The neural substrates of transdiagnostic cognitive-linguistic heterogeneity in primary progressive aphasia.

BACKGROUND: Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants. METHODS: Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes). RESULTS: Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations. CONCLUSIONS: Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.

Distinctive Frontal and Occipitotemporal Surface Features in Neglectful Parenting.

Although the brain signatures of adaptive human parenting are well documented, the cortical features associated with maladaptive caregiving are underexplored. We investigated whether cortical thickness and surface area vary in a small group of mothers who had neglected their children (24 in the neglect group, NG) compared to a control group of mothers with non-neglectful caregiving (21 in the control group, CG). We also tested whether the cortical differences were related to dyadic mother-child emotional availability (EA) in a play task with their children and whether alexithymia involving low emotional awareness that characterizes the NG could play a role in the cortical-EA associations. Whole-brain analysis of the cortical mantle identified reduced cortical thickness in the right rostral middle frontal gyrus and an increased surface area in the right lingual and lateral occipital cortices for the NG with respect to the CG. Follow-up path analysis showed direct effects of the right rostral middle frontal gyrus (RMFG) on the emotional availability (EA) and on the difficulty to identify feelings (alexithymia factor), with a marginal indirect RMFG-EA effect through this factor. These preliminary findings extend existing work by implicating differences in cortical features associated with neglectful parenting and relevant to mother-child interactive bonding.

Neglectful maternal caregiving involves altered brain volume in empathy-related areas.

The maternal brain undergoes adaptations to sensitive caregiving that are critical for infant well-being. We investigated structural alterations associated with neglectful caregiving and their effects on mother-child interactive behavior. High-resolution 3D volumetric images were obtained on 25 neglectful (NM) and 23 non-neglectful control (CM) mothers. Using voxel-based morphometry, we compared differences in gray and white matter (GM and WM, respectively) volume. Mothers completed an empathy scale and participated with their children in a play task (Emotional Availability Scale, EA). Neglectful mothers showed smaller GM volume in the right insula, anterior/middle cingulate (ACC/MCC), and right inferior frontal gyrus and less WM volume in bilateral frontal regions than did CM. A greater GM volume was observed in the right fusiform and cerebellum in NM than in CM. Regression analyses showed a negative effect of greater fusiform GM volume and a positive effect of greater right frontal WM volume on EA. Mediation analyses showed the role of emotional empathy in the positive effect of the insula and right inferior frontal gyrus and in the negative effect of the cerebellum on EA. Neglectful mothering involves alterations in emotional empathy-related areas and in frontal areas associated with poor mother-child interactive bonding, indicating how critical these areas are for sensitive caregiving.

Anatomical and functional changes in the brain after simultaneous interpreting training: A longitudinal study.

In the recent literature on bilingualism, a lively debate has arisen about the long-term effects of bilingualism on cognition and the brain. These studies yield inconsistent results, in part because they rely on comparisons between bilingual and monolingual control groups that may also differ on other variables. In the present neuroimaging study, we adopted a longitudinal design, assessing the long-term anatomical and cognitive effects of an extreme form of bilingualism, namely simultaneous interpreting. We compared a group of students starting interpreting training with a closely matched group of translators, before and after nine months of training. We assessed behavioral performance and neural activity during cognitive control tasks, as well as the structural connectivity between brain regions that are involved in cognitive control. Despite the lack of behavioral differences between the two groups over time, functional and structural neural differences did arise. At the functional level, interpreters showed an increase of activation in the right angular gyrus and the left superior temporal gyrus in two non-verbal cognitive control tasks (the Simon task and a color-shape switch task), relative to the translators. At the structural level, we identified a significant increment of the structural connectivity in two different subnetworks specifically for the interpreters. The first network, the frontal-basal ganglia subnetwork, has been related to domain-general and language-specific cognitive control. The second subnetwork, in which the cerebellum and the supplementary motor area (SMA) play a key role, has recently also been proposed as an important language control network. These results suggest that interpreters undergo plastic changes in specific control-related brain networks to handle the extreme language control that takes place during interpreter training.

Complex brain network properties in late L2 learners and native speakers.

Whether the neural mechanisms that underlie the processing of a second language in highly proficient late bilinguals (L2 late learners) are similar or not to those that underlie the processing of the first language (L1) is still an issue under debate. In this study, a group of late learners of Spanish whose native language is English and a group of Spanish monolinguals were compared while they read sentences, some of which contained syntactic violations. A brain complex network analysis approach was used to assess the time-varying topological properties of the functional networks extracted from the electroencephalography (EEG) recording. Late L2 learners showed a lower degree of parallel information transfer and a slower propagation between regions of the brain functional networks while processing sentences containing a gender mismatch condition as compared with a standard sentence configuration. In contrast, no such differences between these conditions were detected in the Spanish monolinguals. This indicates that when a morphosyntactic language incongruence that does not exist in the native language is presented in the second language, the neural activation pattern is configured differently in highly proficient late bilinguals than in monolinguals.

Brain morphometry of Dravet syndrome.

The aim of this study was to identify differential global and local brain structural patterns in Dravet Syndrome (DS) patients as compared with a control subject group, using brain morphometry techniques which provide a quantitative whole-brain structural analysis that allows for specific patterns to be generalized across series of individuals. Nine patients with the diagnosis of DS that tested positive for mutation in the SCN1A gene and nine well-matched healthy controls were investigated using voxel brain morphometry (VBM), cortical thickness and cortical gyrification measurements. Global volume reductions of gray matter (GM) and white matter (WM) were related to DS. Local volume reductions corresponding to several white matter regions in brainstem, cerebellum, corpus callosum, corticospinal tracts and association fibers (left inferior fronto-occipital fasciculus and left uncinate fasciculus) were also found. Furthermore, DS showed a reduced cortical folding in the right precentral gyrus. The present findings describe DS-related brain structure abnormalities probably linked to the expression of the SCN1A mutation.

