Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease.

BACKGROUND: Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design. METHODS: A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months. RESULTS: In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline. CONCLUSIONS: Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.

Understanding patient-reported outcome measures in Huntington disease: at what point is cognitive impairment related to poor measurement reliability?

PURPOSE: Symptom progression in Huntington disease (HD) is associated with cognitive decline which may interfere with the self-report of symptoms. Unfortunately, data to support or refute the psychometric reliability of patient-reported outcomes (PROs) as HD progresses are limited. This is problematic given that PROs are increasingly recognized as important measures of efficacy for new treatments. METHODS: We examined PRO data from the HDQLIFE Measurement System (Speech Difficulties; Swallowing Difficulties; Chorea) in 509 individuals with premanifest, early-stage, or late-stage HD. Clinician-administered assessments of motor functioning (items from the UHDRS) and standardized objective assessments of cognition (Stroop, Symbol Digit Modalities) were also collected. We examined item bias using differential item functioning (DIF) across HD stage (premanifest, early-, late-) and relative to cognitive performance. We also examined the correlations between self-report and clinician ratings. Regression models that considered total cognitive ability were utilized to determine psychometric reliability of the PROs. RESULTS: Most PRO items were free from DIF for both staging and cognition. There were modest correlations between PROs and clinician report (ranged from - 0.40 to - 0.60). Modeling analyses indicated that psychometric reliability breaks down with poorer cognition and more progressed disease stage; split-half reliability was compromised (i.e., split-half reliability < 0.80) when scores were < 136 for Chorea, < 109 for Speech Difficulties, and < 179 for Swallowing Difficulties. CONCLUSIONS: Results indicate that the psychometric reliability of PROs can be compromised as HD symptoms progress and cognition declines. Clinicians should consider PROs in conjunction with other types of assessments when total cognition scores exceed critical thresholds.

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD).

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. METHODS: New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. RESULTS: Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. CONCLUSIONS: HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.

Automated differentiation of pre-diagnosis Huntington's disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: the IMAGE-HD study.

We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pre-HD individuals from controls and we utilised feature selection and dimension reduction to increase the robustness of the discrimination method. Thirty six symptomatic HD (symp-HD), 35 pre-HD, and 36 control individuals participated as part of the IMAGE-HD study and underwent T1-weighted MRI, and DTI using a Siemens 3 Tesla scanner. Volume and DTI measures [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for each group within five regions of interest (ROI; caudate, putamen, pallidum, accumbens and thalamus). QDA was then performed in a stepwise manner to differentiate pre-HD individuals from controls, based initially on unimodal analysis of motor or neurocognitive measures, or on volume, MD or FA measures from within the caudate, pallidum and putamen. We then tested for potential improvements to this model, by examining multi-modal MRI classifications (volume, FA and MD), and also included motor and neurocognitive measures, and additional brain regions (i.e., accumbens and thalamus). Volume, MD and FA differed across the three groups, with pre-HD characterised by significant volumetric reductions and increased FA within caudate, putamen and pallidum, relative to controls. The QDA results demonstrated that the differentiation of pre-HD from controls was highly accurate when both volumetric and diffusion data sets from basal ganglia (BG) regions were used. The highest discriminative accuracy however was achieved in a multi-modality approach and when including all available measures: motor and neurocognitive scores and multi-modal MRI measures from the BG, accumbens and thalamus. Our QDA findings provide evidence that combined multi-modal imaging measures can accurately classify individuals up to 15 years prior to onset when therapeutic intervention is likely to have maximal effects in slowing the trajectory of disease development.

Listeria monocytogenes and hemolytic Listeria innocua in poultry.

Listeria monocytogenes is a ubiquitous, saprophytic, Gram-positive bacterium and occasional food-borne pathogen, often associated with ready-to-eat meat products. Because of the increased consumer interest in organic, all natural, and free range poultry products, it is important to understand L. monocytogenes in the context of such systems. Pasture-reared poultry were surveyed over the course of two 8-wk rearing periods. Cecal, soil, and grass samples were collected for Listeria isolation and characterization. Seven of 399 cecal samples (or 1.75%) were Listeria-positive. All positive cecal samples were obtained from broilers sampled at 2 wk of age. Grass and soil samples were collected from the pasture both before and after introduction of the poultry. Environmental samples collected after introduction of poultry were significantly more likely to contain Listeria (P < 0.001). The results of analytical profile index Listeria, sigB allelic typing, and hlyA PCR tests found that both L. monocytogenes and L. innocua, including hemolytic L. innocua, were recovered from the cecal and environmental (grass/soil) samples. The sigB allelic typing also revealed that (1) positive samples could be composed of 2 or more allelic types; (2) allelic types found in cecal samples could also be found in the environment; and (3) allelic types could persist through the 2 rearing periods. Our data indicate that both pasture-reared poultry and their environment can be contaminated with L. monocytogenes and hemolytic L. innocua.

Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield.

How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.

Detection of Huntington's disease decades before diagnosis: the Predict-HD study.

OBJECTIVE: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington's disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis. METHODS: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor. RESULTS: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies. CONCLUSIONS: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.

Effects of age on tissues and regions of the cerebrum and cerebellum.

Normal volunteers, aged 30 to 99 years, were studied with MRI. Age was related to estimated volumes of: gray matter, white matter, and CSF of the cerebrum and cerebellum; gray matter, white matter, white matter abnormality, and CSF within each cerebral lobe; and gray matter of eight subcortical structures. The results were: 1) Age-related losses in the hippocampus were significantly accelerated relative to gray matter losses elsewhere in the brain. 2) Among the cerebral lobes, the frontal lobes were disproportionately affected by cortical volume loss and increased white matter abnormality. 3) Loss of cerebral and cerebellar white matter occurred later than, but was ultimately greater than, loss of gray matter. It is estimated that between the ages of 30 and 90 volume loss averages 14% in the cerebral cortex, 35% in the hippocampus, and 26% in the cerebral white matter. Separate analyses were conducted in which genetic risk associated with the Apolipoprotein E epsilon4 allele was either overrepresented or underrepresented among elderly participants. Accelerated loss of hippocampal volume was observed with both analyses and thus does not appear to be due to the presence of at-risk subjects. MR signal alterations in the tissues of older individuals pose challenges to the validity of current methods of tissue segmentation, and should be considered in the interpretation of the results.

Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type.

OBJECTIVE: To examine associations between dementia severity and quantitative magnetic resonance imaging measures of cortical gray matter volume and abnormal white matter volume in 52 patients diagnosed with probable Alzheimer disease. DESIGN: Analysis of the relationship between magnetic resonance imaging volume measures and dementia severity using multiple regression and Pearson correlations. SETTING: Alzheimer's Disease Research Center, University of California, San Diego. PARTICIPANTS: Twenty-three men and 29 women with probable Alzheimer disease (average age, 71.7 years; average education, 13.3 years). MAIN OUTCOME MEASURES: The Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination. RESULTS: Using simultaneous multiple regression, magnetic resonance imaging volumetric measures of cortical gray matter and abnormal white matter were independently associated with dementia severity measured by either the MDRS or the Mini-Mental State Examination. Cortical gray matter volume and abnormal white matter volume also made independent contributions to performance in 4 of 5 cognitive domains assessed by the MDRS. Regional analysis indicated that limbic cortical gray matter volume and nonlimbic cortical gray matter volume were also correlated with the MDRS score; however, in the regression analysis the individual gray matter measures were not independently associated with MDRS performance. A similar analysis revealed statistically independent relationships of limbic gray matter volume and abnormal white matter volume, but not nonlimbic cortical gray matter volume, to Mini-Mental State Examination performance. CONCLUSIONS: Quantitative magnetic resonance methods provided strong evidence that cortical gray matter volume, which may reflect atrophy, and abnormal white matter volume are independently related to dementia severity in probable Alzheimer disease: lower gray matter and higher abnormal white matter volumes are associated with more severe dementia.

Longitudinal cognitive and motor changes among presymptomatic Huntington disease gene carriers.

OBJECTIVE: To determine whether longitudinal changes in cognitive and motor function can be detected among clinically presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN: A longitudinal, case-control, double-blind study comparing presymptomatic gene carriers and non-gene carriers at risk for HD examined an average of 3.7 years apart. SETTING: The Department of Medical and Molecular Genetics at a general clinic research center in Indianapolis, Ind. PARTICIPANTS: A sample of 43 at-risk individuals consisting of presymptomatic gene carriers (n = 12) and non-gene carriers (n = 31). MEASURES: Huntington disease gene status was determined by molecular testing of the HD gene. Subscales from the Wechsler Adult Intelligence Scale-Revised and a quantified neurologic rating scale were administered. RESULTS: Scores on the digit symbol subscale of the Wechsler Adult Intelligence Scale-Revised (P<.05) and 2 neurologic variables-optokinetic nystagmus (P<.01) and rapid alternating movements (P<.005)-declined more rapidly among presymptomatic gene carriers than among non-gene carriers. At follow-up examination, compared with nongene carriers, presymptomatic gene carriers had significantly lower scores on the digit symbol subscale (P = .02) and for 4 neurologic variables-rapid alternating movements (P<.005), optokinetic nystagmus (P<.001), overall ocular movements (P<.02), and chorea of the trunk (P<.02). CONCLUSIONS: Psychomotor speed, optokinetic nystagmus, and rapid alternating movements demonstrated significant decline early in the pathological process of HD. These results suggest that subtle worsening of psychomotor, oculomotor, and motor functions occurs before the onset of signs sufficient to make a clinical diagnosis in individuals who have inherited the HD allele.

Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group.

OBJECTIVE: To compare rates and anatomical patterns of brain atrophy during 3 stages of human immunodeficiency virus (HIV) disease. DESIGN: Comparisons of multiple serial brain magnetic resonance images in men without HIV infection and HIV-infected men in Centers for Disease Control and Prevention (CDC, Atlanta, Ga) stages A, B, and C. SETTING: Longitudinal cohort study of the San Diego HIV Neurobehavioral Research Center, San Diego, Calif. PARTICIPANTS: Eighty-six HIV-1-positive (HIV-positive) and 23 HIV-negative men who were similar in age and risk group. The number of HIV-positive men in each CDC stage was as follows: A, 33; B, 19; C, 34. All HIV-positive men were free of clinically detectable opportunistic neurologic illness. MAIN OUTCOME MEASURES: Regional volumes of serial magnetic resonance images converted to standardized slope estimates of change in regional volumes of interest. RESULTS: Medically asymptomatic men (CDC stage A) and medically symptomatic men (CDC stage C) had more rapid loss of cortical tissues than did HIV-negative men as manifested by higher slopes (Tukey honestly significant difference test, P=.02 and P=.001, respectively) for cortical fluid volume. Accelerated ventricular volume enlargement occurred only in men with CDC stage C disease. Reduction in the volume of white matter was accelerated in participants with CDC stage C disease compared with participants with CDC stage A disease. Of the gray matter regions, only the caudate nucleus sustained accelerated volume loss during CDC stage C disease. Participants whose systemic disease progressed to a higher CDC stage had significantly accelerated ventricular volume increases and caudate atrophy. Rates of cortical and subcortical fluid volume increases and reductions in the volumes of white matter and the caudate nucleus were significantly related to the rate of decline in the CD4+ lymphocyte count. CONCLUSIONS: In the absence of cerebral opportunistic disease, HIV infection causes progressive atrophy within the gray and white matter in the brain. These changes were most severe in the most advanced stage of disease but were evident even in medically asymptomatic HIV-positive persons. Within the gray matter, the caudate nucleus exhibited progressive volume loss linked to disease stage and the rate of decline of the CD4+ cell count. Structural brain changes can begin in the early stages of HIV infection and accelerate during advanced illness.

Clinical markers of early disease in persons near onset of Huntington's disease.

OBJECTIVE: There is increasing evidence that neuron loss precedes the phenotypic expression of Huntington's disease (HD). As genes for late-onset neurodegenerative diseases are identified, the need for accurate assessment of phenoconversion (i.e., the transition from health to the disease phenotype) will be important. METHODS: Prospective longitudinal evaluation using the Unified Huntington's Disease Rating Scale (UHDRS) was conducted by Huntington Study Group members from 36 sites. There were 260 persons considered "at risk" for HD who initially did not have manifest disease and had at least one subsequent evaluation. Repeat UHDRS data, obtained an average of 2 years later, showed that 70 persons were given a diagnosis of definite HD based on the quantified neurologic examination. RESULTS: Baseline cognitive performances were consistently worse for the at-risk group who demonstrated conversion to a definitive diagnosis compared with those who did not. Longitudinal change scores showed that the at-risk group who did not demonstrate manifest disease during the follow-up study period demonstrated improvements in all cognitive tests, whereas performances in the at-risk group demonstrating conversion to disease during the study declined across cognitive domains. CONCLUSIONS: Neuropsychological measures show impairment 2 years before the development of more manifest motor disease. Findings suggest that these brief cognitive measures administered over time may capture early striatal neural loss in HD.

De novo nonreciprocal translocation 1;8 confirmed by fluorescent in situ hybridization.

Constitutional nonreciprocal translocations are extremely rare, and even their existence is controversial. We report on a newborn infant with a de novo nonreciprocal translocation between chromosomes 1 and 8 resulting in 1q42.3 deletion syndrome. Fluorescent in situ hybridization with whole chromosome paints confirmed the conventional cytogenetic diagnosis.

Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity.

This study addressed the effects of a commonplace stressful event on interferon production and natural killer (NK) cell activity and numbers. The quantity of interferons (IFN) produced by concanavalin A stimulated leukocytes obtained from 40 medical students during examinations was significantly lower when compared with IFN levels produced by peripheral blood leukocytes (PBLs) taken 6 weeks earlier (baseline). In addition, three different assays measuring NK cells also showed significant decrements during examinations when compared with baseline samples. These assays included lysis of MOLT-4 target cells, percentage of anti-Leu-7+ (NK) cells, and percentage of large granular lymphocytes. Self-report data documented the significantly greater distress associated with examinations in comparison with baseline samples. The data have implications for immunosuppressive disorders and stress-associated illnesses.

Regional cerebral volume loss associated with verbal learning and memory in dementia of the Alzheimer type.

Twenty-seven research participants with dementia of the Alzheimer type were studied with the California Verbal Learning Test (D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1987) and standardized volume measures of the mesial temporal cortical gray matter, neocortical gray matter, thalamus, and caudate nuclei, from magnetic resonance imaging. A pattern of atrophic brain changes in the mesial temporal lobes (MTL) and the thalamus, with relatively less severe atrophy in the neocortical gray matter, was associated with poorer learning of the word list. Similar patterns of brain atrophy were observed for measures of delayed recall and recognition hits. However, for delayed recall, neither contribution was statistically significant, and for recognition hits, MTL was only at the trend level for significance. These results provide evidence that the verbal memory deficit of Alzheimer's disease (AD) is associated not only with the mesial temporal limbic cortex, thought to be the site of earliest and most severe pathology in AD, but also with damage in the thalamus.

Depression and anxiety: role of the locus coeruleus and corticotropin-releasing factor.

Based on studies of depression and anxiety using animal (rat) models, it is suggested that, contrary to a widely accepted theory, increased activity of locus coeruleus (LC) neurons does not appear to potentiate anxiety; instead, the influence of LC activity may be opposite to this. First, studies are described that indicate that behavioral changes resembling what is seen in human clinical depression occur in rats exposed to highly stressful conditions, and the research is then traced, which links this stress-induced depression to disturbance of normal noradrenergic regulation of LC activity. Second, the potential role of corticotrophin releasing factor (CRF) in stress-induced behavioral depression is explored. CRF infused into the LC did not produce behavioral depression in the swim test but did increase anxiety; by comparison, CRF infused into the parabrachial nucleus lateral to LC increased both depression and anxiety. Finally, to further explore the relationship between LC activity and anxiety, drugs were infused into LC region to attempt to specifically activate or depress firing of LC neurons. In contrast to expectations, infusion to decrease firing of LC cells increased anxious behavior, while infusion to increase firing decreased anxious behavior. Several other studies are discussed that point to a similar conclusion. It is suggested that, at least in rats, the capacity of stress-inducing or aversive stimuli to activate LC neurons does not potentiate anxiety under environmental conditions that elicit this response, but, rather, the increased activity of the LC/dorsal noradrenergic system under such conditions may exert a counterbalancing, antianxiety influence.

Oculomotor control in asymptomatic and recently diagnosed individuals with the genetic marker for Huntington's disease.

We compared oculomotor control among individuals in the early stages of Huntington's disease (HD), with that of individuals who are presymptomatic HD gene carriers (PSGC) and nongene carriers (NGC). The oculomotor testing paradigm included both traditional tests and a novel experimental procedure to assess visual scanning. Traditional tests elicited saccades, pursuit and optokinetic nystagmus (OKN). HD patients demonstrated marked delay in the initiation of volitional saccades (anti-saccade and memory-guided saccades), a reduced number of correct volitional saccades, reduced velocity of saccades, and a decreased OKN gain. We also studied visual scanning while the participants completed the Digit Symbol Subscale of the Wechsler Adult Intelligence Survey-Revised (WAIS-R). The HD participants demonstrated an abnormal gaze strategy, which may be associated with attention and/or planning deficits. Differences between the PSGC and NGC groups were only observed for two measures: PSGC had a decreased number of memory-guided saccades and a subtle delay in the initiation of volitional saccades. Our results suggest that oculomotor measures are a sensitive biomarker in the early stage of HD and demonstrate that the combination of more traditional oculomotor tests with visual scanning tests is useful in the evaluation of visual performance.

Stress-related impairments in cellular immunity.

The percentages of total T-lymphocytes (OKT-3+), helper T-cells (OKT-4+), and suppressor T-cells (OKT-8+) were significantly lower in blood samples obtained from 40 medical students during examinations, compared to baseline values obtained 6 weeks earlier. In addition, the response of T-lymphocytes to stimulation by phytohemagglutinin and concanavilin A was also significantly lower during examinations, compared to baseline. Self-report data documented significantly greater distress associated with examinations. The data have implications for immunosuppressive disorders and stress-related illnesses.

An animal model for measuring behavioral responses to anxiogenic and anxiolytic manipulations.

A method for measuring behavioral responses of rats to both anxiolytic and anxiogenic manipulations, the open field drink test (OFDT), is described. This method utilizes the concept that in the open field, appetitive behavior is reduced because of the ambient level of fear experienced in such an environment. For the OFDT, rats were given restricted access to water for 1 h per day for 3 days, and then their behavior was assessed in an open field that contained a water spout at its center. Use of the open field permitted a number of measures to be taken; of these, "time spent drinking" was most sensitive in detecting differences. Three experiments showed that the OFDT: a) permitted dissociation between behavioral responses to an anxiolytic (diazepam) and an anxiogenic (FG7142) drug, b) detected a dose-response relationship for an anxiolytic drug (diazepam), and c) detected behavioral responses to environmental manipulations designed to increase fear (presence of an olfactory cue from rats that had received foot shock). Advantages of this test over previously described methods are outlined, and several guidelines are provided to aid investigators in using this behavioral test.

Assessing frontal lobe behavioral syndromes with the frontal lobe personality scale.

Reliability and construct validity are reported for the Frontal Lobe Personality Scale (FLOPS), a brief neurobehavior rating scale. The FLOPS Family form was completed by family members of 24 frontal lobe brain-damaged patients, 15 non-frontal lobe brain- damaged patients, and 48 healthy controls. Intrascale reliability was demonstrated (internal consistency.96; split half.93). Validity studies of frontal lobe patients post-lesion compared to their pre-lesion status, to healthy controls, and of frontal lobe patients pre- and post-lesion compared to non-frontal lobe patients pre- and post-lesion, indicated that frontal lobe patients post-lesion showed significantly more frontal behavior than (a) pre-lesion frontal lobe patients, (b) healthy controls, and (c) post-lesion non-frontal lobe patients. The FLOPS appears to be useful for quantifying frontal lobe behavior in clinical and research settings.