Frontal theta and posterior alpha in resting EEG: A critical examination of convergent and discriminant validity

Prior research has identified two resting EEG biomarkers with potential for predicting functional outcomes in depression: theta current density in frontal brain regions (especially rostral anterior cingulate cortex) and alpha power over posterior scalp regions. As little is known about the discriminant and convergent validity of these putative biomarkers, a thorough evaluation of these psychometric properties was conducted toward the goal of improving clinical utility of these markers. Resting 71-channel EEG recorded from 35 healthy adults at two sessions (1-week retest) were used to systematically compare different quantification techniques for theta and alpha sources at scalp (surface Laplacian or current source density [CSD]) and brain (distributed inverse; exact low resolution electromagnetic tomography [eLORETA]) level. Signal quality was evaluated with signal-to-noise ratio, participant-level spectra, and frequency PCA covariance decomposition. Convergent and discriminant validity were assessed within a multitrait-multimethod framework. Posterior alpha was reliably identified as two spectral components, each with unique spatial patterns and condition effects (eyes open/closed), high signal quality, and good convergent and discriminant validity. In contrast, frontal theta was characterized by one low-variance component, low signal quality, lack of a distinct spectral peak, and mixed validity. Correlations between candidate biomarkers suggest that posterior alpha components constitute reliable, convergent, and discriminant biometrics in healthy adults. Component-based identification of spectral activity (CSD/eLORETA-fPCA) was superior to fixed, a priori frequency bands. Improved quantification and conceptualization of frontal theta is necessary to determine clinical utility.     

Ligand-induced changes in the subcellular distribution of insulin receptors in rat liver: effects of colchicine

The in vivo effects of colchicine on the subcellular distribution of insulin receptors have been studied in insulin-injected rats and in control animals. Colchicine (0.1 mg/100 g or 10 mg/100 g body weight, i.v.) did not affect the ability of plasma membranes and Golgi fractions of control rats to bind insulin. As previously reported (Desbuquois et al., 1982), the injection of native insulin (8 nmol, i.v.) caused a 50% decrease in the insulin binding activity of plasma membranes and a concomitant 50% increase in insulin binding to Golgi fractions. These changes occurred at 4 and 40 min after insulin injection but were no longer detectable at 3 h. Colchicine treatment did not affect the initial changes in the distribution of insulin receptors induced by insulin; however, in rats treated with the low dose of colchicine, insulin binding to plasma membranes at 3 h was not fully restored. Colchicine treatment did not alter the amount of acid-extractable insulin associated with Golgi fractions of insulin-injected rats. The time course of uptake of 125I-insulin was similar in plasma membranes, microsomal fraction and Golgi fractions of colchicine-treated (0.1 mg/100 g) and of untreated rats. These results suggest that colchicine does not interfere with the endocytosis of insulin receptors induced by their ligand and has little effect, if any, on the reinsertion of internalized receptors in the plasma membrane.     

Sulfonamidwirkung auf Mutter und Kind Unter der Geburt

Zusammenfassung 35 Frauen erhielten zu verschiedenen Zeitpunkten vor der Geburt des Kindes Sulfonamide.Sulfanilamid und seine Derivate (Prontalbin, Albucid, Eubasinum) gehen durch die Placenta in den kindlichen Kreislauf über.Für die Azofarbstoffe (Prontosil rubrum) ist die Placenta undurchgängig, nur das im Körper abgespaltene Sulfanilamid geht über.Der kindliche Sulfonamidblutspiegel liegt unter dem der Mutter.Die Konzentration im Fruchtwasser hängt von der Menge des ausgeschiedenen fetalen Harns ab, welcher reichlich Sulfonamid enthält.Eine schädliche Wirkung der Sulfonamide ist weder bei der Mutter noch beim Kind klinisch nachweisbar.     

Millisecond encoding precision of auditory cortex neurons

Neurons in auditory cortex are central to our perception of sounds. However, the underlying neural codes, and the relevance of millisecond-precise spike timing in particular, remain debated. Here, we addressed this issue in the auditory cortex of alert nonhuman primates by quantifying the amount of information carried by precise spike timing about complex sounds presented for extended periods of time (random tone sequences and natural sounds). We investigated the dependence of stimulus information on the temporal precision at which spike times were registered and found that registering spikes at a precision coarser than a few milliseconds significantly reduced the encoded information. This dependence demonstrates that auditory cortex neurons can carry stimulus information at high temporal precision. In addition, we found that the main determinant of finely timed information was rapid modulation of the firing rate, whereas higher-order correlations between spike times contributed negligibly. Although the neural coding precision was high for random tone sequences and natural sounds, the information lost at a precision coarser than a few milliseconds was higher for the stimulus sequence that varied on a faster time scale (random tones), suggesting that the precision of cortical firing depends on the stimulus dynamics. Together, these results provide a neural substrate for recently reported behavioral relevance of precisely timed activity patterns with auditory cortex. In addition, they highlight the importance of millisecond-precise neural coding as general functional principle of auditory processing—from the periphery to cortex.     

