Performance on, and correlates of, the Brief Visuospatial Memory Test-Revised after traumatic brain injury.

OBJECTIVE: This study investigated the performance on, and correlates of, the Brief Visuospatial Memory Test - Revised (BVMT-R) in patients with traumatic brain injury (TBI). METHODS: Participants included 100 patients with TBI and 100 demographically matched controls. We first used regression analysis to determine predictors of BVMT-R performance in the clinical group. We then used analysis of variance as well as logistic regression to determine how BVMT-R findings differed between the clinical and control groups. RESULTS: Injury severity and visuospatial ability both contributed to the prediction of BVMT-R Total Recall and Delayed Recall scores in the TBI group. Mean differences between the TBI and control groups on these variables were statistically significant, but overall individual classification accuracy was limited at 59%. CONCLUSIONS: The BVMT-R has some clinical utility in the evaluation of patients with TBI but should not be used in isolation.

The ERG1A K+ Channel Is More Abundant in Rectus abdominis Muscle from Cancer Patients Than that from Healthy Humans.

BACKGROUND: The potassium channel encoded by the ether-a-gogo-related gene 1A (erg1a) has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1A has not been reported in human skeletal muscle. METHODS AND RESULTS: Here, using immunohistochemistry, we detect ERG1A immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report the detection of ERG1A immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1A immunofluorescence at a statistically greater level (53.6%; p < 0.05) in the skeletal muscle of older cancer patients than in age-matched healthy adults. Importantly, using immunoblot, we reveal that lower mass ERG1A protein is 61.5% (p < 0.05) more abundant in the skeletal muscle of cachectic older adults than in healthy age-matched controls. Additionally, we report that the ERG1A protein is detected in a cultured human rhabdomyosarcoma line that may be a good in vitro model for the study of ERG1A in muscle. CONCLUSIONS: The data demonstrate that ERG1A is detected more abundantly in the atrophied skeletal muscle of cancer patients, suggesting it may be related to muscle loss in humans as it has been shown to be in mice experiencing muscle atrophy as a result of malignant tumors.

MERG1A Protein Abundance Increases in the Atrophied Skeletal Muscle of Denervated Mice, But Does Not Affect NFκB Activity.

Skeletal muscle atrophy may occur with disease, injury, decreased muscle use, starvation, and normal aging. No reliably effective treatments for atrophy are available, thus research into the mechanisms contributing to muscle loss is essential. The ERG1A K+ channel contributes to muscle loss by increasing ubiquitin proteasome proteolysis (UPP) in the skeletal muscle of both unweighted and cachectic mice. Because the mechanisms which produce atrophy vary based upon the initiating factor, here we investigate atrophy produced by denervation. Using immunohistochemistry and immunoblots, we demonstrate that ERG1A protein abundance increases significantly in the Gastrocnemius muscle of rodents 7 days after both sciatic nerve transection and hind limb unweighting. Further, we reveal that ectopic expression of a Merg1a encoded plasmid in normal mouse Gastrocnemius muscle has no effect on activity of the NFκB transcription factor family, a group of proteins which contribute to muscle atrophy by modulation of the UPP. Further, although NFκB activity increases significantly after denervation, we show that expression of a plasmid encoding a dominant negative Merg1a mutant in Gastrocnemius muscle prior to denervation, has no effect on NFκB activity. Thus, although the ERG1A K+ channel increases UPP, it does not do so through modulation of NFκB transcription factors.

Ether-a-go-go related gene-1a potassium channel abundance varies within specific skeletal muscle fiber type.

