Chawla, M., Biwer, L., Turk, M., Hoang, L., Uprety, A., Fitzhugh, M., De Both, M., Coleman, P., Trouard, T., Alexander, G. E., Mitchell, K., Barnes, C., Hale, T., & Huentelman, M. (2016). Gradual hypertension induction in middle-aged CYP1A1-REN2 transgenic rats produces significant impairments in spatial memory. ..
Alexander, G. E., Prohovnik, I., Stern, Y., & Mayeux, R. (1994). WAIS-R subtest profile and cortical perfusion in Alzheimer's disease. Brain and Cognition, 24(1), 24-43.
Alexander, G. E., Lin, L., Yoshimaru, E., Bharadwaj, P. K., Bergfield, K. L., Hoang, L., Chawla, M., Chen, K., Moeller, J. R., Barnes, C. A., & Trouard, T. P. (2016). Age-Related Regional Network Covariance of Magnetic Resonance Imaging Gray Matter in the Rat. ..
BIO5 Collaborators
Gene E Alexander, Carol A Barnes
Schapiro, M. B., Murphy, D. G., Hagerman, R. J., Azari, N. P., Alexander, G. E., Miezejeski, C. M., Hinton, V. J., Horwitz, B., Haxby, J. V., Kumar, A., White, B., & Grady, C. L. (1995). Adult fragile X syndrome: Neuropsychology, brain anatomy, and metabolism. American Journal of Medical Genetics - Neuropsychiatric Genetics, 60(6), 480-493.
PMID: 8825884;Abstract:
To understand the implications of suboptimal gene expression in fragile X syndrome [fra(X)], we sought to define the central nervous abnormalities in fra(X) syndrome to determine if abnormalities in specific brain regions or networks might explain the cognitive and behavioral abnormalities in this syndrome. Cranial and ventricular volumes were measured with quantitative computed tomography (CT), regional cerebral metabolic rates for glucose (rCMRglc) were measured with [18-F]-2-fluoro-2-deoxy-D-glucose (18FDG), and patterns of cognition were determined with neuropsychological testing in ten healthy, male patients with karyotypically proven fra(X) syndrome (age range 20-30 yr). Controls for the CT studies were 20 healthy males (age range 21- 37 yr), controls for the PET studies were 9 healthy males (age range 22-31 yr), and controls for the neuropsychological tests were 10 young adult, male Down syndrome (DS) subjects (age range 22-31 yr). The mean mental age of the fra(X) syndrome group was 5.3 yr (range 3.5-7.5 yr; Stanford-Binet Intelligence Scale). Despite comparable levels of mental retardation, the fra(X) subjects showed poorer attention/short term memory in comparison to the DS group. Further, the fra(X) subjects showed a relative strength in verbal compared to visuospatial attention/short term memory. As measured with quantitative CT, 8 fra(X) subjects had a significant (P 0.05) 12% greater intracranial volume (1,410 ± 86 cm3) as compared to controls(1,254 ± 122 cm3). Volumes of the right and left lateral ventricles and the third ventricle did not differ between groups. Seven of eight patients had greater right lateral ventricle volumes than left, as opposed to 9 out of 20 controls (P 0.05). Global gray matter CMR-glc in nine fra(X) patients was 9.79 ± 1.28 mg/100 g/minute and did not differ from 8.84 ± 1.31 mg/100 g/minute in the controls. R/L asymmetry in metabolism of the superior parietal lobe was significantly higher in the patients than controls. A preliminary principal component analysis of metabolic data showed that the fra(X) subjects tended to form a separate subgroup that is characterized by relative elevation of normalized metabolism in the lenticular nucleus, thalamus, and premotor regions. Further, a discriminant function, that reflected rCMRglc interactions of the right lenticular and left premotor regions, distinguished the fra(X) subjects from controls. These regions are part of a major group of functionally and anatomically related brain regions and appear disturbed as well in autism with which fra(X) has distinct behavioral similarities. These results show a cognitive profile in fra(X) syndrome that is distinct from that of Down syndrome, that the larger brains in fragile X syndrome are not accompanied by generalized cerebral cortical atrophy or hypoplasia, and that distinctive alterations in resting regional glucose metabolism, measured with 18 FDG and PET, occur in fra(X) syndrome.
Alexander, G., Ryan, L., Cardoza, J. A., Barense, M. D., Kawa, K. H., Wallentin-Flores, J., Arnold, W. T., & Alexander, G. E. (2012). Age-related impairment in a complex object discrimination task that engages perirhinal cortex. Hippocampus, 22(10).
Previous lesion studies have shown compromised complex object discrimination in rats, monkeys, and human patients with damage to the perirhinal cortical region (PRC) of the medial temporal lobe. These findings support the notion that the PRC is involved in object discrimination when pairs of objects have a high degree of overlapping features but not when object discrimination can be resolved on the basis of a single feature (e.g., size or color). Recent studies have demonstrated age-related functional changes to the PRC in animals (rats and monkeys) resulting in impaired complex object discrimination and object recognition. To date, no studies have compared younger and older humans using paradigms previously shown to engage the PRC. To investigate the influence of age on complex object discrimination in humans, the present study used an object matching paradigm for blob-like objects that have previously been shown to recruit the PRC. Difficulty was manipulated by varying the number of overlapping features between objects. Functional MRI data was acquired to determine the involvement of the PRC in the two groups during complex object discrimination. Results indicated that while young and older adults performed similarly on the easy version of the task, most older adults were impaired relative to young participants when the number of overlapping features increased. fMRI results suggest that older adults do not engage bilateral anterior PRC to the same extent as young adults. Specifically, complex object matching performance in older adults was predicted by the degree to which they engage left anterior PRC. These results provide evidence for human age-related changes in PRC function that impact complex object discrimination.
