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Goal Management Training® (GMT) teaches strategies to reduce cognitive load and improve focus in everyday tasks. The aim of this study was to ascertain feasibility, acceptability, and efficacy potential of GMT for people (≥50 years) with stable HIV infection scoring low on tests of cognitive ability. A two-sample, parallel, controlled trial was carried out. Feasibility was demonstrated, as 21/30 participants in the GMT group attended ≥8 of the 9 sessions and completed at least half of the homework. There was no change on the primary performance-based cognitive outcomes in the GMT group or in the control group (n = 23). There was a meaningful improvement in self-reported cognition in those adherent to the intervention. GMT is a promising intervention for people aging with HIV who are dealing with cognitive difficulties affecting their everyday life and should be further investigated.

PurposeTauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).Study designProspective, multi-centre, observational study.Materials and methodspRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness.ResultsA significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 μm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness.ConclusionThe finding that the temporal pRNFL in the TDP-43 group was on average 15.46 μm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.

Abstract Background Individuals differ in how they remember the past: some richly re-experience specific details of past episodes, whereas others recall only the gist of past events. Little research has examined how such trait mnemonics, or lifelong individual differences in memory capacities, relate to cognitive aging. We specifically examined trait episodic autobiographical memory (AM, the tendency to richly re-experience episodic details of past events) in relation to complaints of everyday cognitive functioning, which are known to increase with age. Although one might predict that individuals reporting higher trait-level episodic AM would be resistant to age-related decline in everyday function, we made the opposite prediction. That is, we predicted that those with lower trait-level episodic AM would be better equipped with compensatory strategies, practiced throughout the lifespan, to cope with age-related memory decline. Those with higher trait-level episodic AM would have enhanced sensitivity to age-related cognitive changes due to their tendency to rely on their perceived above-average memory function. Methods We tested these predictions in 959 older adults aged 50–93 using online subjective and objective measures of memory and cognitive function. Our key measures of interest were the Survey of Autobiographical Memory, a measure of autobiographical memory abilities; and the Cognitive Failures Questionnaire, a measure of everyday cognitive function. Results In keeping with our prediction, we found that complaints of day-to-day memory slips and errors (normally elevated with age) remained stable or even decreased with age among those reporting lower trait-level episodic AM, whereas those reporting higher trait-level episodic AM reported the expected age-related increase in such errors. This finding was specific to episodic AM and not observed for other autobiographical memory capacities (e.g., semantic, spatial). It was further unaccounted for by response bias or objectively assessed cognitive abilities. Conclusions Congenitally low trait-level episodic AM may paradoxically confer a functional advantage in aging. This could be due to well-developed non-episodic strategies not present in those with higher abilities, who are more sensitive to age-related memory decline attributable to medial temporal lobe changes. Our findings emphasize the importance of considering individual differences when studying cognitive aging trajectories.

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.

The comparison of memory performance during free and fixed viewing conditions has been used to demonstrate the involvement of eye movements in memory encoding and retrieval, with stronger effects at encoding than retrieval. Relative to conditions of free viewing, participants generally show reduced memory performance following sustained fixation, suggesting that unrestricted eye movements benefit memory. However, the cognitive basis of the memory reduction during fixed viewing is uncertain, with possible mechanisms including disruption of visual-mnemonic and/or imagery processes with sustained fixation, or greater working memory demands required for fixed relative to free viewing. To investigate one possible mechanism for this reduction, we had participants perform a working memory task—an auditory n-back task—during free and fixed viewing, as well as a repetitive finger tapping condition, included to isolate the effects of motor interference independent of the oculomotor system. As expected, finger tapping significantly interfered with n-back performance relative to free viewing, as indexed by a decrease in accuracy and increase in response times. By contrast, there was no evidence that fixed viewing interfered with n-back performance relative to free viewing. Our findings failed to support a hypothesis of increased working memory load during fixation. They are consistent with the notion that fixation disrupts long-term memory performance through interference with visual processes.

We propose a new sparsification method for the singular value decomposition-called the constrained singular value decomposition (CSVD)-that can incorporate multiple constraints such as sparsification and orthogonality for the left and right singular vectors. The CSVD can combine different constraints because it implements each constraint as a projection onto a convex set, and because it integrates these constraints as projections onto the intersection of multiple convex sets. We show that, with appropriate sparsification constants, the algorithm is guaranteed to converge to a stable point. We also propose and analyze the convergence of an efficient algorithm for the specific case of the projection onto the balls defined by the norms L1 and L2. We illustrate the CSVD and compare it to the standard singular value decomposition and to a non-orthogonal related sparsification method with: 1) a simulated example, 2) a small set of face images (corresponding to a configuration with a number of variables much larger than the number of observations), and 3) a psychometric application with a large number of observations and a small number of variables. The companion R-package, csvd, that implements the algorithms described in this paper, along with reproducible examples, are available for download from https://github.com/vguillemot/csvd.

Although electroconvulsive therapy (ECT) is a widely used and effective treatment for refractory depression, the neural underpinnings of its therapeutic effects remain poorly understood. To address this issue, here, we focused on a core cognitive deficit associated with depression, which tends to be reliably ameliorated through ECT, specifically, the ability to learn visuospatial information. Thus, we pursued three goals. First, we tested whether ECT can “normalize” the functional brain organization patterns associated with visuospatial memory and whether such corrections would predict post-ECT improvements in learning visuospatial information. Second, we investigated whether, among healthy individuals, stronger expression of the neural pattern, susceptible to adjustments through ECT, would predict reduced incidence of depression-relevant cognition and affect. Third, we sought to quantify the heritability of the ECT-correctable neural profile. Thus, in a task fMRI study with a clinical and a healthy comparison sample, we characterized two functional connectome patterns: one that typifies trait depression (i.e., differentiates patients from healthy individuals) and another that is susceptible to “normalization” through ECT. Both before and after ECT, greater expression of the trait depression neural profile was associated with more frequent repetitive thinking about past personal events (affective persistence), a hallmark of depressogenic cognition. Complementarily, post-treatment, stronger expression of the ECT-corrected neural profile was linked to improvements in visuospatial learning, a mental ability which is markedly impaired in depression. Subsequently, using data from the Human Connectome Project (HCP) (N = 333), we demonstrated that the functional brain organization of healthy participants with greater levels of subclinical depression and higher incidence of its associated cognitive deficits (affective persistence, impaired learning) shows greater similarity to the trait depression neural profile and reduced similarity to the ECT-correctable neural profile, as identified in the patient sample. These results tended to be specific to learning-relevant task contexts (working memory, perceptual relational processing). Genetic analyses based on HCP twin data (N = 128 pairs) suggested that, among healthy individuals, a functional brain organization similar to the one normalized by ECT in the patient sample is endogenous to cognitive contexts that require visuospatial processing that extends beyond the here-and-now. Broadly, the present findings supported our hypothesis that some of the therapeutic effects of ECT may be due to its correcting the expression of a naturally occurring pattern of functional brain organization that facilitates integration of internal and external cognition beyond the immediate present. Given their substantial susceptibility to both genetic and environmental effects, such mechanisms may be useful both for identifying at risk individuals and for monitoring progress of interventions targeting mood-related pathology. Keywords: Depression, Electroconvulsive therapy, Autobiographical memory, Functional networks, Genes

Objective To examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth. Methods Pregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis. Results As the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count. Conclusion In a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.