Memory-related Tasks Research Articles

Individual differences in L1 and L2 anaphora resolution: effects of implicit prosodic cues and working memory

Abstract The present experimental studies shed light on effects of implicit prosodic cues on anaphora resolution as well as on how these differ both within and between L1 and L2 speaker groups. In two self-paced reading studies, L1 and L2 participants read poem-like texts that contained anaphoric ambiguity. These stimuli were designed to include a rhyming scheme and meter that were either regular or disrupted. We expected a rhyme cue on a nonsubject pronoun antecedent (in the regularly metered and rhyming version of the texts) to induce competition effects in L1 speakers and cause them to adapt their interpretative preferences and processing strategies; yet, for L2 speakers we hypothesized that effects would either not be observed or that they would be attenuated. Additionally, we examined whether comprehender-dependent factors would modulate effects in each group. We tested both L1 and L2 participants on memory-related tasks. We also measured L1 speakers’ print exposure and L2ers’ proficiency in English. Results revealed L1–L2 dissimilarities in interpretative preferences and reading behavior, as L2 speakers were not equally sensitive to the prosodic cues introduced. The examination of memory-related measures provided evidence of within-group differences and between-group parallels: higher working memory in both groups modulated anaphora resolution, although for L2 speakers there was no additional influence of context.

The interaction between cannabinoids and long-term synaptic plasticity: A survey on memory formation and underlying mechanisms.

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre- and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory-related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long-term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.

Potential role of oxytocin in the regulation of memories and treatment of memory disorders

Oxytocin (OXT) is an “affiliative” hormone or neurohormone or neuropeptide consists of nine amino acids, synthesized in magnocellular neurons of paraventricular (PVN) and supraoptic nuclei (SON) of hypothalamus. OXT receptors are widely distributed in various region of brain and OXT has been shown to regulate various social and nonsocial behavior. Hippocampus is the main region which regulates the learning and memory. Hippocampus particularly regulates the acquisition of new memories and retention of acquired memories. OXT has been shown to regulate the synaptic plasticity, neurogenesis, and consolidation of memories. Further, findings from both preclinical and clinical studies have suggested that the OXT treatment improves performance in memory related task. Various trials have suggested the positive impact of intranasal OXT in the dementia patients. However, these studies are limited in number. In the present study authors have highlighted the role of OXT in the formation and retrieval of memories. Further, the study demonstrated the outcome of OXT treatment in various memory and related disorders.

The Impact of Digital Technologies on Memory and Memory Studies

With the widespread integration of smartphones, computers, and the internet, information access and processing have undergone significant changes. This paper investigates both positive and negative implications, acknowledging the extension of cognitive capacities through easy access to vast databases and external memory aids while also addressing concerns about diminished memory consolidation and reliance on shallow encoding strategies. Examining the interdisciplinary field of memory studies, the study also highlights collaborative efforts among scholars in psychology, neuroscience, sociology, and information science to comprehend the impact of digital technologies on memory, and emphasizes the challenges and future directions in memory research, including issues like digital amnesia, information overload, and privacy concerns. Overall, the paper underscores the need for understanding the relationship between human memory and digital tools, enabling the development of strategies to enhance memory, counteract potential adverse effects, and promote a balanced utilization of digital resources in memory-related tasks.

Sex based differences in functional connectivity during a working memory task: an fNIRS study.

