Reid L. Skeel

Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington's disease

The purpose of this study was to evaluate the therapeutic effects of the transplantation of bone-marrow mesenchymal stem cells (MSCs), genetically engineered to over-express brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) on motor deficits and neurodegeneration in YAC 128 transgenic mice. MSCs, harvested from mouse femurs, were genetically engineered to over-express BDNF and/or NGF and these cells, or the vehicle solution, were injected into the striata of four-month old YAC 128 transgenic and wild-type mice. Assessments of motor ability on the rotarod and the severity of clasping were made one day prior to transplantation and once monthly, thereafter, to determine the effects of the transplanted cells on motor function. The mice were sacrificed at 13-months of age for immunohistological examination. All YAC 128 mice receiving transplants had reduced clasping, relative to vehicle-treated YAC 128 mice, while YAC 128 mice that were transplanted with MSCs which were genetically engineered to over-express BDNF, had the longest latencies on the rotarod and the least amount of neuronal loss within the striatum of the YAC 128 mice. These results indicate that intrastriatal transplantation of MSCs that over-express BDNF may create an environment within the striatum that slows neurodegenerative processes and provides behavioral sparing in the YAC 128 mouse model of HD. Further research on the long-term safety and efficacy of this approach is needed before its potential clinical utility can be comprehensively assessed.

Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson's disease

To investigate the role of the basal ganglia in working memory and sentence comprehension, 14 patients with Parkinsons disease (PD) were administered experimental measures of semantic and phonological working memory, and a measure of sentence comprehension, while receiving dopaminergic medications and after a period of withdrawal from these medications. An age- and education- matched control group (N=14) received the same measures. Comparison with control subjects revealed deficits in patients with PD in sentence processing regardless of medication status, but no deficits in working memory. In contrast to previous studies, withdrawal of dopaminergic medications had no significant impact on task- related working memory functions or on sentence comprehension. Results suggest that basal ganglia dysfunction does not solely account for sentence comprehension deficits seen in PD.

Personality and performance-based measures in the prediction of alcohol use.

Research has demonstrated a variable relationship between alcohol consumption and self-report personality measures of novelty seeking and harm avoidance. Research has also demonstrated a relationship between performance-based measures of risk taking and substance use. The current study compared the utility of personality measures and performance-based measures in the prediction of alcohol use. The authors hypothesized that the domains would contribute uniquely and would also interact in the prediction of alcohol consumption. Data on alcohol consumption were collected on a daily basis for 2 weeks. Performance-based measures included the Bechara Gambling Task and the Balloon Analogue Risk Task. The Tridimensional Personality Questionnaire was the primary personality measure. Results partially supported hypotheses, in that personality measures showed strong relationships with alcohol use and interacted with performance-based measures in predicting alcohol consumption. Thus, both behavioral and personality measures contributed to prediction of alcohol consumption, and performance-based measures played a moderating role. Results suggest that a combination of behavioral and self-report personality measures may be useful for those screening groups for risk factors for excessive alcohol consumption.

Neuropsychological Deficit Profiles in Systemic Lupus Erythematosus

Although neuropsychological deficits have been reported in several cognitive domains in patients with systemic lupus erythematosus (SLE), there is considerable variability in the literature about which neuropsychological domains are most affected. Similar to studies that demonstrated that specific profiles of neuropsychological deficits exist for those with traumatic brain injury (TBI; Johnstone, Hexum, & Ashkanazi, 1995), this study examined whether a specific pattern of deficits is present in SLE. By comparing reading scores (as estimates of premorbid ability) to tests of concurrent cognitive abilities (i.e., memory, attention, etc.), it was determined that SLE presents a profile distinct from TBI, with the most significant impairments noted in expressive language (Zdiff = -1.39), attention (Zdiff = -0.41), and speed of processing (Zdiff = -0.40). In contrast to TBI, no impairment was noted in intelligence, memory, or cognitive flexibility. Results suggest that memory problems reported by individuals with SLE may be related to inattention. Clinical implications are discussed.

The Relationship Between Visual Contrast Sensitivity and Neuropsychological Performance in a Healthy Elderly Sample

Visual acuity and contrast sensitivity are two visual domains affected by normal aging; however, the potential impact of well-documented changes in these abilities on neuropsychological assessment is relatively unstudied. The current study examined the relationship between these abilities and neuropsychological performance in a healthy, community-based elderly sample. Fifty-one individuals (Age: M = 79.6) were assessed for visual acuity and visual contrast sensitivity, and received a brief neuropsychological battery. Results indicated contrast sensitivity was significantly related to neuropsychological performance on visually based measures, but not auditory measures. Visual acuity was only weakly related to neuropsychological performance. Clinical implications for assessment of elderly individuals are discussed.

