Elsevier

Neurobiology of Aging

Volume 33, Issue 4, April 2012, Pages 826.e1-826.e13
Neurobiology of Aging

Abstract of online article
Executive functions and neurocognitive aging: dissociable patterns of brain activity

https://doi.org/10.1016/j.neurobiolaging.2011.06.005Get rights and content

Abstract

Studies of neurocognitive aging report altered patterns of brain activity in older versus younger adults performing executive function tasks. We review the extant literature, using activation likelihood estimation meta-analytic methods, to compare age-related differences in the pattern of brain activity across studies examining 2 categories of tasks associated with executive control processing: working memory and inhibition. In a direct contrast of young and older adult activations, older adults engaged bilateral regions of dorsolateral prefrontal cortex as well as supplementary motor cortex and left inferior parietal lobule during working memory. In contrast, age-related changes during inhibitory control were observed in right inferior frontal gyrus and presupplementary motor area. Additionally, when we examined task-related differences within each age group we observed the predicted pattern of differentiated neural response in the younger subjects: lateral prefrontal cortex activity associated with working memory versus right anterior insula/frontal opercular activity associated with inhibition. This separation was largely maintained in older subjects. These data provide the first quantitative meta-analytic evidence that age-related patterns of functional brain change during executive functioning depend on the specific control process being challenged.

Introduction

Neurocognitive changes in healthy aging have now been reported for almost 2 decades. Early work from Grady and colleagues (1994) first reported age-related differences in patterns of functional brain activity during a perceptual matching task using positron emission tomography. With the advent of functional magnetic resonance imaging, the number of investigations of neurocognitive aging has expanded exponentially and now include studies of numerous cognitive domains (see Spreng et al., 2010). Of these, executive functions have received the most attention. Functional brain imaging studies of executive control processes report robust differences in brain activity between older and younger subjects, particularly under conditions of high executive control demand (e.g., Grady et al., 1998, Jonides et al., 2000, Milham et al., 2002, Nielson et al., 2002, Postle et al., 1999, Reuter-Lorenz et al., 2000). These differences have been replicated across studies (see Park and Reuter-Lorenz, 2009, Reuter-Lorenz and Cappell, 2008 for reviews) and have generated several theoretical accounts of neurocognitive aging in the domain of executive functions.

The most commonly reported age-related pattern of brain activity during executive function tasks (e.g., working memory, inhibition, and task-switching) is increased recruitment of lateral aspects of the prefrontal cortex (PFC) bilaterally (Rypma and D'Esposito, 2000, Jonides et al., 2000, Townsend et al., 2006). These changes may reflect increased PFC modulation of processing operations in posterior cortices in response to noisier (i.e., reduced processing specificity) signaling in these regions (Persson et al., 2006). Increased lateral PFC activity may also reflect greater demands for executive control as cognitive operations become less automated with age, resulting in a general “posterior to anterior shift” (PASA) in functional brain activity (Davis et al., 2008) or as neural circuits become increasingly inefficient (compensation-related utilization of neural circuits hypothesis; CRUNCH; Reuter-Lorenz and Cappell, 2008). Recently, this increased demand for frontally-mediated control processes has been characterized as “neural scaffolding” (Park and Reuter-Lorenz, 2009). As age-related structural and functional brain changes, including cortical thinning, white matter changes, and reductions in hippocampal activation, lead to inefficient and/or noisy processing, demands for controlled processing operations are increased. In response, lateral prefrontal brain regions are recruited to provide a “neural scaffold” in support of new learning and sustained behavioral performance, particularly in the context of novel or complex tasks. A similar pattern has been observed in young adults as task challenge is increased requiring new strategy learning (Erickson et al., 2007a and see Hillary et al., 2006 for a review of functional brain changes in healthy young, aging, and neurological populations). While each of these theories argue that functional brain changes, particularly engagement of lateral PFC regions, occurs in normal aging they differ somewhat with respect to the mechanism underlying these changes. The work of Persson and colleagues (Persson et al., 2006) or the PASA account (Davis et al., 2008) suggest that lateral PFC recruitment may represent additional demands for frontally-mediated neuromodulation of posterior neural processing operations. In contrast, the CRUNCH (Reuter-Lorenz and Cappell, 2008) and neural scaffolding hypotheses (Park and Reuter-Lorenz, 2009) suggest that as brain circuits become less efficient with age, additional or alternate neural resources are engaged to compensate for degraded processing operations in both frontal and posterior brain regions. Further discussion of these mechanistic accounts is beyond the scope of the current study (but see Turner and D'Esposito, 2010, for a review). However, it is interesting to note that while each of these accounts converge around the notion of increased recruitment of lateral PFC to support controlled (i.e., executive) processing, to our knowledge, there has been no direct examination of how age-related changes are manifest for specific executive control processes.

