Executive control function, brain activation and white matter hyperintensities in older adults

doi:10.1016/j.neuroimage.2009.11.019

NeuroImage

Volume 49, Issue 4, 15 February 2010, Pages 3436-3442

https://doi.org/10.1016/j.neuroimage.2009.11.019 Get rights and content

Abstract

Context

Older adults responding to executive control function (ECF) tasks show greater brain activation on functional MRI (fMRI). It is not clear whether greater fMRI activation indicates a strategy to compensate for underlying brain structural abnormalities while maintaining higher performance.

Objective

To identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities.

Design

Cross-sectional analysis. Main variables of interest: fMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), and volume of white matter hyperintensities and of total brain atrophy.

Setting

Cohort of community-dwelling older adults.

Participants

Data were obtained on 25 older adults (20 women, 81 years mean age).

Outcome measure

Accuracy (number of correct response/total number of responses) while performing the Digit Symbol Substitution Test.

Results

Greater accuracy was significantly associated with greater peak fMRI activation, from ECF regions, including left middle frontal gyrus and right posterior parietal cortex. Greater WMH was associated with lower activation within accuracy-related regions. The interaction of accuracy by white matter hyperintensity volume was significant within the left posterior parietal region. Specifically, the correlation of white matter hyperintensity volume with fMRI activation varied as a function of accuracy and it was positive for greater accuracy. Associations with brain atrophy were not significant.

Conclusions

Recruitment of additional areas and overall greater brain activation in older adults is associated with higher performance. Posterior parietal activation may be particularly important to maintain higher accuracy in the presence of underlying brain connectivity structural abnormalities.

Introduction

Functional neuroimaging studies of executive control function (ECF) have shown that older adults have greater brain activation within the fronto-parietal regions and also activate additional regions compared to younger adults (Calautti and Serrati, 2001, Mattay and Fera, 2002, Ward and Frackowiak, 2003, Persson and Sylvester, 2004, Heuninckx and Wenderoth, 2005, Rosano and Aizenstein, 2005). This increased activation in the aging brain is well documented for various processes (Cabeza, 2002, Reuter-Lorenz and Lustig, 2005) including motor control (Mattay and Fera, 2002, Ward and Frackowiak, 2003) and working memory (Cabeza et al., 2004). Despite previous substantial work, (McIntosh and Sekuler, 1999, Reuter-Lorenz and Jonides, 2000, Reuter-Lorenz, 2001, Rypma, 2001, Cabeza and Anderson, 2002, Grady, 2002, Cabeza and Daselaar, 2004, Reuter-Lorenz and Lustig, 2005, Park and Reuter-Lorenz, 2009) it is not clear whether increased brain activation in older adults is a response to underlying age-related brain structural abnormalities and whether it is important to maintain higher performance.

Previous neuroimaging studies indicate that greater brain activation occurs when there is an imbalance between the difficulty of the task and the neural/behavioral resources of the individual. For example, young adults have greater brain activation in response to tasks of greater difficulty. (Grady, 1996, Rypma and D, 1999) Similarly, work done by us (Rosano, Aizenstein et al. 2005) and others, (Langenecker and Nielson, 2004, Persson and Sylvester, 2004) indicate that older adults performing ECF tasks sometimes have greater brain activation compared to younger adults. The decline of neural resources with age can be detected on brain structural MRI as white matter hyperintensities and greater atrophy. Such brain structural abnormalities may be responsible for the patterns of neural activation observed during performance of ECF tasks in older adults. In the presence of such impairments, the brain may respond to the task either with greater activation within ECF-related fronto-parietal regions or more “diffuse” activation with recruitment of non-ECF regions, or both. However, it is not known whether these changes in brain structure and activation are associated with better or worse ECF performance. If greater brain activation in individuals with brain structural impairment is associated with greater accuracy, then this would indicate that older adults' brain activation may be a compensatory strategy to maintain performance.

