Language-related Regions Research Articles

(TS)2WM: Tumor Segmentation and Tract Statistics for Assessing White Matter Integrity with Applications to Glioblastoma Patients

Glioblastoma (GBM) brain tumor is the most aggressive white matter (WM) invasive cerebral primary neoplasm. Due to its inherently heterogeneous appearance and shape, previous studies pursued either the segmentation precision of the tumors or qualitative analysis of the impact of brain tumors on WM integrity with manual delineation of tumors. This paper aims to develop a comprehensive analytical pipeline, called (TS)2WM, to integrate both the superior performance of brain tumor segmentation and the impact of GBM tumors on the WM integrity via tumor segmentation and tract statistics using the diffusion tensor imaging (DTI) technique. The (TS)2WM consists of three components: (i) A dilated densely connected convolutional network (D2C2N) for automatically segment GBM tumors. (ii) A modified structural connectome processing pipeline to characterize the connectivity pattern of WM bundles. (iii) A multivariate analysis to delineate the local and global associations between different DTI-related measurements and clinical variables on both brain tumors and language-related regions of interest. Among those, the proposed D2C2N model achieves competitive tumor segmentation accuracy compared with many state-of-the-art tumor segmentation methods. Significant differences in various DTI-related measurements at the streamline, weighted network, and binary network levels (e.g., diffusion properties along major fiber bundles) were found in tumor-related, language-related, and hand motor-related brain regions in 62 GBM patients as compared to healthy subjects from the Human Connectome Project.

Altered functional connectivity during speech perception in congenital amusia.

Individuals with congenital amusia have a lifelong history of unreliable pitch processing. Accordingly, they downweight pitch cues during speech perception and instead rely on other dimensions such as duration. We investigated the neural basis for this strategy. During fMRI, individuals with amusia (N = 15) and controls (N = 15) read sentences where a comma indicated a grammatical phrase boundary. They then heard two sentences spoken that differed only in pitch and/or duration cues and selected the best match for the written sentence. Prominent reductions in functional connectivity were detected in the amusia group between left prefrontal language-related regions and right hemisphere pitch-related regions, which reflected the between-group differences in cue weights in the same groups of listeners. Connectivity differences between these regions were not present during a control task. Our results indicate that the reliability of perceptual dimensions is linked with functional connectivity between frontal and perceptual regions and suggest a compensatory mechanism.

Mapping language from MEG beta power modulations during auditory and visual naming

Evaluation of language dominance is an essential step prior to epilepsy surgery. There is no consensus on an optimal methodology for determining language dominance using magnetoencephalography (MEG). Oscillatory dynamics are increasingly recognized as being of fundamental importance for brain function and dysfunction. Using task-related beta power modulations in MEG, we developed an analysis framework for localizing and lateralizing areas relevant to language processing in patients with focal epilepsy. We examined MEG responses from 29 patients (age 42 ​± ​13 years, 15M/14F) during auditory description naming (ADN) and visual picture naming (PN). MEG data were preprocessed using a combination of spatiotemporal filtering, signal thresholding, and ICA decomposition. Beta-band 17–25Hz power decrements were examined at both sensor and source levels. Volumetric grids of anatomical source space were constructed in MNI space at 8 ​mm isotropic resolution, and beta-band power changes were estimated using the dynamic imaging of coherent sources beamformer technique. A 600 ​ms temporal-window that ends 100 ​ms before speech onset was selected for analysis, to focus on later stages of word production such as phonologic selection and motor speech preparation. Cluster-based permutation testing was employed for patient- and group-level statistical inferences. Automated anatomic labeling atlas-driven laterality indices (LIs) were computed for 13 left and right language- and motor speech-related cortical regions. Group localization of ADN and PN consistently revealed significant task-related decrements of beta-power within language-related areas in the frontal, temporal and parietal lobes as well as motor-related regions of precentral/premotor and postcentral/somatomotor gyri. A region-of-interest analysis of ADN and PN suggested a strong correlation of r ​= ​0.74 (p ​< ​0.05, FDR corrected) between the two tasks within the language-related brain regions, with the highest spatial overlap in the prefrontal areas. Laterality indices (LIs) consistently showed left dominance (LI ​> ​0.1) for most individuals (93% and 82% during ADN and PN, respectively), with average LIs of 0.40 ​± ​0.25 and 0.34 ​± ​0.20 for ADN and PN, respectively. Source analysis of task-related beta power decrements appears to be a reliable method for lateralizing and localizing brain activations associated with language processing in patients with epilepsy.

