Susac syndrome and pregnancy: disease management.

Susac syndrome (SS) consists of a triad of vision loss, hearing loss, and encephalopathy due to autoimmune-mediated vascular endothelial injury. Herein we describe a 25-year-old previously healthy woman who presented at 20 weeks' gestation with symptoms of confusion, difficulty walking, and vision and hearing loss. She had branch-retinal artery occlusions on funduscopic examination, and sensorineural hearing loss. Additionally, non-contrast enhanced brain magnetic resonance imaging showed multiple white matter and callosal lesions consistent with ischemia. She was treated initially with aspirin, corticosteroids, and intravenous immunoglobulin with early improvement, although recurrent disease was treated with cyclophosphamide and rituximab after induction of premature delivery (at 35 weeks' gestation) to spare the fetus possible toxicity. We additionally discuss a general overview of SS, what is known about pregnancy and this disease, and issues regarding diagnostic and treatment approaches for SS during pregnancy.

Recurrent varicella zoster virus myelopathy.

Myelopathy is an uncommon complication of VZV infection and may develop in the absence of rash. We report the rare recurrence of myelopathy in an immunocompetent adult who initially developed myelopathy after ophthalmic-distribution zoster. Recurrent myelopathy two years later caused by VZV was verified by the presence of new-onset clinical symptoms and signs consistent with myelopathy, new lesions in the spinal cord detected by MRI, and evidence of intrathecal synthesis of anti-VZV IgG antibody in CSF. After virological verification and antiviral therapy, myelopathy did not recur and anti-VZV IgG antibody could not be detected in CSF. In contrast to earlier cases of recurrent VZV myelopathy in immunocompetent adults that developed weeks to months after the first episode of myelopathy, this is the first instance of recurrence years later.

Gray matter volume differences and the effects of smoking on gray matter in schizophrenia.

OBJECTIVE: Many studies have evaluated differences in gray matter volume in schizophrenia, but have not considered the possible effects of smoking, which is extraordinarily common in people with the illness. The present study used voxel-based morphometry (VBM) to examine differences in gray matter in subjects with schizophrenia and evaluate the effects of smoking on this measure. METHODS: Thirty-two subjects with schizophrenia (14 smokers, 18 non-smokers) and 32 healthy comparison subjects participated in the study. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS: Reduced gray matter was observed in the schizophrenia group in the orbitofrontal cortex, bilateral insula and superior temporal gyri (STG), bilateral dorsolateral prefrontal cortices (DLPFC), medial frontal gyrus, and cingulate gyrus. Within this group, smoking subjects had greater lateral prefrontal and STG gray matter volumes relative to non-smoking subjects. CONCLUSIONS: The finding of reduced gray matter volume in prefrontal and temporal regions in schizophrenia is consistent with prior anatomical tracing and whole-brain voxel-based studies. Greater gray matter volumes in smoking relative to non-smoking subjects with schizophrenia highlight a potential experimental confound in volumetric studies and suggests that smoking may be associated with a relative preservation of lateral prefrontal and temporal gray matter in schizophrenia.

FMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia.

OBJECTIVE: Nicotine temporarily normalizes smooth pursuit eye movement deficits in schizophrenia. This study used functional magnetic resonance imaging (fMRI) to examine changes in brain hemodynamic response associated with nicotine administration during a smooth pursuit eye movement task in subjects with schizophrenia. METHOD: Nine subjects with schizophrenia performed the eye movement task while undergoing fMRI. Subjects then were given nicotine or placebo and repeated the task while being scanned. Subjects repeated the procedure the following week, receiving the counterbalanced condition. RESULTS: Compared with placebo, nicotine was associated with greater activity in the anterior and posterior cingulate gyri, precuneus, and area MT/MST and less activity in the hippocampus and parietal eye fields. CONCLUSIONS: Changes in area MT/MST and the cingulate gyrus are consistent with an improvement in perception and attention to moving stimuli. The most important observed difference between nicotine and placebo--less activation of the hippocampus after nicotine than after placebo administration--is consistent with nicotinic receptor mediation of inhibitory neuronal dysfunction in schizophrenia.

Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume.

OBJECTIVE: Structural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. HYPOTHESES: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum). METHODS: We conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold. RESULTS: Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls. CONCLUSIONS: Female adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.

Neurobiology of smooth pursuit eye movement deficits in schizophrenia: an fMRI study.

OBJECTIVE: Smooth pursuit eye movements are abnormal in patients with schizophrenia. The investigators used functional magnetic resonance imaging (fMRI) to compare brain hemodynamic response during a smooth pursuit eye movement task in patients with schizophrenia and healthy comparison subjects. METHOD: Fourteen patients with schizophrenia and 14 healthy comparison subjects performed a smooth pursuit eye movement task while undergoing 1.5-T fMRI. Echo-planar images from the blocked design were evaluated with both a whole-brain random-effects analysis and a region-of-interest analysis. Smooth pursuit deficits were assessed outside the fMRI apparatus by using infrared oculography and were assessed during scanning by evaluating echo-planar time-series data from the eyes. RESULTS: Compared to the healthy subjects, the patients with schizophrenia exhibited greater activity in both posterior hippocampi and the right fusiform gyrus during smooth pursuit eye movements. The region-of-interest analysis revealed subtle activity deficits in frontal and occipital regions in the patients with schizophrenia. Smooth pursuit deficits in the subjects with schizophrenia included lower gain (eye velocity relative to target velocity) and a higher percentage of total eye movements due to anticipatory saccades, compared with the healthy subjects. CONCLUSIONS: The observed group differences are consistent with evidence for diminished inhibitory function in the hippocampus as well as for a disturbance in a frontotemporal network subserving smooth pursuit eye movements in schizophrenia.

Functional magnetic resonance imaging of brain activity in the visual oddball task.

Abnormalities in the P300 ERP, elicited by the oddball task and measured using EEG, have been found in a number of central nervous system disorders including schizophrenia, Alzheimer's disease, and alcohol dependence. While electrophysiological studies provide high temporal resolution, localizing the P300 deficit has been particularly difficult because the measurements are collected from the scalp. Knowing which brain regions are involved in this process would elucidate the behavioral correlates of P300. The aim of this study was to determine the brain regions involved in a visual oddball task using fMRI. In this study, functional and high-resolution anatomical MR images were collected from seven normal volunteers. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Activations were detected (P<0.01) bilaterally in the supramarginal gyrus (SMG; BA 40), superior parietal lobule (BA 7), the posterior cingulate gyrus, thalamus, inferior occipitotemporal cortex (BA 19/37), insula, dorsolateral prefrontal cortex (BA 9), anterior cingulate cortex (ACC), medial frontal gyrus (BA 6), premotor area, and cuneus (BA 17). Our results are consistent with previous studies that have observed activation in ACC and SMG. Activation of thalamus, insula, and the occipitotemporal cortex has been reported less consistently. The present study lends further support to the involvement of these structures in visual target detection.

Resting-state activity in the left executive control network is associated with behavioral approach and is increased in substance dependence.

BACKGROUND: Individuals with drug addictions report increased willingness to approach rewards. Approach behaviors are thought to involve executive control processes and are more strongly represented in the left compared to right prefrontal cortex. A direct link between approach tendencies and left hemisphere activity has not been shown in the resting brain. We hypothesized that compared to controls, substance dependent individuals (SDI) would have greater left hemisphere activity in the left executive control network (ECN) at rest. METHODS: Twenty-five SDI and 25 controls completed a Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) questionnaire and underwent a resting-state fMRI scan. Group independent component analysis was performed. We used template matching to identify the left and right ECN separately and compared the corresponding components across groups. Across group, BAS scores were correlated with signal fluctuations in the left ECN and BIS scores with right ECN. RESULTS: BAS scores were higher in SDI compared to controls (p<.003) and correlated with signal fluctuation in the left ECN. SDI showed significantly more activity than controls in the left prefrontal cortex of the left ECN. Conversely, SDI showed less activity than controls in the right prefrontal cortex of the right ECN. CONCLUSIONS: Results from this study suggest that approach tendencies are related to the left ECN, even during rest. Higher resting-state signal in the left ECN may play a role in heightened approach tendencies that contribute to drug-seeking behavior.

Functional dissociation of attentional selection within PFC: response and non-response related aspects of attentional selection as ascertained by fMRI.

In this experiment using a color-word Stroop task, we explored whether different regions of prefrontal cortex bias selection of response-related processes as compared with non-response-related processes. To manipulate demands at the level of response selection, we varied the degree of overlap between stimulus-response mappings in a manual Stroop task. To vary demands at a non-response level, we compared activation for incongruent trials (e.g. the word 'purple' in blue ink) that contain two color representations, one in the word and one in the ink color, to neutral trials (e.g. the word 'drawer' in blue ink), which contain only one color representation, that in the ink color. These manipulations had differential effects within prefrontal cortex. Both a region of right inferior frontal cortex and caudal regions of the cingulate were sensitive to the selection demands at the response-level and insensitive to demands at the non-response level. In contrast, a more anterior region of left dorsolateral prefrontal cortex was sensitive to the number of color representations (i.e. incongruent versus neutral trials), but not to the overlap in stimulus-response mappings. Therefore, this study indicates a functional differentiation for implementing attentional control within prefrontal cortex.

Common and distinct neural substrates of attentional control in an integrated Simon and spatial Stroop task as assessed by event-related fMRI.

The purpose of this experiment was to directly examine the neural mechanisms of attentional control involved in the Simon task as compared to a spatial Stroop task using event-related fMRI. The Simon effect typically refers to the interference people experience when there is a stimulus-response conflict. The Stroop effect refers to the interference people experience when two attributes of the same stimulus conflict with each other. Although previous imaging studies have compared the brain activation for each of these tasks performed separately, none had done so in an integrated task that incorporates both types of interference, as was done in the current experiment. Both tasks activated brain regions that serve as a source of attentional control (dorsolateral prefrontal cortex) and posterior regions that are sites of attentional control (the visual processing stream-middle occipital and inferior temporal cortices). In addition, there were also specific brain regions activated to a significantly greater degree by one task and/or only by a single task. The brain regions significantly more activated by the Simon task were those sensitive to detection of response conflict, response selection, and planning (anterior cingulate cortex, supplementary motor areas, and precuneus), and visuospatial-motor association areas. In contrast, the regions significantly more activated by the Stroop task were those involved in biasing the processing toward the task-relevant attribute (inferior parietal cortex). These findings suggest that the interference effects of these two tasks are caused by different types of conflict (stimulus-response conflict for the Simon effect and stimulus-stimulus conflict for the Stroop effect) but both invoke similar sources of top-down modulation.

Monitoring eye movements during fMRI tasks with echo planar images.

Verifying task compliance during functional magnetic resonance imaging (fMRI) experiments is an essential component of experimental design. To date, studies of oculomotor tasks such as smooth pursuit eye movements have either measured task performance outside the magnet and assumed similar performance during functional neuroimaging, or have used MR-compatible eye movement recording devices, which can be costly and technically difficult to use. We describe a simple method to visualize and quantify eye movements during an imaging experiment using the gradient echo images. We demonstrate that local eye movements will influence whole-head motion correction procedures, resulting in inaccurate movement parameters and potentially lowering the sensitivity to detect activations.

A functional MRI study of visual oddball: evidence for frontoparietal dysfunction in subjects at risk for alcoholism.

Attending to rare stimuli interspersed among repetitive frequent stimuli produces a positive scalp potential at 300 to 600 ms after the target stimulus onset; this potential is known as the P300 wave. Although there is clear evidence of low visual P300 in subjects at high risk (HR) for developing alcoholism, the functional neuroanatomical correlates have not been studied. Functional and high-resolution anatomical magnetic resonance images were collected during the performance of a visual oddball task, from six control (low risk-LR) subjects with high P300s and eight HR subjects with low P300s. All the HR subjects were offspring of male alcoholics. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Target counts showed that all subjects performed the task comparably. Analysis of the functional magnetic resonance imaging (fMRI) data revealed two areas with significantly lower activation in the HR group when compared to the LR group: the bilateral inferior parietal lobule (BA 40), and the bilateral inferior frontal gyrus (BA 44). Inferior parietal lobule showed significantly lower activation in the HR group in contrast to the LR group, and inferior frontal gyrus was not activated in the HR group but was only activated in the LR group. This finding indicates that a dysfunctional frontoparietal circuit may underlie the low P300 responses seen in HR subjects. This perhaps implies a deficiency in the rehearsal component of the working memory system.