With the exception of a few studies of memory (Persson and Nyberg, 2006, Persson et al., 2006), previous reports of ECF-related activation could not answer this question because they did not examine the relationship of brain activation with behavioral performance concurrently with brain MRI abnormalities. Studies examining each of these associations individually report that greater fMRI activation in older adults is associated with better performance(Reuter-Lorenz, 1999, Cabeza and Anderson, 2002, Langenecker and Nielson, 2004, Rosano and Aizenstein, 2005), while greater brain MRI structural abnormalities are associated with poorer cognitive function (West, 1996, Gunning-Dixon and Raz, 2000). Recently, a few studies have begun to examine the interaction of fMRI brain activation with structural abnormalities, (Nordahl et al., 2006, Brassen et al., 2009) but did not account for performance.

The objective of this work is to determine whether brain activation in older adults with brain structural impairment is associated with better performance on an ECF task. We will examine fMRI patterns of activation in the whole brain to assess whether greater activation is localized within ECF-related regions or it extends to recruit additional non-ECF regions or both.

Section snippets

Participants

Participants for this study were recruited from a larger group of older adults, who had completed a 1-year physical activity randomized controlled trial LIFE-P (Lifestyle Interventions and Independence For Elders—Pilot) (Pahor, Blair et al. 2006) (www.ClinicalTrials.gov, registration # NCT00116194). The design of the LIFE-P has been described in detail elsewhere (Pahor, Blair et al. 2006). The primary mode of exercise for the intervention group was walking for at least 150 min/week and the

Results

Of the thirty participants who received a brain fMRI, two were excluded from this analysis due to incomplete behavioral data and three were excluded for excessive motion artifacts (± 3.5 mm in x, y, or z translation or ± 3° pitch, roll or yaw). Table 1 shows characteristics for the participants included in this analysis. Associations of accuracy with other measures (Table 1) were in the expected direction though not significant (p > 0.05). Accuracy and response time of the sDSST were significantly

Discussion

The results of this functional neuroimaging study support the compensation model of cognitive aging in several ways. First, greater accuracy was associated with greater fMRI activation, mainly from ECF regions. Specifically, prefrontal cortices showed greater fMRI activation during sDSST performance with higher accuracy. Second, we found that higher WMH was associated with lower activation in regions that were also important for accuracy and that the accuracy-related networks seemed to

Acknowledgments

The authors thank P. Vincent, P. Kost, P. Varlashkin and S. Urda, for assistance in obtaining the data necessary for this analysis. This work is supported in part by the Intramural Research Program, National Institute of Aging (NIA 263-MA-706016).

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Executive control function, brain activation and white matter hyperintensities in older adults

Abstract

Context

Objective

Design

Setting

Participants

Outcome measure

Results

Conclusions

Introduction

Section snippets

Participants

Results

Discussion

Acknowledgments

Neurobiol. Aging

Neuroimage

Comput. Biomed. Res.

Neuroimage

Neuroimage

Neuroimage

Curr. Opin. Neurobiol.

Neuroimage

Graph. Models Image Proc.

Neuroimage

Emergence of a powerful connection between sensory and cognitive functions across the adult life span: a new window to the study of cognitive aging?

Psychol. Aging

Hemispheric asymmetry reduction in older adults: the HAROLD model.

Psychol. Aging

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

Cereb. Cortex.

Effects of age on brain activation during auditory-cued thumb-to-index opposition: A positron emission tomography study.

Stroke

Statistical parametric maps in functional imaging: a general linear approach.

Hum. Brain Mapp.

Effect of task difficulty on cerebral blood flow during perceptual matching for faces.

Hum. Brain Mapp.

Introduction to the special section on aging, cognition, and neuroimaging.

Psychol. Aging

The cognitive correlates of white matter abnormalities in normal aging: a quantitative review.

Neuropsychology

Neural basis of aging: the penetration of cognition into action control.

J. Neurosci.

Cross-level unification: a computational exploration of the link between deterioration of neurotransmitter systems dedifferentiation of cognitive abilities in old age