Relational Memory Performance Research Articles

Acute Effects of High-Intensity Resistance Exercise on Recognition of Relational Memory, Lactate, and Serum and Plasma Brain-Derived Neurotrophic Factor.

Baumgartner, NW, Belbis, MD, Kargl, C, Holmes, MJ, Gavin, TP, Hirai, DM, and Kao, S-C. Acute effects of high-intensity resistance exercise on recognition of relational memory, lactate, and serum and plasma brain-derived neurotrophic factor. J Strength Cond Res XX(X): 000-000, 2024-Acute aerobic exercise improves memory, but this phenomenon is understudied in response to resistance exercise (RE) despite evidence that RE-induced increases in lactate and brain-derived neurotrophic factor (BDNF) play mechanistic roles in memory performance. To determine the acute effect of RE on lactate, BDNF, and their associations with object and relational memory, blood lactate, and serum and plasma BDNF were taken from 36 adults (average age 23.64 ± 3.89 years; 18 woman) before and immediately after 42 minutes of high-intensity RE and a rest condition on counterbalanced days. Subjects then immediately studied a series of paired objects and completed object and relational recognition tasks. Results revealed a condition by trial interaction, previously studied objects were remembered less accurately following RE (d = 0.66) but recognition occurred faster (d = 0.28), indicating a speed-accuracy tradeoff following RE. There was no effect of either intervention on relational recognition performance. Lactate (d = 3.68) and serum BDNF (d = 0.74) increased following RE, whereas there was no time-related change in lactate and serum BDNF following rest. However, changes in lactate and BDNF did not predict any measures of object (rs < 0.25, ps > 0.16) or relation recognition (rs < 0.28, ps > 0.13). Collectively, these findings suggest that acute high-intensity RE selectively improves the processing speed of recognizing objects at the cost of less accurate recognition of previously studied objects. Furthermore, changes in object and relational memory performance are unlikely driven by acute increases in lactate or BDNF following high-intensity RE.

Influence of mild cognitive impairment and body mass index on white matter integrity assessed by diffusion tensor imaging.

Mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease, is characterized by decreased memory and cognition, which are linked to degenerative changes in the brain. To assess whether white matter (WM) integrity is compromised in MCI, we collected diffusion-weighted images from 60 healthy older adults (OA) (69.16 ± 0.7) and 20 older adults with amnestic MCI (72.45 ± 1.9). WM integrity differences were examined using Tract-Based Spatial Statistics (TBSS). We hypothesized that those with MCI would have diminished WM integrity relative to OA. In a whole-brain comparison, those with MCI showed higher axial diffusivity in the splenium (SCC) and body of the corpus callosum (BCC), superior corona radiata (SCR), and the retrolenticular part of the internal capsule (RLIC) (p's < .05 TFCE-corrected). Additionally, significant between-group connectivity differences were observed using probabilistic tractography between the SCC, chosen from the TBSS results, and forceps major and minor (p-value's < .05). To further relate a physical health indicator to WM alterations, linear regression showed significant interactions between cognitive status and body mass index (BMI) on diffusivity outcome measures from probabilistic tractography (p-value-'s < .05). Additionally, we examined the association between relational memory, BMI, and WM integrity. WM integrity was positively associated with relational memory performance. These findings suggest that these regions may be more sensitive to early markers of neurodegenerative disease and health behaviors, suggesting that modifiable lifestyle factors may affect white matter integrity.

Artificial Neural Network Based Audio Reinforcement for Computer Assisted Rote Learning

The dual-channel assumption of the cognitive theory of multimedia learning suggests that importing a large amount of information through a single (visual or audio) channel overloads that channel, causing partial loss of information, while importing it simultaneously through multiple channels relieves the burden on them and leads to the registration of a larger amount of information. In light of such knowledge, this study investigates the possibility of reinforcing visual stimuli with audio for supporting e-learners in memorization tasks. Specifically, we consider three kinds of learning material and two kinds of audio stimuli and partially reinforce each kind of material with each kind of stimuli in an arbitrary way. In a series of experiments, we determine the particular type of audio, which offers the highest improvement for each kind of material. Our work stands out as being the first study investigating the differences in memory performance in relation to different combinations of learning content and stimulus. Our key findings from the experiments are: (i) E-learning is more effective in refreshing memory rather than studying from scratch, (ii) Non-informative audio is more suited to verbal content, whereas informative audio is better for numerical content, (iii) Constant audio triggering degrades learning performance and thus audio triggering should be handled with care. Based on these findings, we develop an ANN-based estimator to determine the proper moment for triggering audio (i.e. when memory performance is estimated to be declining) and carry out follow-up experiments for testing the integrated framework. Our contributions involve (i) determination of the most effective audio for each content type, (ii) estimation of memory deterioration based on learners’ interaction logs, and (iii) the proposal of improvement of memory registration through auditory reinforcement. We believe that such findings constitute encouraging evidence the memory registration of e-learners can be enhanced with content-aware audio incorporation.

