The Neurobiology of Life Course Socioeconomic Conditions and Associated Cognitive Performance in Middle to Late Adulthood.

Despite major advances, our understanding of the neurobiology of life course socioeconomic conditions is still scarce. This study aimed to provide insight into the pathways linking socioeconomic exposures-household income, last known occupational position, and life course socioeconomic trajectories-with brain microstructure and cognitive performance in middle to late adulthood. We assessed socioeconomic conditions alongside quantitative relaxometry and diffusion-weighted magnetic resonance imaging indicators of brain tissue microstructure and cognitive performance in a sample of community-dwelling men and women (N = 751, aged 50-91 years). We adjusted the applied regression analyses and structural equation models for the linear and nonlinear effects of age, sex, education, cardiovascular risk factors, and the presence of depression, anxiety, and substance use disorders. Individuals from lower-income households showed signs of advanced brain white matter (WM) aging with greater mean diffusivity (MD), lower neurite density, lower myelination, and lower iron content. The association between household income and MD was mediated by neurite density (B = 0.084, p = 0.003) and myelination (B = 0.019, p = 0.009); MD partially mediated the association between household income and cognitive performance (B = 0.017, p < 0.05). Household income moderated the relation between WM microstructure and cognitive performance, such that greater MD, lower myelination, or lower neurite density was only associated with poorer cognitive performance among individuals from lower-income households. Individuals from higher-income households showed preserved cognitive performance even with greater MD, lower myelination, or lower neurite density. These findings provide novel mechanistic insights into the associations between socioeconomic conditions, brain anatomy, and cognitive performance in middle to late adulthood.

Mean Oxygen Saturation during Sleep Is Related to Specific Brain Atrophy Pattern.

OBJECTIVE: There is much controversy about the neurobiological mechanisms underlying the effects of sleep-disordered breathing on the brain. The aim of this study was to investigate the association between markers of sleep-related hypoxemia and brain anatomy. METHODS: We used data from a large-scale cohort from the general population (n = 775, 50.6% males, age range = 45-86 years, mean age = 60.3 ± 9.9) that underwent full polysomnography and brain magnetic resonance imaging to correlate respiratory variables with regional brain volume estimates. RESULTS: After adjusting for age, gender, and cardiovascular risk factors, only mean oxygen saturation during sleep was associated with bilateral volume of hippocampus (right: p = 0.001; left: p < 0.001), thalamus (right: p < 0.001; left: p < 0.001), putamen (right: p = 0.001; left: p = 0.001), and angular gyrus (right: p = 0.011; left: p = 0.001). We observed the same relationship in left hemispheric amygdala (p = 0.010), caudate (p = 0.008), inferior frontal gyrus (p = 0.004), and supramarginal gyrus (p = 0.003). The other respiratory variables-lowest oxygen saturation, percentage of sleep time with oxygen saturation < 90%, apnea-hypopnea index, and oxygen desaturation index-did not show any significant association with brain volumes. INTERPRETATION: Lower mean oxygen saturation during sleep was associated with atrophy of cortical and subcortical brain areas known for high sensitivity to oxygen supply. Their vulnerability to hypoxemia may contribute to behavioral phenotype and cognitive decline in patients with sleep-disordered breathing. ANN NEUROL 2020;87:921-930.

Degeneracy and disordered brain networks in psychiatric patients using multivariate structural covariance analyzes.

Introduction: In this study, we applied multivariate methods to identify brain regions that have a critical role in shaping the connectivity patterns of networks associated with major psychiatric diagnoses, including schizophrenia (SCH), major depressive disorder (MDD) and bipolar disorder (BD) and healthy controls (HC). We used T1w images from 164 subjects: Schizophrenia (n = 17), bipolar disorder (n = 25), major depressive disorder (n = 68) and a healthy control group (n = 54). Methods: We extracted regions of interest (ROIs) using a method based on the SHOOT algorithm of the SPM12 toolbox. We then performed multivariate structural covariance between the groups. For the regions identified as significant in t term of their covariance value, we calculated their eigencentrality as a measure of the influence of brain regions within the network. We applied a significance threshold of p = 0.001. Finally, we performed a cluster analysis to determine groups of regions that had similar eigencentrality profiles in different pairwise comparison networks in the observed groups. Results: As a result, we obtained 4 clusters with different brain regions that were diagnosis-specific. Cluster 1 showed the strongest discriminative values between SCH and HC and SCH and BD. Cluster 2 had the strongest discriminative value for the MDD patients, cluster 3 - for the BD patients. Cluster 4 seemed to contribute almost equally to the discrimination between the four groups. Discussion: Our results suggest that we can use the multivariate structural covariance method to identify specific regions that have higher predictive value for specific psychiatric diagnoses. In our research, we have identified brain signatures that suggest that degeneracy shapes brain networks in different ways both within and across major psychiatric disorders.

