Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging

D’Esposito, Mark; Deouell, Leon Y.; Gazzaley, Adam

doi:10.1038/nrn1246

Cited by 739 publications

(594 citation statements)

References 107 publications

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“…In regard to the use of fMRI to study aging, peak stimulus-related BOLD responses are similar in young and older adults, [26][27][28] although some work has shown that the magnitude of the BOLD response can be reduced in older adults, at least in some brain regions 29 . In addition, it is important to keep in mind that there are alterations in the cerebral vasculature with age, and these have the potential to influence the BOLD signal in as yet unknown ways 30,31 . Alhough much remains to be done to understand the impact of aging on the physiology underlying the BOLD signal, the relatively small age differences noted in the properties of these signals and recent work suggesting a small vascular contribution to BOLD signals in older adults during cognitive tasks 32 encourage the continued use of this technique to study cognitive aging.…”

Section: Introductionmentioning

confidence: 99%

The cognitive neuroscience of ageing

2012

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PrefaceThe availability of neuroimaging technology has spurred a marked increase in the human cognitive neuroscience literature, including the study of cognitive aging. Although there is a growing consensus that the aging brain retains considerable plasticity of function, currently measured primarily by means of functional magnetic resonance imaging, it is less clear how age differences in brain activity relate to cognitive performance. The field also is hampered by the complexity of the aging process itself and the large number of factors that are influenced by age. In this review, current trends and unresolved issues in the cognitive neuroscience of aging are discussed.

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Section: Introductionmentioning

confidence: 99%

The cognitive neuroscience of ageing

2012

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“…The recent finding of decreased BOLD response in presymptomatic carriers of familial AD mutation but increased BOLD response in APOE e4 carriers (albeit only four subjects) challenges the argument that increased BOLD is related to cognitive compensation (e.g., recruitment of additional neural resources indicating greater cognitive effort required to maintain performance at an equivalent level to healthy peers) and raises the possibility of an unidentified effect of the APOE allelic variant on cerebral vascular reactivity (Ringman et al, 2011). Since the BOLD signal reflects local changes in deoxyhemoglobin content, which in turn exhibits a complex dependence on changes in cerebral blood flow (CBF), cerebral blood volume, and the cerebral metabolic rate of oxygen consumption (Buxton et al, 2004), group differences in the BOLD response may also reflect variations in cerebrovascular functioning that become more pronounced with age or disease and can be confused with alterations in neural activity (D'Esposito et al, 2003). Therefore, direct assessment of CBF through perfusion imaging offers considerable promise as a noninvasive technique for detecting such early and oftentimes subtle functional brain changes that occur in preclinical or prodromal stages.…”

Section: Introductionmentioning

confidence: 99%

Effect of Mild Cognitive Impairment and APOE Genotype on Resting Cerebral Blood Flow and its Association with Cognition

Wierenga

Dev

Shin

et al. 2012

J Cereb Blood Flow Metab

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Using whole-brain pulsed arterial spin labeling magnetic resonance imaging, resting cerebral blood flow (CBF) was measured in 20 mild cognitive impairment (MCI; 11 e3 and 9 e4) and 40 demographically matched cognitively normal (CN; 27 e3 and 13 e4) participants. An interaction of apolipoprotein (APOE) genotype (e3 and e4) and cognitive status (CN and MCI) on quantified gray-matter CBF corrected for partial volume effects was found in the left parahippocampal and fusiform gyri (PHG/FG), right middle frontal gyrus, and left medial frontal gyrus. In the PHG/FG, CBF was elevated for CN e4 carriers but decreased for MCI e4 carriers. The opposite pattern was seen in frontal regions: CBF was decreased for CN e4 carriers but increased for MCI e4 carriers. Cerebral blood flow in the PHG/FG was positively correlated with verbal memory for CN e4 adults (r = 0.67, P = 0.01). Cerebral blood flow in the left medial frontal gyrus was positively correlated with verbal memory for MCI e4 adults (r = 0.70, P = 0.05). Findings support dynamic pathophysiologic processes in the brain associated with Alzheimer's disease risk and indicate that cognitive status and APOE genotype have interactive effects on CBF. Correlations between CBF and verbal memory suggest a differential neurovascular compensatory response in posterior and anterior cortices with cognitive decline in e4 adults.

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“…There is increasing recognition that, by its structural implication in neuro-vascular coupling, underlying vascular architecture is a key player in hemodynamically based functional imaging techniques (including fMRI and PET) (Harrison et al, 2002;d'Esposito et al, 2003;Logothetis and Wandell, 2004;Lauwers et al, 2008;Weber et al, 2008). In particular, the spatial resolution and specificity of such techniques are bound to the density of blood capillary vasculature and blood flow regulating structures (Harel et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

Lorthois¹,

Cassot²,

Lauwers³

2011

NeuroImage

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OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible. In a companion paper (Lorthois et al., Neuroimage, in press), we perform the first simulations of blood flow in an anatomically accurate large human intra-cortical vascular network (~10000 segments), using a 1D non-linear model taking into account the complex rheological properties of blood flow in microcirculation. This model predicts blood pressure, blood flow and hematocrit distributions, volumes of functional vascular territories, regional flow at voxel and network scales, etc. Using the same approach, we study flow reorganizations induced by global arteriolar vasodilations (an isometabolic global increase in cerebral blood flow). For small to moderate global vasodilations, the relationship between changes in volume and changes in flow is in close agreement with Grubb's law, providing a quantitative tool for studying the variations of its exponent with underlying vascular architecture. A significant correlation between blood flow and vascular structure at the voxel scale, practically unchanged with respect to baseline, is demonstrated. Furthermore, the effects of localized arteriolar vasodilations, representative of a local increase in metabolic demand, are analyzed. In particular, localized vasodilations induce flow changes, including vascular steal, in the neighboring arteriolar trunks at small distances (b 300 μm), while their influence in the neighboring veins is much larger (about 1 mm), which provides an estimate of the vascular point spread function. More generally, for the first time, the hemodynamic component of various functional neuroimaging techniques has been isolated from metabolic and neuronal components, and a direct relationship with several known characteristics of the BOLD signal has been demonstrated. IntroductionThere is increasing recognition that, by its structural implication in neuro-vascular coupling, underlying vascular architecture is a key player in hemodynamically based functional imaging techniques (including fMRI and PET) (Harrison et al., 2002;d'Esposito et al., 2003;Logothetis and Wandell, 2004;Lauwers et al., 2008;Weber et al., 2008). In particular, the spatial resolution and specificity of such techniques are bound to the density of blood capillary vasculature and blood flow regulating structures (Harel et al., 2006). This is especially important in the context of high field fMRI Harel et al., 2006), because, despite a dramatic increase in the theoretical spatial resolution obtained by using higher magnetic fields, associated with other hardware advancements, "the spatial extent of the hemodynamic response ultimately will impose a fundamental limitation on the spatial resolution of fMRI modalities" ).However, little is known about the fundamentals of the relationship between vascular structure and hemodynamic changes induced by brain activation. A growing body of evidence indicates that neurons, glia, and cerebral blood vessels, actin...

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Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging

Cited by 739 publications

References 107 publications

The cognitive neuroscience of ageing

The cognitive neuroscience of ageing

Effect of Mild Cognitive Impairment and APOE Genotype on Resting Cerebral Blood Flow and its Association with Cognition

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

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