A Randomized, Controlled Pilot Study of Mindfulness-Based Stress Reduction in Healthy Older Adults.

OBJECTIVES: As the aging population increases, it is critical to find ways to sustain older adults' health and well-being. Mindfulness-Based Stress Reduction (MBSR) may be one approach, but its effects are difficult to discern because few studies have conducted randomized controlled trials with an active control group and blinded examiners. We begin to address these gaps with a pilot study examining the feasibility of conducting an MBSR intervention with an active control condition in healthy older adults. METHODS: Participants were randomly assigned to one of two classes, MBSR or Brain Health education. Classes were matched for time, format, and instructor. The study examined acceptability, practicality, implementation, and preliminary efficacy using a range of participant questionnaires, instructor ratings, cognitive measures assessed by blinded examiners, and attendance. RESULTS: Both MBSR and the Brain Health class evidenced high rates of recruitment, participant satisfaction, and retention. Implementation procedures were successful, and preliminary results revealed similar levels of efficacy across both classes. CONCLUSIONS: This study demonstrates the feasibility of an MBSR intervention in healthy older adults. CLINICAL IMPLICATIONS: MBSR, with its focus on improving stress and self-awareness, has the potential to be an approach that can improve aging adults' health and coping skills.

An empirical comparison of univariate versus multivariate methods for the analysis of brain-behavior mapping.

Lesion symptom mapping (LSM) tools are used on brain injury data to identify the neural structures critical for a given behavior or symptom. Univariate lesion symptom mapping (ULSM) methods provide statistical comparisons of behavioral test scores in patients with and without a lesion on a voxel by voxel basis. More recently, multivariate lesion symptom mapping (MLSM) methods have been developed that consider the effects of all lesioned voxels in one model simultaneously. In the current study, we provide a much-needed systematic comparison of several ULSM and MLSM methods, using both synthetic and real data to identify the potential strengths and weaknesses of both approaches. We tested the spatial precision of each LSM method for both single and dual (network type) anatomical target simulations across anatomical target location, sample size, noise level, and lesion smoothing. Additionally, we performed false positive simulations to identify the characteristics associated with each method's spurious findings. Simulations showed no clear superiority of either ULSM or MLSM methods overall, but rather highlighted specific advantages of different methods. No single method produced a thresholded LSM map that exclusively delineated brain regions associated with the target behavior. Thus, different LSM methods are indicated, depending on the particular study design, specific hypotheses, and sample size. Overall, we recommend the use of both ULSM and MLSM methods in tandem to enhance confidence in the results: Brain foci identified as significant across both types of methods are unlikely to be spurious and can be confidently reported as robust results.

An improved spatial span test of visuospatial memory.

In the widely used Corsi Block Test and Wechsler Spatial Span Tests, participants must reproduce sequences of blocks in the order touched by the examiner until two trials are missed at the same sequence length. The examiner records either the maximum number of blocks correctly reported or the total number of correct lists. Here, we describe a computerized spatial span test (C-SST) that uses psychophysical procedures to quantify visuospatial mean span (MnS) with sub-digit precision. Results from 187 participants ranging in age from 18 to 82 years showed that accuracy declined gradually with list length around the MnS (by ∼30% per item). Simulation studies revealed high variance and biases in CBT and Wechsler measures, and demonstrated that the C-SST provided the most accurate estimate of true span (i.e., the sequence length producing 50% correct). MnS declined more rapidly with age than mean digit span (MnDS) measured in the same participants. Response times correlated with both MnS and MnDS scores. Error analysis showed that omission and transposition errors predominated, with weaker primacy and recency effects in spatial span than digit span testing. The C-SST improves the precision of spatial span testing and reveals significant differences between visuospatial and verbal working memory.

Hemispheric asymmetries in cortical and subcortical anatomy.

