Coherent spontaneous activity identifies a hippocampal-parietal memory network.

Mallinckrodt Institute of Radiology, and Department of Neurology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA.
Journal of Neurophysiology (Impact Factor: 3.04). 01/2007; 96(6):3517-31. DOI: 10.1152/jn.00048.2006
Source: PubMed

ABSTRACT Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF.

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    ABSTRACT: The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alter-ations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN–HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25–80 y old), we have demonstrated age-related decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which age-related elevation of connectivity between left and right HC was found along with attenuated HC–cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural re-cruitment and HC–cortical connectivity during active memory encod-ing, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico–hippo-campal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing. hippocampus | DMN | resting state | episodic memory | aging T he brain is not idle at rest (1). Rather, intrinsic neuronal signaling, which manifests as spontaneous fluctuations in the blood oxygen level-dependent (BOLD) functional MRI (fMRI) signal, is ubiquitous in the human brain and consumes a substantial portion of the brain's energy (2). Coherent spontaneous activity has been revealed in a hierarchy of networks that span large-scale functional circuits in the brain (3–6). These resting-state networks (RSNs) show moderate-to-high test–retest reliability (7) and rep-licability (8), and some have been found in the monkey (9) and infant (10) brain. In the adult human brain, RSNs include sensory motor, visual, attention, and mnemonic networks, as well as the default mode network (DMN). There is evidence that the DMN entails interacting subsystems and hubs that are implicated in ep-isodic memory (11–13). One major hub encompasses the posterior cingulate cortex and the retrosplenial cortex. Other hubs include the lateral parietal cortex and the medial prefrontal cortex. In addition, a hippocampus (HC) subsystem is distinct from, yet in-terrelated with, the major cortical DMN hubs (12, 14). The functional architecture of the DMN and other RSNs is af-fected by different conditions, such as Alzheimer's disease (AD), Parkinson's disease, and head injury, suggesting that measurements of the brain's intrinsic activity may be a sensitive biomarker and a putative diagnostic tool (for a review, see ref. 15). Alterations of the DMN have also been shown in age-comparative studies (16, 17), but the patterns of alterations are not homogeneous across different DMN components (18). Reduced functional connectivity among major cortical DMN nodes has been reported in aging (16, 17) and also in AD (19) and for asymptomatic APOE e4 carriers at increased risk of developing AD (20). Reduced cortical DMN connectivity has been linked to age-impaired performance on episodic memory (EM) tasks (21, 22). For instance, Wang and colleagues (21) showed that functional connectivity between cortical and HC hubs promoted performance on an EM task and was substantially weaker among low-performing elderly. This and other findings suggest that reduc-tions in the DMN may be a basis for age-related EM impairment. However, elevated connectivity has been observed for the HC in individuals at genetic risk for AD (23, 24) and for elderly with memory complaints (25). Furthermore, a trend toward elevated functional connectivity for the medial temporal lobe (MTL) sub-system was observed in healthy older adults (26). Critically, higher subcortical RSN connectivity was found to correlate negatively with EM performance in an aging sample (27). Moreover, a recent combined fMRI/EEG study observed age increases in HC EEG beta power during rest (28). Thus, the association of aging with components of the DMN is complex, and it has been argued that age-related increases in functional connectivity need further examination (18). Such increases could reflect a multitude of processes, including age-related degenerative effects on the brain's gray and white matter (18). Additionally, increases in HC functional connectivity may reflect alterations in proteolytic processes, such as amyloid de-position (29). Amyloid deposition is most prominent in posterior cortical regions of the DMN (29). It has been argued that there
    Proceedings of the National Academy of Sciences 11/2014; · 9.81 Impact Factor
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    ABSTRACT: Mutations affecting the PAX6 gene result in aniridia, a condition characterized by the lack of an iris and other panocular defects. Among humans with aniridia, structural abnormalities also have been reported within the brain. The current study examined the functional implications of these deficits through "resting state" or task-free functional magnetic resonance imaging (fMRI) in 12 individuals with aniridia and 12 healthy age- and gender-matched controls. Using independent components analysis (ICA) and dual regression, individual patterns of functional connectivity associated with three intrinsic connectivity networks (ICNs; executive control, primary visual, and default mode) were compared across groups. In all three analyses, the aniridia group exhibited regions of greater connectivity correlated with the network, while the controls did not show any such regions. These differences suggest that individuals with aniridia recruit additional neural regions to supplement function in critical intrinsic networks, possibly due to inherent structural or sensory abnormalities related to the disorder.
    Frontiers in Human Neuroscience 12/2014; 8:1013. · 2.90 Impact Factor
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    ABSTRACT: Complex systems are described according to two central dimensions: (a) the randomness of their output, quantified via entropy; and (b) their complexity, which reflects the organization of a system's generators. Whereas some approaches hold that complexity can be reduced to uncertainty or entropy, an axiom of complexity science is that signals with very high or very low entropy are generated by relatively non-complex systems, while complex systems typically generate outputs with entropy peaking between these two extremes. In understanding their environment, individuals would benefit from coding for both input entropy and complexity; entropy indexes uncertainty and can inform probabilistic coding strategies, whereas complexity reflects a concise and abstract representation of the underlying environmental configuration, which can serve independent purposes, e.g., as a template for generalization and rapid comparisons between environments. Using functional neuroimaging, we demonstrate that, in response to passively processed auditory inputs, functional integration patterns in the human brain track both the entropy and complexity of the auditory signal. Connectivity between several brain regions scaled monotonically with input entropy, suggesting sensitivity to uncertainty, whereas connectivity between other regions tracked entropy in a convex manner consistent with sensitivity to input complexity. These findings suggest that the human brain simultaneously tracks the uncertainty of sensory data and effectively models their environmental generators. Copyright © 2014. Published by Elsevier Inc.
    NeuroImage 12/2014; 108. · 6.13 Impact Factor

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