Differential relationships between thought dimensions and momentary affect in daily life.

Commonly used to characterize mind wandering, task-unrelated thought has long been associated with negative affective outcomes. However, less is known about how other thought dimensions including intentionality and freedom of movement interact with task-unrelated thought to modulate momentary affect in everyday life. To address this, we used ecological momentary assessments to prompt participants to report their thought patterns and affective valence five times a day for seven consecutive days. Each assessment asked participants to report on their affective valence as well as several thought dimensions including their task-relatedness, intentionality and freedom of movement. We examined the latter two thought dimensions alone as well as how they interacted with the commonly examined dimension of task-relatedness with respect to their relationship to momentary affect. We replicated the well-established negative relationship between task-unrelated thought and momentary affect. Furthermore, unintentional task-unrelated thought was associated with more negative affect than intentional thought. This pattern was also observed more broadly in thoughts regardless of their task relevance. In contrast, freely moving thought was positively related to momentary affect in general. A significant interaction between task-relatedness and freedom of movement of thought revealed that the commonly reported negative relationship between task-unrelated thought and more negative affect is mitigated by freely moving thought. In summary, our findings indicate that these various thought dimensions have unique relationships with momentary affect, highlighting the importance of accounting for thought dimensions in establishing its affective and possibly other functional consequences.

Is our self based on reward? Self-relatedness recruits neural activity in the reward system.

Every organism has to evaluate incoming stimuli according to their current and future significance. The immediate value of stimuli is coded by the reward system, but the processing of their long-term relevance implements a valuation system that implicates self-relatedness. The neuronal relationship between reward and self-relatedness remains unclear though. Using event-related functional MRI, we investigated whether self-relatedness induces neural activity in the reward system. Self-relatedness induced signal changes in the same regions that were recruited during reward including the bilateral nucleus accumbens (NACC), ventral tegmental area (VTA) and ventromedial prefrontal cortex (VMPFC). The fMRI signal time courses revealed no differences in early BOLD signals between reward and self-relatedness. In contrast, both conditions differed in late BOLD signals with self-relatedness showing higher signal intensity. In sum, our findings indicate sustained recruitment of the reward system during self-relatedness. These findings may contribute to a better understanding of the reward-based nature of our self.

Motor and somatosensory evoked potentials in mice infected with Theiler's murine encephalomyelitis virus.

We used an in vivo technique to record spinal motor and somatosensory evoked potentials in SJL/J and B10 mice chronically (4-10 months) infected with Daniel's strain of Theiler's murine encephalomyelitis virus (TMEV). SJL/J mice demonstrated primary spinal cord demyelination with chronic TMEV infection, whereas B10 mice were resistant to TMEV induced demyelination. Analysis based on the velocity of the initial peak of evoked responses demonstrated significantly slower conduction velocities in infected SJL/J mice as compared to age-matched uninfected SJL/J controls (p < 0.01) and infected B10 mice (p < 0.01). We noted no significant differences in conduction velocities of spinal evoked potentials recorded between uninfected SJL/J mice, uninfected B10 mice and infected B10 mice. Chronic infection with TMEV in susceptible SJL/J mice is associated with slowed conduction of spinal motor and somatosensory evoked potentials. This sensitive electrophysiologic assay will provide an in vivo method to test therapeutic regimens to inhibit demyelination or promote remyelination.

Influence of deletion of T cell receptor V beta genes on the Theiler's virus model of multiple sclerosis.

To determine the role of TCR V beta genes in a model of multiple sclerosis (MS), we studied Theiler's virus infection in congenic mice with deletion of TCR V beta chromosome. Congenic mice expressing the V beta a [50% deletion of TCR V beta] or V beta c 70% deletion of TCR V beta] haplotype were generated in mice resistant [B10 (H-2b)], intermediate [B10.K (H-2k), B10.RIII (H-2r)] or susceptible [B10.S (H-2s), and B10.Q (H-2q)] to Theiler's virus induced demyelination. Deletion of TCR V beta genes (V beta a or V beta c) did not convert B10 or B10.K congenic mice to susceptibility. In contrast, congenic B10.RIII-V beta c developed prominent demyelination and 10- to 100-fold increase in virus-antigen expression in spinal cord compared to B10.RIII mice. No effect on the extent of demyelination was observed in B10.S-V beta a, B10.S-V beta c or B10.Q-V beta c mice. These experiments illustrate the critical interactions between MHC, TCR, and background genes in susceptibility to immune-mediated disease.

Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin.

Intracerebral infection of susceptible strains of mice with Theiler's virus, a picornavirus, results in central nervous system demyelination, which is similar to multiple sclerosis. Immunogenetic experiments indicate that the MHC (H-2) and, in particular, the D region that controls class I-restricted immune responses, is an important determinant to development of demyelination. We tested whether disruption of beta 2-microglobulin (beta 2-m) would abrogate resistance to demyelinating disease normally observed in H-2b mice. All (C57BI/6 x 129)F3 mice transgenic for homozygous beta 2-m gene disruption (-/-) developed chronic demyelination after Theiler's murine encephalomyelitis virus infection, whereas none of the infected littermates with normal expression of class I MHC (beta 2-m, +/+) developed demyelination. Demyelinated lesions showed class II MHC expression, macrophages, and TNF but no class I MHC expression or CD8+ T cells. No correlation was observed between development of demyelination and delayed-type hypersensitivity responses to virus Ag. Despite the presence of demyelinating lesions, none of the infected beta 2-m (-/-) mice developed neurologic deficits. Infectious virus and virus Ag persisted in the central nervous systems of infected beta 2-m (-/-) mice but not in beta 2-m (+/+) mice. These experiments support the hypothesis that a class I immune response mediated by CD8+ T cells is important in resistance to Theiler's murine encephalomyelitis virus-induced demyelination. Development of chronic neurologic deficits as observed in immunocompetent susceptible strains of mice may be dependent on the presence of class I MHC and CD8+ T cells.

Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler's virus.

Intracerebral inoculation of resistant mice (C57BL/10SNJ) with Theiler's murine encephalomyelitis virus (TMEV) results in acute encephalitis followed by subsequent clearance of virus from the central nervous system (CNS). In contrast, infection of susceptible mice (SJL/J) results in virus persistence and chronic immune-mediated demyelination. Both resistance and susceptibility to TMEV-induced disease appear to be immune mediated, since immunosuppression results in enhanced encephalitis in resistant mice but diminished demyelination in susceptible mice. The purpose of these experiments was to determine whether anti-TMEV cytotoxic T lymphocytes (CTLs) are generated during acute and chronic TMEV infection. Nonspecific lectin-dependent cellular cytotoxicity was used initially to detect the cytolytic potential of lymphocytes infiltrating the CNS irrespective of antigen specificity. Using TMEV-infected targets, H-2-restricted TMEV-specific CTLs of the CD8+ phenotype were demonstrated in lymphocytes from the CNS of susceptible and resistant mice, arguing against the hypothesis that the ability to generate CD8+ CTLs mediates resistance. In chronically infected SJL/J mice, TMEV-specific CTL activity was detected in the CNS as late as 226 days postinfection. These experiments demonstrate that virus-specific CTLs are present in the CNS during both acute and chronic TMEV infection. Anti-TMEV CTLs in the CNS of chronically infected SJL/J mice may play a role in demyelination through their ability to lyse TMEV-infected glial cells.

Persistence of Theiler's virus infection following promotion of central nervous system remyelination.

Chronic infection of SJL/J mice with the Daniel's strain of Theiler's virus develop primary demyelination, viral persistence but minimal central nervous system (CNS)-type remyelination. In contrast, treatment of virus-infected mice with sera or immunoglobulin G (IgG) from mice immunized with homogenized spinal cord (SCH) emulsified in incomplete Freund's adjuvant promotes CNS remyelination. We measured levels of infectious virus, virus antigen and virus-specific antibody to determine if treatments which promote CNS remyelination are able to modulate infection. Levels of virus-specific antibody were higher in mice treated with SCH/IgG than control treatment groups and correlated positively with extent of remyelination. Although number of virus antigen-positive cells in spinal cord was less in mice treated with SCH/IgG than mice treated with phosphate buffered saline (PBS)/IgG, there was only a slight negative correlation with extent of remyelination by regression analysis. Titers of infectious virus isolated three to six months following infection were not different among treatment groups. Even though treatment of mice with SCH/IgG reduced number of virus antigen-positive cells and enhanced levels of virus-specific antibody, CNS remyelination can occur despite presence of infectious virus.