Navigated repetitive transcranial magnetic stimulation as preoperative assessment in patients with brain tumors

We aimed to investigate clinical parameters that affected the results of navigated repetitive transcranial magnetic stimulation (nrTMS) language mapping by comparing the results of preoperative nrTMS language mapping with those of direct cortical stimulation (DCS) mapping. In the prospective, non-randomized study, patients had to meet all of the following inclusion criteria: the presence of left- or right-side brain tumors in the vicinity of or inside the areas anatomically associated with language functions; awake brain surgery scheduled; and age >18 years. Sixty one patients were enrolled, and this study included 42 low-grade gliomas and 19 high-grade gliomas (39 men, 22 women; mean age, 41.1 years, range 18–72 years). The tumor was located in the left and right hemisphere in 50 (82.0%) and 11 (18.0%) patients, respectively. In the 50 patients with left-side gliomas, nrTMS language mapping showed 81.6% sensitivity, 59.6% specificity, 78.5% positive predictive value, and 64.1% negative predictive value when compared with the respective DCS values for detecting language sites in all regions. We then investigated how some parameters, including age, tumor type, tumor volume, and the involvement of anatomical language-related regions, affected different subpopulations. Based on the receiver operating curve statistics, subgroup analysis showed that the non-involvement of language-related regions afforded significantly better the area under the curve (AUC) values (AUC = 0.81, 95% confidence interval (CI): 0.74–0.88) than the involvement of language-related regions (AUC = 0.58, 95% CI: 0.50–0.67; p < 0.0001). Our findings suggest that nrTMS language mapping could be a reliable method, particularly in obtaining responses for cases without tumor-involvement of classical perisylvian language areas.

Language and spatial dysfunction in Alzheimer disease with white matter thorn-shaped astrocytes.

Alzheimer disease (AD) shows a broad array of clinical presentations, but the mechanisms underlying these phenotypic variants remain elusive. Aging-related astrogliopathy (ARTAG) is a relatively recent term encompassing a broad array of tau deposition in astroglia outside the range of traditional tauopathies. White matter thorn-shaped astrocyte (WM-TSA) clusters, a specific ARTAG subtype, has been associated with atypical language presentation of AD in a small study lacking replication. To interrogate the impact of WM-TSA in modifying clinical phenotype in AD, we investigated a clinicopathologic sample of 83 persons with pure cortical AD pathology and heterogeneous clinical presentations. We mapped WM-TSA presence and density throughout cortical areas and interrogated whether WM-TSA correlated with atypical AD presentation or worse performance in neuropsychological testing. WM-TSA was present in nearly half of the cases and equally distributed in typical and atypical AD presentations. Worsening language and visuospatial functions were correlated with higher WM-TSA density in language-related and visuospatial-related regions, respectively. These findings were unrelated to regional neurofibrillary tangle burden. Next, unsupervised clustering divided the participants into 2 groups: a high-WM-TSA (n = 9) and low-WM-TSA (n = 74) pathology signature. The high-WM-TSA group scored significantly worse in language but not in other cognitive domains. The negative impact of WM-TSA pathology to language and possibly visuospatial networks suggests that WM-TSA is not as benign as other ARTAG types and may be explored as a framework to understand the mechanisms and impact of astrocytic tau deposition in AD in humans.

Changes in Language Function and Recovery-Related Prognostic Factors in First-Ever Left Hemispheric Ischemic Stroke.

ObjectiveTo investigate longitudinal changes in language function in left-hemispheric ischemic stroke patients as well as factors that influence language recovery until 1 year after stroke onset.MethodsWe analyzed data from 235 patients with first-ever left-hemispheric ischemic stroke. All patients completed the Korean version of the Frenchay Aphasia Screening Test (K-FAST) at 7 days (T1), 3 months (T2), 6 months (T3), and 1 year (T4) after stroke onset. Repeated measures analysis of variance (ANOVA) was used to investigate changes in language function between time points. Subgroup analysis was performed according to the K-FAST scores at T1. Stroke lesion volume was assessed using diffusion tensor images, and involvement of language-related brain regions was examined. Multiple regression analysis was used to analyze factors influencing improvement of K-FAST score.ResultsThe K-FAST scores at T1, T2, T3, and T4 differed significantly (p<0.05). In the subgroup analysis, only the severe group showed continuous significant improvement by 1 year. Factors that negatively influenced improvement of language function were the age at onset, initial National Institutes of Health Stroke Scale (NIHSS) score, and initial K-FAST score, whereas education level and stroke lesion volume positively affected recovery. Involvement of language-related brain regions did not significantly influence long-term language recovery after ischemic stroke.ConclusionRecovery of language function varied according to the severity of the initial language deficit. The age at stroke onset, education level, initial severity of aphasia, initial NIHSS score, and total stroke lesion volume were found to be important factors for recovery of language function.

