Working Memory In Adults Research Articles

Investigating 7,8-Dihydroxyflavone to combat maternal immune activation effects on offspring gene expression and behaviour

Infection during pregnancy is a substantial risk factor for the unborn child to develop autism or schizophrenia later in life, and is thought to be driven by maternal immune activation (MIA). MIA can be modelled by exposing pregnant mice to Polyinosinic: polycytidylic acid (Poly-I:C), a viral mimetic that induces an immune response and recapitulates in the offspring many neurochemical features of ASD and schizophrenia, including altered BDNF-TrkB signalling and disruptions to excitatory/inhibitory balance. Therefore, we hypothesised that a BDNF mimetic, 7,8-Dihydroxyflavone (7,8-DHF), administered prophylactically to the dam may prevent the neurobehavioural sequelae of disruptions induced by MIA. Dams were treated with 7,8-DHF in the drinking water (0.08 mg/ML) from gestational day (GD) 9–20 and were exposed to Poly-I:C at GD17 (20 mg/kg, i.p.). Foetal brains were collected 6 h post Poly-I:C exposure for RT-qPCR analysis of BDNF, cytokine, GABAergic and glutamatergic gene targets. A second adult cohort were tested in a battery of behavioural tests relevant to schizophrenia and the prefrontal cortex and ventral hippocampus dissected for RT-qPCR analysis. Foetal brains exposed to Poly-I:C showed increased IL-6, but reduced expression of Ntrk2 and multiple GABAergic and glutamatergic markers. Anxiety-like behaviour was observed in adult offspring prenatally exposed to poly-I:C, which was accompanied by altered expression of Gria2 in the prefrontal cortex and Gria4 in the ventral hippocampus. While 7–8 DHF normalised the expression of some glutamatergic (Grm5) and GABAergic (Gabra1) genes in Poly-I:C exposed offspring, it also led to substantial alterations in offspring not exposed to Poly-I:C. Furthermore, mice exposed to 7,8-DHF prenatally showed increased pre-pulse inhibition and reduced working memory in adulthood. These data advance understanding of how 7,8-DHF and MIA prenatal exposure impacts genes critical to excitatory/inhibitory pathways and related behaviour.

Motor control and working memory in adults with neurological injuries: search neuropsychological and electrophysiological evidence of cognitive-motor interaction

Motor control and working memory in adults with neurological injuries: search neuropsychological and electrophysiological evidence of cognitive-motor interaction

Impacts of age and environment on postnatal microglial activity: Consequences for cognitive function following early life adversity.

Early life adversity (ELA) increases the likelihood of later-life neuropsychiatric disorders and cognitive dysfunction. Importantly, ELA, neuropsychiatric disorders, and cognitive deficits all involve aberrant immune signaling. Microglia are the primary neuroimmune cells and regulate brain development. Microglia are particularly sensitive to early life insults, which can program their responses to future challenges. ELA in the form of maternal separation (MS) in rats alters later-life microglial morphology and the inflammatory profile of the prefrontal cortex, a region important for cognition. However, the role of microglial responses during MS in the development of later cognition is not known. Therefore, here we aimed to determine whether the presence of microglia during MS mediates long-term impacts on adult working memory. Clodronate liposomes were used to transiently deplete microglia from the brain, while empty liposomes were used as a control. We hypothesized that if microglia mediate the long-term impacts of ELA on working memory in adulthood, then depleting microglia during MS would prevent these deficits. Importantly, microglial function shifts throughout the neonatal period, so an exploratory investigation assessed whether depletion during the early versus late neonatal period had different effects on adult working memory. Surprisingly, empty liposome treatment during the early, but not late, postnatal period induced microglial activity changes that compounded with MS to impair working memory in females. In contrast, microglial depletion later in infancy impaired later life working memory in females, suggesting that microglial function during late infancy plays an important role in the development of cognitive function. Together, these findings suggest that microglia shift their sensitivity to early life insults across development. Our findings also highlight the potential for MS to impact some developmental processes only when compounded with additional neuroimmune challenges in a sex-dependent manner.

