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Biomedical subjects

Scott K Holland

Publications and source records attributed to Scott K Holland.

At least 19 recordsLinked to original sources

Cortical reorganization in children with unilateral sensorineural hearing loss.

Previous studies have shown evidence of cortical reorganization following unilateral sensorineural hearing loss (USNHL). In addition, study participants with right USNHL have shown greater deficits in academic and language performance compared with those with left USNHL. A preliminary functional magnetic resonance imaging investigation was performed on a small cohort of participants, four with left USNHL and four with right USNHL, using the paradigm of listening to random tones. While the participants with left USNHL displayed greater activation in the right superior temporal gyrus, those with right USNHL displayed greater activation in the left inferior frontal area immediately anterior to the superior temporal gyrus. The results provide preliminary evidence of disparate neural circuitry supporting auditory processing in participants with left and right USNHL.

Acoustic Stimulation↗

Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study.

A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5-18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full-scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito-parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts.

Adolescent↗

BOLD fMRI signal increases with age in selected brain regions in children.

To determine whether the BOLD signal used in fMRI is age dependent in childhood, 332 healthy children (age 4.9-18.9 years) performed tasks in a periodic block design during 3 T fMRI: (1) a verb generation task interleaved with a finger tapping task; (2) a word-picture matching task interleaved with an image discrimination task. Significant correlations between percent signal change in BOLD effect and age occurred in left Broca's, middle frontal, Wernicke's, and inferior parietal regions, and anterior cingulate during the verb generation task; in precentral, postcentral, middle frontal, supplementary motor, and precuneus regions during the finger tapping task; and in bilateral lingula gyri during the word-picture matching task. Thus, BOLD effect increases with age in children during sensorimotor and language tasks.

Adolescent↗

Voxel-based morphometry in adolescents with bipolar disorder: first results.

Bipolar disorder is an increasingly recognized cause of significant morbidity in the pediatric age group. However, there is still a large degree of uncertainty regarding the underlying neurobiological deficits. In this preliminary study, we performed automated volumetric studies and whole-brain voxel-based morphometry (VBM) on gray matter. Imaging data from 10 adolescents with bipolar disorder were compared with data from 52 age- and gender-matched healthy controls. Previously defined brain parcellations and optimized VBM protocols were used, based on custom-made pediatric reference data. An additional, exploratory whole-brain comparison was also implemented. The volumetric region-of-interest study revealed significantly greater gray matter volume in central gray matter structures bilaterally (including the basal ganglia and the thalamus) and the left temporal lobe in the bipolar group. VBM confirmed bilaterally larger basal ganglia. Localized gray matter deficits in bipolar subjects were found in the medial temporal lobe, orbito-frontal cortex, and the anterior cingulate, confirming and extending earlier studies.

Adolescent↗

The effect of musical training on the neural correlates of math processing: a functional magnetic resonance imaging study in humans.

The neural correlates of the previously hypothesized link between formal musical training and mathematics performance are investigated using functional magnetic resonance imaging (fMRI). FMRI was performed on fifteen normal adults, seven with musical training since early childhood, and eight without, while they mentally added and subtracted fractions. Musical training was associated with increased activation in the left fusiform gyrus and prefrontal cortex, and decreased activation in visual association areas and the left inferior parietal lobule during the mathematical task. We hypothesize that the correlation between musical training and math proficiency may be associated with improved working memory performance and an increased abstract representation of numerical quantities.

Adult↗

Comparison of three methods for generating group statistical inferences from independent component analysis of functional magnetic resonance imaging data.

PURPOSE: To evaluate the relative effectiveness of three previously proposed methods of performing group independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data. MATERIALS AND METHODS: Data were generated via computer simulation. Components were added to a varying number of subjects between 1 and 20, and intersubject variability was simulated for both the added sources and their associated time courses. Three methods of group ICA analyses were performed: across-subject averaging, subject-wise concatenation, and row-wise concatenation (e.g., across time courses). RESULTS: Concatenating across subjects provided the best overall performance in terms of accurate estimation of the sources and associated time courses. Averaging across subjects provided accurate estimation (R > 0.9) of the time courses when the sources were present in a sufficient fraction (about 15%) of 100 subjects. Concatenating across time courses was shown not to be a feasible method when unique sources were added to the data from each subject, simulating the effects of motion and susceptibility artifacts. CONCLUSION: Subject-wise concatenation should be used when computationally feasible. For studies involving a large number of subjects, across-subject averaging provides an acceptable alternative and reduces the computational load.

Computer Simulation↗

A STAP algorithm approach to fMRI: a simulation study.

PURPOSE: To adapt the space-time adaptive processing (STAP) algorithm, previously developed in the field of sensor array processing and applied to radar signal processing, for use in construction of brain activation maps in functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: STAP is a two-dimensional filter in which both the spatial and temporal responses are controlled adaptively. It processes space-time data as a complete spatiotemporal set. Unlike presently used fMRI techniques, STAP locates activated regions both spatially and in frequency. RESULTS: Computer simulations incorporating actual MRI noise indicate that STAP exhibits a high degree of accuracy in detecting the small signal intensity changes inherent in fMRI. CONCLUSION: Because STAP processes space-time data as a single data matrix, it exhibits potential over currently available fMRI methods in providing a measure of the full spatiotemporal extent of a task-related activity.

Algorithms↗

Event-related fMRI technique for auditory processing with hemodynamics unrelated to acoustic gradient noise.

Acoustic noise from the imaging gradients presents a major difficulty in functional MRI (fMRI) studies of auditory cortical function. For studies involving hearing-impaired pediatric subjects, the auditory stimuli should be presented during completely silent gradient intervals. In addition, the scan time is limited by constraints involving subject motion and subject compliance. A novel event-related method for conducting fMRI studies of auditory function is proposed. Auditory stimuli are presented during completely silent gradient intervals, but using a variable TR. A general nonlinear model (GNLM) is proposed as a postprocessing methodology for the data. The technique increases the flexibility of the experimental design, with minimal loss of sensitivity compared to standard fMRI acquisition techniques, and may therefore be useful for fMRI studies of auditory function in hearing-impaired pediatric subjects.

Adult↗

High-resolution functional MRI at 3T in healthy and epilepsy subjects: hippocampal activation with picture encoding task.

Functional MRI (fMRI) studies of memory with coarse resolution of 4 x 4 x 5 mm often fail to demonstrate blood oxygenation level-dependent (BOLD) activation in the hippocampal formation. This failure occurs when nonactivating white matter is averaged with the signal from hippocampal gray matter, attenuating the total BOLD signal from a single voxel due to the "partial volume effect." In this study, we evaluated the suitability of high-resolution fMRI at 3T (voxel size 2 x 2 x 3 mm) for improved visualization of hippocampal activation during memory encoding in 21 healthy and 6 epilepsy subjects. We used a picture encoding task (block design) that involved memorization of indoor and outdoor scenes along with an appropriate resting task. Region-of-interest (ROI) analysis was performed; laterality indices (LIs) were calculated based on hippocampal ROIs (hROIs) or on global medial temporal ROIs (mtROIs). In 19 healthy subjects, robust bilateral BOLD signal changes within both ROIs were noted. The mean LI+/-SD for the hROIs is -0.12+/-0.06 and that for the medial temporal ROIs -0.12+/-0.05, with correlation between the LIs (r = 0.59, P = 0.009). Good concordance was noted between the surgical outcome and memory lateralization with the fMRI task employed in this study. The preliminary results are encouraging, and with continuing improvements in MRI scanner technology, we expect fMRI of the hippocampal formation at higher resolution to be possible and preferable. Furthermore, these results suggest that a larger study to test the utility of high-resolution fMRI in epilepsy presurgical evaluation is needed.

Adult↗

A preliminary FMRI study of sustained attention in euthymic, unmedicated bipolar disorder.

