Heterozygous deletion of the LRFN2 gene is associated with working memory deficits.

Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective working memory deficits, with borderline intellectual functioning. Further investigations identified a defect in executive function, and auditory-verbal processes. These data were consistent with brain MRI and FDG-PET functional brain imaging, which, when compared with controls, revealed abnormal brain volume and hypometabolism of gray matter structures implicated in working memory. We performed electron microscopy immunogold labeling demonstrating the localization of LRFN2 at synapses of cerebellar and hippocampal rat neurons, often associated with the NR1 subunit of N-methyl-D-aspartate receptors (NMDARs). Altogether, the combined approaches imply a role for LRFN2 in LD, specifically for working memory processes and executive function. In conclusion, the identification of familial cases of clinically homogeneous endophenotypes of LD might help in both the management of patients and genetic counseling for families.

An empirical test of the independence between declarative and procedural working memory in Oberauer's (2009) theory.

It has recently been suggested that working memory could be conceived as two symmetrical subsystems with analogous structure and processing principles: a declarative working memory storing objects of thought available for cognitive operations, and a procedural working memory holding representations of what to do with these objects (Oberauer, Psychology of learning and motivation 51: 45-100, 2009). Within this theoretical framework, the two subsystems are thought to be independent and fueled by their own capacity. The present study tested this hypothesis through two experiments using a complex span task in which participants were asked to maintain consonants for further recall while performing response selection tasks. In line with Oberauer's conception, the load of the procedural working memory was varied by manipulating the number of stimulus-response mappings of the response selection task. Increasing the number of these mappings had a strong detrimental effect on recall performance. Besides contradicting Oberauer's proposal, this finding supports models that assume a resource-sharing between processing and storage in working memory.

Individual differences in Sternberg's memory scanning task.

This study provides a new perspective on both the cognitive processes actually implemented and the effect of a simple experimental control - the recall constraint - in Sternberg's memory scanning task. These findings were highlighted by adopting a new approach based on the comparison of qualitative and quantitative results. The analysis of individual processing, on 72 adults, each participating in one of two experimental conditions (with or without sequence recall), highlighted a large variability in quantitative results as well as qualitative procedures. Based on the participants' retrospective verbalisations, two categories of strategies were identified: (1) the procedures used to memorize the sequence of digits, and (2) the procedures used to compare this sequence with the test digit, which includes strategies for coding the items and processes for searching them in memory. The analysis of the strategies shows that their frequencies of use depend not only on the experimental condition, but also on the participants, the level of task difficulty and the interaction between participants and level of difficulty. This variability questions the accuracy of Sternberg's mean model. Furthermore, this approach suggests some answers to the old debate concerning the exhaustive search pattern for the yes response. Indeed, our results show three types of strategies that can be identified according to the different models of search suggested in the literature. The "exhaustive" search, that would only be involved in the recall condition and only for some of the participants, the "self-terminating" search and the "immediate" strategy, which can be identified with a model of parallel search with limited resources. Thus our study suggests that the different search models are appropriate but depend on both the specific experimental conditions and participant's strategy. Our results should help to improve the interpretation of data collected with this paradigm in cognitive and neuroscientific studies of memory.