Comparing the effectiveness of CBT and low-frequency rTMS in reducing symptom severity and depression and improving working memory in adults with OCD: a clinical trial

Objective This study aims to compare the effectiveness of cognitive-behavioral therapy (CBT) and low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) in reducing symptom severity and depression and improving working memory in adults with obsessive–compulsive disorder (OCD). Methods This is a randomized clinical trial conducted on 24 adults with OCD, randomly assigned into two groups of CBT (n = 12, received CBT with exposure and response prevention (ERP) individually at 20 sessions) and rTMS (n = 12, received LF (1-Hz) rTMS over the right dorsolateral prefrontal cortex (DLPFC) at 10 sessions). They completed the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, and two N-Back tasks before, immediately, and 1 month after interventions. Results Results showed a significant difference between the two methods in reducing the severity of OCD symptoms (p < 0.05) and depression (p = 0.002) immediately after interventions where the CBT with ERP was more effective, but no significant difference was found in terms of working memory (p > 0.05). No significant difference was found between groups in any study variables 1 month after interventions. Conclusion Individual CBT with ERP is superior to LF rTMS for reducing the severity of symptoms and depression in OCD patients. However, there is no difference between them in improving working memory.

Differences in auditory verbal working memory between adults who do and do not stutter on an N-back task

PurposeThe purpose of this study was to investigate auditory verbal working memory in adults who do (AWS) and do not (AWNS) stutter using a highly demanding linguistic N-back task. MethodsFifteen AWS and 15 AWNS matched in age, gender and educational level were asked to hear series of words and respond by pressing a “yes” button if the word they just heard was the same as the word one, two, or three trials back. Words were either phonologically similar (i.e., Phonological Linguistic Condition) or phonologically dissimilar (i.e., Neutral Linguistic Condition). Accuracy and false alarms rates as well as reaction time on correct target trials, missed target trials and false alarms were collected and analyzed. ResultsDifferences were not found between AWS and AWNS in accuracy. Both groups were more accurate and significantly faster in 1- followed by 2- followed by 3-back trials. However, AWS were significantly slower than AWNS in the 2-back level, regardless of linguistic condition. Furthermore, AWS demonstrated more false alarms compared to AWNS. ConclusionResults revealed differences in auditory verbal working memory and interference control between AWS and AWNS when processing highly linguistically demanding stimuli.

Complex working memory in adults with and without stuttering disorders: Performance patterns and predictive relationships

PurposeAvailable studies of working memory (WM) in speakers who stutter tend to rely on parent report, focus on phonological WM, or measure WM in combination with other processes. The present research aimed to: (1) compare complex WM in adults who stutter (AWS) and adults who do not stutter (AWNS); (2) characterize group performance patterns; and (2) determine whether WM predicts stuttering severity. MethodsEighteen AWS and 20 AWNS completed parallel verbal and spatial span tasks in which to-be-remembered items were interleaved with a distracting task across varying set sizes. Dependent variables included the number of correctly recalled items, accuracy on distraction tasks, and detailed analyses of item-level responses. We further examined whether span scores predicted subjective and objective measures of stuttering severity. ResultsRelative to AWNS, AWS showed poorer recall, specifically on short set sizes in the spatial task. Groups performed similarly on distraction tasks and showed comparable error patterns. Predictive relationships differed by span task and severity measure. Lower verbal span scores predicted greater stuttering impact and more overt stuttering behaviors; lower spatial span scores predicted lower impact and was unrelated to overt behaviors. ConclusionsFindings suggest that AWS differ subtly from AWNS in WM performance. Group differences became more apparent under certain task conditions but could not be attributed to specific underlying processes. Data further indicated a complex relationship between WM and stuttering severity. Overall, results corroborate previous studies linking stuttering to domain-general weaknesses, but highlight the need for additional research to clarify the nature of this relationship.

Associations between nesting, stereotypy, and working memory in deer mice: response to levetiracetam

BackgroundSome deer mice (Peromyscus maniculatus bairdii) exhibit various phenotypes of persistent behaviors. It remains unknown if and how said phenotypes associate with early-life and adult cognitive perturbations, and whether potentially cognitive enhancing drugs might modify such associations. Here, we explored the longitudinal relationship between early-life behavioral flexibility and the expression of persistent behavior in adulthood. We also investigated how said phenotypes might associate with working memory in adulthood, and how this association might respond to chronic exposure to the putative cognitive enhancer, levetiracetam (LEV).Methods76 juvenile deer mice were assessed for habit-proneness in the Barnes maze (BM) and divided into two exposure groups (n = 37–39 per group), i.e., control and LEV (75 mg/kg/day). After 56 days of uninterrupted exposure, mice were screened for nesting and stereotypical behavior, and then assessed for working memory in the T-maze.ResultsJuvenile deer mice overwhelmingly utilize habit-like response strategies, regardless of LNB and HS behavior in adulthood. Further, LNB and HS are unrelated in terms of their expression, while LEV reduces the expression of LNB, but bolsters CR (but not VA). Last, an increased level of control over high stereotypical expression may facilitate improved working memory performance.ConclusionLNB, VA and CR, are divergent in terms of their neurocognitive underpinnings. Chronic LEV administration throughout the entire rearing period may be of benefit to some phenotypes, e.g., LNB, but not others (CR). We also show that an increased level of control over the expression of stereotypy may facilitate improved working memory performance.

Glycemic control level alters working memory neural dynamics in adults with type 2 diabetes.

Poor glycemic control in type 2 diabetes has been associated with accentuated age-related cognitive decline, although the underlying neural mechanisms are not well understood. The current study sought to identify the impact of glycemic control on the neural dynamics serving working memory in adults with type 2 diabetes. Participants (n = 34, ages = 55-73) performed a working memory task while undergoing MEG. Significant neural responses were examined relative to poorer (A1c > 7.0%) or tighter glycemic control (A1c < 7.0%). Those with poorer glycemic control showed diminished responses within left temporal and prefrontal regions during encoding and showed diminished responses within right occipital cortex during maintenance but showed an enhanced activity in the left temporal, occipital, and cerebellar regions during maintenance. Notably, left temporal activity in encoding and left lateral occipital activity in maintenance significantly predicted performance on the task such that diminished temporal activity led to longer reaction times, which were driven by the poorer glycemic control group. Greater lateral occipital activity during maintenance was associated with both lower accuracy and longer reaction times across all participants. These findings suggest that glycemic control has a robust impact on the neural dynamics serving working memory, with distinct effects by subprocess (e.g. encoding vs. maintenance) and direct effects on behavior.

Comparing visual and auditory working memory in adults with stutter and normal adults

Comparing visual and auditory working memory in adults with stutter and normal adults

Individual differences in executive attention and inhibitory control are related to spatial memory biases in adults.

Executive attention is involved in working memory; however, the role of executive attention in the maintenance of information in spatial working memory is debated. This study examined whether inhibitory control was related to spatial working memory biases in adults in a simple spatial memory task where participants had to remember one location on an otherwise blank computer screen. On some trials, a distractor was presented during the maintenance period. Eighty-four participants completed the spatial working memory task and a battery of cognitive control measures. When a distractor was presented during the maintenance period of the spatial memory task, performance on two of the cognitive control measures, a measure of overall attention and a measure of inhibitory control was related to memory errors. When a distractor was not presented during the spatial memory task, memory errors were not related to performance on the cognitive control tasks. Overall, these effects demonstrated that attention is related to maintaining locations in spatial working memory in adults, and inhibitory control may also be related such that those with more efficient inhibitory control were less influenced by distractors presented during the maintenance period.

