Top-down suppression deficit underlies working memory impairment in normal aging

Gazzaley, Adam; Cooney, Jeffrey W.; Rissman, Jesse; D’Esposito, Mark

doi:10.1038/nn1543

Cited by 826 publications

(837 citation statements)

References 13 publications

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Section: Discussionsupporting

confidence: 89%

“…Reduced functional integrity of anterior fiber pathways and the subsequent degradation of information flow could result in nonselective activation of processes that reflect an inevitable breakdown rather than active compensation. In either case, these results are consistent with models that suggest there is generalized degradation of inhibitory processes with aging (Hasher and Zacks 1988;Gazzaley et al 2005).In younger adults, regional activations tended to be quite succinct and focal. Overall, older adults showed patterns of activation that were quite similar to those seen in younger adults, but activity was more widespread during all attention conditions, covering significantly greater area in activated regions.…”

supporting

confidence: 88%

“…Gaeta, Friedman and Ritter demonstrated that while younger subjects showed minimal processing of irrelevant information, in older adults unattended auditory stimuli passed into attentional focus and received unwarranted additional processing (Gaeta et al 2003). Gazzaley et al have recently provided direct evidence for age-related loss of suppression of taskirrelevant information and the effect of this deficit on working memory function (Gazzaley et al 2005). In an FMRI design that separated suppression of task-irrelevant information from enhancement of task-relevant information, they demonstrated agerelated impaired suppression of irrelevant (unattended) but preserved enhancement of relevant (attended) scenes or faces.…”

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confidence: 99%

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

2006

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Age-related deficits in visual selective attention suggest that the efficiency of inhibitory processes is particularly affected by aging. To investigate whether processing inefficiencies observed in visual attention are similar in auditory attention and when shifting attention across modalities, we conducted an FMRI study with healthy young and older adults using a task that required sustained auditory and visual selective attention and cross-modal attention shifts. Older adults in this study performed as well as the younger adults, but showed age-related differences in BOLD responses. The most striking of these differences were bilateral frontal and parietal regions of significantly increased activation in older adults during both focused and shifting attention. Our data suggest that this increased activation did not reflect new recruitment, but reliance on brain regions typically used by younger adults when task demands are greater. Older adults' activation patterns suggested that even during focused attention conditions they were "shifting" attention to stimuli in the unattended modality. Increased activation during processing of both task-relevant and task-irrelevant information implies age-related loss of processing selectivity. These patterns may reflect both task-specific compensatory neural recruitment and degradation of sensory inhibition. 2Selective attention modulates sensory response to enhance selected relative to non-selected information. Electrophysiological studies have shown that the neural response in visual cortex is increased when visual information is attended (Heinze et al. 1994;Hillyard et al. 1998;Mangun et al. 1998). However, attention driven modulation of sensory cortex is not simple signal enhancement (gain), but also reflects neural specificity for the attended information that results from some combination of augmentation of selected and inhibition of non-selected or less relevant stimulation (Murray and Wojciulik 2004).While selective attention may remain grossly intact with normal aging, some components of attentional processing are affected. Hasher and Zacks (Hasher and Zacks 1988) proposed a model in which age-related deficits in attentional selectivity underlie changes in memory function. They suggested that an ineffective inhibitory system would allow irrelevant information into working memory buffers resulting in the association of large numbers of less specific memory traces. Additionally, an inefficient inhibitory system would affect the ability to suppress irrelevant pathways during memory retrieval and may reflect a central mechanism underlying both distractibility and memory deficits in older adults. A number of studies have suggested that there are age-related decreases in attention modulated neural specificity -most commonly observed as a decreased efficiency in the inhibition of unattended or less relevant information. Single cell recordings in senescent monkeys have shown significant reduction in selectivity of neurons in primary visual cortex that may reflect...

