Faculty Bibliography

Background: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking. Objective: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients' disease course. Methods: The MSSS and average WBNAA loss rate (DeltaWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a 'benign' disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were 'non-benign': EDSS score higher than 3.0. Results: The two cohorts were indistinguishable in age and disease duration. Benign patients' EDSS and MSSS (2.1 +/- 0.7, 1.15 +/- 0.60) were significantly lower than non-benign (4.6 +/- 1.0, 3.6 +/- 1.2; both p < 10(-4)). Their respective average DeltaWBNAA, 0.10 +/- 0.16 and 0.11 +/- 0.12 mM/year, however, were not significantly different (p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, DeltaWBNAA is only sensitive (92.6%) but not specific (2.9%). Conclusion: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that 'benign' MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity

Whether consciousness is an all-or-none or graded phenomenon is an area of inquiry that has received considerable interest in neuroscience and is as of yet, still debated. In this magnetoencephalography (MEG) study we used a single stimulus paradigm with sub-threshold, threshold and supra-threshold duration inputs to assess whether stimulus perception is continuous with or abruptly differentiated from unconscious stimulus processing in the brain. By grouping epochs according to stimulus identification accuracy and exposure duration, we were able to investigate whether a high-amplitude perception-related cortical event was (1) only evoked for conditions where perception was most probable, (2) had invariant amplitude once evoked and (3) was largely absent for conditions where perception was least probable (criteria satisfying an all-on-none hypothesis). We found that averaged evoked responses showed a gradual increase in amplitude with increasing perceptual strength. However, single-trial analyses demonstrated that stimulus perception was correlated with an all-or-none response, the temporal precision of which increased systematically as perception transitioned from ambiguous to robust states. Due to poor signal-to-noise resolution of single-trial data, whether perception-related responses, whenever present, were invariant in amplitude could not be unambiguously demonstrated. However, our findings strongly suggest that visual perception of simple stimuli is associated with an all-or-none cortical-evoked response the temporal precision of which varies as a function of perceptual strength

Purpose:To investigate technical feasibility, test-retest reproducibility, and the ability to differentiate healthy subjects from subjects with osteoarthritis (OA) with diffusion-tensor (DT) imaging parameters and T2 relaxation time.Materials and Methods:This study was approved by the institutional review board and was HIPAA compliant. All subjects provided written informed consent. DT imaging parameters and T2 (resolution = 0.6 x 0.6 x 2 mm) of patellar cartilage were measured at 7.0 T in 16 healthy volunteers and 10 patients with OA with subtle inhomogeneous signal intensity but no signs of cartilage erosion at clinical magnetic resonance (MR) imaging. Ten volunteers were imaged twice to determine test-retest reproducibility. After cartilage segmentation, maps of mean apparent diffusion coefficient (ADC), fractional anisotropy (FA), and T2 relaxation time were calculated. Differences for ADC, FA, and T2 between the healthy and OA populations were assessed with nonparametric tests. The ability of each MR imaging parameter to help discriminate healthy subjects from subjects with OA was assessed by using receiver operating characteristic curve analysis.Results:Test-retest reproducibility was better than 10% for mean ADC (8.1%), FA (9.7%), and T2 (5.9%). Mean ADC and FA differed significantly (P < .01) between the OA and healthy populations, but T2 did not. For ADC, the optimal threshold to differentiate both populations was 1.2 x 10(-3) mm(2)/sec, achieving specificity of 1.0 (16 of 16) and sensitivity of 0.80 (eight of 10). For FA, the optimal threshold was 0.25, yielding specificity of 0.88 (14 of 16) and sensitivity of 0.80 (eight of 10). T2 showed poor differentiation between groups (optimal threshold = 22.9 msec, specificity = 0.69 [11 of 16], sensitivity = 0.60 [six of 10]).Conclusion:In vivo DT imaging of patellar cartilage is feasible, has good test-retest reproducibility, and may be accurate in discriminating healthy subjects from subjects with OA. ADC and FA are two promising biomarkers for early OA.(c) RSNA, 2011

