Neural correlates of post-retrieval monitoring in older adults are preserved under divided attention, but are decoupled from memory performance

Post-retrieval monitoring is associated with engagement of anterior cingulate and dorsolateral prefrontal cortex. Recent fMRI studies reported age-invariant monitoring effects in these regions and an age-invariant correlation between these effects and memory performance. The present study examined monitoring effects during associative recognition (difference in activity elicited by ‘rearranged’ and ‘intact’ test pairs) under single and dual (tone detection) task conditions in young and older adults (Ns = 28 per group). It was predicted that, for the older adults only, dual tasking would attenuate memory performance and monitoring effects and weaken their correlation. Consistent with this prediction, in the older group imposition of the secondary task led to lower memory performance and elimination of the relationship between monitoring effects and performance. However, the size of the effects did not differ between single and dual task conditions. The findings suggest that the decline in older adults’ memory performance in the dual task condition resulted not from impaired monitoring, but from a different cause that also weakened the dependence of performance on monitoring

Divided attention at retrieval does not influence neural correlates of recollection in young or older adults

Age-related decline in episodic memory has been partially attributed to older adults’ reduced domain general processing resources. In the present study, we examined the effects of divided attention (DA) - a manipulation assumed to further deplete the already limited processing resources of older adults - on the neural correlates of recollection in young and older adults. Participants underwent fMRI scanning while they performed an associative recognition test in single and dual (tone detection) task conditions. Recollection effects were operationalized as greater BOLD activity elicited by test pairs correctly endorsed as ‘intact’ than pairs correctly or incorrectly endorsed as ‘rearranged’. Detrimental effects of DA on associative recognition performance were identified in older but not young adults. The magnitudes of recollection effects did not differ between the single and dual (tone detection) tasks in either age group. Across the task conditions, age-invariant recollection effects were evident in most members of the core recollection network. However, while young adults demonstrated robust recollection effects in left angular gyrus, angular gyrus effects were undetectable in the older adults in either task condition. With the possible exception of this result, the findings suggest that DA did not influence processes supporting the retrieval and representation of associative information in either young or older adults, and converge with prior behavioral findings to suggest that episodic retrieval operations are little affected by DA

Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations

Our understanding of the etiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behavior of mice with induced endometriosis and the impact of the GnRH antagonist Cetrorelix on lesion regression and sensory behavior. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were as well as their cellular composition. The severity of pain-like behavior also varied across models. Whilst Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behavior. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes / heterogeneity observed in women should become a standard approach to discovery science in the field of endometriosis

Age-related Differences in Prestimulus Subsequent Memory Effects Assessed with Event-related Potentials

Prestimulus subsequent memory effects (preSMEs)—differences in neural activity elicited by a task cue at encoding that are predictive of later memory performance—are thought to reflect differential engagement of preparatory processes that benefit episodic memory encoding. We investigated age differences in preSMEs indexed by differences in ERP amplitude just before the onset of a study item. Young and older adults incidentally encoded words for a subsequent memory test. Each study word was preceded by a task cue that signaled a judgment to perform on the word. Words were presented for either a short (300 msec) or long (1000 msec) duration with the aim of placing differential benefits on engaging preparatory processes initiated by the task cue. ERPs associated with subsequent successful and unsuccessful recollection, operationalized here by source memory accuracy, were estimated time-locked to the onset of the task cue. In a late time window (1000–2000 msec after onset of the cue), young adults demonstrated frontally distributed preSMEs for both the short and long study durations, albeit with opposite polarities in the two conditions. This finding suggests that preSMEs in young adults are sensitive to perceived task demands. Although older adults showed no evidence of preSMEs in the same late time window, significant preSMEs were observed in an earlier time window (500–1000 msec) that was invariant with study duration. These results are broadly consistent with the proposal that older adults differ from their younger counterparts in how they engage preparatory processes during memory encoding

AGN STORM 2: V. Anomalous Behavior of the CIV Light Curve in Mrk 817

An intensive reverberation mapping campaign on the Seyfert 1 galaxy Mrk817 using the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope (HST) revealed significant variations in the response of the broad UV emission lines to fluctuations in the continuum emission. The response of the prominent UV emission lines changes over a $\sim$60-day duration, resulting in distinctly different time lags in the various segments of the light curve over the 14 months observing campaign. One-dimensional echo-mapping models fit these variations if a slowly varying background is included for each emission line. These variations are more evident in the CIV light curve, which is the line least affected by intrinsic absorption in Mrk817 and least blended with neighboring emission lines. We identify five temporal windows with distinct emission line response, and measure their corresponding time delays, which range from 2 to 13 days. These temporal windows are plausibly linked to changes in the UV and X-ray obscuration occurring during these same intervals. The shortest time lags occur during periods with diminishing obscuration, whereas the longest lags occur during periods with rising obscuration. We propose that the obscuring outflow shields the ultraviolet broad lines from the ionizing continuum. The resulting change in the spectral energy distribution of the ionizing continuum, as seen by clouds at a range of distances from the nucleus, is responsible for the changes in the line response.Comment: 20 pages, 8 figures, submitted to Ap