Ephrin-B1 and ephrin-B2 mediate EphB-dependent presynaptic development via syntenin-1

The development of central nervous system synapses requires precise coordination between presynaptic and postsynaptic components. The EphB family controls postsynaptic development by interacting with glutamate receptors and regulating dendritic filopodia motility, but how EphBs induce the formation of presynaptic specializations is less well understood. Here, we show that knockdown of presynaptic ephrin-B1, ephrin-B2, or syntenin-1, but not ephrin-B3, prevents EphB-dependent presynaptic development. Ephrin-B1, ephrin-B2, and syntenin-1 are clustered together with presynaptic markers, suggesting that these molecules function jointly in presynaptic development. Knockdown of ephrin-B1 or ephrin-B2 reduces the number of synaptic specializations and the colocalization of syntenin-1 with synaptic markers. Simultaneous knockdown of ephrin-B1 and ephrin-B2 suggests that they function independently in the formation of synaptic contacts, but act together to recruit syntenin-1 to presynaptic terminals. Taken together, these results demonstrate that ephrin-B1 and ephrin-B2 function with EphB to mediate presynaptic development via syntenin-1.     

The antimigraine 5-HT 1B/1D receptor agonists,sumatriptan, zolmitriptan and dihydroergotamine,attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain

1. Peripheral lesion to the trigeminal nerve may induce severe pain states. Several lines of evidence have suggested that the antimigraine effect of the triptans with 5-HT(1B/1D) receptor agonist properties may result from inhibition of nociceptive transmission in the spinal nucleus of the trigeminal nerve by these drugs. On this basis, we have assessed the potential antinociceptive effects of sumatriptan and zolmitriptan, compared to dihydroergotamine (DHE), in a rat model of trigeminal neuropathic pain. 2. Chronic constriction injury was produced by two loose ligatures of the infraorbital nerve on the right side. Responsiveness to von Frey filament stimulation of the vibrissal pad was used to evaluate allodynia. 3. Two weeks after ligatures, rats with a chronic constriction of the right infraorbital nerve displayed bilateral mechanical hyper-responsiveness to von Frey filament stimulation of the vibrissal pad with a mean threshold of 0.38+/-0.04 g on the injured side and of 0.43+/-0.04 g on the contralateral (left) side (versus > or =12.5 g on both sides in the same rats prior to nerve constriction injury). 4. Sumatriptan at a clinically relevant dose (100 microg kg(-1), s.c.) led to a significant reduction of the mechanical allodynia-like behaviour on both the injured and the contralateral sides (peak-effects 6.3+/-1.1 g and 4.4+/-0.7 g, respectively). A more pronounced effect was obtained with zolmitriptan (100 microg kg(-1), s.c.) (peak-effects: 7.4+/-0.9 g and 3.2+/-1.3 g) whereas DHE (50-100 microg kg(-1), i.v.) was less active (peak-effect approximately 1.5 g). 5. Subcutaneous pretreatment with the 5-HT(1B/1D) receptor antagonist, GR 127935 (3 mg kg(-1)), prevented the anti-allodynia-like effects of triptans and DHE. Pretreatment with the 5-HT(1A) receptor antagonist, WAY 100635 (2 mg kg(-1), s.c.), did not alter the effect of triptans but significantly enhanced that of DHE (peak effect 4.3+/-0.5 g). 6. In a rat model of peripheral neuropathic pain, which consisted of a unilateral loose constriction of the sciatic nerve, neither sumatriptan (50-300 microg kg(-1)) nor zolmitriptan (50-300 microg kg(-1)) modified the thresholds for paw withdrawal and vocalization in response to noxious mechanical stimulation. 7. These results support the rationale for exploring the clinical efficacy of brain penetrant 5-HT(1B/1D) receptor agonists as analgesics to reduce certain types of trigeminal neuropathic pain in humans.