It is now well understood that executive functions can be fractionated into dissociable processes both behaviorally (e.g., Miyake et al., 2000, Salthouse et al., 2003, Stuss et al., 1995) and neurally (e.g., Chikazoe, 2010, McNab et al., 2008; Wager and Smith, 2003). This raises the question of whether the age-related patterns of functional brain change described above are similarly dissociable depending upon the executive control process being challenged. The goal of the current report is to review the extant literature, using quantitative meta-analytic methods, to compare age-related differences in the pattern of brain activity between 2 executive processes that have been most frequently studied in the cognitive neuroscience literature: working memory and inhibition (Cabeza and Nyberg, 2000; Wager and Smith, 2003). Neurocognitive aging of task switching, the third executive control process identified by Miyake et al. (2000), remains an understudied domain of executive function and was not included in the current analysis (for exceptions, see: DiGirolamo et al., 2001, Esposito et al., 1999, Townsend et al., 2006). Specifically, we investigate whether age-related patterns of functional brain changes are similar across executive processes or whether changes with aging are specific to the executive process being challenged.

Working memory is a system for actively maintaining and manipulating information that is no longer present in the environment, yet must be organized and retained in the service of current and future goals (Wager and Smith, 2003). In younger subjects, working memory is associated with activation of lateral prefrontal cortical regions, typically left-lateralized (Smith and Jonides, 1998, Wager and Smith, 2003). In older adults, working memory tasks also engage PFC regions, however, neural response is greater and more bilateral at lower levels of task demand than in younger adults (Emery et al., 2008, Jonides et al., 2000, Reuter-Lorenz and Cappell, 2008). This pattern has been hypothesized to reflect poor modulation of prefrontal brain activity in response to increasing working memory demands (Reuter-Lorenz and Cappell, 2008; Schneider-Garces et al., 2010). Cappell and colleagues (Cappell et al., 2010) recently tested this hypothesis in a study of verbal working memory in older and younger adults under high and low load conditions. Consistent with their predictions, older adults overrecruited regions of right lateral PFC at lower working memory loads relative to younger subjects and underrecruited lateral prefrontal cortex regions bilaterally at higher memory loads. Thus age-related increases in lateral PFC during working memory may reflect reduced capacity to modulate this region in response to shifting executive control demands. Here we examine whether this account of age-related functional brain changes generalizes beyond working memory to other domains of executive function such as inhibitory control. To our knowledge this has not been investigated.

Inhibitory control is generally defined as intentional control over dominant, automatic, or prepotent responses and has also been widely studied using brain imaging methods (Chikazoe, 2010). As with working memory, the functional neural correlates of inhibitory control in younger adults have been well characterized for both cognitive and motor inhibition tasks (see Buchsbaum et al., 2005). Critical regions include ventral PFC (Chambers et al., 2009, Leung and Cai, 2007, Swann et al., 2009), presupplementary motor areas (Chen et al., 2009, Floden and Stuss, 2006, Li et al., 2006), as well as posterior parietal cortices, subthalamic nuclei, and cerebellar regions (see Chambers et al., 2009, Chikazoe, 2010 for recent reviews). However, the neural correlates of inhibitory control processing in older adults are less well characterized. Several studies have now identified a highly overlapping pattern of brain regions between older and younger adults performing inhibition tasks (e.g., Jonides et al., 1998, Langenecker et al., 2004, Milham et al., 2002, but see Jonides et al., 2000). Others report greater age-related recruitment of dorsolateral aspects of PFC bilaterally as inhibitory control demands increase (e.g., Mathis et al., 2009, Wood et al., 2009), a pattern more consistent with the working memory literature. A recent study of age-related functional brain changes under variable inhibitory control demands argued that these changes reflected poor modulation of these regions resulting in greater functional brain response within lateral PFC (Prakash et al., 2009), a conclusion strikingly similar to that of Cappell and colleagues (Cappell et al., 2010) who investigated these age-related changes in the context of working memory.

