Differentiation of Related Events in Hippocampus Supports Memory Reinstatement in Development.

Adults are capable of either differentiating or integrating similar events in memory based on which representations are optimal for a given situation. Yet how children represent related memories remains unknown. Here, children (7-10 years old) and adults formed memories for separate yet overlapping events.

A month in review: longitudinal dynamics between daily PTSD symptom networks, affect, and drinking behaviors in female college students.

Introduction: Sexual victimization (SV) is common among college women, with approximately half of those who have experienced SV meeting criteria for posttraumatic stress disorder (PTSD) within a year. Both SV and PTSD are associated with alcohol misuse among college women, often explained by the self-medication hypothesis. Existing literature focuses on overall PTSD severity rather than potential day-to-day fluctuations in specific symptoms, which might play a crucial role in understanding alcohol misuse risk.

Developmental refinements to neural attentional state during semantic memory retrieval through adolescence.

Despite the fact that attention undergoes protracted development, little is known about how it may support memory refinements in childhood and adolescence. Here, we asked whether people differentially focus their attention on semantic or perceptual information over development during memory retrieval. First, we trained a multivoxel classifier to characterize whole-brain neural patterns reflecting semantic versus perceptual attention in a cued attention task.

Metabolic control of adaptive β-cell proliferation by the protein deacetylase SIRT2.

Selective and controlled expansion of endogenous β-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of β-cell proliferation to avoid excessive β-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of β-cell proliferation whose inactivation results in controlled β-cell expansion: the protein deacetylase Sirtuin 2 (SIRT2).

Anterior Hippocampal Engagement during Memory Formation Predicts Subsequent False Recognition of Similar Experiences.

People better remember experiences when they orient to meaning over surface-level perceptual features. Such an orientation-related memory boost has been associated with engagement of both hippocampus (HPC) and neocortex during encoding. However, less is known about the neural mechanisms by which a cognitive orientation toward meaning might also promote memory errors, with one open question being whether the HPC-a region traditionally implicated in precise memory formation-also contributes to behavioral imprecision.

Time separating spatial memories does not influence their integration in humans.

Humans can navigate through similar environments-like grocery stores-by integrating across their memories to extract commonalities or by differentiating between each to find idiosyncratic locations. Here, we investigate one factor that might impact whether two related spatial memories are integrated or differentiated: Namely, the temporal delay between experiences. Rodents have been shown to integrate memories more often when they are formed within 6 hours of each other.

Development of human hippocampal subfield microstructure and relation to associative inference.

The hippocampus is a complex brain structure composed of subfields that each have distinct cellular organizations. While the volume of hippocampal subfields displays age-related changes that have been associated with inference and memory functions, the degree to which the cellular organization within each subfield is related to these functions throughout development is not well understood. We employed an explicit model testing approach to characterize the development of tissue microstructure and its relationship to performance on 2 inference tasks, one that required memory (memory-based inference) and one that required only perceptually available information (perception-based inference).

Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change.

Memories of structured input become increasingly distorted across development.

Trajectories of cognitive and neural development suggest that, despite early emergence, the ability to extract environmental patterns changes across childhood. Here, 5- to 9-year-olds and adults (N = 211, 110 females, in a large Canadian city) completed a memory test assessing what they remembered after watching a stream of shape triplets: the particular sequence in which the shapes occurred and/or their group-level structure. After accounting for developmental improvements in overall memory, all ages remembered specific transitions, while memory for group membership was only observed in older children and adults (age by test-type interaction η  = .

Development of human hippocampal subfield microstructure and relation to associative inference.

The hippocampus is a complex brain structure composed of subfields that each have distinct cellular organizations. While the volume of hippocampal subfields displays age-related changes that have been associated with inference and memory functions, the degree to which the cellular organization within each subfield is related to these functions throughout development is not well understood. We employed an explicit model testing approach to characterize the development of tissue microstructure and its relationship to performance on two inference tasks, one that required memory (memory-based inference) and one that required only perceptually available information (perception-based inference).

Development of a Conceptual Model of the Patient Experience in Small Cell Lung Cancer: A Qualitative Interview Study.

Introduction: Small cell lung cancer (SCLC) is a subtype of lung cancer, the second most common cancer diagnosis worldwide. Currently, there is little published qualitative research that provides insight into the disease-related symptoms and impacts that are relevant to patients living with SCLC as directly reported by patients themselves.

Methods: This qualitative, cross-sectional, noninterventional, descriptive study included concept elicitation interviews with participants diagnosed with SCLC and the development of a conceptual model of clinical treatment benefit.

Learning strategy differentially impacts memory connections in children and adults.

Even once children can accurately remember their experiences, they nevertheless struggle to use those memories in flexible new ways-as in when drawing inferences. However, it remains an open question as to whether the developmental differences observed during both memory formation and inference itself represent a fundamental limitation on children's learning mechanisms, or rather their deployment of suboptimal strategy. Here, 7-9-year-old children (N = 154) and young adults (N = 130) first formed strong memories for initial (AB) associations and then engaged in one of three learning strategies as they viewed overlapping (BC) pairs.

