Dynamics of spontaneous transitions between global brain states

Phase patterns of human scalp alpha EEG activity show spontaneous transitions between different globally phase-synchronized states. We studied the dynamical properties of these transitions using the method of symbolic dynamics. We found greater predictability (deterministicity) and heterogeneity in the dynamics than what was expected from corresponding surrogate series in which linear correlations are retained. A possible explanation of these observations within the framework of chaotic itinerancy is discussed.     

The validity of the face-selective ERP N170 component during simultaneous recording with functional MRI

Despite the wide interest in the neural mechanisms of face processing and numerous event-related potential (ERP) and functional MRI (fMRI) studies of face-selective neural responses, no study, to date, has collected these two measures simultaneously. The main reason for the absence of such an investigation is that MRI data acquisition generates major artifacts, which completely conceals the EEG signal. Recently, artifact removal algorithms have been developed. Our goal was to examine the validity of the face-selective ERP component N170 and its functional effects such as category selectivity and hemispherical laterality, when recorded simultaneously with functional MRI. In our experiment, half of the scans were collected during fMRI acquisition and half without fMRI acquisition. The validity of the N170 was then measured for its amplitude, latency, face selectivity (the difference between the amplitude to faces and objects), laterality (the difference between the amplitude to faces over the right and the left hemispheres) and the laterality of the face selectivity effect, by correlating these measures across subjects between data collected without fMRI and with fMRI data acquisition, after applying artifact removal procedures. We found high validity coefficients for all N170 measures. Furthermore, ERP data collected outside the scanner on a different day were highly correlated with data collected during MR acquisition for the N170 amplitude, latency, and selectivity index but moderate for laterality indices. Our study demonstrates that face-selective ERP effects are preserved in simultaneous recording with fMRI. These findings will hopefully encourage researchers to combine the two complementary neuroimaging techniques in future research.     

BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas

The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration, and tumors with BRAF duplication showed significantly increased mRNA levels of BRAF and a downstream target, CCND1, as compared with tumors without duplication. Furthermore, denaturing HPLC showed that activating BRAF mutations were detected in some of the tumors without BRAF duplication. Similarly, a marked proportion of low-grade astrocytomas from adult patients also had BRAF duplication. Both the stable silencing of BRAF through shRNA lentiviral transduction and pharmacological inhibition of MEK1/2, the immediate downstream phosphorylation target of BRAF, blocked the proliferation and arrested the growth of cultured tumor cells derived from low-grade gliomas. Our findings implicate aberrant activation of the MAPK pathway due to gene duplication or mutation of BRAF as a molecular mechanism of pathogenesis in low-grade astrocytomas and suggest inhibition of the MAPK pathway as a potential treatment.     

C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis

The guanine nucleotide exchange factor C3G, along with the CrkII adaptor protein, mediates GTP activation of the small GTPase proteins Rap1 and R-Ras, facilitating their activation of downstream signaling pathways, which had been found to be important in the pathogenesis of glomerulonephritis. We found that expression of C3G protein was upregulated in glomerular epithelial cells in an experimental model of accelerated anti-GBM antibody-induced glomerulonephritis expression. To determine the consequence of its increased expression, we transfected C3G (using adenoviral constructs) into cultured glomerular epithelial cells and measured the activated forms (i.e., GTP-bound) forms of Rap1 and R-Ras. Activation of Rap1 was not affected by C3G; however, the basal level of GTP-bound R-Ras was decreased. Further, C3G over-expression enhanced the activation of R-Ras in response to endothelin. Overexpression of C3G also led to a significant reduction in glomerular epithelial cell spreading and decreased the cells' E-cadherin expression and augmented their migration. We found that C3G was overexpressed in accelerated anti-GBM antibody-induced glomerulonephritis and suggest that this modulates glomerular epithelial cell morphology and behavior.     

Synovial cyst that compressed the peroneal nerve: case report

We report a case of synovial cyst that induced the compression of the peroneal nerve. The patient presented with foot drop and impossibility to stand on his right heel associated with numbness of anterolateral surfaces of the right shin and the dorsal surface of the foot within a 1-month period. Based on the clinical examination and electroneuromyography data, the compression of nerve by soft elastic mass was confirmed. We treated the patient by total microsurgical excision of the soft elastic mass adherent to the right peroneal nerve at the top third of the patient’s shin. Histological study revealed the cyst of synovial membrane. During the postoperative period, a force in extensors of the right foot was restored. On the seventh day, the patient began to step on his right heel, while the zone of tenderness and temperature hypoesthesia in the area of the peroneal nerve innervation remained.     

Manually-stimulated recovery of motor function after facial nerve injury requires intact sensory input

We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial-facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. We found that, without MS, this input was reduced compared to intact animals. The number of synaptophysin-positive terminals returned to normal values following MS. Thus, MS appears to counteract the deafferentation of regenerated facial motoneurons. Second, we performed FFA and, in addition, eliminated the trigeminal sensory input to facial motoneurons by extirpation of the ipsilateral infraorbital nerve (IONex). In this paradigm, without MS, vibrissal motor performance and pattern of end-plate reinnervation were as aberrant as after FFA without MS. MS did not influence the reinnervation pattern after IONex and functional recovery was even worse than after IONex without MS. Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage.