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1.  The trail making test in India 
Indian Journal of Psychiatry  2007;49(2):113-116.
The trail making test (TMT) is a short and convenient estimate of cognitive functions, principally attention and working memory. Like most neuropsychological tests, it is derived from and primarily applicable to English-speaking individuals. Norms for other ethnic minorities may differ significantly. The application of majority or mixed norms to specific ethnic subcultures may introduce systematic bias. To examine the impact of an English test on primarily nonEnglish-speaking individuals, outpatients attending the dermatology department of a large Indian hospital (n = 120) were asked to complete the English version of the TMT. The time taken to complete the TRAILS was unexpectedly long, although all the subjects scored within normal limits on the modified mini mental status examination and a test for general knowledge. Possible reasons for the delayed completion times are discussed below.
doi:10.4103/0019-5545.33258
PMCID: PMC2917075  PMID: 20711393
Cognitive dysfunction; schizophrenia; trail making test
2.  EQUIVALENCY OF SPANISH LANGUAGE VERSIONS OF THE TRAIL MAKING TEST PART B INCLUDING OR EXCLUDING “CH” 
The Clinical neuropsychologist  2008;22(4):662-665.
Spanish speakers commonly use two versions of the alphabet, one that includes the sound “Ch” between C and D and another that goes directly to D, as in English. Versions of the Trail Making Test Part B (TMT-B) have been created accordingly to accommodate this preference. The pattern and total number of circles to be connected are identical between versions. However, the equivalency of these alternate forms has not been reported. We compared the performance of 35 healthy Spanish speakers who completed the “Ch” form (CH group) to that of 96 individuals who received the standard form (D group), based on whether they mentioned “Ch” in their oral recitation of the alphabet. The groups had comparable demographic characteristics and overall neuropsychological performance. There were no significant differences in TMT-B scores between the CH and D groups, and relationships with demographic variables were comparable. The findings suggest that both versions are equivalent and can be administered to Spanish speakers based on their preference without sacrificing comparability.
doi:10.1080/13854040701476976
PMCID: PMC3059802  PMID: 17853122
Alphabet; CH; Equivalent forms; Spanish; Trails B
3.  Cognitive correlates of HVOT performance differ between individuals with mild cognitive impairment and normal controls 
Objective
To clinically characterize performance on the Hooper Visual Organization Test (HVOT) among participants with mild cognitive impairment (MCI) and to identify naming and executive functioning correlates associated with HVOT performance among MCI participants and normal controls (NC).
Background
The HVOT is a common neuropsychological instrument that measures visuospatial skills and agnosia. It has, however, been criticized for its multifactorial nature, as several studies have reported executive or language correlates of HVOT performance. To our knowledge, simultaneous comparison of executive functioning and language demands of the HVOT has never been performed among an older cohort.
Methods
The HVOT, two tests of executive functioning [Trail Making Test, Part B (TMT-B), Controlled Oral Word Association (COWA)] and two tests of naming [abbreviated Boston Naming Test (BNT), Animal Naming] were administered to 222 NC, 166 MCI, and 68 Alzheimer’s disease (AD) individuals.
Results
HVOT scores were significantly different between all three groups in the expected direction (AD < MCI < NC). Linear regression among NC participants revealed that COWA, age, and BNT were significantly associated with HVOT scores, accounting for 12%, 6%, and 4% of HVOT variance, respectively. Among MCI participants, the BNT accounted for 43% of HVOT variance. Neither TMT-B nor Animal Naming was a significant predictor for either group.
Conclusion
Among NC participants, rapid word generation (i.e., COWA), a measure of executive functioning, is the most salient predictor of HVOT performance. In contrast, lexical retrieval (i.e., BNT) is the most salient language or executive functioning predictor of HVOT performance among MCI participants. These findings extend previous claims that the HVOT is multifactorial by suggesting that reduced HVOT performance in MCI patients may be related to mild lexical retrieval impairments.
doi:10.1016/j.acn.2006.06.001
PMCID: PMC2746420  PMID: 16893623
Object recognition; Mild cognitive impairment; Hooper Visual Organization Test
4.  The Relationship between Tests of Neurocognition and Performance on a Laparoscopic Simulator 
Minimally Invasive Surgery  2010;2010:486174.
