Working Memory Performance Research Articles

Results from a randomized controlled trial of zonisamide in the treatment of alcohol use disorder

There is preliminary evidence that the anticonvulsant medication Zonisamide (ZON) may be an effective, well-tolerated treatment for alcohol use disorder (AUD). However, further evaluation of its efficacy for treating patients with AUD is needed, and much remains unknown about ZON’s therapeutic mechanisms. The present study aimed to evaluate the efficacy and tolerability of ZON in a double-blind, placebo-controlled, randomized trial. Eighty-one adults (ages 21-65) diagnosed with AUD were randomly assigned to receive either ZON (at a target dose of 400 mg/d) or a pill placebo over 12 weeks, followed by a two-week taper. All participants also received a computerized alcohol reduction program, Take Control (TC). Primary drinking outcomes were average daily drinks, percentage drinking days, and percentage heavy drinking days. Further, we evaluated changes in AUD clinical severity and performance on neuropsychological measures. For both groups, drinking outcomes generally decreased, as did AUD clinical severity, though group differences were not statistically significant. Neuropsychological testing performance was similar for both groups at baseline; however, at post-treatment, participants in the ZON group demonstrated poorer working memory and lower performance on verbal fluency tests compared to the placebo group, and these differences were statistically significant with moderate-large effect sizes. One serious adverse event was reported among individuals receiving ZON. Study findings indicate that ZON combined with TC does not demonstrate superior effectiveness for reducing average daily drinks in this clinical sample with principal AUD compared to placebo and TC, and treatment with ZON may be associated with reduced neurocognitive performance over time.

Visual Working Memory in Adolescents with Autism Spectrum Disorder.

Previous research suggests that individuals with autism spectrum disorder (ASD) may experience working memory (WM) problems, but the nature of the underlying disruption remains unknown. A recent study (Bodner et al. 2019) found that young adults with ASD experienced intact WM capacity but disruptions in their ability to efficiently filter and allocate attention. The goal of the present study was to extend this work and evaluate potential disruptions in WM capacity and attentional allocation ability in adolescents with ASD. A sample of 38 adolescents with ASD and 39 adolescents without ASD aged 11-15 years completed a computerized WM task. In brief, participants were shown visual arrays consisting of four or six colored stimuli (circles and squares). After a short delay, memory for one of the stimuli was probed. Importantly, participants were informed beforehand that one of the shapes (e.g., circles) was more likely to be probed compared to the other shape (e.g., squares) - thus making it strategically beneficial to focus primarily on the high frequency shapes. The ASD group demonstrated overall lower WM capacity compared to the non-ASD group. However, no group differences were seen in attentional allocation. There was also no evidence of sex-related differences in WM performance in adolescents with ASD. Taken together with previous findings, the current results suggest that adolescents with ASD show disruptions in WM capacity that are resolved by adulthood. Future longitudinal research is needed to further disentangle the component processes of WM and the developmental trajectories of these components.

Cortex level connectivity between ACT-R modules during EEG-based n-back task

AbstractFinding the synchronization between Electroencephalography (EEG) and human cognition is an essential aspect of cognitive neuroscience. Adaptive Control of Thought-Rational (ACT-R) is a widely used cognitive architecture that defines the cognitive and perceptual operations of the human mind. This study combines the ACT-R and EEG-based cortex-level connectivity to highlight the relationship between ACT-R modules during the EEG-based n-back task (for validating working memory performance). Initially, the source localization method is performed on the EEG signal, and the mapping between ACT-R modules and corresponding brain scouts (on the cortex surface) is performed. Once the brain scouts are identified for ACT-R modules, then those scouts are called ACT-R scouts. The linear (Granger Causality: GC) and non-linear effective connectivity (Multivariate Transfer Entropy: MTE) methods are applied over the scouts’ time series data. From the GC and MTE analysis, for all n-back tasks, information flow is observed from the visual-to-imaginal ACT-R scout for storing the visual stimuli (i.e., input letter) in short-term memory. For 2 and 3-back tasks, causal flow exists from imaginal to retrieval ACT-R scout and vice-versa. Causal flow from procedural to the imaginal ACT-R scout is also observed for all workload levels to execute the set of productions. Identifying the relationship among ACT-R modules through scout-level connectivity in the cortical surface facilitates the effects of human cognition in terms of brain dynamics.

Improving cognitive function in Chinese children with ADHD and/or RD through computerized working memory training

BackgroundPrior research has found that children with attention-deficit hyperactivity disorder (ADHD) and reading difficulties (RD) are at an elevated risk of developing further cognitive deficits and developmental challenges [1]. ADHD and RD are characterized by a deficit in working memory, which negatively affects learning and behavior. The main aims of this study were to design a working memory training app and examine its effectiveness through a 5-week training program in Chinese children with ADHD and/or RD.MethodsThere were three experimental groups, with 26 participants in the ADHD group, 38 participants in the RD group, and 24 participants in the ADHD + RD group. The typically developing (TD) control group had 32 participants. All participants completed the pretest and posttest assessments on executive function and reading performance.ResultsThe findings indicate that the experimental groups improved performance in verbal and visual-spatial working memory as well as Chinese word reading. There was an overall reduction in functional impairment following the training, in contrast to the TD group.ConclusionThis study showed that working memory can be improved through computerized training in children with ADHD and/or RD. The implications of future research in working memory are discussed.Trial registrationClinical Trials Identifier: NCT06567444 (retrospectively registered) on 20 August 2024.

Maternal trauma exposure is linked to adult offspring's cognitive functioning in the context of mass violence.

This study aimed to examine whether mothers' level of trauma exposure and posttraumatic stress disorder (PTSD) symptoms are related to their offspring's cognitive functioning. Mothers exposed to the 1994 genocide perpetrated against the Tutsi (N = 181) and one of their adult offspring were recruited in Rwanda. Mothers and their offspring answered questionnaires on sociodemographic information, the level of trauma exposure, and PTSD symptoms. They also performed a backward digit span task and a similarity task to assess their working memory and abstract reasoning, respectively. Hierarchical regression models were used to analyze the data. Mothers' level of trauma exposure, but not PTSD symptoms, was significantly related to their offspring's abstract reasoning performance after controlling for offspring's age, sex, and economic status. The relationship between mothers' level of trauma exposure, PTSD symptoms, and their offspring's working memory performance was not significant. Offspring's education was significantly linked to their working memory and abstract reasoning performance. The findings demonstrate that the intergenerational transmission of trauma can impact the cognitive functioning of the next generation. These results also illustrate the profound and long-term human impact of mass violence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Theta-gamma-coupling as predictor of working memory performance in young and elderly healthy people

The relationship between working memory (WM) and neuronal oscillations can be studied in detail using brain stimulation techniques, which provide a method for modulating these oscillations and thus influencing WM. The endogenous coupling between the amplitude of gamma oscillations and the phase of theta oscillations is crucial for cognitive control. Theta/gamma peak-coupled transcranial alternating current stimulation (TGCp-tACS) can modulate this coupling and thus influence WM performance. This study investigated the effects of TGCp-tACS on WM in older adults and compared their responses with those of younger participants from our previous work who underwent the same experimental design. Twenty-eight older subjects underwent both TGCp-tACS and sham stimulation sessions at least 72 h apart. Resting-state electroencephalography (EEG) was recorded before and after the interventions, and a WM task battery with five different WM tasks was performed during the interventions to assess various WM components. Outcomes measured included WM task performance (e.g., accuracy, reaction time (RT)) and changes in power spectral density (PSD) in different frequency bands. TGCp-tACS significantly decreased accuracy and RT on the 10- and 14-point Sternberg tasks and increased RT on the Digit Symbol Substitution Test in older adults. In contrast, younger participants showed a significant increase in accuracy only on the 14-item Sternberg task. Electrophysiological analysis revealed a decrease in delta and theta PSD and an increase in high gamma PSD in both younger and older participants after verum stimulation. In conclusion, theta-gamma coupling is essential for WM and modulation of this coupling affects WM performance. The effects of TGCp-tACS on WM vary with age due to natural brain changes. To better support older adults, the study suggests several strategies to improve cognitive function, including: Adjusting stimulation parameters, applying stimulation to two sites, conducting multiple sessions, and using brain imaging techniques for precise targeting.

