L. Stephen Miller

Risk factors for potentially harmful informal caregiver behavior.

Objectives: Caring for a sick or disabled relative has been linked to compromised caregiver health, and risk factors for negative caregiver outcomes have been studied extensively, but little attention has been given to care recipient and caregiver health as risk factors for potentially harmful behavior by informal caregivers. This article explores such risk factors.

DICCCOL: Dense Individualized and Common Connectivity-Based Cortical Landmarks

Is there a common structural and functional cortical architecture that can be quantitatively encoded and precisely reproduced across individuals and populations? This question is still largely unanswered due to the vast complexity, variability, and nonlinearity of the cerebral cortex. Here, we hypothesize that the common cortical architecture can be effectively represented by group-wise consistent structural fiber connections and take a novel data-driven approach to explore the cortical architecture. We report a dense and consistent map of 358 cortical landmarks, named Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOLs). Each DICCCOL is defined by group-wise consistent white-matter fiber connection patterns derived from diffusion tensor imaging (DTI) data. Our results have shown that these 358 landmarks are remarkably reproducible over more than one hundred human brains and possess accurate intrinsically established structural and functional cross-subject correspondences validated by large-scale functional magnetic resonance imaging data. In particular, these 358 cortical landmarks can be accurately and efficiently predicted in a new single brain with DTI data. Thus, this set of 358 DICCCOL landmarks comprehensively encodes the common structural and functional cortical architectures, providing opportunities for many applications in brain science including mapping human brain connectomes, as demonstrated in this work.

Relationship between Serum and Brain Carotenoids, α-Tocopherol, and Retinol Concentrations and Cognitive Performance in the Oldest Old from the Georgia Centenarian Study

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and β-carotene concentrations were most consistently related to better cognition (P < 0.05) in the whole population and in the centenarians. Only serum lutein was significantly related to better cognition in the octogenarians. In brain, lutein and β-carotene were related to cognition with lutein being consistently associated with a range of measures. There were fewer significant relationships for α-tocopherol and a negative relationship between brain retinol concentrations and delayed recognition. These findings suggest that the status of certain carotenoids in the old may reflect their cognitive function. The protective effect may not be related to an antioxidant effect given that α-tocopherol was less related to cognition than these carotenoids.

Gender and impulsivity differences in licit substance use

Gender differences in ratings of impulsivity have shown increased impulsivity in men. Research also suggests higher impulsivity is correlated with increased use of alcohol, nicotine, and caffeine. In a large sample of young adults (N = 332), self-report data were collected on licit substance use and impulsivity/nonconformity. Among men, significant differences were found between higher and lower impulsivity groups for alcohol and caffeine use but not for nicotine use. Among women, significant differences were found between higher and lower impulsivity groups for alcohol and nicotine use but not for caffeine use. The data suggest the importance of recognizing gender differences in the relationship between personality factors and licit substance use.

Executive Function Mechanisms of Theory of Mind

This study examined the relationship between Executive Function (EF) and Theory of Mind (ToM) using the Delis-Kaplan Executive Function System (D-KEFS) and three tests of ToM (Reading the Mind in the Eyes test (RMET), Strange Stories test, and Faux Pas test). Separate regression analyses were conducted, and EF predictors varied by ToM test. No EF domains accounted for significant variance in RMET scores; only estimated IQ scores were significant predictors of RMET performance. Verbal fluency and deductive reasoning were significant predictors of performance on the Strange Stories test, while verbal fluency, problem solving, and gender accounted for a significant variance in the Faux Pas test. Results suggest that the ToM tests each utilized differing cognitive mechanisms.

Complex span tasks and hippocampal recruitment during working memory

The working memory (WM) system is vital to performing everyday functions that require attentive, non-automatic processing of information. However, its interaction with long term memory (LTM) is highly debated. Here, we used fMRI to examine whether a popular complex WM span task, thought to force the displacement of to-be-remembered items in the focus of attention to LTM, recruited medial temporal regions typically associated with LTM functioning to a greater extent and in a different manner than traditional neuroimaging WM tasks during WM encoding and maintenance. fMRI scans were acquired while participants performed the operation span (OSPAN) task and an arithmetic task. Results indicated that performance of both tasks resulted in significant activation in regions typically associated with WM function. More importantly, significant bilateral activation was observed in the hippocampus, suggesting it is recruited during WM encoding and maintenance. Right posterior hippocampus activation was greater during OSPAN than arithmetic. Persitimulus graphs indicate a possible specialization of function for bilateral posterior hippocampus and greater involvement of the left for WM performance. Recall time-course activity within this region hints at LTM involvement during complex span.

Depression and Quality of Informal Care: A Longitudinal Investigation of Caregiving Stressors

This research examined longitudinal associations between caregiving stressors, caregiver depression, and quality of care. Informal caregivers of elderly care recipients were interviewed at baseline (N = 310) and again one year later (N = 213). Hierarchical regression analyses indicated that increases in caregiving stressors (i.e., caregiver physical health symptoms, caregiver activity restriction, and care recipient controlling and manipulative behavior) were related to increased caregiver depression. In turn, increased caregiver depression and decreased caregiver respectful behavior predicted increases in potentially harmful behavior. These results extend previous cross-sectional findings and indicate that changes in caregiving stressors, caregiver depression, and caregiver respect over time may signal that intervention is warranted in order to forestall or prevent poor quality of care.

Axonal Fiber Terminations Concentrate on Gyri

Convoluted cortical folding and neuronal wiring are 2 prominent attributes of the mammalian brain. However, the macroscale intrinsic relationship between these 2 general cross-species attributes, as well as the underlying principles that sculpt the architecture of the cerebral cortex, remains unclear. Here, we show that the axonal fibers connected to gyri are significantly denser than those connected to sulci. In human, chimpanzee, and macaque brains, a dominant fraction of axonal fibers were found to be connected to the gyri. This finding has been replicated in a range of mammalian brains via diffusion tensor imaging and high-angular resolution diffusion imaging. These results may have shed some lights on fundamental mechanisms for development and organization of the cerebral cortex, suggesting that axonal pushing is a mechanism of cortical folding.

A Statistical Interpretive Method for Neuropsychological Test Data

The accurate interpretation of large numbers of neuropsychological tests within a flexible battery approach is a difficult and sometimes controversial process. We present a statistically based method of interpretation (Rohlings Interpretive Method or RIM) and evaluation of neuropsychological data that allows for varying numbers of tests along a varying number of cognitive domains, yet remains psychometrically based. This method requires informed clinical judgment in that the level of confidence for tests, cognitive domains, and global indices are used as the backdrop for interpretive decisions. Specific procedures for use are presented in a systematic, detailed fashion to allow the interested reader to replicate the method. Two case examples are presented: a straightforward case of cerebrovascular insult and a more complicated case of mixed etiology. Examples include a variety of different neuropsychological tests commonly used in a flexible battery approach. A discussion of the practicality, ease of use, and potential limitations of this method are further presented.

Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults

Low carotenoid status (especially of the xanthophylls, lutein [L], and zeaxanthin [Z]) is common in older adults and has been associated with a number of degenerative diseases of the central nervous system ranging from retina (e.g., macular degeneration) to brain (e.g., Alzheimers disease). In this study, we tested whether retinal measures of L + Z (macular pigment optical density [MPOD]), used as a surrogate for brain L + Z levels, were related to cognitive function when comparing healthy older adults with mildly cognitively impaired older adults. Twenty-four subjects with mild cognitive impairment were compared with 24 matched controls. Subjects were matched with respect to age, body mass index, ethnicity, sex, and smoking status. Degree of cognitive impairment and cognitive ability was determined via structured clinical interview. MPOD was measured psychophysically. In healthy older adults, MPOD was only related to visual-spatial and constructional abilities (p = 0.04). For subjects with mild cognitive impairment (MCI), however, MPOD was broadly related to cognition including the composite score on the mini-mental state examination (p = 0.02), visual-spatial and constructional abilities (p = 0.04), language ability (p = 0.05), attention (p = 0.03), and the total scale on the Repeatable Battery for the Assessment of Neuropsychological Status (p = 0.03). It is possible that L/Z status may be more strongly related to cognition when individuals are considered with established onset of cognitive decline.