Assessing the relationship between relational memory and segregation of intrinsic functional brain networks vulnerable to Alzheimer’s Disease during periadolescent development: preliminary findings from the PRANK study

AbstractBackgroundAlzheimer’s disease (AD) is an insidious disease process that is frequently diagnosed following complaints of memory loss. The AD‐related decline in memory abilities has been attributed to functional and pathological changes in the hippocampus and distributed functional networks supporting hippocampal‐dependent memory. Although AD manifests in late life, lifelong risk factors for AD may be influenced by childhood brain development. The default mode network (DMN) is one functional network associated with the hippocampus and has been well‐characterized in adulthood. However, there is a gap in the literature regarding the connection between DMN network properties and relational memory abilities in childhood. Here we report preliminary findings from our ongoing study (Polygenic Risk of Alzheimer’s disease in Nebraska Kids, PRANK). The PRANK study collects functional MRI, cognitive measures, and AD polygenic risk scores from periadolescent children in Nebraska (age 8‐13 years). Here, we report the current findings measuring the relationship between brain network measures and cognitive outcomes from the PRANK study.MethodTo assess the relationship between intrinsic functional networks of the brain and hippocampal‐dependent memory, we applied brain and cognitive measures from a preliminary sample of periadolescent children (N=90) from the PRANK study. Cognitive assessments measured hippocampal‐dependent memory and other cognitive domains. Brain measures included both structural and resting‐state functional MRI data. Two properties of brain networks were measured, modularity and participation coefficient. These measures were derived from resting‐state MRI data with help of the Human Connectome Project’s Connectome Workbench tool. For comparison, brain and cognitive measures were also collected from a separate dataset of healthy young adults.ResultOur analysis observed differences between the PRANK and young adult datasets. The observed between‐group differences included graph theoretic measures of network architecture, particularly modularity. The relationship between relational memory performance and the network properties PRANK participants was also assessed.ConclusionThe ongoing PRANK study seeks to determine the association of brain measures and cognitive performance. Here, our preliminary analysis measured the relationship between brain and cognitive measures in periadolescent children with a focus on brain network properties and relational memory.

Cathepsin B and Muscular Strength are Independently Associated with Cognitive Control.

Although muscular strength has been linked to greater cognitive function across different cognitive domains, the mechanism(s) through which this occurs remain(s) poorly understood. Indeed, while an emerging body of literature suggests peripheral myokines released from muscular contractions may play a role in this relationship, additional research is needed to understand this link. Accordingly, this study sought to compare the influences of a particular myokine, Cathepsin B (CTSB), and muscular strength on hippocampal-dependent relational memory and cognitive control in 40 adults (age = 50.0±7.3 yrs). Overnight fasted venous blood draws were taken to assess plasma CTSB and muscular strength was assessed as maximal isokinetic strength testing using a Biodex dynamometer. Cognitive performance was assessed using a Spatial Reconstruction Task to assess relational memory and a modified Flanker task to assess cognitive control. Neuroelectric function for cognitive control was assessed using event-related potentials (ERPs) recorded during the Flanker task. Initial bivariate correlational analyses revealed that neither sex, age, lean body mass, or muscular strength was associated with CTSB. However, CTSB was inversely associated with reaction time and fractional peak latency of the P3 component of the Flanker task. Muscular strength was also inversely associated with reaction time and positively associated with relational memory performance. However, the influence of muscular strength on relational memory did not persist following adjustment for covariates. Greater circulating CTSB was selectively associated with greater cognitive control as well as faster information processing speed. These findings are the first to link circulating CTSB to both cognitive control and neuroelectric function. Future intervention studies are needed to examine the effects of changes in muscular strength, circulating myokines, and different domains of cognitive function.

Measuring the developmental relationship between memory ability and organization of a functional brain network vulnerable to Alzheimer’s disease: Preliminary findings from the PRANK study

AbstractBackgroundThe hallmark memory impairments of typically presenting Alzheimer’s disease (AD) are associated with pathological changes of the hippocampus. While it is known that the hippocampus is necessary for normal relational memory performance, the development of functional brain networks associated with the hippocampus is not well characterized, particularly in the periadolescent epoch. The development of the hippocampus and its associated functional brain network may be influenced by genetic, environmental, or other risk factors for AD, potentially creating vulnerabilities to AD in later life. This project explores the neurodevelopment of this hippocampal network to determine how individual differences in functional connectivity impact relational memory abilities during the periadolescent epoch. Here, we utilized preliminary data from the NIA‐funded Polygenic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK) study, which aims to improve insight regarding how brain and cognitive development is affected by polygenic risk for Alzheimer’s disease. Our continuing study is recruiting healthy periadolescent individuals (8‐13 years of age). Here we report preliminary cross‐sectional findings from the PRANK study exploring how individual differences in hippocampal resting‐state functional connectivity (RSFC) covary with declarative/relational memory ability.MethodAnalyses were conducted on preliminary data from healthy periadolescent participants (n=40). Declarative/relational memory performance was measured with Cambridge Cognition’s Paired Associates Learning (PAL) task. Resting‐state functional MRI data was analyzed using a seed‐based approach with the bilateral hippocampus as the seed region of interest. RSFC data were analyzed to determine their covariance with relational memory ability (operationalized as PAL performance).ResultOur analysis revealed patterns of hippocampal RSFC that were broadly consistent with prior work, sharing the territory of the default mode network (DMN). We also observed regional covariance between hippocampal RSFC and performance on the PAL task.ConclusionThe present work describes preliminary findings of the ongoing PRANK study. Our preliminary observations are consistent with the perspective that hippocampal RSFC covaries with hippocampal‐dependent declarative/relation memory ability among periadolescent children. To understand whether this hippocampal network development is susceptible to genetic risk factors for AD, future work from the PRANK study will utilize participants’ AD polygenic risk scores to determine whether those scores are related to individual differences of hippocampal RSFC.

HOPE4MCI trial: First trial targeting reduction of hippocampal overactivity to treat mild cognitive impairment due to Alzheimer’s disease with AGB101

AbstractBackgroundAD pathophysiological pathways involving both amyloid and tau have been functionally linked to excessive neural activity, with heightened neural activity causing dysfunction and progressive spread of pathology in the disease from an origin in the medial temporal lobe/hippocampus. Like hippocampal overactivity, recent evidence has demonstrated an association of amyloid and p‐tau 217 in early AD, with progressive elevation of p‐tau217 as the disease progresses. Substantial clinical evidence also indicates that hippocampal overactivity longitudinally predicts subsequent cognitive decline/conversion to dementia due to AD. AGB101 (low dose levetiracetam) demonstrates efficacy on a range of AD‐related molecular, synaptic, electrophysiological, functional and behavioral endpoints across models and species. Clinical proof of concept for this therapeutic hypothesis was demonstrated with AGB101 in a Phase 2A study that showed a reduction in hippocampal overactivity resulted in improvement in task related memory performance. To further examine this hypothesis, the HOPE4MCI trial is investigating the effects of AGB101 (low dose levetiracetam, 220 mg extended release) in a 78‐week protocol using tau biomarkers ([11C]MK 6420 pet imaging and p‐tau 217 plasma) alongside CDR‐SB (sole primary endpoint) for clinical/cognitive efficacy in MCI due to AD.MethodsThis is a multicenter, randomized, double‐blind, placebo‐controlled, 78‐week, fixed‐dose study evaluating AGB101 versus placebo as a treatment for slowing the progression of MCI due to AD. Inclusion criteria: Subjects must meet the following inclusion criteria at screening:1) Subjects between 55 and 85 years old 2) Have MCI due to AD consistent with the NIA‐AA criteria: MMSE (24‐30); CDR (0.5); Impaired delayed recall on the ISLT; essentially preserved ADLs 3) Evidence of an amyloid‐positive PET scan.ResultsThe HOPE4MCI trial has completed enrollment with 164 subjects randomized. Baseline data for CDR‐SB and MMSE are consistent with recently enrolled MCI due to AD (prodromal AD) studies. Subject demographics, screen failure information, safety and dropout information will be presented at the meeting.ConclusionsHOPE4MCI represents the first and only Phase 3 clinical trial targeting the reduction of hippocampal overactivity for slowing the progression of MCI due to AD. The HOPE4MCI trial is supported, in part, by R01AG061091 to RM and R01AG048349 to MG.