MGlu1 Activation Reverses Persistent Deficits in Prefrontal Cortex Inhibitory Transmission and Working Memory Induced by Adolescent Cocaine Exposure

The prefrontal cortex (PFC), a brain region central to cognitive processes such as working memory, and executive function, undergoes complex structural and functional maturation across adolescence, rendering it particularly vulnerable to disruption by external events. Exposure to psychostimulants, such as cocaine, during adolescence produces persistent changes in PFC structure and function which parallel cognitive deficits seen in adulthood. However, the mechanisms of how drug exposure during critical developmental periods alter PFC function and cognition performance in adulthood are not fully understood. Extensive evidence suggests that the balance between excitatory and inhibitory neurotransmission in the PFC plays a fundamental role in many cognitive processes. Furthermore, adolescent exposure to psychostimulants impairs GABA interneuron function and inhibitory transmission in the PFC in adulthood, suggesting that enhancing PFC inhibitory transmission may be a promising strategy to mitigate drug‐induced cognitive deficits observed later in life. Recently, we found that activation of the mGlu1 subtype of metabotropic glutamate receptor increases PFC inhibitory transmission and working memory by selective excitation of somatostatin‐expressing GABA interneurons (SST‐INs), highlighting mGlu1 as a novel target for restoring inhibitory transmission in the PFC and enhancing cognition. These findings lead us to hypothesize that repeated exposure to cocaine during a critical developmental period in adolescence disrupts inhibitory transmission in the PFC via SST‐INs and that this contributes to working memory impairments in adulthood. We further propose that selective activation of mGlu1 with highly selective positive allosteric modulators (PAMs) will reverse cocaine‐induced physiological and behavioral deficits.Here, we leveraged transgenic mouse lines in combination with whole‐cell patch‐clamp electrophysiology, maze‐ and touchscreen‐based automated cognition testing. We found that repeated administration of cocaine during a critical adolescent period (PND 35‐42) significantly impaired PFC SST‐IN, but not parvalbumin‐expressing interneuron (PV‐IN), firing compared to saline‐treated mice. Additionally, adolescent cocaine exposure significantly decreased the frequency of spontaneous excitatory postsynaptic currents onto SST‐INs but not PV‐INs. In parallel, adolescent cocaine‐induced impairments in spatial working memory in adulthood. Importantly, these physiological and behavioral effects of adolescent cocaine exposure were reversed by selective mGlu1 activation. Lastly, repeated amphetamine administration during the same adolescent critical period did not impair SST‐IN function or working memory in adulthood. In sum, these findings provide strong evidence that: 1) cocaine exposure during an adolescent critical period induces persistent and selective deficits in PFC SST‐IN function and spatial working memory in adulthood and 2) selective activation of mGlu1 with PAMs represents a promising novel strategy for reversing cocaine‐induced cognitive impairments.

Prenatal earthquake stress exposure in different gestational trimesters is associated with methylation changes in the glucocorticoid receptor gene (NR3C1) and long-term working memory in adulthood

Prenatal stress exposure is thought to affect the long-term development of the foetal brain via the HPA axis and to change health outcomes in adulthood, including working memory (WM). The potential mechanism is that there is a critical period of brain development of the foetus, which is a result of selective adaptation to the external environment. The human glucocorticoid gene (NR3C1) is associated with memory and cognition. This study investigates the association between earthquake stress during pregnancy and CpG methylation of the NR3C1 exon 1F promoter and its influence on working memory in adulthood. DNA methylation analysis using bisulfite sequencing PCR was quantified in 176 subjects who were exposed or not exposed to intrauterine earthquake and were divided into three groups based on the pregnancy trimester. The Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) were used to assess working memory performance. The methylated NR3C1 exon 1F promoter of the prenatal earthquake exposure (PEE) group was significantly higher than that of the control group (CN). Analysis of subgroups indicated that the subjects in the second trimester of PEE group showed significantly higher methylation than those in the third trimester. Significantly low BVMT-R scores were detected in those who experienced prenatal earthquake in the second trimester of PEE group. Methylated CpG site 1 may play a critical role in contributing to lower BVMT-R scores in the second trimester in the PEE group, and may offer a potential epigenetic mechanism that links prenatal stress and long-term effects on working memory.

Fish oil supplementation may improve attention, working memory and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: a randomised crossover trial.

