Neuroanatomical differences in the memory systems of intellectual giftedness and typical development.

INTRODUCTION: Studying neuro-structural markers of intellectual giftedness (IG) will inform scientific understanding of the processes helping children excel academically. METHODS: Structural and diffusion-weighted MRI was used to compare regional brain shape and connectivity of 12 children with average to high average IQ and 18 IG children, defined as having IQ greater than 145. RESULTS: IG had larger subcortical structures and more robust white matter microstructural organization between those structures in regions associated with explicit memory. TD had more connected, larger subcortical structures in regions associated with implicit memory. CONCLUSIONS: It was found that the memory systems within brains of children with exceptional intellectual abilities are differently sized and connected compared to the brains of typically developing children. These different neurodevelopmental trajectories suggest different learning strategies. A spectrum of intelligence types is envisioned, facilitated by different ratios of implicit and explicit system, which was validated using a large external dataset.

Brain literate: making neuroscience accessible to a wider audience of undergraduates.

The ability to critically evaluate neuroscientific findings is a skill that is rapidly becoming important in non-science professions. As neuroscience research is increasingly being used in law, business, education, and politics, it becomes imperative to educate future leaders in all areas of society about the brain. Undergraduate general education courses are an ideal way to expose students to issues of critical importance, but non-science students may avoid taking a neuroscience course because of the perception that neuroscience is more challenging than other science courses. A recently developed general education cluster course at UCLA aims to make neuroscience more palatable to undergraduates by pairing neuroscientific concepts with philosophy and history, and by building a learning community that supports the development of core academic skills and intellectual growth over the course of a year. This study examined the extent to which the course was successful in delivering neuroscience education to a broader undergraduate community. The results indicate that a majority of students in the course mastered the basics of the discipline regardless of their major. Furthermore, 77% of the non-life science majors (approximately two-thirds of students in the course) indicated that they would not have taken an undergraduate neuroscience course if this one was not offered. The findings also demonstrate that the course helped students develop core academic skills and improved their ability to think critically about current events in neuroscience. Faculty reported that teaching the course was highly rewarding and did not require an inordinate amount of time.

APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging and Alzheimer's disease.

Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimer's disease, associated with regionally specific effects on brain morphology and function during the life span. Furthermore, entorhinal and hippocampal hemispheric asymmetry could be modified by pathology during Alzheimer's disease development. Using high-resolution magnetic resonance imaging and a cortical unfolding technique we investigated whether carrying the APOE-4 allele influences hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients with Alzheimer's disease as well as in middle-aged and older cognitively healthy individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left hemisphere when compared with the right hemisphere across all participants. Non-carriers of the allele showed this asymmetry only in the patient group. Cortical thickness in the hippocampus did not vary between hemispheres among APOE-4 allele carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in entorhinal cortical thickness. Among Alzheimer's disease patients, this asymmetry might be less dependent on the APOE genotype and a more general marker of incipient disease pathology.

Influence of Alzheimer disease family history and genetic risk on cognitive performance in healthy middle-aged and older people.

OBJECTIVES: Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective diagnostic and therapeutic strategies. Carrying the ε4 allele of the apolipoprotein E gene (APOE4) and having a family history of the disease are two such factors, with family history risk reflecting additional yet unknown or rarely studied genetic and perhaps nongenetic risks. Our aim was to determine the influence of APOE genotype and family history status on cognitive performance in healthy individuals. DESIGN: Longitudinal study. SETTING: Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. PARTICIPANTS: Seventy-two cognitively healthy middle-aged and older people (mean age ± SD: 62 ± 9 years). MEASUREMENTS: Neuropsychological examinations at baseline and after 2 years. RESULTS: Subjects with a family history of AD had lower baseline scores in processing speed, executive functioning, memory encoding, and delayed memory when compared with those without a family history. The family history risk factor did not influence degree of cognitive decline over time. By contrast, baseline cognitive performance did not vary according to APOE4 carrier status. Non-APOE4 carriers showed improved cognitive performance in the memory domains at follow-up, while performance of APOE4 carriers did not change. CONCLUSIONS: Our data highlight the unique contributions of each risk factor to cognitive performance in healthy people. Both factors should be modeled in neuropsychological assessments of people at risk for AD.

Family history of Alzheimer's disease and hippocampal structure in healthy people.

OBJECTIVE: Structural brain changes appear years before the onset of Alzheimer's disease, the leading cause of dementia late in life. Determining risk factors for such presymptomatic brain changes may assist in identifying candidates for future prevention treatment trials. In addition to the e4 allele of the apolipoprotein E gene (APOE-4), the major known genetic risk factor, a family history of Alzheimer's disease also increases the risk to develop the disease, reflecting yet unidentified genetic and, perhaps, nongenetic risks. The authors investigated the influence of APOE-4 genotype and family history risks on cortical thickness in medial temporal lobe subregions among volunteers without cognitive impairment. METHOD: High-resolution magnetic resonance imaging (MRI) and a cortical unfolding method were performed on 26 subjects (APOE-4 carriers: N=13; noncarriers: N=13) with at least one first-degree relative with Alzheimer's disease and 25 subjects (APOE-4 carriers: N=12; noncarriers: N=13) without this risk factor. All subjects (mean age: 62.3 years [SD=10.7]; range=38-86 years) were cognitively healthy. RESULTS: Family history of Alzheimer's disease and APOE-4 status were associated with a thinner cortex in the entorhinal region, subiculum, and adjacent medial temporal lobe subfields. Although these associations were additive, family history of Alzheimer's disease explained a greater proportion of the unique variance in cortical thickness than APOE-4 carrier status. CONCLUSIONS: APOE-4 carrier status and family history of Alzheimer's disease are independently associated with and contribute additively to hippocampal cortical thinning.

Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism.

People with the apolipoprotein-Eepsilon4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimer's disease.

Expression profiling of intermingled long-range projection neurons harvested by laser capture microdissection.

Gene expression data are most useful if they can be associated with specific cell types. This is particularly so in an organ such as the brain, where many different cell types lie in close proximity to each other. We used zebra finches (Taeniopygia guttata), fluorescent tracers and laser capture microdissection (LCM) to collect projection neurons and their RNAs from two interspersed populations from the same animal. RNA amplified from each cell class was reverse transcribed, fluorescently labeled, and hybridized to cDNA microarrays of genes expressed in the zebra finch brain. We applied strict fold-expression criteria, supplemented by statistical analysis, to single out genes that showed the most extreme and consistent differential expression between the two cell classes. Confirmation of the true expression pattern of these genes was made by in situ hybridization and Taqman quantitative PCR (qPCR). High quality RNA was obtained, too, from backfilled neurons birth-dated with bromodeoxyuridine (BrdU). We also quantified changes in the levels of three genes after singing behavior using qPCR. Thus, we have brought together a combination of techniques allowing for the molecular profiling of intermingled populations of projection neurons of known connectivity, age and experience, which should constitute a powerful tool for CNS research.