Differences in corticocerebral structure and function between males and females and their effects on behavior and the prevalence of various neuropsychiatric disorders have been considered as a fundamental topic in various fields of neuroscience. Recent studies on working memory (WM) reported the impact of sex on brain connectivity patterns, which reflect the important role of functional connectivity in the sex topic. Working memory, one of the most important cognitive tasks performed by regions of the PFC, can provide evidence regarding the presence of a difference between males and females. The present study aimed to assess sex differences in brain functional connectivity during working memory-related tasks by using functional near-infrared spectroscopy (fNIRS). In this regard, nine males and nine females completed a dual n-back working memory task with two target inputs of color and location stimuli in three difficulty levels (n = 0, 1, 2). Functional connectivity matrices were extracted for each subject for each memory load level. Females made less errors than males while spending more time performing the task for all workload levels except in 0-back related to the color stimulus, where the reaction time of females was shorter than males. The results of functional connectivity reveal the inverse behavior of two hemispheres at different memory workload levels between males and females. In the left hemisphere, males exhibited stronger connectivity compared to the females, while stronger connectivity was observed in the females' right hemisphere. Furthermore, an inverse trend was detected in the channel pairs with significant connectivity in the right hemisphere of males (falling) and females (rising) by enhancing working memory load level. Considering both behavioral and functional results for two sexes demonstrated a better performance in females due to the more effective use of the brain. The results indicate that sex affects functional connectivity between different areas in both hemispheres of the brain during cognitive tasks of varying difficulty levels although the general impression is that spatial capabilities are considered as a performance of the brain's right hemisphere. These results reinforce the presence of a sex effect in the functional imaging studies of hemodynamic function and emphasize the importance of evaluating brain network connectivity for achieving a better scientific understanding of sex differences.

5 Cognitive, Emotional, and Functional Predictors of Clinical Trial Enrollment

Objective:With participant recruitment being a top barrier to AD research progress, the rate of screen failure in Alzheimer’s disease (AD) clinical trials is unsustainable. Although steps have been undertaken to consider solutions to the continued recruitment shortage, there is unfortunately minimal emphasis on reducing screen failure rates based on study inclusion criteria. Here we present information attempting to understand the cognitive, emotional, and functional features of individuals who failed screening measures for AD trials.Participants and Methods:The current study is a retrospective, cross-sectional analysis. Thirty-eight participants (aged 50-83) having (1) previously received a clinical diagnostic workup at a transdisciplinary cognitive specialty clinic and (2) previously screened for a specific industry-sponsored clinical trial of MCI/early AD (EMERGE) met inclusion criteria. Previously collected clinical data were analyzed to identify predictors of AD trial screen pass/fail status.Results:Of the 38 participants in the current study, 14 screen passed into this AD clinical trial, and 24 screen failed. Higher screen failure rates were significantly related to gender, with 83% of female participants screen failing this AD trial versus 45% of male participants. There was no difference in age or education between screen pass/fail groups, nor were differences present for performance on visual or verbal memory tasks, or the MOCA. Conversely, those participants screen failing this AD clinical trial performed significantly worse on nonmemory cognitive domains pertaining to general fund of knowledge, working memory, and executive functioning. Additionally, the screen fail group reported greater levels of anxiety, but not depression nor endorsements on a measure of functional status.Conclusions:Worse performance on non-memory neuropsychological domains was related to screen failure status for the EMERGE AD clinical trial. This finding may be explained by the traditional recruitment pathway from clinic to trials, which beyond the diagnosis of interest is up to the opinion of the physician to determine “fit” for a trial. Higher screen failure rates may result from physicians erroneously viewing more globally-impaired patients as being more appropriate for an AD clinical trial, resulting in greater tendencies towards recruiting patients who are too severe to meet inclusion criteria for a trial. Recruiting patients into clinical trials earlier in their disease course - when disease severity is less - may result in reduced screen failure rates in AD trials. That we could not detect a relationship between memory-related tasks and screen fail/pass status may be explained by either (1) the measures used in the EMERGE trial were not as sensitive to subtle changes in memory, or (2) that memory dysfunction is necessary for a diagnosis of AD but not sufficient to distinguish who will be successfully screened into an AD clinical trial. Overall, these findings have the potential to advance the field by reducing screen failure rates in AD clinical trials by using information already available to clinical trial teams, which will enhance trial-recruitment infrastructure and encourage greater engagement of older adults in AD research.

