Preserved functional organization of auditory cortex in two individuals missing one temporal lobe from infancy.

Human cortical responses to natural sounds, measured with fMRI, can be approximated as the weighted sum of a small number of canonical response patterns (components), each having interpretable functional and anatomical properties. Here, we asked whether this organization is preserved in cases where only one temporal lobe is available due to early brain damage by investigating a unique family: one sibling missing their left temporal lobe from infancy, another missing the right temporal lobe from infancy, and a third anatomically neurotypical. None of the siblings manifested behavioral deficits. We analyzed fMRI responses to diverse natural sounds within the intact hemispheres of these individuals and compared them to 12 neurotypical participants. All siblings manifested typical-like auditory responses in their intact hemispheres. These results suggest that the development of the auditory cortex in each hemisphere does not depend on the existence of the other hemisphere, highlighting the redundancy and equipotentiality of the bilateral auditory system.

Neural populations in the language network differ in the size of their temporal receptive windows.

Despite long knowing what brain areas support language comprehension, our knowledge of the neural computations that these frontal and temporal regions implement remains limited. One important unresolved question concerns functional differences among the neural populations that comprise the language network. Here we leveraged the high spatiotemporal resolution of human intracranial recordings (n = 22) to examine responses to sentences and linguistically degraded conditions. We discovered three response profiles that differ in their temporal dynamics. These profiles appear to reflect different temporal receptive windows, with average windows of about 1, 4 and 6 words, respectively. Neural populations exhibiting these profiles are interleaved across the language network, which suggests that all language regions have direct access to distinct, multiscale representations of linguistic input-a property that may be critical for the efficiency and robustness of language processing.

The language network as a natural kind within the broader landscape of the human brain.

Language behaviour is complex, but neuroscientific evidence disentangles it into distinct components supported by dedicated brain areas or networks. In this Review, we describe the 'core' language network, which includes left-hemisphere frontal and temporal areas, and show that it is strongly interconnected, independent of input and output modalities, causally important for language and language-selective. We discuss evidence that this language network plausibly stores language knowledge and supports core linguistic computations related to accessing words and constructions from memory and combining them to interpret (decode) or generate (encode) linguistic messages. We emphasize that the language network works closely with, but is distinct from, both lower-level - perceptual and motor - mechanisms and higher-level systems of knowledge and reasoning. The perceptual and motor mechanisms process linguistic signals, but, in contrast to the language network, are sensitive only to these signals' surface properties, not their meanings; the systems of knowledge and reasoning (such as the system that supports social reasoning) are sometimes engaged during language use but are not language-selective. This Review lays a foundation both for in-depth investigations of these different components of the language processing pipeline and for probing inter-component interactions.

High-level language brain regions process sublexical regularities.

A network of left frontal and temporal brain regions supports language processing. This "core" language network stores our knowledge of words and constructions as well as constraints on how those combine to form sentences. However, our linguistic knowledge additionally includes information about phonemes and how they combine to form phonemic clusters, syllables, and words. Are phoneme combinatorics also represented in these language regions? Across five functional magnetic resonance imaging experiments, we investigated the sensitivity of high-level language processing brain regions to sublexical linguistic regularities by examining responses to diverse nonwords-sequences of phonemes that do not constitute real words (e.g. punes, silory, flope). We establish robust responses in the language network to visually (experiment 1a, n = 605) and auditorily (experiments 1b, n = 12, and 1c, n = 13) presented nonwords. In experiment 2 (n = 16), we find stronger responses to nonwords that are more well-formed, i.e. obey the phoneme-combinatorial constraints of English. Finally, in experiment 3 (n = 14), we provide suggestive evidence that the responses in experiments 1 and 2 are not due to the activation of real words that share some phonology with the nonwords. The results suggest that sublexical regularities are stored and processed within the same fronto-temporal network that supports lexical and syntactic processes.

The human language system, including its inferior frontal component in "Broca's area," does not support music perception.

Language and music are two human-unique capacities whose relationship remains debated. Some have argued for overlap in processing mechanisms, especially for structure processing. Such claims often concern the inferior frontal component of the language system located within "Broca's area." However, others have failed to find overlap. Using a robust individual-subject fMRI approach, we examined the responses of language brain regions to music stimuli, and probed the musical abilities of individuals with severe aphasia. Across 4 experiments, we obtained a clear answer: music perception does not engage the language system, and judgments about music structure are possible even in the presence of severe damage to the language network. In particular, the language regions' responses to music are generally low, often below the fixation baseline, and never exceed responses elicited by nonmusic auditory conditions, like animal sounds. Furthermore, the language regions are not sensitive to music structure: they show low responses to both intact and structure-scrambled music, and to melodies with vs. without structural violations. Finally, in line with past patient investigations, individuals with aphasia, who cannot judge sentence grammaticality, perform well on melody well-formedness judgments. Thus, the mechanisms that process structure in language do not appear to process music, including music syntax.

Preserved functional organization of human auditory cortex in individuals missing one temporal lobe from infancy.

Human cortical responses to natural sounds, measured with fMRI, can be approximated as the weighted sum of a small number of canonical response patterns (components), each having interpretable functional and anatomical properties. Here, we asked whether this organization is preserved in cases where only one temporal lobe is available due to early brain damage by investigating a unique family: one sibling born without a left temporal lobe, another without a right temporal lobe, and a third anatomically neurotypical. We analyzed fMRI responses to diverse natural sounds within the intact hemispheres of these individuals and compared them to 12 neurotypical participants. All siblings manifested the neurotypical auditory responses in their intact hemispheres. These results suggest that the development of the auditory cortex in each hemisphere does not depend on the existence of the other hemisphere, highlighting the redundancy and equipotentiality of the bilateral auditory system.

Context Sensitivity across Multiple Time scales with a Flexible Frequency Bandwidth.

Everyday auditory streams are complex, including spectro-temporal content that varies at multiple timescales. Using EEG, we investigated the sensitivity of human auditory cortex to the content of past stimulation in unattended sequences of equiprobable tones. In 3 experiments including 82 participants overall, we found that neural responses measured at different latencies after stimulus onset were sensitive to frequency intervals computed over distinct timescales. Importantly, early responses were sensitive to a longer history of stimulation than later responses. To account for these results, we tested a model consisting of neural populations with frequency-specific but broad tuning that undergo adaptation with exponential recovery. We found that the coexistence of neural populations with distinct recovery rates can explain our results. Furthermore, the adaptation bandwidth of these populations depended on spectral context-it was wider when the stimulation sequence had a wider frequency range. Our results provide electrophysiological evidence as well as a possible mechanistic explanation for dynamic and multiscale context-dependent auditory processing in the human cortex.

Evidence for Linear but Not Helical Automatic Representation of Pitch in the Human Auditory System.

The perceptual organization of pitch is frequently described as helical, with a monotonic dimension of pitch height and a circular dimension of pitch chroma, accounting for the repeating structure of the octave. Although the neural representation of pitch height is widely studied, the way in which pitch chroma representation is manifested in neural activity is currently debated. We tested the automaticity of pitch chroma processing using the MMN-an ERP component indexing automatic detection of deviations from auditory regularity. Musicians trained to classify pure or complex tones across four octaves, based on chroma-C versus G (21 participants, Experiment 1) or C versus F# (27, Experiment 2). Next, they were passively exposed to MMN protocols designed to test automatic detection of height and chroma deviations. Finally, in an "attend chroma" block, participants had to detect the chroma deviants in a sequence similar to the passive MMN sequence. The chroma deviant tones were accurately detected in the training and the attend chroma parts both for pure and complex tones, with a slightly better performance for complex tones. However, in the passive blocks, a significant MMN was found only to height deviations and complex tone chroma deviations, but not to pure tone chroma deviations, even for perfect performers in the active tasks. These results indicate that, although height is represented preattentively, chroma is not. Processing the musical dimension of chroma may require higher cognitive processes, such as attention and working memory.

Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex.

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event-related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex.

A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions.

Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization.

Genome holography: deciphering function-form motifs from gene expression data.

BACKGROUND: DNA chips allow simultaneous measurements of genome-wide response of thousands of genes, i.e. system level monitoring of the gene-network activity. Advanced analysis methods have been developed to extract meaningful information from the vast amount of raw gene-expression data obtained from the microarray measurements. These methods usually aimed to distinguish between groups of subjects (e.g., cancer patients vs. healthy subjects) or identifying marker genes that help to distinguish between those groups. We assumed that motifs related to the internal structure of operons and gene-networks regulation are also embedded in microarray and can be deciphered by using proper analysis. METHODOLOGY/PRINCIPAL FINDINGS: The analysis presented here is based on investigating the gene-gene correlations. We analyze a database of gene expression of Bacillus subtilis exposed to sub-lethal levels of 37 different antibiotics. Using unsupervised analysis (dendrogram) of the matrix of normalized gene-gene correlations, we identified the operons as they form distinct clusters of genes in the sorted correlation matrix. Applying dimension-reduction algorithm (Principal Component Analysis, PCA) to the matrices of normalized correlations reveals functional motifs. The genes are placed in a reduced 3-dimensional space of the three leading PCA eigen-vectors according to their corresponding eigen-values. We found that the organization of the genes in the reduced PCA space recovers motifs of the operon internal structure, such as the order of the genes along the genome, gene separation by non-coding segments, and translational start and end regions. In addition to the intra-operon structure, it is also possible to predict inter-operon relationships, operons sharing functional regulation factors, and more. In particular, we demonstrate the above in the context of the competence and sporulation pathways. CONCLUSIONS/SIGNIFICANCE: We demonstrated that by analyzing gene-gene correlation from gene-expression data it is possible to identify operons and to predict unknown internal structure of operons and gene-networks regulation.