Aging is associated with contrasting changes in local and distant cortical connectivity in the human motor system

doi:10.1016/j.neuroimage.2006.03.061

NeuroImage

Volume 32, Issue 2, 15 August 2006, Pages 747-760

https://doi.org/10.1016/j.neuroimage.2006.03.061 Get rights and content

Abstract

Pathophysiological changes in neurological and neuropsychiatric diseases are increasingly described in terms of abnormal network connectivity. However, the anatomical integrity and efficacy of connections among multiple brain regions change with aging, even in healthy adults. We combined low-frequency transcranial magnetic stimulation and positron emission tomography to study the age-related changes in regional activation and effective connectivity, associated with voluntary action by healthy adults between 22 and 68 years old. Contrasting effects of aging on the motor network were seen using analyses of regional activation, effective connectivity mediating task-related neuronal activation and effective connectivity in response to transcranial magnetic stimulation. Low-frequency rTMS reduced cerebral blood flow during both movement and resting conditions, at the site of stimulation and neighboring frontal cortex. Aging was associated with increased movement-related activation in premotor cortex, bilaterally. Increasing age also increased the susceptibility of the cortex to the inhibitory effects of rTMS, at the site of stimulation and its contralateral homologue. Moreover, older subjects showed enhanced local effective connectivity, centered on the left premotor cortex, but reduced effective connectivity between distant motor-related cortical areas. We discuss these results in relation to the HAROLD model of aging and propose that there are differential effects of aging on local and distributed neuronal subpopulations in the motor network. This differential effect of aging has important implications for the study of neurodegenerative and cerebrovascular diseases that primarily affect older people, as well as our understanding of the normal aging process.

Section snippets

Subjects

Ten healthy right-handed adult volunteers (age range 22–68, mean 44, median 41, SD 16, seven men) participated after giving written informed consent. None had a history of hypertension, neurological or psychiatric disease, and they took no regular medication. The study was approved by the Joint Ethics Committee of the Institute of Neurology (UCL) and the National Hospital for Neurology and Neurosurgery (UCLH NHS Trust), London. Ionizing radiation was administered to normal subjects under

Effects of movement and aging on regional activation and connectivity

The selection and execution of finger movements activated an extensive network of cortical and subcortical areas compared with rest. These areas included primary motor and lateral premotor cortex, supplementary motor cortex and cerebellum; there was also a trend towards significant activation of the left dorsolateral prefrontal cortex (Table S1). Within this functional network, older subjects had greater activation of the dorsal premotor cortex bilaterally and in the cerebellum, in association

Effects of aging on regional activations and connectivity

The selection and execution of movements were associated with activation of an extensive cortical and subcortical network consistent with previous neuroimaging studies (Deiber et al., 1991, Frith et al., 1991). Within this network, older subjects have greater movement-related activation of the dorsal premotor cortex bilaterally, as reported previously for simple and complex motor tasks (Mattay et al., 2002, Ward and Frackowiak, 2003). This plasticity occurs in healthy aging subjects under 70

Acknowledgments

This work was supported by the Wellcome Trust. H.R. Siebner was supported by the DFG (DFG Si738/1), BMBF (01 GO 0511) and Volkswagenstiftung (IZ/79 932). Thanks also to Dr. Lucy Lee for help in preparation of the manuscript.

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View full text

Aging is associated with contrasting changes in local and distant cortical connectivity in the human motor system

Abstract

Section snippets

Subjects

Effects of movement and aging on regional activation and connectivity

Effects of aging on regional activations and connectivity

Acknowledgments

Neurobiol. Aging

Brain Res.

NeuroImage

Neurobiol. Aging

Neurosci. Biobehav. Rev.

NeuroImage

NeuroImage

Brain Res. Cogn. Brain Res.

NeuroImage

NeuroImage

NeuroImage

Biol. Psychiatry

Neurosci. Lett.

NeuroImage

Clin. Neurophysiol.

Neuroimage

NeuroImage

Clin. Neurophysiol.

Clin. Neurophysiol.

Clin. Neurophysiol.

Dynamics of neuronal firing correlation: modulation of “effective connectivity”

J. Neurophysiol.

Compensatory enlargement of synaptic size in aging and senile dementia

Boll. Soc. Ital. Biol. Sper.

Diffusion anisotropy in subcortical white matter and cortical gray matter: changes with aging and the role of CSF-suppression

J. Magn. Reson. Imaging

Hemispheric asymmetry reduction in old adults: the HAROLD model

Psychol. Aging

Age-related differences in effective neural connectivity during encoding and recall

NeuroReport

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

Cereb. Cortex

Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging

Neurology

Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects

Arch. Neurol.

Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection

Curr. Opin. Neurobiol.

Cortical areas and the selection of movement: a study with positron emission tomography

Exp. Brain Res.

Abnormal neural integration related to cognition in schizophrenia

Acta Psychiatr. Scand., Suppl.

No man is an island, entire of it self

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

Brain

A fMRI study of age-related differential cortical patterns during cued motor movement

Brain Topogr.

Schizophrenia: a disconnection syndrome?

Clin. Neurosci.

Spatial registration and normalisation of images

Hum. Brain Mapp.

Willed action and the prefrontal cortex in man: a study with PET

Proc. R. Soc. Lond., B Biol. Sci.