The maternal-fetal neurodevelopmental groundings of preterm birth risk.

Background: Altered neurodevelopment is a major clinical sequela of Preterm Birth (PTB) being currently unexplored in-utero. Aims: To study the link between fetal brain functional (FbF) connectivity and preterm birth, using resting-state functional magnetic resonance imaging (rs-fMRI). Study design: Prospective single-centre cohort study. Subjects: A sample of 31 singleton pregnancies at 28-34 weeks assigned to a low PTB risk (LR) (n = 19) or high PTB risk (HR) (n = 12) group based on a) the Maternal Frailty Inventory (MaFra) for PTB risk; b) a case-specific PTB risk gradient. Methods: Fetal brain rs-fMRI was performed on 1.5T MRI scanner. First, directed causal relations representing fetal brain functional connectivity measurements were estimated using the Greedy Equivalence Search (GES) algorithm. HR vs. LR group differences were then tested with a novel ad-hoc developed Monte Carlo permutation test. Second, a MaFra-only random forest (RF) was compared against a MaFra-Neuro RF, trained by including also the most important fetal brain functional connections. Third, correlation and regression analyses were performed between MaFra-Neuro class probabilities and i) the GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Results: First, fewer fetal brain functional connections were evident in the HR group. Second, the MaFra-Neuro RF improved PTB risk prediction. Third, MaFra-Neuro class probabilities showed a significant association with: i) GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Conclusion: Fetal brain functional connectivity is a novel promising predictor of PTB, linked to maternal risk profiles, ahead of birth, and clinical markers of neurodevelopmental risk, at birth, thus potentially "connecting" different PTB phenotypes.

Subcortico-Cortical Functional Connectivity in the Fetal Brain: A Cognitive Development Blueprint.

Recent evidence has shown that patterns of cortico-cortical functional synchronization are consistently traceable by the end of the third trimester of pregnancy. The involvement of subcortical structures in early functional and cognitive development has never been explicitly investigated, notwithstanding their pivotal role in different cognitive processes. We address this issue by exploring subcortico-cortical functional connectivity at rest in a group of normally developing fetuses between the 25th and 32nd weeks of gestation. Results show significant functional coupling between subcortical nuclei and cortical networks related to: (i) sensorimotor processing, (ii) decision making, and (iii) learning capabilities. This functional maturation framework unearths a Cognitive Development Blueprint, according to which grounding cognitive skills are planned to develop with higher ontogenetic priority. Specifically, our evidence suggests that a newborn already possesses the ability to: (i) perceive the world and interact with it, (ii) create salient representations for the selection of adaptive behaviors, and (iii) store, retrieve, and evaluate the outcomes of interactions, in order to gradually improve adaptation to the extrauterine environment.

Bilingualism and healthy aging: Aging effects and neural maintenance.

Speaking more than one language is associated with neurocognitive benefits in seniors (Alladi et al. 2013). Few studies however have tested this hypothesis directly by comparing bilingual seniors who vary in chronological age. We report a Voxel-Based Morphometry (VBM) study showing cumulative effects of age on grey matter volume (GMV) in brain structures that are involved in cognitive control in bilingual seniors and found no differences in RT or accuracy between bilingual and monolingual seniors on a behavioral test of cognitive control called the Attentional Network Task (ANT), and no differences in GMV for selected ROIs between groups. However, chronological age predicted the size of interference and conflict effects for monolingual speakers only. We also observed a more widespread pattern of bilateral aging-effcts in brain regions that are classically associated with aging in monolingual speakers compared to bilingual speakers. Notably, GMV in the dorsal anterior cingulate cortex (dACC) and the level of daily exposure to a second language (L2) independently predict performance on the ANT in bilingual speakers. We conclude that regular (daily) bilingual experience mitigates the typical effects of aging on cognitive control at the behavioral and the neural level.

Interference and conflict monitoring in individuals with amnestic mild cognitive impairment: A structural study of the anterior cingulate cortex.

