Atypical brain aging and its association with working memory performance in major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to aging. Yet, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool quantifying normative neurodevelopmental trajectories. METHODS: 304 MDD participants and 236 non-depressed controls were recruited and scanned from three studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to generate brain centile scores, which were examined for: a) differences in MDD relative to controls; b) differences in individuals with versus without severe childhood maltreatment; and c) correlations with depressive symptom severity, neurocognitive assessment domains, or escitalopram treatment response. RESULTS: Brain centiles were significantly lower in the MDD group compared to controls. It was also significantly correlated with working memory in controls, but not the MDD group. No significant associations were observed in depression severity or antidepressant treatment response with brain centiles. Likewise, childhood maltreatment history did not significantly affect brain centiles. CONCLUSIONS: Consistent with prior work on machine learning models that predict "brain age", brain centile scores differed in people diagnosed with MDD, and MDD was associated with differential relationships between centile scores and working memory. The results support the notion of atypical development and aging in MDD, with implications on neurocognitive deficits associated with aging-related cognitive function.

An empirical analysis of structural neuroimaging profiles in a staging model of depression.

We examine structural brain characteristics across three diagnostic categories: at risk for serious mental illness; first-presenting episode and recurrent major depressive disorder (MDD). We investigate whether the three diagnostic groups display a stepwise pattern of brain changes in the cortico-limbic regions. Integrated clinical and neuroimaging data from three large Canadian studies were pooled (total n = 622 participants, aged 12-66 years). Four clinical profiles were used in the classification of a clinical staging model: healthy comparison individuals with no history of depression (HC, n = 240), individuals at high risk for serious mental illness due to the presence of subclinical symptoms (SC, n = 80), first-episode depression (FD, n = 82), and participants with recurrent MDD in a current major depressive episode (RD, n = 220). Whole-brain volumetric measurements were extracted with FreeSurfer 7.1 and examined using three different types of analyses. Hippocampal volume decrease and cortico-limbic thinning were the most informative features for the RD vs HC comparisons. FD vs HC revealed that FD participants were characterized by a focal decrease in cortical thickness and global enlargement in amygdala volumes. Greater total amygdala volumes were significantly associated with earlier onset of illness in the FD but not the RD group. We did not confirm the construct validity of a tested clinical staging model, as a differential pattern of brain alterations was identified across the three diagnostic groups that did not parallel a stepwise clinical staging approach. The pathological processes during early stages of the illness may fundamentally differ from those that occur at later stages with clinical progression.

Anxious arousal predicts within-person changes in hippocampal volume in adults with a history of childhood maltreatment: A CAN-BIND4 report.

Childhood maltreatment (CM) is a strong transdiagnostic risk factor for future psychopathology. This risk is theorized to emerge partly because of glucocorticoid-mediated atrophy in the hippocampus, which leaves this area sensitive to further volume loss even through adulthood in the face of future stress and the emergence of psychopathology. This proof-of-principle study examines which specific dimensions of internalizing psychopathology in the context of a CM history are associated with decreases in hippocampal volume over a 6-month period. This study included 80 community-recruited adults (ages 18-66 years, 61.3% women) oversampled for a lifetime history of internalizing psychopathology. At baseline and a naturalistic 6-month follow-up, the symptom dimensions of the tripartite model (anxious arousal, anhedonic depression, and general distress) were assessed by self-report. Hippocampal volume was derived through T1-weighted magnetic resonance imaging scanning segmented via the volBrain HIPS pipeline. CM severity was determined via a semistructured, contextual interview with independent ratings. We found that higher levels of anxious arousal predicted decreases in hippocampal volume over time in those with greater severity of CM but were associated at a trend with increases in hippocampal volume over time in those with lower severity of maltreatment. Findings were specific to anxious arousal and the CA1 subregion of the hippocampus. These novel results suggest that for individuals with a history of CM, transdiagnostic interventions that target and reduce psychological and physiological arousal may result in the preservation of hippocampal structure and, thus, improvements in cognitive and emotional regulation in the face of stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Data and alternative models describing the associations among non-infection pandemic stress, event-related rumination, depression, and anxiety.

