Top-down and bottom-up neurodynamic evidence in patients with tinnitus

AbstractAlthough a peripheral auditory (bottom-up) deficit is an essential prerequisite for the generation of tinnitus, central cognitive (top-down) impairment has also been shown to be an inherent neuropathological mechanism. Using an auditory oddball paradigm (for top-down analyses) and a passive listening paradigm (for bottom-up analyses) while recording electroencephalograms (EEGs), we investigated whether top-down or bottom-up components were more critical in the neuropathology of tinnitus, independent of peripheral hearing loss. We observed significantly reduced P300 amplitudes (reflecting fundamental cognitive processes such as attention) and evoked theta power (reflecting top-down regulation in memory systems) for target stimuli at the tinnitus frequency of patients with tinnitus but without hearing loss. The contingent negative variation (reflecting top-down expectation of a subsequent event prior to stimulation) and N100 (reflecting auditory bottom-up selective attention) were different between the healthy and patient groups. Interestingly, when tinnitus patients were divided into two subgroups based on their P300 amplitudes, their P170 and N200 components, and annoyance and distress indices to their tinnitus sound were different. EEG theta-band power and its Granger causal neurodynamic results consistently support a double dissociation of these two groups in both top-down and bottom-up tasks. Directed cortical connectivity corroborates that the tinnitus network involves the anterior cingulate and the parahippocampal areas, where higher-order top-down control is generated. Together, our observations provide neurophysiological and neurodynamic evidence revealing a differential engagement of top-down impairment along with deficits in bottom-up processing in patients with tinnitus but without hearing loss

Functional modulation of AMP-activated protein kinase by cereblon

AbstractMutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation. The ectopic expression of CRBN reduces phosphorylation of AMPK α1 and, thus, inhibits the enzyme in a nutrient-independent manner. Moreover, AMPK α1 can be potently activated by suppressing endogenous CRBN using CRBN-specific small hairpin RNAs. Thus, CRBN may act as a negative modulator of the AMPK signaling pathway in vivo

Automatic Segmentation of Brachial Artery based on Fuzzy C-Means Pixel Clustering from Ultrasound Images

Automatic extraction of brachial artery and measuring associated indices such as flow-mediated dilatation and Intima-media thickness are important for early detection of cardiovascular disease and other vascular endothelial malfunctions. In this paper, we propose the basic but important component of such decision-assisting medical software development – noise tolerant fully automatic segmentation of brachial artery from ultrasound images. Pixel clustering with Fuzzy C-Means algorithm in the quantization process is the key component of that segmentation with various image processing algorithms involved. This algorithm could be an alternative choice of segmentation process that can replace speckle noise-suffering edge detection procedures in this application domain

Structure and spectral features of H+(H2O)(7): Eigen versus Zundel forms

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)(7). For H+(H2O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)(7) [though nearly isoenergetic to the 3D structure for D+(D2O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments. (c) 2006 American Institute of Physics.open353