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Biomedical subjects

Mark J Lowe

Publications and source records attributed to Mark J Lowe.

11 recordsLinked to original sources

An objective method for regularization of fiber orientation distributions derived from diffusion-weighted MRI.

Spherical deconvolution is an elegant method by which the orientation of crossing fibers in the brain can be estimated from a diffusion-weighted MRI measurement. However, higher resolution of fiber directions comes at the cost of higher susceptibility to noise. In this study, we describe the use of linear regularization of the fiber orientation distribution function by Damped Singular Value Decomposition. Furthermore, the degree of regularization is optimized on a voxel-by-voxel basis with no user interaction using Generalized Cross Validation. We find, by simulations, that regularization can improve the reliability of fiber orientation determination when the signal-to-noise ratio is low. Simulations and in vivo measurements indicate that spurious peaks of the fiber orientation distribution function in regions with low anisotropy largely disappear when regularization is introduced. The methods examined are fast enough to be used on a routine basis with diffusion MRI data sets and may improve estimation of water diffusion properties in heterogeneous white matter and boost reliability of fiber tracking through regions of brain with complex fiber geometry.

Brain↗

Functional pathway-defined MRI diffusion measures reveal increased transverse diffusivity of water in multiple sclerosis.

The diffusion properties of water are sensitive to microscopic changes in the white matter of multiple sclerosis (MS) patients. Typical MRI measures of disease burden in MS demonstrate modest to poor correlation with disability. Functional MRI and DTI-based fiber tracking were used to define the interhemispheric white matter pathway connecting bilateral supplementary motor areas (SMA) in 16 MS patients sand 16 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), longitudinal (lambda(1)) and transverse diffusivity (lambda(2)) were measured along this pathway in all subjects. Mean FA was 0.587 +/- 0.032 for patients and 0.608 +/- 0.020 for controls (P < 0.02). Mean MD was (0.821 +/- 0.055) x 10(-3) mm(2) s(-1) for patients and (0.770 +/- 0.020) x 10(-3) mm(2) s(-1) for controls (P < 0.004). Mean lambda(1) values were (1.462 +/- 0.099) x 10(-3) mm(2) s(-1) for patients and (1.400 +/- 0.034) x 10(-3) mm(2) s(-1) for controls (P < 0.02). Mean lambda(2) values were (0.500 +/- 0.047) x 10(-3) mm(2) s(-1) for patients and (0.454 +/- 0.027) x 10(-3) mm(2) s(-1) for controls (P < 0.001). In addition, the correlation between the Multiple Sclerosis Functional Composite (MSFC) and transverse diffusivity was -0.341 (P < 0.05). The component test of the MSFC most related to the SMA pathway studied with our MRI method (Nine-hole Peg Test) showed significant correlation with transverse diffusivity (r = 0.392, P < 0.02), indicating that probing functional pathways with MRI measures can lead to a better reflection of disease status.

Adult↗

Parkinson disease: pattern of functional MR imaging activation during deep brain stimulation of subthalamic nucleus--initial experience.

PURPOSE: To prospectively determine the pattern of functional magnetic resonance (MR) imaging activation at 3 T produced by deep brain stimulation (DBS) of subthalamic nucleus (STN) for treatment of Parkinson disease and to determine the safety of DBS electrode stimulation during functional MR imaging at 3 T. MATERIALS AND METHODS: Informed consent was obtained from all subjects participating in the study, and the study protocol was approved by the institutional review board at the Cleveland Clinic Foundation and was HIPAA compliant. After extensive phantom safety testing of DBS lead systems, five patients (three men, two women; mean age, 49.4 years +/- 14.5 [standard deviation]; range, 31-74 years) with percutaneously extended bilateral DBS electrodes placed in the STN for treatment of Parkinson disease were examined at 3 T on the 1st or 2nd postoperative day. Imaging consisted of a three-dimensional anatomic data set with leads disconnected and a blood oxygen level-dependent functional MR image with a single lead connected to the external pulse generator in the MR imaging control room by using stimulation parameters previously determined to produce optimal stimulation for alleviation of symptoms. A total of nine leads were tested with the functional MR imaging protocol. Subjects underwent neurologic examination immediately before and after MR imaging. RESULTS: All five patients completed the study without change in their neurologic examination and with activation seen in eight of nine electrodes stimulated. Activation was seen in the ipsilateral basal ganglia in all subjects and ipsilateral thalamus in six of the electrodes tested. Two of the electrode stimulations demonstrated additional activation in the STN and/or substantia nigra region adjacent to the electrode tip. For three electrode stimulations, activation was seen in the contralateral superior cerebellum. CONCLUSION: Therapeutically effective DBS of STN can be performed safely during functional MR imaging at 3 T and produces a consistent pattern of ipsilateral activation of deep brain motor structures.

Adult↗

Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study.

BACKGROUND: Functional imaging studies indicate that imbalances in cortico-limbic activity and connectivity may underlie the pathophysiology of MDD. In this study, using functional Magnetic Resonance Imaging (fMRI), we investigated differences in cortico-limbic activity and connectivity between depressed patients and healthy controls. METHODS: Fifteen unmedicated unipolar depressed patients and 15 matched healthy subjects underwent fMRI during which they first completed a conventional block-design activation experiment in which they were exposed to negative and neutral pictures. Next, low frequency blood oxygenation dependent (BOLD) related fluctuations (LFBF) data were acquired at rest and during steady-state exposure to neutral, positive and negative pictures. LFBF correlations were calculated between anterior cingulate cortex (ACC) and limbic regions--amygdala (AMYG), pallidostriatum (PST) and medial thalamus (MTHAL) and used as a measure of cortico-limbic connectivity. RESULTS: Depressed patients had increased activation of cortical and limbic regions. At rest and during exposure to neutral, positive, and negative pictures cortico-limbic LFBF correlations were decreased in depressed patients compared to healthy subjects. CONCLUSIONS: The finding of increased activation of limbic regions and decreased LFBF correlations between ACC and limbic regions is consistent with the hypothesis that decreased cortical regulation of limbic activation in response to negative stimuli may be present in depression.

Adult↗

Media violence exposure and executive functioning in aggressive and control adolescents.

The relationship between media violence exposure and executive functioning was investigated in samples of adolescents with no psychiatric diagnosis or with a history of aggressive-disruptive behavior. Age-, gender-, and IQ-matched samples of adolescents who had no Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV; American Psychiatric Association, 1994) diagnosis (N = 27) and of adolescents who had DSM-IV Disruptive Behavior Disorder diagnoses (N = 27) completed measures of media violence exposure and tests of executive functioning. Moderate to strong relationships were found between higher amounts of media violence exposure and deficits in self-report, parent-report, and laboratory-based measures of executive functioning. A significant diagnosis by media violence exposure interaction effect was found for Conners' Continuous Performance Test scores, such that the media violence exposure-executive functioning relationship was stronger for adolescents who had Disruptive Behavior Disorder diagnoses. Results indicate that media violence exposure is related to poorer executive functioning, and this relationship may be stronger for adolescents who have a history of aggressive-disruptive behavior.

Adolescent↗

Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.

Adult↗

Cardiac-induced physiologic noise in tissue is a direct observation of cardiac-induced fluctuations.

Recent studies have shown that in certain cases, cardiac and respiratory rate fluctuations in BOLD-weighted MRI time courses may be an artifact unique to rapid sampled acquisitions and may not be present in longer repetition-time acquisitions. The implication of this is that, in these cases, cardiac and respiratory rate fluctuations are not aliased into data that undersample these effects and do not affect the resulting time course measurements. In this study, we show that these cases are specific to regions of large cerebrospinal fluid content and are not generally true for gray matter regions of the brain. We demonstrate that in many brain regions of interest, these fluctuations are directly observed as BOLD fluctuations and thus will affect measurements that undersample these effects.

Artifacts↗

Neural correlates of auditory sensory memory and automatic change detection.

An auditory event-related potential component, the mismatch negativity (MMN), reflects automatic change detection and its prerequisite, sensory memory. This study examined the neural correlates of automatic change detection using BOLD fMRI and two rates of presentation previously shown to induce either a large or no MMN. A boxcar block design was employed in two functional scans, each performed twice. A block consisting of 1000-Hz standards (S) alternated with one consisting of 1000-Hz standards and 2000-Hz infrequent deviants (S + D). Presentation rate was either 150 or 2400 ms. Fourteen participants were instructed to ignore all auditory stimulation and concentrate on a film (no audio) by reading subtitles. Data analysis used SPM99 and random effects approach. Cluster statistics (P < 0.05, corrected) were employed at a height threshold of P < 0.001. At the short ISI, there was a significant BOLD response in the right superior temporal gyrus (STG), the left insula, and the left STG (including parts of primary auditory cortex). There were no suprathreshold clusters at the long rate, with S + D blocks inducing no greater activity than S blocks. These results support the hypothesis that the automatic detection of auditory change occurs in the STG bilaterally and relies on the maintenance of sensory memory traces.

