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...

The human brain is not a passive organ simply waiting to be activated by external stimuli. Instead, we propose that the brain continuously employs memory of past experiences to interpret sensory information and predict the immediately relevant future. The basic elements of this proposal include analogical mapping, associative representations and the generation of predictions. This review concentrates on visual recognition as the model system for developing and testing ideas about the role and mechanisms of top-down predictions in the brain. We cover relevant behavioral, computational and neural aspects, explore links to emotion and action preparation, and consider clinical implications for schizophrenia and dyslexia. We then discuss the extension of the general principles of this proposal to other cognitive domains.

Humans’ ability to rapidly and accurately detect, identify, and classify faces under variable conditions derives from a network of brain regions highly tuned to face information. The fusiform face area (FFA) is thought to be a computational hub for face processing, however temporal dynamics of face information processing in FFA remains unclear. Here we use multivariate pattern classification to decode the temporal dynamics of expression-invariant face information processing using electrodes placed directly upon FFA in humans. Early FFA activity (50-75 ms) contained information regarding whether participants were viewing a face. Activity between 200-500 ms contained expression-invariant information about which of 70 faces participants were viewing along with the individual differences in facial features and their configurations. Long-lasting (500+ ms) broadband gamma frequency activity predicted task performance. These results elucidate the dynamic computational role FFA plays in multiple face processing stages and indicate what information is used in performing these visual analyses.

Objects are more easily recognized in their typical context. However, is contextual information activated early enough to facilitate the perception of individual objects, or is contextual facilitation caused by postperceptual mechanisms? To elucidate this issue, we first need to study the temporal dynamics and neural interactions associated with contextual processing. Studies have shown that the contextual network consists of the parahippocampal, retrosplenial, and medial prefrontal cortices. We used functional MRI, magnetoencephalography, and phase synchrony analyses to compare the neural response to stimuli with strong or weak contextual associations. The context network was activated in functional MRI and preferentially synchronized in magnetoencephalography (MEG) for stimuli with strong contextual associations. Phase synchrony increased early (150-250 ms) only when it involved the parahippocampal cortex, whereas retrosplenial-medial prefrontal cortices synchrony was enhanced later (300-400 ms). These results describe the neural dynamics of context processing and suggest that context is activated early during object perception.phase locking | oscillations | beta | visual cognition W e know from experience that specific contexts are associated with specific objects. Seeing a jumbo-sized bucket of popcorn in a movie theater would not surprise anyone familiar with American movie theaters. However, at the opera, champagne and chocolate might be the more common sight. Whether and how context can facilitate visual recognition has been the subject of much research and vigorous debate. Behavioral research studying the effects of contextual information in visual perception has shown that information about context can facilitate recognition of visual scenes and objects (1-5). However, Hollingworth and Henderson (6) have argued that at least some of this contextual facilitation is attributable to a response bias and that any contextual influence may be the result of later postidentification processes rather than early activation of contextual information during recognition (6, 7). Here, we address the central question of when in the recognition process contextual information is activated by examining the temporal dynamics of neural regions involved in processing contextual information. Furthermore, we use this information regarding the temporal dynamics of the areas involved in contextual processing to help elucidate the functions of the individual members of the context network.In the past decade, neuroimaging studies using stimuli with strong and weak contextual associations have identified the components and basic properties of the network that mediates context-based associations; studies (8-

The nature of the visual representation for words has been fiercely debated for over 150 y. We used direct brain stimulation, pre-and postsurgical behavioral measures, and intracranial electroencephalography to provide support for, and elaborate upon, the visual word form hypothesis. This hypothesis states that activity in the left midfusiform gyrus (lmFG) reflects visually organized information about words and word parts. In patients with electrodes placed directly in their lmFG, we found that disrupting lmFG activity through stimulation, and later surgical resection in one of the patients, led to impaired perception of whole words and letters. Furthermore, using machine-learning methods to analyze the electrophysiological data from these electrodes, we found that information contained in early lmFG activity was consistent with an orthographic similarity space. Finally, the lmFG contributed to at least two distinguishable stages of word processing, an early stage that reflects gist-level visual representation sensitive to orthographic statistics, and a later stage that reflects more precise representation sufficient for the individuation of orthographic word forms. These results provide strong support for the visual word form hypothesis and demonstrate that across time the lmFG is involved in multiple stages of orthographic representation. (1), whereas Wernicke firmly rejected that notion, proposing that reading only necessitates representations of visual letters that feed forward into the language system (2). Similarly, the modern debate revolves around whether there is a visual word form system that becomes specialized for the representation of orthographic knowledge (e.g., the visual forms of letter combinations, morphemes, and whole words) (1, 3, 4). One side of the debate is characterized by the view that the brain possesses a visual word form area that is "a major, reproducible site of orthographic knowledge" (5), whereas the other side disavows any need for reading-specific visual specialization, arguing instead for neurons that are "general purpose analyzers of visual forms" (6).The visual word form hypothesis has attracted great scrutiny because the historical novelty of reading makes it highly unlikely that evolution has created a brain system specialized for reading; this places the analysis of visual word forms in stark contrast to other processes that are thought to have specialized neural systems, such as social, verbal language, or emotional processes, which can be seen in our evolutionary ancestors. Thus, testing the word form hypothesis is critical not only for understanding the neural basis of reading, but also for understanding how the brain organizes information that must be learned through extensive experience and for which we have no evolutionary bias.Advances in neuroimaging and lesion mapping have focused the modern debate surrounding the visual word form hypothesis on the left midfusiform gyrus (lmFG). This focus reflects widespread agreement that the lmFG region plays a critical role ...

