Intrinsic Variability of GM Density Maps and its Implications to VBM Studies

Voxel Based Morphometry (VBM) has been gaining popularity as an unbiased objective neuroimaging technique for identifying structural changes in the brain. VBM involves a voxel-wise comparison of the local concentration of gray matter (GM) in whole brain MRI scans. Although it was originally devised to examine structural abnormalities in patients, the technique has also been used successfully with healthy subjects. Recent VBM studies have investigated the impact of learning and practice on brain structure. Unlike certain medical conditions that may cause dramatic structural changes, effects observed in healthy subjects are expected to be small, therefore imposing stringent requirements on the sensitivity of the technique. The success of such studies depends on high quality imaging and subsequent accurate segmentation of GM. Segmentation results are inevitably affected by the presence of other tissues with similar intensity (dura matter, large blood vessels etc.), imaging artifacts (blood flow and eye movement, susceptibility artifacts etc.). Since these factors are non-homogeneous throughout the brain, segmentation is highly reproducible in some areas of cortex while it is less reliable in other areas. This non-homogeneity makes VBM sensitivity selective to areas where segmentation happens to be more robust. We studied the intrinsic variability of GM density maps derived from scans obtained under identical conditions, i.e. the same subject, scanner and protocol. The data was acquired on GE Signa 1.5, (SPGR) and Philips Achieva 3T (MPRAGE) scanners. A distinction should be made between variability observed among scans acquired within the same session and that observed for different sessions, since the latter will also be affected by such factors as different head positioning and the somewhat altered state of both the subject and the scanner. The figure summarizes within-session variability of GM density maps observed using the GE Signa. Six SPGR scans were obtained in each of four subjects in one session, and the scan sessions were repeated nine weeks later as a part of longitudinal VBM study. Variability for one subject/session was estimated by computing the standard deviation of six GM density maps obtained using SPM5 unified segmentation/normalization framework and VBM5 toolkit. These were normalized by applying a transformation estimated as follows: all six scans were coregistered and averaged to obtain a low noise structural image volume and a single normalization transformation was estimated from it. Eight variability maps in standard (MNI) space corresponding to session/subject pairs were averaged to produce a map shown in the Figure. The color coded variability map is superimposed onto the GM probability density map (only the right hemisphere is shown in the figure). We will present the findings of within and between session variability analyses derived from our data and from data obtained in other laboratories, and discuss implications and methodological considerations for planning and interpreting VBM studies of GM density. Preliminary results indicate that although different scanners and protocols produce varying patterns of GM variability maps, certain areas (e.g. tip of the temporal lobe) may consistently show increased variability

Second-language learning and changes in the brain

International audiencePresumably, second-language (L2) learning is mediated by changes in the brain. Little is known about what changes in the brain, how the brain changes, or when these changes occur during learning. Here, we illustrate by way of example how modern brain-based methods can be used to discern some of the changes that occur during L2 learning. Preliminary results from three studies indicate that classroom based L2 instruction can result in changes in the brain's electrical activity, in the location of this activity within the brain, and in the structure of the learners' brains. These changes can occur during the earliest stages of L2 acquisition

When “He” can also be “She”: an ERP study of reflexive pronoun resolution in written mandarin Chinese

The gender information in written Chinese third person pronouns is not symmetrically encoded: the character for "he" (, with semantic radical , meaning human) is used as a default referring to every individual, while the character for "she" (, with semantic radical , meaning woman) indicates females only. This critical feature could result in different patterns of processing of gender information in text, but this is an issue that has seldom been addressed in psycholinguistics. In Chinese, the written forms of the reflexive pronouns are composed of a pronoun plus the reflexive "/self" (/himself and /herself). The present study focuses on how such gender specificity interacts with the gender type of an antecedent, whether definitional (proper name) or stereotypical (stereotypical role noun) during reflexive pronoun resolution. In this event-related potential (ERP) study, gender congruity between a reflexive pronoun and its antecedent was studied by manipulating the gender type of antecedents and the gender specificity of reflexive pronouns (default: /himself vs. specific: /herself). Results included a P200 "attention related" congruity effect for /himself and a P600 "integration difficulty" congruity effect for /herself. Reflexive pronoun specificity independently affected the P200 and N400 components. These results highlight the role of /himself as a default applicable to both genders and indicate that only the processing of /herself supports a two-stage model for anaphor resolution. While both reflexive pronouns are evaluated at the bonding stage, the processing of the gender-specific reflexive pronoun is completed in the resolution stage

The role of the anterior cingulate cortex in prediction error and signaling surprise