Implicit learning of symmetry of human movement and gray matter density: Evidence against pure domain general and pure domain specific theories of implicit learning

Theories of the neural basis of implicit learning postulated that specific regions were responsible for specific structures (e.g., supra-finite state) regardless of domain (e.g., vision, movement); others assumed that implicit learning was the adaptation that occurred within neural regions dealing with each domain. We explored whether people could implicitly learn to detect symmetry in biological motion, and if so, based on voxel-based morphometry (VBM), whether the learning was associated with language-related regions involved with supra-finite state grammars (such as symmetry) or motor-related regions. To explore the relevance of motor-related regions, we investigated brain structural changes in athletes compared with non-athletes and the advantage of athletes in implicit learning of action symmetry. Further, we examined whether motor imagery ability could account for the role of motor-related regions in this learning. Participants passively observed and memorized a number of biological motion sequences instantiating a symmetry rule and then judged new sequences as grammatical or not. Behaviorally, the implicit acquisition of symmetry could extend to process biological motion. Athletes showed superior classification accuracy and kinesthetic imagery ability, and gave more familiarity attributions. VBM results showed that athletes exhibited greater gray matter density in the right cerebellum, as well as the left lingual gyrus, the left precuneus, the left calcarine gyrus, and the right thalamus. Correlation analysis showed that the cerebellar gray matter density was positively associated with classification accuracy, which was mediated by kinesthetic imagery ability. Moreover, gray matter density of the left inferior frontal cortex was also positively associated with classification accuracy, indicating the involvement of regions related to symmetry learning across domains. The study provides initial evidence that implicit learning involves both adaptation within brain regions responsible for the specific domain as well as brain regions processing the same structure across domains, at least in a case of supra-finite state grammars.

Resting-state Functional Connectivity between Dorsolateral Prefrontal Cortex and Left Temporal Language-related Region in Unaffected First-degree Relatives of Schizophrenia Patients

According to the large body of literature data, patients with schizophrenia demonstrate altered (decreased) functional connectivity (FC) between the brain regions involved in executive functions and language (in particular, dorsolateral prefrontal cortex (DLPFC) and left temporal regions). However, the analysis of similar FC in the genetic risk group has not been done, although such data are significant for studying the neurobiological markers of schizophrenia, linked to the genetic architecture of the disorder (its traits or so-called endophenotypes). The aim of this study was to investigate whether FC between the DLPFC and left temporal language-related region was altered in unaffected first-degree relatives of patients with schizophrenia. First-degree unaffected relatives of patients with schizophrenia (12 subjects) and healthy individuals without family history of mental disorders (13 subjects) underwent resting-state functional magnetic resonance imaging at 3T Philips scanner. The FC between the regions of interest (left/right DLPFC, on the one hand, and left temporal region, on the other hand) was compared between groups as well as indexes of Verbal fluency and the Scale of Prodromal Symptoms (SOPS). As compared to controls, the relatives of patients with schizophrenia were characterized by increased FC between the left DLPFC and left temporal language-related region, although they did not differ in the other indexes, and there were no correlations between the indexes and FC. The findings might reflect some compensatory functional processes in unaffected first-degree relatives of schizophrenic patients.

Accelerated Clustered Sparse Acquisition to Improve Functional MRI for Mapping Language Functions.