Objective. To estimate if there is a relationship between the results of tests of neurocognition and performance on a laparoscopic surgery simulator. Methods and Materials. Twenty participants with no prior laparoscopic experience had baseline cognitive tests administered (Trail Making Test, Part A and B (TMT-A and TMT-B), Grooved Peg Board Test, Symbol Digit Modalities Test, Symbol Digit Recall Test, and Stroop Interference Test), completed a demographic questionnaire, and then performed laparoscopy using a simulator. We correlated the results of cognitive tests with laparoscopic surgical performance. Results. One cognitive test sensitive to frontal lobe function, TMT-A, significantly correlated with laparoscopic surgical performance on the simulator (correlation coefficient of 0.534 with P < .05). However, the correlation between performance and other cognitive tests (TMT-B, Grooved Peg Board Test, Symbol Digit Modalities Test, Symbol Digit Recall Test, and Stroop Interference Test) was not statistically significant. Conclusion. Laparoscopic performance may be related to measures of frontal lobe function. Neurocognitive tests may predict motor skills abilities and performance on laparoscopic simulator.
doi:10.1155/2010/486174
PMCID: PMC3196331  PMID: 22091352
5.  Executive functions in schizophrenia 
Indian Journal of Psychiatry  2005;47(1):21-26.
Background:
Executive functions constitute the core deficit in schizophrenic illness and have been related to structural and functional deficits, cognitive impairments and final outcome.
Aim:
To study the various dimensions of executive functions such as goal formulation, planning, behavioural programming and effective performance.
Methods:
By using direct and indirect clinical neuropsychological methods, 31 patients were studied neuropsychologically by the trail-making test (TMT), Raven matrices and fluency tests, and their symptom patterns were quantified using the Positive and Negative Syndrome Scale (PANSS).
Results:
The patients had varying degrees of involvement of different dimensions of executive functions. There was an inverse relationship to TMT and a positive correlation with Raven matrices and fluency tests.
Conclusion:
The dimensions of executive functions did not show any significant relationship with age, duration of illness or most scores in PANSS. Our findings are relevant for remediation and rehabilitation measures.
doi:10.4103/0019-5545.46069
PMCID: PMC2918311
Executive functions; neurocognition; schizophrenia
6.  A Bias Against Disconfirmatory Evidence Is Associated With Delusion Proneness in a Nonclinical Sample 
Schizophrenia Bulletin  2007;33(4):1023-1028.
Previous work has suggested that a bias against disconfirmatory evidence (BADE) may be associated with the schizophrenia spectrum. The current investigation focused on whether a BADE (1) overlaps with traditional measures of memory and executive functions or selectively taps into a unique aspect of cognition and (2) is correlated with delusional ideation but not with other aspects of schizotypy. Sixty-eight undergraduate students were administered the Schizotypal Personality Questionnaire (SPQ), the BADE test, the Rey Auditory Verbal Learning Test (RAVLT), the Wisconsin Card Sorting Test (WCST), the Trail Making Tests A and B (TMT), and tests used to estimate IQ. Factor analysis of all cognition measures resulted in a 6-factor solution, 4 of which reflected the 4 domains of neuropsychological tests (WCST, RAVLT, TMT, and IQ), and 2 of which reflected different aspects of the BADE test: Initial Belief and Integration of Disconfirmatory Evidence. This solution suggests that BADE measures were independent from the other cognitive domains measured. Integration of Disconfirmatory Evidence was the only factor that correlated with delusion-content subscales of the SPQ, providing support for the contribution of a BADE to delusional ideation.
doi:10.1093/schbul/sbm013
PMCID: PMC2632321  PMID: 17347526
schizotypy; delusions; cognition; decision making; reasoning
7.  Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance 
Neurobiology of Aging  2010;33(7):1203-1214.e2.
The current study tested the accuracy of primary MRI and cerebrospinal fluid (CSF) biomarker candidates and neuropsychological tests for predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. In a cross-validation paradigm, predictor models were estimated in the training set of AD (N = 81) and elderly control subjects (N = 101). A combination of CSF t-tau/Aβ1-4 ratio and MRI biomarkers or neuropsychological tests (free recall and trail making test B (TMT-B)) showed the best statistical fit in the AD vs. HC comparison, reaching a classification accuracy of up to 64% when applied to the prediction of MCI conversion (3.3-year observation interval, mean = 2.3 years). However, several single-predictor models showed a predictive accuracy of MCI conversion comparable to that of any multipredictor model. The best single predictors were right entorhinal cortex (prediction accuracy = 68.5% (95% CI (59.5, 77.4))) and TMT-B test (prediction accuracy 64.6% (95% CI (55.5, 73.4%))). In conclusion, short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects.