Differing effectiveness of transcranial random noise stimulation and transcranial direct current stimulation for enhancing working memory in healthy individuals: a randomized controlled trial

BackgroundTranscranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (DLPFC) is a promising technique for enhancing working memory (WM) performance in healthy and psychiatric populations. However, limited information is available about the effectiveness of transcranial random noise stimulation (tRNS) applied to the left DLPFC on WM. This study investigated the effectiveness of tRNS on WM compared with that of tDCS, which has established functional evidence.MethodsThis randomized, double-blind, sham-controlled trial enrolled 120 healthy right-handed adults who were randomly allocated to four stimulation groups: tRNS + direct current (DC) offset, tRNS, tDCS, or sham. Each stimulus was placed over the left DLPFC and had a current intensity of 2 mA applied for 20 min during the dual n-back task. The dual n-back task was repeated thrice: pre-stimulation, during stimulation, and post-stimulation. The d-prime scores, and response times were calculated as the main outcome measures. A linear mixed model was created to identify the main effects and interactions between the groups and times, with the group and time as fixed effects, and baseline performance and the subject as a covariate and random effect, respectively. The relationships between the benefit of each stimulus and baseline WM performance were also examined.ResultsFor the d-prime score during stimulation, the tRNS group significantly performed better than the sham group at online assessment (β = 0.310, p = 0.001). In the relationships between the benefit of each stimulus and baseline WM performance, the tRNS group had significantly larger negative line slopes than the sham group for the d-prime score (β = −0.233, p = 0.038).ConclusionstRNS applied to the left DLPFC significantly improved WM performance and generated greater benefits for healthy individuals with lower WM performance. These findings highlight the potential utility of tRNS for enhancing WM performance in individuals with lower WM performance and contribute evidence for clinical application to patients with cognitive decline.Trial RegistrationThis study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000047365) on April 1, 2022; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054021.

Verbal and Spatial Working Memory Capacity in Blind Adults and the Possible Influence of Age at Blindness Onset: A Systematic Review and Meta-analysis.

The loss of a sense, such as vision, forces individuals to adapt to their environment and its demands in a variety of ways. In the case of blindness, significant neurofunctional and cognitive changes have been documented. However, there is no clear consensus on the differences in performance between adult blind participants and sighted controls in cognitive processes such as working memory (WM). Two variables are important, including the cognitive task used to measure working memory and the age at which vision loss occurs. This review is aimed at exploring potential disparities in verbal and spatial WM performance between blind and sighted adults, as well as understanding how these differences may be influenced by the age of vision loss. A systematic search across PsycArticles, PsycInfo, Medline, and Web of Science databases identified 21 pertinent studies. The studies were categorized, and effect sizes were calculated through meta-analysis, distinguishing between verbal (auditory simple forward and backward span, complex span, and n-back) and visuospatial WM tasks (adapted Corsi-block and simple storage tasks, imagery tasks, and complex storage tasks). Visual sensory loss induces adaptations affecting WM function in blind participants. In the verbal domain, improved phonological processing and/or serial item position encoding might facilitate WM retrieval. In contrast, in spatial WM, an over-reliance on serial processing may hinder strategic grouping in blind individuals. This review highlights the need to further explore the role of age at the time of vision loss. Although evidence suggests that adaptations to serial processing may be more pronounced in early development, particularly in comparison to those who become blind in adulthood, the available data are limited. The study calls for further research to deepen our understanding of cognitive adaptations and their temporal dynamics in response to vision loss.

Association between working memory performance and parent and teacher ratings of working memory in 11-year-old children born preterm

ABSTRACT Working memory (WM) difficulties are often observed in children born preterm. We examined whether performance-based measures of WM components are associated with parent- and teacher-rated WM difficulties in the everyday life of children born very preterm and/or at very low birth weight (VPT/VLBW) at 11 years (n = 165). The WM components as defined in the original Baddeley’s model – phonological loop (PL), visuospatial sketchpad (VS), and central executive (CE) – were assessed with tasks from the Working Memory Test Battery for Children (WMTB-C) and the Wechsler Intelligence Scale for Children – Fourth edition (WISC-IV). Parents and teachers completed the WM subscale of the Behavioral Rating Inventory for Executive Functions (BRIEF). Measures of WM components were modestly associated with BRIEF scores, explaining 18.9% of the variance in parent-rated and 14.0% of teacher-rated WM difficulties. CE was the component most consistently associated with parent- and teacher-rated everyday WM. To conclude, our results suggest that tasks that utilize CE functions may best reflect WM outside of controlled test settings in the follow-up of VPT/VLBW children. However, performance and rating-scale measures provide unique information and are both needed to comprehensively assess WM skills.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Examination of Congruity between Subjective and Objective Working Memory in Veterans with Mild TBI and Relation to Psychiatric Symptoms and Childhood Trauma.

