Memory Training Research Articles

Phosphatidylserine-binding molecules induce the formation of tumor cell-derived microvesicles for enhanced cancer immunotherapy

Engineered microvesicles (MVs) derived from tumor cells, which preserve tumor-specific characteristics, have been extensively investigated as delivery systems or vaccines for cancer therapy. However, the negatively charged phosphatidylserine (PS) exposed on the surface of tumor-derived MVs can induce immune tolerance, evade immune responses and dampen immunotherapy effectiveness. Here, we report a functional molecule (FaZn) that not only actively targets PS exposed on tumor cell surfaces, inducing membrane blebbing and producing PS-blocked tumor cell-derived MVs (FaZn-MVs) but also directly generates stable PS-blocked MVs in situ within tumors, serving as an antigen repository. FaZn-MVs not only activate T-cell-mediated immune responses akin to a prophylactic vaccine, demonstrating robust protection against tumors but also suppress tumor growth in mice and offer long-term immune surveillance. Furthermore, when FaZn-MVs are combined with programmed death ligand 1 (PD-L1) inhibitors, they enhance potent antitumor immune responses, leading to significant improvements in survival and immune memory. This work establishes a promising method for the in vivo generation of personalized tumor microvesicle vaccines with PS blockade, revealing a promising strategy for activating antitumor immune responses.

Gaming Disorders: Navigating the Fine Line between Entertainment and Addiction-Gaming History, Health Risks, Social Consequences, and Pathways to Prevention.

The number of people immersed in excessive gaming has increased in this age of rapid digitalization. The World Health Organization and American Psychiatric Association Organization recognize a gaming disorder as a condition that results in significant problems in daily life as a result of excessive gaming. Both organizations emphasize the similarities to behavioral addictions such as gambling. We examined the appropriate usage of video games from the perspectives of health and management in this study. For the general population, video games provide positive impacts such as stress alleviation and memory improvement. Game playing leads to a loss of time and money for the individual. It also has a negative impact on the individual's family and social life, evolving into a social problem. Gaming addiction is often accompanied by psychological disorders and other addictions, and long-term medical treatment, including approaches to the individual's psychological background and cognitive-behavioral therapy, is necessary. Therefore, the prevention of gaming disorder is essential. From a societal standpoint, action is required in three contexts: the government, game developers, and within the household as a whole. Simultaneously, the public needs to understand the positive potential of gaming, such as e-sports.

Probiotic therapy modulates the brain-gut-liver microbiota axis in a mouse model of traumatic brain injury

The interplay between gut microbiota and host health is crucial for maintaining the overall health of the body and brain, and it is even more crucial how changes in the bacterial profile can influence the aftermath of traumatic brain injury (TBI). We studied the effects of probiotic treatment after TBI to identify potential changes in hepatic lipid species relevant to brain function. Bioinformatic analysis of the gut microbiota indicated a significant increase in the Firmicutes/Bacteroidetes ratio in the probiotic-treated TBI group compared to sham and untreated TBI groups. Although strong correlations between gut bacteria and hepatic lipids were found in sham mice, TBI disrupted these links, and probiotic treatment did not fully restore them. Probiotic treatment influenced systemic glucose metabolism, suggesting altered metabolic regulation. Behavioral tests confirmed memory improvement in probiotic-treated TBI mice. While TBI reduced hippocampal mRNA expression of CaMKII and CREB, probiotics reversed these effects yet did not alter BDNF mRNA levels. Elevated pro-inflammatory markers TNF-α and IL1-β in TBI mice were not significantly affected by probiotic treatment, pointing to different mechanisms underlying the probiotic benefits. In summary, our study suggests that TBI induces dysbiosis, alters hepatic lipid profiles, and preemptive administration of Lactobacillus helveticus and Bifidobacterium longum probiotics can counter neuroplasticity deficits and memory impairment. Altogether, these findings highlight the potential of probiotics for attenuating TBI's detrimental cognitive and metabolic effects through gut microbiome modulation and hepatic lipidomic alteration, laying the groundwork for probiotics as a potential TBI therapy.