Relational memory weakness in autism despite the use of a controlled encoding task.

Recent work challenged past findings that documented relational memory impairments in autism. Previous studies often relied solely on explicit behavioral responses to assess relational memory integrity, but successful performance on behavioral tasks may rely on other cognitive abilities (e.g., executive functioning) that are impacted in some autistic individuals. Eye-tracking tasks do not require explicit behavioral responses, and, further, eye movements provide an indirect measure of memory. The current study examined whether memory-specific viewing patterns toward scenes differ between autistic and non-autistic individuals. Using a long-term memory paradigm that equated for complexity between item and relational memory tasks, participants studied a series of scenes. Following the initial study phase, scenes were re-presented, accompanied by an orienting question that directed participants to attend to either features of an item (i.e., in the item condition) or spatial relationships between items (i.e., in the relational condition) that might be subsequently modified during test. At test, participants viewed scenes that were unchanged (i.e., repeated from study), scenes that underwent an "item" modification (an exemplar switch) or a "relational" modification (a location switch), and scenes that had not been presented before. Eye movements were recorded throughout. During study, there were no significant group differences in viewing directed to regions of scenes that might be manipulated at test, suggesting comparable processing of scene details during encoding. However, there was a group difference in explicit recognition accuracy for scenes that underwent a relational change. Marginal group differences in the expression of memory-based viewing effects during test for relational scenes were consistent with this behavioral outcome, particularly when analyses were limited to scenes recognized correctly with high confidence. Group differences were also evident in correlational analyses that examined the association between study phase viewing and recognition accuracy and between performance on the Picture Sequence Memory Test and recognition accuracy. Together, our findings suggest differences in the integrity of relational memory representations and/or in the relationships between subcomponents of memory in autism.

Sex-Specific Alterations in Spatial Memory and Hippocampal AKT-mTOR Signaling in Adult Mice Pre-exposed to Ketamine and/or Psychological Stress During Adolescence

BackgroundKetamine (KET) is administered to manage major depression in adolescent patients. However, the long-term effects of juvenile KET exposure on memory-related tasks have not been thoroughly assessed. We examined whether exposure to KET, psychological stress, or both results in long-lasting alterations in spatial memory in C57BL/6 mice. Furthermore, we evaluated how KET and/or psychological stress history influenced hippocampal protein kinase B–mechanistic target of rapamycin (AKT-mTOR)–related signaling. MethodsOn postnatal day 35, male and female mice underwent vicarious defeat stress (VDS), a form of psychological stress that reduces sociability in both sexes, with or without KET exposure (20 mg/kg/day, postnatal days 35–44). In adulthood (postnatal day 70), mice were assessed for spatial memory performance on a water maze task or euthanized for hippocampal tissue collection. ResultsJuvenile pre-exposure to KET or VDS individually increased the latency (seconds) to locate the escape platform in adult male, but not female, mice. However, juvenile history of concomitant KET and VDS prevented memory impairment. Furthermore, individual KET or VDS pre-exposure, unlike their combined history, decreased hippocampal AKT-mTOR signaling in adult male mice. Conversely, KET pre-exposure alone increased AKT-mTOR in the hippocampus of adult female mice. Lastly, rapamycin-induced decreases of mTOR in naïve adult female mice induced spatial memory retrieval deficits, mimicking adult male mice with a history of exposure to VDS or KET. ConclusionsOur preclinical model shows how KET treatment for the management of adolescent psychological stress–induced sequelae does not impair spatial memory later in life. However, juvenile recreational KET misuse, like psychological stress history, results in long-term spatial memory deficits and hippocampal AKT-mTOR signaling changes in a sex-specific manner.