doi:10.1016/j.neurobiolaging.2010.10.019
PMCID: PMC3328615  PMID: 21159408
Alzheimer's disease; Dementia; Mild cognitive impairment; Mild cognitive impairment (MCI); Autopsy-confirmation; Biomarkers; Early detection; Cerebrospinal fluid; Cerebrospinal fluid (CSF); Aβ1-42; Tau; p-tau; MRI; Hippocampus; Volumetry; Entorhinal cortex; Prodromal; ADNI
8.  TRAIL MAKING TEST PREDICTS PHYSICAL IMPAIRMENT AND MORTALITY IN OLDER PERSONS 
OBJECTIVE
To examine whether performance in Trail Making Test (TMT) predicts mobility impairment and mortality in older persons.
DESIGN
Prospective cohort study.
SETTING
Community-dwelling older persons enrolled in the InCHIANTI Study.
PARTICIPANTS
865 participants ≥65 years, free of major cognitive impairment (MMSE >21), with complete baseline data on Trail Making Test (TMT) performance. Of these, 583 performed the Short Physical Performance Battery (SPPB) both at baseline and after 6-years. Of the initial 865 participants, 222 died during 9-years of follow-up.
MEASUREMENTS
The Trail Making Test (TMT-A, TMT-B, TMT-B minus A) and the Short Physical Performance Battery for the assessment of lower extremity function were administered at baseline and at 6-years follow-up. Impaired mobility was defined as an SPPB <10. Vital status was ascertained over a 9-year follow-up.
RESULTS
Of 679 participants free of ADL disability and with SPPB ≥10 at baseline, 53 (11.0 %) developed impaired mobility (SPPB score < 10) during the follow-up. Participants in the lowest quartile of TMT-performance at baseline were significantly more likely to develop a SPPB score < 10 during the 6 years follow-up compared to those in the highest quartile. After adjusting for potential confounders this prognostic effect was substantially maintained. Also, worse performance on the TMT was associated with significantly greater decline of SPPB score over the 6-year follow- up, after adjusting for age, sex and, baseline SPPB score. During a nine-years follow-up, 222 participants (25.7 %) died. The proportion of participants who died was higher in the lowest performance quartile compared with the best performance quartile of TMT score, for TMT-A; TMT-B; and TMT B-A scores.
CONCLUSION
Performance in the Trail Making Test is a strong, independent predictor of mobility impairment, accelerated decline in lower extremity function and mortality among older adults living in the community. The Trail Making Test is a useful addition to geriatric assessment.
doi:10.1111/j.1532-5415.2010.02780.x
PMCID: PMC2935170  PMID: 20398153
Trail Making Test; neuropsychological tests; physical impairment; mortality
9.  The Shape Trail Test: Application of a New Variant of the Trail Making Test 
PLoS ONE  2013;8(2):e57333.
Objective
The Trail making test (TMT) is culture-loaded because of reliance on the Latin alphabet, limiting its application in Eastern populations. The Shape Trail Test (STT) has been developed as a new variant. This study is to examine the applicability of the STT in a senile Chinese population and to evaluate its potential advantages and disadvantages.
Method
A total of 2470 participants were recruited, including 1151 cognitively normal control (NC), 898 amnestic mild cognitive impairment (aMCI), and 421 mild Alzheimer disease (AD) patients. Besides the STT, the Mini mental state examination and a comprehensive neuropsychological battery involving memory, language, attention, executive function and visuospatial ability were administered to all the participants. In a subgroup of 100 NC and 50 AD patients, both the STT and the Color Trail Test (CTT) were performed.
Results
In NC, the time consumed for Part A and B (STT-A and STT-B) significantly correlated with age and negatively correlated with education (p<0.01). STT-A and B significantly differed among the AD, aMCI and NC. The number that successfully connected within one minute in Part B (STT-B-1 min) correlated well with STT-B (r = 0.71, p<0.01) and distinguished well among NC, aMCI and AD. In the receiver operating characteristic curve analysis, the AUCs (area under the curve) for STT-A, STT-B, and STT-B-1min in identifying AD were 0.698, 0.694 and 0.709, respectively. The STT correlated with the CTT, but the time for completion was longer.