Functional magnetic resonance imaging (fMRI) is a useful method for noninvasive presurgical functional mapping. However, the scanner environment is inherently unsuitable for the examination of auditory and language functions, due to the loud acoustic noise produced by the scanner. Interleaved acquisition methods alleviate this problem by providing a silent period for stimulus presentation and/or response control (sparse sampling) but at the expense of a diminished amount of data collected. There are possible improvements to these sparse acquisition methods that increase the amount of data by acquiring several images per event (clustered sampling). We tested accelerated clustered fMRI acquisition in comparison with conventional sparse sampling in a pilot study. The clustered and sparse acquisition techniques (7.4 minutes scanning time per protocol) were directly compared in 15 healthy subjects (8 men; mean age: 24 ± 3 years) using both a motor (tongue movement) and a language (overt picture-naming) task. Functional imaging data were analyzed using Statistical Parametric Mapping software (SPM12 Wellcome Department of Imaging Neuroscience, London, UK). For both tasks, activation levels were compared and Euclidean distances (EDs) between cluster centers (i.e., local activation maxima and centers of gravity) were calculated. Overlaps and laterality indices were computed for the picture-naming task. In addition, the feasibility of the clustered acquisition protocol in a clinical setting was assessed in one pilot patient. For both tasks, activation levels were higher using the clustered acquisition protocol, reflected by bigger cluster sizes (p < 0.05). Mean ED between cluster centers ranged between 9.9 ± 5.4 mm (left superior temporal gyrus; centers of gravity) and 16.6 ± 13.2 mm (left inferior frontal gyrus; local activation maxima) for the picture-naming task. Overlaps between sparse and clustered acquisition reached 88% (Simpson overlap coefficient). A similar activation pattern for both acquisition methods was also confirmed in the clinical case. Despite some drawbacks inherent to the acquisition technique, the clustered sparse sampling protocol showed increased sensitivity for activation in language-related cortical regions with short scanning times. Such scanning techniques may be particularly advantageous for investigating patients with contraindications for long scans (e.g., reduced attention span).

Refined Functional Magnetic Resonance Imaging and Magnetoencephalography Mapping Reveals Reorganization in Language-Relevant Areas of Lesioned Brains

Neurosurgical decisions regarding interventions close to brain areas with language-related functions remain highly challenging because of the risk of postoperative dysfunction. To minimize these risks, improvements in the preoperative mapping of language-related regions are required, especially as space-occupying lesions often lead to altered cortical topography and language area reorganization. The degree of deviation and language area reorganization were investigated in 26 functional magnetic resonance imaging- and magnetoencephalography-dissociable cortical sub-areas displaying language-related activations in each of 18 patients with brain lesions and 3 healthy volunteers (during visual language tasks). Both modalities showed good congruency of the language areas. The mean spatial distance of the centroids and maxima was 9.06 mm and 10.58 mm, respectively, allowing us to define more specific anatomical positions. Postoperatively, language abilities increased in 11% (2 of 18) of the patients, remained unchanged in 83% (15 of 18) of the patients, and decreased in 6% (1 of 18) of the patients, respectively. Signs of language function reorganization detected on both functional magnetic resonance imaging and magnetoencephalography were present in 29% (5 of 17) of the patients. Attenuation of neurovascular coupling was found postoperatively in 17% (3 of 18) of the patients. Monohemispheric language processing cannot be assumed always in patients with brain lesions. The more detailed subdivision of language-relevant brain areas shown in this study can help to achieve more radical tumor resection without postoperative language deficits.

Altered Functional Connectivity and Brain Network Property in Pregnant Women With Cleft Fetuses.

Non-syndromic clefts of the lip and/or palate (NSCLP) is the most common congenital anomaly in the craniofacial region. NSCLP is a highly gene-associated malformation. We speculate that pregnant women with NSCLP fetuses (pregnancies with NSCLP) may have specific brain changes during pregnancy. To explore characteristic brain function changes of pregnancies with NSCLP, we analyzed resting-state fMRI (rs-fMRI) data of 42 pregnant women (21 pregnancies with NSCLP and 21 pregnancies with normal fetuses) to compare intergroup differences of (fractional) amplitude of low frequency fluctuations (fALFF/ALFF), regional homogeneity (Reho), functional connectivity (FC) and network topological properties. Compared with the control group, increased ALFF in the left hippocampus, the right fusiform and the left anterior cingulate (ACG), increased Reho in left middle occipital gyrus (MOG) and right medial frontal gyrus (MFG) were found for pregnancies with NSCLP. Meanwhile, FC between the left supramarginal gyrus (SMG) and bilateral olfactory cortex (OLF), FC between left precentral gyrus (PreCG) and right MFG, FC between right inferior frontal gyrus (IFG) and left inferior temporal gyrus (ITG) were enhanced in pregnancies with NSCLP. Besides, FC between left PreCG and left amygdala, bilateral para-hippocampal gyrus, FC between left amygdala and left MFG, right IFG were decreased. Graph theory-based analysis explored increased degree centrality (DC), betweenness centrality (BC) and nodal efficiency (Ne) in the left ITG and left SMG for pregnancies with NSCLP. Pregnancies with NSCLP has widespread decreased FC within neural networks of speech and language, which indicated that they were more likely to be associated with defects in speech and language skills. At the same time, increased topological indices showed that speech and language related regions played dominant role in their brain networks. These findings may provide clues for early detection of NSCLP fetuses.

