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With the explosion of digital media and technologies, scholars, educators and the public have become increasingly vocal about the role that an ‘attention economy’ has in our lives1. The rise of the current digital culture coincides with longstanding scientific questions about why humans sometimes remember and sometimes forget, and why some individuals remember better than others2–6. Here we examine whether spontaneous attention lapses—in the moment7–12, across individuals13–15 and as a function of everyday media multitasking16–19—negatively correlate with remembering. Electroencephalography and pupillometry measures of attention20,21 were recorded as eighty young adults (mean age, 21.7 years) performed a goal-directed episodic encoding and retrieval task22. Trait-level sustained attention was further quantified using task-based23 and questionnaire measures24,25. Using trial-to-trial retrieval data, we show that tonic lapses in attention in the moment before remembering, assayed by posterior alpha power and pupil diameter, were correlated with reductions in neural signals of goal coding and memory, along with behavioural forgetting. Independent measures of trait-level attention lapsing mediated the relationship between neural assays of lapsing and memory performance, and between media multitasking and memory. Attention lapses partially account for why we remember or forget in the moment, and why some individuals remember better than others. Heavier media multitasking is associated with a propensity to have attention lapses and forget. Lapses in attention before remembering partially account for why we remember or forget in the moment, why some individuals remember better than others, and why heavier media multitasking is related to worse memory.

ObjectiveTo determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF β-amyloid (Aβ)42/Aβ40 and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU).MethodsCU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word–picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied “target” objects, novel “foil” objects, and perceptually similar “lure” objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education.ResultsAge and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target–lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aβ42 was not significantly associated with p-tau181 or memory.ConclusionsTests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

Goal-directed behavior can benefit from proactive adjustments of cognitive control that occur in anticipation of forthcoming cognitive control demands (CCD). Predictions of forthcoming CCD are thought to depend on learning and memory in two ways: First, through direct experience, associative encoding may link previously experienced CCD to its triggering item, such that subsequent encounters with the item serve to cue retrieval of (i.e., predict) the associated CCD. Second, in the absence of direct experience, pattern completion and mnemonic integration mechanisms may allow CCD to be generalized from its associated item to other items related in memory. While extant behavioral evidence documents both types of CCD prediction, the neurocognitive mechanisms giving rise to these predictions remain largely unexplored. Here, we tested two hypotheses: (1) memory-guided predictions about CCD precede control adjustments due to the actual CCD required; and (2) generalization of CCD can be accomplished through integration mechanisms that link partially overlapping CCD-item and item-item associations in memory. Supporting these hypotheses, the temporal dynamics of theta and alpha power in human electroencephalography data (n= 43, 26 females) revealed that an associative CCD effect emerges earlier than interaction effects involving actual CCD. Furthermore, generalization of CCD from one item (X) to another item (Y) was predicted by a decrease in alpha power following the presentation of the X-Y pair. These findings advance understanding of the mechanisms underlying memory-guided adjustments of cognitive control.SIGNIFICANCE STATEMENTCognitive control adaptively regulates information processing to align with task goals. Experience-based expectations enable adjustments of control, leading to improved performance when expectations match the actual control demand required. Using EEG, we demonstrate that memory for past cognitive control demand proactively guides the allocation of cognitive control, preceding adjustments of control triggered by the demands of the present environment. Furthermore, we demonstrate that learned cognitive control demands can be generalized through mnemonic integration processes, enabling the spread of expectations about cognitive control demands to items associated in memory. We reveal that this generalization is linked to decreased alpha oscillation in medial frontal channels. Collectively, these findings provide new insights into how memory-control interactions facilitate goal-directed behavior.

We report a diagnostically challenging case of a 64-year-old man with a history of remote head trauma who developed mild behavioral changes and dyscalculia. He was diagnosed with clinical Alzheimer’s disease (AD), with additional features consistent with behavioral variant frontotemporal dementia. Structural magnetic resonance imaging revealed atrophy in bilateral frontal and parietal cortices and hippocampi on visual inspection and left frontal pole and bilateral anterior temporal encephalomalacia, suspected to be due to head trauma. Consistent with the diagnosis of Alzheimer’s pathology, positron emission tomography (PET) with Pittsburgh compound B suggested the presence of beta-amyloid. Fluorodeoxyglucose PET demonstrated hypometabolism in bilateral frontal and temporoparietal cortices. Voxel-based morphometry showed atrophy predominant in ventral frontal regions (bilateral orbitofrontal cortex, pregenual anterior cingulate/medial superior frontal gyrus), bilateral mid cingulate, bilateral lateral temporal cortex, and posterior insula. Bilateral caudate, thalamus, hippocampi, and cerebellum were prominently atrophied. Unexpectedly, a pathologic hexanucleotide repeat expansion in C9ORF72 was identified in this patient. This report underscores the clinical variability in C9ORF72 expansion carriers and the need to consider mixed pathologies, particularly when imaging studies are inconsistent with a single syndrome or pathology.

Hexanucleotide repeat expansion in C9orf72 represents the most common genetic cause of familial and sporadic behavioural variant frontotemporal dementia. Previous studies show that some C9orf72 carriers with behavioural variant frontotemporal dementia exhibit distinctive atrophy patterns whereas others show mild or undetectable atrophy despite severe behavioural impairment. To explore this observation, we examined intrinsic connectivity network integrity in patients with or without the C9orf72 expansion. We studied 28 patients with behavioural variant frontotemporal dementia, including 14 C9orf72 mutation carriers (age 58.3 +/- 7.7 years, four females) and 14 non-carriers (age 60.8 +/- 6.9 years, four females), and 14 age- and sex-matched healthy controls. Both patient groups included five patients with comorbid motor neuron disease. Neuropsychological data, structural brain magnetic resonance imaging, and task-free functional magnetic resonance imaging were obtained. Voxel-based morphometry delineated atrophy patterns, and seed-based intrinsic connectivity analyses enabled group comparisons of the salience, sensorimotor, and default mode networks. Single-patient analyses were used to explore network imaging as a potential biomarker. Despite contrasting atrophy patterns in C9orf72 carriers versus non-carriers, patient groups showed topo-graphically similar connectivity reductions in the salience and sensorimotor networks. Patients without C9orf72 expansions exhibited increases in default mode network connectivity compared to controls and mutation carriers. Across all patients, behavioural symptom severity correlated with diminished salience network connectivity and heightened default mode network connectivity. In C9orf72 carriers, salience network connectivity reduction correlated with atrophy in the left medial pulvinar thalamic nucleus, and this region further showed diminished connectivity with key salience network hubs. Single-patient analyses revealed salience network disruption and default mode network connectivity enhancement in C9orf72 carriers with earlystage or slowly progressive symptoms. The findings suggest that patients with behavioural variant frontotemporal dementia with or without the C9orf72 expansion show convergent large-scale network breakdowns despite distinctive atrophy patterns. Medial pulvinar degeneration may contribute to the behavioural variant frontotemporal dementia syndrome in C9orf72 carriers by disrupting salience network connectivity. Task-free functional magnetic resonance imaging shows promise in detecting earlystage disease in C9orf72 carriers and may provide a unifying biomarker across diverse anatomical variants.