Review of the Neural Processes of Working Memory Training: Controlling the Impulse to Throw the Baby Out With the Bathwater

Background: Smartphone technology has enabled the creation of many working memory training (WMT) Apps, with those peer-reviewed described in a recent review. WMT claims to improve working memory, attention deficits, hyperactivity and fluid intelligence, in line with plasticity brain changes. Critics argue that WMT is unable to achieve “far-transfer”—the attainment of benefits to cognition from one taught context to another dissimilar context—associated with improved quality of life. However, brain changes after a course of WMT in frontoparietal and striatal circuits—that often occur prior to behavioral changes—may be a better indicator of far-transfer efficacy, especially to improve impulse control commonly dysregulated in those with addictive disorders, yet not commonly examined in WMT studies. Method: In contrast to previous reviews, the aim here is to focus on the findings of brain imaging WMT training studies across various imaging modalities that use various paradigms, published via PubMed, Scopus, Medline, and Google Scholar. Results: 35 brain imaging studies utilized fMRI, structural imaging (MRI, DTI), functional connectivity, EEG, transcranial direct current stimulation (tDCS), cerebral perfusion, and neurogenetic analyses with tasks based on visuospatial and auditory working memory, dual and standard n-back. Discussion: Evidence suggests that repeated WMT reduces brain activation in frontoparietal and striatal networks reflective of increased neural circuitry efficiency via myelination and functional connectivity changes. Neural effects of WMT may persist months after training has ended, lead to non-trained task transfer, be strengthened by auxiliary methods such as tDCS and be related to COMT polymorphisms. WMT could be utilized as an effective, non-invasive intervention for working memory deficits to treat impulse and affective control problems in people with addictive disorders

Phonological working memory is adversely affected in adults with anorexia nervosa: a systematic literature review

Purpose: Cognitive restraint has potentiating and deleterious effects on working memory (WM) in anorexia nervosa (AN). Conflicting evidence may be due to heterogeneity of tasks examining different WM components (e.g., verbal/auditory versus visuospatial), and differences in adolescent versus adult AN. Additionally, differential cognitive profiles of restricting versus binge/purging subtypes, comorbid psychiatric disorders and psychotropic medication use may confound findings. Methods: To address these conflicts, 25 studies, published between 2016 and 2021, investigating WM in children, adolescents and adults with AN were systematically reviewed using PRISMA guidelines. Results: In 71% of WM tasks, no difference in performance between AN patients and age-matched controls was reported, while 29% of WM tasks showed worse performance. Adults with AN displayed deficits in 44% of the verbal/auditory tasks, while performance remained unaffected in 86% of visuospatial tasks. Conclusion: Examining age groups and WM subsystems separately revealed novel findings of differentially affected WM components in AN. Comorbidities and psychotropic medications were common among AN participants and should be regarded as critical confounding factors for WM measures. Future studies examining different components of WM, acknowledging these confounding factors, may reveal specific deficits in AN to aid treatment improvement strategies

Disease-Associated Mutations Prevent GPR56-Collagen III Interaction

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown

Loss of Regulator of G Protein Signaling 5 Exacerbates Obesity, Hepatic Steatosis, Inflammation and Insulin Resistance

BACKGROUND: The effect of regulator of G protein signaling 5 (RGS5) on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC) or a high-fat diet (HF). METHODOLOGY/PRINCIPAL FINDINGS: Male, 8-week-old RGS5 knockout (KO) and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IκBα and NF-κBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3β phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance

Nematode and Arthropod Genomes Provide New Insights into the Evolution of Class 2 B1 GPCRs

Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.This work was supported by the Portuguese Foundation for Science and Technology (FCT) project PTDC/BIA-BCM/114395/2009, by the European Regional Development Fund through COMPETE and FCT under the project ‘‘PEst-C/MAR/LA0015/2011.’’ RCF is in receipt of an FCT grant (SFRH/BPD/89811/2012) and JCRC is supported by auxiliary research contract FCT Pluriannual funds attributed to CCMAR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Differential influence of a selective melanocortin MC4 receptor antagonist (HS014) on melanocortin-induced behavioral effects in rats

We injected i.c.v. the natural agonist alpha-MSH (melanocyte-stimulating hormone) and the first selective melanocortin MC, receptor antagonist HS014 (cyclic [AcCys(11), D-Nal(14), Cys(18), Asp-NH222]-beta-MSH(11-22) in rats and scored a number of behavioral effects which have been related to the melanocortic peptides. The results showed that HS014 (5 mu g/rat) completely blocked alpha-MSH (3 and 5 mu g/rat)-induced grooming, yawning and stretching. Penile erections induced by alpha-MSH were, however, only partially blocked by HS014. Injections of alpha-MSH decreased food intake in food-deprived rats, whereas HS014 increased food intake. When the peptides were given together, the food intake was similar to that of saline treated controls. Locomotion/exploration and resting were not influenced by either peptide. Our data show that exogenous alpha-MSH decreases food intake, and that an endogenous central melanocortinergic inhibitory tone on feeding prevails which can be blocked with HS014, leading to an increase in food intake. Our data also provide evidence that grooming, stretching and yawning in rats may be mediated by the melanocortin MC, receptor, whereas penile erections might perhaps be mediated by some other melanocortin receptor. (C) 1998 Elsevier Science B.V. All rights reserved