Amnestic mild cognitive impairment (aMCI) is a clinical condition characterized by memory impairment in the absence of any other cognitive impairment and is commonly associated with high conversion to Alzheimer's disease. Recent evidence shows that executive functions and selective attention mechanisms could also be impaired in aMCI. In this study, we investigated performance differences (i.e., reaction times [RTs] and accuracy) between a group of aMCI participants and a group of age-matched healthy individuals on the attentional network task (ANT) focusing on situations with increased interference. In particular, we assessed the relationship between interference and conflict effects and grey matter volumes (GMVs) of the anterior cingulate cortex (ACC)/pre-supplementary motor area in the entire sample because of its crucial role in conflict monitoring. When compared with controls, aMCI participants were less accurate on the ANT, showing increased interference and conflict effects, but no differences in RTs. In addition, aMCI participants exhibited lower GMV in the ACC than controls. While better accuracy for interference and conflict effects was associated with an increase of GMV in the ACC for both groups, RTs from the interference effect were negatively correlated with GMV of the ACC only in aMCI participants. In other words, lower GMV values of the ACC were paralleled with significantly impaired performance in terms of interference resolution. In conclusion, our study suggests the presence of a selective impairment in interference and conflict monitoring in aMCI, which in turn is associated with decreased GMVs in the ACC.

Alternating Dynamics of Segregation and Integration in Human EEG Functional Networks During Working-memory Task.

Brain functional networks show high variability in short time windows but mechanisms governing these transient dynamics remain unknown. In this work, we studied the temporal evolution of functional brain networks involved in a working memory (WM) task while recording high-density electroencephalography (EEG) in human normal subjects. We found that functional brain networks showed an initial phase characterized by an increase of the functional segregation index followed by a second phase where the functional segregation faded after the prevailing the functional integration. Notably, wrong trials were associated with different or disrupted sequences of the segregation-integration profiles and measures of network centrality and modularity were able to identify crucial aspects of the oscillatory network dynamics. Additionally, computational investigations further supported the experimental results. The brain functional organization may respond to the information processing demand of a WM task following a 2-step atomic scheme wherein segregation and integration alternately dominate the functional configurations.

The impact of different 18FDG PET healthy subject scans for comparison with single patient in SPM analysis.

BACKGROUND: Statistical Parametric Mapping (SPM) has been applied for single-subject evaluation of [18F]FDG uptake in Alzheimer Disease (AD). In a single-subject framework, the patient is compared to a dataset of [18F]FDG PET images from healthy subjects (HS) evaluating brain metabolic abnormalities. No studies exist that assess the effects on SPM analysis of HS [18F]FDG PET datasets acquired from different subjects and using different PET scanners including the same or different PET scanners than those used for patients. This work aims to elucidate this issue from a methodological perspective. METHODS: We considered six different [18F]FDG PET datasets, from different HS populations, acquired by different PET scanners. We applied SPM5 procedures for single-subject comparison with each of the six HS datasets in 10 probable AD patients showing the typical [18F]FDG pattern. We also implemented the same comparison in 3 probable AD patients and in 7 patients with a clinical diagnosis of Mild Cognitive Impariment (MCI), showing subtle changes on visual inspection of [18F]FDG distribution. RESULTS: Considering the 10 patients with the typical [18F]FDG pattern, the results were comparable for all the SPM maps. In the 3 probable AD patients with subtle changes in [18F]FDG distribution, no significant AD pattern emerged when a small number (<20) of HS was used, whereas a significant AD pattern appeared when a large (>50) HS image set was used. In the 7 considered MCI patients the use of a large (>50) HS image set allowed to assess significant hypometabolic patterns related to a probable neurodegenerative pathology. CONCLUSIONS: The use of large HS datasets of PET scans (>50) is recommended for single-subject SPM analysis. On condition that appropriate preprocessing steps are provided, large HS datasets can include HS images acquired with different PET systems, not including images from the same scanner of that used for patients.

Language Control in Bilinguals: Monitoring and Response Selection.

