Identification of Negative BOLD Responses in Epilepsy Using Windkessel Models.

Alongside positive blood oxygenation level-dependent (BOLD) responses associated with interictal epileptic discharges, a variety of negative BOLD responses (NBRs) are typically found in epileptic patients. Previous studies suggest that, in general, up to four mechanisms might underlie the genesis of NBRs in the brain: (i) neuronal disruption of network activity, (ii) altered balance of neurometabolic/vascular couplings, (iii) arterial blood stealing, and (iv) enhanced cortical inhibition. Detecting and classifying these mechanisms from BOLD signals are pivotal for the improvement of the specificity of the electroencephalography-functional magnetic resonance imaging (EEG-fMRI) image modality to identify the seizure-onset zones in refractory local epilepsy. This requires models with physiological interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a Windkessel model with viscoelastic compliance/inductance in combination with dynamic models of both neuronal population activity and tissue/blood O2 to classify the hemodynamic response functions (HRFs) linked to the above mechanisms in the irritative zones of epileptic patients. First, we evaluated the most relevant imprints on the BOLD response caused by variations of key model parameters. Second, we demonstrated that a general linear model is enough to accurately represent the four different types of NBRs. Third, we tested the ability of a machine learning classifier, built from a simulated ensemble of HRFs, to predict the mechanism underlying the BOLD signal from irritative zones. Cross-validation indicates that these four mechanisms can be classified from realistic fMRI BOLD signals. To demonstrate proof of concept, we applied our methodology to EEG-fMRI data from five epileptic patients undergoing neurosurgery, suggesting the presence of some of these mechanisms. We concluded that a proper identification and interpretation of NBR mechanisms in epilepsy can be performed by combining general linear models and biophysically inspired models.

Lesion Network Localization of Seizure Freedom following MR-guided Laser Interstitial Thermal Ablation.

Treatment-resistant epilepsy is a common and debilitating neurological condition, for which neurosurgical cure is possible. Despite undergoing nearly identical ablation procedures however, individuals with treatment-resistant epilepsy frequently exhibit heterogeneous outcomes. We hypothesized that treatment response may be related to the brain regions to which MR-guided laser ablation volumes are functionally connected. To test this, we mapped the resting-state functional connectivity of surgical ablations that either resulted in seizure freedom (N = 11) or did not result in seizure freedom (N = 16) in over 1,000 normative connectomes. There was no difference seizure outcome with respect to the anatomical location of the ablations, and very little overlap between ablation areas was identified using the Dice Index. Ablations that did not result in seizure-freedom were preferentially connected to a number of cortical and subcortical regions, as well as multiple canonical resting-state networks. In contrast, ablations that led to seizure-freedom were more functionally connected to prefrontal cortices. Here, we demonstrate that underlying normative neural circuitry may in part explain heterogenous outcomes following ablation procedures in different brain regions. These findings may ultimately inform target selection for ablative epilepsy surgery based on normative intrinsic connectivity of the targeted volume.

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation.

OBJECTIVE: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. METHODS: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. RESULTS: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). INTERPRETATION: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753.

Functional imaging localization of complex organic hallucinations.

Background: fMRI of mental phenomena is quite difficult to perform because lack of patient's cooperation or because the symptoms are stable. In some exceptional cases, however, fMRI and DTI are capable to provide insights on the anatomy of organic hallucinations. Methods: In this report we describe a 14-year-old boy with a left fronto-dorsal tumor who experienced chronic complex brief, frequent and repetitive complex visual and auditory hallucinations. His clinical picture included multiple and severe social and mood problems. During a presurgical fMRI mapping the patient complained of having the visual and auditory hallucinations. A block-design FMRI paradigm was obtained from the event timecourse. Deterministic DTI of the brain was obtained seeding the lesion as ROI. The patient underwent surgery and electrocorticography of the lesional area. Results: The fMRI of the hallucinations showed activation in the left inferior frontal gyrus (IFG) and the peri-lesional area. The tractography of the tumor revealed structural aberrant connectivity to occipital and temporal areas in addition to the expected connectivity with the IFG via the aslant fasciculus and homotopic contralateral areas. Intraoperative EEG demonstrated epileptic discharges in the tumor and neighboring areas. After resection, the patient's hallucinations stopped completely. He regained his normal social life and recover his normal mood. He remained asymptomatic for 90 days. Afterwards, hallucinations reappeared but with less intensity. Conclusions: To our knowledge, this is the first reported case of combined functional and structural connectivity imaging demonstrating brain regions participating in a network involved in the generation of complex auditory and visual hallucinations.

