Micheal D Phillips’s research while affiliated with Intermountain Medical Center and other places

Background Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. Objective In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual–spatial episodic memory. Methods Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. Results After adjusting for disease duration, immediate recall performance on a visual–spatial episodic memory task was significantly predicted by hippocampal volume (p < 0.003). Delayed recall on the same task was significantly predicted by volume of the left thalamus (p < 0.003). For both memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures (p < 0.002). Conclusion Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

Purpose To explore the relative robustness of functional MRI (fMRI) activation volume and blood oxygen level-dependent (BOLD) signal change as fMRI metric, and to study the effect of relative robustness on the correlation between fMRI activation and cortical gamma amino butyric acid (GABA) in healthy controls and patients with multiple sclerosis (MS). Methods fMRI data were acquired from healthy controls and patients with MS, with the subjects peforming self paced bilateral finger tapping in block design. GABA spectroscopy was performed with voxel placed on the area of maximum activation during fMRI. Activation volume and BOLD signal changes at primary motor cortex (M1), as well as GABA concentration were calculated for each patient. Results Activation volume correlated with BOLD signal change in healthy controls, but no such correlation was observed in patients with MS. This difference was likely the result of higher intersubject noise variance in the patient population. GABA concentration correlated with M1 activation volume in patients but not in controls, and did not correlate with any fMRI metric in patients or controls. Conclusion Our data suggest that activation volume is a more robust measure than BOLD signal change in a group with high intersubject noise variance as in patients with MS. Additionally, this study demonstrated difference in correlation behavior between GABA concentration and the 2 fMRI metrics in patients with MS, suggesting that GABA - activation volume correlation is more appropriate measure in the patient group.

Background Imaging can provide noninvasive neural markers of disease progression in multiple sclerosis (MS) that are related to behavioral and cognitive symptoms. Past work suggests that diffusion tensor imaging (DTI) provides a measure of white matter pathology, including demyelination and axonal counts. Objectives In the current study, the authors investigate the relationship of DTI measures in the cingulum bundle to common deficits in MS, including episodic memory, working memory, and information processing speed. Methods Fifty-seven patients with MS and 17 age- and education-matched controls underwent high-spatial resolution diffusion scans and cognitive testing. Probabilistic tracking was used to generate tracks from the posterior cingulate cortex to the entorhinal cortex. Results Radial and axial diffusivity values were significantly different between patients and controls (p < 0.031), and in patients bilateral diffusion measures were significantly related to measures of episodic memory and speed of processing (p < 0.033). Conclusions The tractography-based measures of posterior cingulum integrity reported here support further development of DTI as a viable measure of axonal integrity and cognitive function in patients with MS.

Introduction: Diffusion tensor imaging (DTI) measures in patients with multiple sclerosis (MS), particularly those measures associated with a specific white matter pathway, have consistently shown correlations with function. This study sought to investigate correlations between DTI measures in the fornix and common cognitive deficits in MS patients, including episodic memory, working memory and attention. Materials and methods: Patients with MS and group age- and sex-matched controls underwent high-resolution diffusion scanning (1-mm isotropic voxels) and cognitive testing. Manually drawn forniceal regions of interest were applied to individual maps of tensor-derived measures, and mean values of transverse diffusivity (TD), mean diffusivity (MD), longitudinal diffusivity (LD) and fractional anisotropy (FA) were calculated. Results: In 40 patients with MS [mean age ± S.D.=42.55 ± 9.1 years; Expanded Disability Status Scale (EDSS)=2.0 ± 1.2; Multiple Sclerosis Functional Composite (MSFC) score=0.38 ± 0.46] and 20 healthy controls (mean age ± S.D.=41.35 ± 9.7 years; EDSS=0.0 ± 0; MSFC score=0.74 ± 0.24), we found that FA, MD and TD values in the fornix were significantly different between groups (P<.03), and patient performance on the Brief Visuospatial Memory Test-Revised (BVMT-R) was correlated with DTI measures (P<.03). Discussion: These results are consistent with findings of axonal degeneration in MS and support the use of DTI as an indicator of disease progression.

Purpose To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls. Materials and Methods A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks. Results In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10–4) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037). Discussion These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression.

Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks. This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension-type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by-products of frequent attacks or long duration of illness with these changes. The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2' shortening. Because iron accumulation should cause shortening of both T2 and T2', although the lack of significance in observed T2' difference could be due to increased variance in T2' the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.

ALBERTS, J.L., S.M. LINDER, A.L. PENKO, M.J. LOWE, and M. PHILLIPS. It is not about the bike, it is about the pedaling: forced exercise and parkinson's disease. Exerc. Sport Sci. Rev., Vol. 39, No. 4, pp. 177-186, 2011. Forced exercise has resulted in neuroprotective effects and improved motor function in animal studies. These promising results have not yet been translated fully to humans with Parkinson's disease (PD), as traditional exercise interventions have not yielded global improvements in function. A novel forced exercise intervention is described that has resulted in improved motor function and central nervous system function in PD patients.

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Understanding the GABA concentration, in vivo, is important to understand normal brain function. Using MEGA point-resolved spectroscopy sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex was measured using a voxel identified from a functional magnetic resonance imaging scan. The GABA level in a 20×20×20-mm(3) voxel consisting of 37%±7% gray matter, 52%±12% white matter and 11%±8% cerebrospinal fluid in the sensorimotor region was measured to be 1.43±0.48 mM. In addition, using linear regression analysis, GABA concentrations within gray and white matter were calculated to be 2.87±0.61 and 0.33±0.11 mM, respectively.

Surgery is often the only effective treatment for intractable epilepsy, but its benefits must be balanced by potential disruption of eloquent cortical functions. Wada test is the standard technique to lateralize language before surgery; however, it is invasive and associated with complications. fMRI provides an attractive noninvasive alternative, which has been previously shown to correlate with Wada results. However this correlation is imperfect since standard fMRI laterality indices are dependent on a particular arbitrary statistical threshold used in the data processing. We report a novel automated, threshold-independent fMRI methodology to assess language lateralization, which we hypothesize provides a robust and unbiased pre-operative assessment. This hemispheric histogram analysis method can accurately interrogate language lateralization, as validated against the Wada test.