Enhancement of spatial memories at the associative and relational levels after a full night of sleep and likelihood of dream incorporation

This study evaluated the effect of sleep in mediating the performance of associative and relational spatial memories in an immersive spatialised task. It also investigated how items presented during the task were incorporated into participants' dreams. A total of 54 participants were assigned to either a wake or sleep condition in their home setting: 27 participants stayed awake during a normal day between the learning and the testing phases of a spatial task, while 27 other participants slept in their home according to their usual sleep schedule. Subjective dream experiences during the night were reported by the participants using a paper/pencil diary. Results showed that memory performances for the testing phase were greater for the Sleep group at both associative and relational levels compared to an equivalent period of wake. The examination of dream reports revealed that 6 dream reports out of 17 (35.29%) collected in the Sleep group incorporated items related to the task. To our knowledge, this study is the first to demonstrate a protective effect of sleep on associative and relational memory performance using an immersive spatialised VR task and with a full night's sleep occurring in a home setting that respected the participant's usual sleep schedule. As a perspective, we proposed methodological improvements for future studies investigating dreams and their relationship with memory processes.

Effect of a short rest period on associative and relational memory performance: A Virtual Reality study

Virtual reality immerses individuals in 3D environments where spatial properties are similar to those of real life. Virtual reality can therefore be effective and relevant in the study of memory processing, especially when spatial properties are involved. We studied the effect of a 20-minute rest period on memory performance for associative and relational learnings. Eighty-one participants were placed in a virtual environment in which they learned 24 associations implicating objects and their respective precise location. As expected, the performance of associative memory was improved by a rest period between study and test phases. We discuss these results and the benefits of using an immersive virtual environment for such memory investigation. In addition, elaborating our environment was highly informative and led to several recommendations that we believe could be useful for researchers who would like to rely on virtual reality for investigating memory.

Spatial relational memory in individuals with traumatic brain injury

ABSTRACTIntroduction: Relational memory is the ability to bind arbitrary relations between elements of experience into durable representations and the flexible expression of these representations. It is well known that individuals with traumatic brain injury (TBI) have declarative memory impairments, but less is known about how TBI affects relational memory binding, the deficit at the heart of declarative, or relational, memory impairment. The aim of the current study is to examine such deficits.Method: We used a spatial reconstruction task (SRT) with 29 individuals with TBI and 23 normal comparison (NC) participants to investigate four different types of spatial relations: (A) identity-location relations, i.e., the relationship between a specific item and its known location; (B) item–item relations, or the relationship between one item and another; (C) item–display relations, or the relationship between an item and its position in the display; and (D) compound–item relations, i.e., relations that involve combinations of A, B, and C.Results: Our data revealed that individuals with TBI showed impairments in learning identity–location relations and increased compound errors compared to NCs. We also found evidence that when item identity is disregarded, individuals with TBI do not perform differently from NCs. An exploratory analysis revealed that while relational memory performance was significantly correlated with scores on the California Verbal Learning Test (CVLT), more participants with TBI exhibited impairment on the SRT than of the CVLT.Conclusions: Our findings show that relational memory is impaired following TBI, and provide preliminary evidence for an easy-to-administer task with increased sensitivity to memory impairment.

