Recognition Memory in Noonan Syndrome

Abstract

Noonan syndrome (NS) and the clinically related NS with multiple lentiginous (NMLS) are genetic conditions characterized by upregulated RAS mitogen activated protein kinase (RAS-MAPK) signaling, which is known to impact hippocampus-dependent memory formation and consolidation. The aim of the present study was to provide a detailed characterization of the recognition memory of children and adolescents with NS/NMLS. We compared 18 children and adolescents affected by NS and NMLS with 22 typically developing (TD) children, matched for chronological age and non-verbal Intelligence Quotient (IQ), in two different experimental paradigms, to assess familiarity and recollection: a Process Dissociation Procedure (PDP) and a Task Dissociation Procedure (TDP). Differences in verbal skills between groups, as well as chronological age, were considered in the analysis. Participants with NS and NSML showed reduced recollection in the PDP and impaired associative recognition in the TDP, compared to controls. These results indicate poor recollection in the recognition memory of participants with NS and NSML, which cannot be explained by intellectual disability or language deficits. These results provide evidence of the role of mutations impacting RAS-MAPK signaling in the disruption of hippocampal memory formation and consolidation.

Keywords: PTPN11; RAS–MAPK; developmental disorders; episodic memory; hippocampal memory processes.

Figure 1

Examples of items in the Process Dissociation Procedure. Two recognition memory tests were given: one with inclusion, the other with exclusion instructions in the test phase. Although the study phase was identical, instructions differed for the test phases of the two conditions. Each study phase consisted of two blocks of stimuli: one set of 15 colored drawings and a set of 15 words spoken aloud by the examiner. During the test phase (immediately after the study phase), the participants were shown a set of 45 black-and-white line drawings (corresponding to 30 studied and 15 unstudied items) in random order. In the inclusion condition, participants are instructed to recognize as “old” all previously presented items, regardless of the list on which they had seen them, and to reject the novel items. In the exclusion condition, participants are instructed to recognize as “old” only the items presented visually, and to reject those presented in the other list as well as the novel items.

Figure 2

Examples of items in the Task Dissociation Procedure. The experimental setting included two memory tasks: the single-item recognition task and the associative recognition task. Each task consisted of three learning trials. In the study phase of the single item recognition task, participants were presented with 9 flowers. Immediately after the study phase, 9 triplets of flowers were presented; each triplet consisted of a previously studied flower (target item) and two new flowers presented vertically. The associative recognition task was administered immediately after the single item recognition task. The study phase consisted of the presentation of 9 pairs, each including a butterfly and a flower photo. Each recognition item included a butterfly and a flower triplet composed of the flower that had been presented together with the probe butterfly during the study phase, and two others that had been presented together with two different butterflies during the study phase. The participants were requested to indicate the flower that had been presented with the butterfly during the study phase.