There is conflicting evidence regarding congruence between subjective cognitive decline and objective cognitive performance for individuals with a history of mild traumatic brain injury (mTBI). The current study investigated the congruity between subjective and objective cognition, particularly working memory, among veterans with an mTBI history, accounting for post-traumatic stress disorder (PTSD) and childhood trauma. Participants included 35 veterans with a history of mTBI sustained during deployment. Participants completed measures of subjective [i.e., Behavioral Inventory Rating of Executive Functioning (BRIEF)] and objective working memory (i.e., WAIS-IV working memory index). Congruity between subjective and objective working memory was examined using linear regression. Bonferroni-corrected correlations were run to explore relationships among working memory, psychiatric symptoms, mTBI severity, and childhood trauma. Among Veterans with mTBI, subjective working memory and objective working memory performance were not significantly related (p > 0.05); however, the overall model was significant (p < 0.0001), and childhood trauma was a notable predictor (p = 0.02). Greater PTSD, depression, and sleep symptoms were significantly related to increased subjective working memory concerns, even after Bonferroni adjustments (ps < 0.0001). Better objective working memory was significantly related to a fewer number of childhood traumatic events; however, this did not sustain corrections. The majority of individuals (67%) endorsed significant working memory complaints, despite objectively performing within normal limits (within 1 SD and above). Subjective-objective working memory congruity among veterans with mTBI was limited. Subjective, but not objective, working memory concerns were associated with greater PTSD, depression, and sleep symptoms. Childhood trauma was a notable factor that contributed to both subjective and objective cognitive concerns. There remains clinical value in assessing subjective cognitive concerns given the strong relationships with psychiatric problems and, hence, a focus for intervention.

Meaning-Centred Coping Predicted Lower Depressive Symptoms among Caregivers with Complicated Grief.

Complicated grief is characterised by persistent low mood, intense distress and cognitive impairment. This study aimed to explore coping strategies (i.e. emotion-, problem- and meaning-centred) used by bereaved individuals facing complicated grief and how these strategies may predict psychological and cognitive outcomes. In a cross-sectional study, 20 bereaved individuals (5 males, 15 females) that aged 27 years old-65 years old (mean = 42.25, standard deviation [SD] = 9.30) were recruited following the loss of a loved one due to physical illness. Participants were screened for complicated grief and subsequently completed self-report assessments of coping strategies and depressive symptoms using Brief Grief Questionnaire (BGQ), Brief Coping Orientation to Problems Experienced (COPE) Questionnaire, Meaning-Centered Coping Scale (MCCS) and Patient Health Questionnaire-9 Items (PHQ-9). Following that, participants underwent a neurocognitive assessment of working memory using the 2-Back task. Caregivers with complicated grief suffered from moderate severity of depressive symptoms (mean = 17.45, SD = 4.43) as they were coping with the losses. Furthermore, the findings showed that MCC significantly predicted lower levels of depressive symptoms (b = -0.50, t (16) = -2.25, P = 0.04). However, coping strategies did not significantly predict working memory performance. These findings highlight the potential benefits of MCC in alleviating depressive symptoms in bereaved individuals and underscore its contribution to the development of grief interventions. Grief therapists can emphasise this coping strategy to promote healing and resilience in patients in the grief work.

Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.

Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking. Adult male rats were trained to perform a "simple" or "complex" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression. Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence. These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.

Effect of negative emotional stimuli on working memory: Impact of voluntary and automatic attention.

Emotions are known to influence cognitive performance, particularly working memory (WM) in both its aspects, processing, and maintenance. One explanatory mechanism might be that negative stimuli capture attentional resources, leaving fewer resources for attentional maintenance and processing of information in WM. However, this attentional capture was only investigated using WM tasks in which participants were explicitly asked to process negative items. The aim of this paper was to determine whether explicit processing of emotional stimuli is necessary to impair WM performance, or if their mere presence is enough to capture attention. For this purpose, participants performed a complex span task in which they alternated between memorizing a series of neutral words and processing either emotional images or neutral ones. In Experiment 1, participants were instructed to explicitly process emotional images, whereas in Experiment 2, emotional images were presented without any processing being required. In both experiments, we observed a decrease in memory performance when the images were negative compared to neutral. Whether or not voluntary processing is involved, emotional images seem to capture attentional resources, which in turn leads to a decline in memory performance. These results were discussed in relation to attentional theories and the influence of emotion on the specific mechanisms of WM.