NEUROPLASTICIDADE E REABILITAÇÃO NEUROLÓGICA: A INFLUÊNCIA DA ATIVIDADE FÍSICA EM UMA REVISÃO INTEGRATIVA

This study aims to review and synthesize the evidence on the influence of physical activity and cognitive stimulation on neuroplasticity, especially in the context of neurological rehabilitation. The integrative review included relevant scientific articles, analyzing the impact of these interventions on neural reorganization and improvement of cognitive functions in individuals with neurological conditions. The results indicate that regular practice of physical activities and cognitive stimulation are essential to promote neuroplasticity, with studies showing significant improvements in memory, attention and other cognitive aspects in populations affected by neurodegenerative diseases. In addition, physical interventions have shown benefits in regulating the "biological clock" and reaction time, particularly in the elderly. These findings reinforce the importance of integrating physical activities and cognitive stimulation in neurological rehabilitation programs to improve the quality of life of patients and suggest the development of new therapeutic strategies based on these principles.

Rosemary extract activates oligodendrogenesis genes in mouse brain and improves learning and memory ability

Rosemary (Rosmarinus officinalis L.) is a rich source of dietary bioactive compounds such as rosmarinic acid and carnosol with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. In the present study, we investigated rosemary as a potential new therapeutic agent for cognitive function and other symptoms of aging. In this present study, we have aimed to investigate the effects of oral administration of rosemary extract (RME) on learning and memory in the context of other biomarkers-related cognitive function and neurotransmitter levels in senescent accelerated prone 8 (SAMP8) mouse, a model of accelerating aging and Alzheimer’s disease. The Morris water maze (MWM) test showed improved spatial learning and memory behavior in RME treated SAMP8 mouse. Moreover, RME decreased Aβ42 and inflammatory cytokine levels and increased BDNF, Sirt1, and neurotransmitter levels in SAMP8 mouse. Whole-genome microarray analysis revealed that RME significantly increased gene expression related to oligodendrocyte differentiation, myelination, and ATP production in the hippocampus and decreased gene expression related to stress, neuroinflammation, and apoptosis. Also, in the SAMP8 hippocampus, RME significantly increased Olig1 and Olig2 expression. Altogether, our study is the first to report improvement of spatial learning and memory of RME, modulation of genes important for oligodendrogenesis, and Anti-neuroinflammatory effect by suppressing Aβ42 levels in mouse brain and thus highlights the prospects of RME in the treatment of cognitive dysfunction and aging.

The Impact of Working Memory Training on Children’s Cognitive and Noncognitive Skills

The Impact of Working Memory Training on Children’s Cognitive and Noncognitive Skills

Evaluation of the Ameliorative Potential of 3,5-bis(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione against Scopolamine-Induced Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, marked by cognitive impairment. Currently, the available treatment provides only symptomatic relief and there is a great need to design and formulate new drugs to stabilize AD. In the search for a new anti-Alzheimer's drug, 3,5-bis(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione (THTT), a tetrahydro-2H-1,3,5-thiadiazine-2-thione derivative, was investigated against a scopolamine-induced Alzheimer's model. The selected test compound was administered intraperitoneally in three doses (15 mg/kg, 30 mg/kg, and 45 mg/kg). The test compound exhibited an IC50 value of 69.41 µg/mL, indicating its ability to inhibit the acetylcholinesterase enzyme. An antioxidant DPPH assay revealed that the IC50 value of the test compound was 97.75 µg/mL, which shows that the test compound possesses antioxidant activity. The results of behavior tests including the Y-maze and elevated plus maze (EPM) show that the test compound improved short-term memory and spatial memory, respectively. Furthermore, in the Morris water maze (MWM) and light/dark model, the test compound shows improvements in learning and memory. Moreover, the results of histological studies show that the test compound can protect the brain against the harmful effects of scopolamine. Overall, the findings of our investigation suggest that our chosen test compound has disease-modifying and neuroprotective activities against the scopolamine-induced Alzheimer's model. The test compound may be beneficial, subject to further elaborate investigation for anti-amyloid disease-modifying properties in AD.

Effects of computerized working memory training on neuroplasticity in healthy individuals: A combined neuroimaging and neurotransmitter study

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

A randomized clinical trial to evaluate feasibility, tolerability, and preliminary target engagement for a novel executive working memory training in adolescents with ADHD

ObjectiveWorking memory training for Attention-Deficit/Hyperactivity Disorder (ADHD) has focused on increasing working memory capacity, with inconclusive evidence for its effectiveness. Alternative training targets are executive working memory (EWM) processes that promote flexibility or bolster stability of working memory contents to guide behavior via selective attention. This randomized, placebo-controlled study was designed to assess feasibility, tolerability, and behavioral target engagement of a novel EWM training for ADHD. Method62 ADHD-diagnosed adolescents (12–18 years) were randomized to EWM training or placebo arms for 20 remotely coached sessions conducted over 4–5 weeks. Primary outcome measures were behavioral changes on EWM tasks. Secondary outcomes were intervention tolerability, trial retention, and responsiveness to adaptive training difficulty manipulations. ResultsLinear regression analyses found intervention participants showed medium effect size improvements, many of which were statistically significant, on Shifting and Filtering EWM task accuracy and Shifting and Updating reaction time measures. Intervention participants maintained strong self-rated motivation, mood, and engagement and progressed through the adaptive difficulty measures, which was further reflected in high trial retention. ConclusionsThe results suggest that these EWM processes show promise as training targets for ADHD. The subsequent NIMH R33-funded extension clinical trial will seek to replicate and extend these findings.

Multisensory training based on an APP for enhanced verbal working memory in older adults

With the increasing aging population, contemporary society faces the imperative to develop approaches that efficiently delay the age-related decline in working memory capacity, which is a critical area within cognitive aging research. Nevertheless, there is insufficient evidence to support the efficacy of verbal working memory training across various sensory modalities (visual, auditory, and audiovisual) in enhancing the verbal working memory capacity of older adults. In this study, 60 healthy older adults (mean age = 67.07 ± 3.79 years, comprising 34 women and 26 men, mean education = 15.55 ± 2.53 years) were randomly assigned to one of four groups: visual verbal working memory (V-VWM) group, auditory verbal working memory (A-VWM) group, visual-auditory verbal working memory (VA-VWM) group, and a control group. The training duration spanned 12 days. We also investigated whether baseline level and education predicted the outcomes. Findings indicated that V-VWM training had a large effect on improving V-VWM task performance (Cohen's d = 1.765), A-VWM training showed a substantial effect on A-VWM task performance (Cohen's d = 1.904), and VA-VWM training demonstrated a significant effect on VA-VWM task performance (Cohen's d = 2.319) over pretest scores in older adults. Enhancements achieved through V-VWM training exhibited near transfer effects, improving performance in both A-VWM and VA-VWM tasks. In contrast, gains from A-VWM training were selectively transferred to the VA-VWM task. Furthermore, VA-VWM training led to improvements not only in V-VWM and A-VWM tasks but also extended to verbal operation span task with a significant 29.7 % increase. However, no significant transfer effects were observed for the DSF and DSB tasks across the three training groups. The maintenance effect of VA-VWM training persisted for two weeks across tasks involving VA-VWM, V-VWM, and A-VWM. The baseline of VWM span score influence the effect of V-VWM training and transfer effect of VA-VWM training. Education level did not predict the training effects of V-VWM, A-VWM, and VA-VWM. These findings highlight the nuanced effects of sensory-specific verbal working memory training in older adults, emphasizing the potential of tailored interventions to enhance specific aspects of cognitive function, while also highlighting the promising applications of mobile device training in enhancing cognitive skills among the elderly.

Cerebral blood flow and structural connectivity after working memory or physical training in paediatric cancer survivors – Exploratory findings

ABSTRACT Paediatric cancer survivors often suffer from cognitive long-term difficulties. Consequently, strengthening cognition is of major clinical relevance. This study investigated cerebral changes in relation to cognition in non-brain tumour paediatric cancer survivors after working memory or physical training compared to a control group. Thirty-four children (≥one-year post-treatment) either underwent eight weeks of working memory training (n = 10), physical training (n = 11), or a waiting period (n = 13). Cognition and MRI, including arterial spin labelling and diffusion tensor imaging, were assessed at three time points (baseline, post-training, and three-month follow-up). Results show lower cerebral blood flow immediately after working memory training (z = −2.073, p = .038) and higher structural connectivity at the three-month follow-up (z = −2.240, p = .025). No cerebral changes occurred after physical training. Short-term changes in cerebral blood flow correlated with short-term changes in cognitive flexibility (r = −.667, p = .049), while long-term changes in structural connectivity correlated with long-term changes in working memory (r = .786, p = .021). Despite the caution given when interpreting data from small samples, this study suggests a link between working memory training and neurophysiological changes. Further research is needed to validate these findings.