While these latter findings suggest that patterns of age-related functional brain changes during executive function tasks may be generalizable across specific processes falling within the domain of executive functioning (or at least between working memory and inhibition), to our knowledge no study has directly tested this possibility in both younger and older adults. McNab and colleagues (McNab et al., 2008) recently compared brain activity during working memory and inhibition task performance in younger adults using within-subject contrasts. The 2 processes activated distinct functional brain networks, however, overlapping activity was observed in a small area of right inferior frontal gyrus. These results are consistent with previous reviews of working memory (e.g., Wager and Smith, 2003) and inhibitory control (e.g., Chambers et al., 2009, Simmonds et al., 2008) that suggest these 2 executive functions are implemented in discrete but overlapping brain networks in younger adults.

Numerous reports have now examined age-related functional brain changes associated with working memory and inhibition independently. However, we were unable to identify any reports that directly compared these 2 processes in younger and older adults in a single study. Here we review the findings of these previous single task reports to examine whether functional brain changes in older adults performing working memory and inhibitory control tasks are dissociable. We use the activation likelihood estimation (ALE) approach for neuroimaging data (Laird et al., 2005, Turkeltaub et al., 2002) as this meta-analytic method provides a quantitative estimate of the degree of overlap in functional activation patterns across multiple studies. Specifically, we investigated whether age-related neurocognitive changes overlapped for working memory and inhibitory control tasks. This would be evidence for a common pattern of age-related functional brain changes in executive functioning (i.e., greater bilateral activity in PFC in older adults for both task categories). Alternatively, if age-related brain changes differ between working memory and inhibition tasks, this would suggest that age-related functional brain changes in the domain of executive functioning are dependent on the specific executive process being taxed. We investigate this with several ALE analyses. First we present the quantitative review of studies examining age-related changes within each task by reporting reliable patterns of activation for working memory and inhibitory control within each age group. Next we directly contrast the task-related activation patterns for young and older subjects. Finally, we contrast task-related activation patterns within each age-group separately.

Section snippets

Selection of studies

Neuroimaging studies examining aging and executive function were selected using a systematic search process. Peer-reviewed articles, published in English between January 1982 and March 2010, were selected from the search results of 3 separate databases: MEDLINE, PsycInfo, and Science Citation Index. Searches were conducted using the following terms: (1) keyword: “age” or “aging” or “ageing” or “age-related” or “older adults” or “adult life-span”; and (2) keyword: “neuroimaging” or “cerebral

Working memory

Studies of working memory showed reliable recruitment of lateral PFC, posterior parietal, and subcortical brain structures in younger adult subjects. Significant ALE clusters were evident in dorsal and ventral aspects of left lateral PFC, right dorsolateral PFC, bilateral parietal regions, visual association cortices, and subcortical nuclei including the thalamus and basal ganglia (Fig. 1A, and Supplementary Table S1 for a list of the cluster maxima coordinates). This recruitment pattern was

Age-related changes in working memory

As predicted, the ALE meta-analytic data demonstrated more reliable recruitment of dorsolateral PFC bilaterally (right greater than left) in older relative to younger adults during working memory, a finding consistent with previous reviews (Smith and Jonides, 1998, Wager and Smith, 2003). These results are also convergent with findings from individual studies that report greater and less lateralized recruitment of dorsolateral PFC in older relative to younger subjects, particularly at lower

Disclosure statement

The authors report no conflict of interests in the conduct of this research.

References (79)

  • S.A. Langenecker et al.

    fMRI of healthy older adults during Stroop interference

    Neuroimage

    (2004)
  • T.M. Lee et al.

    Age-related differences in response regulation as revealed by functional MRI

    Brain Res

    (2006)
  • M.P. Milham et al.

    Attentional control in the aging brain: insights from an fMRI study of the stroop task

    Brain Cogn

    (2002)
  • A. Miyake et al.

    The unity and diversity of executive functions and their contributions to complex “Frontal Lobe” tasks: a latent variable analysis

    Cogn. Psychol

    (2000)
  • R.S. Prakash et al.