In the past two decades, reinforcement learning (RL) has become a popular framework for understanding brain function. A key component of RL models, prediction error, has been associated with neural signals throughout the brain, including subcortical nuclei, primary sensory cortices, and prefrontal cortex. Depending on the location in which activity is observed, the functional interpretation of prediction error may change: Prediction errors may reflect a discrepancy in the anticipated and actual value of reward, a signal indicating the salience or novelty of a stimulus, and many other interpretations. Anterior cingulate cortex (ACC) has long been recognized as a region involved in processing behavioral error, and recent computational models of the region have expanded this interpretation to include a more general role for the region in predicting likely events, broadly construed, and signaling deviations between expected and observed events. Ongoing modeling work investigating the interaction between ACC and additional regions involved in cognitive control suggests an even broader role for cingulate in computing a hierarchically structured surprise signal critical for learning models of the environment. The result is a predictive coding model of the frontal lobes, suggesting that predictive coding may be a unifying computational principle across the neocortex. This paper reviews the brain mechanisms responsible for surprise; focusing on the Anterior Cingulate Cortex (ACC), long-known to play a role in behavioral-error, with a recently-expanded role in predicting likely' events and signaling deviations between expected and observed events. It argues for ACC's role in in surprise and learning, based on recent modelling work. As such, the paper provides the neuroscience complement to the psychological and computational proposals of other papers in the volume

Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling

Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS–PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination

Right hemisphere has the last laugh: neural dynamics of joke appreciation

Understanding a joke relies on semantic, mnemonic, inferential, and emotional contributions from multiple brain areas. Anatomically constrained magnetoencephalography (aMEG) combining high-density whole-head MEG with anatomical magnetic resonance imaging allowed us to estimate where the humor-specific brain activations occur and to understand their temporal sequence. Punch lines provided either funny, not funny (semantically congruent), or nonsensical (incongruent) replies to joke questions. Healthy subjects rated them as being funny or not funny. As expected, incongruous endings evoke the largest N400m in left-dominant temporo-prefrontal areas, due to integration difficulty. In contrast, funny punch lines evoke the smallest N400m during this initial lexical–semantic stage, consistent with their primed “surface congruity” with the setup question. In line with its sensitivity to ambiguity, the anteromedial prefrontal cortex may contribute to the subsequent “second take” processing, which, for jokes, presumably reflects detection of a clever “twist” contained in the funny punch lines. Joke-selective activity simultaneously emerges in the right prefrontal cortex, which may lead an extended bilateral temporo-frontal network in establishing the distant unexpected creative coherence between the punch line and the setup. This progression from an initially promising but misleading integration from left frontotemporal associations, to medial prefrontal ambiguity evaluation and right prefrontal reprocessing, may reflect the essential tension and resolution underlying humor

Vowel reduction in word-final position by early and late Spanish-English bilinguals

Vowel reduction is a prominent feature of American English, as well as other stress-timed languages. As a phonological process, vowel reduction neutralizes multiple vowel quality contrasts in unstressed syllables. For bilinguals whose native language is not characterized by large spectral and durational differences between tonic and atonic vowels, systematically reducing unstressed vowels to the central vowel space can be problematic. Failure to maintain this pattern of stressed-unstressed syllables in American English is one key element that contributes to a ?foreign accent? in second language speakers. Reduced vowels, or ?schwas,? have also been identified as particularly vulnerable to the co-articulatory effects of adjacent consonants. The current study examined the effects of adjacent sounds on the spectral and temporal qualities of schwa in word-final position. Three groups of English-speaking adults were tested: Miami-based monolingual English speakers, early Spanish-English bilinguals, and late Spanish-English bilinguals. Subjects performed a reading task to examine their schwa productions in fluent speech when schwas were preceded by consonants from various points of articulation. Results indicated that monolingual English and late Spanish-English bilingual groups produced targeted vowel qualities for schwa, whereas early Spanish-English bilinguals lacked homogeneity in their vowel productions. This extends prior claims that schwa is targetless for F2 position for native speakers to highly-proficient bilingual speakers. Though spectral qualities lacked homogeneity for early Spanish-English bilinguals, early bilinguals produced schwas with near native-like vowel duration. In contrast, late bilinguals produced schwas with significantly longer durations than English monolinguals or early Spanish-English bilinguals. Our results suggest that the temporal properties of a language are better integrated into second language phonologies than spectral qualities. Finally, we examined the role of nonstructural variables (e.g. linguistic history measures) in predicting native-like vowel duration. These factors included: Age of L2 learning, amount of L1 use, and self-reported bilingual dominance. Our results suggested that different sociolinguistic factors predicted native-like reduced vowel duration than predicted native-like vowel qualities across multiple phonetic environments