Time-dependent post-imperative negative variation indicates adaptation and problem solving in migraine patients.

According to the Seligman theory of learned helplessness, depression is caused by a repetitive experience of loss of control resulting in internal, stable and global attributional styles for negative events. In depressed patients and healthy controls experiencing such events, an increased amplitude of the post-imperative negative variation (PINV) has been described. The aim of the study was to investigate a possible correlation between migraine, depression, learned helplessness and PINV. 24 patients suffering from migraine without aura and 24 healthy controls were exposed to a situation of loss of control whilst the contingent negative variation (CNV) from C3, C4 and Cz were recorded. Before conducting the experiment, the subjects were asked to answer the Beck Depression Inventory (BDI) and the German attributional style questionnaire (GASQ). Amplitudes of total CNV, early and late component and PINV were calculated in eight blocks of four recordings each. The results confirm findings of a pronounced PINV in situations of loss of control, though high amplitudes were not correlated with low values in the GASQ and therefore with learned helplessness. High PINV in migraine patients correlated with high scores in the BDI and the list of the complaints questionnaire. However, this was not the case in healthy controls. In this experimental situation, PINV in migraine patients can be interpreted as an expectancy potential in order to avoid failure and helplessness.

Cortical habituation deficit in tinnitus sufferers: contingent negative variation as an indicator of duration of the disease.

Cortical attention and habituation parameters are altered in patients suffering from tinnitus. The aim of the study was to quantify cortical attention and habituation parameters in tinnitus patients by recording the contingent negative variation (CNV) response and to correlate amplitudes of different CNV parameters with duration of disease. Twenty patients suffering from tinnitus (median: 44 years) and twenty age- and sex-matched healthy controls (median: 41 years) were tested by a CNV paradigm. We recorded overall CNV, initial CNV, and terminal CNV and calculated habituation slopes. All CNV parameters were Spearman-correlated with individual duration of disease. Highly significant between groups differences emerged in total (tinnitus: -8.4 uV vs. controls: -3.8 uV), initial (-11.2 vs. -6.0 uV), and terminal CNV (-11.9 vs. -6.5 uV) demonstrating higher negative amplitudes in tinnitus patients. Habituation differed in total and terminal CNV, indicating missing habituation in tinnitus patients. Overall CNV (ϱ = -.365) and initial CNV (ϱ = -.529) showed a medium Spearman correlation with duration of disease. We conclude that the correlation between duration of tinnitus and the initial CNV amplitudes indicates an altered state of cortical excitability that can also be observed in more negative CNV-amplitudes in tinnitus patients. We assume that this state indicates a chronicity process in tinnitus disease.

mRNA expression of the murine glycoprotein (transmembrane) nmb (Gpnmb) gene is linked to the developing retinal pigment epithelium and iris.

The murine homologue of the human glycoprotein (transmembrane) NMB (GPNMB) gene was identified by subtractive cloning from in vitro cultured murine primary osteoblast cells and subsequent RACE-PCR. GPNMB is a highly glycosylated type I transmembrane protein that shares significant sequence homology to several melanosomal proteins. Increasing expression of Gpnmb mRNA was observed during differentiation of murine primary osteoblast cell cultures. To address the potential functions of GPNMB we analysed its mRNA-expression during murine embryonic development. In early development Gpnmb mRNA is detected at high levels in the outer layer of the retina. Later in development expression gets restricted to the retinal pigment epithelium and iris. At the cytoplasmic domain of GPNMB, a conserved di-leucin-based endosomal/melanosomal-sorting signal (ExxPLL) was located, present as well in several known melanosomal proteins. To analyse the subcellular localization we used EGFP-tagged GPNMB transfected in COS7 and HEK293 cells. In both non-pigmented cell lines, the EGFP-GPNMB fusion protein was localized to vesicular, endosomal like structures. Sequence homology to known melanosomal proteins, mRNA expression and subcellular localization are suggestive for GPNMB as an intracellular, endosomal/melanosomal compartment specific protein important for melanin biosynthesis and the development of the retinal pigment epithelium and iris. As the gene coding for human GPNMB was localized to chromosome 7p15, a locus involved in the human inherited disease cystoid macular edema, also known as dominant cystoid macular dystrophy (OMIM 153880) we highly suggest that GPNMB is a candidate gene for this human inherited disease.