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Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Adult↗

Psycholinguistic studies on the syntactic behavior of idioms.

Six experiments examined why some idioms can be syntactically changed and still retain their figurative meanings (e.g., John laid down the law can be passivized as The law was laid down by John), while other idioms cannot be syntactically altered without losing their figurative meanings (e.g., John kicked the bucket cannot be passivized into The bucket was kicked by John). Our thesis was that the syntactic behavior of idioms is determined, to a large extent, but speakers' assumptions about the way in which parts of idioms contribute to their figurative interpretations as a whole. The results of our studies indicated that idioms whose individual semantic components contribute to their overall figurative meanings (e.g., go out on a limb) were judged as more syntactically flexible or productive than nondecomposable phrases (e.g., kick the bucket). These findings suggested that idioms do not form a unique class of linguistic items (e.g., as "dead" metaphors), but can share many of the same compositional properties normally associated with more "literal" language. The implications of these data for theories of syntactic productivity of idioms and for models of idiom comprehension are discussed.

Humans↗

A computer model of pancreatic islet glycolysis.

We have modeled an experiment with perifused pancreatic islet cells using our BIOSSIM language. The experiment and the resulting model are concerned with glucose uptake and glycolysis by the beta-cells of pancreatic islets. Although glycolysis appears to be involved in insulin release, we do not have enough information to represent insulin release in detail. The rapid entry of glucose into the beta-cell is promoted by a carrier having a very high tissue capacity. Phosphorylation of glucose by the low affinity enzyme glucokinase appears to be limiting for glycolysis. The effects of several hexose diphosphate activators of phosphofructokinase are modeled. Model behavior is described. The kinetic parameters of the enzyme submodels are given. Because of the difficulties of preparing large amounts of experimental material, information on pancreatic islet metabolism is limited. This model is a plausible explanation of the experimental results. Recent work on the genetically engineered glucose transporter and glucokinase is discussed.

Animals↗

Communication disorders: a power analytic assessment of recent research.

This study assessed the relative statistical power of contemporary research in communication disorders. Results of the analysis, based upon an evaluation of two major journals, revealed overall mean power figures of 0.16, 0.44, and 0.73 for small, medium, and large effect sizes, respectively. Interdisciplinary comparisons indicated that low statistical power is not unique to research in communication disorders, but is apparent in other behavioral science areas as well. Several alternatives are offered to the researcher who will want to ensure sufficient power for his investigation on an a priori basis. The implications of this study are discussed in reference to the experimenter/clinician model.

Audiology↗

Using hit curves to compare search algorithm performance.

Databases continue to grow but the metrics available to evaluate information retrieval systems have not changed. Large collections such as MEDLINE and the World Wide Web contain many relevant documents for common queries. Ranking is therefore increasingly important and successful information retrieval systems, such as Google, have emphasized ranking. However, existing evaluation metrics such as precision and recall, do not directly account for ranking. This paper describes a novel way of measuring information retrieval performance using weighted hit curves adapted from the field of statistical detection to reflect multiple desirable characteristics such as relevance, importance, and methodologic quality. In statistical detection, hit curves have been proposed to represent occurrence of interesting events during a detection process. Similarly, hit curves can be used to study the position of relevant documents within large result sets. We describe hit curves in light of a formal model of information retrieval, show how hit curves represent system performance including ranking, and define ways to statistically compare performance of multiple systems using hit curves. We provide example scenarios where traditional measures are less suitable than hit curves and conclude that hit curves may be useful for evaluating retrieval from large collections where ranking performance is crucial.

Algorithms↗

Integrating local and scientific knowledge: an example in fisheries science.

Attempting to predict the spatial dynamics fish stocks, as required for management, is an ominous task given our incomplete understanding of biological and ecological mechanisms underpinning behavioral responses of fish. Large gaps still exist in our basic scientific knowledge. Nonetheless, the knowledge of fishers and fishery managers is not incorporated into our scientific analyses, even though such information is rich in observation since knowledge of fish behavior and distribution is a prerequisite for their profession. Combining such observations with more conventional scientific studies and theoretical interpretations provides a means by which we may bridge some gaps in our knowledge. Presented here is an example of how both local and scientific knowledge can be integrated in a heuristic model. The model, CLUPEX, is developed in the framework of a fuzzy logic expert system and uses linguistic statements written in natural language to capture and combine knowledge sources in the form of IF... THEN rules. The rules are inferred from interviews with experts and fishery professionals including fishers, fishery managers, scientists, and First Nations people. The knowledge base, comprised of the set of rules, is flexible in the sense that it can easily be modified to add additional information or change current information. Using input pertaining to biotic and abiotic environmental conditions, CLUPEX uses the rules to provide quantitative and qualitative predictions on the structure, dynamics and mesoscale distribution of shoals of migratory adult herring during different life stages of their annual life cycle.

