10.1073͞pnas.0504604102), the authors note that Eq. 1 was incorrectly given as P ϭ f ssͩ ͩ1 ϩ m ͪ ϩ Dͩ 2 ϩ m ͪͪ both in the text and in Fig. 2. The correct equation is as follows:The corrected figure and its legend appear below. The error does not affect the conclusions of the article. Fig. 2.Comprehensive characterization of the promoter library. Several orthogonal metrics were used to characterize the promoter library and ensure the consistent behavior of all its members for various genes and culturing conditions. We show here three metrics that were chosen for quantifying transcriptional of the promoters: (i) the dynamics of GFP production based on fluorescence, (ii) measurement of the relative mRNA transcript levels in the cultures, and (iii) testing of the MIC for chloramphenicol in an additional library of constructs where the promoter drove the expression of chloramphenicol acetyltransferase. The overall strong correlation between the various metrics suggests a broad-range utility of the promoter library for a variety of genes and conditions. (A) Mouse C127 cells were transduced with retrovirus expressing BPV-1 E7 with a FLAG͞HA epitope tag at either the C terminus (E7-C) or N terminus (E7-N), or with no tag (E7). Cells were lysed, and proteins were immunoprecipitated by using either an anti-FLAG antibody (Left) or an anti-BPV-1 E7 antibody (Right). Proteins were resolved by SDS͞PAGE on a 15% polyacrylamide gel and probed by immunoblotting using the anti-E7 antibody. (B) Cells were assayed for anchorage-independent growth with transduced BPV-1 oncogenes: C127 control cells, cells expressing BPV-1 E7 alone, BPV-1 E6 alone, E6 and E7, E6 and C-terminal FLAG͞HA-tagged E7 (E7-C), and E6 and N-terminal FLAG͞HA-tagged E7 (E7-N). Cells were suspended in 0.3% Noble agar, DMEM, and 10% FBS and grown for 14 days. Representative fields are shown at ϫ10 magnification. For further details, see Cortical analysis related to visual object recognition is traditionally thought to propagate serially along a bottom-up hierarchy of ventral areas. Recent proposals gradually promote the role of top-down processing in recognition, but how such facilitation is triggered remains a puzzle. We tested a specific model, proposing that low spatial frequencies facilitate visual object recognition by initiating top-down processes projected from orbitofrontal to visual cortex. The present study combined magnetoencephalography, which has superior temporal resolution, functional magnetic resonance imaging, and a behavioral task that yields successful recognition with stimulus repetitions. Object recognition elicited differential activity that developed in the left orbitofrontal cortex 50 ms earlier than it did in recognition-related areas in the temporal cortex. This early orbitofrontal activity was directly modulated by the presence of low spatial frequencies in the image. Taken together, the dynamics we revealed provide strong support for the proposal of how top-down facilitation of object recognition is initiated, and our observations a...

Object recognition is traditionally viewed as a hierarchical, bottom-up neural process. This view has been challenged recently by theoretical models and by findings indicating that top-down processes are involved in facilitating recognition. However, how such high-level information can be activated quickly enough to facilitate the bottom-up processing is yet unknown. We propose that such top-down facilitation is triggered by magnocellular information projected early and rapidly to the orbitofrontal cortex. Using human neuroimaging, we show that stimuli designed to bias processing toward the magnocellular pathway differentially activated the orbitofrontal cortex compared with parvocellular-biased stimuli. Although the magnocellular stimuli had a lower contrast than the parvocellular stimuli, they were recognized faster and just as accurately. Moreover, orbitofrontal activity predicted the performance advantage for the magnocellular, but not for the parvocellular-biased, stimuli, whereas the opposite was true in the fusiform gyrus. Last, analyses of effective connectivity using dynamic causal modeling showed that magnocellular-biased stimuli significantly activated pathways from occipital visual cortex to orbitofrontal cortex and from orbitofrontal cortex to fusiform gyrus. Conversely, parvocellular-biased stimuli significantly activated a pathway from the occipital visual cortex to fusiform gyrus. Our findings support the proposal that fast magnocellular projections linking early visual and inferotemporal object recognition regions with the orbitofrontal cortex facilitate object recognition by enabling the generation of early predictions.

Summary Objective The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine. Methods Using resting-state functional MRI, we compared functional connectivity between PAG and a subset of brain areas involved in nociceptive/somatosensory processing and pain modulation in 17 subjects with migraine, during a pain free state, versus 17 gender- and age-matched controls. We also assessed the relation between intrinsic resting-state correlations within PAG networks and the average monthly frequency of migraine attacks, as well as allodynia. Results Our findings show stronger connectivity between the PAG and several brain areas within nociceptive and somatosensory processing pathways in migraineurs versus controls. In addition, as the monthly frequency of migraine attacks worsens, the strength of the connectivity in some areas within these pathways increases while a significant decrease in functional resting-state connectivity between the PAG and brain regions with a predominant role in pain modulation (prefrontal cortex, anterior cingulate, amygdala) can be evidenced. Finally, migraineurs with a history of allodynia exhibit significantly reduced connectivity between PAG, prefrontal regions and anterior cingulate compared to migraineurs without allodynia. Conclusions These data reveal interictal dysfunctional dynamics within pain pathways in migraine manifested as an impairment of the descending pain modulatory, likely leading to loss of pain inhibition, and hyperexcitability primarily in nociceptive areas.