Alpha tACS Improves Cognition and Modulates Neurotransmission in Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) is characterized by a marked shift of electroencephalographic (EEG) power and dominant rhythm, from the α toward the θ frequency range. Transcranial alternate current stimulation (tACS) is a non-invasive brain stimulation technique that allows entrainment of cerebral oscillations at desired frequencies. Our goal is to evaluate the effects of occipital α-tACS on cognitive functions and neurophysiological measures in patients with DLB. We conducted a double-blind, randomized, sham-controlled, cross-over clinical trial in 14 participants with DLB. Participants were randomized to receive either α-tACS (60 minutes of 3 mA peak-to-peak stimulation at 12 Hz) or sham stimulation applied over the occipital cortex. Clinical evaluations were performed to assess visuospatial and executive functions, as well as verbal episodic memory. Neurophysiological assessments and EEG recordings were conducted at baseline and following both α-tACS and sham stimulations. Occipital α-tACS was safe and well-tolerated. We observed a significant enhancement in visuospatial abilities and executive functions, but no improvement in verbal episodic memory. We observed an increase in short latency afferent inhibition, a neurophysiological marker indirectly and partially dependent on cholinergic transmission, coinciding with an increase in α power and a decrease in Δ power following α-tACS stimulation, effects not seen with sham stimulation. This study demonstrates that occipital α-tACS is safe and enhances visuospatial and executive functions in patients with DLB. Improvements in indirect markers of cholinergic transmission and EEG changes indicate significant neurophysiological engagement. These findings justify further exploration of α-tACS as a therapeutic option for DLB patients. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

MSK1 is required for the experience- and ampakine-dependent enhancement of spatial reference memory and reversal learning and for the induction of Arc and BDNF

There is considerable interest in the development of nootropics, pharmacological agents that can improve cognition across a range of both cognitive modalities and cognitive disabilities. One class of cognitive enhancers, the ampakines, has attracted particular attention by virtue of improving cognition associated with animal models of neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as in age-related cognitive impairment. Ampakines elevate CNS levels of BDNF, and it is through this elevation that their beneficial actions are believed to occur. However, what transduces the elevation of BDNF into long-lasting cognitive enhancement is not known. We have previously shown that MSK1, by virtue of its ability to regulate gene transcription, converts the elevation of BDNF associated with environmental enrichment into molecular, synaptic, cognitive and genomic adaptations that underlie enrichment-induced enhanced synaptic plasticity and learning and memory, a property that MSK1 retains across the lifespan. To establish whether MSK1 similarly converts ampakine-induced elevations of BDNF into cognitive enhancement we tested an ampakine (CX929) in male WT mice and in male mice in which the kinase activity of MSK1 was inactivated. We found that MSK1 is required for the ampakine-dependent improvement in spatial reference memory and cognitive flexibility, and for the elevations of BDNF and the plasticity-related protein Arc associated with ampakines and experience. These observations implicate MSK1 as a key enabler of the beneficial effects of ampakines on cognitive function, and furthermore identify MSK1 as a hub for BDNF-elevating nootropic strategies.

Co-production of the ‘EPIC’ multidimensional tool-kit to support neurodivergent children and young people at home and school: a feasibility and pilot study