Adult↗

Clustered components analysis for functional MRI.

A common method of increasing hemodynamic response (SNR) in functional magnetic resonance imaging (fMRI) is to average signal timecourses across voxels. This technique is potentially problematic because the hemodynamic response may vary across the brain. Such averaging may destroy significant features in the temporal evolution of the fMRI response that stem from either differences in vascular coupling to neural tissue or actual differences in the neural response between two averaged voxels. Two novel techniques are presented in this paper in order to aid in an improved SNR estimate of the hemodynamic response while preserving statistically significant voxel-wise differences. The first technique is signal subspace estimation for periodic stimulus paradigms that involves a simple thresholding method. This increases SNR via dimensionality reduction. The second technique that we call clustered components analysis is a novel amplitude-independent clustering method based upon an explicit statistical data model. It includes an unsupervised method for estimating the number of clusters. Our methods are applied to simulated data for verification and comparison to other techniques. A human experiment was also designed to stimulate different functional cortices. Our methods separated hemodynamic response signals into clusters that tended to be classified according to tissue characteristics.

Algorithms↗

Multiple sclerosis: low-frequency temporal blood oxygen level-dependent fluctuations indicate reduced functional connectivity initial results.

PURPOSE: To study the correlation of low-frequency blood oxygenation level-dependent (BOLD) fluctuations on magnetic resonance (MR) images obtained of the left- and right-hemisphere primary motor regions in healthy control subjects and patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sixteen healthy volunteers and 20 patients with MS underwent MR imaging with a 1.5-T imager by using a protocol designed to monitor low-frequency BOLD fluctuations. Data for low-frequency BOLD fluctuations were acquired with subjects at rest and during continuous performance of a bilateral finger-tapping task. These data were low-pass filtered (<0.08 Hz), and cross correlations of all acquired pixels to a region of interest in the left precentral gyrus were calculated. Confidence levels were calculated from the cross correlations. The fraction of pixels in the right precentral gyrus above a confidence level of 95% for correlation with the left precentral gyrus was calculated for each subject. RESULTS: A plot of the fraction of the right precentral gyrus with high correlation with the left precentral gyrus for the finger-tapping state versus the resting state showed a clear discrimination between patients with MS and control subjects. Compared with control subjects, patients with MS generally had a smaller fraction of the pixels in the right precentral gyrus above the confidence level. This finding indicates that our method results in greater than 60% sensitivity and 100% specificity for discriminating patients with MS from control subjects. No significant correlation was found between clinical measures of MS disease and correlations of low-frequency BOLD fluctuations between left and right precentral gyri. CONCLUSION: On the basis of the connectivity measure of low-frequency BOLD fluctuations, patients with MS exhibited lower functional connectivity between right- and left-hemisphere primary motor cortices when compared with that in control subjects.

Adult↗

Media violence exposure and frontal lobe activation measured by functional magnetic resonance imaging in aggressive and nonaggressive adolescents.

OBJECTIVE: To understand better the relation between media violence exposure, brain functioning, and trait aggression, this study investigated the association between media violence exposure and brain activation as measured by functional magnetic resonance imaging (fMRI) in groups of normal adolescents and adolescents with disruptive behavior disorder (DBD) with aggressive features. METHODS: Seventy-one participants underwent neuropsychologic evaluation and assessment of exposure to violent media. Subjects also were evaluated with fMRI while performing a counting Stroop (CS) task. RESULTS: Frontal lobe activation was reduced in aggressive subjects compared with control subjects. In addition, differences in frontal lobe activation were associated with differences in media violence exposure. Specifically, activation during performance of the CS in control subjects with high media violence exposure resembled that seen in DBD subjects. CONCLUSIONS: Our findings suggest that media violence exposure may be associated with alterations in brain functioning whether or not trait aggression is present.

Adolescent↗