Chronic hyperglycaemia increases the vulnerability of the hippocampus to oxidative damage induced during post-hypoglycaemic hyperglycaemia in a mouse model of chemically induced type 1 diabetes

Aims/hypothesisChronic hyperglycaemia and recurrent hypoglycaemia are independently associated with accelerated cognitive decline in type 1 diabetes. Recurrent hypoglycaemia in rodent models of chemically induced (streptozotocin [STZ]) diabetes leads to cognitive impairment in memory-related tasks associated with hippocampal oxidative damage. This study examined the hypothesis that post-hypoglycaemic hyperglycaemia in STZ-diabetes exacerbates hippocampal oxidative stress and explored potential contributory mechanisms.MethodsThe hyperinsulinaemic glucose clamp technique was used to induce equivalent hypoglycaemia and to control post-hypoglycaemic glucose levels in mice with and without STZ-diabetes and Nrf2−/− mice (lacking Nrf2 [also known as Nfe2l2]). Subsequently, quantitative proteomics based on stable isotope labelling by amino acids in cell culture and biochemical approaches were used to assess oxidative damage and explore contributory pathways.ResultsEvidence of hippocampal oxidative damage was most marked in mice with STZ-diabetes exposed to post-hypoglycaemic hyperglycaemia; these mice also showed induction of Nrf2 and the Nrf2 transcriptional targets Sod2 and Hmox-1. In this group, hypoglycaemia induced a significant upregulation of proteins involved in alternative fuel provision, reductive biosynthesis and degradation of damaged proteins, and a significant downregulation of proteins mediating the stress response. Key differences emerged between mice with and without STZ-diabetes following recovery from hypoglycaemia in proteins mediating the stress response and reductive biosynthesis.Conclusions/interpretationThere is a disruption of the cellular response to a hypoglycaemic challenge in mice with STZ-induced diabetes that is not seen in wild-type non-diabetic animals. The chronic hyperglycaemia of diabetes and post-hypoglycaemic hyperglycaemia act synergistically to induce oxidative stress and damage in the hippocampus, possibly leading to irreversible damage/modification to proteins or synapses between cells. In conclusion, recurrent hypoglycaemia in sub-optimally controlled diabetes may contribute, at least in part, to accelerated cognitive decline through amplifying oxidative damage in key brain regions, such as the hippocampus.Data availabilityThe datasets generated during and/or analysed during the current study are available in ProteomeXchange, accession no. 1-20220824-173727 (www.proteomexchange.org). Additional datasets generated during and/or analysed during the present study are available from the corresponding author upon reasonable request.Graphical abstract

Hippocampus-based behavioral, structural, and molecular dynamics across the estrous cycle.

The activity of neurons in the rodent hippocampus contributes to diverse behaviors, with the activity of ventral hippocampal neurons affecting behaviors related to anxiety and emotion regulation, and the activity of dorsal hippocampal neurons affecting performance in learning- and memory-related tasks. Hippocampal cells also express receptors for ovarian hormones, estrogen and progesterone, and are therefore affected by physiological fluctuations of those hormones that occur over the rodent estrous cycle. In this review, we discuss the effects of cycling ovarian hormones on hippocampal physiology. Starting with behavior, we explore the role of the estrous cycle in regulating hippocampus-dependent behaviors. We go on to detail the cellular mechanisms through which cycling estrogen and progesterone, through changes in the structural and functional properties of hippocampal neurons, may be eliciting these changes in behavior. Then, providing a basis for these cellular changes, we outline the epigenetic, chromatin regulatory mechanisms through which ovarian hormones, by binding to their receptors, can affect the regulation of behavior- and synaptic plasticity-related genes in hippocampal neurons. We also highlight an unconventional role that chromatin dynamics may have in regulating neuronal function across the estrous cycle, including in sex hormone-driven X chromosome plasticity and hormonally-induced epigenetic priming. Finally, we discuss directions for future studies and the translational value of the rodent estrous cycle for understanding the effects of the human menstrual cycle on hippocampal physiology and brain disease risk.

The Effect of Task Interruption on Working Memory Performance.