BackgroundInterventions focused on cognitive function in neurodivergent children typically focus on single functions, e.g. working memory training. They are often focused on ‘deficit’ models and lack an emphasis on understanding areas of individual strengths and difficulties as a prerequisite to appropriate support. The multidimensional nature and phenotypic variability of cognitive profiles in these children indicate a need for a multicomponent-tailored intervention programme focused on understanding and supporting an individual child’s cognitive functioning.AimsThe ‘EPIC’ intervention (Edinburgh Psychoeducation Intervention for Children and Young People) is focused on improving cognition, learning and behaviour in neurodivergent children such as those with attention deficit hyperactivity disorder (ADHD) or who are autistic. Building on our previous co-production work, this study aimed to use a participatory methods approach to develop EPIC practices and materials in relation to our key principles which include psychoeducation, multicomponent, individualised approach, strengths and difficulties profiling and pairing of a child’s individual strengths and difficulties with internal and external strategies. We also set out to assess the feasibility and acceptability of EPIC, and pilot this novel tool-kit intervention with neurodivergent children and their parents and teachers.MethodsThe intervention practices, materials and strategies of EPIC were co-produced with neurodivergent children, their parents, teachers and clinicians taking a strengths and difficulties approach. Identification of psychoeducation activities and strategy practices (e.g. mind-maps, chunking), testing of feasibility and collection of pilot data were conducted over a bi-weekly 8-week programme. Eleven neurodivergent children aged 7 to 12 completed the 16-session individualised programme. Acceptability and feasibility were ascertained via qualitative reports elicited within child and teacher interviews and child ratings of enjoyment. Pilot evaluation data was collected pre- and post-intervention participation, and across cognitive assessments (CANTAB, BRIEF), educational attainment (WIAT) and parent and teacher questionnaires measuring clinical symptoms and behaviour (Conners, AQ, SDQ, self-perception). Data was compared with a matched neurodivergent treatment-as-usual control group (N = 9).ResultsThe co-produced EPIC intervention was both feasible to deliver and acceptable to children, parents and their teachers. Pilot data identified that the 8-week intervention improved cognition (short-term and working memory) and literacy (receptive vocabulary, oral word fluency, listening comprehension). Improvements in the intervention group were also found for parent-reported child behavioural difficulties and aggression, and teacher-reported scholastic competence. Effect sizes generated (Cohen’s d) ranged from 0.65 to 2.83. Parents reported continuing to use EPIC strategies when interviewed over a year after participating in the programme.ConclusionThe current study met our objectives fully. ‘EPIC’ (Edinburgh Psychoeducation Intervention for Children and Young People) is feasible in home and school contexts and improves a range of aspects of cognition, learning and behaviour in neurodivergent children. Our findings show EPIC is suitable to be assessed within a full-scale trial.

Examining the bidirectional longitudinal associations between body mass index and episodic memory following bariatric surgery

BackgroundThe relationship between obesity and episodic memory (i.e., conscious memory for specific events) is hypothesized to be bidirectional. Indeed, studies have shown that metabolic and bariatric surgery (MBS) is associated with episodic memory improvement, and better memory is associated with better postsurgical weight-loss outcomes. However, direct tests of the hypothesized bidirectional association between episodic memory and body mass index (BMI) in MBS are lacking, as few studies have employed repeated, prospective assessments of memory in conjunction with bidirectional modeling techniques. ObjectivesThe present study used latent change score analysis to examine the bidirectional longitudinal associations between episodic memory and BMI in the 2 years following MBS. SettingUniversity hospital; public practice. MethodsEpisodic memory function and BMI were assessed in adults prior to MBS, and at 1, 6, 12, 18, and 24-months postsurgery. ResultsA total of 124 participants (41% lost at 2-year follow-up) showed, on average, favorable weight-loss and episodic memory outcomes following MBS. Crucially, presurgery episodic memory predicted initial change in BMI at 1-month postsurgery, and postsurgery episodic memory at 1- and 6-months predicted change in BMI at 6- and 12-months postsurgery. No evidence was found for pre- and postsurgery BMI predicting changes in episodic memory. ConclusionsResults supported a unidirectional prospective relationship between episodic memory and weight change following MBS, such that better memory pre- and postsurgery predicted improved weight-loss outcomes. These findings highlight the likely importance of episodic memory function for weight change and support the potential benefit of targeting memory processes to improve weight-loss outcomes.

Direct serotonin release in humans shapes aversive learning and inhibition

The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.

Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.

Trolox, Ferulic, Sinapic, and Cinnamic Acid Derivatives of Proline and GABA with Antioxidant and/or Anti-Inflammatory Properties.

