Poor Spatial Working Memory Research Articles

Loss of spines in the prelimbic cortex is detrimental to working memory in mice with early-life adversity

Adverse experiences in early life can shape neuronal structures and synaptic function in multiple brain regions, leading to deficits of distinct cognitive functions later in life. Focusing on the pyramidal cells of the prelimbic cortex (PrL), a main subregion of the medial prefrontal cortex, the impact of early-life adversity (ELA) was investigated in a well-established animal model generated by changing the rearing environment during postnatal days 2 to 9 (P2-P9), a sensitive developmental period. ELA has enduring detrimental impacts on the dendritic spines of PrL pyramidal cells, which is most apparent in a spatially circumscribed region. Specifically, ELA affects both thin and mushroom-type spines, and ELA-provoked loss of spines is observed on selective dendritic segments of PrL pyramidal cells in layers II-III and V-VI. Reduced postsynaptic puncta represented by postsynaptic density protein-95 (PSD-95), but not synaptophysin-labelled presynaptic puncta, in ELA mice supports the selective loss of spines in the PrL. Correlation analysis indicates that loss of spines and postsynaptic puncta in the PrL contributes to the poor spatial working memory of ELA mice, and thin spines may play a major role in working memory performance. To further understand whether loss of spines affects glutamatergic transmission, AMPA- and NMDA-receptor-mediated synaptic currents (EPSCs) were recorded in a group of Thy1-expressing PrL pyramidal cells. ELA mice exhibited a depressed glutamatergic transmission, which is accompanied with a decreased expression of GluR1 and NR1 subunits in the PrL. Finally, upregulating the activation of Thy1-expressing PrL pyramidal cells via excitatory DREADDs can efficiently improve the working memory performance of ELA mice in a T-maze-based task, indicating the potential of a chemogenetic approach in restoring ELA-provoked memory deficits.

Eye Movements Detect Differential Change after Participation in Male Collegiate Collision versus Non-Collision Sports.

Although neuroimaging studies of collision (COLL) sport athletes demonstrate alterations in brain structure and function from pre- to post-season, reliable tools to detect behavioral/cognitive change relevant to functional networks associated with participation in collision sports are lacking. This study evaluated the use of eye-movement testing to detect change in cognitive and sensorimotor processing among male club collegiate athletes after one season of participation in collision sports of variable exposure. We predicted that COLL (High Dose [hockey], n = 8; Low Dose [rugby], n = 9) would demonstrate longer reaction times (antisaccade and memory-guided saccade [MGS] latencies), increased inhibitory errors (antisaccade error rate), and poorer spatial working memory (MGS spatial accuracy) at post-season, relative to pre-season, whereas non-collision collegiate athletes (NON-COLL; n = 17) would remain stable. We also predicted that whereas eye-movement performance would detect pre- to post-season change, ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) performance would remain stable. Our data showed that NON-COLL had shorter (improved performance) post- versus pre-season antisaccade and MGS latencies, whereas COLL groups showed stable, longer, or attenuated reduction in latency (ps ≤ 0.001). Groups did not differ in antisaccade error rate. On the MGS task, NON-COLL demonstrated improved spatial accuracy over time, whereas COLL groups showed reduced spatial accuracy (p < 0.05, uncorrected). No differential change was observed on ImPACT. This study provides preliminary evidence for eye-movement testing as a sensitive marker of subtle changes in attentional control and working memory resulting from participation in sports with varying levels of subconcussive exposure.

The Impact of Perceived Neighborhoods in Childhood and Adulthood on Daily Cognitive Function

Neighborhood experiences may have a cumulative effect on cognitive health outcomes across the lifespan. We investigated independent and combined associations between current and retrospective childhood neighborhoods and daily cognitive function in 209 adults (Mage=47.07; range: 25-65) who participated in a 14-day ecological momentary assessment study. Participants reported perceptions of their current neighborhood and the neighborhood they lived in at age 5; including neighborhood cohesion, safety, violence, and physical conditions. Greater current neighborhood violence was independently associated with poorer spatial working memory. Childhood neighborhood violence was not significantly associated with performance. The interaction between current and childhood neighborhood ratings was significant: individuals who reported greater childhood neighborhood violence, but lower current violence had better performance than those who experienced consistently high or low neighborhood violence. Effects for other neighborhood domains were not significant. Results indicate that neighborhood influences on cognition in adulthood may be moderated by childhood neighborhood experiences.