Language control refers to the cognitive mechanism that allows bilinguals to correctly speak in one language avoiding interference from the nontarget language. Bilinguals achieve this feat by engaging brain areas closely related to cognitive control. However, 2 questions still await resolution: whether this network is differently engaged when controlling nonlinguistic representations, and whether this network is differently engaged when control is exerted upon a restricted set of lexical representations that were previously used (i.e., local control) as opposed to control of the entire language system (i.e., global control). In the present event-related functional magnetic resonance imaging study, we investigated these 2 questions by employing linguistic and nonlinguistic blocked switching tasks in the same bilingual participants. We first report that the left prefrontal cortex is driven similarly for control of linguistic and nonlinguistic representations, suggesting its domain-general role in the implementation of response selection. Second, we propose that language control in bilinguals is hierarchically organized with the dorsal anterior cingulate cortex/presupplementary motor area acting as the supervisory attentional system, recruited for increased monitoring demands such as local control in the second language. On the other hand, prefrontal, inferior parietal areas and the caudate would act as the response selection system, tailored for language selection for both local and global control.

Semantic feature degradation and naming performance. Evidence from neurodegenerative disorders.

The failure to name an object in Alzheimer's disease (AD) and in the semantic variant of the primary progressive aphasia (sv-PPA) has been generally attributed to semantic memory loss, with a progressive degradation of semantic features. Not all features, however, may have the same relevance in picture naming. We analyzed the relationship between picture naming performance and the loss of semantic features in patients with AD with or without naming impairment, with sv-PPA and in matched controls, assessing the role of distinctiveness, semantic relevance and feature type (sensorial versus non-sensorial) with a sentence verification task. The results showed that distinctive features with high values of semantic relevance were lost only in all patients with naming impairment. The performance on the sensorial distinctive features with high relevance was the best predictor of naming performance only in sv-PPA, while no difference between sensorial and non-sensorial features was found in AD patients.

Bilingualism provides a neural reserve for aging populations.

It has been postulated that bilingualism may act as a cognitive reserve and recent behavioral evidence shows that bilinguals are diagnosed with dementia about 4-5 years later compared to monolinguals. In the present study, we investigated the neural basis of these putative protective effects in a group of aging bilinguals as compared to a matched monolingual control group. For this purpose, participants completed the Erikson Flanker task and their performance was correlated to gray matter (GM) volume in order to investigate if cognitive performance predicts GM volume specifically in areas affected by aging. We performed an ex-Gaussian analysis on the resulting RTs and report that aging bilinguals performed better than aging monolinguals on the Flanker task. Bilingualism was overall associated with increased GM in the ACC. Likewise, aging induced effects upon performance correlated only for monolinguals to decreased gray matter in the DLPFC. Taken together, these neural regions might underlie the benefits of bilingualism and act as a neural reserve that protects against the cognitive decline that occurs during aging.

Functional correlates of preserved naming performance in amnestic Mild Cognitive Impairment.

Naming abilities are typically preserved in amnestic Mild Cognitive Impairment (aMCI), a condition associated with increased risk of progression to Alzheimer's disease (AD). We compared the functional correlates of covert picture naming and word reading between a group of aMCI subjects and matched controls. Unimpaired picture naming performance was associated with more extensive activations, in particular involving the parietal lobes, in the aMCI group. In addition, in the condition associated with higher processing demands (blocks of categorically homogeneous items, living items), increased activity was observed in the aMCI group, in particular in the left fusiform gyrus. Graph analysis provided further evidence of increased modularity and reduced integration for the homogenous sets in the aMCI group. The functional modifications associated with preserved performance may reflect, in the case of more demanding tasks, compensatory mechanisms for the subclinical involvement of semantic processing areas by AD pathology.

Abstract and concrete categories? Evidences from neurodegenerative diseases.

We assessed the performance of patients with a diagnosis of Alzheimer׳s disease (AD) and of the semantic variant of primary progressive aphasia (sv-PPA) in a series of tasks involving both abstract and concrete stimuli, which were controlled for most of the variables that have been shown to affect performance on lexical-semantic tasks. Our aims were to compare the patients׳ performance on abstract and concrete stimuli and to assess category-effects within the abstract and concrete domains. The results showed: (i) a better performance on abstract than concrete concepts in sv-PPA patients. (ii) Category-related effects in the abstract domain, with emotion concepts being preserved in AD and social relations being selectively impaired in sv-PPA. In addition, a living-non living dissociation may be (infrequently) observed in individual AD patients after controlling for an extensive set of potential confounds. Thus, differences between and within the concrete or abstract domain may be present in patients with semantic memory disorders, mirroring the different brain regions involved by the different pathologies.

The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia.

