David J. Madden

Bio: David J. Madden is an academic researcher from Duke University. The author has contributed to research in topics: Visual search & Cognition. The author has an hindex of 58, co-authored 158 publications receiving 13044 citations. Previous affiliations of David J. Madden include University of California, Davis & University of North Carolina at Chapel Hill.

Toward discovery science of human brain function

Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

Abstract: The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior–posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application.

Age-Related Differences in Multiple Measures of White Matter Integrity: A Diffusion Tensor Imaging Study of Healthy Aging

Abstract: Diffusion tensor imaging (DTI) measures diffusion of molecular water, which can be used to calculate indices of white matter integrity. Early DTI studies of aging primarily focused on two global measures of integrity; the average rate (mean diffusivity, MD) and orientation coherence (fractional anisotropy, FA) of diffusion. More recent studies have added measures of water movement parallel (axial diffusivity, AD) and perpendicular (radial diffusivity, RD) to the primary diffusion direction, which are thought to reflect the neural bases of age differences in diffusion (i.e., axonal shrinkage and demyelination, respectively). In the present study, patterns of age differences in white matter integrity were assessed by comparing younger and healthy older adults on multiple measures of integrity (FA, AD, RD). Results revealed two commonly reported patterns (Radial Increase Only and Radial/Axial Increase), and one relatively novel pattern (Radial Increase/Axial Decrease) that varied by brain region and may reflect differential aging of microstructural (e.g., degree of myelination) and macrostructural (e.g., coherence of fiber orientation) properties of white matter. In addition, larger age differences in FA in frontal white matter were consistent with the anterior-posterior gradient of age differences in white matter integrity. Together, these findings complement other recent studies in providing information about patterns of diffusivity that are characteristic of healthy aging.

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Abstract: Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

The processing-speed theory of adult age differences in cognition.

Abstract: A theory is proposed to account for some of the age-related differences reported in measures of Type A or fluid cognition. The central hypothesis in the theory is that increased age in adulthood is associated with a decrease in the speed with which many processing operations can be executed and that this reduction in speed leads to impairments in cognitive functioning because of what are termed the limited time mechanism and the simultaneity mechanism. That is, cognitive performance is degraded when processing is slow because relevant operations cannot be successfully executed (limited time) and because the products of early processing may no longer be available when later processing is complete (simultaneity). Several types of evidence, such as the discovery of considerable shared age-related variance across various measures of speed and large attenuation of the age-related influences on cognitive measures after statistical control of measures of speed, are consistent with this theory.

Exercise and physical activity for older adults

Abstract: The purpose of this Position Stand is to provide an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The Position Stand is divided into three sections: Section 1 briefly reviews the structural and functional changes that characterize normal human aging, Section 2 considers the extent to which exercise and physical activity can influence the aging process, and Section 3 summarizes the benefits of both long-term exercise and physical activity and shorter-duration exercise programs on health and functional capacity. Although no amount of physical activity can stop the biological aging process, there is evidence that regular exercise can minimize the physiological effects of an otherwise sedentary lifestyle and increase active life expectancy by limiting the development and progression of chronic disease and disabling conditions. There is also emerging evidence for significant psychological and cognitive benefits accruing from regular exercise participation by older adults. Ideally, exercise prescription for older adults should include aerobic exercise, muscle strengthening exercises, and flexibility exercises. The evidence reviewed in this Position Stand is generally consistent with prior American College of Sports Medicine statements on the types and amounts of physical activity recommended for older adults as well as the recently published 2008 Physical Activity Guidelines for Americans. All older adults should engage in regular physical activity and avoid an inactive lifestyle.

Fitness Effects on the Cognitive Function of Older Adults: A Meta-Analytic Study

Abstract: A meta-analytic study was conducted to examine the hypothesis that aerobic fitness training enhances the cognitive vitality of healthy but sedentary older adults. Eighteen intervention studies published between 1966 and 2001 were entered into the analysis. Several theoretically and practically important results were obtained. Most important fitness training was found to have robust but selective benefits for cognition, with the largest fitness-induced benefits occurring for executive-control processes. The magnitude of fitness effects on cognition was also moderated by a number of programmatic and methodological factors, including the length of the fitness-training intervention, the type of the intervention, the duration of training sessions, and the gender of the study participants. The results are discussed in terms of recent neuroscientific and psychological data that indicate cognitive and neural plasticity is maintained throughout the life span.