Spatial working memory in young adolescents with different childhood trajectories of internalizing, conduct and hyperactivity/inattention problems.

In children, internalizing and externalizing problems impact on learning. However, there is limited research on the specific impact of such problems on spatial working memory (SWM), strongly related to cognitive ability and children's learning. We explored distinct trajectories of internalizing problems and externalizing problems (conduct problems and hyperactivity/inattention) in a large general-population sample of children followed from age 3 to age 11years. We then assessed their role in SWM performance at age 11years. Data were drawn from the UK's Millennium Cohort Study. Our analytic sample was children with data on SWM at age 11years (N=12,589). There were two stages of data analysis. Trajectory group membership was firstly estimated by group-based trajectory modelling for internalizing problems, conduct problems, and hyperactivity/inattention at ages 3-11years. Multiple regression then assessed the relationship between SWM at age 11years and trajectory group membership after accounting for confounders. Trajectories of internalizing, conduct, and hyperactivity/inattention symptoms across ages 3 to 11years were related to SWM at age 11years, even after controlling for confounding variables. For each of the three symptom domains, poor SWM was most consistently found in children with chronically high levels of symptoms. In general, atypical patterns of internalizing problems, conduct problems, and hyperactivity/inattention in childhood were related to poorer SWM in early adolescence.

Astroglial Mechanisms Underlying Chronic Insomnia Disorder: A Clinical Study.

PurposeThe objective of this study was to investigate whether the serum biomarkers S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) change in patients with chronic insomnia disorder (CID), and if this is the case, whether the altered levels of these serum biomarkers are associated with poor sleep quality and cognitive decline in CID.Patients and MethodsFifty-seven CID outpatients constituted the CID group; thirty healthy controls (HC) were also enrolled. Questionnaires, polysomnography, Chinese-Beijing Version of Montreal Cognitive Assessment (MoCA-C) and Nine Box Maze Test (NBMT) were used to assess their sleep and neuropsychological function. Serum S100B, GFAP, BDNF, and GDNF were evaluated using enzyme-linked immunosorbent assay.ResultsThe CID group had higher levels of S100B and GFAP and lower levels of BDNF and GDNF than the HC group. Spearman correlation analysis revealed that poor sleep quality, assessed by subjective and objective measures, was positively correlated with S100B level and negatively correlated with BDNF level. GFAP level correlated positively with poor subjective sleep quality. Moreover, S100B and GFAP levels correlated negatively with general cognitive function assessed using MoCA-C. GFAP level correlated positively with poor spatial working memory (SWM) in the NBMT; BDNF level was linked to poor SWM and object recognition memory (ORcM) in the NBMT. However, principal component analysis revealed that serum S100B level was positively linked to the errors in object working memories, BDNF and GDNF concentrations were negatively linked with errors in ORcM, and GFAP concentration was positively correlated with the errors in the SWM and spatial reference memories.ConclusionSerum S100B, GFAP, BDNF, and GDNF levels were altered in patients with CID, indicating astrocyte damage, and were associated with insomnia severity or/and cognitive dysfunction.

Sleep Symptoms Differentially Predict Cognition in Younger and Older-Onset Parkinson's Disease