Anatomical connectivity changes in the bilingual brain.

How the brain deals with more than one language and whether we need different or extra brain language sub-networks to support more than one language remain unanswered questions. Here, we investigate structural brain network differences between early bilinguals and monolinguals. Using diffusion-weighted MRI (DW-MRI) tractography techniques and a network-based statistic (NBS) procedure, we found two structural sub-networks more connected by white matter (WM) tracts in bilinguals than in monolinguals; confirming WM brain plasticity in bilinguals. One of these sub-networks comprises left frontal and parietal/temporal regions, while the other comprises left occipital and parietal/temporal regions and also the right superior frontal gyrus. Most of these regions have been related to language processing and monitoring; suggesting that bilinguals develop specialized language sub-networks to deal with the two languages. Additionally, a complex network analysis showed that these sub-networks are more graph-efficient in bilinguals than monolinguals and this increase seems to be at the expense of a whole-network graph-efficiency decrease.

Automated discrimination of brain pathological state attending to complex structural brain network properties: the shiverer mutant mouse case.

Neuroimaging classification procedures between normal and pathological subjects are sparse and highly dependent of an expert's clinical criterion. Here, we aimed to investigate whether possible brain structural network differences in the shiverer mouse mutant, a relevant animal model of myelin related diseases, can reflect intrinsic individual brain properties that allow the automatic discrimination between the shiverer and normal subjects. Common structural networks properties between shiverer (C3Fe.SWV Mbp(shi)/Mbp(shi), n = 6) and background control (C3HeB.FeJ, n = 6) mice are estimated and compared by means of three diffusion weighted MRI (DW-MRI) fiber tractography algorithms and a graph framework. Firstly, we found that brain networks of control group are significantly more clustered, modularized, efficient and optimized than those of the shiverer group, which presented significantly increased characteristic path length. These results are in line with previous structural/functional complex brain networks analysis that have revealed topologic differences and brain network randomization associated to specific states of human brain pathology. In addition, by means of network measures spatial representations and discrimination analysis, we show that it is possible to classify with high accuracy to which group each subject belongs, providing also a probability value of being a normal or shiverer subject as an individual anatomical classifier. The obtained correct predictions (e.g., around 91.6-100%) and clear spatial subdivisions between control and shiverer mice, suggest that there might exist specific network subspaces corresponding to specific brain disorders, supporting also the point of view that complex brain network analyses constitutes promising tools in the future creation of interpretable imaging biomarkers.

Brain hemispheric structural efficiency and interconnectivity rightward asymmetry in human and nonhuman primates.

Evidence for interregional structural asymmetries has been previously reported for brain anatomic regions supporting well-described functional lateralization. Here, we aimed to investigate whether the two brain hemispheres demonstrate dissimilar general structural attributes implying different principles on information flow management. Common left hemisphere/right hemisphere structural network properties are estimated and compared for right-handed healthy human subjects and a nonhuman primate, by means of 3 different diffusion-weighted magnetic resonance imaging fiber tractography algorithms and a graph theory framework. In both the human and the nonhuman primate, the data support the conclusion that, in terms of the graph framework, the right hemisphere is significantly more efficient and interconnected than the left hemisphere, whereas the left hemisphere presents more central or indispensable regions for the whole-brain structural network than the right hemisphere. From our point of view, in terms of functional principles, this pattern could be related with the fact that the left hemisphere has a leading role for highly demanding specific process, such as language and motor actions, which may require dedicated specialized networks, whereas the right hemisphere has a leading role for more general process, such as integration tasks, which may require a more general level of interconnection.

Rightward shift in temporal order judgements in the wake of the attentional blink

Cambio hacia la derecha en los juicios de orden temporal durante el parpadeo atencional. El orden temporal de dos eventos, cada uno de ellos presentado en un hemicampo visual diferente, puede ser juzgado correctamente por observadores típicos inclusive cuando la diferencia detiempo entre las presentaciones sea muy pequeña. El presente trabajo analiza la influencia de un proceso endógeno sobre el juicio de orden temporal (JOT) y nos muestra que la percepción del orden temporal está tambiénafectada cuando los recursos atencionales disponibles son reducidos mediante un paradigma de parpadeo atencional (PA). A los participantes se les presentaron los siguientes estímulos: un primer estímulo visual (T1) en el centro de fijación y luego de un intervalo de tiempo variable (280 ó 1030 ms), un par de estímulos lateralizados (T2). Para la tarea dual con elintervalo de tiempo de 280 ms entre T1 y T2, la precisión en el JOT se deterioró, evidenciando un PA. Sin embargo, durante el PA en lugar de la asimetría favorable al lado izquierdo, aparece un significativo sesgo en contra de ese lado

The temporal order of two events, each presented in a different visual hemifield, is judged correctly by typical observers even when their onsets differ only slightly. The present study examined the influence of an endogenous process on TOJ, and shows that the perception of temporal order is also affected when available attentional resources are reduced via an attentional blink (AB) paradigm. Participants were presented with a first visual target stimulus (T1) at fixation and after a delay (either 280 or 1030 ms) a pair of lateralized stimulus occurred (T2). For the dual task and with the 280 delay between T1 and T2, accuracy in the TOJ deteriorated evincing an AB. However, instead of the left favoring asymmetry in normal attention conditions, a significant bias away from the left space emerged during the AB (AU)