Trail Making Test error analysis in classic motor neuron disease

The use of non-traditional scores in neuropsychological assessment allows for pattern analysis of test performance, commonly referred to as Quantified Process Approach (QPA). In the present study, the QPA was taken to study error rates on the Trail Making Test (TMT) in 26 non-demented patients with classic motor neuron disease (cMND), who commonly present with impaired cognitive flexibility, and 26 matched healthy controls. Between-group comparisons revealed that cMND patients exhibited higher total error rates on the TMT Part B (TMT-B) relative to controls (p < 0.001), though no significant associations were noted between TMT errors and measures of attention and executive function obtained using the Stroop Neuropsychological Screening Test, the Wechsler Adult Intelligence Scale Digit Symbol and Digit Span subtests and the Wisconsin Card Sorting Test. Moreover, the percentage of cMND patients with normal TMT-B time-to-completion who committed at least one error (either sequential or perseverative errors) in TMT-B was significantly higher compared to controls (p = 0.005). These findings suggest that error analysis using the QPA may increase the clinical utility of TMT and should be considered in addition to time-to-completion scores, in the neuropsychological assessment of patients with cMND.     

Prefrontal cortex white matter tracts in prodromal Huntington disease

Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large‐scale analysis using multisite diffusion‐weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT‐HD study collected imaging and neuropsychological data on gene‐positive HD participants without a clinical diagnosis (i.e., prodromal) and gene‐negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto‐occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG‐age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long‐range tracts essential for cross‐region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717–3732, 2015. © 2015 Wiley Periodicals, Inc.     

D-KEFS Trail Making Test performance in patients with lateral prefrontal cortex lesions.

This study evaluated cognitive set-shifting in 12 patients with focal lesions in the lateral prefrontal cortex (LPC) by examining their performance on the Trail Making Test from the Delis-Kaplan Executive Function System (D-KEFS). Patients with LPC lesions performed significantly worse than controls on the D-KEFS Trail Making Test on the Letter Sequencing, Number-Letter Switching (set-shifting), and Motor Speed conditions. Patients with LPC lesions performed significantly more slowly on the Number-Letter Switching condition even after controlling for performance on the four baseline conditions of the test. In addition, patients with LPC lesions exhibited significantly elevated error rates on the Number-Letter Switching condition. Results suggest that LPC lesions can lead to impaired cognitive set-shifting on a visual-motor sequencing task.     

An fMRI study of the Trail Making Test

This study investigated the cerebral correlates of the Trail Making Test (TMT), used commonly as a measure of frontal lobe function. Such work sheds additional light on the known shortcomings of the TMT as a localizing instrument, as indicated, for example, by studies of patients with focal brain lesions. Functional magnetic resonance imaging (fMRI) was used to record brain activity while participants performed the TMT using a custom-built, fiber-optic fMRI-compatible writing device, the "virtual stylus". Unlike in a previous fMRI study that used a verbal adaptation of the TMT, the virtual stylus enabled a closer depiction of the brain regions engaged by the actual paper-and-pencil task. Twelve, right-handed healthy young adults participated. In Part A of the task, participants were required to link in ascending order numbers (1-2-3 ...) that were randomly distributed on a computer screen. In Part B, participants were required to link alternately between numbers and letters (1-A-2-B ...). Although behavioral performance was somewhat less than typically obtained with the TMT due to use of the virtual stylus, distinct left-sided dorsolateral and medial frontal activity was revealed when comparing Part B versus Part A. These findings agree with existing literature showing sensitivity of the TMT to frontal regions in the left hemisphere. However, other activity was also observed (left middle and superior temporal gyrus) reinforcing that the brain-behavior correlations for the TMT are multifaceted and not restricted to the frontal lobe.     

Multicomponent analysis of a digital Trail Making Test

Objective: The purpose of the current study was to use a newly developed digital tablet-based variant of the TMT to isolate component cognitive processes underlying TMT performance.Method: Similar to the paper-based trail making test, this digital variant consists of two conditions, Part A and Part B. However, this digital version automatically collects additional data to create component subtest scores to isolate cognitive abilities. Specifically, in addition to the total time to completion and number of errors, the digital Trail Making Test (dTMT) records several unique components including the number of pauses, pause duration, lifts, lift duration, time inside each circle, and time between circles. Participants were community-dwelling older adults who completed a neuropsychological evaluation including measures of processing speed, inhibitory control, visual working memory/sequencing, and set-switching. The abilities underlying TMT performance were assessed through regression analyses of component scores from the dTMT with traditional neuropsychological measures.Results: Results revealed significant correlations between paper and digital variants of Part A (r_s = .541, p < .001) and paper and digital versions of Part B (r_s = .799, p < .001). Regression analyses with traditional neuropsychological measures revealed that Part A components were best predicted by speeded processing, while inhibitory control and visual/spatial sequencing were predictors of specific components of Part B. Exploratory analyses revealed that specific dTMT-B components were associated with a performance-based medication management task.Conclusions: Taken together, these results elucidate specific cognitive abilities underlying TMT performance, as well as the utility of isolating digital components.     