Animals↗

Adapting current Arden Syntax knowledge for an object oriented event monitor.

Arden Syntax for Medical Logic Module (MLM)1 was designed for writing and sharing task-specific health knowledge in 1989. Several researchers have developed frameworks to improve the sharability and adaptability of Arden Syntax MLMs, an issue known as "curly braces" problem. Karadimas et al proposed an Arden Syntax MLM-based decision support system that uses an object oriented model and the dynamic linking features of the Java platform.2 Peleg et al proposed creating a Guideline Expression Language (GEL) based on Arden Syntax's logic grammar.3 The New York Presbyterian Hospital (NYPH) has a collection of about 200 MLMs. In a process of adapting the current MLMs for an object-oriented event monitor, we identified two problems that may influence the "curly braces" one: (1) the query expressions within the curly braces of Arden Syntax used in our institution are cryptic to the physicians, institutional dependent and written ineffectively (unpublished results), and (2) the events are coded individually within a curly braces, resulting sometimes in a large number of events - up to 200.

Decision Support Systems, Clinical↗

High-frequency gamma oscillations and human brain mapping with electrocorticography.

Invasive EEG recordings with depth and/or subdural electrodes are occasionally necessary for the surgical management of patients with epilepsy refractory to medications. In addition to their vital clinical utility, electrocorticographic (ECoG) recordings provide an unprecedented opportunity to study the electrophysiological correlates of functional brain activation in greater detail than non-invasive recordings. The proximity of ECoG electrodes to the cortical sources of EEG activity enhances their spatial resolution, as well as their sensitivity and signal-to-noise ratio, particularly for high-frequency EEG activity. ECoG recordings have, therefore, been used to study the event-related dynamics of brain oscillations in a variety of frequency ranges, and in a variety of functional-neuroanatomic systems, including somatosensory and somatomotor systems, visual and auditory perceptual systems, and cortical networks responsible for language. These ECoG studies have confirmed and extended the original non-invasive observations of ERD/ERS phenomena in lower frequencies, and have discovered novel event-related responses in gamma frequencies higher than those previously observed in non-invasive recordings. In particular, broadband event-related gamma responses greater than 60 Hz, extending up to approximately 200 Hz, have been observed in a variety of functional brain systems. The observation of these "high gamma" responses requires a recording system with an adequate sampling rate and dynamic range (we use 1000 Hz at 16-bit A/D resolution) and is facilitated by event-related time-frequency analyses of the recorded signals. The functional response properties of high-gamma activity are distinct from those of ERD/ERS phenomena in lower frequencies. In particular, the timing and spatial localization of high-gamma ERS often appear to be more specific to the putative timing and localization of functional brain activation than alpha or beta ERD/ERS. These findings are consistent with the proposed role of synchronized gamma oscillations in models of neural computation, which have in turn been inspired by observations of gamma activity in animal preparations, albeit at somewhat lower frequencies. Although ECoG recordings cannot directly measure the synchronization of action potentials among assemblies of neurons, they may demonstrate event-related interactions between gamma oscillations in macroscopic local field potentials (LFP) generated by different large-scale populations of neurons engaged by the same functional task. Indeed, preliminary studies suggest that such interactions do occur in gamma frequencies, including high-gamma frequencies, at latencies consistent with the timing of task performance. The neuronal mechanisms underlying high-gamma activity and its unique response properties in humans are still largely unknown, but their investigation through invasive methods is expected to facilitate and expand their potential clinical and research applications, including functional brain mapping, brain-computer interfaces, and neurophysiological studies of human cognition.

Animals↗

Genomic history of the Caucasus: A systematic review and meta-analysis of ancient DNA studies.

The Caucasus region represents a unique natural laboratory for paleogenetic research due to its complex topography, long-standing role as a migratory corridor and glacial refugium, and exceptional preservation conditions for ancient DNA. This review synthesizes recent genome-wide studies to reconstruct the demographic history shaping the distinctive genetic landscape of modern Caucasus populations. The analysis reveals a deep pattern of continuity, isolation, and periodic admixture. Early genetic differentiation emerged in the Neolithic and Chalcolithic, forming distinct steppe and mountain population clusters. The Bronze Age was a pivotal period marked by large-scale gene flow from the Eurasian Steppe, particularly linked to the Yamnaya expansion, and interactions with Iranian and Anatolian-related groups. Despite these influences, many populations demonstrate remarkable genetic continuity from the Bronze Age to the present day. Significant knowledge gaps persist, particularly for the Paleolithic, Mesolithic, and Neolithic of the North Caucasus, as well as for the Late Medieval and Early Modern periods across the entire region. Addressing these gaps through targeted archaeogenomic studies is crucial for understanding the fine-scale processes that formed the hierarchical structure and high linguistic diversity of Caucasus populations, offering a powerful model for studying human adaptation, interaction, and language-genetics dynamics in a mountainous environment.