Abstract Background: Both disrupted sleep and cognitive impairment are frequent in Parkinson’s disease (PD), but the evidence for a relationship between self-reported sleep disturbance and cognitive symptoms has been equivocal. If sleep symptoms differentially predict cognition in different subtypes, effects may be obscured in a general PD sample. Objective: First, to determine whether the associations between participant and disease variables, sleep symptoms and cognitive performance vary by subtype (younger and older-onset); then to establish whether these effects remain when the sample is reanalysed as a whole. Methods: Multi-group path analyses were used to model the relationships between participant and PD variables; factor scores derived from our bifactor analysis of the Parkinson's Disease Sleep Scale-Revised; and, measures of memory and executive function. Path analyses were replicated as single group analyses. Results: Increased general sleep disturbance predicted better verbal recall in younger-onset PD and poorer visual episodic memory in older-onset PD. Increased insomnia scores predicted better verbal recognition memory in younger-onset PD, better verbal fluency in both groups and poorer spatial working memory (SWM) in older-onset PD. Higher OSA and RBD scores predicted poorer spatial recognition memory and spatial working memory in younger-onset PD, but did not predict cognition in older-onset PD. Many regression coefficients were weakened or reduced to non-significance in the single-sample models. Conclusions: The relationships between participant variables, sleep, and cognition were markedly different in younger and older-onset PD. The influence of sex and premorbid IQ as moderating variables warrant further investigation.

The role of spatial store and executive strategy in spatial working memory: a comparison between patients with obsessive–compulsive disorder and controls

ABSTRACTIntroduction: Patients with obsessive–compulsive disorder (OCD) showed impaired spatial working memory (SWM). We evaluated whether patients and healthy controls (HCs) differed in spatial store capacity, and whether they differed in the relative weight of spatial store capacity and/or executive strategy in SWM.Methods: Thirty inpatients with OCD and 31 age- and education-matched HCs underwent the CANTAB SWM, SRM (a measure of spatial store). The severity of OC symptoms was assessed using the Y-BOCS. Statistical significance: α = 0.05.Results: Patients showed poorer performance than HCs in all neuropsychological outcomes. Both poorer SRM and SWM strategy were significantly associated with poorer SWM in the entire sample. No significant interaction between SRM and Group was found, while a significant interaction between SWM strategy and Group emerged; in patients the magnitude of this association was approximately twofold larger than in HCs. OC symptom severity did not correlate with neuropsychological performance.Conclusions: Patients with OCD had poorer spatial store capacity than HCs. However, the weight of poorer executive strategy in SWM was greater in patients than HCs, whereas the weight of spatial store was similar. We provided a direct evidence that an impairment in the executive component might be the crucial factor influencing the poorer SWM of these patients.

Sex‐specific and Obesity‐specific Association of Serum Uric Acid with Cognitive Function in Older Adults

Lower serum uric acid concentrations have been linked to cognitive dysfunction. Uric acid is an antioxidant that accounts for over half of the free radical scavenging activity in humans. Higher serum concentrations of uric acid have been associated with slower progression of several neurodegenerative diseases. On the other hand, elevated serum uric acid levels have been associated with poorer processing speed and executive functioning and greater white matter atrophy. Our aim in this study was to ascertain the relation between uric acid and cognitive function in older adults with mild cognitive decline (defined at 1–1.5 SD below the mean on the Montreal Cognitive Assessment, MoCA). Cognitive function was assessed using the MoCA and Cambridge Neuropsychological Test Automated Battery (CANTAB). Mean concentrations of serum uric acid in 107 individuals (mean age = 72.7 ± 4.3 years) were 5.9 ± 2.3 mg/dl; males had significantly higher uric acid concentrations (6.3 ± 1.1 mg/dl) compared to females (5.4 ± 1.1 mg/dl). Obese individuals’ concentrations were higher (6.2 ± 1.1 mg/dl) as compared to overweight (6.0 ± 1.1 mg/dl) and normal weight individuals (5.1 ± 1.2 mg/dl). Hyperuricemia (in males, serum uric acid &gt; 7mg/dl and in females, serum uric acid &gt; 6mg/dl) was present in 24% of the individuals. Compared with normouricemic individuals, hyperuricemic had significantly (p &lt; 0.05) elevated serum triglyceride levels (122.1 ± 67 vs. 184.5 ± 152 mg/dl) and higher waist circumference (39.3 ±4 vs. 41.1 ± 3 in). Serum uric acid was positively correlated with BMI, waist circumference, serum creatinine, serum glucose, serum cholesterol ( p &lt; 0.00001). Serum uric acid was negatively associated with MoCA scores (r2 = −0.23, p = 0.02). When stratified by sex, serum uric acid was positively associated with errors made on the CANTAB spatial working memory task (t = 2.6, p = 0.014) in men, but not in women. Similarly, when stratified by BMI, serum uric acid was positively associated with spatial working memory errors (t = 2.9, p = 0.013) and rapid visual processing errors (t = 3.0, p = 0.01) from the CANTAB in obese individuals but not in normal or overweight individuals. In summary, among older adults, higher serum uric acid concentrations are linked to poorer cognitive function in all individuals, poorer spatial working memory in men and obese individuals, and poorer processing in obese individuals compared to other groups. These findings indicate a potential role for serum uric acid concentrations in cognitive function in older adults.Support or Funding InformationThis research was funded by grants from the United States Department of Agriculture (2010‐2342‐02 and 2015‐2809‐01) to the first author and a small grant from the Nutrition Research Institute to the first and last authors.