AGN STORM 2. IV. Swift X-ray and ultraviolet/optical monitoring of Mrk 817

The AGN STORM 2 campaign is a large, multiwavelength reverberation mapping project designed to trace out the structure of Mrk 817 from the inner accretion disk to the broad emission line region and out to the dusty torus. As part of this campaign, Swift performed daily monitoring of Mrk 817 for approximately 15 months, obtaining observations in X-rays and six UV/optical filters. The X-ray monitoring shows that Mrk 817 was in a significantly fainter state than in previous observations, with only a brief flare where it reached prior flux levels. The X-ray spectrum is heavily obscured. The UV/optical light curves show significant variability throughout the campaign and are well correlated with one another, but uncorrelated with the X-rays. Combining the Swift UV/optical light curves with Hubble UV continuum light curves, we measure interband continuum lags, $\tau(\lambda)$, that increase with increasing wavelength roughly following $\tau(\lambda) \propto \lambda^{4/3}$, the dependence expected for a geometrically thin, optically thick, centrally illuminated disk. Modeling of the light curves reveals a period at the beginning of the campaign where the response of the continuum is suppressed compared to later in the light curve - the light curves are not simple shifted and scaled versions of each other. The interval of suppressed response corresponds to a period of high UV line and X-ray absorption, and reduced emission line variability amplitudes. We suggest that this indicates a significant contribution to the continuum from the broad line region gas that sees an absorbed ionizing continuum.Comment: 20 pages, 13 figures, 3 tables, accepted for publication in Ap

AGN STORM 2. I. First results: A Change in the Weather of Mrk 817

We present the first results from the ongoing, intensive, multiwavelength monitoring program of the luminous Seyfert 1 galaxy Mrk 817. While this active galactic nucleus was, in part, selected for its historically unobscured nature, we discovered that the X-ray spectrum is highly absorbed, and there are new blueshifted, broad, and narrow UV absorption lines, which suggest that a dust-free, ionized obscurer located at the inner broad-line region partially covers the central source. Despite the obscuration, we measure UV and optical continuum reverberation lags consistent with a centrally illuminated Shakura–Sunyaev thin accretion disk, and measure reverberation lags associated with the optical broad-line region, as expected. However, in the first 55 days of the campaign, when the obscuration was becoming most extreme, we observe a de-coupling of the UV continuum and the UV broad emission-line variability. The correlation recovered in the next 42 days of the campaign, as Mrk 817 entered a less obscured state. The short C IV and Lyα lags suggest that the accretion disk extends beyond the UV broad-line region. Unified

AGN STORM 2. VIII. Investigating the Narrow Absorption Lines in Mrk 817 Using HST-COS Observations*

We observed the Seyfert 1 galaxy Mrk 817 during an intensive multiwavelength reverberation mapping campaign for 16 months. Here, we examine the behavior of narrow UV absorption lines seen in the Hubble Space Telescope/Cosmic Origins Spectrograph spectra, both during the campaign and in other epochs extending over 14 yr. We conclude that, while the narrow absorption outflow system (at −3750 km s−1 with FWHM = 177 km s−1) responds to the variations of the UV continuum as modified by the X-ray obscurer, its total column density (log NH = 19.5 - + 0.13 0.61 cm−2 ) did not change across all epochs. The adjusted ionization parameter (scaled with respect to the variations in the hydrogen-ionizing continuum flux) is log UH = −1.0 - + 0.3 0.1. The outflow is located at a distance smaller than 38 pc from the central source, which implies a hydrogen density of nH > 3000 cm−3. The absorption outflow system only covers the continuum emission source and not the broad emission line region, which suggests that its transverse size is small (< 1016 cm), with potential cloud geometries ranging from spherical to elongated along the line of sight

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

AGN STORM 2. IV. Swift X-Ray and Ultraviolet/Optical Monitoring of Mrk 817

The AGN STORM 2 campaign is a large, multiwavelength reverberation mapping project designed to trace out the structure of Mrk 817 from the inner accretion disk to the broad emission line region and out to the dusty torus. As part of this campaign, Swift performed daily monitoring of Mrk 817 for approximately 15 months, obtaining observations in X-rays and six UV/optical filters. The X-ray monitoring shows that Mrk 817 was in a significantly fainter state than in previous observations, with only a brief flare where it reached prior flux levels. The X-ray spectrum is heavily obscured. The UV/optical light curves show significant variability throughout the campaign and are well correlated with one another, but uncorrelated with the X-rays. Combining the Swift UV/optical light curves with Hubble Space Telescope UV continuum light curves, we measure interband continuum lags, τ(λ), that increase with increasing wavelength roughly following τ(λ) ∝ λ 4/3, the dependence expected for a geometrically thin, optically thick, centrally illuminated disk. Modeling of the light curves reveals a period at the beginning of the campaign where the response of the continuum is suppressed compared to later in the light curve—the light curves are not simple shifted and scaled versions of each other. The interval of suppressed response corresponds to a period of high UV line and X-ray absorption, and reduced emission line variability amplitudes. We suggest that this indicates a significant contribution to the continuum from the broad-line region gas that sees an absorbed ionizing continuum