In this study, electroencephalography (EEG) was used to examine the relationship between two leading hypotheses of cognitive aging, the inhibitory deficit and the processing speed hypothesis. We show that older adults exhibit a selective deficit in suppressing task-irrelevant information during visual working memory encoding, but only in the early stages of visual processing. Thus, the employment of suppressive mechanisms are not abolished with aging but rather delayed in time, revealing a decline in processing speed that is selective for the inhibition of irrelevant information. EEG spectral analysis of signals from frontal regions suggests that this results from excessive attention to distracting information early in the time course of viewing irrelevant stimuli. Subdividing the older population based on working memory performance revealed that impaired suppression of distracting information early in the visual processing stream is associated with poorer memory of task-relevant information. Thus, these data reconcile two cognitive aging hypotheses by revealing that an interaction of deficits in inhibition and processing speed contributes to agerelated cognitive impairment.aging ͉ working memory ͉ inhibitory deficit ͉ distraction ͉ attention C ognitive impairment associated with normal aging impacts multiple domains [e.g., attention, working memory (WM) and episodic memory (1)], prompting a search for underlying neural mechanisms that might account for such widespread deficits. Two of the leading cognitive aging hypotheses are the ''processing speed hypothesis,'' in which performance deficits are attributed to a decline in processing speed (2), and the ''inhibitory deficit hypothesis,'' which proposes that impairment in diverse cognitive abilities are the result of an inability to reduce interference from task-irrelevant information (3). Despite widespread behavioral evidence, physiological data characterizing the neural underpinnings of these age-related deficits, and notably the interactions between them, are limited.A recent functional magnetic resonance imaging (fMRI) study supports the presence of an age-related top-down modulation deficit in inhibitory control (4). Top-down modulation is the neural process that underlies our ability to focus on relevant information and ignore irrelevant distractions via both the enhancement and suppression of sensory cortical activity (5, 6). The fMRI data revealed that, although older adults were able to enhance visual cortical activity for relevant information to the same extent as younger individuals, they were unable to adequately suppress activity associated with irrelevant information, and this suppression deficit correlated with their impaired WM performance (4).The current study is directed at exploring the relationship between the inhibitory deficit and processing speed hypothesis, a goal that necessitates obtaining high temporal resolution neural data to dissect the time-course of age-related processing changes. Because of the vascular nature of the fMRI blood o...

Long-term potentiation (LTP) is a candidate synaptic mechanism underlying learning and memory that has been studied extensively at the cellular and molecular level in laboratory animals. To date, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. Inquiry into the functional significance of LTP has been hindered by the absence of a human model. Here we give the first demonstration that the rapid repetitive presentation of a visual checkerboard (a photic 'tetanus') leads to a persistent enhancement of one of the early components of the visual evoked potential in normal humans. The potentiated response is largest in the hemisphere contralateral to the tetanized visual hemifield and is limited to one component of the visual evoked response (the N1b). The selective potentiation of only the N1b component makes overall brain excitability changes unlikely and suggests that the effect is due instead to an LTP process. While LTP is known to exist in the human brain, the ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders.

The negative impact of external interference on working memory (WM) performance is well documented; yet, the mechanisms underlying this disruption are not sufficiently understood. In this study, electroencephalogram and functional magnetic resonance imaging (fMRI) data were recorded in separate experiments that each introduced different types of visual interference during a period of WM maintenance: distraction (irrelevant stimuli) and interruption (stimuli that required attention). The data converged to reveal that regardless of the type of interference, the magnitude of processing interfering stimuli in the visual cortex (as rapidly as 100 ms) predicted subsequent WM recognition accuracy for stored items. fMRI connectivity analyses suggested that in the presence of distraction, encoded items were maintained throughout the delay period via connectivity between the middle frontal gyrus and visual association cortex, whereas memoranda were not maintained when subjects were interrupted but rather reactivated in the postinterruption period. These results elucidate the mechanisms of external interference on WM performance and highlight similarities and differences of distraction and multitasking.