INTRODUCTION: The DCDC2 gene is involved in neuronal migration. Heterotopias have been found within the white matter of DCDC2-knockdown rats. A deletion in DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named 'regulatory element associated with dyslexia 1' (READ1), increases the risk for dyslexia. We hypothesized that DCDC2d can be associated to alterations of the white matter structure in general and in dyslexic brains. METHODS: Based on a full-factorial analysis of covariance (ANCOVA) model, we investigated voxel-based diffusion tensor imaging (VB-DTI) data of four groups of subjects: dyslexia with/without DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects upon correlation patterns between fractional anisotropy (FA) and reading scores. RESULTS: We found that FA was reduced in the left arcuate fasciculus and splenium of the corpus callosum in subjects with versus without DCDC2d, irrespective of dyslexia. Subjects with dyslexia and DCDC2d showed reduced FA, mainly in the left hemisphere and in the corpus callosum; their counterpart without DCDC2d showed similar FA alterations. Noteworthy, a conjunction analysis in impaired readers revealed common regions with lower FA mainly in the left hemisphere. When we compared subjects with dyslexia with versus without DCDC2d, we found lower FA in the inferior longitudinal fasciculus and genu of the corpus callosum, bilaterally. Normal readers with versus without DCDC2d had FA increases and decreases in both the right and left hemisphere. DISCUSSION: The major contribution of our study was to provide evidence relating genes, brain and behaviour. Overall, our findings support the hypothesis that DCDC2d is associated with altered FA. In normal readers, DCDC2-related anatomical patterns may mark some developmental cognitive vulnerability to learning disabilities. In subjects with dyslexia, DCDC2d accounted for both common - mainly located in the left hemisphere - and unique - a more severe and extended pattern - alterations of white matter fibre tracts.

Bilingualism protects anterior temporal lobe integrity in aging.

Cerebral gray-matter volume (GMV) decreases in normal aging but the extent of the decrease may be experience-dependent. Bilingualism may be one protective factor and in this article we examine its potential protective effect on GMV in a region that shows strong age-related decreases-the left anterior temporal pole. This region is held to function as a conceptual hub and might be expected to be a target of plastic changes in bilingual speakers because of the requirement for these speakers to store and differentiate lexical concepts in 2 languages to guide speech production and comprehension processes. In a whole brain comparison of bilingual speakers (n = 23) and monolingual speakers (n = 23), regressing out confounding factors, we find more extensive age-related decreases in GMV in the monolingual brain and significantly increased GMV in left temporal pole for bilingual speakers. Consistent with a specific neuroprotective effect of bilingualism, region of interest analyses showed a significant positive correlation between naming performance in the second language and GMV in this region. The effect appears to be bilateral though because there was a nonsignificantly different effect of naming performance on GMV in the right temporal pole. Our data emphasize the vulnerability of the temporal pole to normal aging and the value of bilingualism as both a general and specific protective factor to GMV decreases in healthy aging.

The neural substrates of inferential and referential semantic processing.

INTRODUCTION: A distinction has been proposed, on theoretical grounds, between referential and inferential semantic abilities. The former account for the relationship of words to the world, the latter for the relationship of words among themselves. The hypothesis of, at least partially, different neurological underpinnings for this distinction has been supported by the presence of double dissociations in neurological patients between tasks that can be considered to tap the cognitive processes involving these two different classes of semantic knowledge, such as, for example, picture naming (referential) and naming to a verbal definition (inferential). METHODS: We report here the results of a functional magnetic resonance experiment, contrasting the pattern of brain activity associated with, respectively, "referential" (picture naming, word-to-picture matching) and "inferential" (naming to definition, word-to-word matching) tasks. RESULTS: All tasks activate an extensive set of brain areas involving both hemispheres, corresponding to the "common semantic network". In addition, left hemispheric temporal areas are selectively engaged by the inferential tasks. Conversely, a specific activation of the right fusiform gyrus is associated with the referential tasks. CONCLUSIONS: These findings suggest that while inferential tasks, as compared with referential tasks, engage additional processing resources subserved by left hemispheric language areas involved in lexical retrieval, referential tasks (as compared with inferential tasks) recruit right hemispheric areas generally associated with nonverbal conceptual and structural object processing. These findings are compatible with the double dissociations reported in neurological patients.