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2 × 4 week crossover study, twenty-six participants were randomised to sequence of supplementation with fish oil (FO, 5·2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15 %. Compliance was 94 % and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0·3 × sd (P = 0·032) after FO v. SO, and the odds for d2 errors were 30 % lower (P = 0·016), which was supported by improved Conners scores of attention (P = 0·023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3·5(-6·0; -1·0), n 10 v. -0·2(-2·5;2·2), n 11 without ADHD, Pinteraction = 0·096), who also improved their behavioural regulation index by 0·3 × sd after FO (Pinteraction = 0·016). Participants without ADHD gained most in d2 test performance (OR = 0·4(0·2;0·7) v. 0·9(0·6;1·3) in those with ADHD, Pinteraction = 0·002), but their executive function score was exacerbated after FO (5·9(0·0,11·8), Pinteraction = 0·039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.

Neonatal blockade of NR2A-containing but not NR2B-containing NMDA receptor induces spatial working memory deficits in adult rats

The immature brain is highly sensitive to disturbances in the functioning of N-methyl-d-aspartate (NMDA) receptor in rodents, and blockade of the receptor during postnatal brain development period causes schizophrenia-like behavior in adulthood. During the postnatal period, NR2A- and NR2B-containing NMDA receptors are highly expressed, and these two subunits show different expression patterns in the brain. However, the functions of these two NMDA receptors are unknown. In this study, we treated rats with an NR2A-preferring NMDA receptor antagonist (PEAQX, 10 mg/kg), an NR2B-selective NMDA receptor antagonist (ifenprodil, 7.5 mg/kg), or a nonselective blocker of the NMDA receptor (MK-801, 0.4 mg/kg) during the neonatal period. Rats neonatally treated with MK-801 or PEAQX showed spatial working memory deficits in the Y-maze test. PEAQX-treated rats also showed greater reactivity to acoustic stimuli and hypersensitivity to acute MK-801 challenge. However, ifenprodil treatment did not cause any detectable behavioral changes. These results suggest that the NR2A-containing NMDA receptor is indispensable for proper brain development in rats, and functional disturbances in this subunit impair hippocampus-dependent spatial working memory in adulthood.

Early childhood poverty and adult executive functioning: Distinct, mediating pathways for different domains of executive functioning.

Executive functioning in adulthood is associated with early-in-life disadvantage. Furthermore, distinct and independent underlying processes account for differences in specific domains of adult executive functioning. The duration of poverty from birth to age 9 is associated with reduced adult inhibitory control assessed by the Flanker task (n=233, M=23.52years). This effect is largely explained by lower levels of maternal responsiveness in adolescence. Early poverty also related to worse working memory in adulthood, and this effect is partially explained by elevated allostatic load during adolescence, an index of chronic physiological stress.

Semantic knowledge influences visual working memory in adults and children.

We can retain only a portion of the visual information that we encounter within our visual working memory. Which factors influence how much information we can remember? Recent studies have demonstrated that the capacity of visual working memory is influenced by the type of information to be remembered and is greater for real-world objects than for abstract stimuli. One explanation for this effect is that the semantic knowledge associated with real-world objects makes them easier to maintain in working memory. Previous studies have indirectly tested this proposal and led to inconsistent conclusions. Here, we directly tested whether semantic knowledge confers a benefit for visual working memory by using familiar and unfamiliar real-world objects. We found a mnemonic benefit for familiar objects in adults and children between the ages of 4 and 9 years. Control conditions ruled out alternative explanations, namely the possibility that the familiar objects could be more easily labeled or that there were differences in low-level visual features between the two types of objects. Together, these findings demonstrate that semantic knowledge influences visual working memory, which suggests that the capacity of visual working memory is not fixed but instead fluctuates depending on what has to be remembered.

Music Training, Working Memory, and Neural Oscillations: A Review.