Voluntary explicit versus involuntary conceptual memory are associated with dissociable fMRI responses in hippocampus, amygdala, and parietal cortex for emotional and neutral word pairs.

Although functional neuroimaging studies have supported the distinction between explicit and implicit forms of memory, few have matched explicit and implicit tests closely, and most of these tested perceptual rather than conceptual implicit memory. We compared event-related fMRI responses during an intentional test, in which a group of participants used a cue word to recall its associate from a prior study phase, with those in an incidental test, in which a different group of participants used the same cue to produce the first associate that came to mind. Both semantic relative to phonemic processing at study, and emotional relative to neutral word pairs, increased target completions in the intentional test, but not in the incidental test, suggesting that behavioral performance in the incidental test was not contaminated by voluntary explicit retrieval. We isolated the neural correlates of successful retrieval by contrasting fMRI responses to studied versus unstudied cues for which the equivalent "target" associate was produced. By comparing the difference in this repetition-related contrast across the intentional and incidental tests, we could identify the correlates of voluntary explicit retrieval. This contrast revealed increased bilateral hippocampal responses in the intentional test, but decreased hippocampal responses in the incidental test. A similar pattern in the bilateral amygdale was further modulated by the emotionality of the word pairs, although surprisingly only in the incidental test. Parietal regions, however, showed increased repetition-related responses in both tests. These results suggest that the neural correlates of successful voluntary explicit memory differ in directionality, even if not in location, from the neural correlates of successful involuntary implicit (or explicit) memory, even when the incidental test taps conceptual processes.

Exploring the basis and boundary conditions of SenseCam-facilitated recollection.

SenseCam review has been shown to promote and sustain subsequent access to memories that might otherwise remain inaccessible. While SenseCam review facilitates recollection for personally experienced events, we know little about the boundary conditions under which this operates and about how underlying processing mechanisms can be optimally recruited to offset memory impairments of the sort that occur in dementia. This paper considers some of these issues with a view to targeting future research that not only clarifies our evolving body of theory about how memory works, but also informs about how memory-assistive technologies for patients might be employed to maximal effect. We begin by outlining key factors that are known to influence recollection. We then examine variability in the decline of memory function both in normal ageing and in dementia. Attention is drawn to similarities in the recollection deficits associated with depression and dementia, and we suggest that this may reflect shared underlying mechanisms. We conclude by discussing how one particular theoretical rationale can be intersected with key SenseCam capabilities to define priorities for ongoing and future SenseCam research.

Gradient of electro-convulsive therapy's antidepressant effects along the longitudinal hippocampal axis.

Despite decades of successful treatment of therapy-resistant depression and major scientific advances in the field, our knowledge about electro-convulsive therapy's (ECT) mechanisms of action is still scarce. Building on strong empirical evidence for ECT-induced hippocampus anatomy changes, we sought to test the hypothesis that ECT has a differential impact along the hippocampus longitudinal axis. We acquired behavioural and brain anatomy magnetic resonance imaging (MRI) data in patients with depressive episode undergoing ECT (n = 9) or pharmacotherapy (n = 24) and healthy controls (n = 30) at two time points 3 months apart. Using whole-brain voxel-based statistical parametric mapping and topographic analysis focused on the hippocampus, we observed ECT-induced gradient of grey matter volume increase along the hippocampal longitudinal axis with predominant impact on its anterior portion. Clinical outcome measures showed strong correlations with both baseline volume and rate of ECT-induced change exclusively for the anterior, but not posterior hippocampus. We interpret our findings confined to the anterior hippocampus and amygdala as additional evidence of the regional specific impact of ECT that unfolds its beneficial effect on depression via the "limbic" system. Main limitations of the study are patients' polypharmacy, heterogeneity of psychiatric diagnosis, and long-time interval between scans.

Component processes of conceptual priming and associative cued recall: the roles of preexisting representation and depth of processing.