This study used electroencephalography to explore the behavioral and electrophysiological effects of task interruption on performance. Task interruption is known to harm work performance, especially on working memory-related tasks. However, most studies pay little attention to cognitive processes by exploring brain activity and ignore the cumulative effect of sequential interruptions. Thirty-four healthy participants performed a spatial 2-back in three conditions: (1) interruptions with simple math questions, (2) suspensions with prolonged fixation cross, and (3) a pure 2-back. The measured outcomes comprise performance data, ERP amplitudes, EEG power, and subjective workload. Work performance decreased in the resumption trials, and cumulative interruptions had a more destructive effect on performance. EEG results showed that the P2 and P3 amplitudes induced by the 2-back task significantly increased after interruptions; theta and alpha power increased after interruptions. The P3 amplitude and alpha power induced by interruptions were significantly higher than that induced by suspensions. Behavioral data revealed the disruptive effect of interruptions on postinterruption performance and the cumulative effect of interruptions on accuracy. Changes in ERP amplitudes and EEG power indicate the mechanisms of attention reallocation and working memory during interruptions. Larger P3 amplitudes and alpha power after interruptions than after suspensions suggested the inhibition of irrelevant information. These results may support the memory for goals model and improve the understanding of the effects of interruption on working memory. Focusing upon the mechanisms at play during the interruption process can support interruption management to ensure work safety and efficiency.

Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset.

Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis. In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture. We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p < 0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ε4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p < 0.05). Age of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ε4 status to a specific decline in memory performance in EOAD.

Structure-Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance.

Aging and neurodegenerative diseases lead to decline in thinking and memory ability. The subfields of the hippocampus (HCsf) play important roles in memory formation and recall. Imaging techniques sensitive to the underlying HCsf tissue microstructure can reveal unique structure-function associations and their vulnerability in aging and disease. The goal of this study was to use magnetic resonance elastography (MRE), a noninvasive MR imaging-based technique that can quantitatively image the viscoelastic mechanical properties of tissue to determine the associations of HCsf stiffness with different cognitive domains across the lifespan. Eighty-eight adult participants completed the study (age 23-81 years, male/female 36/51), in which we aimed to determine which HCsf regions most strongly correlated with different memory performance outcomes and if viscoelasticity of specific HCsf regions mediated the relationship between age and performance. Our results revealed that both interference cost on a verbal memory task and relational memory task performance were significantly related to cornu ammonis 1-2 (CA1-CA2) stiffness (p = 0.018 and p = 0.011, respectively), with CA1-CA2 stiffness significantly mediating the relationship between age and interference cost performance (p = 0.031). There were also significant associations between delayed free verbal recall performance and stiffness of both the dentate gyrus-cornu ammonis 3 (DG-CA3; p = 0.016) and subiculum (SUB; p = 0.032) regions. This further exemplifies the functional specialization of HCsf in declarative memory and the potential use of MRE measures as clinical biomarkers in assessing brain health in aging and disease.SIGNIFICANCE STATEMENT Hippocampal subfields are cytoarchitecturally unique structures involved in distinct aspects of memory processing. Magnetic resonance elastography is a technique that can noninvasively image tissue viscoelastic mechanical properties, potentially serving as sensitive biomarkers of aging and neurodegeneration related to functional outcomes. High-resolution in vivo imaging has invigorated interest in determining subfield functional specialization and their differential vulnerability in aging and disease. Applying MRE to probe subfield-specific cognitive correlates will indicate that measures of subfield stiffness can determine the integrity of structures supporting specific domains of memory performance. These findings will further validate our high-resolution MRE method and support the potential use of subfield stiffness measures as clinical biomarkers in classifying aging and disease states.

Transcranial Direct Current Stimulation Combined With Listening to Preferred Music Alters Cortical Speech Processing in Older Adults.