Previous research studies have reported many hemispherical asymmetries in cortical and subcortical anatomy, but only a subset of findings is consistent across studies. Here, we used improved Freesurfer-based automated methods to analyse the properties of the cortex and seven subcortical structures in 138 young adult subjects. Male and female subjects showed similar hemispheric asymmetries in gyral and sulcal structures, with many areas associated with language processing enlarged in the left hemisphere (LH) and a number of areas associated with visuospatial processing enlarged in the right hemisphere (RH). In addition, we found greater (non-directional) cortical asymmetries in subjects with larger brains. Asymmetries in subcortical structures included larger LH volumes of thalamus, putamen and globus pallidus and larger RH volumes of the cerebellum and the amygdala. We also found significant correlations between the subcortical structural volumes, particularly of the thalamus and cerebellum, with cortical area. These results help to resolve some of the inconsistencies in previous studies of hemispheric asymmetries in brain anatomy.

White matter microstructure throughout the brain correlates with visual imagery in grapheme-color synesthesia.

In this study we show, for the first time, a correlation between the neuroanatomy of the synesthetic brain and a metric that measures behavior not exclusive to the synesthetic experience. Grapheme-color synesthetes (n=20), who experience colors triggered by viewing or thinking of specific letters or numbers, showed altered white matter microstructure, as measured using diffusion tensor imaging, compared with carefully matched non-synesthetic controls. Synesthetes had lower fractional anisotropy and higher perpendicular diffusivity when compared to non-synesthetic controls. An analysis of the mode of anisotropy suggested that these differences were likely due to the presence of more crossing pathways in the brains of synesthetes. Additionally, these differences in white matter microstructure correlated negatively, and only for synesthetes, with a measure of the vividness of their visual imagery. Synesthetes who reported the most vivid visual imagery had the lowest fractional anisotropy and highest perpendicular diffusivity. We conclude that synesthetes as a population vary along a continuum while showing categorical differences in neuroanatomy and behavior compared to non-synesthetes.

Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities.

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

Computerized measures of finger tapping: effects of hand dominance, age, and sex.

Computerized measures of digit tapping rate were obtained over 3 successive, 10-sec. periods in the right and left index fingers, from a community sample of 1,519 participants (ages 18 to 65 years; 607 men, 912 women). Differences between the dominant and non-dominant hands were found for tapping rate, movement initiation, and button down times, and the decline in tapping rate over the successive, 10-sec. periods. Declines were found in tapping rate in older participants in association with increased intertap variability. Men had higher tapping rates than women in all age ranges. The computerized finger tapping test is an efficient and precise measure of tapping speed and kinetics of potential utility in research and clinical studies of motor performance.

BCG vaccination at birth and COVID-19: a case-control study among U.S. military Veterans.

In the early stages of the COVID-19 global pandemic, caused by the SARS-CoV-2 virus, low- and middle-income countries (LMICs) appeared to be experiencing lower morbidity and mortality rates than high-income countries, particularly the United States. Various suggestions put forward to account for this included the possibility that LMICs might be experiencing off-target benefits of infant vaccination with BCG, intended primarily to protect against tuberculosis. A number of ecologic epidemiological studies that considered COVID-19 morbidity and mortality rates across countries appeared to support this suggestion. Ecologic studies, however, are primarily hypothesis-generating, given their well-known limitations in extrapolating to the individual-person level. The present study, which employed anonymized records of U.S. Military Veterans treated by the Department of Veterans Affairs was principally a case-control study of COVID-19 infections with a retrospective cohort study of mortality nested within the infections. Controls were a random sample of Veterans not recorded as having had COVID-19. There were 263,039 controls and 167,664 COVID-19 cases, of whom 5,016 died. The combination of country and year of birth was used as a surrogate for infant BCG vaccination. The study did not support the hypothesis that BCG in infancy was protective against COVID-19. The odds ratio for infection was 1.07 (95% confidence interval [CI]: 1.03, 1.11) and the risk ratio for mortality among the COVID-19 cases was 0.86 (95% CI: 0.63, 1.18). The potential for non-differential exposure misclassification was a concern, possibly biasing measures of association toward the null value.

