Emotion regulation during encoding reduces negative and enhances neutral mnemonic discrimination in individuals with depressive symptoms.

Individuals with depression exhibit dysfunctional emotion regulation, general episodic memory deficits, and a negativity bias, where negative experiences are better remembered. Recent work suggests that the negativity bias in depression may be driven by enhanced mnemonic discrimination, a memory measure that relies on hippocampal pattern separation - a computation that processes experiences with overlapping features as unique. Previously, we found that individuals with depressive symptoms show enhanced negative and impaired neutral mnemonic discrimination. The current study aimed to investigate emotion regulation as an approach toward modifying memory encoding of negative and neutral events in individuals with depressive symptoms. Here we show that applying psychological distancing (a cognitive reappraisal strategy characterized by taking a third-person perspective toward negative events) during encoding was associated with reduced negative and enhanced neutral mnemonic discrimination during retrieval in individuals with depressive symptoms. These results suggest that applying emotion regulation techniques during encoding may provide an effective approach toward altering dysfunctional memory in those with depressive symptoms. Given that pharmacological treatments often fail to treat depression, emotion regulation provides a powerful and practical approach toward modifying cognitive and emotional processes. Future neuroimaging studies will be important to determine how emotion regulation impacts the neural mechanisms underlying these findings.

Revisiting Functional Dysconnectivity: a Review of Three Model Frameworks in Schizophrenia.

PURPOSE OF REVIEW: Over the last decade, evidence suggests that a combination of behavioral and neuroimaging findings can help illuminate changes in functional dysconnectivity in schizophrenia. We review the recent connectivity literature considering several vital models, considering connectivity findings, and relationships with clinical symptoms. We reviewed resting state fMRI studies from 2017 to 2023. We summarized the role of two sets of brain networks (cerebello-thalamo-cortical (CTCC) and the triple network set) across three hypothesized models of schizophrenia etiology (neurodevelopmental, vulnerability-stress, and neurotransmitter hypotheses). RECENT FINDINGS: The neurotransmitter and neurodevelopmental models best explained CTCC-subcortical dysfunction, which was consistently connected to symptom severity and motor symptoms. Triple network dysconnectivity was linked to deficits in executive functioning, and the salience network (SN)-default mode network dysconnectivity was tied to disordered thought and attentional deficits. This paper links behavioral symptoms of schizophrenia (symptom severity, motor, executive functioning, and attentional deficits) to various hypothesized mechanisms.

A novel face-name mnemonic discrimination task with naturalistic stimuli.

Difficulty remembering faces and names is a common struggle for many people and gets more difficult as we age. Subtle changes in appearance from day to day, common facial characteristics across individuals, and overlap of names may contribute to the difficulty of learning face-name associations. Computational models suggest the hippocampus plays a key role in reducing interference across experiences with overlapping information by performing pattern separation, which enables us to encode similar experiences as distinct from one another. Thus, given the nature of overlapping features within face-name associative memory, hippocampal pattern separation may be an important underlying mechanism supporting this type of memory. Furthermore, cross-species approaches find that aging is associated with deficits in hippocampal pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation and provide a more sensitive measure of age-related cognitive decline compared to traditional memory tasks. However, traditional face-name associative memory tasks do not parametrically vary overlapping features of faces and names to tax hippocampal pattern separation and often lack naturalistic facial features (e.g., hair, accessories, similarity of features, emotional expressions). Here, we developed a face-name mnemonic discrimination task where we varied face stimuli by similarity, race, sex, and emotional expression as well as the similarity of name stimuli. We tested a sample of healthy young and older adults on this task and found that both age groups showed worsening performance as face-name interference increased. Overall, older adults struggled to remember faces and face-name pairs more than young adults. However, while young adults remembered emotional faces better than neutral faces, older adults selectively remembered positive faces. Thus, the use of a face-name association memory task designed with varying levels of face-name interference as well as the inclusion of naturalistic face stimuli across race, sex, and emotional expressions provides a more nuanced approach relative to traditional face-name association tasks toward understanding age-related changes in memory.

Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination.