Emerging evidence suggests transcranial direct current stimulation (tDCS) can improve cognitive performance in older adults. Similarly, music listening may improve arousal and stimulate subsequent performance on memory-related tasks. We examined the synergistic effects of tDCS paired with music listening on auditory neurobehavioral measures to investigate causal evidence of short-term plasticity in speech processing among older adults. In a randomized sham-controlled crossover study, we measured how combined anodal tDCS over dorsolateral prefrontal cortex (DLPFC) paired with listening to autobiographically salient music alters neural speech processing in older adults compared to either music listening (sham stimulation) or tDCS alone. EEG assays included both frequency-following responses (FFRs) and auditory event-related potentials (ERPs) to trace neuromodulation-related changes at brainstem and cortical levels. Relative to music without tDCS (sham), we found tDCS alone (without music) modulates the early cortical neural encoding of speech in the time frame of ∼100–150 ms. Whereas tDCS by itself appeared to largely produce suppressive effects (i.e., reducing ERP amplitude), concurrent music with tDCS restored responses to those of the music+sham levels. However, the interpretation of this effect is somewhat ambiguous as this neural modulation could be attributable to a true effect of tDCS or presence/absence music. Still, the combined benefit of tDCS+music (above tDCS alone) was correlated with listeners’ education level suggesting the benefit of neurostimulation paired with music might depend on listener demographics. tDCS changes in speech-FFRs were not observed with DLPFC stimulation. Improvements in working memory pre to post session were also associated with better speech-in-noise listening skills. Our findings provide new causal evidence that combined tDCS+music relative to tDCS-alone (i) modulates the early (100–150 ms) cortical encoding of speech and (ii) improves working memory, a cognitive skill which may indirectly bolster noise-degraded speech perception in older listeners.

Dose-Dependent Regulation on Prefrontal Neuronal Working Memory by Dopamine D1 Agonists: Evidence of Receptor Functional Selectivity-Related Mechanisms.

Low doses of dopamine D1 agonists improve working memory-related behavior, but high doses eliminate the improvement, thus yielding an ‘inverted-U’ dose-response curve. This dose-dependency also occurs at the single neuron level in the prefrontal cortex where the cellular basis of working memory is represented. Because signaling mechanisms are unclear, we examined this process at the neuron population level. Two D1 agonists (2-methyldihydrexidine and CY208,243) having different signaling bias were tested in rats performing a spatial working memory-related T-maze task. 2-Methyldihydrexidine is slightly bias toward D1-mediated β-arrestin-related signaling as it is a full agonist at adenylate cyclase and a super-agonist at β-arrestin recruitment, whereas CY208,243 is slightly bias toward D1-mediated cAMP signaling as it has relatively high intrinsic activity at adenylate cyclase, but is a partial agonist at β-arrestin recruitment. Both compounds had the expected inverted U dose-dependency in modulating prefrontal neuronal activities, albeit with important differences. Although CY208,243 was superior in improving the strength of neuronal outcome sensitivity to the working memory-related choice behavior in the T-maze, 2-methyldihydrexidine better reduced neuron-to-neuron variation. Interestingly, at the neuron population level, both drugs affected the percentage, uniformity, and ensemble strength of neuronal sensitivity in a complicated dose-dependent fashion, but the overall effect suggested higher efficiency and potency of 2-methyldihydrexidine compared to CY208,243. The differences between 2-methyldihydrexidine and CY208,243 may be related to their specific D1 signaling. These results suggest that D1-related dose-dependent regulation of working memory can be modified differentially by functionally selective ligands, theoretically increasing the balance between desired and undesired effects.

Role of Sleep in Formation of Relational Associative Memory.