HYPOTHESIS: Reactivation of herpes simplex virus type 1 (HSV-1) in geniculate ganglion neurons (GGNs) is an etiologic mechanism of Bell's palsy (BP) and delayed facial palsy (DFP) after otologic surgery. BACKGROUND: Several clinical studies, including temporal bone studies, antibody, titers, and intraoperative studies, suggest that reactivation of HSV-1 from latently infected GGNs may lead to both BP and DFP. However, it is difficult to study these processes in humans or live animals. METHODS: Primary cultures of GGNs were latently infected with Patton strain HSV-1 expressing a green fluorescent protein-late lytic gene chimera. Four days later, these cultures were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1 in other neurons. Cultures were monitored daily by fluorescent microscopy. Titers of media from lytic, latent, and latent/TSA treated GGN cultures were obtained using plaque assays on Vero cells. RNA was harvested from latently infected GGN cultures and examined for the presence of viral transcripts using reverse transcription-polymerase chain reaction. RESULTS: Latently infected GGN cultures displayed latency-associated transcripts only, whereas lytically infected and reactivated latent cultures produced other viral transcripts, as well. The GGN cultures displayed a reactivation rate of 65% after treatment with TSA. Media from latently infected cultures contained no detectable infectious HSV-1, whereas infectious virus was observed in both lytically and latently infected/TSA-treated culture media. CONCLUSION: We have shown that cultured GGNs can be latently infected with HSV-1, and HSV-1 in these latently infected neurons can be reactivated using TSA, yielding infectious virus. These results have implications for the cause of both BP and DFP

Affective empathy (AE) is distinguished clinically and neurally from cognitive empathy (CE). While AE is selectively disrupted in psychopathy, autism is associated with deficits in CE. Despite such dissociations, AE and CE together contribute to normal human empathic experience. A dimensional measure of individual differences in AE 'relative to' CE captures this interaction and may reveal brain-behavior relationships beyond those detectable with AE and CE separately. Using resting-state fMRI and measures of empathy in healthy adults, we show that relative empathic ability (REA) is reflected in the brain's intrinsic functional dynamics. Dominance of AE was associated with stronger functional connectivity among social-emotional regions (ventral anterior insula, orbitofrontal cortex, amygdala, perigenual anterior cingulate). Dominance of CE was related to stronger connectivity among areas implicated in interoception, autonomic monitoring and social-cognitive processing (brainstem, superior temporal sulcus, ventral anterior insula). These patterns were distinct from those observed with AE and CE separately. Finally, REA and the strength of several functional connections were associated with symptoms of psychopathology. These findings suggest that REA provides a dimensional index of empathic function and pathological tendencies in healthy adults, which are reflected in the intrinsic functional dynamics of neural systems associated with social and emotional cognition

BACKGROUND: Emerging neuroscientific and genetic findings emphasize the dimensional rather than the categorical aspects of psychiatric disorders. However, the integration of dimensional approaches within the current categorical diagnostic framework remains unclear. Here, we used resting state functional magnetic resonance imaging to examine whether dimensional measures of psychiatric symptomatology capture brain-behavior relationships unaccounted for by categorical diagnoses. Additionally, we examined whether dimensional brain-behavior relationships are modified by the presence of a categorically defined illness, attention-deficit/hyperactivity disorder (ADHD). METHODS: Resting state functional magnetic resonance imaging scans were collected from 37 typically developing children (aged 10.2 +/- 2; 21 female subjects) and 37 children meeting DSM-IV Text Revision criteria for ADHD (9.7 +/- 2; 11 female subjects). Parent-rated Child Behavior Checklist Externalizing and Internalizing scores served as dimensional measures in our analyses of default network (DN) resting state functional connectivity (RSFC). RESULTS: Regardless of diagnosis, we observed several significant relationships between DN RSFC and both internalizing and externalizing scores. Increased internalizing scores were associated with stronger positive intra-DN RSFC, while increased externalizing scores were associated with reduced negative RSFC between DN and task-positive regions such as dorsal anterior cingulate cortex. Several of these brain-behavior relationships differed depending on the categorical presence of ADHD. CONCLUSIONS: Our findings suggest that while categorical diagnostic boundaries provide an inadequate basis for understanding the pathophysiology of psychiatric disorders, psychiatric illness cannot be viewed simply as an extreme of typical neural or behavioral function. Efforts to understand the neural underpinnings of psychiatric illness should incorporate both categorical and dimensional clinical assessments

BACKGROUND:: To define the clinical neuro-ophthalmic abnormalities of patients with familial dysautonomia (FD). METHODS:: Sixteen patients (32 eyes) with the clinical and molecular diagnoses of FD underwent thorough neuro-ophthalmic clinical evaluation. RESULTS:: Visual acuity ranged from 0.05 to 1.0 decimal units and was reduced in 15 of 16 patients. Mild to moderate corneal opacities were found in most patients but were visually significant in only 2 eyes. Red-green color vision was impaired in almost all cases. Depression of the central visual fields was present on automated visual fields in all patients, even in those with normal visual acuity. Temporal optic nerve pallor was present in all cases and was associated with retinal nerve fiber layer loss in the papillomacular region. Various ocular motility abnormalities also were observed. CONCLUSION:: Patients with FD have a specific type of optic neuropathy with predominant loss of papillomacular nerve fibers, a pattern similar to other hereditary optic neuropathies caused by mutations either in nuclear or in mitochondrial DNA, affecting mitochondrial protein function. Defects of eye movements, particularly saccades, also appear to be a feature of patients with FD

PURPOSE: To evaluate the feasibility of performing single breathhold three-dimensional (3D) thoracic noncontrast MR angiography (NC-MRA) using highly accelerated parallel imaging. MATERIALS AND METHODS: We developed a single breathhold NC MRA pulse sequence using balanced steady state free precession (SSFP) readout and highly accelerated parallel imaging. In 17 subjects, highly accelerated noncontrast MRA was compared against electrocardiogram-triggered contrast-enhanced MRA. Anonymized images were randomized for blinded review by two independent readers for image quality, artifact severity in eight defined vessel segments and aortic dimensions in six standard sites. NC-MRA and CE-MRA were compared in terms of these measures using paired sample t- and Wilcoxon tests. RESULTS: The overall image quality (3.21 +/- 0.68 for NC-MRA versus 3.12 +/- 0.71 for CE-MRA) and artifact (2.87 +/- 1.01 for NC-MRA versus 2.92 +/- 0.87 for CE-MRA) scores were not significantly different, but there were significant differences for the great vessel and coronary artery origins. NC-MRA demonstrated significantly lower aortic diameter measurements compared with CE-MRA; however, this difference was not considered clinically relevant (>3 mm difference) for less than 12% of segments, most commonly at the sinotubular junction. Mean total scan time was significantly lower for NC-MRA compared with CE-MRA (18.2 +/- 6.0 s versus 28.1 +/- 5.4 s, respectively; P < 0.05). CONCLUSION: Single breathhold NC-MRA is feasible and can be a useful alternative for evaluation and follow-up of thoracic aortic diseases. J. Magn. Reson. Imaging 2011;. (c) 2011 Wiley Periodicals, Inc

Attention-deficit/hyperactivity disorder (ADHD) has long been thought to reflect dysfunction of prefrontal-striatal circuitry, with involvement of other circuits largely ignored. Recent advances in systems neuroscience-based approaches to brain dysfunction have facilitated the development of models of ADHD pathophysiology that encompass a number of different large-scale resting-state networks. Here we review progress in delineating large-scale neural systems and illustrate their relevance to ADHD. We relate frontoparietal, dorsal attentional, motor, visual and default networks to the ADHD functional and structural literature. Insights emerging from mapping intrinsic brain connectivity networks provide a potentially mechanistic framework for an understanding of aspects of ADHD such as neuropsychological and behavioral inconsistency, and the possible role of primary visual cortex in attentional dysfunction in the disorder

Purpose: To evaluate the ability of magnetization transfer (MT) contrast-prepared magnetic resonance (MR) imaging to help distinguish healthy from cirrhotic liver by using a spectrum of MT pulse frequency offsets. Materials and Methods: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all subjects. After optimization of the MT sequence by using agar phantoms with protein concentrations ranging from 0% to 4%, 20 patients with cirrhosis and portal hypertension and 20 healthy volunteers with no known liver disease underwent liver MR imaging that included eight separate breath-hold MT contrast sequences, each performed by using a different MT pulse frequency offset (range, 200-2500 Hz). Regions of interest were then placed to calculate the MT ratio for the liver, fat, and muscle in the volunteer group and for the liver in the cirrhosis group. Results: MT ratio increased with decreasing MT pulse frequency offset for each of the four phantoms and the assessed in vivo tissues, consistent with previous reports. At all frequency offsets, MT ratio increased with increasing phantom protein concentration. In volunteers, at frequency offsets greater than 400 Hz, the MT ratio was significantly greater for muscle (range, 34.4%-54.9%) and significantly lower for subcutaneous fat (range, 10.3%-12.6%), compared with that for the liver (range, 22.8%-46.9%; P < .001 all comparisons). However, the MT ratio was nearly identical between healthy (range, 26.0%-80.0%) and cirrhotic livers (range, 26.7%-81.2%) for all frequency offsets (P = .162-.737), aside from a minimal difference in MT ratio of 1.7% at a frequency offset of 2500 Hz (22.8% in healthy liver vs 24.5% in cirrhotic liver) that was not significant when the Bonferroni correction was applied (P = .015). Conclusion: Findings of this study confirm the ability of the MT contrast-prepared sequence to help distinguish substances of varying protein concentration and suggest that MT imaging is unlikely to be of clinical utility in differentiating healthy and cirrhotic livers. (c) RSNA, 2011