Toward Robust Functional Neuroimaging Genetics of Cognition.

A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of FOXP2 correlated with variation in task-based activation in left inferior frontal and precentral gyri, whereas a SNP at the KIAA0319/TTRAP/THEM2 locus was associated with variable functional asymmetry of the superior temporal sulcus. Here, we directly test each claim using a closely matched neuroimaging genetics approach in independent cohorts comprising 427 participants, four times larger than the original study of 94 participants. Despite demonstrating power to detect associations with substantially smaller effect sizes than those of the original report, we do not replicate any of the reported associations. Moreover, formal Bayesian analyses reveal substantial to strong evidence in support of the null hypothesis (no effect). We highlight key aspects of the original investigation, common to functional neuroimaging genetics studies, which could have yielded elevated false-positive rates. Genetic accounts of individual differences in cognitive functional neuroimaging are likely to be as complex as behavioral/cognitive tests, involving many common genetic variants, each of tiny effect. Reliable identification of true biological signals requires large sample sizes, power calculations, and validation in independent cohorts with equivalent paradigms.SIGNIFICANCE STATEMENT A pervasive idea in neuroscience is that neuroimaging-based measures of brain function, being closer to underlying neurobiology, are more amenable for uncovering links to genetics. This is a core assumption of prominent studies that associate common DNA variants with altered activations in task-based fMRI, despite using samples (10-100 people) that lack power for detecting the tiny effect sizes typical of genetically complex traits. Here, we test central findings from one of the most influential prior studies. Using matching paradigms and substantially larger samples, coupled to power calculations and formal Bayesian statistics, our data strongly refute the original findings. We demonstrate that neuroimaging genetics with task-based fMRI should be subject to the same rigorous standards as studies of other complex traits.

Alternating-color words influence Chinese sentence reading: Evidence from neural connectivity

In order to investigate how language and attention systems are affected by word boundary information during reading, we conducted a functional magnetic resonance imaging (fMRI) experiment in which text-color in naturally unspaced Chinese sentences were systematically manipulated in three experimental conditions, that is, text-color alternation consistent or inconsistent with word boundary (i.e., alternating-color word and non-word conditions), as well as a mono-color baseline condition. Twenty college students (14 females; 23.1 years old) were required to silently read 72 sentences during fMRI scanning. We found that the conditions of word boundary modulated the brain connections between the visual word form area (VWFA) and dorsal attention regions, and between the VWFA and language-related regions. These results suggest that the coordination between the VWFA and dorsal attention regions plays an important role in grouping characters and guiding the saccade according to perceptual grouping based on color, and that the connection between VWFA and MTG could be the neural mechanism of lexical access during Chinese text reading.

Close yet independent: Dissociation of social from valence and abstract semantic dimensions in the left anterior temporal lobe.

The anterior temporal lobe (ATL) is engaged in various types of semantic dimensions. One consistently reported dimension is social information, with abstract words describing social behaviors inducing stronger activations in the ATL than nonsocial words. One potential factor that has been systematically confounded in this finding is emotional valence, given that abstract social words tend to be associated with emotional feelings. We investigated which factors drove the ATL sensitivity using a 2 (social/nonsocial) × 2 (valenced/neutral) factorial design in an fMRI study with relatively high spatial resolutions. We found that sociality and valence were processed in different ATL regions without significant interactions: The social effect was found in the left anterior superior temporal sulcus (aSTS), whereas the valence effect activated small clusters in the bilateral temporal poles (TP). In the left ATL, the social- and valence-related clusters were distinct from another superior ATL area that exhibited a general "abstractness" effect with little modulation of sociality or valence. These subregions exhibited distinct whole-brain functional connectivity patterns during the resting state, with the social cluster functionally connected to the default mode network, the valence cluster connected to the adjacent temporal regions and amygdala, and the abstractness cluster connected to a distributed network including a set of language-related regions. These results of activation profiles and connectivity patterns together indicate that the way in which the left ATL supports semantic processing is highly fine-grained, with the neural substrate for social semantic effects dissociated from those for emotional valence and abstractness.