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Section: Discussionsupporting

confidence: 89%

supporting

confidence: 88%

mentioning

confidence: 99%

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

2006

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“…Although the lack of significant lag-adaptation suppression (GrillSpector et al, 2006) of the evoked responses was surprising, it is classically known that attention can attenuate the effect of neural suppression (Gazzaley et al, 2005). Here, participants were asked to pay attention to any deviants presented in the auditory, visual or audiovisual modalities during lag-adaptation.…”

Section: Evoked Activity and Attention To Timementioning

confidence: 99%

Encoding of event timing in the phase of neural oscillations

2014

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a b s t r a c t a r t i c l e i n f oTime perception is a critical component of conscious experience. To be in synchrony with the environment, the brain must deal not only with differences in the speed of light and sound but also with its computational and neural transmission delays. Here, we asked whether the brain could actively compensate for temporal delays by changing its processing time. Specifically, can changes in neural timing or in the phase of neural oscillation index perceived timing? For this, a lag-adaptation paradigm was used to manipulate participants' perceived audiovisual (AV) simultaneity of events while they were recorded with magnetoencephalography (MEG). Desynchronized AV stimuli were presented rhythmically to elicit a robust 1 Hz frequency-tagging of auditory and visual cortical responses. As participants' perception of AV simultaneity shifted, systematic changes in the phase of entrained neural oscillations were observed. This suggests that neural entrainment is not a passive response and that the entrained neural oscillation shifts in time. Crucially, our results indicate that shifts in neural timing in auditory cortices linearly map participants' perceived AV simultaneity. To our knowledge, these results provide the first mechanistic evidence for active neural compensation in the encoding of sensory event timing in support of the emergence of time awareness.

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“…For 13 young and 13 older subjects, 18 axial slices were acquired with a time repeat (TR) = 2 s and a 0.5 mm gap between slices and for 13 young and 11 older subjects, 10 oblique slices, parallel to the calcarine sulcas, were acquired with a 1.1 s TR and a 1 mm gap between slices. The 2 s TR data were collected as part of other studies (Gazzaley, et al 2005a;Gazzaley, et al 2005b). EPI distortions between the two shots due to motion or other phase changes were decreased using navigator echos (Ehman and Felmlee 1989;Kim, et al 1996).…”

Section: Data Collectionmentioning

confidence: 99%

Reducing vascular variability of fMRI data across aging populations using a breathholding task

Handwerker¹,

Gazzaley²,

Inglis³

et al. 2006

Human Brain Mapping

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The magnitude and shape of Blood Oxygen Level Dependent (BOLD) responses in functional Magnetic Resonance Imaging (fMRI) studies vary across brain regions, subjects, and populations. This variability may be secondary to neural activity or vasculature differences, thus complicating interpretations of BOLD signal changes in fMRI experiments. We compare the BOLD responses to neural activity and a vascular challenge and test a method to dissociate these influences in 26 younger subjects (ages 18-36) and 24 older subjects (ages 51-78). Each subject performed a visuomotor saccade task (a vascular response to neural activity) and a breath holding task (vascular dilation induced by hypercapnia) during separate runs in the same scanning session. For the saccade task, signal magnitude showed a significant decrease with aging in FEF, SEF, and V1, and a delayed time-to-peak with aging in V1. The signal magnitudes from the saccade and hypercapnia tasks showed significant linear regressions within subjects and across individuals and populations. These two tasks had weaker, but sometimes significant, linear regressions for time-to-peak and coherence phase measures. The significant magnitude decrease with aging in V1 remained after dividing the saccade task magnitude by the hypercapnia task magnitude implying that the signal decrease is neural in origin. These findings may lead to a method to identify vascular reactivity induced differences in the BOLD response across populations and the development of methods to account for the influence of these vasculature differences in a simple, noninvasive manner.Handwerker, Daniel A 3

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Top-down suppression deficit underlies working memory impairment in normal aging

Cited by 826 publications

References 13 publications

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

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

Encoding of event timing in the phase of neural oscillations

Reducing vascular variability of fMRI data across aging populations using a breathholding task

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