Summary:Purpose: Patients with psychogenic nonepileptic seizures (PNES) and those with epileptic seizures (ES) purportedly have roughly equal neurocognitive deficits. However, recent findings suggest that patients with somatoform disorders exhibit more variable effort on neurocognitive testing than do controls. We reexamined neurocognitive function in patients with ESs and PNES by using symptom validity testing to control for variability in effort.Methods: Patients referred for video-EEG monitoring were administered the Word Memory Test (WMT), a measure of symptom validity, as part of neuropsychological evaluation. Patients classified with ictal video-EEG recordings as having ES (n = 41) or PNES (n = 43) were compared on neurocognitive and WMT performance and demographic, psychiatric, and medical variables.Results: Striking rates of WMT failure were observed in the PNES (51.2%) group, but not in the ES (8.1%) group (p = <0.001) after controlling for false-positive errors. Although the PNES and ES groups reported equivalent neurologic histories, the PNES group exhibited less objective evidence of impairment as measured by valid neuropsychological testing, MRI of the brain, and video-EEG monitoring.Conclusions: Many patients with PNES do not put forth maximal effort during neuropsychological assessment. When patients with PNES put forth valid effort, they demonstrate less objective evidence of neuropathologic injury or disease than do patients with ES. The cognitive impairment reported by this group appears to be more a function of motivational (although not necessarily intentional) factors than of verifiable neuropathology.

Objectives/Hypothesis To identify functional network architecture differences in the brains of children with unilateral hearing loss (UHL) using resting state functional connectivity MRI (rs-fcMRI). Study Design Prospective observational study Methods Children (7 to 17 years) with severe to profound hearing loss in one ear, along with their normal hearing (NH) siblings, were recruited and imaged using rs-fcMRI. Eleven children had right UHL, 9 had left UHL, and 13 had normal hearing. Forty-one brain regions of interest culled from established brain networks such as the default mode (DMN), cingulo-opercular (CON), and frontoparietal networks (FPN), as well as regions for language, phonological and visual processing were analyzed using regionwise correlations and conjunction analysis to determine differences in functional connectivity between the UHL and normal hearing children. Results When compared to the NH group, children with UHL showed increased connectivity patterns between multiple networks, such as between the CON and visual processing centers. However, there were decreased, as well as aberrant connectivity patterns with the co-activation of the DMN and FPN, a relationship that is usually negatively correlated. Conclusion Children with UHL demonstrate multiple functional connectivity differences between brain networks involved with executive function, cognition, and language comprehension that may represent adaptive as well as maladaptive changes. These findings suggest possible interventions or habilitation, beyond amplification, might be able to affect some children's requirement for additional help at school.

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Summary Peripheral T cell tolerance is challenging to induce in partially lymphopenic hosts and this is relevant for clinical situations involving transplant tolerance. While the shortage of regulatory cells is thought to be one reason for this, T cell-intrinsic tolerance processes such as anergy are also poorly triggered in such hosts. In order to understand the latter, we used a T cell deficient mouse model system where adoptively transferred autoreactive T cells are significantly tolerized in a cell intrinsic fashion, without differentiation to regulatory T cells. Intriguingly these T cells often retain sufficient effector functions to trigger autoimmune pathology. Here we find that the high population density of the autoreactive T cells that accumulated in such a host limits the progression of the cell-intrinsic tolerance process in T cells. Accordingly, reducing the cell density during a second transfer allowed T cells to further tune down their responsiveness to antigenic stimulation. The retuning of T cells was reflected by a loss of the T cell’s abilities to proliferate, produces cytokines or help B cells. We further suggest, based on altering the levels of chronic antigen using miniosmotic pumps, that the effects of cell-density on T cell re-tuning may reflect the effective changes in the antigen dose perceived by individual T cells. This could proportionally elicit more negative feedback downstream of the TCR. Consistent with this, the retuned T cells showed signaling defects both proximal and distal to the TCR. Therefore, similar to the immunogenic activation of T cells, cell-intrinsic T cell tolerance may also involve a quantitative and progressive process of tuning down its antigen-responsiveness. The progress of such tuning seems to be stabilized at multiple intermediate stages by factors such as cell density, rather than just absolute antigen levels.