develop valid DMN-based imaging phenotypes in stress-related psychiatric conditions. This protocol aims to integrate these methods to investigate DMN structure and function in PTSD, relating findings to illness severity and relevant clinical factors.     

Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss

The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network.     

Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network

The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain’s intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.     

Predicting regional neurodegeneration from the healthy brain functional connectome

Neurodegenerative diseases target large-scale neural networks. Four competing mechanistic hypotheses have been proposed to explain network-based disease patterning: nodal stress, transneuronal spread, trophic failure, and shared vulnerability. Here, we used task-free fMRI to derive the healthy intrinsic connectivity patterns seeded by brain regions vulnerable to any of five distinct neurodegenerative diseases. These data enabled us to investigate how intrinsic connectivity in health predicts region-by-region vulnerability to disease. For each illness, specific regions emerged as critical network "epicenters" whose normal connectivity profiles most resembled the disease-associated atrophy pattern. Graph theoretical analyses in healthy subjects revealed that regions with higher total connectional flow and, more consistently, shorter functional paths to the epicenters, showed greater disease-related vulnerability. These findings best fit a transneuronal spread model of network-based vulnerability. Molecular pathological approaches may help clarify what makes each epicenter vulnerable to its targeting disease and how toxic protein species travel between networked brain structures.     

Impact of Working Memory Load on fMRI Resting State Pattern in Subsequent Resting Phases

Background

The default-mode network (DMN) is a functional network with increasing relevance for psychiatric research, characterized by increased activation at rest and decreased activation during task performance. The degree of DMN deactivation during a cognitively demanding task depends on its difficulty. However, the relation of hemodynamic responses in the resting phase after a preceding cognitive challenge remains relatively unexplored. We test the hypothesis that the degree of activation of the DMN following cognitive challenge is influenced by the cognitive load of a preceding working-memory task.

Methodology/Principal Findings

Twenty-five healthy subjects were investigated with functional MRI at 3 Tesla while performing a working-memory task with embedded short resting phases. Data were decomposed into statistically independent spatio-temporal components using Tensor Independent Component Analysis (TICA). The DMN was selected using a template-matching procedure. The spatial map contained rest-related activations in the medial frontal cortex, ventral anterior and posterior cingulate cortex. The time course of the DMN revealed increased activation at rest after 1-back and 2-back blocks compared to the activation after a 0-back block.

Conclusion/Significance

We present evidence that a cognitively challenging working-memory task is followed by greater activation of the DMN than a simple letter-matching task. This might be interpreted as a functional correlate of self-evaluation and reflection of the preceding task or as relocation of cerebral resources representing recovery from high cognitive demands. This finding is highly relevant for neuroimaging studies which include resting phases in cognitive tasks as stable baseline conditions. Further studies investigating the DMN should take possible interactions of tasks and subsequent resting phases into account.     

Non-stationarity in the "resting brain's" modular architecture

Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness. We hypothesized that some of this variability rather than representing noise in the measurement process, is related to a fundamental feature of connectivity within ICNs, which is their non-stationary nature. To test this hypothesis, we used a large (n = 892) population-based sample of older subjects to construct a well characterized atlas of 68 functional regions, which were categorized based on independent component analysis network of origin, anatomical locations, and a functional meta-analysis. These regions were then used to construct dynamic graphical representations of brain connectivity within a sliding time window for each subject. This allowed us to demonstrate the non-stationary nature of the brain's modular organization and assign each region to a "meta-modular" group. Using this grouping, we then compared dwell time in strong sub-network configurations of the default mode network (DMN) between 28 subjects with Alzheimer's dementia and 56 cognitively normal elderly subjects matched 1:2 on age, gender, and education. We found that differences in connectivity we and others have previously observed in Alzheimer's disease can be explained by differences in dwell time in DMN sub-network configurations, rather than steady state connectivity magnitude. DMN dwell time in specific modular configurations may also underlie the TF-fMRI findings that have been described in mild cognitive impairment and cognitively normal subjects who are at risk for Alzheimer's dementia.     

An altered balance of integrated and segregated brain activity is a marker of cognitive deficits following sleep deprivation

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state.

Can the cognitive changes that result from sleep deprivation be explained by information processing within and between large-scale networks in the brain? This study shows that the ratio of within- vs between-network integration is tightly associated with deficits in cognitive performance.     

Quantifying the Reconfiguration of Intrinsic Networks during Working Memory

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory.     

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Brain Networks during Free Viewing of Complex Erotic Movie: New Insights on Psychogenic Erectile Dysfunction

Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other’s actions. Moreover, the between group differences in the SN nodes suggested a decreased recognition of autonomical and sexual arousal changes in EDp.     

Age-Related Changes in Task Related Functional Network Connectivity

Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.     

Default-mode-like network activation in awake rodents

During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN), an intrinsic central nervous system (CNS) network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease states (e.g., Alzheimer''s, schizophrenia or chronic pain). However, whether the DMN exists in awake rodents has not been characterized. The current data provides evidence that awake rodents also possess ‘DMN-like’ functional connectivity, but only subsequent to habituation to what is initially a novel magnetic resonance imaging (MRI) environment as well as physical restraint. Specifically, the habituation process spanned across four separate scanning sessions (Day 2, 4, 6 and 8). At Day 8, significant (p<0.05) functional connectivity was observed amongst structures such as the anterior cingulate (seed region), retrosplenial, parietal, and hippocampal cortices. Prior to habituation (Day 2), functional connectivity was only detected (p<0.05) amongst CNS structures known to mediate anxiety (i.e., anterior cingulate (seed region), posterior hypothalamic area, amygdala and parabracial nucleus). In relating functional connectivity between cingulate-default-mode and cingulate-anxiety structures across Days 2-8, a significant inverse relationship (r = −0.65, p = 0.0004) was observed between these two functional interactions such that increased cingulate-DMN connectivity corresponded to decreased cingulate anxiety network connectivity. This investigation demonstrates that the cingulate is an important component of both the rodent DMN-like and anxiety networks.