Humans↗

Dyslexia and the failure to form a perceptual anchor.

In a large subgroup of dyslexic individuals (D-LDs), reading difficulties are part of a broader learning and language disability. Recent studies indicate that D-LDs perform poorly in many psychoacoustic tasks compared with individuals with normal reading ability. We found that D-LDs perform as well as normal readers in speech perception in noise and in a difficult tone comparison task. However, their performance did not improve when these same tasks were performed with a smaller stimulus set. In contrast to normal readers, they did not benefit from stimulus-specific repetitions, suggesting that they have difficulties forming perceptual anchors. These findings are inconsistent with previously suggested static models of dyslexia. Instead, we propose that D-LDs' core deficit is a general difficulty in dynamically constructing stimulus-specific predictions, deriving from deficient stimulus-specific adaptation mechanisms. This hypothesis provides a direct link between D-LDs' high-level difficulties and mechanisms at the level of specific neuronal circuits.

Adaptation, Psychological↗

Metric-space indexes as a basis for scalable biological databases.

Biochemical databases will be best served by the development of new specialized database management systems whose storage managers are based on metric-space indexing techniques and the development a database query languages that embody semantics derived from biochemical models of similarity and evolution. Important biochemical data types cannot be effectively mapped to low dimensional coordinate systems on which O(log n) indexing methods rely. It is clear from an abundance of bioinformatic discoveries that biochemical data is not random and exhibits interesting structure with respect to clustering. Metric-space indexing exploits a data set's intrinsic clustering to speed the execution of similarity queries, even when the data cannot be mapped to a coordinate system. Database management systems that seamlessly integrate semantically rich query languages with a metric-storage and retrieval mechanism will allow biologists to simply and concisely develop informatic studies that have traditionally been large and labor intensive.

Computational Biology↗

Preschoolers' imitation of intonation contours.

This study evaluated normally developing preschoolers' imitation of intonation contours modeled in a sentence elicitation task. Three intonation contours (declarative, interrogative, and monotone) were presented to 3- and 5-year-old children. Acoustic analyses using the Visi-Pitch and Apple IIe computer system, along with perceptual ratings, measured the extent to which preschoolers imitated a modeled intonation contour. The results indicated that, as a group, the children were perceived to imitate or partially imitate the preceding intonation contour modeled by the adult. The 5-year-old children imitated modeled contours more frequently than did the 3-year-old children. In contrast, the 3-year-old children primarily partially imitated the intonation contours. Further analysis revealed that between-group differences were due largely to accuracy in imitating the interrogative contour. These findings establish reference data on normal children and implicate the use of both acoustic and perceptual analyses in order to develop and interpret intervention strategies aimed at children with prosodic problems.

Child Language↗

The efficiency of different search strategies in estimating parsimony jackknife, bootstrap, and Bremer support.

BACKGROUND: For parsimony analyses, the most common way to estimate confidence is by resampling plans (nonparametric bootstrap, jackknife), and Bremer support (Decay indices). The recent literature reveals that parameter settings that are quite commonly employed are not those that are recommended by theoretical considerations and by previous empirical studies. The optimal search strategy to be applied during resampling was previously addressed solely via standard search strategies available in PAUP*. The question of a compromise between search extensiveness and improved support accuracy for Bremer support received even less attention. A set of experiments was conducted on different datasets to find an empirical cut-off point at which increased search extensiveness does not significantly change Bremer support and jackknife or bootstrap proportions any more. RESULTS: For the number of replicates needed for accurate estimates of support in resampling plans, a diagram is provided that helps to address the question whether apparently different support values really differ significantly. It is shown that the use of random addition cycles and parsimony ratchet iterations during bootstrapping does not translate into higher support, nor does any extension of the search extensiveness beyond the rather moderate effort of TBR (tree bisection and reconnection branch swapping) plus saving one tree per replicate. Instead, in case of very large matrices, saving more than one shortest tree per iteration and using a strict consensus tree of these yields decreased support compared to saving only one tree. This can be interpreted as a small risk of overestimating support but should be more than compensated by other factors that counteract an enhanced type I error. With regard to Bremer support, a rule of thumb can be derived stating that not much is gained relative to the surplus computational effort when searches are extended beyond 20 ratchet iterations per constrained node, at least not for datasets that fall within the size range found in the current literature. CONCLUSION: In view of these results, calculating bootstrap or jackknife proportions with narrow confidence intervals even for very large datasets can be achieved with less expense than often thought. In particular, iterated bootstrap methods that aim at reducing statistical bias inherent to these proportions are more feasible when the individual bootstrap searches require less time.

Bayes Theorem↗

A paradox in the evolution of primate vocal learning.

The importance of auditory feedback in the development of spoken language in humans is striking. Paradoxically, although auditory-feedback-dependent vocal plasticity has been shown in a variety of taxonomic groups, there is little evidence that our nearest relatives--non-human primates--require auditory feedback for the development of species-typical vocal signals. Because of the apparent lack of developmental plasticity in the vocal production system, neuroscientists have largely ignored the neural mechanisms of non-human primate vocal production and perception. Recently, the absence of evidence for vocal plasticity from developmental studies has been contrasted with evidence for vocal plasticity in adults. We argue that this new evidence makes non-human primate vocal behavior an attractive model system for neurobiological analysis.

Acoustic Stimulation↗

The Longue Durée of genetic ancestry: multiple genetic marker systems and Celtic origins on the Atlantic facade of Europe.

Celtic languages are now spoken only on the Atlantic facade of Europe, mainly in Britain and Ireland, but were spoken more widely in western and central Europe until the collapse of the Roman Empire in the first millennium a.d. It has been common to couple archaeological evidence for the expansion of Iron Age elites in central Europe with the dispersal of these languages and of Celtic ethnicity and to posit a central European "homeland" for the Celtic peoples. More recently, however, archaeologists have questioned this "migrationist" view of Celtic ethnogenesis. The proposition of a central European ancestry should be testable by examining the distribution of genetic markers; however, although Y-chromosome patterns in Atlantic Europe show little evidence of central European influence, there has hitherto been insufficient data to confirm this by use of mitochondrial DNA (mtDNA). Here, we present both new mtDNA data from Ireland and a novel analysis of a greatly enlarged European mtDNA database. We show that mtDNA lineages, when analyzed in sufficiently large numbers, display patterns significantly similar to a large fraction of both Y-chromosome and autosomal variation. These multiple genetic marker systems indicate a shared ancestry throughout the Atlantic zone, from northern Iberia to western Scandinavia, that dates back to the end of the last Ice Age.

Base Sequence↗

Metrics for cortical map organization and lateralization.

Cerebral lateralization refers to the poorly understood fact that some functions are better controlled by one side of the brain than the other (e.g. handedness, language). Of particular concern here are the asymmetries apparent in cortical topographic maps that can be demonstrated electrophysiologically in mirror-image locations of the cerebral cortex. In spite of great interest in issues surrounding cerebral lateralization, methods for measuring the degree of organization and asymmetry in cortical maps are currently quite limited. In this paper, several measures are developed and used to assess the degree of organization, lateralization, and mirror symmetry in topographic map formation. These measures correct for large constant displacements as well as curving of maps. The behavior of the measures is tested on several topographic maps obtained by self-organization of an initially random artificial neural network model of a bihemispheric brain, and the results are compared with subjective assessments made by humans.

Brain Mapping↗

MOLE: a data management application based on a protein production data model.

MOLE (mining, organizing, and logging experiments) has been developed to meet the growing data management and target tracking needs of molecular biologists and protein crystallographers. The prototype reported here will become a Laboratory Information Management System (LIMS) to help protein scientists manage the large amounts of laboratory data being generated due to the acceleration in proteome research and will furthermore facilitate collaborations between groups based at different sites. To achieve this, MOLE is based on the data model for protein production devised at the European Bioinformatics Institute (Pajon A, et al., Proteins in press).

Algorithms↗

Disentangling the dynamic core: a research program for a neurodynamics at the large-scale.

My purpose in this paper is to sketch a research direction based on Francisco Varela's pioneering work in neurodynamics (see also Rudrauf et al. 2003, in this issue). Very early on he argued that the internal coherence of every mental-cognitive state lies in the global self-organization of the brain activities at the large-scale, constituting a fundamental pole of integration called here a "dynamic core". Recent neuroimaging evidence appears to broadly support this hypothesis and suggests that a global brain dynamics emerges at the large scale level from the cooperative interactions among widely distributed neuronal populations. Despite a growing body of evidence supporting this view, our understanding of these large-scale brain processes remains hampered by the lack of a theoretical language for expressing these complex behaviors in dynamical terms. In this paper, I propose a rough cartography of a comprehensive approach that offers a conceptual and mathematical framework to analyze spatio-temporal large-scale brain phenomena. I emphasize how these nonlinear methods can be applied, what property might be inferred from neuronal signals, and where one might productively proceed for the future. This paper is dedicated, with respect and affection, to the memory of Francisco Varela.

Brain↗