Examination of relational memory in multidimensional schizotypy

We report the first study to examine the association of positive, negative, and disorganized schizotypy with relational memory. Relational memory refers to memory for relations among multiple elements of an experience, and this form of episodic memory is different from memory for individual elements themselves. Using a cornerstone task from the neurocognitive literature that is designed specifically to assess relational memory, we found that negative schizotypy, but not positive or disorganized schizotypy, is associated with impaired relational memory performance. The deficit was observed both in poorer accuracy and slower response time. The results demonstrate the importance of examining schizotypy as a multidimensional construct, and indicate that using a total schizotypy score both obscures the nature of the association with various dimensions of schizotypy and also explains only half of the variance accounted for by taking into consideration the multidimensionality of schizotypy. These results add to previous findings that negative schizotypy is associated with a wide array of episodic memory deficits linked to impairment in retrieval and processing of contextual information.

Serum Lutein is related to Relational Memory Performance.

Dietary carotenoids, plant pigments with anti-oxidant properties, accumulate in neural tissue and are often found in lower concentrations among individuals with obesity. Given previous evidence of negative associations between excess adiposity and memory, it is possible that greater carotenoid status may confer neuroprotective effects among persons with overweight or obesity. This study aimed to elucidate relationships between carotenoids assessed in diet, serum, and the macula (macular pigment optical density (MPOD)) and relational memory among adults who are overweight or obese. Adults aged 25–45 years (N = 94) completed a spatial reconstruction task. Task performance was evaluated for accuracy of item placement during reconstruction relative to the location of the item during the study phase. Dietary carotenoids were assessed using 7-day diet records. Serum carotenoids were measured using high-performance liquid chromatography. Hierarchical linear regression analyses were used to determine the relationship between carotenoids and task performance. Although initial correlations indicated that dietary lutein, beta-carotene, and serum beta-carotene were positively associated with memory performance, these relationships were not sustained following adjustment for age, sex, and BMI. Serum lutein remained positively associated with accuracy in object binding and inversely related to misplacement error after controlling for covariates. Macular carotenoids were not related to memory performance. Findings from this study indicate that among the carotenoids evaluated, lutein may play an important role in hippocampal function among adults who are overweight or obese.

Relational memory is associated with academic achievement in preadolescent children

Abstract Objectives Cognitive functions supported by the hippocampus, including relational memory and the implementation of effective learning strategies, are purported to be vital to academic success. Yet there is little evidence tying performance on standardized measures of academic achievement to performance on hippocampal-dependent tasks. Methods This study tested the association between relational memory performance and academic achievement. Preadolescent participants (N = 181; mean age = 8.7 years; 97 females) completed the Kaufman Test of Educational Achievement, 2nd edition (KTEA-II) along with the Mnemonic Similarity Task (MST) and a task designed to assess both spatial relational memory and the resolution of memory for highly similar studied objects. A subset of participants (n = 40) completed an additional spatial reconstruction relational memory task. Results While performance on the MST and object memory resolution were not significantly associated with academic achievement, relational memory performance was positively associated with mathematics, written language, and overall academic achievement. The association between relational memory and academic achievement remained significant even after controlling for demographic factors including age, sex, and socioeconomic status. Conclusions These findings suggest that the processes underlying relational memory performance are critical for academic success during preadolescence.

Double dissociation of structure-function relationships in memory and fluid intelligence observed with magnetic resonance elastography

Brain tissue mechanical properties, measured in vivo with magnetic resonance elastography (MRE), have proven to be sensitive metrics of neural tissue integrity. Recently, our group has reported on the positive relationship between viscoelasticity of the hippocampus and performance on a relational memory task in healthy young adults, which highlighted the potential of sensitive MRE measures for studying brain health and its relation to cognitive function; however, structure-function relationships outside of the hippocampus have not yet been explored. In this study, we examined the relationships between viscoelasticity of both the hippocampus and the orbitofrontal cortex and performance on behavioral assessments of relational memory and fluid intelligence. In a sample of healthy, young adults (N = 53), there was a significant, positive relationship between orbitofrontal cortex viscoelasticity and fluid intelligence performance (r = 0.42; p = .002). This finding is consistent with the previously reported relationship between hippocampal viscoelasticity and relational memory performance (r = 0.41; p = .002). Further, a significant double dissociation between the orbitofrontal-fluid intelligence relationship and the hippocampal-relational memory relationship was observed. These data support the specificity of regional brain MRE measures in support of separable cognitive functions. This report of a structure-function relationship observed with MRE beyond the hippocampus suggests a future role for MRE as a sensitive neuroimaging technique for brain mapping.