Inhibitory control and working memory predict rhythm production abilities in patients with neurocognitive deficits

Deficits in rhythm perception and production have been reported in a variety of psychiatric, neurodevelopmental and neurologic disorders. Since correlations between rhythmic abilities and cognitive functions have been demonstrated in neurotypical individuals, we here investigate whether and how rhythmic abilities are associated with cognitive functions in 35 participants with neurocognitive deficits due to acquired brain lesions. We systematically assessed a diverse set of rhythm perception and production abilities including time and beat perception and finger-tapping tasks. Neuropsychological tests were applied to assess separable cognitive functions. Using multiple regression analyses we show that lower variability in aligning movements to a pacing sequence was predicted by better inhibitory control and better working memory performance. Working memory performance also predicted lower variability of rhythmic movements in the absence of an external pacing sequence and better anticipatory timing to sequences with gradual tempo changes. Importantly, these predictors remained significant for all regression models when controlling for other cognitive variables (i.e., cognitive flexibility, information processing speed, and verbal learning ability) and potential confounders (i.e., age, symptom strength of depression, manual dexterity, duration of illness, severity of cognitive impairment, and musical experience). Thus, all rhythm production abilities were significantly predicted by measures of executive functions. In contrast, rhythm perception abilities (time perception/beat perception) were not predicted by executive functions in this study. Our results, enhancing the understanding of cognitive underpinnings of rhythmic abilities in individuals with neurocognitive deficits, may be a first mandatory step to further potential therapeutic implications of rhythm-based interventions in neuropsychological rehabilitation.

A proposed methodology for measuring the effects of binaural beats in music on concentration, working memory, and calmness following the Garcia-Argibay Protocol

Binaural beats are perceived when two different frequencies are presented dichotically to a listener, causing the perception of a beating sound. They have been associated with beneficial effects on cognitive functions such as learning, concentration, and creativity. Studies however often yield incomparable or inconclusive results, due to inconsistent methodologies. Through a systematic examination, following the Garcia-Argibay Protocol, we aim to provide a more detailed understanding of the effects of binaural beats in music on cognitive functions. Specifically, we will compare auditory stimulation with music containing binaural beats of the alpha and gamma frequencies to a control condition presenting music without binaural beats. We will measure the differential effect of 12 Hz and 40 Hz binaural beats on working memory performance, operationalized through the N-back task, and investigate the impact of these frequencies on concentration levels measured via the global-local task. Lastly, heart rate will be used as a continuous measurement throughout the experiment in order to evaluate the effectiveness of the different frequencies in inducing calmness.

Eye-tracking training improves visuospatial working memory of children with attention-deficit/hyperactivity disorder and autism spectrum disorder.

Given the close connection between eye movement and frontal lobe functions and some evidence supporting the effect of eye-tracking training on enhancing cognitive performance mediated by the frontal lobe, this study aimed to explore if after-school eye-tracking training can improve the visuospatial working memory (VSWM) and cognitive flexibility performance in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). This study is a non-randomized cluster trial. Forty children from eight primary schools were selected, half receiving eye-tracking training for 20 sessions over 9 months, while the other half served as a waitlist control. They were matched on demographic characteristics and baseline cognitive performance. Their VSWM and cognitive flexibility were assessed at the beginning and end of the study. Results showed that children who received eye-tracking training, but not those on a waitlist, exhibited significant improvements in the total score and working memory span of the VSWM tests, and the correct responses in cognitive flexibility tests. Specifically, VSWM performance at higher span levels (5 or above) yielded a greater improvement. The findings suggest that eye-tracking training can be a feasible and effective after-school program for improving working memory and cognitive flexibility performance in children with ADHD and ASD. This study was prospectively registered at ClinicalTrials.gov (https://clinicaltrials.gov/, trial number: NCT05428657).