Here we present cross-sectional data collected from 1507 participants through the Qualtrics online survey platform. Participants were recruited from Reddit, Facebook, and the Queen's University undergraduate participant pool, and were instructed to complete a pandemic stress survey, the Beck Depression Inventory-II (BDI-II) [1], the Beck Anxiety Inventory (BAI) [2], a modified version of Event-Related Rumination Inventory (ERRI) [3], and a demographics questionnaire. For the 1069 participants who were not exposed to COVID-19 infection, we calculated the sum of each scale/subscale and performed a multiple mediation analysis using MPlus. The results indicated that three models (one primary model and two alternative models) had comparable statistical power to explain the variance as we tested different configurations of predictor, mediator, and outcome variables. Given the cross-sectional nature of the present study, we could not conclude which model was most valid. Therefore, we share our original data and tested models here for others to use. They are useful for researchers who wish to replicate our results, conduct new analyses with these data, or design future studies.

The impact of non-infection pandemic stress on depression and anxiety severity: Investigating mediation by intrusive and deliberate rumination.

BACKGROUND: Social restrictions to curb COVID-19's spread have had adverse effects on population mental health. Rumination is one mechanism through which pandemic stress (PS) might translate into psychopathology. In particular, intrusive rumination (IR) is believed to be problematic. In this study, we investigated whether IR and deliberate rumination (DR) mediated the associations between PS and both depression and anxiety severity. METHODS: 1090 participants recruited online and from an undergraduate psychology participation pool completed an assessment of COVID-19 PS, as well as the Event-Related Rumination Inventory, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Total scores for PS, IR, DR, depression, and anxiety severity were tested in a parallel mediation model. RESULTS: PS positively predicted IR, DR, depression, and anxiety severity. IR positively predicted 1depression and anxiety severity, whereas DR did not. Indirect effects of PS on depression and anxiety severity were significant for IR, but not DR. Direct effects of PS on anxiety and depression severity were significant. Taken together, IR partially mediated the association between PS and both measures of psychopathology, and DR did not. LIMITATIONS: This study was limited by its cross-sectional design and the lack of assessment of when PS exposure occurred. CONCLUSIONS: Regarding PS that is unrelated to infection by COVID-19, IR is one mechanism through which psychopathology may emerge, whereas DR appears to be benign. Promoting a shift from IR to DR may therefore be one strategy for mitigating the negative effects of PS and other stressors on mental health.

Human Variation in Error-Based and Reinforcement Motor Learning Is Associated With Entorhinal Volume.

Error-based and reward-based processes are critical for motor learning and are thought to be mediated via distinct neural pathways. However, recent behavioral work in humans suggests that both learning processes can be bolstered by the use of cognitive strategies, which may mediate individual differences in motor learning ability. It has been speculated that medial temporal lobe regions, which have been shown to support motor sequence learning, also support the use of cognitive strategies in error-based and reinforcement motor learning. However, direct evidence in support of this idea remains sparse. Here we first show that better overall learning during error-based visuomotor adaptation is associated with better overall learning during the reward-based shaping of reaching movements. Given the cognitive contribution to learning in both of these tasks, these results support the notion that strategic processes, associated with better performance, drive intersubject variation in both error-based and reinforcement motor learning. Furthermore, we show that entorhinal cortex volume is larger in better learning individuals-characterized across both motor learning tasks-compared with their poorer learning counterparts. These results suggest that individual differences in learning performance during error and reinforcement learning are related to neuroanatomical differences in entorhinal cortex.

Memory decay distinguishes subtypes of gist.