Reduced structural brain asymmetry during neonatal life is potentially related to autism spectrum disorders in children born extremely preterm.

Disruption of the normal patterns of structural brain asymmetry, and in language-related areas, has been reported in individuals with autism spectrum disorder (ASD). We tested the hypothesis that 16 children born extremely preterm (EPT), and diagnosed with ASD at 6.5 years of age (EPT-ASD), would have different patterns of brain structural asymmetry, particularly in language-related areas, to 21 EPT children without ASD and 15 term-born children. They all underwent neonatal magnetic resonance imaging scans at 40 weeks of gestation. ASD diagnoses and the Weschler Intelligence Scale for Children-Fourth Edition, were performed in the EPT children, but not in the term group. Asymmetry indices (AIs) were assessed at three levels: global (hemispheres), lobar (brain lobes), and modular (primary sensorimotor, unimodal, and higher-order association areas). AIs were also assessed in language-related regions and correlational analyses were performed between these AIs and verbal scores. The EPT-ASD group showed reduced structural asymmetry at the modular level, mainly involving the higher-order association cortices and the language-related areas. Predominant positive correlations between language functioning and leftward AIs in the inferior frontal gyrus (opercular) and supplementary cortices, and rightward asymmetry in the angular and supramarginal gyri, were identified in the EPT-ASD group. The overall results suggest that reduced brain structural asymmetry identified during the neonatal period would be a risk factor for the development of ASD in EPT infants. This finding could identify EPT children at risk at an early stage, so that tailored interventions could be used to optimize their functions and quality of life. Autism Res 2019, 12: 1334-1343. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Babies born before the expected date (preterm) are more likely to develop autism, due to abnormal brain development. Compared with children without autism, preterm children with autism did not display the important physical differences between the two sides of their brain that are needed for normal functioning. As this alteration was found just after birth, this information could be used to identify children who are likely to develop autism, so that they can get medical support at an earlier age.

Phonological picture-word interference in language mapping with transcranial magnetic stimulation: an objective approach for functional parcellation of Broca's region.

Functional imaging data suggest different regions for semantic, syntactic, and phonological processing in an anterior-to-posterior direction along the inferior frontal gyrus. Language mapping by use of neuro-navigated transcranial magnetic stimulation (TMS) is frequently applied in clinical research to identify language-related cortical regions. Recently, we proposed a high spatial resolution approach for more detailed language mapping of cortical sub-areas such as Broca's region. Here, we employed a phonological picture-word interference paradigm in healthy subjects to reveal functional specialization in Broca's region for phonological processing. The behavioral phonological priming effect is characterized by accelerated naming responses to target pictures accompanied by phonologically related auditory distractor words. We hypothesized that the inhibitory effects of TMS on language processing would reduce phonological priming only at stimulation sites involved in phonological processing. In active as compared to sham TMS, we found reduced phonological facilitation specifically at sites overlapping with the probabilistic cytoarchitectonic area 44. Our findings complemented functional imaging data by revealing structure-function relationship in Broca's region. The introduction of a reactiontime based interference paradigm into TMS language mapping increases the objectivity of the method and allows to explore functional specificity with high temporal resolution. Findings may help to interpret results in clinical applications.

The facilitative effect of gestures on the neural processing of semantic complexity in a continuous narrative

Gestures are elemental components of social communication and aid comprehension of verbal messages; however, little is known about the potential role of gestures in facilitating processing of semantic complexity in an ecologically valid setting. The goal of this study was to investigate whether cognitive load, as indexed by semantic complexity, is modulated by the presentation of gestures accompanying speech. Twenty healthy participants watched 16 video clips of a short narrative while instructed to carefully listen to and watch the narrator while functional magnetic resonance imaging (fMRI) data were acquired. The videos contained passages with and without various co-speech gestures, as well as passages where the semantic complexity was either low or high, as measured by the metric of idea density. Increasing semantic complexity led to reduced activation within the default mode network (DMN); whereas, presents of gestures decreased activation in language-related regions (left middle temporal gyrus and left inferior frontal gyrus) and increased activation in high-level visual and multimodal regions of occipitotemporal cortex. Most interestingly, an interaction between semantic complexity and gestures was observed in a language-related area in left anterior temporal cortex; specifically, increasing gestures led to a greater drop in activation with high vs. Low semantic complexity. These results provide evidence that the facilitation of gestures on semantic processing, particularly for complex narratives, is reflected in the neural substrates of language processing.