Fiber pathways supporting early literacy development in 5-8-year-old children.

The development of fluent reading is an extended process that requires the recruitment of a comprehensive system of perisylvian brain regions connected by an extensive network of fiber pathways. In the present cross-sectional study, we focused on fiber pathways-the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and vertical occipital fasciculus (VOF)-proposed to support early literacy in typical 5-8-year-old children. We related quantitative metrics of fiber pathway microstructure in these pathways to early literacy measures of phonological awareness and decoding. We found that diffusion properties of the AF, ILF, and VOF not only show age-related differences, but also are predictive of early literacy skills after controlling for the effects of age, general white matter development, sex, IQ, and phonological skill. Perhaps most novel, we provide evidence supporting the involvement of the recently re-identified VOF in early literacy, and further, we provide evidence that a bilateral network of fiber pathways supports early literacy development.

Nontask-Related Brain Lateralization Biomarkers in Children: The Asymmetry of Language Areas on Functional Connectivity Functional Magnetic Resonance Imaging.

In this work, we will test the hypothesis that the connectivity of language areas in normal children is asymmetric between the hemispheres. Intrahemispheric region of interest (ROI)-to-ROI connectivity was assessed in 40 normal right-handed children. Asymmetries were assessed (1) between the hemispheres (global language connectivity); (2) between Brodmann areas (BAs) pairs (pairwise connectivity); and (3) between two homotopic BA (Global BA connectivity). Sixteen BAs were selected: 6, 7, 9, 19, 21, 22, 37, 38, 39, 40, 41, 42, 44, 45, 46, and 47. T scores for connectivity of each BA pair were ascertained using the MATLAB toolbox CONN. Lateralization index (LI) scores based on T-values were obtained. Only LIs with 2SD above the mean were considered as significant. Comparisons between T-value groups (per side and per BA) were performed utilizing double-sided T-tests. Null hypothesis was rejected for p < 0.05. There was not a statistical difference between global left and right connectivity strength (p = 0.40). There was significant pairwise connectivity asymmetry for the following pairs: BA7-BA44 (LI = 0.662); BA21-BA42 (LI = -0.616); BA21-BA40 (LI = -0.595); BA38-BA44 (LI = 0.470); BA39-BA44 (LI = -0.903); and BA42-BA47 (LI = -0.445). Language-related brain connectivity asymmetries have been demonstrated in a group of children and young adolescents. Two pairs related to Broca's area were left dominant (BA44-BA38 and BA44-BA7) and four pairs right dominant (BA42-BA47, BA39-BA44, BA21-BA40, and BA21-BA42).

Presurgical hyperconnectivity of the ablation volume is associated with seizure-freedom after magnetic resonance-guided laser interstitial thermal therapy.

PURPOSE: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI. METHODS: Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free. RESULTS: Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network. CONCLUSIONS: These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification.

Executive Functions Brain System: An Activation Likelihood Estimation Meta-analytic Study.

BACKGROUND AND OBJECTIVE: To characterize commonalities and differences between two executive functions: reasoning and inhibitory control. METHODS: A total of 5,974 participants in 346 fMRI experiments of inhibition or reasoning were selected. First level analysis consisted of Analysis of Likelihood Estimation (ALE) studies performed in two pooled data groups: (a) brain areas involved in reasoning and (b) brain areas involved in inhibition. Second level analysis consisted of two contrasts: (i) brain areas involved in reasoning but not in inhibition and (ii) brain areas involved in inhibition but not in reasoning. Lateralization Indexes were calculated. RESULTS: Four brain areas appear as the most critical: the dorsolateral aspect of the frontal lobes, the superior parietal lobules, the mesial aspect of the premotor area (supplementary motor area), and some subcortical areas, particularly the putamen and the thalamus. ALE contrasts showed significant differentiation of the networks, with the reasoning > inhibition-contrast showing a predominantly leftward participation, and the inhibition > reasoning-contrast, a clear right advantage. CONCLUSION: Executive functions are mediated by sizable brain areas including not only cortical, but also involving subcortical areas in both hemispheres. The strength of activation shows dissociation between the hemispheres for inhibition (rightward) and reasoning (leftward) functions.

Presurgical thalamocortical connectivity is associated with response to vagus nerve stimulation in children with intractable epilepsy.

Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5-21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.

Should Broca's area include Brodmann area 47?

BACKGROUND: Understanding brain organization of speech production has been a principal goal of neuroscience. Historically, brain speech production has been associated with so-called Broca's area (Brodmann area ­BA- 44 and 45), however, modern neuroimaging developments suggest speech production is associated with networks rather than with areas. The purpose of this paper was to analyze the connectivity of BA47 ( pars orbitalis) in relation to language . METHOD: A meta-analysis was conducted to assess the language network in which BA47 is involved. The Brainmap database was used. Twenty papers corresponding to 29 experimental conditions with a total of 373 subjects were included. RESULTS: Our results suggest that BA47 participates in a "frontal language production system" (or extended Broca's system). The BA47  connectivity found is also concordant with a minor role in language semantics. CONCLUSIONS: BA47 plays a central role in the language production system.

Atypical language representation in children with intractable temporal lobe epilepsy.

This study evaluated language organization in children with intractable epilepsy caused by temporal lobe focal cortical dysplasia (FCD) alone or dual pathology (temporal lobe FCD and hippocampal sclerosis, HS). We analyzed clinical, neurological, fMRI, neuropsychological, and histopathologic data in 46 pediatric patients with temporal lobe lesions who underwent excisional epilepsy surgery. The frequency of atypical language representation was similar in both groups, but children with dual pathology were more likely to be left-handed. Atypical receptive language cortex correlated with lower intellectual capacity, verbal abstract conceptualization, receptive language abilities, verbal working memory, and a history of status epilepticus but did not correlate with higher seizure frequency or early seizure onset. Histopathologic substrate had only a minor influence on neuropsychological status. Greater verbal comprehension deficits were noted in children with atypical receptive language representation, a risk factor for cognitive morbidity.

How Extended Is Wernicke's Area? Meta-Analytic Connectivity Study of BA20 and Integrative Proposal.

Understanding the functions of different brain areas has represented a major endeavor of contemporary neurosciences. The purpose of this paper was to pinpoint the connectivity of Brodmann area 20 (BA20) (inferior temporal gyrus, fusiform gyrus) in language tasks. A meta-analysis was conducted to assess the language network in which BA20 is involved. The DataBase of Brainmap was used; 11 papers corresponding to 12 experimental conditions with a total of 207 subjects were included in this analysis. Our results demonstrated seven clusters of activation including other temporal lobe areas (BA3, BA21), the insula, and the prefrontal cortex; minor clusters in the cingulate gyrus and the occipital lobe were observed; however, the volumes of all the activation clusters were small. Our results suggest that regardless of BA20 having certain participation in language processes it cannot be considered as a core language processing area (Wernicke's area); nonetheless, it could be regarded as kind of language processing marginal area, participating in "extended Wernicke's area" or simply "Wernicke's system." It is suggested that "core Wernicke's area" roughly corresponds to BA21, BA22, BA41, and BA42, while a "language associations area" roughly corresponds to BA20, BA37, BA38, BA39, and BA40 ("extended Wernicke's area" or "Wernicke's system").

Connectivity of BA46 involvement in the executive control of language.

BACKGROUND: Understanding the functions of different brain areas has represented a major endeavor of contemporary neurosciences. Modern neuroimaging developments suggest cognitive functions are associated with networks rather than with specific areas. OBJECTIVES: The purpose of this paper was to analyze the connectivity of Brodmann area (BA) 46 (anterior middle frontal gyrus) in relation to language. METHODS: A meta-analysis was conducted to assess the language network in which BA46 is involved. The DataBase of Brainmap was used; 19 papers corresponding to 60 experimental conditions with a total of 245 subjects were included. RESULTS: Our results suggest the core network of BA46. The localization and modules involved suggest BA46 participation in a "frontal language production system" (or extended Broca's system). The depicted BA46 connectivity is also concordant with a minor role in language semantics and language understanding. CONCLUSION: It was concluded that BA46 plays a central role in the language production system, most likely related to its executive control.

[The language area of the brain: a functional reassessment]. / Área cerebral del lenguaje: una reconsideración functional.