The relationship between performance-based visual acuity screening, self-reported visual acuity, and neuropsychological performance.

Despite frequent cautions in the literature concerning the importance of visual acuity in neuropsychological testing, there are few published empirical investigations of what constitutes “sufficient” visual acuity, nor are there published guidelines for performance-based visual screening techniques. The current study attempted to validate the utility of a visual acuity screening technique by examining individuals with varying visual ability on neuropsychological measures. Results revealed declines on neuropsychological measures associated with reduced visual acuity, as well as discrepancies between self-reported and measured visual acuity, with neuropsychological performance being more closely related to a performance-based measure of visual acuity than to self-reported visual acuity. Clinical implications are discussed.

Cortisol and self-report measures of anxiety as predictors of neuropsychological performance.

Although increased anxiety and cortisol reactivity can disrupt neural activity and impact cognition, little research has evaluated associations between anxiety, cortisol, and performance on neuropsychological instruments. The current study investigated the relationship between exogenous salivary cortisol activity and self-report state anxiety on measures tapping a variety of cognitive domains. Fifty-eight male participants were randomly assigned to either a control (no stress induction) or an experimental condition simulating testing anxiety. Self-report state anxiety measures and saliva samples were jointly collected on three occasions. The experimental group generally performed worse than controls on declarative memory and working memory tests. Cortisol and self-report anxiety were not correlated. Inverse relationships were demonstrated between self-report anxiety and neuropsychological test scores. Baseline levels of cortisol at session arrival were positively associated with facilitative memory effects, though there was little association between changes in cortisol and cognitive performance. This study highlights the importance of considering the impact of anxiety during neuropsychological evaluations.

Effects of Bone-Marrow–Derived MSC Transplantation on Functional Recovery in a Rat Model of Spinal Cord Injury: Comparisons of Transplant Locations and Cell Concentrations

Spinal cord injury (SCI) is a widely disabling condition, constraining those affected by it to wheelchairs and requiring intense daily care and assistance. Cell replacement therapies, targeting regeneration of cells in the injured cord, are currently gaining momentum in the field of SCI research. Previous studies indicate that mesenchymal stem cells (MSCs) can reduce functional deficits through immunomodulation and production of trophic factors in a variety of neurological disorders. The present study assessed the efficacy of transplanted bone marrow–derived MSCs at different concentrations and locations for promoting functional recovery following SCI. Although effects were modest, MSCs facilitated an increase in the base of support, as measured by increased distance between the plantar surface of the hind paws, following incomplete contusive SCI, and reduced the density of astroglial scarring. Varying the concentrations or locations of transplanted cells did not provide additional benefits on these measures. These findings indicate that MSC transplants are safe at relatively high concentrations and confer therapeutic benefits that, when used as an adjunctive treatment, could significantly enhance functional recovery following SCI.

Learning style, judgements of learning, and learning of verbal and visual information

The concept of learning style is immensely popular despite the lack of evidence showing that learning style influences performance. This study tested the hypothesis that the popularity of learning style is maintained because it is associated with subjective aspects of learning, such as judgements of learning (JOLs). Preference for verbal and visual information was assessed using the revised Verbalizer-Visualizer Questionnaire (VVQ). Then, participants studied a list of word pairs and a list of picture pairs, making JOLs (immediate, delayed, and global) while studying each list. Learning was tested by cued recall. The results showed that higher VVQ verbalizer scores were associated with higher immediate JOLs for words, and higher VVQ visualizer scores were associated with higher immediate JOLs for pictures. There was no association between VVQ scores and recall or JOL accuracy. As predicted, learning style was associated with subjective aspects of learning but not objective aspects of learning.

Is it random or impulsive responding? The effect of working memory load on decision-making

Research has suggested individuals with limited working memory (WM) capacity make more impulsive choices than individuals without such limited capacity; however, the specificity of increased impulsivity has been challenged on the grounds that limited WM may lead to an increase in random responding rather than a true increase in impulsivity. Furthermore, whereas some previous research have demonstrated sex differences in decision-making, with males tending to make a higher proportion of impulsive decisions than females, the overall results in this area have been mixed. Thus, the current study specifically controlled for the impact of sex, a potential key issue within this area. In this study, 120 subjects (60 males) were randomly assigned to a WM load or control group and completed a decision-making task requiring rapid decisions. The task utilised three probability of loss conditions. The main findings centred on an interaction between sex and WM load, with males showing increased impulsive decision-making in WM load conditions, whereas females did not show a change in decision-making patterns under WM load. Results of this study support the claim that decreased WM capacity increases impulsive decision-making rather than random responding in men, whereas WM load was unrelated to risk-taking in women.