An Italian battery for the assessment of semantic memory disorders.

We report the construction and standardization of a new comprehensive battery of tests for the assessment of semantic memory disorders. The battery is constructed on a common set of 48 stimuli, belonging to both living and non-living categories, rigidly controlled for several confounding variables, and is based on an empirically derived corpus of semantic features. It includes six tasks, in order to assess semantic memory through different modalities of input and output: two naming tasks, one with colored pictures and the other in response to an oral description, a word-picture matching task, a picture sorting task, a free generation of features task and a sentence verification task. Normative data on 106 Italian subjects pooled across homogenous subgroups for age, sex and education are reported. The new battery allows an in-depth investigation of category-specific disorders and of progressive semantic memory deficits at features level, overcoming some of the limitations of existing tests.

Language proficiency modulates the engagement of cognitive control areas in multilinguals.

Language proficiency should modulate the regions involved in language control in predictable ways during language switching. However, prior studies reveal inconsistent effects on the regions involved in language monitoring [pre-Supplementary Motor Area/Anterior Cingulate Cortex (pre-SMA/ACC)] and language selection (left caudate) conceivably because variations in relative proficiency are confounded with other between-group differences. We circumvented this problem in an fMRI (functional Magnetic Resonance Imaging) study of overt picture naming in trilingual participants. In this case, the difference between a high-proficient and a low-proficient further language can be assessed within subjects with no between-group confound. We also used a monolingual group to assess the neural correlates of switching between two categories of response within the same language. We report a novel result: relative language proficiency dissociates response of the pre-SMA/ACC and left caudate during language switching. Switching between languages increased pre-SMA/ACC response regardless of proficiency differences. By contrast, left caudate response did vary with proficiency differences. Switching from the most to the least proficient language increased the response. Within-language switching, as contrasted with between-language switching, elicited a comparable increase in pre-SMA/ACC response but a decrease in left caudate response. Taken together, our data support a wider role of pre-SMA/ACC in task monitoring and establish the critical role of the left caudate in the selection of the less proficient language in language switching.

Beyond the abstract-concrete dichotomy: mode of acquisition, concreteness, imageability, familiarity, age of acquisition, context availability, and abstractness norms for a set of 417 Italian words.

The main objective of this study is to investigate the abstract-concrete dichotomy by introducing a new variable: the mode of acquisition (MoA) of a concept. MoA refers to the way in which concepts are acquired: through experience, through language, or through both. We asked 250 participants to rate 417 words on seven dimensions: age of acquisition, concreteness, familiarity, context availability, imageability, abstractness, and MoA. The data were analyzed by considering MoA ratings and their relationship with the other psycholinguistic variables. Distributions for concreteness, abstractness, and MoA ratings indicate that they are qualitatively different. A partial correlation analysis revealed that MoA is an independent predictor of concreteness or abstractness, and a hierarchical multiple regression analysis confirmed MoA as being a valid predictor of abstractness. Strong correlations with measures for the English translation equivalents in the MRC database confirmed the reliability of our norms. The full database of MoA ratings and other psycholinguistic variables may be downloaded from http://brm.psychonomic-journals.org/content/supplemental or www.abstract-project.eu.

Negation in the brain: modulating action representations.

Sentential negation is a universal syntactic feature of human languages that reverses the truth value expressed by a sentence. An intriguing question concerns what brain mechanisms underlie our ability to represent and understand the meaning of negative sentences. We approach this issue by investigating action-related language processing and the associated neural representations. Using functional magnetic resonance imaging we measured brain activity in 18 healthy subjects during passive listening of sentences characterized by a factorial combination of polarity (affirmative vs. negative) and concreteness (action-related vs. abstract). Negation deactivated cortical areas and the left pallidum. Compared to abstract sentences, action-related sentences activated the left-hemispheric action-representation system. Crucially, the polarity by concreteness interactions showed that the activity within the action-representation system was specifically reduced for negative action-related vs. affirmative action-related sentences (compared to abstract sentences). Accordingly, functional integration within this system as measured by Dynamic Causal Modeling was specifically weaker for negative action-related than for affirmative action-related sentences. This modulation of action representations indicates that sentential negation transiently reduces the access to mental representations of the negated information.