Conclusion
The TMT is a sensitive test of visual search and sequencing. The STT is a meaningful attempt to develop a “culture-fair” variant of the TMT in addition to the CTT.
doi:10.1371/journal.pone.0057333
PMCID: PMC3577727  PMID: 23437370
10.  Computerised cognitive assessment of concussed Australian Rules footballers 
Background—"Paper and pencil" neuropsychological tests play an important role in the management of sports related concussions. They provide objective information on the athlete's cognitive function and thus facilitate decisions on safe return to sport. It has been proposed that computerised cognitive tests have many advantages over such conventional tests, but their role in this domain is yet to be established.
Objectives—To measure cognitive impairment after concussion in a case series of concussed Australian Rules footballers, using both computerised and paper and pencil neuropsychological tests. To investigate the role of computerised cognitive tests in the assessment and follow up of sports related concussions.
Methods—Baseline measures on the Digit Symbol Substitution Test (DSST), Trail Making Test-Part B (TMT), and a simple reaction time (SRT) test from a computerised cognitive test battery (CogState) were obtained in 240 players. Tests were repeated in players who had sustained a concussive injury. A group of non-injured players were used as matched controls.
Results—Six concussions were observed over a period of nine weeks. At the follow up, DSST and TMT scores did not significantly differ from baseline scores in both control and concussed groups. However, analysis of the SRT data showed an increase in response variability and latency after concussion in the injured athletes. This was in contrast with a decrease in response variability and no change in latency on follow up of the control players (p<0.02).
Conclusion—Increased variability in response time may be an important cognitive deficit after concussion. This has implications for consistency of an athlete's performance after injury, as well as for tests used in clinical assessment and follow up of head injuries.
Key Words: concussion; football; neuropsychology; cognitive; head injury
doi:10.1136/bjsm.35.5.354
PMCID: PMC1724390  PMID: 11579074
11.  Assessment of cognitive function in patients with essential hypertension treated with lercanidipine 
Objectives
The aim of this longitudinal, open-label, comparative, multicenter study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine.
Methods
Hypertensive patients aged 40 years or older were treated with lercanidipine (10mg daily) after 7–10 days washout period. The duration of the study was 6 months. Blood pressure (BP) was measured every 4 weeks (JNC 6th report). In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT).
Results
In the study population of 467 patients, BP decreased from 154.4/95.3 mmHg at baseline to 134.8/80.7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% an angiotensin-converting enzyme inhibitor, and 6% doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation) MMSE scores improved from 32.35 (2.59) to 33.25 (2.36) (p<0.0001). Patients with good BP control scored significantly better than those with inadequate BP control (p<0.05), which was already observed at the first month.
Conclusions
The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be associated with a decrease in BP.
PMCID: PMC1994004  PMID: 17323604
lercanidipine; hypertension; cognitive function
12.  Impaired Set-Shifting Ability in Patients with Eating Disorders, Which Is Not Moderated by Their Catechol-O-Methyltransferase Val158Met Genotype 
Psychiatry Investigation  2010;7(4):298-301.
The aim of this study was to examine the set-shifting ability in women with both anorexia nervosa (AN) and bulimia nervosa (BN) and to investigate whether it is contributed by the catechol-O-methyltransferase (COMT) Val158Met genotype. A total of 102 Korean participants-40 women with lifetime AN, 28 women with lifetime BN, and 34 healthy women of comparable age and intelligence quotient- were examined. A neuropsychological battery of tests was applied and blood samples were obtained for COMT Val158Met genotyping. Set-shifting impairments Trail Making Test (TMT, Part B) were found in patients with AN and BN, respectively. Furthermore, the eating disorders were also linked to deficits in attentional mechanisms (TMT, Part A) and motor skills (Finger Tapping Test). Finally, set-shifting and its link to eating disorders were not moderated by COMT Val158Met genotype.
doi:10.4306/pi.2010.7.4.298
PMCID: PMC3022318  PMID: 21253415
Eating disorders; Set-shifting ability; Anorexia nervosa; Bulimia nervosa; Catechol-O-methyltransferase
13.  A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case-control and family-based sample of German ancestry 
Schizophrenia research  2010;118(1-3):98-105.
Background
Dysbindin (DTNBP1) is a widely-studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity.