Increasing relational memory in childhood with unitization strategies.

Young children often experience relational memory failures, which are thought to result from immaturity of the recollection processes presumed to be required for these tasks. However, research in adults has suggested that relational memory tasks can be accomplished using familiarity, a process thought to be mature by the end of early childhood. The goal of the present study was to determine whether relational memory performance could be improved in childhood by teaching young children memory strategies that have been shown to increase the contribution of familiarity in adults (i.e., unitization). Groups of 6- and 8-year-old children were taught to use visualization strategies that either unitized or did not unitize pictures and colored borders. Estimates of familiarity and recollection were extracted by fitting receiver operator characteristic curves (Yonelinas, Journal of Experimental Psychology: Learning, Memory, and Cognition 20, 1341-1354, 1994, Yonelinas, Memory & Cognition 25, 747-763, 1997) based on dual-process models of recognition. Bayesian analysis revealed that strategies involving unitization improved memory performance and increased the contribution of familiarity in both age groups.

Effects of hydration on relational memory among preadolescent children

BackgroundEpidemiological data demonstrate that a majority of children in many industrialized countries are inadequately hydrated. However, the implications of water intake or hydration on children's physical and mental health remain understudied. Specifically, there is a gap in knowledge pertaining to the impact of changes in hydration and children's cognitive function.ObjectiveThe current study assessed the effects of changes in water consumption on relational memory among preadolescent children. In addition, we aimed to understand the within condition relationships between markers of hydration and children's memory performance.MethodsA counter‐balanced crossover design was used. Children between 9–10 years (N=26, 11 females) underwent high (HIGH; 2L/d) and low (LOW; 1L/d) water conditions for 4d. Following each condition, children completed a spatial reconstruction task designed to assess hippocampal‐dependent relational memory. Urine osmolality was assessed using pooled samples collected during the 24‐hr period (24‐h UOsm) preceding cognitive testing.Results24‐h UOsm was significantly lower in the HIGH (393 ± 168 mOsm/kg) compared to LOW fluid intake condition (787 ± 206 mOsm/kg; p&lt;0.01). Between condition analyses yielded no significant effects for relational memory performance (all p's &gt; .117). However, within condition analyses revealed that 24‐h UOsm was correlated with relational memory performance. During the HIGH condition, higher 24‐h UOsm was associated with greater swap (r = .540, p = .004), misplacement (r = .429, p = .029), and edge resizing (r = .474, p = .014) errors. During the LOW condition, higher 24‐h UOsm was correlated with greater misplacement (r = .403, p = .041), edge resizing (r = .390, p = .049), and edge deflection (r = .478, p = .013) errors.ConclusionsAlthough the intervention did not significantly change relational memory performance, lower urine osmolality, i.e. better hydration, was associated with superior relational memory within each condition. Comprehensive understanding of fluid modulation effects on children's cognitive performance will need to account for baseline hydration, a limitation of the present work.Support or Funding InformationSupported by Danone Research

Aerobic fitness, hippocampal viscoelasticity, and relational memory performance

The positive relationship between hippocampal structure, aerobic fitness, and memory performance is often observed among children and older adults; but evidence of this relationship among young adults, for whom the hippocampus is neither developing nor atrophying, is less consistent. Studies have typically relied on hippocampal volumetry (a gross proxy of tissue composition) to assess individual differences in hippocampal structure. While volume is not specific to microstructural tissue characteristics, microstructural differences in hippocampal integrity may exist even among healthy young adults when volumetric differences are not diagnostic of tissue health or cognitive function. Magnetic resonance elastography (MRE) is an emerging noninvasive imaging technique for measuring viscoelastic tissue properties and provides quantitative measures of tissue integrity. We have previously demonstrated that individual differences in hippocampal viscoelasticity are related to performance on a relational memory task; however, little is known about health correlates to this novel measure. In the current study, we investigated the relationship between hippocampal viscoelasticity and cardiovascular health, and their mutual effect on relational memory in a group of healthy young adults (N=51). We replicated our previous finding that hippocampal viscoelasticity correlates with relational memory performance. We extend this work by demonstrating that better aerobic fitness, as measured by VO2max, was associated with hippocampal viscoelasticity that mediated the benefits of fitness on memory function. Hippocampal volume, however, did not account for individual differences in memory. Therefore, these data suggest that hippocampal viscoelasticity may provide a more sensitive measure to microstructural tissue organization and its consequences to cognition among healthy young adults.

