Elsevier

Cortex

Volume 64, March 2015, Pages 271-280
Cortex

Research report
Resting-state anticorrelations between medial and lateral prefrontal cortex: Association with working memory, aging, and individual differences

https://doi.org/10.1016/j.cortex.2014.12.001Get rights and content

Abstract

We examined how variation in working memory (WM) capacity due to aging or individual differences among young adults is associated with intrinsic or resting-state anticorrelations, particularly between (1) the medial prefrontal cortex (MPFC), a component of the default-mode network (DMN) that typically decreases in activation during external, attention-demanding tasks, and (2) the dorsolateral prefrontal cortex (DLPFC), a component of the fronto-parietal control network that supports executive functions and WM and typically increases in activation during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC anticorrelations between healthy younger and older participants (Experiment 1) and related the magnitudes of these anticorrelations to individual differences on two behavioral measures of WM capacity in two independent groups of young adults (Experiments 1 and 2). Relative to younger adults, older adults exhibited reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater WM capacity. These findings show that variation in MPFC-DLPFC anticorrelations, whether related to aging or to individual differences, may reflect an intrinsic functional brain architecture supportive of WM capacity.

Introduction

Working memory (WM) capacity, defined as the amount of goal-relevant information that can be both maintained and manipulated, declines with age (Craik, Morris, & Gick, 1990) and varies considerably among individuals (Engle, 2002). In contrast to measures of simple short-term maintenance of information (e.g., digit span), greater WM capacity is associated with superior performance in a broad range of high-level cognitive domains, including reading comprehension, problem solving, and inhibitory control (Conway, Kane, & Engle, 2003). WM capacity is thought to reflect central executive capability (Baddeley, 1992, Engle, 2002), and to depend on dorsolateral prefrontal cortex (DLPFC), parietal cortex, anterior cingulate cortex, and the basal ganglia (D'Esposito, 2007, D'Esposito et al., 1999, Frank et al., 2001, Levy and Goldman-Rakic, 2000). Here, we asked whether a relationship exists between variation in WM capacity, due to aging or across younger individuals, and the intrinsic functional architecture of the human brain as measured by resting-state functional connectivity.

Spontaneous fluctuations in functionally related brain regions are correlated with each other in the absence of external stimuli, and the patterns of these correlations have been thought to reveal intrinsic relations of brain regions (Beckmann et al., 2005, Biswal et al., 1995, Greicius et al., 2003). During rest, in young adults, there are strong correlations between components of the default-mode network (DMN), brain regions that are commonly deactivated during external or attention-demanding tasks involving mental control (Fox et al., 2005, Fransson, 2005, Greicius et al., 2003, Raichle et al., 2001). Anatomically, the DMN includes medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), left and right lateral parietal (LLP and RLP) cortices, and bilateral medial temporal lobe (MTL) regions (Buckner, Andrews-Hanna, & Schacter, 2008).

Resting-state correlations among the components of the DMN appear to be significantly reduced in age-associated pathologies (Greicius et al., 2004, Hedden et al., 2009) and in typically aging older adults (Andrews-Hanna et al., 2007, Balsters et al., 2013, Damoiseaux et al., 2008, Grady et al., 2010, Mowinckel et al., 2012, Sala-Llonch et al., 2012, Sambataro et al., 2010). This may be due, in part, to the particular vulnerability of long-range DMN functional connections to the effects of normal aging (Allen et al., 2011, Andrews-Hanna et al., 2007, Fillippini et al., 2012, Hafkemeijer et al., 2012, Tomasi and Volkow, 2012) or a consequence of more motion-related artifactual time points in elderly participants (Power et al., 2012, Van Dijk et al., 2012). Although widespread reductions in resting functional connectivity are observed with advancing age, some studies also report localized increases in resting-state functional connectivity. Older adults, relative to younger adults, have shown increased frontal-lobe coherence (Fillippini et al., 2012) and increased functional connectivity within fronto-parietal cortical regions (Mowinckel et al., 2012).

Networks in the brain appear to have an intrinsic organization such that different networks may exhibit negative functional connectivity, or are anticorrelated with one another at rest. In young adults, components of the DMN are negatively correlated with brain networks comprised of regions commonly activated for external tasks that demand attention and mental control, including the DLPFC (Fox et al., 2005, Fransson, 2005). Evaluation of negatively correlated networks has proven controversial due to global signal regression, a method used commonly to mitigate physiological noise in resting-state functional imaging studies. Global signal regression is known to mathematically generate anticorrelations (Murphy et al., 2009, Saad et al., 2012). Given these issues, valid analysis of negatively correlated networks has developed into a topic of particular interest in the field (Chang and Glover, 2009, Fox et al., 2005, Hampson et al., 2010, Saad et al., 2012, Van Dijk et al., 2010, Weissenbacher et al., 2009). With the caveat that prior studies of the influence of age on anticorrelations have employed global signal regression, there is evidence that healthy aging is also characterized by reduced negative correlations at rest between the DMN and cortical regions commonly recruited during attention-demanding tasks (Wu et al., 2011).

