Faculty Bibliography

This study examined the effect of increasing material-specific verbal and visual memory impairment severity on Rey 15-Item Test (RFIT) and RFIT/Recognition Trial performance. Data from 146 clinically referred patients (109 valid/37 invalid) who completed the RFIT, Brief Visuospatial Memory Test-Revised, and Rey Auditory Verbal Learning Test were analyzed. Rey Auditory Verbal Learning Test/BVMT memory impairment was operationalized as ≥40T (no memory impairment), 30T-39T (mild memory impairment), or ≤29T (severe memory impairment). Medium-to-large correlations emerged between the RFIT and memory measures. Significantly more patients with impaired visual memory, and to a lesser extent verbal memory, failed the RFIT and RFIT/Recognition. RFIT and RFIT/Recognition produced areas under the curve = .80-.90 for detecting invalidity and strong associated psychometric properties among patients without memory impairment, but both yielded low and largely unacceptable accuracy (areas under the curve = .57-.71) when verbal or visual memory impairment of any severity was present. In sum, RFIT performance was significantly affected by increasing material-specific memory deficits, such that it produced acceptable accuracy among unimpaired patients, but accuracy greatly diminished with memory impairment, which is antithetical to a sound performance validity test. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

INTRODUCTION:Validity indicators embedded within standard neuropsychological tests have received increasing attention as more efficient measures for sampling performance validity throughout an evaluation. This cross-sectional study examined multiple performance validity tests (PVTs) embedded in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Working Memory (WMI) and Processing Speed (PSI) Indices for detecting invalid test performance. METHOD:This cross-sectional study examined data from a mixed clinical neuropsychiatric sample of 110 patients referred for outpatient evaluation. The sample was composed of 85 patients with valid neuropsychological performance and 25 with invalid performance based on multiple independent criterion PVTs. Among the patients with valid performance, 54% were cognitively impaired, whereas 46% were cognitively unimpaired. RESULTS: CONCLUSION:Overall, results indicated that embedded WAIS-IV WMI and PSI are useful embedded PVTs in conditions in which cognitive impairment is not expected; however, these embedded PVTs demonstrated questionable utility among patients with cognitive impairment due to poor sensitivity, if adequate specificity is maintained, suggesting limited efficacy among patients with cognitive impairment due to risk of false-positive classification.

Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two-dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1-60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin-based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. Stem Cells Translational Medicine 2019;8:512-521.

Sensory neurons of the peripheral nervous system are critical in health and disease. Sensory neurons derived from induced pluripotent stem (iPS) cells are now being used increasingly for in vitro models of neuropathy, pain, and neurotoxicity. DNA methylation is critical for neurodevelopment and has been implicated in many neuronal diseases, but has not been examined in iPS-derived sensory neurons. In order to better characterize the iPS-derived sensory neuron model, we have undertaken a genome-wide DNA methylation study on the cells from human iPS to iPS-derived sensory neurons during differentiation through reduced representation and bisulfite sequencing. We report decreasing DNA methylation with iPS-derived sensory neuronal differentiation that is reflected in increasing numbers and proportions of hypomethylated individual CpGs and regions, as well as lowered DNMT3b expression. Furthermore, genes with changes in DNA methylation near their TSS suggest key pathways that may be involved in iPS-derived sensory neuronal differentiation. These findings provide insights into sensory neuronal differentiation and can be used for further in vitro modelling of disease states.

Neuropsychological assessment is critical for understanding the impact of seizures on cognition and informing treatment decisions. While focus is often placed on examining groups based on seizure type/epilepsy syndrome, an alternate approach emphasizes empirically derived groups based solely on cognitive performance. This approach has been used to identify cognitive phenotypes in temporal lobe epilepsy (TLE). The current study sought to replicate prior work by Hermann and colleagues (2007) and identify cognitive phenotypes in a separate, larger cohort of 185 patients with TLE (92 left TLE, 93 right TLE). Cluster analysis revealed 3- and 4-cluster solutions, with clusters differentiated primarily by overall level of performance in the 3-cluster solution (Low, Middle, and High performance) and by more varying cognitive phenotypes in the 4-cluster solution (Globally Low, Low Executive Functioning/Speed, Low Language/Memory, and Globally High). Differences in cognitive performance as well as demographic and clinical seizure variables are presented. A greater proportion of the patients with left TLE were captured by Cluster 3 (Low Language/Memory) than by the other 3 clusters, though this cluster captured only approximately one-third of the overall group with left TLE. Consistent with prior findings, executive functioning and speed emerged as additional domains of interest in this sample of patients with TLE. The current results extend prior work examining cognitive phenotypes in TLE and highlight the importance of identifying the comprehensive range of potential cognitive profiles in TLE.