Trail Making Test A improves performance characteristics of the International HIV Dementia Scale to identify symptomatic HAND

Although HIV-associated dementia (HAD) occurs in less than 5 % of individuals with access to combination antiretroviral therapy, rates of milder forms of HIV-associated neurocognitive disorder (HAND) are much higher. We sought to define an optimal cut point for the International HIV Dementia Scale (IHDS) in Thailand for the identification of symptomatic HAND, defined as both HAD and mild neurocognitive disorder. We then sought to determine if adding a simple test from a larger neuropsychological battery could improve the performance characteristics for identifying symptomatic HAND. In this study, subjects comprising 75 seropositive adults in Bangkok, Thailand, completed neuropsychological tests and underwent a full neurological assessment. HAND diagnoses were determined by consensus conference using the 2007 Frascati criteria, blinded to the IHDS results. The optimal IHDS cut point was determined by receiver operating characteristic analysis with cross-validation. Individual neuropsychological tests were then evaluated and combined with the IHDS to test performance characteristics. The IHDS was poor at detecting symptomatic HAND at the optimized cut point of ≤10 (sensitivity, 53.3 %; specificity, 89.8 %). Trail Making Test A was most effective in improving performance characteristics when combined with the IHDS, with net sensitivity of 86 % and specificity of 79 %. In this setting, the IHDS performed poorly in identifying symptomatic HAND, but was substantially improved by the addition of Trail Making Test A, which typically requires less than 2 min to complete. This combination should be validated in a larger setting since it may address the critical need for HAND screening instruments in international settings.     

Heritability of Trail Making Test performance in multiplex schizophrenia families: implications for the search for an endophenotype

The impairment of the Trail Making Test (TMT) performance as a measure of executive function deficits has been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that it might be considered as a familial vulnerability marker, but its heritability estimates are not well known. This study investigated the genetic heritability of impairments in TMT performance using a sample of 80 schizophrenia patients, 145 unaffected first-degree relatives and 127 healthy controls from families with multiple members with schizophrenia. Consistent with previous reports in the literature, relatives performed in between healthy controls and schizophrenia patients. Based on these results, a variance component-analysis provided small, but significant additive heritability estimates for performance indices relating performance in TMT-version A to TMT-version B. These results showed that this significant but small evidence of heritability on the one hand suggests an association with genetic predisposition to schizophrenia, but that TMT performance is also associated with epigenetic or environmental factors.     

Clinical Utility of the Trail Making Test Practice Time

The Trail Making Test (TMT) is one of the most frequently used measures in clinical neuropsychology. Data obtained from the TMT practice times were analyzed to determine their utility in predicting success and failure on the full version of the test and to allow establishment of criteria by which to judge administration or discontinuation of the full test. Results indicated that TMT practice times were useful in predicting successful completion of Part A and B of the TMT. Tables are provided which describe the classification accuracy of various TMT practice times. These tables allow clinicians to select a practice-time cutoff and then use the cutoff as a heuristic to assist in the decision to administer the remainder of that particular part of the TMT or discontinue the test. A 20-s cutoff resulted in optimal prediction of successful completion (&lt; 180 s) of TMT Part A. A cutoff of 30 s optimally predicted successful completion (&lt; 300 s) of TMT Part B.     

Clinical utility of the Trail Making Test practice time

The Trail Making Test (TMT) is one of the most frequently used measures in clinical neuropsychology. Data obtained from the TMT practice times were analyzed to determine their utility in predicting success and failure on the full version of the test and to allow establishment of criteria by which to judge administration or discontinuation of the full test. Results indicated that TMT practice times were useful in predicting successful completion of Part A and B of the TMT. Tables are provided which describe the classification accuracy of various TMT practice times. These tables allow clinicians to select a practice-time cutoff and then use the cutoff as a heuristic to assist in the decision to administer the remainder of that particular part of the TMT or discontinue the test. A 20-s cutoff resulted in optimal prediction of successful completion (< 180 s) of TMT Part A. A cutoff of 30 s optimally predicted successful completion (< 300 s) of TMT Part B.     

Exploring the Validity of the Comprehensive Trail Making Test

The present study is the first independent investigation of the Comprehensive Trail Making Test (CTMT; Reynolds, 2002 Reynolds , C. R. , Pearson , N. A. , & Voress , J. K. ( 2002 ). Developmental Test of visual perception, adolescent and adult: Examiner's manual . Austin , TX : PRO-ED . [Google Scholar]) with both clinical and non-clinical samples. We examined convergent and divergent validity by exploring relationships between the CTMT and other measures. Discriminant validity was examined by comparing CTMT scores of non-clinical and clinical groups. Results indicate that the CTMT was largely unrelated to measures of processing speed and nonverbal reasoning, verbal processing, and psychiatric symptoms. The CTMT Composite score was able to differentiate between clinical and non-clinical groups with a large effect size. Overall, although further research is needed, results tentatively suggest that the CTMT may be a useful addition to a multifaceted neuropsychological test battery.     

