Publications by Year: 2010

BACKGROUND: Timing abilities are critical to the successful management of everyday activities and personal safety, and timing abnormalities have been argued to be fundamental to impulsiveness, a core symptom of attention-deficit/hyperactivity disorder (ADHD). Despite substantial evidence of timing deficits in ADHD youth, only two studies have explicitly examined timing in ADHD adults and only at the suprasecond time scale. Also, the neural substrates of these deficits are largely unknown for both youth and adults with ADHD. The present study examined subsecond sensorimotor timing and its neural substrates in ADHD adults. METHODS: Using functional magnetic resonance imaging, we examined paced and unpaced finger tapping in a sample of 20 unmedicated adults with ADHD and 19 control subjects comparable on age, sex, and estimated IQ. The blood oxygenation level-dependent contrast response was used to estimate task-related neural activity. RESULTS: Behavioral data showed no between-group differences in mean tapping rates but greater within-subject variability in tap-to-tap intervals for ADHD adults relative to control subjects. Importantly, ADHD adults had greater clock rather than motor variability, consistent with a central timing locus for the atypical movements. The imaging results demonstrated that, relative to control subjects, ADHD adults showed less activity in a number of regions associated with sensorimotor timing, including prefrontal and precentral gyri, basal ganglia, cerebellum, inferior parietal lobule, superior temporal gyri, and insula. CONCLUSIONS: Our findings show that subsecond timing abnormalities in ADHD youth persist into adulthood and suggest that abnormalities in the temporal structure of behavior observed in ADHD adults result from atypical function of corticocerebellar and corticostriatal timing systems.

OBJECTIVES: To assess the visibility and the course of the incisive canal and the visibility and the location of the lingual foramen using cone-beam computed tomography (CBCT). METHODS: In total, 100 CBCT examinations of patients for preoperative planning were used for this study. The examinations were taken using the NewTom 3G CBCT unit, applying a standardized exposure protocol. Image reconstruction from the raw data was performed using the NewTom software. Three experts were asked to assess the visibility of the incisive canal using a four-point rating scale. The position of the incisive canal was recorded in relation to the lower, buccal and lingual border of the mandible using the application provided by the CBCT software. RESULTS: The incisive canal was definitely visible in 83.5% of the scans and the mean endpoint was approximately 15 mm anterior to the mental foramen. The mean distance from the lower border of the mandible was 11.5 mm and its course was closer to the buccal border of the mandible in 87% of the scans. The lingual foramen was definitely visible in 81% of the scans. CONCLUSIONS: The high detection rate of the incisive canal and the lingual foramen in the anterior region of the mandible using CBCT indicates the potential high preoperative value of CBCT scan for surgical procedures in the anterior mandible.

Corpus callosum (CC) area abnormalities have been reported in magnetic resonance imaging (MRI) studies of adults and youths with bipolar disorder (BPD), suggesting interhemispheric communication may be abnormal in BPD and may be present early in the course of illness and affect normal neuromaturation of this structure throughout the lifecycle. Neuroimaging scans from 44 youths with DSM-IV BPD and 22 healthy controls (HC) were analyzed using cross-sectional area measurements and a novel method of volumetric parcellation. Univariate analyses of variance were conducted on CC subregions using both volume and traditional area measurements. Youths with BPD had smaller middle and posterior callosal regions, and reduced typical age-related increases in CC size. The cross-sectional area and novel volumetric methodologies resulted in similar findings. Future longitudinal assessments of CC development would track the evolution of callosal abnormalities in youths with BPD and allow exploration of the functional significance of these findings.

Clinical blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is becoming increasingly valuable in, e.g., presurgical planning, but the commonly used gradient-echo echo-planar imaging (GE-EPI) technique is sometimes hampered by macroscopic field inhomogeneities. This can affect the degree of signal change that will occur in the GE-EPI images as a response to neural activation and the subsequent blood oxygenation changes, i.e., the BOLD sensitivity (BS). In this study, quantitative BS maps were calculated directly from gradient-echo field maps obtainable on most clinical scanners. In order to validate the accuracy of the calculated BS-maps, known shim gradients were applied and field maps and GE-EPI images of a phantom were acquired. Measured GE-EPI image intensity was then compared with the calculated (predicted) image intensity (pII) which was obtained from the field maps using theoretical expressions for image-intensity loss. The validated expressions for pII were used to calculate the corresponding predicted BOLD sensitivity (pBS) maps in healthy volunteers. Since the field map is assumed to be valid throughout an entire fMRI experiment, the influence of subject motion on the pBS maps was also assessed. To demonstrate the usefulness of such maps, pBS was investigated for clinically important functional areas including hippocampus, Broca’s area and primary motor cortex. A systematic left/right pBS difference was observed in Broca’s area and in the hippocampus, most likely due to magnetic field inhomogeneity of the particular MRI-system used in this study. For all subjects, the hippocampus showed pBS values above unity with a clear anterior-posterior gradient and with an abrupt drop to zero pBS in the anterior parts of hippocampus. It is concluded that GE field maps can be used to accurately predict BOLD sensitivity and that this parameter is useful to assess spatial variations which will influence fMRI experiments.

OBJECTIVE: Data-driven methods for fMRI analysis are useful, for example, when an a priori model of signal variations is unavailable. However, activation sources are typically assumed to be linearly mixed, although non-linear properties of fMRI data, including resting-state data, have been observed. In this work, the non-linear locally linear embedding (LLE) algorithm is introduced for dimensionality reduction of fMRI time series data. MATERIALS AND METHODS: LLE performance was optimised and tested using simulated and volunteer data for task-evoked responses. LLE was compared with principal component analysis (PCA) as a preprocessing step to independent component analysis (ICA). Using an example data set with known non-linear properties, LLE-ICA was compared with PCA-ICA and non-linear PCA-ICA. A resting-state data set was analysed to compare LLE-ICA and PCA-ICA with respect to identifying resting-state networks. RESULTS: LLE consistently found task-related components as well as known resting-state networks, and the algorithm compared well to PCA. The non-linear example data set demonstrated that LLE, unlike PCA, can separate non-linearly modulated sources in a low-dimensional subspace. Given the same target dimensionality, LLE also performed better than non-linear PCA. CONCLUSION: LLE is promising for fMRI data analysis and has potential advantages compared with PCA in terms of its ability to find non-linear relationships.

OBJECTIVE: Although attention deficit hyperactivity disorder (ADHD) in adults is associated with significant morbidity and dysfunction and afflicts both sexes, relatively few imaging studies have examined female subjects and none have had sufficient power to adequately examine sex differences. The authors examined sex differences in the neural functioning of adults with ADHD during performance of a verbal working memory task. METHOD: The participants were 44 adults with ADHD matched on age, sex, and estimated IQ to 49 comparison subjects. Accuracy and reaction time on an N-back task were measured to assess working memory. The blood-oxygen-level-dependent functional MRI response was used as a measure of neural activity. RESULTS: A group-by-sex analysis of variance showed no between-group differences in either reaction time or percent correct for the working memory task. For both sexes combined, the adults with ADHD showed less activity than comparison subjects in prefrontal regions. However, sex-by-group analyses revealed an interaction, such that male ADHD subjects showed significantly less activity in right frontal, temporal, and subcortical regions and left occipital and cerebellar regions relative to male comparison subjects, whereas female ADHD subjects showed no differences from female comparison subjects. Exploratory correlation analyses revealed negative associations between working-memory-related activation and number of hyperactive symptoms for men and number of inattentive symptoms for women. CONCLUSIONS: Male but not female adults with ADHD showed significantly altered patterns of neural activity during a verbal working memory task. Men and women showed different associations between neural activity and ADHD symptoms.

A multiple hypothesis tracking approach to the segmentation of small 3D vessel structures is presented. By simultaneously tracking multiple hypothetical vessel trajectories, low contrast passages can be traversed, leading to an improved tracking performance in areas of low contrast. This work also contributes a novel mathematical vessel template model, with which an accurate vessel centerline extraction is obtained. The tracking is fast enough for interactive segmentation and can be combined with other segmentation techniques to form robust hybrid methods. This is demonstrated by segmenting both the liver arteries in CT angiography data, which is known to pose great challenges, and the coronary arteries in 32 CT cardiac angiography data sets in the Rotterdam Coronary Artery Algorithm Evaluation Framework, for which ground-truth centerlines are available.

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women’s menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

The quantitative assessment of the anatomic consequences of cerebral infarction is critical in the study of the etiology and therapeutic response in patients with stroke. We present here an overview of the operation of "WebParc," a computational system that provides measures of stroke lesion volume and location with respect to canonical forebrain neural systems nomenclature. Using a web-based interface, clinical imaging data can be registered to a template brain that contains a comprehensive set of anatomic structures. Upon delineation of the lesion, we can express the size and localization of the lesion in terms of the regions that are intersected within the template. We demonstrate the application of the system using MRI-based diffusion-weighted imaging and document measures of the validity and reliability of its uses. Intra- and inter-rater reliability is demonstrated, and characterized relative to the various classes of anatomic regions that can be assessed. The WebParc system has been developed to meet criteria of both efficiency and intuitive operator use in the real time analysis of stroke anatomy, so as to be useful in support of clinical care and clinical research studies. This article is an overview of its base-line operation with quantitative anatomic characterization of lesion size and location in terms of stroke distribution within the separate gray and white matter compartments of the brain.