We tested the hypothesis that Part B of the Trail Making Test (TMT) is a measure of cognitive set-shifting ability in 55 normal subjects with the conventional (written) TMT and a verbal adaptation, the "verbal TMT" (vTMT). The finding of a significant association between Parts B of TMT and vTMT (r = 0,59, p < 0,001), after correcting for age and education, supports the view that Part B of TMT is a valid measure of the ability to alternate between cognitive categories. (+info)
Differential rates of regional brain change in callosal and ventricular size: a 4-year longitudinal MRI study of elderly men.
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Brain structure changes in size with normal aging, but the rate at which different structures change is controversial. We used magnetic resonance imaging (MRI) performed twice, 4 years apart, to compare rates of age-related size change of the corpus callosum, which has been inconsistently observed to thin with age, with change in the lateral ventricles, which are well established to enlarge. Subjects were 215 community dwelling, elderly men (70-82 years old at initial MRI), who were participants in a longitudinal study of cardiovascular risk factors. Percent change in size was significant for both the callosal and ventricular measures, but annual rate of ventricular expansion (2.9%) was significantly greater than annual rate of callosal thinning (-0.9%). Callosal regions showed statistically equivalent rates of shrinkage; ventricular dilatation was symmetrical. Neither callosal and ventricular rates of change correlated with each other (r = 0.01), nor did genu and splenium rates of change correlate with each other (r = 0.05). Tests of speeded processing were administered contemporaneously with both MRIs to examine functional ramifications of observed brain changes. Decline in the Mini-Mental State Examination was related to thinning of the splenium, and decline in Stroop test word reading was selectively related to thinning of the callosal body. These longitudinal data support the contentions that differential rates of change occur in different brain regions in normal aging, age-related callosal thinning contributes to functional declines, and rate of change in one region can be independent of rate of change in another region, even within a brain structure. (+info)
Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.
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The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs. (+info)
The cerebral correlates of set-shifting: an fMRI study of the trail making test.
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The trail making test (TMT) pertains to a family of tests that tap the ability to alternate between cognitive categories. However, the value of the TMT as a localizing instrument remains elusive. Here we report the results of a functional magnetic resonance imaging (fMRI) study of a verbal adaptation of the TMT (vTMT). The vTMT takes advantage of the set-shifting properties of the TMT and, at the same time, minimizes the visuospatial and visuomotor components of the written TMT. Whole brain BOLD fMRI was performed during the alternating execution of vTMTA and vTMTB in seven normal adults with more than 12 years of formal education. Brain activation related to the set-shifting component of vTMTB was investigated by comparing performance on vTMTB with vTMTA, a simple counting task. There was a marked asymmetry of activation in favor of the left hemisphere, most notably in dorsolateral prefrontal cortex (BA 6 lateral, 44 and 46) and supplementary motor area/cingulate sulcus (BA 6 medial and 32). The intraparietal sulcus (BA 7 and 39) was bilaterally activated. These findings are in line with clinico-anatomic and functional neuroimaging data that point to a critical role of the dorsolateral and medial prefrontal cortices as well as the intraparietal sulci in the regulation of cognitive flexibility, intention, and the covert execution of saccades/anti-saccades. Many commonly used neuropsychological paradigms, such as the Stroop, Wisconsin Card Sorting, and go - no go tasks, share some patterns of cerebral activation with the TMT. (+info)
Effects of acute tryptophan depletion on executive function in healthy male volunteers.
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BACKGROUND: Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). METHODS: Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. RESULTS: Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. CONCLUSIONS: The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions. (+info)
Psychometric properties of the Mid-Range Expanded Trail Making Test. An examination of learning-disabled and non-learning-disabled children.
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By systematically varying the stimuli within the Mid-Range Trail Making Test (MTMT), it may eventually be possible to isolate the cognitive demands of this test. Toward this end, the Mid-Range Expanded TMT (METMT) was developed by adding five new forms to the original forms A and B. To insure its appropriateness for clinical and experimental use, the current study sought to quantify the psychometric properties of this new test. The results indicate that the METMT is reliable and has adequate construct, criterion, and factoral validity. The results also cross-validated the findings of Davis et al. [J. Clin. Psychol. 45 (1989) 423.], suggesting that brief neuropsychological evaluations can effectively differentiate normal learners from learning-disabled children. The present study suggests that the MTMT is robust to alterations of its stimulus dimensions. Preliminary METMT normative data are presented. (+info)
Demographic effects on the Trail Making Test in a drug abuse treatment sample.
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Appreciation of the importance of screening for cognitive impairment among substance abusing populations has increased in recent years. In this article, demographic effects on the Trail Making Test (TMT), a test often used for screening for cognitive impairment, are examined in a sample of patients in drug abuse treatment programs. A sample of 5,619 males and 2,902 females was drawn from electronic files of data from the Drug Abuse Treatment Outcome Study (DATOS). The DATOS was a naturalistic cohort study that collected data from 1991 to 1993 in 96 programs in 11 cities in the US. Data were analyzed to determine the effects of demographic variables on the two parts of the TMT in this large sample of patients. Consistent with previous research, demographic variables such as age, gender, education level, and ethnicity were statistically significantly related to both TMT Parts A and B. More importantly, however, the percentage of variance accounted for was quite small. These results suggest that, while clearly present, demographic effects on the TMT are weak. (+info)
Trail Making Test A and B: normative data stratified by age and education.
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Normative data for the Trail Making Test (TMT) A and B are presented for 911 community-dwelling individuals aged 18-89 years. Performance on the TMT decreased with increasing age and lower levels of education. Based on these results, the norms were stratified for both age (11 groups) and education (2 levels). The current norms represent a more comprehensive set of norms than previously available and will increase the ability of neuropsychologists to determine more precisely the degree to which scores on the TMT reflect impaired performance for varying ages and education. (+info)