    Age-related differences in the involvement of the prefrontal cortex in attentional control

    Brain Cogn

    (2009)
  • E. Ricciardi et al.

    Cholinergic modulation of visual working memory during aging: a parametric PET study

    Brain Res. Bull

    (2009)
  • D.J. Simmonds et al.

    Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent

    Neuropsychologia

    (2008)
  • S.M. Smith et al.

    Advances in functional and structural MR image analysis and implementation as FSL

    Neuroimage

    (2004)
  • R.N. Spreng et al.

    Reliable differences in brain activity between young and old adults: A quantitative meta-analysis across multiple cognitive domains

    Neurosci. Biobehav. Rev

    (2010)
  • J. Townsend et al.

    Changing channels: an fMRI study of aging and cross-modal attention shifts

    Neuroimage

    (2006)
  • P.E. Turkeltaub et al.

    Meta-analysis of the functional neuroanatomy of single-word reading: method and validation

    Neuroimage

    (2002)
  • D.C. Van Essen

    A population-average, landmark- and surface-based (PALS) atlas of human cerebral cortex

    Neuroimage

    (2005)
  • D.C. Zhu et al.

    Brain activation during interference resolution in young and older adults: an fMRI study

    Neuroimage

    (2010)
  • B.R. Buchsbaum et al.

    Meta-analysis of neuroimaging studies of the Wisconsin card-sorting task and component processes

    Hum. Brain Mapp

    (2005)
  • R. Cabeza et al.

    Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval

    Cereb. Cortex

    (2004)
  • R. Cabeza et al.

    Imaging cognition, II: an empirical review of 275 PET and fMRI studies

    J. Cogn. Neurosci

    (2000)
  • J. Chikazoe

    Localizing performance of go/no-go tasks to prefrontal cortical subregions

    Curr. Opin. Psychiatry

    (2010)
  • S.J. Colcombe et al.

    The implications of cortical recruitment and brain morphology for individual differences in inhibitory function in aging humans

    Psychol. Aging

    (2005)
  • R.W. Cox et al.

    Software tools for analysis and visualization of fMRI data

    NMR Biomed

    (1997)
  • S.W. Davis et al.

    Que PASA?The posterior-anterior shift in aging

    Cereb. Cortex

    (2008)
  • G.J. DiGirolamo et al.

    General and task-specific frontal lobe recruitment in older adults during executive processes: a fMRI investigation of task-switching

    Neuroreport

    (2001)
  • S.B. Eickhoff et al.

    Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty

    Hum. Brain Mapp. um

    (2009)
  • K.I. Erickson et al.

    Training-induced functional activation changes in dual-task processing: an FMRI study

    Cereb. Cortex

    (2007)
  • G. Esposito et al.

    Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation

    Brain

    (1999)
  • D. Floden et al.

    Inhibitory control is slowed in patients with right superior medial frontal damage

    J. Cogn. Neurosci

    (2006)
  • U. Freo et al.

    Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine

    Am. J. Psychiatry

    (2005)
  • C.L. Grady

    Cognitive neuroscience of aging

    Ann. N. Y. Acad. Sci

    (2008)
  • C.L. Grady et al.

    Age-related changes in cortical blood flow activation during visual processing of faces and location

    J. Neurosci

    (1994)
  • M.W. Haut et al.

    The effect of education on age-related functional activation during working memory

    Aging Neuropsychol. Cogn

    (2005)
  • Cited by (219)

    • Comparing neural activity during autobiographical memory retrieval between younger and older adults: An ALE meta-analysis

      2022, Neurobiology of Aging
      Citation Excerpt :

      To this point, neuroimaging studies indicate that these retrieval routes also rely on separable brain regions – such that direct retrieval strongly engages many of the above-mentioned AM regions, but generative retrieval additionally recruits lateral prefrontal regions to strategically search for an AM (Addis et al., 2012). These brain regions and the executive processes they mediate are disproportionately affected in older adults (Glisky & Glisky, 2008; Turner & Spreng, 2012; West, 1996), which suggests that different cueing methods and the retrieval process they evoke can modulate age differences in neural activity. Second, there is noticeable variability in the baseline tasks to which AM retrieval is compared across the studies.

    View all citing articles on Scopus
    View full text