Trail Making Test in Chronic Toxic Encephalopathy: Performance and Discriminative Potential

The objective of this study was to examine the influence of chronic toxic encephalopathy (CTE) on Trail Making Test (TMT) performance, with special focus on the discriminative potential of this test. We assessed TMT performance in patients diagnosed with CTE, patients with similar symptoms but no diagnosis, and healthy participants. Inferior performance was seen in CTE, and increasing age had a negative effect on TMT performance only for the CTE group. This effect was most pronounced in TMT-B. However, the ability of the TMT to identify CTE was low, whereas all healthy participants were identified as healthy. Thus, the sensitivity of TMT alone was low, but it succeeded in correctly classifying normal subjects. The pattern of results indicates that normal TMT performance may be seen in individuals with mild to moderate brain syndromes, such as CTE, whereas poor performance should not be expected in healthy individuals.     

Brief Communication: Trail Making Test and Malingering among Substance Abusers

The Trail Making Test (TMT) is often used for screening cognitive impairments in substance abusers. A possible limitation of the TMT in clinical settings is that substance abusers may malinger and give poor effort. In this study, previously validated cutting scores for malingering were applied to a sample of 7689 substance abusers (primary drug of abuse-number of subjects: Alcohol-1000, Marijuana-259, Hallucinogen-128, Cocaine/crack-4306, Heroin-1548, Narcotics/other opiates-191, Sedatives-72, Amphetamines-185) in drug abuse treatment programs. A mixed race sample was drawn from electronic files of data from the Drug Abuse Treatment Outcome Study (DATOS). The DATOS was a naturalistic, prospective cohort study that collected data from 1991-1993 in 96 programs in 11 cities in the United States. Data were analyzed to determine the number of substance abusers that fell beyond the preset malingering cutting scores on the TMT in this very large sample of substance abusing patients in treatment settings. The TMT variables of seconds to complete Part A and Part B, and the ratio score of Part B divided by Part A (B/A), ranged from no subjects beyond the preset cutting score for Part B to 2.28% (175 of 7689 subjects) for Part A to 9.74% (749 of 7689 subjects) for the ratio score. Most substance abusers fell within preset cutting score ranges, a finding that suggests that their scores are valid. Another interpretation of the data, however, is that the cutoff scores were not particularly sensitive to biased responding. Further research is indicated.     

Demographic effects on the Trail Making Test in sedatives abusers

Demographic effects on the Trail Making test (TMT), a test often used to screen for cognitive impairment, were examined in a sample of sedatives abusers in drug abuse treatment programs. A sample was drawn from electronic files of data from the Drug Abuse Treatment Outcome Study (DATOS). The DATOS was a naturalistic, prospective cohort study that collected data from 1991-1993 in 96 programs in 11 cities in the United States. The number of sedatives abusers' scores available for analysis were 72. Data were analyzed to determine the effects of sex, ethnicity, age, and education variables on the two parts of the TMT in this large treatment sample of sedatives abusers. None of the demographic variables were statistically significantly related to TMT parts A and B, when considered as single variables. In addition, R-Square values for overall models were low (A = .15, B = .18), suggesting that demographic effects on the TMT in a sample of sedative abusers are very weak.     

Demographic effects on the Trail Making Test in marijuana abusers

Demographic effects on the Trail Making Test (TMT), a test often used for screening for cognitive impairment, were examined in a sample of marijuana abusers in drug abuse treatment programs. A sample was drawn from electronic files of data from the Drug Abuse Treatment outcome Study (DATOS). The DATOS was a naturalistic, prospective cohort study that collected data from 1991-1993 in 96 programs in 11 cities in the United States. The number of marijuana abusers' scores available for analysis were 259. Data were analyzed to determine the effects of sex, ethnicity, age, and education variables on the two parts of the TMT in this large treatment sample of marijuana abusers. The variables of age and education level were statistically significantly related to TMT parts A and B, and ethnicity was statistically significant for part B of the TMT. R-Square values for overall models were moderate (A = .15, B = .18) suggesting that demographic effects on the TMT are weak.     

Demographic effects on the Trail Making Test in amphetamine abusers

Demographic effects on the Trail Making Test (TMT), a test often used for screening for cognitive impairment, were examined in a sample of amphetamine abusers in drug abuse treatment programs. A sample was drawn from electronic files of data from the Drug Abuse Treatment Outcome Study (DATOS). The DATOS was a naturalistic, prospective cohort study that collected data from 1991-1993, in 96 programs in 11 cities in the United States. The number of amphetamine abusers scores available for analysis were 185. Data were analyzed to determine the effects of sex, ethnicity, age, and education variables on the two parts of the TMT in this large treatment sample of amphetamine abusers. No variables were statistically significant for either parts A and B of the TMT. R-square values for overall models were also negligible (A = .03, B = .08) suggesting that demographic effects on the TMT account for a minuscule amount of overall variance in terms of amphetamine abusers' TMT performance.