Repeated exposure to a stimulus facilitates its processing. This is reflected in faster and more accurate identification, reduced perceptual identification thresholds, and more efficient classifications for repeated compared with novel items. Here, we test a hypothesis that this experience-based behavioral facilitation is a result of enhanced communication between distinct cortical regions, which reduces local processing demands. A magnetoencephalographic investigation revealed that repeated object classification led to decreased neural responses in the prefrontal cortex and temporal cortex. Critically, this decrease in absolute activity was accompanied by greater neural synchrony (a measure of functional connectivity) between these regions with repetition. Additionally, the onset of the enhanced interregional synchrony predicted the degree of behavioral facilitation. These findings suggest that object repetition results in enhanced interactions between brain regions, which facilitates performance and reduces processing demands on the regions involved.functional communication ͉ learning ͉ magnetoencepholography ͉ synchrony ͉ memory P revious experience with a stimulus facilitates its subsequent processing and leads to a fundamental form of learning termed priming. This experience-based facilitation manifests in faster and more accurate responses for repeated stimuli relative to novel stimuli. Because priming is an elementary form of learning, revealing the cognitive and neural mechanisms that underlie repetition priming is critical to our complete understanding of how experience facilitates behavior.Previous neuroimaging studies have consistently demonstrated reduced neural activity particularly in prefrontal cortex (PFC) and temporal cortex for repeated relative to novel stimuli during object-recognition and object-decision tasks (1-5). The regions that show response reductions are those that are critical to processing a stimulus in the context of the particular experimental paradigm (6). The findings of neural response reduction coupled with behavioral facilitation in repetition priming have led to the proposal that these neural reductions reflect more efficient stimulus processing and/or improvements in stimulusrelated decision processes (3, 6-10). Specifically, repetition is hypothesized to induce local neural changes that speed access to relevant object knowledge thereby facilitating performance. However, recent work has demonstrated the importance of cross-cortical interactions, particularly top-down inf luences originating from the PFC, in object processing (11, 12). Furthermore, these interactions between top-down and bottom-up processes may be critical to the neural and behavioral manifestations of priming (3,4,6,12,13). Here, we present results consistent with a mechanism by which the interactions between cortical regions involved in identification and object representations in the temporal cortex (14, 15) and executive and selection processes in the PFC (16-18) are selectively optimized with repetitio...

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson's disease (n = 11), with essential tremor (n = 9) and without a movement disorder (n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson's disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson's disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson's disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson's disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson's disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases.

Determining the dynamics of functional connectivity is critical for understanding the brain. Recent functional magnetic resonance imaging (fMRI) studies demonstrate that measuring correlations between brain regions in resting state activity can be used to reveal intrinsic neural networks. To study the oscillatory dynamics that underlie intrinsic functional connectivity between regions requires high temporal resolution measures of electrophysiological brain activity, such as magnetoencephalography (MEG). However, there is a lack of consensus as to the best method for examining connectivity in resting state MEG data. Here we adapted a wavelet-based method for measuring phase-locking with respect to the frequency of neural oscillations. This method employs anatomical MRI information combined with MEG data using the minimum norm estimate inverse solution to produce functional connectivity maps from a "seed" region to all other locations on the cortical surface at any and all frequencies of interest. We test this method by simulating phase-locked oscillations at various points on the cortical surface, which illustrates a substantial artifact that results from imperfections in the inverse solution. We demonstrate that normalizing resting state MEG data using phase-locking values computer on empty room data reduces much of the effects of this artifact. We then use this method with eight subjects to reveal intrinsic interhemispheric connectivity in the auditory network in the alpha frequency band in a silent environment. This spectral resting-state functional connectivity imaging method may allow us to better understand the oscillatory dynamics underlying intrinsic functional connectivity in the human brain.