Spatial working memory and attention skills are predicted by maternal stress during pregnancy

IntroductionExperimental evidence in rodents shows that maternal stress during pregnancy (MSDP) negatively impacts spatial learning and memory in the offspring. We aim to investigate the association between MSDP (i.e., life events) and spatial working memory, as well as attention skills (attention shifting and attention focusing), in humans. The moderating roles of child sex, maternal anxiety during pregnancy and postnatal care are also investigated. MethodsParticipants were 236 mother–child dyads that were followed from the second trimester of pregnancy until 4years postpartum. Measurements included questionnaires and independent observations. ResultsMSDP was negatively associated with attention shifting at 18months when concurrent maternal anxiety was low. MSDP was associated with poorer spatial working memory at 4years of age, but only for boys who experienced poorer postnatal care. ConclusionConsistent with results observed in rodents, MSDP was found to be associated with spatial working memory and attention skills. These results point to postnatal care and maternal anxiety during pregnancy as potential targets for interventions that aim to buffer children from the detrimental effects of MSDP.

Characterization of a normal control group: Are they healthy?

We examined the health of a control group (18–81years) in our aging study, which is similar to control groups used in other neuroimaging studies. The current study was motivated by our previous results showing that one third of the elder control group had moderate to severe white matter hyperintensities and/or cortical volume loss which correlated with poor performance on memory tasks. Therefore, we predicted that cardiovascular risk factors (e.g., hypertension, high cholesterol) within the control group would account for significant variance on working memory task performance. Fifty-five participants completed 4 verbal and spatial working memory tasks, neuropsychological exams, diffusion tensor imaging (DTI), and blood tests to assess vascular risk. In addition to using a repeated measures ANOVA design, a cluster analysis was applied to the vascular risk measures as a data reduction step to characterize relationships between conjoint risk factors. The cluster groupings were used to predict working memory performance. The results show that higher levels of systolic blood pressure were associated with: 1) poor spatial working memory accuracy; and 2) lower fractional anisotropy (FA) values in multiple brain regions. In contrast, higher levels of total cholesterol corresponded with increased accuracy in verbal working memory. An association between lower FA values and higher cholesterol levels were identified in different brain regions from those associated with systolic blood pressure. The conjoint risk analysis revealed that Risk Cluster Group 3 (the group with the greatest number of risk factors) displayed: 1) the poorest performance on the spatial working memory tasks; 2) the longest reaction times across both spatial and verbal memory tasks; and 3) the lowest FA values across widespread brain regions. Our results confirm that a considerable range of vascular risk factors are present in a typical control group, even in younger individuals, which have robust effects on brain anatomy and function. These results present a new challenge to neuroimaging studies both for defining a cohort from which to characterize ‘normative’ brain circuitry and for establishing a control group to compare with other clinical populations.

071 Neuropsychological effects of sleep disturbance in healthy subjects

BackgroundCognitive impairment is a major source of morbidity in mood disorders. Sleep disturbance affects 90% of patients with these disorders and remains an under-researched, potentially significant contributor to these common...

Sentence comprehension in postinstitutionalized school-age children.