4.1 Glutamatergic Alterations Across the Schizophrenia Illness Course

Abstract Background: Glutamate may decline with age (or illness course) in schizophrenia at a greater rate than the psychiatrically healthy population as suggested by a meta-analysis. However, no studies have specifically addressed this question. Therefore, we investigated glutamate levels with magnetic resonance spectroscopy (MRS), in younger and older participants with schizophrenia in 2 separate studies with differing samples and methods. Regions strongly implicated in the pathophysiology of schizophrenia-related disorders, the anterior cingulate and the medial temporal lobe, were investigated. Methods: MR scanning was conducted on a 3T Siemens Tim Trio equipped with a 32-channel head coil. One hundred and sixty-seven participants completed Study 1, and 86 participants completed Study 2. For Study 1, spectra were acquired from the anterior cingulate using phase rotation STEAM (PR-STEAM) (13,14): TR/TM/TE = 2000/10/6.5 ms, NEX = 128, and phases: φ1 = 135°, φ2 = 22.5°, φ13 = 112.5°, φADC = 0° and a water reference (NEX = 16). Glutamate and glutamine were quantified. For Study 2, spectra were acquired from the medial temporal lobe (i.e., hippocampus) and parietal lobe using a PRESS sequence (TR/TE = 2000, 30 ms, NEX = 256 for hippocampus and 128 for parietal and a water reference NEX = 16). Patients were evaluated for psychopathology, and all participants completed cognitive testing with a focus on attention and working memory for Study 1 and relational memory for Study 2. Results: For Study 1, results revealed significant age (P < .001) and diagnosis (P = .001) effects for glutamate such that glutamate was lower in participants with schizophrenia compared to controls and in older versus younger participants. There was also a significant age effect (P = .007) for glutamine such that glutamine levels increased with age in both the groups. Higher anterior cingulate glutamate was related to better attention (P < .001) and working memory (P = .04). For Study 2, hippocampal glutamate was lower in older but not younger participants with schizophrenia (P = .03, Diagnosis × Age interaction). Parietal glutamate was lower in participants with schizophrenia irrespective of age (P = .013). Better relational memory performance was related to higher levels of parietal glutamate (P < .01). Conclusion: Participants with schizophrenia were distinguished by lower anterior cingulate and parietal glutamate levels, but there was no evidence of accelerated glutamate aging in these brain regions. Lower hippocampal glutamate levels observed in older participants with schizophrenia suggests that the hippocampus may be particularly vulnerable to aging in schizophrenia. Glutamatergic interventions targeted at increasing levels in the anterior cingulate and parietal cortex and halting the decline in the hippocampus may improve cognitive function and quality of life in patients with schizophrenia.

Macular Carotenoids, Aerobic Fitness, and Central Adiposity Are Associated Differentially with Hippocampal-Dependent Relational Memory in Preadolescent Children

To examine the associations of macular pigment carotenoids (lutein, meso-zeaxanthin, and zeaxanthin), aerobic fitness, and central adiposity with hippocampal-dependent relational memory in prepubescent children. Children between 7 and 10 years of age (n = 40) completed a task designed to assess relational memory performance and participated in aerobic fitness, adiposity, and macular pigment optical density (MPOD) assessment. Aerobic fitness was assessed via a modified Balke treadmill protocol designed to measure maximal oxygen volume. Central adiposity was assessed via dual-energy x-ray absorptiometry. MPOD was measured psychophysically by the use of customized heterochromatic flicker photometry. Statistical analyses included correlations and hierarchical linear regression. Aerobic fitness and MPOD were associated negatively with relational memory errors (P < .01), whereas central adiposity was associated positively with relational memory errors (P < .05). Hierarchical regression analysis revealed that MPOD accounted for a significant amount of the variance in relational memory performance even after we accounted for aerobic fitness (β = -0.388, P = .007). Even after we adjusted for aerobic fitness and central adiposity, factors known to relate to hippocampal-dependent memory, MPOD positively and significantly predicted hippocampal-dependent memory performance. ClinicalTrials.gov: NCT01619826.

Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory.

It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD) patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed.