Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). RESULTS: We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). CONCLUSIONS: While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies.

Optogenetic drive of neocortical pyramidal neurons generates fMRI signals that are correlated with spiking activity.

Local fluctuations in the blood oxygenation level-dependent (BOLD) signal serve as the basis of functional magnetic resonance imaging (fMRI). Understanding the correlation between distinct aspects of neural activity and the BOLD response is fundamental to the interpretation of this widely used mapping signal. Analysis of this question requires the ability to precisely manipulate the activity of defined neurons. To achieve such control, we combined optogenetic drive of neocortical neurons with high-resolution (9.4 T) rodent fMRI and detailed analysis of neurophysiological data. Light-driven activation of pyramidal neurons resulted in a positive BOLD response at the stimulated site. To help differentiate the neurophysiological correlate(s) of the BOLD response, we employed light trains of the same average frequency, but with periodic and Poisson distributed pulse times. These different types of pulse trains generated dissociable patterns of single-unit, multi-unit and local field potential (LFP) activity, and of BOLD signals. The BOLD activity exhibited the strongest correlation to spiking activity with increasing rates of stimulation, and, to a first approximation, was linear with pulse delivery rate, while LFP activity showed a weaker correlation. These data provide an example of a strong correlation between spike rate and the BOLD response. This article is part of a Special Issue entitled Optogenetics (7th BRES).

Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral tegmental area in humans.

Recent studies suggest that memory formation in the hippocampus is modulated by the motivational significance of events, allowing past experience to adaptively guide behavior. The effects of motivation on memory are thought to depend on interactions between the hippocampus, the ventral tegmental area (VTA), and the nucleus accumbens (NAcc). Indeed, animal studies reveal anatomical pathways for circuit-level interaction between these regions. However, a homologue circuit connectivity in humans remains to be shown. We characterized this circuitry in humans by exploiting spontaneous low-frequency modulations in the fMRI signal (termed resting-state functional connectivity), which are thought to reflect functionally related regions and their organization into functional networks in the brain. We examined connectivity in this network across two datasets (hi-resolution, n = 100; standard resolution, n = 894). Results reveal convergent connectivity between the hippocampus, and both the NAcc and the VTA centered on ventral regions in the body of the hippocampus. Additionally, we found individual differences in the strength of connectivity within this network. Together, these results provide a novel task-independent characterization of circuitry underlying interactions between the hippocampus, NAcc, and VTA and provide a framework with which to understand how connectivity might reflect and constrain the effects of motivation on memory.

Mapping brain networks in awake mice using combined optical neural control and fMRI.

Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.

Diffusion tensor imaging detects areas of abnormal white matter microstructure in patients with partial ornithine transcarbamylase deficiency.

BACKGROUND AND PURPOSE: OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive deficits. MATERIALS AND METHODS: Nineteen adults with partial OTCD and 18 adult control subjects ages 19-59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control groups. RESULTS: FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with age. CONCLUSIONS: Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working memory.

Students' performance on makeup examinations and other evaluations.

In two studies, one involving a lower-division psychology course and the other involving an upper-division psychology course, students who missed required examinations had lower test scores, quiz scores, comprehensive final test scores, and attendance than students who did not miss required examinations. In addition, students in the upper-division psychology course who missed required examinations had a lower mean makeup examination test score than on their required examination.

TRH test abnormalities in psychiatric disorders.

Blunted responses to thyrotropin-releasing hormone (TRH) stimulation have been found consistently in depressed patients, and have been reported in other affective disorders as well. In a smaller number of schizophrenic subjects, TRH tests have generally been normal. Thus, it has been suggested that this test may have diagnostic utility in distinguishing schizophrenia from affective disorders. In the present study the TRH test was performed upon a sample of 51 subjects that included 17 schizophrenics in order to further study the diagnostic or symptom specificity of this endocrine test. Abnormal TRH tests were present in both schizophrenic and affectively disturbed patients. There were no correlations with ratings of depression or other aspects of psychopathology. Factors which may have previously obscured abnormal TRH tests in schizophrenia are discussed.

Parkinsonism due to subdural hematoma. Case report.

The authors describe the case of a 38-year-old woman who presented with parkinsonian syndrome associated with chronic subdural hematoma. Gradual disappearance of the symptomatology followed removal of the hematoma. Chronic subdural hematoma may in rare instances cause a parkinsonian syndrome, probably by a pressure effect on basal ganglia structures or by altering the function of neurotransmitters.

Gallstones in a retroperitoneal abscess: a late complication of perforation of the gallbladder.

The case of a 72-year-old female with a retroperitoneal abscess which contained cholesterol gallstones is presented. The pathogenesis of this unusual complication of gallbladder disease is discussed.

Paranoid delusions and auditory hallucinations associated with digoxin intoxication.

The 83-year-old woman in this case report developed paranoid delusions and auditory hallucinations in association with toxic serum levels of digoxin, while remaining alert, unagitated, and coherent in thinking. No cardiovascular or metabolic abnormalities were discovered to account for her psychiatric symptoms. Her mental status rapidly returned to normal as serum digoxin declined to therapeutic levels.