Tim Simon

Individuals with chromosome 22q11.2 deletion syndrome have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with 22q11.2DS and typically developing controls ages 6-15 years saw images within a grid and after a delay, then indicated the positions of the images in the correct temporal order. Children with 22q11.2DS made more spatial and temporal errors than controls. Females with 22q11.2DS made more spatial and temporal errors than males. These results extend findings of impaired spatiotemporal processing into the memory domain in 22q11.2DS by documenting their influence on working memory performance. © AAIDD.

Mutations of the fragile X mental retardation 1 gene are the genetic cause of fragile X syndrome. Large expansions of the CGG repeat consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein. Carriers with a premutation allele are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the '. when pathway' during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression. © 2014 Elsevier B.V.

Fragile X premutation carriers are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first-ever graph theoretical network analyses in fXPCs using 30-direction diffusion-weighted magnetic resonance images acquired from 42 healthy controls aged 18-44 years and 46 fXPCs. Globally, we found no differences between the fXPCs and HCs within each gender for all global graph theoretical measures. In male fXPCs, global efficiency was significantly negatively associated with the number of CGG repeats. For nodal measures, significant group differences were found between male fXPCs and male HCs in the right fusiform and the right ventral diencephalon, and in the left hippocampus [for nodal clustering coefficient ]. In female fXPCs, CC in the left superior parietal cortex correlated with counting performance in an enumeration task. © 2014 Wiley Periodicals, Inc.

High prevalence of autism spectrum disorders has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history AND a standardized observation measure and suggests that ASD is not as common as previously reported in 22q11.2DS. Differences in methodology, along with comorbid conditions such as anxiety, likely contribute to false elevations in ASD prevalence and information from multiple sources should be included in the evaluation of ASD. © 2013 Springer Science+Business Media New York.

Background: Chromosome 22q11.2 deletion syndrome, fragile X syndrome, and Turner syndrome are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention. Methods: Girls with 22q11.2DS, FXS, or TS and typically developing girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting, and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices. Results: Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system. Conclusions: These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory. © 2014 Quintero et al.; licensee BioMed Central Ltd.

Objective: Fragile X premutation carriers have an expansion of 55 -200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance. Method: Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs and healthy age-matched controls performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks. Results: Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII. Conclusion: Antisaccades require inhibitory control to inhibit reflexive eye movements. We found that eye movements are sensitive to impaired inhibitory control in fXPCs asymptomatic for FXTAS. Thus, eye movements may be useful in assessing FXTAS risk or disease progression. © 2014 American Psychological Association.