PLAIN LANGUAGE SUMMARYLow- and middle-income countries (LMICs) have appeared to be much less affected by the COVID-19 pandemic, caused by the SARS-CoV-2 virus, than might have been expected from the effects of the virus in more-developed countries. It has been suggested that BCG vaccination of infants against tuberculosis in LMICs might be providing cross-protection against COVID-19. BCG has never been routinely administered in the United States and is not currently administered in most other developed countries.Some epidemiology studies, known as "ecologic" studies have provided support for the idea that BCG is protecting against COVID-19. However, ecologic studies, with group (i.e., country) measures of exposure and health outcomes, are difficult to interpret in terms of cause and effect.More interpretable are studies that use individual-person measures of exposure and health outcome. We carried out such a study using data from several hundred-thousand U.S. military Veterans, many of whom were born in LMICs and would have received BCG vaccination as infants. Many U.S. Veterans have had COVID-19, and many of those have died of it.Our study, the first of its kind, found no evidence to support the idea that infant BCG vaccination protects against infection or death from COVID-19.

Regional variation, hemispheric asymmetries and gender differences in pericortical white matter.

Brain white matter tissue composition can be quantified using Diffusion Tensor Imaging (DTI) and Magnetization Transfer Imaging (MTI). Fractional Anisotropy (FA), derived from DTI, indexes the integrity, density and organization of axons. Magnetization Transfer Ratio (MTR), derived from MTI, indexes to the presence of cell membranes and myelin. The combined use of FA and MTR provides a more complete picture of white matter structure than either imaging modality in isolation. Here we describe the regional distribution of FA and MTR measurements of pericortical white matter in 56 young, healthy right-handed subjects. Significant regional and lobar differences are seen for both measures along with a significant gender difference in FA. Highly consistent hemispheric asymmetries in FA and MTR were observed, suggesting that the greater fiber coherence and increased myelination of fibers in left hemisphere perisylvian regions may provide a structural basis for left-hemisphere language dominance.

Case study: A selective tactile naming deficit for letters and numbers due to interhemispheric disconnection.

The role of white matter pathways in cognition is a topic of active investigation that is vital to both the fields of clinical neurology and cognitive neuroscience. White matter pathways provide critical connectivity amongst numerous specialized brain regions thereby enabling higher level cognition. While the effects of dissections and lesions of the corpus callosum have been reported, it is less understood how unilateral focal white matter lesions may impact cognitive processes. Here, we report a unique case study in which a small left lateralized stroke in the white matter adjacent to the body of the corpus callosum selectively impaired the ability to name letters and numbers presented to the ipsilesional, left hand. Naming of letters, numbers and objects was tested in both the visual and tactile modalities in both hands. Diffusion-weighted imaging showed a marked reduction in white matter pathway integrity through the body of the corpus callosum. Clinically, this case highlights the significant impact that a focal white matter lesion can have on higher-level cognition, specifically the integration of verbal and tactile information. Moreover, this case adds to prior reports on tactile agnosia by including DTI imaging data and emphasizing the role that white matter pathways through the body of the corpus callosum play in integrating tactile input from the right hemisphere with verbal naming capabilities of the left hemisphere. Finally, the findings also provoke fresh insight into alternative strategies for rehabilitating cognitive functioning when structural connectivity may be compromised.

Auditory Comprehension Deficits in Post-stroke Aphasia: Neurologic and Demographic Correlates of Outcome and Recovery.

Introduction: One of the most challenging symptoms of aphasia is an impairment in auditory comprehension. The inability to understand others has a direct impact on a person's quality of life and ability to benefit from treatment. Despite its importance, limited research has examined the recovery pattern of auditory comprehension and instead has focused on aphasia recovery more generally. Thus, little is known about the time frame for auditory comprehension recovery following stroke, and whether specific neurologic and demographic variables contribute to recovery and outcome. Methods: This study included 168 left hemisphere chronic stroke patients stroke patients with auditory comprehension impairments ranging from mild to severe. Univariate and multivariate lesion-symptom mapping (LSM) was used to identify brain regions associated with auditory comprehension outcomes on three different tasks: Single-word comprehension, yes/no sentence comprehension, and comprehension of sequential commands. Demographic variables (age, gender, and education) were also examined for their role in these outcomes. In a subset of patients who completed language testing at two or more time points, we also analyzed the trajectory of recovery in auditory comprehension using survival curve-based time compression. Results: LSM analyses revealed that poor single-word auditory comprehension was associated with lesions involving the left mid- to posterior middle temporal gyrus, and portions of the angular and inferior-middle occipital gyri. Poor yes/no sentence comprehension was associated almost exclusively with the left mid-posterior middle temporal gyrus. Poor comprehension of sequential commands was associated with lesions in the left posterior middle temporal gyrus. There was a small region of convergence between the three comprehension tasks, in the very posterior portion of the left middle temporal gyrus. The recovery analysis revealed that auditory comprehension scores continued to improve beyond the first year post-stroke. Higher education was associated with better outcome on all auditory comprehension tasks. Age and gender were not associated with outcome or recovery slopes. Conclusions: The current findings suggest a critical role for the posterior left middle temporal gyrus in the recovery of auditory comprehension following stroke, and that spontaneous recovery of auditory comprehension can continue well beyond the first year post-stroke.

Neural Underpinnings of Proactive Interference in Working Memory: Evidence From Patients With Unilateral Lesions.

Proactive interference in working memory refers to the fact that memory of past experiences can interfere with the ability to hold new information in working memory. The left inferior frontal gyrus (LIFG) has been proposed to play an important role in resolving proactive interference in working memory. However, the role of white matter pathways and other cortical regions has been less investigated. Here we investigated proactive interference in working memory using the Recent Probes Test (RPT) in 15 stroke patients with unilateral chronic lesions in left (n = 7) or right (n = 2) prefrontal cortex (PFC), or left temporal cortex (n = 6). We examined the impact of lesions in both gray and white matter regions on the size of the proactive interference effect. We found that patients with left PFC lesions performed worse overall, but the proactive interference effect in this patient group was comparable to that of patients with right PFC lesions, temporal lobe lesions, and controls. Interestingly, the size of the interference effect was significantly correlated with the degree of damage in the extreme/external capsule and marginally correlated with the degree of damage in the inferior frontal occipital fasciculus (IFOF). These findings suggests that ventral white matter pathways connecting the LIFG to left posterior regions play a role in resolving proactive interference in working memory. This effect was particularly evident in one patient with a very large interference effect (>3 SDs above controls) who had mostly spared LIFG, but virtually absent ventral white matter pathways (i.e., passing through the extreme/external capsules and IFOF). This case study further supports the idea that the role of the LIFG in resolving interference in working memory is dependent on connectivity with posterior regions via ventral white matter pathways.

Consonant identification in consonant-vowel-consonant syllables in speech-spectrum noise.

Identification functions of 20 initial and 20 final consonants were characterized in 9600 randomly sampled consonant-vowel-consonant (CVC) tokens presented in speech-spectrum noise. Because of differences in the response criteria for different consonants, signal detection measures were used to quantify identifiability. Consonant-specific baseline signal-to-noise ratios (SNRs) were adjusted to produce a d(') of 2.20 for each consonant. Consonant identification was measured at baseline SNRs (B), at B-6, and at B+6 dB. Baseline SNRs varied by more than 40 dB for different consonants. Confusion analysis revealed that single-feature place-of-articulation errors predominated at the highest SNR, while combined-feature errors predominated at the lowest SNR. Most consonants were identified at lower SNRs in initial than final syllable position. Vowel nuclei (/a/, /i/, or /u/) significantly influenced the identifiability of 85% of consonants, with consistent vowel effects seen for consonant classes defined by manner, voicing, and place. Manner and voicing of initial and final consonants were processed independently, but place cues interacted: initial and final consonants differing in place of articulation were identified more accurately than those sharing the same place. Consonant identification in CVCs reveals contextual complexities in consonant processing.

Multimodal surface-based morphometry reveals diffuse cortical atrophy in traumatic brain injury.

BACKGROUND: Patients with traumatic brain injury (TBI) often present with significant cognitive deficits without corresponding evidence of cortical damage on neuroradiological examinations. One explanation for this puzzling observation is that the diffuse cortical abnormalities that characterize TBI are difficult to detect with standard imaging procedures. Here we investigated a patient with severe TBI-related cognitive impairments whose scan was interpreted as normal by a board-certified radiologist in order to determine if quantitative neuroimaging could detect cortical abnormalities not evident with standard neuroimaging procedures. METHODS: Cortical abnormalities were quantified using multimodal surfaced-based morphometry (MSBM) that statistically combined information from high-resolution structural MRI and diffusion tensor imaging (DTI). Normal values of cortical anatomy and cortical and pericortical DTI properties were quantified in a population of 43 healthy control subjects. Corresponding measures from the patient were obtained in two independent imaging sessions. These data were quantified using both the average values for each lobe and the measurements from each point on the cortical surface. The results were statistically analyzed as z-scores from the mean with a p < 0.05 criterion, corrected for multiple comparisons. False positive rates were verified by comparing the data from each control subject with the data from the remaining control population using identical statistical procedures. RESULTS: The TBI patient showed significant regional abnormalities in cortical thickness, gray matter diffusivity and pericortical white matter integrity that replicated across imaging sessions. Consistent with the patient's impaired performance on neuropsychological tests of executive function, cortical abnormalities were most pronounced in the frontal lobes. CONCLUSIONS: MSBM is a promising tool for detecting subtle cortical abnormalities with high sensitivity and selectivity. MSBM may be particularly useful in evaluating cortical structure in TBI and other neurological conditions that produce diffuse abnormalities in both cortical structure and tissue properties.

The Dyad-Adaptive Paced Auditory Serial Addition Test (DA-PASAT): Normative data and the effects of repeated testing, simulated malingering, and traumatic brain injury.

The Paced Auditory Serial Addition Test (PASAT) is widely used to evaluate processing speed and executive function in patients with multiple sclerosis, traumatic brain injury, and other neurological disorders. In the PASAT, subjects listen to sequences of digits while continuously reporting the sum of the last two digits presented. Four different stimulus onset asynchronies (SOAs) are usually tested, with difficulty increasing as SOAs are reduced. Ceiling effects are common at long SOAs, while the digit delivery rate often exceeds the subject's processing capacity at short SOAs, causing some subjects to stop performing altogether. In addition, subjects may adopt an "alternate answer" strategy at short SOAs, which reduces the test's demands on working-memory and processing speed. Consequently, studies have shown that the number of dyads (consecutive correct answers) is a more sensitive measure of PASAT performance than the overall number of correct sums. Here, we describe a 2.5-minute computerized test, the Dyad-Adaptive PASAT (DA-PASAT), where SOAs are adjusted with a 2:1 staircase, decreasing after each pair of correct responses and increasing after misses. Processing capacity is reflected in the minimum SOA (minSOA) achieved in 54 trials. Experiment 1 gathered normative data in two large populations: 1617 subjects in New Zealand ranging in age from 18 to 65 years, and 214 Californians ranging in age from 18 to 82 years. Minimum SOAs were influenced by age, education, and daily hours of computer-use. Minimum SOA z-scores, calculated after factoring out the influence of these factors, were virtually identical in the two control groups, as were response times (RTs) and dyad ratios (the proportion of hits occurring in dyads). Experiment 2 measured the test-retest reliability of the DA-PASAT in 44 young subjects who underwent three test sessions at weekly intervals. High intraclass correlation coefficients (ICCs) were found for minSOAs (0.87), response times (0.76), and dyad ratios (0.87). Performance improved across test sessions for all measures. Experiment 3 investigated the effects of simulated malingering in 50 subjects: 42% of simulated malingerers produced abnormal (p< 0.05) minSOA z-scores. Simulated malingerers with abnormal scores were distinguished with 87% sensitivity and 69% specificity from control subjects with abnormal scores by excessive differences between training performance and the actual test. Experiment 4 investigated patients with traumatic brain injury (TBI): patients with mild TBI performed within the normal range while patients with severe TBI showed deficits. The DA-PASAT reduces the time and stress of PASAT assessment while gathering sensitive measures of dyad processing that reveal the effects of aging, malingering, and traumatic brain injury on performance.

Attention modulates sound processing in human auditory cortex but not the inferior colliculus.

Auditory attention powerfully influences perception and modulates sound processing in auditory cortex, but the extent of attentional modulation in the subcortical auditory pathway remains poorly understood. We examined the effects of intermodal attention using functional magnetic resonance imaging of the inferior colliculus and auditory cortex in a demanding intermodal selective attention task using a silent imaging paradigm designed to optimize inferior colliculus activations. Both the inferior colliculus and auditory cortex showed strong activations to sound, but attentional modulations were restricted to auditory cortex.

Improving the resolution of functional brain imaging: analyzing functional data in anatomical space.

The accurate mapping of functional magnetic resonance imaging (fMRI) activations to anatomical structures is critical for fMRI studies of brain organization. In the commonly used functional space analysis method, functional images are realigned to a functional reference image and processed in low-resolution functional space. The average functional activations are then projected into high-resolution anatomical space for visualization. Here, we describe a new technique, anatomical space analysis (ASA), whereby low-resolution functional images are first coregistered and resampled directly into high-resolution anatomical space with all subsequent data processing performed in high-resolution space. A major advantage of ASA is that minor scanner sampling instabilities and small head movements can increase spatial resolution by providing multiple samples of the relationship between functional and anatomical space. Both simulations and analyses of real fMRI data show that ASA improves the precision, objectivity and reproducibility of functional brain mapping.

The Bay Area Verbal Learning Test (BAVLT): Normative Data and the Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury.

Verbal learning tests (VLTs) are widely used to evaluate memory deficits in neuropsychiatric and developmental disorders. However, their validity has been called into question by studies showing significant differences in VLT scores obtained by different examiners. Here we describe the computerized Bay Area Verbal Learning Test (BAVLT), which minimizes inter-examiner differences by incorporating digital list presentation and automated scoring. In the 10-min BAVLT, a 12-word list is presented on three acquisition trials, followed by a distractor list, immediate recall of the first list, and, after a 30-min delay, delayed recall and recognition. In Experiment 1, we analyzed the performance of 195 participants ranging in age from 18 to 82 years. Acquisition trials showed strong primacy and recency effects, with scores improving over repetitions, particularly for mid-list words. Inter-word intervals (IWIs) increased with successive words recalled. Omnibus scores (summed over all trials except recognition) were influenced by age, education, and sex (women outperformed men). In Experiment 2, we examined BAVLT test-retest reliability in 29 participants tested with different word lists at weekly intervals. High intraclass correlation coefficients were seen for omnibus and acquisition scores, IWIs, and a categorization index reflecting semantic reorganization. Experiment 3 examined the performance of Experiment 2 participants when feigning symptoms of traumatic brain injury. Although 37% of simulated malingerers showed abnormal (p < 0.05) omnibus z-scores, z-score cutoffs were ineffective in discriminating abnormal malingerers from control participants with abnormal scores. In contrast, four malingering indices (recognition scores, primacy/recency effects, learning rate across acquisition trials, and IWIs) discriminated the two groups with 80% sensitivity and 80% specificity. Experiment 4 examined the performance of a small group of patients with mild or severe TBI. Overall, both patient groups performed within the normal range, although significant performance deficits were seen in some patients. The BAVLT improves the speed and replicability of verbal learning assessments while providing comprehensive measures of retrieval timing, semantic organization, and primacy/recency effects that clarify the nature of performance.

A Computerized Test of Design Fluency.

