Working memory (WM), the ability to store and manipulate information for short periods of time, is an important predictor of scholastic aptitude and a critical bottleneck underlying higher-order cognitive processes, including controlled attention and reasoning. Recent interventions targeting WM have suggested plasticity of the WM system by demonstrating improvements in both trained and untrained WM tasks. However, evidence on transfer of improved WM into more general cognitive domains such as fluid intelligence (Gf) has been more equivocal. Therefore, we conducted a metaanalysis focusing on one specific training program, n-back. We searched PubMed and Google Scholar for all n-back training studies with Gf outcome measures, a control group, and healthy participants between 18 and 50 years of age. In total, we included 20 studies in our analyses that met our criteria and found a small but significant positive effect of nback training on improving Gf. Several factors that moderate this transfer are identified and discussed. We conclude that short-term cognitive training on the order of weeks can result in beneficial effects in important cognitive functions as measured by laboratory tests.

Working memory (WM) is a fundamental cognitive ability that supports complex thought but is limited in capacity. Thus, WM training interventions have become very popular as a means of potentially improving WM-related skills. Another promising intervention that has gained increasing traction in recent years is transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation that can modulate cortical excitability and temporarily increase brain plasticity. As such, it has the potential to boost learning and enhance performance on cognitive tasks. This study assessed the efficacy of tDCS to supplement WM training. Sixty-two participants were randomized to receive either right prefrontal, left prefrontal, or sham stimulation with concurrent visuospatial WM training over the course of seven training sessions. Results showed that tDCS enhanced training performance, which was strikingly preserved several months after training completion. Furthermore, we observed stronger effects when tDCS was spaced over a weekend break relative to consecutive daily training, and we also demonstrated selective transfer in the right prefrontal group to nontrained tasks of visual and spatial WM. These findings shed light on how tDCS may be leveraged as a tool to enhance performance on WM-intensive learning tasks.

Working memory (WM), the ability to store and manipulate information for short periods of time, is an important predictor of scholastic aptitude and a critical bottleneck underlying higher-order cognitive processes, including controlled attention and reasoning. Recent interventions targeting WM have suggested plasticity of the WM system by demonstrating improvements in both trained and untrained WM tasks. However, evidence on transfer of improved WM into more general cognitive domains such as fluid intelligence (Gf) has been more equivocal. Therefore, we conducted a metaanalysis focusing on one specific training program, n-back. We searched PubMed and Google Scholar for all n-back training studies with Gf outcome measures, a control group, and healthy participants between 18 and 50 years of age. In total, we included 20 studies in our analyses that met our criteria and found a small but significant positive effect of nback training on improving Gf. Several factors that moderate this transfer are identified and discussed. We conclude that short-term cognitive training on the order of weeks can result in beneficial effects in important cognitive functions as measured by laboratory tests.

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Seizures are a common co-occurring condition in those with fragile X syndrome (FXS), and in those with idiopathic autism spectrum disorder (ASD). Seizures are also associated with ASD in those with FXS. However, little is known about the rate of seizures and how commonly these problems co-occur with ASD in boys with the FMR1 premutation. We, therefore, determined the prevalence of seizures and ASD in boys with the FMR1 permutation compared with their sibling counterparts and population prevalence estimates. Fifty premutation boys who presented as clinical probands (N = 25), or non-probands (identified by cascade testing after the proband was found) (N = 25), and 32 non-carrier controls were enrolled. History of seizures was documented and ASD was diagnosed by standardized measures followed by a team consensus of ASD diagnosis. Seizures (28%) and ASD (68%) were more prevalent in probands compared with non-probands (0 and 28%), controls (0 and 0%), and population estimates (1 and 1.7%). Seizures occurred more frequently in those with the premutation and co-morbid ASD particularly in probands compared with those with the premutation alone (25 vs. 3.85%, p = 0.045). Although cognitive and adaptive functioning in non-probands were similar to controls, non-probands were more likely to meet the diagnosis of ASD than controls (28 vs. 0%, p < 0.0001). In conclusion, seizures were relatively more common in premutation carriers who presented clinically as probands of the family and seizures were commonly associated with ASD in these boys. Therefore, boys with the premutation, particularly if they are probands should be assessed carefully for both ASD and seizures.

Our recent meta-analysis concluded that training on working memory can improve performance on tests of fluid intelligence (Au et al., Psychon Bull Rev, 22(2), 366-377, 2015). Melby-Lervåg and Hulme (Psychon Bull Rev, doi: 10.3758/s13423-015-0862-z ) challenge this conclusion on the grounds that it did not take into consideration baseline differences on a by-study level and that the effects were primarily driven by purportedly less rigorous studies that did not include active control groups. Their re-analysis shows that accounting for baseline differences produces a statistically significant, but considerably smaller, overall effect size (g = 0.13 vs g = 0.24 in Au et al.), which loses significance after excluding studies without active controls. The present report demonstrates that evidence of impact variation by the active/passive nature of control groups is ambiguous and also reveals important discrepancies between Melby-Lervåg and Hulme's analysis and our original meta-analysis in terms of the coding and organization of data that account for the discrepant effect sizes. We demonstrate that there is in fact no evidence that the type of control group per se moderates the effects of working memory training on measures of fluid intelligence and reaffirm the original conclusions in Au et al., which are robust to multiple methods of calculating effect size, including the one proposed by Melby-Lervåg and Hulme.

Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.

BackgroundFragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available.MethodsNeuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years) who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis.ResultsHistologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII) compared with age-matched normal controls.ConclusionsSignificant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS.