Mapping cortical activations underlying covert and overt language production using high-density diffuse optical tomography

Gold standard neuroimaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and more recently electrocorticography (ECoG) have provided profound insights regarding the neural mechanisms underlying the processing of language, but they are limited in applications involving naturalistic language production especially in developing brains, during face-to-face dialogues, or as a brain-computer interface. High-density diffuse optical tomography (HD-DOT) provides high-fidelity mapping of human brain function with comparable spatial resolution to that of fMRI but in a silent and open scanning environment similar to real-life social scenarios. Therefore, HD-DOT has potential to be used in naturalistic settings where other neuroimaging modalities are limited. While HD-DOT has been previously validated against fMRI for mapping the neural correlates underlying language comprehension and covert (i.e., silent ) language production, HD-DOT has not yet been established for mapping the cortical responses to overt (i.e., out loud ) language production. In this study, we assessed the brain regions supporting a simple hierarchy of language tasks: silent reading of single words, covert production of verbs, and overt production of verbs in normal hearing right-handed native English speakers (n = 33). First, we found that HD-DOT brain mapping is resilient to movement associated with overt speaking. Second, we observed that HD-DOT is sensitive to key activations and deactivations in brain function underlying the perception and naturalistic production of language. Specifically, statistically significant results were observed that show recruitment of regions in occipital, temporal, motor, and prefrontal cortices across all three tasks after performing stringent cluster-extent based thresholding. Our findings lay the foundation for future HD-DOT studies of imaging naturalistic language comprehension and production during real-life social interactions and for broader applications such as presurgical language assessment and brain-machine interfaces

Decoding visual information from high-density diffuse optical tomography neuroimaging data

BACKGROUND: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise of HD-DOT for facilitating field applications of neuroimaging, decoding of brain activity as measured by HD-DOT has yet to be evaluated. OBJECTIVE: To assess the feasibility and performance of decoding with HD-DOT in visual cortex. METHODS AND RESULTS: To establish the feasibility of decoding at the single-trial level with HD-DOT, a template matching strategy was used to decode visual stimulus position. A receiver operating characteristic (ROC) analysis was used to quantify the sensitivity, specificity, and reproducibility of binary visual decoding. Mean areas under the curve (AUCs) greater than 0.97 across 10 imaging sessions in a highly sampled participant were observed. ROC analyses of decoding across 5 participants established both reproducibility in multiple individuals and the feasibility of inter-individual decoding (mean AUCs \u3e 0.7), although decoding performance varied between individuals. Phase-encoded checkerboard stimuli were used to assess more complex, non-binary decoding with HD-DOT. Across 3 highly sampled participants, the phase of a 60° wide checkerboard wedge rotating 10° per second through 360° was decoded with a within-participant error of 25.8±24.7°. Decoding between participants was also feasible based on permutation-based significance testing. CONCLUSIONS: Visual stimulus information can be decoded accurately, reproducibly, and across a range of detail (for both binary and non-binary outcomes) at the single-trial level (without needing to block-average test data) using HD-DOT data. These results lay the foundation for future studies of more complex decoding with HD-DOT and applications in clinical populations

The Rodin-Ohno hypothesis that two enzyme superfamilies descended from one ancestral gene: an unlikely scenario for the origins of translation that will not be dismissed