INTRODUCTION: During the late 19th and early 20th century, a 'brain language area' was proposed corresponding to the peri-Sylvian region of the left hemisphere as concluded by clinical observations. This point of view has continued up today. AIM: Departing from contemporary neuroimaging studies, to re-analyze the location and extension the brain language area with regard to the different Brodmann areas. MATERIALS AND METHODS: Using the method known as metaanalytic connectivity modeling seven meta-analytic studies of fMRI activity during the performance of different language tasks are analyzed. RESULTS: It was observed that two major brain systems can be distinguished: lexical/semantic, related with the Wernicke's area, that includes a core Wernicke's area (recognition of words) and an extended Wernicke's area (word associations); and grammatical system (language production and grammar) corresponding to the Broca's complex in the frontal lobe, and extending subcortically It is proposed that the insula plays a coordinating role in interconnecting these two brain language systems. CONCLUSIONS: Contemporary neuroimaging studies suggest that the brain language are is notoriously more extended than it was assumed one century ago based on clinical observations. As it was assumed during the 19th century, the insula seemingly plays a critical role in language.

TITLE: Area cerebral del lenguaje: una reconsideracion funcional.Introduccion. Hacia finales del siglo XIX y comienzos del siglo XX, y basandose en observaciones clinicas, se propuso que existe un 'area del lenguaje' en el cerebro que corresponde, en general, a la region perisilviana del hemisferio izquierdo. Tal idea ha continuado existiendo desde entonces. Objetivo. Partiendo de los estudios contemporaneos de imagenes cerebrales, reanalizar la localizacion y extension del area del lenguaje con relacion a las diferentes areas de Brodmann. Materiales y metodos. Utilizando la metodologia conocida como metaanalytic connectivity modeling, se revisan varios estudios metaanaliticos en los cuales se analizan las imagenes de resonancia magnetica funcional durante la realizacion de tareas linguisticas. Resultados. Se encontro que existen dos sistemas linguisticos diferentes en el cerebro: un sistema lexico/semantico, relacionado con el area de Wernicke, y que incluye un area de Wernicke central (reconocimiento de palabras) y un area de Wernicke extendida (asociaciones linguisticas); y un sistema gramatical, dependiente del complejo de Broca (produccion del lenguaje y gramatica), en el lobulo frontal, y que se extiende subcorticalmente. Se propone tambien que la insula desempeña un papel de coordinacion de estos dos sistemas linguisticos cerebrales. Conclusion. Los estudios contemporaneos de neuroimagen sugieren que el area del lenguaje en el cerebro es notoriamente mas amplia de lo que se supuso hace un siglo basandose en observaciones clinicas. Tal como se consideraba durante el siglo XIX, la insula parece desempeñar un papel critico en el lenguaje.

How Localized are Language Brain Areas? A Review of Brodmann Areas Involvement in Oral Language.

The interest in understanding how language is "localized" in the brain has existed for centuries. Departing from seven meta-analytic studies of functional magnetic resonance imaging activity during the performance of different language activities, it is proposed here that there are two different language networks in the brain: first, a language reception/understanding system, including a "core Wernicke's area" involved in word recognition (BA21, BA22, BA41, and BA42), and a fringe or peripheral area ("extended Wernicke's area:" BA20, BA37, BA38, BA39, and BA40) involved in language associations (associating words with other information); second, a language production system ("Broca's complex:" BA44, BA45, and also BA46, BA47, partially BA6-mainly its mesial supplementary motor area-and extending toward the basal ganglia and the thalamus). This paper additionally proposes that the insula (BA13) plays a certain coordinating role in interconnecting these two brain language systems.

Pediatric applications of functional magnetic resonance imaging.

Pediatric functional MRI has been used for the last 2 decades but is now gaining wide acceptance in the preoperative workup of children with brain tumors and medically refractory epilepsy. This review covers pediatrics-specific difficulties such as sedation and task paradigm selection according to the child's age and cognitive level. We also illustrate the increasing uses of functional MRI in the depiction of cognitive function, neuropsychiatric disorders and response to pharmacological agents. Finally, we review the uses of resting-state fMRI in the evaluation of children and in the detection of epileptogenic regions.

Fiber tracking of the frontal aslant tract and subcomponents of the arcuate fasciculus in 5-8-year-olds: Relation to speech and language function.