Memories are thought to become more gist-like over time. Multiple related memories might form generalized memory representations, losing specific details but enhancing or retaining gist. The time course within which gist memory emerges, however, is the subject of less consensus. To address this question, we focused our design on four kinds of gist: inferential gist (relations extracted across non-contiguous events), statistical learning (regularities extracted from a series), summary gist (a theme abstracted from a temporally contiguous series of items), and category gist (characterization of a stimulus at a higher level in the semantic hierarchy). Seventy participants completed memory encoding tasks addressing these types of gist and corresponding retrieval tasks the same evening, the morning after, and one week later, as well as an MRI at a later time point. We found little evidence that gist slowly emerges over time or that gist traces are more resistant to forgetting than detail traces. Instead, we found that initial gist memory shortly after encoding was either retained over time or decayed. Inferential gist and statistical learning were retained over a week, whereas memory for category and summary gist decayed. We discuss several interpretations for differences between these two subtypes of gist. Individual differences in REM or slow-wave sleep and hippocampal volumes did not predict changes in memory for these four kinds of gist in a healthy young adult population.

Brain meta-state transitions demarcate thoughts across task contexts exposing the mental noise of trait neuroticism.

Researchers have observed large-scale neural meta-state transitions that align to narrative events during movie-viewing. However, group or training-derived priors have been needed to detect them. Here, we introduce methods to sample transitions without any priors. Transitions detected by our methods predict narrative events, are similar across task and rest, and are correlated with activation of regions associated with spontaneous thought. Based on the centrality of semantics to thought, we argue these transitions serve as general, implicit neurobiological markers of new thoughts, and that their frequency, which is stable across contexts, approximates participants' mentation rate. By enabling observation of idiosyncratic transitions, our approach supports many applications, including phenomenological access to the black box of resting cognition. To illustrate the utility of this access, we regress resting fMRI transition rate and movie-viewing transition conformity against trait neuroticism, thereby providing a first neural confirmation of mental noise theory.

Multimodal brain data and core dimensions of creativity.

The current dataset incorporates multimodal brain imaging and creativity test data from a sample of 66 healthy young adults, all of whom were healthy right-handed English speakers, aged 22 to 35, with normal or corrected-to-normal hearing and vision. The participants completed measures of divergent thinking (Abbreviated Torrance Test for Adults; ATTA), everyday creativity (Creative Behaviour Inventory; CBI), and creative achievement (Creative Achievement Questionnaire; CAQ), consistent with the known multidimensional nature of creativity. They also completed high-resolution anatomical scans (T1-weighted and T2-weighted), diffusion tensor imaging scans, and resting state fMRI scans. The data were originally used in the article Neuroimaging predictors of creativity in healthy adults by Sunavsky and Poppenk [1] to test a set of confirmatory predictions regarding the volumetric, structural connectivity, and functional connectivity correlates of creativity. The data are uniquely high-dimensional in measuring both multiple dimensions of creativity as well as multimodal brain data, and may be valuable to researchers for testing models of individual differences in creativity, or who are seeking to integrate multiple datasets for large-scale, multi-site analysis of creativity.

Uncal apex position varies with normal aging.

The uncal apex is an anatomical landmark frequently used for segmenting the hippocampus into its anterior and posterior segments, a necessary step for computing many measurements of its long axis. It functions well, as it is both local to the hippocampus and easy to identify. However, in spite of widespread use and definition in the EADC-ADNI Harmonized Hippocampal Protocol (HarP), how the uncal apex is influenced by gross hippocampal changes during normal aging has not been established, nor has the possible impact on measures of anterior hippocampus (aHPC) and posterior hippocampus (pHPC) volume. Here I drew upon three large data sets to describe and confirm these relationships, investigating them in one large data set and replicating my findings in the two others, evaluating a total of 4,434 hippocampi. I found the uncal apex fell in an increasingly more anterior position with increasing age. This age-related retraction of the uncus began after age 36, with the sharpest effects arising after age 60. This phenomenon exaggerates age-related aHPC volume decreases while simultaneously underestimating age-related pHPC volume decreases, a pattern I confirmed by juxtaposing uncal apex and MNI space-based landmarking. A hippocampally based reference frame was also rendered unstable by age-related shifts in the posterior extent of the hippocampus. Both the uncal apex and hippocampal reference frame should therefore be used with caution in aging research, or in research involving other demographic or disease factors known to evoke gross changes in the hippocampus. Instead, MNI coordinate-based heuristics may be appropriate for segmenting the hippocampus in study designs involving such factors. Apex-based segmentation is still attractive, however, in study designs where advanced age and atrophy are not used as regressors, including investigations into long-axis effects in healthy young adults. Progress toward localizing functional divisions within the hippocampus is needed to identify best practices for the field.