In this study, the authors investigated sentence comprehension and spatial working memory abilities in a sample of internationally adopted, postinstitutionalized (PI) children. The authors compared the performance of these PI children with that of an age-matched group of children living with their birth families. They hypothesized that PI children would perform below clinical threshold on tasks of sentence comprehension and that poor sentence comprehension would be associated with poor performance in working memory. Twenty-three PI children and 36 comparison children were administered sentence comprehension and spatial memory tasks from standardized assessments. Some oral sentence comprehension skills and the spatial working memory skills were weaker in the school-age PI children than in the age-matched comparison children. A mediational analysis demonstrated that poor spatial working memory performance partially explains the sentence comprehension differences between the 2 groups. These findings provide valuable information to better plan early intervention and special education for PI children.

Dysfunctional neural network of spatial working memory contributes to developmental dyscalculia

The underlying neural mechanisms of developmental dyscalculia (DD) are still far from being clearly understood. Even the behavioral processes that generate or influence this heterogeneous disorder are a matter of controversy. To date, the few studies examining functional brain activation in children with DD mainly focus on number and counting related tasks, whereas studies on more general cognitive domains that are involved in arithmetical development, such as working memory are virtually absent. There are several studies showing a close relationship between DD and spatial working memory [Camos, V. (2008). Low working memory capacity impedes both efficiency and learning of number transcoding in children. Journal of Experimental Child Psychology, 99(1), 37-57; McLean, J. F., & Hitch, G. J. (1999). Working memory impairments in children with specific arithmetic learning difficulties. Journal of Experimental Child Psychology, 74(3), 240-260; Rosselli, M., Matute, E., Pinto, N., & Ardila, A. (2006). Memory abilities in children with subtypes of dyscalculia. Developmental Neuropsychology, 30(3), 801-818; Siegel, L. S., & Ryan, E. B. (1989). The development of working memory in normally achieving and subtypes of learning disabled children. Child Development, 60(4), 973-980]. The relationship between these two mechanisms is still matter of debate, but this study follows the assumption that poor spatial working memory capacity may hinder the acquisition of spatial number representations in children with DD [Geary, D. C. (1993). Mathematical disabilities: Cognitive, neuropsychological, and genetic components. Psychological Bulletin, 114(2), 345-362; von Aster, M., & Shalev, R. S. (2007). Number development and developmental dyscalculia. Developmental Medicine and Child Neurology, 49(11), 868-873]. Using functional MRI the current study compares brain activity associated with spatial working memory processes in 8-10-year-old children with DD and normally achieving controls. Both groups showed significant spatial working memory related activity in a network including occipital and parietal regions. Children with DD showed weaker neural activation compared to the control group during a spatial working memory task in the right intraparietal sulcus (IPS), the right insula and the right inferior frontal lobe. Performance tests outside the scanner showed impaired working memory proficiency in children with DD. Bringing behavioral performance and neural activity together we found significant correlations of right IPS activity with performance on the verbal digit span forward and the spatial Corsi Block Tapping test. Our findings demonstrate for the first time an involvement of spatial working memory processes in the neural underpinnings of DD. These poor spatial working memory processes may inhibit the formation of spatial number representations (mental numberline) as well as the storage and retrieval of arithmetical facts.

Antisaccade task performance in patients at ultra high risk for developing psychosis

Patients with schizophrenia consistently perform worse than healthy controls on the antisaccade task in which the subject is required to inhibit a reflexive saccade to a suddenly appearing visual target and look in the opposite direction. To our knowledge there is no research yet showing how patients at ultra high risk (UHR) for developing psychosis perform on the antisaccade task. The aim of the present study was to investigate antisaccade task performance in UHR patients. Patients were eligible for the study when they met criteria for one or more of the following groups: Attenuated symptoms or brief limited intermitted psychotic symptoms or a first-degree family member with a psychotic disorder and reduced functioning or basic symptoms. In 35 UHR patients we assessed antisaccades, neuropsychological test performance and symptomatology. Antisaccade task results were compared with those obtained in 42 age- and intelligence-matched patients with recent-onset schizophrenia and 28 matched healthy controls. Antisaccade error rate was significantly higher in the UHR patients than in the controls. Schizophrenia patients performed worse than the UHR patients and the control subjects. We found a trend towards higher antisaccade error rate at baseline in the UHR patients who later made the transition to psychosis compared to the UHR patients who did not make the transition to psychosis. Poor spatial working memory function was related to increased antisaccade errors in the UHR group. Abnormal antisaccade task performance is also present in patients at UHR for developing psychosis. Subsequent research needs to clarify if increased antisaccade error rate is predictive of a psychotic episode. In UHR patients, poor antisaccade performance may reflect working memory dysfunction.