Degenerative conditions, such as neurodegenerative disorders (Alzheimer's disease (AD), Parkinson's disease (PD)) and cardiovascular diseases, are complex, multifactorial disorders whose pathophysiology has not been fully elucidated yet. As a result, the available treatment options cannot eliminate these diseases radically, but only alleviate the symptoms. Both inflammatory processes and oxidation are key factors in the development and evolution of neurodegeneration, while acetylcholinesterase inhibitors are the most used therapeutic options against AD. In this work, following the multi-targeting compound approach, we designed and synthesized a series of proline and gamma-aminobutyric acid (GABA) amides with various acidic moieties that possess an antioxidant and/or anti-inflammatory potency. Proline is the pharmacophore of nootropic drugs (e.g., piracetam) used for memory improvement, while GABA is the main inhibitory neurotransmitter in the central nervous system. The designed molecules were subjected to a preliminary screening of their bioactivity in antioxidant and anti-inflammatory assays, as well as against acetylcholinesterase. Most of the synthesized compounds could inhibit lipid peroxidation (IC50 as low as 8 μΜ) and oxidative protein glycation (inhibition of up to 48%) and reduce the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH). In addition, all of the compounds were moderate inhibitors of lipoxygenase (LOX) (up to 46% at 100 μΜ) and could decrease carrageenan-induced paw edema in rats by up to 55%. Finally, some of the compounds were moderate acetylcholinesterase inhibitors (IC50 as low as 219 μΜ). The results confirmed the design rationale, indicating that the compounds could be further optimized as multi-targeting molecules directed against degenerative conditions.

The effects of working memory training on working memory, self-regulation, and analogical reasoning of preschool children.

This study examined the effects of working memory training (WMT) on WM and fluid intelligence. A novel four-pronged model of mediated learning, cognitive functions, task characteristics and metacognition is presented as a conceptual basis for the Modifiability of a Working Memory Program (MWMP). Our basic assumption is that increasing WM depends on a synchronized combination of the four components. A group of typically developed preschool children (n = 62) participated in the experimental group, receiving the MWMP. They were compared with a control group (n = 56) of preschool children who engaged in a substitute program. This comparison allowed us to discern the specific effects of the MWMP. All participants received tests of WM, self-regulation and analogical reasoning before and after the intervention. The MWMP was administered to children in the experimental group for 10 weekly sessions, each lasting 40 minutes, in small groups of two children. The children in the control group engaged in didactic activities that were part of a school curriculum routine for kindergartners for the same length of time. We used ANCOVA analysis to compare the Treatment x Time with age and socioeconomic status as covariates. The findings revealed a higher improvement in some WM and self-regulation tests among children in the experimental group compared to those in the control group. However, no significant transfer effects were observed in analogical thinking. The findings confirm the effectiveness of a non-computerized WMT among kindergartners and support our four-pronged theoretical model. We also discuss earlier findings on far-transfer effects and educational implications. We suggest that future WM studies adopt the following: (1) the development of training methods that are theoretically anchored; (2) training procedures should not rely heavily on computerized exercises but can be adapted to group characteristics, educational settings and cost-effectiveness aspects; (3) varying the task characteristics and training strategies to stimulate task-intrinsic motivation; (4) identifying training strategies to produce cognitive improvements underlying WM; (5) intervention should target individuals in early development as much as possible; (6) development of training procedures that facilitate motivation; and (7) providing empirical evidence of far-transfer effects for WM training. The empirical evidence should link gains in WM capacity and achievements in academic and other life domains.

Executive functions and divergent thinking in young adults: Evidence from individual differences and cognitive training studies

The interplay between executive functions and divergent thinking remains a debated question in creativity research. To address this issue, two studies were conducted from different perspectives. The first study explored which of the executive functioning components—namely working memory, inhibition, and shifting—predicted divergent thinking. A sample of 203 college students performed a battery of tasks assessing divergent thinking, executive functions, and related cognitive variables (fluid intelligence, verbal fluency, and processing speed). After statistically controlling for these variables, only working memory emerged as a significant predictor of creativity scores in the Alternative Uses Task, while inhibition and shifting did not. In the second study, a cognitive training approach was employed to further elucidate the potential efficacy of working memory training in fostering divergent thinking. The results found that the experimental group, which received a 15-day dual n-back task training, demonstrated greater improvements in the creativity score of the Alternative Uses Task compared to the control group, suggesting a transfer effect from working memory training to divergent thinking. This research underscores the plasticity of divergent thinking and highlights a plausible avenue for enhancing creativity through targeted cognitive training.