Neuroimaging predictors of creativity in healthy adults.

Neuroimaging has revealed numerous neural predictors of individual differences in creativity; however, with most of these identified in only one study, sometimes involving very small samples, their reliability is uncertain. To contribute to a convergent cognitive neuroscience of creativity, we conducted a pre-registered conceptual replication and extension study in which we assessed previously reported predictors of creativity using a multimodal approach, incorporating volumetric, white matter, and functional connectivity neuroimaging data. We assessed sets of pre-registered predictors against prevailing measures of creativity, including visual and verbal tests of divergent thinking, everyday creative behaviour, and creative achievement. We then conducted whole-brain exploratory analyses. Greater creativity was broadly predicted by features of the inferior frontal gyrus (IFG) and inferior parietal lobe (IPL), including both local grey matter and white matter predictors in the IFG, the superior longitudinal fasciculus that connects them, and IFG-IPL functional connectivity. As IFG and IPL are important nodes within executive control and default mode networks (DMN), respectively, this result supports the view that executive modulation of DMN activity optimizes creative ideation. Furthermore, white matter integrity of the basal ganglia was also a generalizable creativity predictor, and exploratory analyses revealed the anterior lobe of the cerebellum and the parahippocampal gyrus to both be reliable predictors of creativity across neuroimaging modalities. This pattern aligns with proposals ascribing roles of working and long-term memory to problem-solving and imagination. Overall, our findings help to consolidate some, but not all, neural correlates of individual differences that have been discussed in the cognitive neuroimaging of creativity, yielding a subset that appear particularly promising for focused future investigation.

Multiple-object Tracking as a Tool for Parametrically Modulating Memory Reactivation.

Converging evidence supports the "nonmonotonic plasticity" hypothesis, which states that although complete retrieval may strengthen memories, partial retrieval weakens them. Yet, the classic experimental paradigms used to study effects of partial retrieval are not ideally suited to doing so, because they lack the parametric control needed to ensure that the memory is activated to the appropriate degree (i.e., that there is some retrieval but not enough to cause memory strengthening). Here, we present a novel procedure designed to accommodate this need. After participants learned a list of word-scene associates, they completed a cued mental visualization task that was combined with a multiple-object tracking (MOT) procedure, which we selected for its ability to interfere with mental visualization in a parametrically adjustable way (by varying the number of MOT targets). We also used fMRI data to successfully train an "associative recall" classifier for use in this task: This classifier revealed greater memory reactivation during trials in which associative memories were cued while participants tracked one, rather than five, MOT targets. However, the classifier was insensitive to task difficulty when recall was not taking place, suggesting that it had indeed tracked memory reactivation rather than task difficulty per se. Consistent with the classifier findings, participants' introspective ratings of visualization vividness were modulated by MOT task difficulty. In addition, we observed reduced classifier output and slowing of responses in a postreactivation memory test, consistent with the hypothesis that partial reactivation, induced by MOT, weakened memory. These results serve as a "proof of concept" that MOT can be used to parametrically modulate memory retrieval-a property that may prove useful in future investigation of partial retrieval effects, for example, in closed-loop experiments.

Neural pattern change during encoding of a narrative predicts retrospective duration estimates.

What mechanisms support our ability to estimate durations on the order of minutes? Behavioral studies in humans have shown that changes in contextual features lead to overestimation of past durations. Based on evidence that the medial temporal lobes and prefrontal cortex represent contextual features, we related the degree of fMRI pattern change in these regions with people's subsequent duration estimates. After listening to a radio story in the scanner, participants were asked how much time had elapsed between pairs of clips from the story. Our ROI analyses found that duration estimates were correlated with the neural pattern distance between two clips at encoding in the right entorhinal cortex. Moreover, whole-brain searchlight analyses revealed a cluster spanning the right anterior temporal lobe. Our findings provide convergent support for the hypothesis that retrospective time judgments are driven by 'drift' in contextual representations supported by these regions.

Briefly cuing memories leads to suppression of their neural representations.

Previous studies have linked partial memory activation with impaired subsequent memory retrieval (e.g., Detre et al., 2013) but have not provided an account of this phenomenon at the level of memory representations: How does partial activation change the neural pattern subsequently elicited when the memory is cued? To address this question, we conducted a functional magnetic resonance imaging (fMRI) experiment in which participants studied word-scene paired associates. Later, we weakly reactivated some memories by briefly presenting the cue word during a rapid serial visual presentation (RSVP) task; other memories were more strongly reactivated or not reactivated at all. We tested participants' memory for the paired associates before and after RSVP. Cues that were briefly presented during RSVP triggered reduced levels of scene activity on the post-RSVP memory test, relative to the other conditions. We used pattern similarity analysis to assess how representations changed as a function of the RSVP manipulation. For briefly cued pairs, we found that neural patterns elicited by the same cue on the pre- and post-RSVP tests (preA-postA; preB-postB) were less similar than neural patterns elicited by different cues (preA-postB; preB-postA). These similarity reductions were predicted by neural measures of memory activation during RSVP. Through simulation, we show that our pattern similarity results are consistent with a model in which partial memory activation triggers selective weakening of the strongest parts of the memory.

Long-axis specialization of the human hippocampus.

Investigation of the hippocampus has historically focused on computations within the trisynaptic circuit. However, discovery of important anatomical and functional variability along its long axis has inspired recent proposals of long-axis functional specialization in both the animal and human literatures. Here, we review and evaluate these proposals. We suggest that various long-axis specializations arise out of differences between the anterior (aHPC) and posterior hippocampus (pHPC) in large-scale network connectivity, the organization of entorhinal grid cells, and subfield compositions that bias the aHPC and pHPC towards pattern completion and separation, respectively. The latter two differences give rise to a property, reflected in the expression of multiple other functional specializations, of coarse, global representations in anterior hippocampus and fine-grained, local representations in posterior hippocampus.

Evidence for the differential salience of disgust and fear in episodic memory.

Studies of emotional memory typically focus on the memory-enhancing effects of emotional dimensions such as arousal and valence. However, it is unclear to what extent different emotional categories could have distinct effects on memory over and above these dimensional influences. We tested this possibility by investigating the impact of two negative, highly arousing, and withdrawal-related emotions-disgust and fear--on attention and subsequent memory. To index differential attention during encoding, participants performed a speeded line discrimination task (LDT) while viewing disgusting and fearful photographs of similar valence and arousal, which were assessed for later memory. LDT performance was slower, and subsequent recall and recognition were greater, for disgusting compared to both fearful and neutral images. Disgust enhancement of memory remained significant even when controlling for attention at encoding and for arousal, visual salience, and conceptual distinctiveness. Receiver-operating curve analyses indicated that disgust enhancement of memory was due to increased sensitivity, rather than response bias. Thus, disgust appears to have a special salience in memory relative to certain other emotions, suggesting that a purely dimensional model of emotional influences on cognition is inadequate to account for their effects. We speculate that disgust enhancement of memory could arise from an origin in conditioned taste aversion, a highly enduring form of implicit memory.