The near and far transfer effects of computerized working memory training in typically developing preschool children: Evidence from event-related potentials

Working memory (WM) refers to the ability to actively maintain and process information needed to complete complex tasks such as comprehension, learning, and reasoning. Recent studies have examined the efficacy of computerized working memory training (WMT) in improving cognitive functions in general and WM in particular, with mixed results. Thus, to what extent can WMT produce near and far transfer effects to cognitive function is currently unclear. This study investigated the transfer effects of a computerized WMT for preschool children and also examined the possible neural correlates using the event-related potential (ERP) technique. A total of 50 Chinese preschoolers (64.44 ± 7.76 months old; 24 girls) received 4-week training during school hours. Compared with those in the active control group, children in the training group showed better gains in behavioral performance in the WM task and significantly more changes in ERP markers of the WM and inhibitory control tasks (near transfer effect). However, no evidence was found for transfer to fluid intelligence (far transfer effect). These findings suggest that WMT is capable of enhancing cognitive functioning in preschool children, and as such this work has important implications for educational practice and it may help to design and refine cognitive interventions for typically developing children and those with WM problems or other cognitive deficits (e.g., children with attention-deficit/hyperactivity disorder).

Perinatal risk factors and neurocognitive outcomes in children and adolescents with sickle cell disease.

The literature on cognitive and academic outcomes for children with sickle cell disease (SCD) who experience perinatal risk factors is limited. We aimed to evaluate if low birthweight (LBW), gestational age, and history of neonatal intensive care unit (NICU) admission were associated with neurocognitive functioning, grade retention, or receipt of early intervention or formal educational support in children with SCD. This prospective birth cohort study included 336 participants, ages 8-18, with SCD, who received cognitive testing as part of standard of care and whose caregivers completed behavioral rating scales. Multivariable generalized linear regression models were used to examine associations between perinatal risks and outcome variables, after adjusting for demographic and medical covariates. The prevalence of NICU admission and LBW were 12.03% and 13.50%, respectively. Lower birthweight, earlier gestational age, and NICU admission were associated with worse working memory performance and receipt of early intervention services. Lower birthweight and NICU admission were also associated with slower processing speed. History of NICU admission was associated with caregiver ratings of hyperactivity and emotional dysregulation. The effects of perinatal risk factors on neurocognitive, academic, or educational outcomes were not dependent on SCD genotype. History of LBW or NICU admission was associated with worse cognitive outcomes and increased use of early intervention services among children with SCD. Early identification of perinatal risk factors will help identify children who will benefit from formal developmental or neuropsychological evaluations to manage the comorbidity of SCD and perinatal risks and facilitate increased intervention.

Cell Type-Specific Profiles and Developmental Trajectories of Transcriptomes in Primate Prefrontal Layer 3 Pyramidal Neurons: Implications for Schizophrenia.

In schizophrenia, impaired working memory is associated with transcriptome alterations in layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC). Distinct subtypes of L3PNs that send axonal projections to the DLPFC in the opposite hemisphere (callosal projection [CP] neurons) or the parietal cortex in the same hemisphere (ipsilateral projection [IP] neurons) play critical roles in working memory. However, how the transcriptomes of these L3PN subtypes might shift during late postnatal development when working memory impairments emerge in individuals later diagnosed with schizophrenia is not known. The aim of this study was to characterize and compare the transcriptome profiles of CP and IP L3PNs across developmental transitions from prepuberty to adulthood in macaque monkeys. The authors used retrograde labeling to identify CP and IP L3PNs in the DLPFC of prepubertal, postpubertal, and adult macaque monkeys, and used laser microdissection to capture these neurons for RNA sequencing. At all three ages, CP and IP L3PNs had distinct transcriptomes, with the number of genes differentially expressed between neuronal subtypes increasing with age. For IP L3PNs, age-related shifts in gene expression were most prominent between prepubertal and postpubertal animals, whereas for CP L3PNs such shifts were most prominent between postpubertal and adult animals. These findings demonstrate the presence of cell type-specific profiles and developmental trajectories of the transcriptomes of PPC-projecting IP and DLPFC-projecting CP L3PNs in monkey DLPFC. The evidence that IP L3PNs reach a mature transcriptome earlier than CP L3PNs suggests that these two subtypes differentially contribute to the maturation of working memory performance across late postnatal development and that they may be differentially vulnerable to the disease process of schizophrenia at specific stages of postnatal development.