Method
Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT.
Results
No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pairwise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pairwise comparisons.
Conclusions
Our results, based on one of the largest sample of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.
doi:10.1016/j.schres.2009.12.025
PMCID: PMC2856768  PMID: 20083391
polymorphism; COMT; epistasis; endophenotype; cognitive function
14.  The Trail Making Test in Prodromal Huntington Disease: Contributions of Disease Progression to Test Performance 
We examined the Trail Making Test (TMT) in a sample of 767 participants with prodromal Huntington disease (prodromal HD) and 217 healthy comparisons to determine the contributions of motor, psychiatric, and cognitive changes to TMT scores. Eight traditional and derived TMT scores were also evaluated for their ability to differentiate prodromal participants closer to estimated age of diagnosis from those farther away and prodromal individuals from healthy comparisons. Results indicate that motor signs only mildly affected part A, and psychiatric symptoms did not affect either part. Tests of perceptual processing, visual scanning, and attention were primarily associated with part A, and executive functioning (response inhibition, set-shifting), processing speed, and working memory were associated with part B. Additionally, TMT scores differentiated between healthy comparisons and prodromal HD individuals as far as 9–15 years before estimated diagnosis. In participants manifesting prodromal motor signs and psychiatric symptoms, the TMT primarily measures cognition and is able to discriminate between groups based on health status and estimated time to diagnosis.
doi:10.1080/13803395.2010.541228
PMCID: PMC3159183  PMID: 21302170
Huntington disease; cognition; motor; psychiatric; neurodegenerative
15.  Sequential Cognitive Skills in Emphysema Patients Following Lung Volume Reduction Surgery: A Two Year Longitudinal Study 
PURPOSE
This study compared visuomotor speed and cognitive flexibility in emphysema patients treated either with standard multidisciplinary medical therapy (MT) or lung volume reduction surgery (LVRS), followed over a 2-year period.
METHODS
MT patients (n=544) and 542 LVRS patients completed the Trail Making Test (TMT) Parts A and B prior to randomization (baseline). Testing was repeated at 1 and 2 years.
RESULTS
There were no differences on scores for TMT Part A and B between the LVRS and MT groups at baseline or at years 1 and 2. No significant difference between MT and LVRS was noted in terms of overall change in TMT Part A and B over 2 years. The MT group had a significant improvement on TMT-Part A at each followup time compared to baseline (P<.03) but the LVRS group did not. Both the MT and LVRS groups had a significant decline in performance (increase in time to completion) on TMT-Part B when comparing year 1 to baseline (P<.0001).
CONCLUSION
Emphysema patients who received LVRS or MT as treatment performed similarly on measures of visuomotor speed and flexibility at baseline and 1 and 2 year followup. Both groups showed improvement on visuomotor speed during the first year yet overall cognitive flexibility declined. By the second year neither group had any significant change from baseline. These findings suggest that improvement on visuomotor speed and flexibility, observed in a previous 6-month study of LVRS subjects, was not sustained at 1 and 2 year followup.
doi:10.1097/HCR.0b013e3182343bc8
PMCID: PMC3221608  PMID: 22089885
Lung volume reduction surgery; Medical therapy; Sequential skills
16.  Familial resemblance for executive functions in families of schizophrenic and bipolar patients 
Psychiatry Research  2006;144(2-3):131-138.
Executive dysfunctions are considered to be putative markers of familial/genetic vulnerability to both schizophrenia and bipolar disorder. However, familial resemblance must be demonstrated before executive functions are used as a potential endophenotype. The aim of this study was to investigate familial resemblance for executive functions in families of schizophrenic and bipolar subjects. We assessed executive functions by means of two tests – the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT) - in 351 subjects from five populations: schizophrenic patients, bipolar patients, a group of relatives for each patient group and controls. For both tests, cognitive assessment results were consistent with previous studies: schizophrenic patients showed the greatest impairment, followed by bipolar patients and then the two groups of relatives. In families of bipolar patients we observed familial resemblance for the WCST and part A and part B of the TMT. However, by contrast with the classical point of view, considering executive measures to be markers of genetic vulnerability to schizophrenia, we did not demonstrate familial resemblance for either of the two executive tests in families of schizophrenic patients. Thus, executive measures, as assessed by WCST or TMT, should not be used as endophenotypes in genetic studies of schizophrenia unless confounders are identified and their effects eliminated.