The authors investigated depth-of-processing effects on conceptual priming by comparing incidental (implicit) and intentional (explicit) tests of word association. In Experiment 1, depth of processing at study influenced priming of weak and medium associates but not of strong associates. In Experiment 2, depth of processing influenced priming of weak associates but not of compound phrases (e.g., coathanger), whose preexperimental association strength matched that of weak associates. In Experiment 3, the same pattern persisted when study was auditory and test was visual, ensuring that priming was conceptual and not perceptual. In all experiments, in matched intentional tests, depth-of-processing effects occurred for all association strengths and for both phrases and associates, suggesting that the incidental tests were uncontaminated by voluntary retrieval, because they showed depth-of-processing effects only for some materials and not others, within the same participants and tests. Because depth-of-processing effects on involuntary free-association priming depend on the presence versus absence of a cohesive preexperimental representation, the memory-systems and conceptual/perceptual processing approaches to memory-test dissociations require modification to account for component processes of conceptual priming.

Level of processing and age affect involuntary conceptual priming of weak but not strong associates.

Memory for weak and strong semantic associates was compared in intentional associate-cued-recall and incidental free-association tests. This design yielded four conditions (weak/intentional, strong/intentional, weak/incidental, and strong/ incidental) on which younger and older adults were compared. Level of processing (LOP) and age effects occurred for the weak/intentional, strong/intentional, and weak/incidental conditions, but not for the strong/incidental condition. Because participants could not distinguish weak from strong associates during the memory tests, these results suggest that free-association priming was involuntary and was not contaminated by voluntary retrieval strategies. Instead, they suggest that encoding deficits related to shallower LOP and older age reduce involuntary free-association priming mainly for associates without cohesive preexperimental representations.

Disgust enhances the recollection of negative emotional images.

Memory is typically better for emotional relative to neutral images, an effect generally considered to be mediated by arousal. However, this explanation cannot explain the full pattern of findings in the literature. Two experiments are reported that investigate the differential effects of categorical affective states upon emotional memory and the contributions of stimulus dimensions other than pleasantness and arousal to any memory advantage. In Experiment 1, disgusting images were better remembered than equally unpleasant frightening ones, despite the disgusting images being less arousing. In Experiment 2, regression analyses identified affective impact--a factor shown previously to influence the allocation of visual attention and amygdala response to negative emotional images--as the strongest predictor of remembering. These findings raise significant issues that the arousal account of emotional memory cannot readily address. The term impact refers to an undifferentiated emotional response to a stimulus, without requiring detailed consideration of specific dimensions of image content. We argue that ratings of impact relate to how the self is affected. The present data call for further consideration of the theoretical specifications of the mechanisms that lead to enhanced memory for emotional stimuli and their neural substrates.

The memory enhancement effect of emotion is absent in conceptual implicit memory.

Memory for emotional stimuli is superior to memory for neutral stimuli. This study investigated whether this memory advantage is present in implicit memory. Memory was tested with a test of explicit memory (associate cued recall) and a test of conceptual implicit memory (free association) identical in all respects apart from the retrieval instructions. After studying emotional and neutral paired associates, participants saw the first member of the pair, the cue; in the test of explicit memory participants were instructed to recall the associate; in the test of implicit memory participants were instructed to generate the first word coming to mind associated to the word. Depth of study processing dissociated performance in the tests, confirming that the free-association test was not contaminated by an intentional retrieval strategy. Emotional pairs were better recalled than neutral pairs in the test of explicit memory but not in the equivalent test of implicit memory. The absence of an emotion effect in implicit memory implies that emotional material does not have a privileged global mnemonic status; intentional retrieval is necessary for observing the emotion-related memory advantage.

Recognition memory for pictorial material in subclinical depression.

Depression has been associated with impaired recollection of episodic details in tests of recognition memory that use verbal material. In two experiments, the remember/know procedure was employed to investigate the effects of dysphoric mood on recognition memory for pictorial materials that may not be subject to the same processing limitations found for verbal materials in depression. In Experiment 1, where the recognition test took place two weeks after encoding, subclinically depressed participants reported fewer know judgements which were likely to be at least partly due to a remember-to-know shift. Although pictures were accompanied by negative or neutral captions at encoding, no effect of captions on recognition memory was observed. In Experiment 2, where the recognition test occurred soon after viewing the pictures, subclinically depressed participants reported fewer remember judgements. All participants reported more remember judgements for pictures of emotionally negative content than pictures of neutral content. Together, these findings demonstrate that recognition memory for pictorial stimuli is compromised in dysphoric individuals in a way that is consistent with a recollection deficit for episodic detail and also reminiscent of that previously reported for verbal materials. These findings contribute to our developing understanding of how mood and memory interact.

The amygdala response to images with impact.

Effective photojournalism provokes an emotional reaction and leaves a lasting impression upon the viewer. Striking and memorable images are often said to possess 'impact'. Within cognitive neuroscience memorable emotional images evoke a greater amygdala response. Research to date has focused on arousal as a causative factor, while the contribution of appraisal dimensions relating to salience of an item, goal relevance, or impact are yet to be addressed. We explored how differences in ratings of impact influenced amygdala activity to negative emotional images matched for valence, arousal and other factors. Increased amygdala activation was found to high impact when compared to neutral images, or high impact when compared to low impact images (matched for arousal). Our findings demonstrate that the amygdala response to emotional stimuli is not a function of arousal (or valence) alone and accord more with the proposal that the amygdala responds to the significance or relevance of an event.

Reducing specificity of autobiographical memory in nonclinical participants: The role of rumination and schematic models.

Two experiments are reported in which nondysphoric participants, not prone to excessive levels of rumination in everyday life, were asked to retrieve autobiographical memories using the Williams and Broadbent ( 1986 ) procedure (AMT). In the first experiment, two variants of a self-related category fluency task were interleaved among sets of autobiographical memory cues. In one variant (blocked) a normal model of analytic rumination was induced by grouping prompts on a single superordinate theme together. In the other (intermixed) prompts from several different themes were grouped together. It was predicted that the blocked variant would reduce the number of specific memories recollected and increase the number of categoric memories relative to the intermixed variant. This prediction was confirmed and provides the first demonstration of a bidirectional causal influence of analytic rumination on the balance between specific and categoric retrievals. A second experiment showed no alteration in this balance when the same fluency manipulation involved animal-related categories rather than self-related ones. The results support a two component model of autobiographical retrieval being driven in part by the extent to which an analytic mode of processing is adopted in the short term and in part by the level of differentiation in self-related schematic models.

Level of processing and the process-dissociation procedure: elusiveness of null effects on estimates of automatic retrieval.

We describe two experiments that used the process-dissociation procedure to investigate the effects of level of processing on estimates of controlled and automatic retrieval processes in word-stem completion tasks. Despite our best endeavours, we found the null effect of level of processing on estimates of automatic retrieval reported by Toth, Reingold, and Jacoby (1994) elusive. Estimates of automatic retrieval were not independent of level of processing but inversely related to it. In part, the reason was that, following deeper levels of processing, instructions to exclude recollected words led to floor effects. But the inverse relationship persisted even when floor effects were avoided. Only participants who were not given strict instructions in the exclusion task-and who also qualified as lax responders based on answers in a structured post-test interview-showed no effect of level of processing on estimates of automatic retrieval. This null effect apparently occurred because these participants failed to exclude words that they in fact recollected from the study list. This finding violates the critical assumption that in this task participants exclude recollected words. The results are therefore paradoxical. Successful replication of the null effect occurred only under conditions that preclude the very use of the procedure. This paradox has important implications for views on how consciousness should be conceived in relation to memory.

Recollection deficits in dysphoric mood: an effect of schematic models and executive mode?

Depression and dysphoric mood states are often accompanied by quantitative or qualitative shifts in performance across a range of retention tasks. This study focuses on the recollection of both autobiographical events and word lists in dysphoric states. Recollection occurs when people are aware of some contextual detail allied to the encoding experience. This study establishes the presence of a recollection deficit in dysphoria in two distinct paradigms. In both autobiographical recall and in recognition memory, recollection in a dysphoric group was at lower levels than recollection in matched controls. The study examines the hypothesis that the extent of recollection is influenced by two factors: (1) the degree of differentiation of schematic mental models; and (2) the executive mode that predominates when memory tasks are carried out, with the latter assumed to be altered by rumination. The relationship between responses based on recollection and alternative mnemonic responses could be predicted by measures of these two factors. The results are discussed in terms of the Interacting Cognitive Subsystems model (Teasdale & Barnard, 1993) and the perspective it offers on the relationship between meaning systems and executive functions (Barnard, 1999).

Recognition memory and decision processes: a meta-analysis of remember, know, and guess responses.

A meta-analysis of proportions of remember, know, and guess responses was carried out on observations from 86 experimental conditions in 23 different recognition memory experiments. Unlike remember and know responses, guess responses revealed no memory for the test items that elicited them. A signal detection analysis of these data showed that A' estimates of the strength of the memory trace depended on response criteria. A' estimates increased significantly when know responses were added to remember responses, and decreased significantly when guess responses were added to remember and know responses. It was guessing, rather than knowing, that was most strongly correlated with overall response criteria. Nor were remembering and knowing correlated significantly. These results do not support a quantitative trace strength model according to which these responses merely reflect different response criteria. They support theories that ascribe remembering and knowing to qualitatively distinct memory systems or processes.