Background Because amino acid activation is rate-limiting for uncatalyzed protein synthesis, it is a key puzzle in understanding the origin of the genetic code. Two unrelated classes (I and II) of contemporary aminoacyl-tRNA synthetases (aaRS) now translate the code. Observing that codons for the most highly conserved, Class I catalytic peptides, when read in the reverse direction, are very nearly anticodons for Class II defining catalytic peptides, Rodin and Ohno proposed that the two superfamilies descended from opposite strands of the same ancestral gene. This unusual hypothesis languished for a decade, perhaps because it appeared to be unfalsifiable. Results The proposed sense/antisense alignment makes important predictions. Fragments that align in antiparallel orientations, and contain the respective active sites, should catalyze the same two reactions catalyzed by contemporary synthetases. Recent experiments confirmed that prediction. Invariant cores from both classes, called Urzymes after Ur = primitive, authentic, plus enzyme and representing ~20% of the contemporary structures, can be expressed and exhibit high, proportionate rate accelerations for both amino-acid activation and tRNA acylation. A major fraction (60%) of the catalytic rate acceleration by contemporary synthetases resides in segments that align sense/antisense. Bioinformatic evidence for sense/antisense ancestry extends to codons specifying the invariant secondary and tertiary structures outside the active sites of the two synthetase classes. Peptides from a designed, 46-residue gene constrained by Rosetta to encode Class I and II ATP binding sites with fully complementary sequences both accelerate amino acid activation by ATP ~400 fold. Conclusions Biochemical and bioinformatic results substantially enhance the posterior probability that ancestors of the two synthetase classes arose from opposite strands of the same ancestral gene. The remarkable acceleration by short peptides of the rate-limiting step in uncatalyzed protein synthesis, together with the synergy of synthetase Urzymes and their cognate tRNAs, introduce a new paradigm for the origin of protein catalysts, emphasize the potential relevance of an operational RNA code embedded in the tRNA acceptor stems, and challenge the RNA-World hypothesis. Reviewers This article was reviewed by Dr. Paul Schimmel (nominated by Laura Landweber), Dr. Eugene Koonin and Professor David Ardell

The study of children with developmental language disorder beyond English: a tutorial

The main goal of this tutorial is to promote the study of children with developmental language disorder (DLD) across different languages of the world. The cumulative effect of these efforts is likely to be a set of more compelling and comprehensive theories of language learning difficulties and, possibly, of language acquisition in general. Benefits to children and local societies are also likely to accrue. After presenting some of the initial considerations involved in the cross-linguistic study of children with language disorders, we provide examples of the types of questions that might be asked. The examples are informed by our own collaborative work studying children DLD across the languages of Cantonese, Finnish, German, Hebrew, Hungarian, Italian, Spanish, Swedish, and Turkish, as well as English. Examples from investigators’ work on other languages are also included. We discuss within-language comparisons of children with DLD and their same-age and younger typically developing peers as well as between-language comparisons of children with DLD. Examples concern issues of morphophonology, prosody, syntactic movement, verb paradigm complexity, and underlying mechanisms, among others. These examples—tied as they are to current theories and hypotheses—are necessarily limited to the types of languages already receiving investigative attention. Through the participation of child language scholars from a wider set of disciplines we can expand the number and types of languages studied and, as a consequence, greatly enhance our understanding of childhood language disorders

Sources of Misinterpretation in the Input and Their Implications for Language Intervention With English-Speaking Children

Purpose: In English and related languages, many preschool-age children with developmental language disorder (DLD) have difficulties using tense and agreement consistently. In this review article, we discuss two potential input-related sources of this difficulty and offer several possible strategies aimed at circumventing input obstacles. Method: We review a series of studies from English, supplemented by evidence from computational modeling and studies of other languages. Collectively, the studies show that instances of failures to express tense and agreement in DLD resemble portions of larger sentences in everyday input in which tense and agreement marking is appropriately absent. Furthermore, experimental studies show that children\u27s use of tense and agreement can be swayed by manipulating details in fully grammatical input sentences. Results: The available evidence points to two particular sources of input that may contribute to tense and agreement inconsistency. One source is the appearance of subject + nonfinite verb sequences that appear in auxiliary-fronted questions (e.g., Is [the girl running]? Does [the boy like popcorn]?) and as dependent clauses in more complex sentences (e.g., Help [her wash the dishes]; We saw [the frog hopping]). The other source is the frequent appearance of bare stems in the input, whether nonfinite (e.g., go in Make him go fast) or finite (e.g., go in I go, you go). Conclusions: Although the likely sources of input are a natural part of the language that all children hear, procedures that alter the distribution of this input might be used in the early stages of intervention. Subsequent steps can incorporate more explicit comprehension and production techniques. A variety of suggestions are offered