doi:10.1016/j.psychres.2005.11.013
PMCID: PMC1933530  PMID: 17011636
Adult; Bipolar Disorder; epidemiology; genetics; Cognition Disorders; diagnosis; epidemiology; genetics; Family; Female; Humans; Male; Neuropsychological Tests; Phenotype; Prevalence; Schizophrenia; epidemiology; genetics; Severity of Illness Index; exectutive dysfunction; genetics; endophenotype; cognition
17.  Poor Trail Making Test Performance Is Directly Associated with Altered Dual Task Prioritization in the Elderly – Baseline Results from the TREND Study 
PLoS ONE  2011;6(11):e27831.
Background
Deterioration of executive functions in the elderly has been associated with impairments in walking performance. This may be caused by limited cognitive flexibility and working memory, but could also be caused by altered prioritization of simultaneously performed tasks. To disentangle these options we investigated the associations between Trail Making Test performance—which specifically measures cognitive flexibility and working memory—and dual task costs, a measure of prioritization.
Methodology and Principal Findings
Out of the TREND study (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders), 686 neurodegeneratively healthy, non-demented elderly aged 50 to 80 years were classified according to their Trail Making Test performance (delta TMT; TMT-B minus TMT-A). The subjects performed 20 m walks with habitual and maximum speed. Dual tasking performance was tested with walking at maximum speed, in combination with checking boxes on a clipboard, and subtracting serial 7 s at maximum speeds. As expected, the poor TMT group performed worse when subtracting serial 7 s under single and dual task conditions, and they walked more slowly when simultaneously subtracting serial 7 s, compared to the good TMT performers. In the walking when subtracting serial 7 s condition but not in the other 3 conditions, dual task costs were higher in the poor TMT performers (median 20%; range −6 to 58%) compared to the good performers (17%; −16 to 43%; p<0.001). To the contrary, the proportion of the poor TMT performance group that made calculation errors under the dual tasking situation was lower than under the single task situation, but higher in the good TMT performance group (poor performers, −1.6%; good performers, +3%; p = 0.035).
Conclusion
Under most challenging conditions, the elderly with poor TMT performance prioritize the cognitive task at the expense of walking velocity. This indicates that poor cognitive flexibility and working memory are directly associated with altered prioritization.
doi:10.1371/journal.pone.0027831
PMCID: PMC3218043  PMID: 22114705
18.  The Relationship Between Gray Matter Morphometry and Neuropsychological Performance in a Large Sample of Cognitively Healthy Adults 
Brain imaging and behavior  2007;1(1-2):3-10.
Voxel-based morphometry (VBM) was used to examine the relationship between gray matter (GM) volume and performance on two commonly used clinical neuropsychological measures of frontal lobe or executive function, the Trail Making Test part B (TrailsB) and the Controlled Oral Word Association Test (COWAT) in 221 cognitively healthy adults between the ages of 18 and 84. We hypothesized that these measures would be associated with GM volume in the dorsolateral frontal lobes. Voxel-based multiple regression was used to correlate cognitive function with modulated GM probability maps while controlling for age, education, gender, and total intracranial volume. A relationship with TrailsB was found in bilateral lateral inferior frontal gyri and left basal ganglia. A relationship with COWAT was found in the left lateral inferior and middle frontal gyri. Lesion studies have long implicated the importance of these regions for executive function. The present results confirm and extend those prior findings to healthy adults.
doi:10.1007/s11682-007-9000-5
PMCID: PMC2558675  PMID: 18836573
VBM; Executive function; Frontal lobe; MRI
19.  Is the N-Back Task a Valid Neuropsychological Measure for Assessing Working Memory? 
The n-back is a putative working memory task frequently used in neuroimaging research; however, literature addressing n-back use in clinical neuropsychological evaluation is sparse. We examined convergent validity of the n-back with an established measure of working memory, digit span backward. The relationship between n-back performance and scores on measures of processing speed was also examined, as was the ability of the n-back to detect potential between-groups differences in control and Parkinson's disease (PD) groups. Results revealed no correlation between n-back performance and digit span backward. N-back accuracy significantly correlated with a measure of processing speed (Trail Making Test Part A) at the 2-back load. Relative to controls, PD patients performed less accurately on the n-back and showed a trend toward slower reaction times, but did not differ on any of the neuropsychological measures. Results suggest the n-back is not a pure measure of working memory, but may be able to detect subtle differences in cognitive functioning between PD patients and controls.
doi:10.1093/arclin/acp063
PMCID: PMC2770861  PMID: 19767297
Working memory; Executive function; Information processing speed; Parkinson's disease; Neuropsychology
20.  Predictors of Decision-Making on the Iowa Gambling Task: Independent Effects of Lifetime History of Substance Use Disorders and Performance on the Trail Making Test 
Brain and cognition  2007;66(3):243-252.