Introduction: While antidepressants are one of the first-line treatments for depression, the mechanisms underlying antidepressant action are unclear. Furthermore, the extent to which antidepressants impact emotional and cognitive dysfunction in depression requires more fine-grained approaches toward measuring these impacts in humans. Depression is associated with emotion and mood dysregulation in addition to cognitive deficits. Depressed individuals experience general memory impairment as well as a negativity bias in episodic memory, where negative events are better remembered than positive or neutral events. One potential mechanism hypothesized to underlie the negativity bias in memory is dysfunctional hippocampal pattern separation, in which depressed individuals tend to show impaired general pattern separation but enhanced negative pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation in humans and provide a powerful approach to develop a mechanistic account for cognitive dysfunction in depression. While antidepressants have been examined primarily in rodent models in the context of hippocampal pattern separation, this has yet to be examined in humans. Methods: Here, we investigated how antidepressant usage and their perceived efficacy was associated with emotional mnemonic discrimination, given our prior work indicating a negativity bias for mnemonic discrimination in individuals with greater depressive symptoms. Results: We found that individuals who reported a greater improvement in their depressive symptoms after taking antidepressants (responders) showed reduced negative and enhanced neutral mnemonic discrimination compared to those with little to no improvement (non-responders). Perceived antidepressant efficacy was the strongest predictor of a reduction in the negativity bias for mnemonic discrimination, even when controlling for current depressive symptoms, antidepressant type, and other relevant factors. Discussion: These results suggest that antidepressants, when effective, can shift memory dynamics toward healthy function.

A Review of the Default Mode Network in Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder.

Functional magnetic resonance imaging (fMRI) has been widely used to examine the relationships between brain function and phenotypic features in neurodevelopmental disorders. Techniques such as resting-state functional connectivity (FC) have enabled the identification of the primary networks of the brain. One fMRI network, in particular, the default mode network (DMN), has been implicated in social-cognitive deficits in autism spectrum disorders (ASD) and attentional deficits in attention deficit hyperactivity disorder (ADHD). Given the significant clinical and genetic overlap between ASD and ADHD, surprisingly, no reviews have compared the clinical, developmental, and genetic correlates of DMN in ASD and ADHD and here we address this knowledge gap. We find that, compared with matched controls, ASD studies show a mixed pattern of both stronger and weaker FC in the DMN and ADHD studies mostly show stronger FC. Factors such as age, intelligence quotient, medication status, and heredity affect DMN FC in both ASD and ADHD. We also note that most DMN studies make ASD versus ADHD group comparisons and fail to consider ASD+ADHD comorbidity. We conclude, by identifying areas for improvement and by discussing the importance of using transdiagnostic approaches such as the Research Domain Criteria (RDoC) to fully account for the phenotypic and genotypic heterogeneity and overlap of ASD and ADHD.

Assessing intragenomic variation of the internal transcribed spacer two: Adapting the Illumina metagenomics protocol.

Primary and secondary structural data from the internal transcribed spacer two (ITS2) have been used extensively for diversity studies of many different eukaryotic organisms, including the green algae. Ease of amplification is due, at least in part, to the fact that ITS2 is part of the tandemly-repeated rRNA array. The potential confounding influence of intragenomic variability has yet to be addressed except in a few organisms. Moreover, few of the assessments of intragenomic variation have taken advantage of the deep sequencing capacity of sequence-by-synthesis protocols. We present results from our adaptation of the 16S Metagenomics Sequencing Library Preparation/Illumina protocol for deep sequencing of the ITS2 genes in selected isolates of the green algal genus, Haematococcus. Deep sequencing yielded from just under 20,000 to more than 500,000 merged reads, outpacing results from recent pyrosequencing efforts. Furthermore, a conservative evaluation of these data revealed a range of three to six ITS2 sequence haplotypes (defined as unique sets of nucleotide polymorphisms) across the taxon sampling. The frequency of the dominant haplotype ranged from 0.35 to 0.98. In all but two cases, the haplotype with the greatest frequency corresponded to a sequence obtained by the Sanger method using PCR templates. Our data also show that results from the sequencing-by-synthesis approach are reproducible. In addition to advancing our understanding of ribosomal RNA variation, the results of this investigation will allow us to begin testing hypotheses regarding the maintenance of homogeneity across multi-copy genes.