Relational memory, the ability to make and remember associations between objects, is an essential component of mammalian reasoning. In relational memory tasks, it has been shown that periods of offline processing, such as sleep, are critical to making indirect associations. To understand biophysical mechanisms behind the role of sleep in improving relational memory, we developed a model of the thalamocortical network to test how slow-wave sleep affects performance on an unordered relational memory task. First, the model was trained in the awake state on a paired associate inference task, in which the model learned to recall direct associations. After a period of subsequent slow-wave sleep, the model developed the ability to recall indirect associations. We found that replay, during sleep, of memory patterns learned in awake increased synaptic connectivity between neurons representing the item that was overlapping between tasks and neurons representing the unlinked items of the different tasks; this forms an attractor that enables indirect memory recall. Our study predicts that overlapping items between indirectly associated tasks are essential for relational memory, and sleep can reactivate pathways to and from overlapping items to the unlinked objects to strengthen these pathways and form new relational memories.SIGNIFICANCE STATEMENT Experimental studies have shown that some types of associative memory, such as transitive inference and relational memory, can improve after sleep. Still, it remains unknown what specific mechanisms are responsible for these sleep-related changes. In this new work, we addressed this problem by building a thalamocortical network model that can learn relational memory tasks and that can be simulated in awake or sleep states. We found that memory traces learned in awake were replayed during slow waves of NREM sleep and revealed that replay increased connections to and from overlapping memory items to form new relational memories. Our work discovered specific mechanisms behind the role of sleep in associative memory and made testable predictions about how sleep augments associative learning.

Mental-Imagery-Based Mnemonic Training: A New Kind of Cognitive Training.

We investigated the immediate and maintenance effects of mental-imagery-based mnemonic training on improving youths’ working memory, long-term memory, arithmetic and spatial abilities, and fluid intelligence. In Experiment 1, 26 Chinese participants (15 boys, 11 girls) aged 10–16 years were divided into an experimental group that received 8 days of mental-imagery-based mnemonic training and a no-contact control group. Participants completed pre-, post-, and three follow-up tests (3, 6, and 12 months after the pre-test). In Experiment 2, 54 Chinese children (28 boys, 26 girls), all 12 years old, were divided into experimental and control groups. Participants completed pre-, post-, and follow-up tests (three months after the pre-test). Results showed that the training significantly affected long-term memory-related task performance but no effects were observed on working memory, arithmetic or spatial ability, or fluid intelligence-related tasks. Moreover, the effect of the training on long-term memory lasted up to one year; the more frequently the training was used, the more effective it was. A content analysis of the feedback submitted by parents of participants in Experiment 2 three months after the training showed that the children used the strategy more for memorizing content such as Chinese and English, as well as for musical scores. Furthermore, there was also the possibility that the training improved abilities and academic performance such as concentration and math performance. Our results provide a basis for the further exploration of mental-imagery-based mnemonic training as a novel training modality.

Characterizing speech heterogeneity in schizophrenia-spectrum disorders.

Schizophrenia-spectrum disorders (SSD) are highly heterogeneous in risk factors, symptom characteristics, and disease course outcome. Although speech anomalies have long been recognized as a core symptom of SSD, speech markers are an unexplored source of symptom heterogeneity that may be informative in recognizing relevant subtypes. This study investigated speech heterogeneity and its relation to clinical characteristics in a large sample of patients with SSD and healthy controls. Speech samples were obtained from 142 patients with SSD and 147 healthy controls by means of open-ended interviews. Speech was analyzed using standardized open-source acoustic speech software. Hierarchical clustering was conducted using acoustic speech markers. Symptom severity was rated with the Positive and Negative Syndrome Scale, and cognition was assessed with the Brief Assessment of Cognition for Schizophrenia. Three speech clusters could be distinguished in the patient group that differed regarding speech properties, independent of medication use. One cluster was characterized by mild speech disturbances, while two severely impaired clusters were recognized (fragmented speakers and prolonged pausers). Both clusters with severely impaired speech had more severe cognitive dysfunction than the mildly impaired speakers. Prolonged pausers specifically had difficulties with memory-related tasks. Prolonged pausing, as opposed to fragmented speaking, related to chronic active psychosis and refractory psychotic symptoms. Based on speech clustering, subtypes of patients emerged with distinct disease trajectories, symptomatology, and cognitive functioning. The identification of clinically relevant subgroups within SSD may help to characterize distinct profiles and benefit the tailoring of early intervention and improvement of long-term functional outcome. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Protease-activated receptor 2 activation induces behavioural changes associated with depression-like behaviour through microglial-independent modulation of inflammatory cytokines