Mechanisms supporting superior source memory for familiar items: a multi-voxel pattern analysis study.

Recent cognitive research has revealed better source memory performance for familiar relative to novel stimuli. Here we consider two possible explanations for this finding. The source memory advantage for familiar stimuli could arise because stimulus novelty induces attention to stimulus features at the expense of contextual processing, resulting in diminished overall levels of contextual processing at study for novel (vs. familiar) stimuli. Another possibility is that stimulus information retrieved from long-term memory (LTM) provides scaffolding that facilitates the formation of item-context associations. If contextual features are indeed more effectively bound to familiar (vs. novel) items, the relationship between contextual processing at study and subsequent source memory should be stronger for familiar items. We tested these possibilities by applying multi-voxel pattern analysis (MVPA) to a recently collected functional magnetic resonance imaging (fMRI) dataset, with the goal of measuring contextual processing at study and relating it to subsequent source memory performance. Participants were scanned with fMRI while viewing novel proverbs, repeated proverbs (previously novel proverbs that were shown in a pre-study phase), and previously known proverbs in the context of one of two experimental tasks. After scanning was complete, we evaluated participants' source memory for the task associated with each proverb. Drawing upon fMRI data from the study phase, we trained a classifier to detect on-task processing (i.e., how strongly was the correct task set activated). On-task processing was greater for previously known than novel proverbs and similar for repeated and novel proverbs. However, both within and across participants, the relationship between on-task processing and subsequent source memory was stronger for repeated than novel proverbs and similar for previously known and novel proverbs. Finally, focusing on the repeated condition, we found that higher levels of hippocampal activity during the pre-study phase, which we used as an index of episodic encoding, led to a stronger relationship between on-task processing at study and subsequent memory. Together, these findings suggest different mechanisms may be primarily responsible for superior source memory for repeated and previously known stimuli. Specifically, they suggest that prior stimulus knowledge enhances memory by boosting the overall level of contextual processing, whereas stimulus repetition enhances the probability that contextual features will be successfully bound to item features. Several possible theoretical explanations for this pattern are discussed.

Distinct patterns of functional and effective connectivity between perirhinal cortex and other cortical regions in recognition memory and perceptual discrimination.

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched perceptual and recognition memory tasks for faces that engaged right PrC equivalently. Multivariate seed analyses revealed distinct patterns of interactions: Right ventrolateral prefrontal and posterior cingulate cortices exhibited stronger functional connectivity with PrC in recognition memory; fusiform regions were part of the pattern that displayed stronger functional connectivity with PrC in perceptual discrimination. Structural equation modeling revealed distinct patterns of effective connectivity that allowed us to constrain interpretation of these findings. Overall, they demonstrate that, even when MTL structures show similar involvement in recognition memory and perceptual discrimination, differential neural mechanisms are reflected in the interplay between the MTL and other cortical regions.

A hippocampal marker of recollection memory ability among healthy young adults: contributions of posterior and anterior segments.

The hippocampus is known to support recollection memory, but the relation between its structure and recollection in healthy adults has not been established. Here we show that the hippocampus (including subiculum, DG, and CA1-CA4), when separated into posterior and anterior segments, can reliably predict recollection in healthy young adults. Better memory was associated with larger posterior and smaller anterior segments, as evaluated relative to the uncal apex. Overall hippocampal volume, however, did not predict memory. This pattern was confirmed in four separate data sets from different studies and laboratories. The relationship between the posterior hippocampus and memory was mediated by the structure's functional connectivity with a neocortical network identified during a postencoding resting-state scan. The relationship was also weakest in an experiment involving no appreciable study-test interval. These findings suggest that enhanced posterior-hippocampal postencoding processes may account for the memory benefit associated with larger posterior hippocampi.