Variation in DMN connectivity has been associated with variation in executive functions and WM capacity. Among older adults, reduced MPFC-PCC connectivity correlated with worse performance on executive-function and other cognitive measures (Andrews-Hanna et al., 2007) and reduced connectivity in a DMN network dominated by the MPFC correlated with worse performance on a trail-making test (Damoiseaux et al., 2008). Neither study reported a correlation between these brain measures and variation among young adults, because that was either not examined (Andrews-Hanna et al., 2007) or was not significant in 10 participants (Damoiseaux et al., 2008). For young adults, there is a report of a positive correlation between magnitude of MPFC-DLPFC anticorrelation and WM capacity, as measured by an n-back task (Hampson et al., 2010). The relation between reduced MPFC-DLPFC resting-state anticorrelation and reduced WM capacity is consistent with findings from patients with schizophrenia (Whitfield-Gabrieli et al., 2009).

Although variability in resting-state functional connectivity has been associated with variation in WM in relation to aging and to individual differences among young adults, there are two major gaps in the current understanding of that association. First, studies of aging have implicated positive correlations with the MPFC as being related to age-associated reduction in WM capacity, whereas the one study of variation among young adults has, instead, implicated negative correlations with MPFC. This leaves open the question about whether age-related changes in WM and individual differences among young adults in WM capacity are associated with shared or distinct variations in intrinsic functional connectivity (no one study has discovered such common variation in both younger and older adults). Second, the above functional connectivity findings were reported before it was well understood that greater movement in older than younger adults can produce artifactual results (Power et al., 2012, Van Dijk et al., 2012) or that global signal regression can mathematically generate anticorrelations (Murphy et al., 2009, Saad et al., 2012). Therefore, it is unknown whether the prior findings would hold when methodological improvements were implemented.

Here, we explored whether there exists shared or distinct characteristics of intrinsic brain function for age-related declines in WM capacity and for individual differences among young adults in WM capacity. We focused on MPFC positive and negative functional connectivity because bi-directional correlations of the MPFC with different regions have been implicated across studies of aging or of individual differences among young adults in relation to executive functions and WM capacity (Andrews-Hanna et al., 2007, Damoiseaux et al., 2008, Hampson et al., 2010). We examined the relation of MPFC-DLPFC anticorrelations and MPFC-PCC positive correlations to WM capacity (Experiment 1) in 27 younger and 27 older healthy adults with capacity measured by the Letter-Number Sequencing subtest from the Wechsler Adult Intelligence Scale (WAIS-III), and in 70 younger adults (Experiment 2) with a composite measure of Operation and Reading Span tests (Turner and Engle, 1989, Unsworth et al., 2005). In both experiments, we implemented methods that minimize the influence of motion artifacts and physiological noise and allow for valid interpretations of negative correlations (Behzadi et al., 2007, Chai et al., 2012; Whitfield-Gabrieli & Nieto-Castanon, 2012).

Section snippets

Participants

Participants were 27 older adults (15 women) between 65 and 89 years of age (M = 75.7 years, SD = 6.7) and 27 younger adults (15 women) between 20 and 33 years of age (M = 24.8, SD = 3.4). Written informed consent for participation in the study was obtained from all participants and approved by the MIT Institutional Review Board. All participants were healthy, right-handed individuals (Oldfield, 1971) from the Boston metropolitan area who satisfied the following criteria: native English

Discussion

We found convergent evidence from aging and from individual differences among young adults of a relation between greater WM capacity and greater magnitude of MPFC-DLPFC anticorrelation. Older adults exhibited both reduced WM and reduced MPFC-DLPFC anticorrelation relative to younger adults. Furthermore, greater WM capacity was associated with greater MPFC-DLPFC anticorrelation in two independent cohorts of young adults (total n = 97) with two different WM measures.

Limitations

One limitation to this study is that the older adult population may have substantially more cortical atrophy and more CSF, which may have differentially affected the normalization procedure. Another limitation is that although the use of different WM measures in Experiments 1 and 2 promote the generalizability of the findings, the different measures precluded a direct replication. Finally, anticorrelations are consistently found in young adults between specific neuroanatomical systems (e.g.,

Conclusion

In older adults, there was reduced WM capacity and the apparent elimination of MPFC-DLPFC anticorrelation. In younger adults, there were associations between greater magnitudes of WM capacity and greater MPFC-DLPFC anticorrelations. These results suggest that intrinsic anticorrelations between the MPFC, a node in the DMN, and DLPFC, a cortical region involved in cognitive control, may serve as a shared indicator of WM capacity both in aging and in individual differences among young adults.

Acknowledgment

We thank Nina Wickens for her help in recruiting and testing participants, and the staff of the Martinos Imaging Center at the McGovern Institute at MIT for help in neuroimaging. This study was supported by NIH/NIA grant R21 AG030770. Funding support for J.B.K was provided by NIH grant T32 GM007484 and the Barbara J. Weedon Fund Fellowship at MIT; support for T.H. was provided by grant K01 AG040197.

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