The ERG1A K+ channel, which is partially responsible for repolarization of the cardiac action potential, has also been reported in skeletal muscle where it modulates ubiquitin proteolysis. Because ERG1A protein appears variably expressed in muscles composed of mixed fiber types, we hypothesized that its abundance in skeletal muscle might differ with fiber type. Indeed, skeletal muscle fibers vary in speed of contraction (fast or slow), which is mainly determined by myosin heavy chain (MyHC) isoform content, but a sarcolemmal K+ channel might also modulate contraction speed. To test our hypothesis, we cryo-sectioned Soleus (SOL), Extensor Digitorum Longus (EDL), and Gastrocnemius muscles from five rats. These muscles were chosen because the SOL and EDL contain an abundance of slow- and fast-twitch fibers, respectively, while the Gastrocnemius has a more heterogeneous composition. The muscle sections were co-immunostained for the ERG1A protein and either the fast- or slow-twitch MyHC to identify fiber type. ERG1A fluorescence was then measured in the sarcolemma of each fiber type and compared. The data reveal that the ERG1A protein is more abundant in the fibers of the SOL than in the EDL muscles, suggesting ERG1A may be more abundant in the slow than the fast fibers, and this was confirmed with immunoblot. However, because of the homogeneity of fiber type within these muscles, it was not possible to get enough data from both fiber types within a single muscle to compare ERG1A composition within fiber type. However, immunohistochemistry of sections from the fiber type heterogeneous Gastrocnemius muscle reveals that slow fibers had, on average, a 17.2% greater ERG1A fluorescence intensity than fast fibers (p<0.03). Further, immunoblot reveals that ERG1A protein is 41.6% more abundant (p=0.051) in old than in young rat Gastrocnemius muscle. We postulate that this membrane bound voltage-gated channel may affect membrane characteristics, the duration of the action potential generated, and/or the speed of contraction. Indeed, ERG1A protein is more abundant in aged and atrophic skeletal muscle, both of which exhibit slower rates of contraction.

Emotional Intelligence in Agenesis of the Corpus Callosum.

People with agenesis of the corpus callosum (AgCC) with normal general intelligence have deficits in complex cognitive processing, as well as in social cognition. It is uncertain the extent to which impoverished processing of emotions may contribute to social processing deficiencies. We used the Mayer-Salovey-Caruso Emotional Intelligence Test to clarify the nature of emotional intelligence in 16 adults with AgCC. As hypothesized, persons with AgCC exhibited greater disparities from norms on tests involving more socially complex aspects of emotions. The AgCC group did not differ from norms on the Experiential subscale, but they were significantly below norms on the Strategic subscale. These findings suggest that the corpus callosum is not essential for experiencing and thinking about basic emotions in a "normal" way, but is necessary for more complex processes involving emotions in the context of social interactions.

Criterion validity of the D-KEFS color-word and verbal fluency switching paradigms following traumatic brain injury.

The present study was composed of two parts examining the clinical utility of the Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color-Word subtests in traumatic brain injury (TBI). In the first part, the performance of 128 outpatients with mild to severe TBI on the Verbal Fluency and Color-Word subtests was examined in relation to two primary indicators of TBI severity: length of coma and the presence of intracranial lesions on neuroimaging through regression analysis. After controlling for education, ethnicity, and complicating premorbid and comorbid factors, length of coma predicted performance on the Color-Word Inhibition/Switching subtest, whereas the presence of diffuse lesions was related to Verbal Fluency Category Switching performance. In the second part of this study, performance on the Category Switching and Inhibition/Switching subtests was compared between a group of 28 participants with moderate-to-severe TBI and demographically matched groups with mild-uncomplicated TBI (n = 28) and neurologically healthy control participants (n = 56). The moderate-to-severe TBI group performed significantly worse on both subtests than the mild-uncomplicated TBI and control groups, and the latter groups did not differ from each other on these subtests. Logistic regression analysis showed that the combined group classification accuracy of these subtests was 66.07%, with an area under the curve (AUC) of .70 and a likelihood ratio of 1.93. The findings provide modest support for the clinical utility of the Color-Word Inhibition/Switching subtest in the cognitive assessment of TBI, while also replicating prior research suggesting clinical utility of the Category Switching subtest in this population.

Decision-making in individuals with agenesis of the corpus callosum: expectancy-valence in the Iowa Gambling Task.

Individuals with agenesis of the corpus callosum (ACC) can have intelligence within the normal range, but nevertheless have deficiencies in decision-making and complex novel problem-solving. The specific nature of these problems is not yet clearly understood. The Iowa Gambling Task was used to test decision-making ability and problem-solving in 40 individuals with complete or partial ACC (full-scale intelligence quotient >80) and 26 control participants. The expectancy-valence (EV) model was applied to the trial-by-trial responses of each participant to elucidate differences in decision processes utilized by each group. The ACC group had a lower overall net gain and fewer advantageous choices than controls, but these differences were not statistically significant. Within the EV model, individuals with ACC exhibited significantly higher attention to losses, less consistency in their choice strategy, and greater frequency of switching between decks. They also showed a tendency to be more influenced by recent trials. This outcome is similar to that seen in individuals with Asperger's disorder. Taken together, these results suggest that individuals with ACC have difficulty in inferring game contingencies and forming a coherent selection strategy, implicating the corpus callosum in these decision processes.