Encoding-phase orientation toward thematic content over perceptual style benefits picture memory.

Orienting toward the meaning versus perceptual features of an experience benefits subsequent memory. Yet given that past work encouraged these orientations with different tasks, it is not clear if this memory benefit is solely due to internal processing factors versus external task-related ones. Moreover, it remains unclear how this benefit generalises from verbal to detailed picture memory.

Investigating the trends in patient-reported outcomes pre-treatment and implications to efficacy analyses: A post-hoc analysis of a cancer clinical trial.

Background: Uncertainty around key elements of an appropriate patient-reported outcome (PRO) baseline assessment introduces trial-specific variation in oncology clinical trials with a poorly understood consequence on drug evaluation decisions. This research investigated the impact of multiple pre-treatment PRO assessments and timing of assessments in a clinical trial.

Methods: A post-hoc analysis of a completed phase 3, open-label, randomized, parallel arm clinical trial in non-small cell lung cancer with two pre-treatment PRO assessments (screening and Week 1 Day 1 [W1D1]).

Is Intention to Treat Still the Gold Standard or Should Health Technology Assessment Agencies Embrace a Broader Estimands Framework?: Insights and Perspectives From the National Institute for Health and Care Excellence and Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E9 (R1) Addendum.

Objectives: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) addendum will have an important impact on the design and analysis of randomized controlled clinical trials, which represent crucial sources of evidence in health technology assessments, and on the intention-to-treat (ITT) principle in particular. This article brings together a task force of health economists and statisticians in academic institutes and the pharmaceutical industry, to examine the implications of the addendum from the perspective of the National Institute for Health and Care Excellence (NICE) and the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) and to address the question of whether the ITT principle should be considered the gold standard for estimating treatment effects.

Methods: We review the ITT principle, as introduced in the ICH E9 guideline.

Towards assessing subcortical "deep brain" biomarkers of PTSD with functional near-infrared spectroscopy.

Assessment of brain function with functional near-infrared spectroscopy (fNIRS) is limited to the outer regions of the cortex. Previously, we demonstrated the feasibility of inferring activity in subcortical "deep brain" regions using cortical functional magnetic resonance imaging (fMRI) and fNIRS activity in healthy adults. Access to subcortical regions subserving emotion and arousal using affordable and portable fNIRS is likely to be transformative for clinical diagnostic and treatment planning.

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report.

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care.

Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep.

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network.

Interpreting Within-Patient Changes on the EORTC QLQ-C30 and EORTC QLQ-LC13.

Introduction: When determining if changes on patient-reported outcome (PRO) scores in clinical trials convey a meaningful treatment benefit, statistical significance tests alone may not communicate the patient perspective. Appraising within-patient changes on PRO scores against established thresholds can determine if improvements or deteriorations experienced by individuals are meaningful. To evaluate the appropriateness of thresholds for interpreting meaningful improvements and deterioration within individuals on the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core instrument (QLQ-C30) and 13-item lung cancer module (QLQ-LC13), a series of psychometric methods were applied to data from a phase III randomized controlled clinical trial in non-small cell lung cancer.

Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase.

Many species synchronize their physiology and behavior to specific hours. It is commonly assumed that sunlight acts as the main entrainment signal for ∼24-h clocks. However, the moon provides similarly regular time information.

Developmental differences in memory reactivation relate to encoding and inference in the human brain.

Despite the fact that children can draw on their memories to make novel inferences, it is unknown whether they do so through the same neural mechanisms as adults. We measured memory reinstatement as participants aged 7-30 years learned new, related information. While adults brought memories to mind throughout learning, adolescents did so only transiently, and children not at all.

General precedes specific in memory representations for structured experience.

Decades of work has shown that learners rapidly extract structure from their environment, later leveraging their knowledge of what is more versus less consistent with prior experience to guide behavior. However, open questions remain about exactly what is remembered after exposure to structure. Memory for specific associations-transitions that unfold over time-is considered a prime candidate for guiding behavior.

Learning exceptions to the rule in human and model via hippocampal encoding.

Category learning helps us process the influx of information we experience daily. A common category structure is "rule-plus-exceptions," in which most items follow a general rule, but exceptions violate this rule. People are worse at learning to categorize exceptions than rule-following items, but improved exception categorization has been positively associated with hippocampal function.

OpenMaze: An open-source toolbox for creating virtual navigation experiments.

Incorporating 3D virtual environments into psychological experiments offers an innovative solution for balancing experimental control and ecological validity. Their flexible application to virtual navigation experiments, however, has been limited because accessible development tools best support only a subset of desirable task design features. We created OpenMaze, an open-source toolbox for the Unity game engine, to overcome this barrier.

The structure of hippocampal circuitry relates to rapid category learning in humans.

Prior work suggests that complementary white matter pathways within the hippocampus (HPC) differentially support the learning of specific versus general information. In particular, while the trisynaptic pathway (TSP) rapidly forms memories for specific experiences, the monosynaptic pathway (MSP) slowly learns generalities. However, despite the theorized significance of such circuitry, characterizing how information flows within the HPC to support learning in humans remains a challenge.