RationaleMajor depressive disorder (MDD) is a leading cause of disability worldwide but currently prescribed treatments do not adequately ameliorate the disorder in a significant portion of patients. Hence, a better appreciation of its aetiology may lead to the development of novel therapies.ObjectivesIn the present study, we have built on our previous findings indicating a role for protease-activated receptor-2 (PAR2) in sickness behaviour to determine whether the PAR2 activator, AC264613, induces behavioural changes similar to those observed in depression-like behaviour.MethodsAC264613-induced behavioural changes were examined using the open field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), and novel object recognition test (NOR). Whole-cell patch clamping was used to investigate the effects of PAR2 activation in the lateral habenula with peripheral and central cytokine levels determined using ELISA and quantitative PCR.ResultsUsing a blood–brain barrier (BBB) permeable PAR2 activator, we reveal that AC-264613 (AC) injection leads to reduced locomotor activity and sucrose preference in mice but is without effect in anxiety and memory-related tasks. In addition, we show that AC injection leads to elevated blood sera IL-6 levels and altered cytokine mRNA expression within the brain. However, neither microglia nor peripheral lymphocytes are the source of these altered cytokine profiles.ConclusionsThese data reveal that PAR2 activation results in behavioural changes often associated with depression-like behaviour and an inflammatory profile that resembles that seen in patients with MDD and therefore PAR2 may be a target for novel antidepressant therapies.

Measuring the association between hippocampal volume and memory abilities vulnerable to Alzheimer’s disease in typically developing periadolescent children: Preliminary findings from the PRANK Study

AbstractBackgroundChildhood development, including the periadolescent period, is associated with significant changes in brain function, brain structure, and cognition. Memory ability, including memory for arbitrary relations, exemplifies cognitive changes that occur during the periadolescent epoch. In adults, declarative/relational memory requires the hippocampus, as demonstrated by the profound memory impairments accompanying hippocampal pathology frequently caused by Alzheimer’s disease (AD). Vulnerability to AD and related memory impairments in late life could be a function of early‐life brain development. Understanding the developmental relationship between hippocampal volume and declarative/relational memory performance would provide any important baseline for comparison of different trajectories. Our ongoing NIA‐funded research project, the Polygenic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK) study, measures brain structure, brain function, cognitive abilities, and Alzheimer’s polygenic risk score in periadolescent children (age 8‐13). Here, we report preliminary data measuring the association between hippocampal volume and memory abilities in the study’s periadolescent sample.MethodA sample of periadolescent children from the PRANK study provided data for the current project (N=40). Structural MRI data were collected using protocols adapted from the Human Connectome Project, and hippocampal volume was measured through manual tracing. Cognitive variables included relational memory operationalized as performance on the Picture Sequence Memory Task (PSMT) from the NIH Toolbox (a standard neuropsychological battery). We then tested the correlation between hippocampal volume and performance on the relational memory task in periadolescent children.ResultWe found preliminary evidence consistent with differences in the neuropsychological profile and brain structure, specifically in hippocampal volume and declarative/relational memory performance. Our preliminary observations were consistent with significant correlations between regional hippocampal volume and memory performance on the PSMT.ConclusionFindings from this preliminary analysis illustrate differences in cognitive abilities in the periadolescent period, in particular, the association between declarative/relational memory and hippocampal volume. Our ongoing PRANK study measures cognitive abilities, brain structure and function, and Alzheimer’s polygenic risk score in periadolescent children. Future work from this study will investigate whether genetic risk for AD is associated with individual differences in brain structure and outcomes on neuropsychological measures in early life.