Theiler's virus-induced demyelination in mice immunosuppressed with anti-IgM and in mice expressing the xid gene.

Intracerebral infection with Theiler's murine encephalomyelitis virus produces chronic immune-mediated demyelination in susceptible strains of mice. We examined the role of Ig in the pathogenesis of demyelination. In susceptible SJL/J mice (H-2s), suppression of B cell responses with IgG fraction of goat anti-mu (anti-mu IgG) from birth resulted in increased numbers and severity of demyelinating lesions in the spinal cord 35 days after infection. In contrast, treatment of resistant C57BL/10 (H-2b), C57BL/6 (H-2b), or B10.D2 (H-2d) mice with anti-mu IgG had no apparent effect since these mice did not develop demyelination or inflammation in the spinal cord following infection. Similar results were obtained with certain strains of B-cell deficient mice that exhibit the xid gene mutation. Male CBA/NJ (xid) showed increased meningeal inflammation and demyelination compared to male CBA/J mice. However, B6.CBAN, C3.CBAN, or C.CBAn mice showed no or minimal evidence of demyelination despite the presence of the xid mutation. In the SJL/J mouse, the majority of the humoral immune response to virus antigen was restricted to the IgG2b and IgM isotypes. These data indirectly support the hypothesis that immunoglobulins protect partially against development of virus-induced demyelination in susceptible but not resistant animals. In addition, the data argue strongly against the hypothesis that TMEV-induced demyelination is mediated predominantly by humoral autoimmune or humoral viral immune mechanisms.

Biochemical and neurophysiological parameters in hemodialyzed patients with chronic renal failure.

Serum concentrations of accumulated solutes, standard clinical biochemistry, and parameters of clinical neuropathy, were determined in hemodialyzed patients with chronic renal failure. Analyses by high-performance liquid chromatography included creatinine, pseudouridine, urate, p-hydroxyhippuric acid, hippuric acid, indoxylsulfate, tryptophan, tyrosine, 3-indoleacetic acid, and a number of as-yet unidentified solutes. Standard biochemical parameters were measured; aluminium, parathyroid hormone, serum electrolytes and enzymes, hemoglobin, bilirubin, phosphate and urea. Measures of clinical neuropathy were: maximal motor nerve conduction velocities, and Hoffmann reflex latency. Several solutes had higher concentrations when nerve function was impaired. Serum total LDH, and total calcium levels correlated positively with values of the Hoffmann reflex, as did serum hippuric acid concentrations. Concentrations of p-hydroxyhippuric acid and two fluorescent compounds correlated negatively with motor nerve conduction velocities. In principal component analysis a number of 'organic acid-like' substances, like hippuric acid and p-hydroxyhippuric acid, were shown to associate multivariately with the neurophysiological variables while urea, creatinine, urate and phosphate were not.

Influence of atropine, pirenzepine and cimetidine on nocturnal gastro-intestinal motility and gastric acid secretion.

The present study was performed to investigate the correlation between gastric H-ion-concentration and interdigestive motility (1) under basal conditions and (2) under the influence of pirenzepine, atropine and cimetidine. During the control period 6.5 (DZ1 5, DZ9 12) MMC's per 12-hour periods (69 +/- 7% gastrointestinal MMC's) were recorded. After administration of pirenzepine and the combination of pirenzepine and cimetidine almost exclusively gastrointestinal MMC's could be identified. On the other hand, atropine did not change the gastrointestinal/intestinal MMC ratio, but reduced total number of MMC's significancy (p less than 0.05). Percentage of observation time with antral pH greater than 4 was significantly increased by the combination of pirenzepine and cimetidine, but not by pirenzepine or cimetidine alone nor by atropine. There was a positive correlation between interdigestive cycle-length and percentage of time with antral pH greater than 4. The effect of pirenzepine on interdigestive motility (1) seems not to be mediated by the inhibition of gastric acid and (2) is different from the effect of atropine.