Poor decision-making and executive function deficits are frequently observed in individuals with substance use disorders (SUDs), and executive deficits may contribute to poor decision-making in this population. This study examined the influence of lifetime history of an alcohol, cocaine, heroin, or polysubstance use disorder on decision-making as measured by the Iowa Gambling Task (IGT) after controlling for executive ability, demographic characteristics, and current substance use. Participants (131 with lifetime history of SUD and 37 controls) completed the IGT and two neuropsychological tests: the Trail Making Test and the Controlled Oral Word Association Test. Control participants performed significantly better than those with a lifetime SUD history on the IGT, but performance on the neuropsychological tests was comparable for the two groups. A lifetime SUD diagnosis was associated with performance on the IGT after controlling for covariates, and Trail Making Test performance was associated with IGT performance in both SUD and control participants.
doi:10.1016/j.bandc.2007.09.001
PMCID: PMC2292486  PMID: 17942206
decision-making; substance use disorder; executive ability; neuropsychological tests; Iowa Gambling Task; Trail Making Test; Controlled Oral Word Association Test
21.  A randomized controlled trial of Tai chi for balance, sleep quality and cognitive performance in elderly Vietnamese 
Objective
To evaluate the effects of Tai chi exercise on balance, sleep quality, and cognitive performance in community-dwelling elderly in Vinh city, Vietnam.
Design
A randomized controlled trial.
Participants
One hundred two subjects were recruited.
Intervention
Subjects were divided randomly into two groups. The Tai chi group was assigned 6 months’ Tai chi training. The control group was instructed to maintain their routine daily activities.
Outcome measures
The Falls Efficacy Scale (FES), Pittsburgh Sleep Quality Index (PSQI), and Trail Making Test (TMT) were used as primary outcome measures.
Results
Participants in the Tai chi group reported significant improvement in TMT (part A) (F [1, 71] = 78.37, P < 0.001) and in TMT (part B), (F [1, 71] = 175.00, P < 0.001) in comparison with the control group. Tai chi participants also reported better scores in FES (F [1, 71] = 96.90, P < 0.001) and in PSQI (F [1,71] = 43.69, P = 0.001) than the control group.
Conclusion
Tai chi is beneficial to improve balance, sleep quality, and cognitive performance of the elderly.
doi:10.2147/CIA.S32600
PMCID: PMC3396052  PMID: 22807627
Tai chi; sleep; balance
22.  Cognitive switching processes in young people with attention-deficit/hyperactivity disorder 
Patients with attention-deficit/hyperactivity disorder (ADHD) can be slow at switching between stimuli, or between sets of stimuli to control behaviour appropriate to changing situations. We examined clinical and experimental parameters that may influence the speed of such processes measured in the trail-making (TMT) and switch-tasks in cases with ADHD combined-type, their non-affected siblings and unrelated healthy controls. The latency for completion of the trail-making task controlling for psychomotor processing (TMT B–A) was longer for ADHD cases, and correlated with Conners’ ratings of symptom-severity across all subjects. The effect decreased with age. Switch-task responses to questions of “Which number?” and “How many?” between sets of 1/111 or 3/333 elicited differential increases in latency with condition that affected all groups. But there was evidence for increased symptom-related intra-individual variability among the ADHD cases, and across all subjects. Young siblings showed familiality for some measures of TMT and switch-task performance but these were modest. The potential influence of moderator variables on the efficiency of processing stimulus change rather than the speed of processing are discussed.
doi:10.1016/j.acn.2007.09.002
PMCID: PMC2215325  PMID: 17976951
ADHD; attention; heritability; risk; siblings; set; switch; trail-making
23.  The Development of a Trial Making Test in Young Children: The TRAILS-P 
The Clinical neuropsychologist  2004;18(3):411-422.