Tests of design fluency (DF) assess a participant's ability to generate geometric patterns and are thought to measure executive functions involving the non-dominant frontal lobe. Here, we describe the properties of a rapidly administered computerized design-fluency (C-DF) test that measures response times, and is automatically scored. In Experiment 1, we found that the number of unique patterns produced over 90 s by 180 control participants (ages 18 to 82 years) correlated with age, education, and daily computer-use. Each line in the continuous 4-line patterns required approximately 1.0 s to draw. The rate of pattern production and the incidence of repeated patterns both increased over the 90 s test. Unique pattern z-scores (corrected for age and computer-use) correlated with the results of other neuropsychological tests performed on the same day. Experiment 2 analyzed C-DF test-retest reliability in 55 participants in three test sessions at weekly intervals and found high z-score intraclass correlation coefficients (ICC = 0.79). Z-scores in the first session did not differ significantly from those of Experiment 1, but performance improved significantly over repeated tests. Experiment 3 investigated the performance of Experiment 2 participants when instructed to simulate malingering. Z-scores were significantly reduced and pattern repetitions increased, but there was considerable overlap with the performance of the control population. Experiment 4 examined performance in veteran patients tested more than one year after traumatic brain injury (TBI). Patients with mild TBI performed within the normal range, but patients with severe TBI showed reduced z-scores. The C-DF test reliably measures visuospatial pattern generation ability and reveals performance deficits in patients with severe TBI.

Computerized Analysis of Verbal Fluency: Normative Data and the Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury.

In verbal fluency (VF) tests, subjects articulate words in a specified category during a short test period (typically 60 s). Verbal fluency tests are widely used to study language development and to evaluate memory retrieval in neuropsychiatric disorders. Performance is usually measured as the total number of correct words retrieved. Here, we describe the properties of a computerized VF (C-VF) test that tallies correct words and repetitions while providing additional lexical measures of word frequency, syllable count, and typicality. In addition, the C-VF permits (1) the analysis of the rate of responding over time, and (2) the analysis of the semantic relationships between words using a new method, Explicit Semantic Analysis (ESA), as well as the established semantic clustering and switching measures developed by Troyer et al. (1997). In Experiment 1, we gathered normative data from 180 subjects ranging in age from 18 to 82 years in semantic ("animals") and phonemic (letter "F") conditions. The number of words retrieved in 90 s correlated with education and daily hours of computer-use. The rate of word production declined sharply over time during both tests. In semantic conditions, correct-word scores correlated strongly with the number of ESA and Troyer-defined semantic switches as well as with an ESA-defined semantic organization index (SOI). In phonemic conditions, ESA revealed significant semantic influences in the sequence of words retrieved. In Experiment 2, we examined the test-retest reliability of different measures across three weekly tests in 40 young subjects. Different categories were used for each semantic ("animals", "parts of the body", and "foods") and phonemic (letters "F", "A", and "S") condition. After regressing out the influences of education and computer-use, we found that correct-word z-scores in the first session did not differ from those of the subjects in Experiment 1. Word production was uniformly greater in semantic than phonemic conditions. Intraclass correlation coefficients (ICCs) of correct-word z-scores were higher for phonemic (0.91) than semantic (0.77) tests. In semantic conditions, good reliability was also seen for the SOI (ICC = 0.68) and ESA-defined switches in semantic categories (ICC = 0.62). In Experiment 3, we examined the performance of subjects from Experiment 2 when instructed to malinger: 38% showed abnormal (p< 0.05) performance in semantic conditions. Simulated malingerers with abnormal scores could be distinguished with 80% sensitivity and 89% specificity from subjects with abnormal scores in Experiment 1 using lexical, temporal, and semantic measures. In Experiment 4, we tested patients with mild and severe traumatic brain injury (mTBI and sTBI). Patients with mTBI performed within the normal range, while patients with sTBI showed significant impairments in correct-word z-scores and category shifts. The lexical, temporal, and semantic measures of the C-VF provide an automated and comprehensive description of verbal fluency performance.