Attention-dependent modulation of neural activity in visual association cortex (VAC) is thought to depend on top-down modulatory control signals emanating from the prefrontal cortex (PFC). In a previous functional magnetic resonance imaging study utilizing a working memory task, we demonstrated that activity levels in scene-selective VAC (ssVAC) regions can be enhanced above or suppressed below a passive viewing baseline level depending on whether scene stimuli were attended or ignored (Gazzaley, Cooney, McEvoy, et al. 2005). Here, we use functional connectivity analysis to identify possible sources of these modulatory influences by examining how network interactions with VAC are influenced by attentional goals at the time of encoding. Our findings reveal a network of regions that exhibit strong positive correlations with a ssVAC seed during all task conditions, including foci in the left middle frontal gyrus (MFG). This PFC region is more correlated with the VAC seed when scenes were remembered and less correlated when scenes were ignored, relative to passive viewing. Moreover, the strength of MFG-VAC coupling correlates with the magnitude of attentional enhancement and suppression of VAC activity. Although our correlation analyses do not permit assessment of directionality, these findings suggest that PFC biases activity levels in VAC by adjusting the strength of functional coupling in accordance with stimulus relevance.

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.

Interference is known to negatively impact the ability to maintain information in working memory (WM), an effect that is exacerbated with aging. Here, we explore how distinct sources of interference, i.e., distraction (stimuli to-be-ignored) and interruption (stimuli requiring attention), differentially influence WM in younger and older adults. EEG was recorded while participants engaged in three versions of a delayed-recognition task: no interference, a distracting stimulus, and an interrupting stimulus presented during WM maintenance. Behaviorally, both types of interference negatively impacted WM accuracy in older adults significantly more than younger adults (with a larger deficit for interruptions). N170 latency measures revealed that the degree of processing both distractors and interruptors predicted WM accuracy in both populations. However, while WM impairments could be explained by excessive attention to distractors by older adults (a suppression deficit), impairment induced by interruption were not clearly mediated by age-related increases in attention to interruptors. These results suggest that distinct underlying mechanisms mediate the impact of different types of external interference on WM in normal aging.

Multitasking negatively influences the retention of information over brief periods of time. This impact of interference on working memory is exacerbated with normal aging. We used functional MRI to investigate the neural basis by which an interruption is more disruptive to working memory performance in older individuals. Younger and older adults engaged in delayed recognition tasks both with and without interruption by a secondary task. Behavioral analysis revealed that working memory performance was more impaired by interruptions in older compared with younger adults. Functional connectivity analyses showed that when interrupted, older adults disengaged from a memory maintenance network and reallocated attentional resources toward the interrupting stimulus in a manner consistent with younger adults. However, unlike younger individuals, older adults failed to both disengage from the interruption and reestablish functional connections associated with the disrupted memory network. These results suggest that multitasking leads to more significant working memory disruption in older adults because of an interruption recovery failure, manifest as a deficient ability to dynamically switch between functional brainnetworks.W orking memory (WM), the ability to store and manipulate information in the mind over brief periods of time, is critical for a wide variety of cognitive abilities and real life activities (1). It has been demonstrated that WM performance is negatively impacted by the presence of external stimuli that are outside the focus of our memory goals (2, 3). This interference occurs whether there is an attempt to ignore these stimuli (i.e., distractions), or attend to them as a component of a concurrent, secondary task (i.e., interruptions, or multitasking) (4). We recently showed that older adults experience a more negative impact by distraction on WM performance compared with younger adults, and an even greater impairment when multitasking (5). There is extensive literature indicating that older adults are highly susceptible to distraction and that this leads to impairment in performance (for review, see refs. 6 and 7). In terms of a greater impact of multitasking on WM in aging, this finding is consistent with the detrimental influence that multitasking has been shown to have on a wide range of activities in older individuals (8-10). Research directed at understanding the basis of age-related interference effects is becoming increasingly important, as older adults remain engaged in the work force later in life (11), which itself is evolving into a more demanding, high-interference environment (12).To explore the neural basis of age-related WM disruption by distractions, we previously conducted a series of experiments using electroencephalography (EEG) and functional MRI (fMRI) recordings. Functional MRI measures revealed that older individuals inappropriately direct excessive attention toward processing visual stimuli that are entirely irrelevant (i.e., distractions), and that this correlates with diminishe...

Selective attention confers a behavioral benefit for both perceptual and working memory (WM) performance, often attributed to top-down modulation of sensory neural processing. However, the direct relationship between early activity modulation in sensory cortices during selective encoding and subsequent WM performance has not been established. To explore the influence of selective attention on WM recognition, we used electroencephalography (EEG) to study the temporal dynamics of top-down modulation in a selective, delayed-recognition paradigm. Participants were presented with overlapped, "double-exposed" images of faces and natural scenes, and were instructed to either remember the face or the scene while simultaneously ignoring the other stimulus. Here, we present evidence that the degree to which participants modulate the early P100 (97-129 ms) eventrelated potential (ERP) during selective stimulus encoding significantly correlates with their subsequent WM recognition. These results contribute to our evolving understanding of the mechanistic overlap between attention and memory.