This review focuses on reports that link music training to working memory and neural oscillations. Music training is increasingly associated with improvement in working memory, which is strongly related to both localized and distributed patterns of neural oscillations. Importantly, there is a small but growing number of reports of relationships between music training, working memory, and neural oscillations in adults. Taken together, these studies make important contributions to our understanding of the neural mechanisms that support effects of music training on behavioral measures of executive functions. In addition, they reveal gaps in our knowledge that hold promise for further investigation. The current review is divided into the main sections that follow: (1) discussion of behavioral measures of working memory, and effects of music training on working memory in adults; (2) relationships between music training and neural oscillations during temporal stages of working memory; (3) relationships between music training and working memory in children; (4) relationships between music training and working memory in older adults; and (5) effects of entrainment of neural oscillations on cognitive processing. We conclude that the study of neural oscillations is proving useful in elucidating the neural mechanisms of relationships between music training and the temporal stages of working memory. Moreover, a lifespan approach to these studies will likely reveal strategies to improve and maintain executive function during development and aging.

New virtual reality tool (Nesplora Aquarium) for assessing attention and working memory in adults: A normative study

Attentional and working memory (WM) processes undergo significant changes during different stages of development. However, currently there are not many continuous performance tools based on virtual reality (VR) for measuring attentional capacity in adults. The present study aimed to obtain normative data for the Nesplora Aquarium VR test in a Spanish population, looking at sex and age variables. In addition, this study also aimed to analyze the psychometric properties of the tool such as scale, internal consistency, and item difficulty and discrimination indices. A total of 1,469 participants from different regions of Spain (57.6% female) with ages ranging from 16 to 90 years old took part in this normative study. Nesplora Aquarium was developed in order to support clinicians in the assessment of attentional processes and WM in adults over 16 years old. It is an 18-minute individual test performed through a VR system. The system provides better visual and auditory immersion in the task than computerized CPTs. This study revealed that the new VR tool, designed to measure adult attention and working memory levels, exhibited good psychometric properties related to reliability and internal consistency. In addition, item difficulty and discrimination values were also acceptable.

Moderate developmental alcohol exposure reduces repetitive alternation in a zebrafish model of fetal alcohol spectrum disorders

The damaging effects of alcohol on a developing fetus are well known and cause a range of conditions known as fetal alcohol spectrum disorder (FASD). High levels of alcohol exposure lead to physical deformity and severe cognitive deficits, but more moderate exposure leads to a range of subtle cognitive effects such as reduced social behavior, higher propensity to develop addictions, and reduced spatial working memory. Previous studies have demonstrated that following exposure to relatively low levels of ethanol during early brain development (equivalent in humans to moderate exposure) zebrafish display a range of social and behavioral differences. Here, our aim was to test the hypothesis that moderate developmental ethanol exposure would affect aspects of learning and memory in zebrafish. In order to do this, we exposed zebrafish embryos to 20 mM [0.12% v/v] ethanol from 2 to 9 dpf to model the effects of moderate prenatal ethanol (MPE) exposure. At 3 months old, adult fish were tested for appetitive and aversive learning, and for spatial alternation in a novel unconditioned y-maze protocol. We found that MPE did not affect appetitive or aversive learning, but exposed-fish showed a robust reduction in repetitive alternations in the y-maze when compared to age matched controls. This study confirms that moderate levels of ethanol exposure to developing embryos have subtle effects on spatial working memory in adulthood. Our data thus suggest that zebrafish may be a promising model system for studying the effects of alcohol on learning and decision-making, but also for developing treatments and interventions to reduce the negative effects of prenatal alcohol.

Polish Listening SPAN: A new tool for measuring verbal working memory

Individual differences in second language acquisition (SLA) encompass differences in working memory capacity, which is believed to be one of the most crucial factors influencing language learning. However, in Poland research on the role of working memory in SLA is scarce due to a lack of proper Polish instruments for measuring this construct. The purpose of this paper is to discuss the process of construction and validation of the Polish Listening Span (PLSPAN) as a tool intended to measure verbal working memory of adults. The article presents the requisite theoretical background as well as the information about the PLSPAN, that is, the structure of the test, the scoring procedures and the steps taken with the aim of validating it.