Preschool children have a more limited verbal repertoire, less proficient manual skills, and more variable attention spans relative to those of school age, with comparatively few neuropsychological tasks available for use in this age range. A prototypic neuropsychological test, the Trail Making Test, was adapted for use with young children, the TRAILS-P, using a developmentally salient storybook format with colorful stimuli in differing conditions with varying executive demands. The TRAILS-P was administered to 103 normally developing preschoolers between 2 and 6 years of age; 30 of these children were retested within one month to determine test reliability. Correlations among latencies to complete each condition and condition errors generally were moderate to high, suggesting coherence in test content. There also was evidence for good test retest reliability. Latency to complete the TRAILS-P conditions differed as a function of the interaction of condition type and age group. Although the youngest children generally took more time to complete all TRAILS-P conditions, 3-year-old children were disproportionately slow to complete the condition that required shifting between stamping stimuli of two classes, with distraction by the additional presence of irrelevant stimuli. In contrast, the number of errors differed only in the 5-year-olds relative to younger children. These findings suggest that executive abilities can be assessed adequately in young children when tasks are designed to take advantage of the developmentally unique features of the preschool period.
doi:10.1080/138540409052416
PMCID: PMC2700546  PMID: 15739812
24.  Impaired Design Fluency Is a Marker of Pathological Cognitive Aging; Results from the Korean Longitudinal Study on Health and Aging 
Psychiatry Investigation  2012;9(1):59-64.
Objective
We investigated neuropsychological markers that can be used to discriminate pathological cognitive aging from normal cognitive aging.
Methods
We administered frontal lobe function tests including the Wisconsin Card Sorting Test (WCST), digit span test, lexical fluency test, fixed condition design fluency test, and Trail Making Test B (TMT-B) to 92 individuals with pathological cognitive aging (PCA) and 222 individuals with normal cognitive aging (NCA). We examined the main effects of participants' diagnoses (PCA, NCA) and age (65-69 years old, 70-74 years old and 75 years old or over) on their test performance using multivariate analysis of variance.
Results
The main effects of both the diagnosis (F=2.860, p=0.002) and the age group (F=2.484, p<0.001) were significant. The PCA group showed lower performance on the backward digit span test (F=14.306, p<0.001), fixed condition design fluency test (F=8.347, p=0.004) and also exhibited perseverative errors in the WCST (F=4.19, p=0.042) compared with the NCA group. The main effect of the diagnosis on the backward digit span test and the fixed condition design fluency test remained significant after Bonferroni correction. The main effect of age remained significant in the TMT-B (F=8.737, p<0.001) after Bonferroni correction. Other test scores were not influenced by diagnosis or age.
Conclusion
The design fluency task may be a good neuropsychological marker to assess pathological cognitive aging.
doi:10.4306/pi.2012.9.1.59
PMCID: PMC3285742  PMID: 22396686
Design fluency; Pathological cognitive aging; Normal cognitive aging; Mild cognitive impairment
25.  Gray matter correlates of set-shifting among neurodegenerative disease, mild cognitive impairment, and healthy older adults 
There is increasing recognition that set-shifting, a form of cognitive control, is mediated by different neural structures. However, these regions have not yet been carefully identified as many studies do not account for the influence of component processes (e.g., motor speed). We investigated gray matter correlates of set-shifting while controlling for component processes. Using the Design Fluency (DF), Trail Making Test (TMT), and Color Word Interference (CWI) subtests from the Delis-Kaplan Executive Function System (D-KEFS), we investigated the correlation between set-shifting performance and gray matter volume in 160 subjects with neurodegenerative disease, mild cognitive impairment, and healthy older adults using voxel-based morphometry. All three set-shifting tasks correlated with multiple, widespread gray matter regions. After controlling for the component processes, set-shifting performance correlated with focal regions in prefrontal and posterior parietal cortices. We also identified bilateral prefrontal cortex and the right posterior parietal lobe as common sites for set-shifting across the three tasks. There was a high degree of multicollinearity between the set-shifting conditions and the component processes of TMT and CWI, suggesting DF may better isolate set-shifting regions. Overall, these findings highlight the neuroanatomical correlates of set-shifting and the importance of controlling for component processes when investigating complex cognitive tasks.
doi:10.1017/S1355617710000408
PMCID: PMC2891121  PMID: 20374676
D-KEFS; Design fluency; Trail making test; Color word interference; Executive function; Voxel-based morphometry

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