A majority rule approach for region-of-interest-guided streamline fiber tractography.

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.

Test-retest reliability of high angular resolution diffusion imaging acquisition within medial temporal lobe connections assessed via tract based spatial statistics, probabilistic tractography and a novel graph theory metric.

This study examined the reliability of high angular resolution diffusion tensor imaging (HARDI) data collected on a single individual across several sessions using the same scanner. HARDI data was acquired for one healthy adult male at the same time of day on ten separate days across a one-month period. Environmental factors (e.g. temperature) were controlled across scanning sessions. Tract Based Spatial Statistics (TBSS) was used to assess session-to-session variability in measures of diffusion, fractional anisotropy (FA) and mean diffusivity (MD). To address reliability within specific structures of the medial temporal lobe (MTL; the focus of an ongoing investigation), probabilistic tractography segmented the Entorhinal cortex (ERc) based on connections with Hippocampus (HC), Perirhinal (PRc) and Parahippocampal (PHc) cortices. Streamline tractography generated edge weight (EW) metrics for the aforementioned ERc connections and, as comparison regions, connections between left and right rostral and caudal anterior cingulate cortex (ACC). Coefficients of variation (CoV) were derived for the surface area and volumes of these ERc connectivity-defined regions (CDR) and for EW across all ten scans, expecting that scan-to-scan reliability would yield low CoVs. TBSS revealed no significant variation in FA or MD across scanning sessions. Probabilistic tractography successfully reproduced histologically-verified adjacent medial temporal lobe circuits. Tractography-derived metrics displayed larger ranges of scanner-to-scanner variability. Connections involving HC displayed greater variability than metrics of connection between other investigated regions. By confirming the test retest reliability of HARDI data acquisition, support for the validity of significant results derived from diffusion data can be obtained.

Integrating Neuropsychology and Brain Imaging for a Referral of Possible Pseudodementia: A Case Report.

The study aimed to highlight the importance of interdisciplinary collaboration and the value for combining normative neuropsychological and neuroradiological measures for clinical purposes. We present the case of "CL," a 65-year-old, right-handed, Caucasian female referred for a neuropsychological evaluation of memory difficulties and depression with the rule-out of pseudodementia. A brain magnetic resonance imaging (MRI) scan was conducted within 24 hours of the neuropsychology exam. Mood measures showed elevated depression and apathy symptoms. The neuropsychological profile showed variable effort, intact comprehension but compromised confrontation naming and verbal memory deficits. Using normative references from 20 female age- and education-matched healthy control peers, CL showed significantly reduced temporal cortex thickness with reduced bilateral hippocampal, right amygdala, and right caudate volumes. Combined data were supportive of a diagnosis of semantic dementia. Examining neuropsychological profiles in combination with neuroimaging standardized metrics relative to peers improved case conceptualization. Standard measures of effort and malingering examined alone and without MRI for the diagnosis of pseudodementia have questionable validity and rationale. We additionally discuss the advantages and limitations/challenges for integrating neuropsychological assessments with normative based MRI brain metrics.

Neuroimaging correlates of everyday action in dementia.

The everyday, functional impairments associated with dementia remain poorly understood from a neuropsychological perspective. This study investigated relations between brain structure volumes and two measures of everyday action-caregiver questionnaire and direct assessment-in 57 participants with dementia. Results showed that caregiver ratings reflecting more functional impairment were strongly associated with smaller volumes of deep white matter. Direct assessment of everyday task performance in a subsample revealed relations between unique neurological substrates and discrete everyday action error types. Findings emphasize differences in functional assessment methods and highlight the role of white matter in functional deficits in dementia.

Health comorbidities and cognition in 1948 patients with idiopathic Parkinson's disease.

BACKGROUND: Health comorbidities, particularly cardiovascular factors, are well known to pose risks for cognitive decline in older adults. This study examined the prevalence and contribution of comorbidities on cognitive performance in a large cohort of Parkinson patients. METHODS: Data on 1948 PD patients were obtained from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) registry, a multi-site initiative from NPF Centers of Excellence. Available comorbidity data included six common conditions (heart/circulation problems, diabetes, arthritis, cancer, respiratory disease, and other neurologic disease) that were clinician-rated for presence and severity. Available cognitive measures included semantic fluency and a 5-word recall memory task. The unique effects of comorbidities on cognition were analyzed (multiple hierarchical regression) controlling for demographic, PD disease severity (duration, Hoehn-Yahr), and medication status. RESULTS: The two most reported comorbidities were arthritis (46.6%) and heart/circulation problems (36.3%), with diabetes affecting 9% of the sample. Severity of heart/circulation problems independently contributed to worse delayed recall performance (p = 0.03). A trend emerged for more severe diabetes as contributing to worse semantic fluency scores (p = 0.06). CONCLUSIONS: This study with a large cohort of PD patients provides evidence for a small detrimental influence of specific health comorbidities, particularly heart/circulatory and diabetes, on general measures of cognition. This effect is present, above and beyond the influences of basic demographic information (age), duration and staging of PD, and medication status. Future studies involving more refined cognitive indices and direct assessment of comorbidities are warranted.

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

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.

Subcortical vascular dementia: integrating neuropsychological and neuroradiologic data.

BACKGROUND: Research criteria for subcortical vascular dementia are based on radiologic evidence of vascular pathology and greater impairment on tests of executive control than memory. The relationship(s) between neuroradiological evidence of subcortical vascular disease and neuropsychological impairments has not been specified. OBJECTIVE: To define these research criteria, the authors rated the severity of MRI white matter abnormalities (WMAs) and neuropsychological data from patients with dementia. METHODS: Sixty-nine outpatients who met the criteria for dementia were studied with neuropsychological tests that assessed executive (mental) control, declarative memory, visuoconstruction (clock drawing), and language (semantic category fluency). MRI-WMAs were rated using a leukoaraiosis (LA) scale (range 0 to 40). RESULTS: First, regression analyses demonstrated that neuropsychological measures accounted for 60.7% of the variance in WMA severity (47.3% of this variance attributable to executive/visuoconstructive test performance, 13.4% attributable to memory/language test performance). Second, patients were grouped according to the severity of WMAs (i.e., low, moderate, and severe white matter groups). Only patients with mild WMA (mean LA = 3.61 +/- 2.63, approximately 2.4 to 15.6% of the subcortical white matter) presented with greater impairment on memory/language tests vs executive control/visuoconstructive tests, a neuropsychological profile typically associated with Alzheimer disease. Patients with moderate WMA (mean LA = 12.76 +/- 2.49, approximately 25.6 to 38.1% of the subcortical white matter) presented with equal impairment on executive/visuoconstructional vs memory/language tests. Patients with severe WMA (mean LA = 21.76 +/- 2.97, approximately 46.9 to 62.4% of the subcortical white matter) displayed a profile of greater executive/visuoconstructional impairment relative to memory/language disabilities. CONCLUSION: A profile of equal impairment on tests of executive control and memory along with radiologic evidence involving about one-fourth of the cerebral white matter as measured by the Leukoaraiosis Scale may be sufficient for a diagnosis of subcortical vascular dementia.

Mental disorders in children and adolescents with sickle cell disease.

This study compares the rate of mental disorders in children and adolescents with sickle cell disease with the rate in a corresponding control population. Using the clinical interview, a diagnosis based on DSM-III-R criteria for the presence of 13 mental disorders common to childhood was considered in a sequential sample of 39 subjects with sickle cell disease and a convenience sample of 26 same-race control subjects. Thirty-one percent of the sickle cell group and 42% of the control group screened positive for one or more of the selected mental disorders. The difference was not significant. When subgroups of mental disorders were considered (anxiety disorders, depressive disorders, disruptive behavior disorders, psychotic disorders, and other selected disorders), the differences were still not significant. This study suggests that children and adolescents with sickle cell disease do not have a greater risk for clinically significant mental disorders than same-race outpatient clinic controls. This study supports other reports in the medical literature that suggest that children attending outpatient medical clinics are at a higher risk for mental disorder than is seen in epidemiologic studies of nonmedical populations.

Bloated irritable bowel syndrome defined by dynamic 99mTc bran scan.

The motility of the ileocaecal region of the gut was studied in 10 women with irritable bowel syndrome (IBS) and bloating and in 8 normal women. Bran labelled with 37 MBq 99mTc was administered after fasting, and a dynamic scan was done after a standard meal 3 h later. Time-activity curves were plotted for the ileum and caecum. In controls, ileal emptying was faster, peak % counts in the caecum were higher, and ileocaecal clearance was greater than in those with IBS. The profound motor dysfunction seen in those with IBS may account for their symptoms, and the "bran scan" could become an important diagnostic aid.

Marine oscillatoria (Trichodesmium): explanation for aerobic nitrogen fixation without heterocysts.

Nitrogen fixation in marine Oscillatoria appears to be associated with differentiated cells located in the center of the colony. These central cells exhibit reduced pigmentation relative to peripherally located cells and do not incorporate 14CO2 in photosynthesis. Central cells apparently do not produce O2 which would deactivate nitrogenase. When central cells are exposed to O2 via disruption of the colonies, N2 fixation (acetylene reduction) decreases sharply even though individual trichomes remain intact. Disruption of colonies in the absence of O2 does not cause reduced nitrogenase activity. In the sea, turbulence from wave action apparently separates trichomes allowing O2 to enter thus decreasing nitrogenase activity. These observations explain how Oscillatoria is able to fix N2 without heterocysts in an aerobic environment and why it blooms virtually always occur in calm seas.