Long association cortical fiber pathways support developing networks for speech and language, but we do not have a clear understanding of how they develop in early childhood. Using diffusion-weighted imaging (DWI) we tracked the frontal aslant tract (FAT), arcuate fasciculus (AF), and AF segments (anterior, long, posterior) in 19 typical 5-8-year-olds, an age range in which significant improvement in speech and language function occurs. While the microstructural properties of the FAT and the right AF did not show age-related differences over the age range we investigated, the left AF evidenced increasing fractional anisotropy with age. Microstructural properties of the AF in both hemispheres, however, predicted receptive and expressive language. Length of the left FAT also predicted receptive language, which provides initial suggestion that this pathway is important for language development. These findings have implications for models of language development and for models of the neurobiology of language more broadly.

Broca's area network in language function: a pooling-data connectivity study.

BACKGROUND AND OBJECTIVE: Modern neuroimaging developments have demonstrated that cognitive functions correlate with brain networks rather than specific areas. The purpose of this paper was to analyze the connectivity of Broca's area based on language tasks. METHODS: A connectivity modeling study was performed by pooling data of Broca's activation in language tasks. Fifty-seven papers that included 883 subjects in 84 experiments were analyzed. Analysis of Likelihood Estimates of pooled data was utilized to generate the map; thresholds at p < 0.01 were corrected for multiple comparisons and false discovery rate. Resulting images were co-registered into MNI standard space. RESULTS: A network consisting of 16 clusters of activation was obtained. Main clusters were located in the frontal operculum, left posterior temporal region, supplementary motor area, and the parietal lobe. Less common clusters were seen in the sub-cortical structures including the left thalamus, left putamen, secondary visual areas, and the right cerebellum. CONCLUSION: Broca's area-44-related networks involved in language processing were demonstrated utilizing a pooling-data connectivity study. Significance, interpretation, and limitations of the results are discussed.

[Angular gyrus connectivity model for language: a functional neuroimaging meta-analysis]. / Modelo de conectividad de la circunvolución angular en el lenguaje: metaanálisis de neuroimágenes funcionales.

INTRODUCTION: Modern functional neuroimaging techniques permit the analysis of the simultaneous activation of diverse brain areas to suggest cognitive connectivity models related to specific cognitive functions. AIM: To analyze the functional networks of the angular gyrus (Brodmann area 39) related to language functions. MATERIALS AND METHODS: The database of BrainMap was used to analyze the activation coordinates of the angular gyrus and brain related areas while performing different language tasks. Eight articles were selected that included 13 experiments, 155 participants and 265 loci. RESULTS: Sixteen activation clusters made a network that included the activation of the two angular gyri, the superior right parietal lobe and right supramarginal gyri; the superior left temporal lobe (middle lateral and medial inferior), and the frontal lobe (bilateral premotor and left prefrontal). CONCLUSIONS: Our findings are in agreement with previous findings using structural connectivity techniques and support the integrative role of the angular gyrus in language functions.

TITLE: Modelo de conectividad de la circunvolucion angular en el lenguaje: metaanalisis de neuroimagenes funcionales.Introduccion. Las tecnicas modernas de neuroimagen funcional permiten analizar la activacion simultanea de diversas areas cerebrales y sugerir modelos de conectividad para funciones cognitivas especificas. Objetivo. Realizar un metaanalisis de las redes funcionales de la region angular (area de Brodmann 39) con relacion al lenguaje. Materiales y metodos. Partiendo de la base de datos BrainMap, se analizaron las coordenadas de activacion en estudios de resonancia magnetica funcional que mostraban una activacion del area de Brodmann 39 durante la realizacion de tareas linguisticas. Se seleccionaron ocho articulos con 13 experimentos, que incluian un total de 155 sujetos, y 265 localizaciones. Resultados. Los resultados mostraron 16 conglomerados de activacion significativos que conformaban una red de coactivacion, la cual incluia las dos regiones angulares, el lobulo parietal superior y la circunvolucion supramarginal derechos, el lobulo temporal izquierdo (cara lateral medial y cara medial inferior) y el lobulo frontal (premotor bilateral y prefrontal izquierdo). Conclusiones. Estos resultados coinciden con los hallazgos obtenidos con tecnicas de conectividad estructural y apoyan el papel integrador de la region angular en funciones linguisticas.