Interactive Effects of a DRD4 Polymorphism, Lead, and Sex on Executive Functions in Children

Prior studies have examined independent effects of a dopamine receptor D4 polymorphism (DRD4-7) and lead exposure on executive functions but not their interaction or the role of sex as a modifier of their effects. Multivariable analyses were used to examine effects of DRD4-7 genotype, 60-month blood lead level, and sex on spatial working memory, rule learning and reversal, spatial span, and planning for 174 children. DRD4-7 was associated with poorer spatial working memory, and increasing blood lead levels were associated with impaired rule learning and reversal, spatial span, and planning. Adverse effects of lead on planning and rule learning and reversal were seen primarily for boys. In addition, the effect of lead on rule learning and reversal was evident predominately for those lacking DRD4-7. We observed independent effects of DRD4-7 and lead on various executive functions and modifications of lead effects by DRD4 genotype and sex.

Haploinsufficiency of the arginine–vasopressin gene is associated with poor spatial working memory performance in rats

Behavioral pharmacological studies have implicated a role for the neurophysin arginine–vasopressin in learning and memory. Vasopressin, and its analogues, can produce either improvements or impairments in mnemonic functions, effects that depend upon the agent administered, the memory process measured and the task employed. As recent data have implicated vasopressin in regulating the cognitive functions of the prefrontal cortex, we sought to determine whether changes in vasopressinergic tone would affect a form of memory that is dependent upon this brain region. To that end, we used a genetic approach to examine how haploinsufficiency of the vasopressin gene affects working memory performance. Specifically, we tested a naturally occurring null-mutant rat on an operant delayed-non-match-to-position task. Male and female heterozygous and wild-type rats were trained to perform this working memory task, and the effects of varying the delay across which they had to maintain task information were systematically varied. Although vasopressin-deficient rats omitted fewer trials and completed trials more quickly, they exhibited delay-dependent deficits of choice accuracy. The genotype effects were not modified by sex. Collectively, these data indicate that even partial vasopressin deficiency can trigger deficits of spatial working memory performance and add to the growing body of results supporting a regulatory control of neocortical-dependent cognitive functions by this neurohormone.

Spatial Working Memoryand Planning Ability: Contrasts between Schizophreniaand Bipolar i Disorder

Working memory may be conceptualized as a multi-component system involving the active maintenance and manipulation of stored information in the service of planning/guiding behaviour. Impaired spatial working memory is a robust finding in schizophrenia patients which has been related to an impairment in frontostriatal connectivity. The purpose of this study was to examine the specificity of this impairment by comparing the mnemonic and executive aspects of working memory performance in schizophrenia and bipolar disorder with psychotic features, focusing particularly on the functional dynamics between task components. Twenty-four patients with schizophrenia, 14 patients with bipolar I disorder (manic phase) and 33 healthy control subjects were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB): including the spatial working memory (between search errors and strategy scores) spatial span (storage capacity) and spatial planning (Stockings of Cambridge: accuracy and latency) tasks. Both patient groups were impaired on the spatial span task, which requires the maintenance and retrieval of stored information. In contrast, only schizophrenia patients showed a significant deficit in between search errors, which requires both maintenance and manipulation of information in working memory. That is, they exhibited both a mnemonic and an executive dysfunction. Spatial span was particularly important to accurate planning ability in bipolar patients. In contrast, in patients with schizophrenia poor spatial working memory was a significant predictor of planning impairments, consistent with failures in goal selection, evaluation and/or execution. Furthermore, initial planning time was positively correlated with the latency to complete a planning sequence. This pattern of slow cognitive processing in schizophrenia patients only, resembled that reported previously in patients with basal ganglia disorders. These findings are discussed in terms of a possible common disturbance in fronto-parietal circuitry in the two disorders together with a specific disturbance of fronto-striatal circuitry in schizophrenia, that is not present in bipolar disorder.