The symptoms of bipolar disorder suggest dysfunction of anterior limbic networks that modulate emotional behavior and that reciprocally interact with dorsal attentional systems. Bipolar patients maintain a constant vulnerability to mood episodes even during euthymia, when symptoms are minimal. Consequently, we predicted that, compared with healthy subjects, bipolar patients would exhibit abnormal activation of regions of the anterior limbic network with corresponding abnormal activation of other cortical areas involved in attentional processing. In all, 10 unmedicated euthymic bipolar patients and 10 group-matched healthy subjects were studied with fMRI while performing the Continuous Performance Task-Identical Pairs version (CPT-IP). fMRI scans were obtained on a 3.0 T Bruker system using an echo planar imaging (EPI) pulse sequence, while subjects performed the CPT-IP and a control condition to contrast group differences in regional brain activation. The euthymic bipolar and healthy subjects performed similarly on the CPT-IP, yet showed significantly different patterns of brain activation. Specifically, bipolar patients exhibited increased activation of limbic, paralimbic, and ventrolateral prefrontal areas, as well as visual associational cortices. Healthy subjects exhibited relatively increased activation in fusiform gyrus and medial prefrontal cortex. In conclusion, these differences suggest that bipolar patients exhibit overactivation of anterior limbic areas with corresponding abnormal activation in visual associational cortical areas, permitting successful performance of an attentional task. Since the differences occurred in euthymia, they may represent trait, rather than state, abnormalities of brain function in bipolar disorder.

Adult↗

Functional magnetic resonance imaging: contemporary and future use.

PURPOSE OF REVIEW: Functional magnetic resonance imaging is a relatively new neuroimaging technique that is being used in both research and clinical applications. Increasing work has been done to elucidate the auditory cortex. RECENT FINDINGS: Current studies focus on enhancing the sensitivity of functional magnetic resonance imaging in studying the auditory cortex and subcortical pathways in response to tonal stimulation, to evaluate the integrity of the auditory cortex before cochlear implantation, and as a screening tool for hearing impairment in the young child. SUMMARY: Recent work has been encouraging: silent functional magnetic resonance imaging techniques allow for better evaluation of the auditory cortex with less confounding scanner noises. Functional magnetic resonance imaging can be safely and reproducibly performed in hearing-impaired children and in the preoperative evaluation of candidates for cochlear implantation.

Adult↗

Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study.

OBJECTIVES: Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder. METHODS: Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups. RESULTS: The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high-medium to large effect sizes. No significant group differences were identified in TADC. CONCLUSIONS: Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.

Adult↗

Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task.

OBJECTIVES: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. METHODS: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. RESULTS: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. CONCLUSIONS: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.

Adult↗

Variability of gray and white matter during normal development: a voxel-based MRI analysis.

This study was aimed at investigating regional and local variability of brain tissue during normal human brain development. We investigated high-resolution MR-imaging data using SPM99 (Wellcome Department, University College London, UK). A pixel-wise variation coefficient of gray and white matter was calculated to visualize local variability. Data from 200 normal children (5-18 years) were analyzed. We found a profound interaction between variability of brain structures and normal development in both gray and white matter. Variability in gray and white matter shows regionally specific, age-related variations, possibly offering a new tool for the assessment of subtle brain abnormalities. Our results emphasize the necessity to take this variability into account when planning pediatric neuroimaging studies.

Adolescent↗

The effect of musical training on music processing: a functional magnetic resonance imaging study in humans.

Previous studies have demonstrated changes in neuronal activity in trained musicians relative to controls while performing various music processing tasks. In this study the neural correlates of the effect of music training on two aspects of music processing, melody and harmony, are investigated using functional magnetic resonance imaging (fMRI). Fifteen subjects, seven with continuous musical training from early childhood to adulthood and eight without, underwent a passive fMRI listening paradigm designed to test the effects of melodic and harmonic processing. Melodic processing activated the most anterior part of the superior temporal gyrus for both musicians and non-musicians, while harmonic processing activated different visual association areas for musicians relative to non-musicians. The inferior parietal lobules were recruited only by musicians for both tasks. We conclude that musical training results in the recruitment of different neural networks for these aspects of music processing.

Acoustic Stimulation↗

Fast high-resolution 3D segmented echo planar imaging for dose mapping using a superheated emulsion chamber.

The superheated emulsion chamber (SEC) consists of superheated droplets of halocarbons in an aqueous gel. The gel resides in a pressure chamber. Brachytherapy sources can be implanted in the SEC for radiation dosimetry studies. Upon irradiation by ionizing radiation, the metastable droplets vaporize to form microbubbles. MRI can be used to determine the distribution of bubbles following irradiation of the SEC. In order to generate sufficient statistical accuracy in the determination of dose distributions around brachytherapy sources, it is necessary to use hundreds of irradiation cycles. Susceptibility-weighted images provide contrast between the gel and the vapor microbubbles. This article describes a 3D, blipped, double-sampled, segmented echo-planar imaging technique for rapidly imaging the SEC at 650 microm isotropic 3D resolution in about 2 min. This method was used with a pressure cycling SEC to acquire hundreds of images in several hours. Results are presented showing the 2D dose distribution generated by an (125)I source as measured in the SEC using this new imaging method.

Brachytherapy↗

Bright spots: correlations of gray matter volume with IQ in a normal pediatric population.

The localization of brain areas related to cognitive functions has yet to be thoroughly explored in children. We therefore set out to apply volumetric, voxel-based, and structural connectivity analyses to magnetic resonance images from a large sample of healthy children. We could confirm a strong correlation of whole-brain gray matter volume and the individual intelligence quotient; however, this correlation only developed with age in our sample, in that it was not present in the younger children. With the application of an optimized protocol for voxel-based morphometry, the anterior cingulate was shown to be directly correlated with a measure of human intelligence. Furthermore, an analysis of structural connectivity identified gray matter volume in several distinct brain areas to be related to cognitive functions. The implications of our findings for normal development, pathological processes, and our understanding of cognition are discussed and related to previous findings.

Aging↗

Using a phantom to compare MR techniques for determining the ratio of intraabdominal to subcutaneous adipose tissue.

OBJECTIVE: Patients who have a greater distribution of intraabdominal adipose tissue as compared with subcutaneous adipose tissue and an increased ratio of intraabdominal adipose tissue to subcutaneous adipose tissue are at greater risk for developing cardiovascular disease and type 2 diabetes mellitus. In previous MR investigations, researchers have used conventional T1-weighted spin-echo images to determine the ratio of intraabdominal adipose tissue to subcutaneous adipose tissue. However, no investigation, to our knowledge, has been performed to determine the accuracy of using different MR sequences to estimate adipose distribution. The purpose of our investigation was to compare MR imaging and segmentation techniques in calculating the ratio of intraabdominal to subcutaneous adipose tissue using an adiposity phantom. MATERIALS AND METHODS: A phantom was created to simulate the distribution of subcutaneous and intraabdominal fat (with known volumes). Axial MR images were obtained twice through the phantom using a 5-mm slice thickness and zero gap for the following T1-weighted sequences: spin-echo, fast Dixon, and three-dimensional (3D) spoiled gradient-echo. An in-house computer software program was then used to segment the volumes of fat and calculate the volume of intraabdominal adipose tissue and subcutaneous adipose tissue and the ratio of intraabdominal to subcutaneous adipose tissue. Each imaging data set was segmented three times, so six sets of data were yielded for each imaging technique. The percentage predicted of the true volume was calculated for each MR imaging technique for each fat variable. The mean percentages for each variable were then compared using one-factor analysis of variance to determine whether differences exist among the three MR techniques. RESULTS: The three MR imaging techniques had statistically significant different means for the predicted true volume of two variables: volume of subcutaneous adipose tissue (p < 0.001) and volume of intraabdominal adipose tissue (p = 0.0426). Estimates based on fast Dixon images were closest to the true volumes for all the variables. All MR imaging techniques performed similarly in estimating the ratio of intraabdominal adipose tissue to subcutaneous adipose tissue (p = 0.9117). The acquisition time for the 3D spoiled gradient-echo images was 10-22 times faster than for the other sequences. CONCLUSION: Conventional T1-weighted spin-echo MR imaging, the current sequence used in practice for measuring visceral adiposity, may not be the optimal MR sequence for this purpose. We found that the T1-weighted fast Dixon sequence was the most accurate at estimating all fat volumes. The T1-weighted 3D spoiled gradient-echo sequence generated similar ratios of intraabdominal to subcutaneous adipose tissue in a fraction of the acquisition time.

Abdominal Cavity↗