Changes in the functional connectivity of auditory and language-related brain regions in children with congenital severe sensorineural hearing loss: An fMRI study

Abstract Early hearing deprivation can affect the development of hearing, language, and vision. Thirty-four infants with congenital severe sensorineural hearing loss (CSSHL) and 20 age- and sex-matched subjects with normal hearing were recruited. The amplitude of low-frequency fluctuation (ALFF) of auditory and language-related brain areas was compared between infants with deafness and control subjects. Relative to subjects with normal hearing, infants with CSSHL had decreased ALFF values in the right Brodmann's area (BA) 22 region and in parts of several language-related regions. As the duration of hearing loss increased, the ALFF values in the left auditory and linguistic brain regions increased. These findings indicate that hearing deprivation affects the functional connectivity between auditory and language-related brain regions and the corresponding sensory and visual functional brain regions and that this functional connectivity decreases as the duration of hearing loss increases. Cochlear implantation performed after 24 months may limit the habilitation of hearing and speech functions due to functional reorganization of the auditory and linguistic brain areas over time.

Electrophysiological modulation and cognitive-verbal enhancement by multi-session Broca's stimulation: a quantitative EEG transcranial direct current stimulation based investigation.

To evaluate transcranial direct current stimulation-induced changes in resting state quantitative EEG and cognitive-verbal performance of second language learners, 16 healthy individuals were randomly recruited to sham and real transcranial direct current stimulation groups receiving eight sessions of second language instruction accompanied by a 2 mA transcranial direct current stimulation over Broca's area with the cathode placed over the left arm. Quantitative EEG was recorded during the resting state after the stimulation session and second language instruction. Reduced theta activity at Fp1, F7, F3, and T5 caused by the stimulus current was reported. Multisession stimulation resulted in a significant increase in current density for beta power (25 Hz) in the language network. Cognitive-verbal pre-post stimulation performances suggest that anodal vs. sham transcranial direct current stimulation significantly improved the subjects test score on digit span, a cognitive-verbal ability. It is concluded that transcranial direct current stimulation of Broca's area increase cognitive-verbal performance by modulating brain electrical activity in language-related regions.

Differential intrinsic functional connectivity changes in semantic variant primary progressive aphasia.

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by semantic memory deficits with relatively preserved motor speech, syntax, and phonology. There is consistent evidence linking focal neurodegeneration of the anterior temporal lobes (ATL) to the semantic deficits observed in svPPA. Less is known about large-scale functional connectivity changes in this syndrome, particularly regarding the interplay between affected and spared language networks that leads to the unique cognitive dissociations typical of svPPA.Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we studied connectivity of networks anchored to three left-hemisphere regions crucially involved in svPPA symptomatology: ATL just posterior to the main atrophic area, opercular inferior frontal gyrus, and posterior inferior temporal lobe. First, in 32 healthy controls, these seeds isolated three networks: a ventral semantic network involving anterior middle temporal and angular gyri, a dorsal articulatory-phonological system involving inferior frontal and supramarginal regions, and a third functional connection between posterior inferior temporal and intraparietal regions likely involved in linking visual and linguistic processes. We then compared connectivity strength of these three networks between 16 svPPA patients and the 32 controls. In svPPA, decreased functional connectivity in the ventral semantic network correlated with weak semantic skills, while connectivity of the network seeded from the posterior inferior temporal lobe, though not significantly different between the two groups, correlated with pseudoword reading skills. Increased connectivity between the inferior frontal gyrus and the superior portion of the angular gyrus suggested possible adaptive changes.Our findings have two main implications. First, they support a functional subdivision of the left IPL based on its connectivity to specific language-related regions. Second, the unique neuroanatomical and linguistic profile observed in svPPA provides a compelling model for the functional interplay of these networks, being either up- or down- regulated in response to disease.