tDCS of right-hemispheric Wernicke's area homologue affects contextual learning of novel lexicon.

Numerous studies have shown robust evidence of the right hemisphere's involvement in the language function, for instance in the processing of intonation, grammar, word meanings, metaphors, etc. However, its role in lexicon acquisition remains obscure. We applied transcranial direct current stimulation (tDCS) over the right-hemispheric homologue of Wernicke's area to assess its putative involvement in the processing of different types of novel semantics. After receiving 15 min of anodal, cathodal, or sham (placebo) tDCS, three groups of healthy participants learnt novel concrete and abstract words in the context of short stories. Learning outcomes were assessed using a battery of tests immediately after this contextual learning session and 24 h later. As a result, an inhibitory effect of cathodal tDCS and a facilitatory effect of anodal tDCS were found for abstract word acquisition only. We also found a significant drop in task performance on the second day of the assessment for both word types in all the stimulation groups, suggesting no significant influence of tDCS on the post-learning consolidation of new memory traces. The results suggest an involvement of Wernicke's right-hemispheric counterpart in initial encoding (but not consolidation) of abstract semantics, which may be explained either by the right hemispheres direct role in processing lexical semantics or by an indirect impact of tDCS on contralateral (left-hemispheric) cortical areas through cross-callosal connections.

Effects of transcranial magnetic stimulation over the left posterior superior temporal gyrus on picture-word interference.

Word-production theories argue that during language production, a concept activates multiple lexical candidates in left temporal cortex, and the intended word is selected from this set. Evidence for theories on spoken-word production comes, for example, from the picture-word interference task, where participants name pictures superimposed by congruent (e.g., picture: rabbit, distractor "rabbit"), categorically related (e.g., distractor "sheep"), or unrelated (e.g., distractor "fork") words. Typically, whereas congruent distractors facilitate naming, related distractors slow down picture naming relative to unrelated distractors, resulting in semantic interference. However, the neural correlates of semantic interference are debated. Previous neuroimaging studies have shown that the left mid-to-posterior STG (pSTG) is involved in the interference associated with semantically related distractors. To probe the functional relevance of this area, we targeted the left pSTG with focal repetitive transcranial magnetic stimulation (rTMS) while subjects performed a picture-word interference task. Unexpectedly, pSTG stimulation did not affect the semantic interference effect but selectively increased the congruency effect (i.e., faster naming with congruent distractors). The facilitatory TMS effect selectively occurred in the more difficult list with an overall lower name agreement. Our study adds new evidence to the causal role of the left pSTG in the interaction between picture and distractor representations or processing streams, only partly supporting previous neuroimaging studies. Moreover, the observed unexpected condition-specific facilitatory rTMS effect argues for an interaction of the task- or stimulus-induced brain state with the modulatory TMS effect. These issues should be systematically addressed in future rTMS studies on language production.

Is it possible to detect cerebral dominance via EEG signals by using deep learning?

Each brain hemisphere is dominant for certain functions such as speech. The determination of speech laterality prior to surgery is of paramount importance for accurate risk prediction. In this study, we aimed to determine speech laterality via EEG signals by using noninvasive machine learning techniques. The retrospective study included 67 subjects aged 18-65 years who had no chronic diseases and were diagnosed as healthy based on EEG examination. The subjects comprised 35 right-hand dominant (speech center located in the left hemisphere) and 32 left-hand dominant individuals (speech center located in the right hemisphere). A spectrogram was created for each of the 18 EEG channels by using various Convolutional Neural Networks (CNN) architectures including VGG16, VGG19, ResNet, MobileNet, NasNet, and DenseNet. These architectures were used to extract features from the spectrograms. The extracted features were classified using Support Vector Machines (SVM) and the classification performances of the CNN models were evaluated using Area Under the Curve (AUC). Of all the CNN models used in the study, VGG16 had a higher AUC value (0.83 ±â€¯0.05) in the determination of speech laterality compared to all other models. The present study is a pioneer investigation into the determination of speech laterality via EEG signals with machine learning techniques, which, to our knowledge, has never been reported in the literature. Moreover, the classification results obtained in the study are promising and lead the way for subsequent studies though not practically feasible.

Transcranial Direct Current Stimulation (tDCS) of Wernicke's and Broca's Areas in Studies of Language Learning and Word Acquisition.

Language is a highly important yet poorly understood function of the human brain. While studies of brain activation patterns during language comprehension are abundant, what is often critically missing is causal evidence of brain areas' involvement in a particular linguistic function, not least due to the unique human nature of this ability and a shortage of neurophysiological tools to study causal relationships in the human brain noninvasively. Recent years have seen a rapid rise in the use of transcranial direct current stimulation (tDCS) of the human brain, an easy, inexpensive and safe noninvasive technique that can modulate the state of the stimulated brain area (putatively by shifting excitation/inhibition thresholds), enabling a study of its particular contribution to specific functions. While mostly focusing on motor control, the use of tDCS is becoming more widespread in both basic and clinical research on higher cognitive functions, language included, but the procedures for its application remain variable. Here, we describe the use of tDCS in a psycholinguistic word-learning experiment. We present the techniques and procedures for application of cathodal and anodal stimulation of core language areas of Broca and Wernicke in the left hemisphere of the human brain, describe the procedures of creating balanced sets of psycholinguistic stimuli, a controlled yet naturalistic learning regime, and a comprehensive set of techniques to assess the learning outcomes and tDCS effects. As an example of tDCS application, we show that cathodal stimulation of Wernicke's area prior to a learning session can impact word learning efficiency. This impact is both present immediately after learning and, importantly, preserved over longer time after the physical effects of stimulation wear off, suggesting that tDCS can have long-term influence on linguistic storage and representations in the human brain.

Anodal tDCS over Wernicke's area improves verbal memory and prevents the interference effect during words learning.

BACKGROUND: Wernicke's area is a key component of the cortical language network, and it is functionally related to the comprehension of oral and written language. In addition to its main role in the perception of language, some other functions related to verbal learning also seem to involve the activity of this cortical region. It is unknown whether different degrees of neuromodulation on this area determine its effect on word learning. OBJECTIVE: We aimed to analyze the influence of the application of anodal transcranial DC stimulation (tDCS) over Wernicke's area at two different intensities on word learning. METHOD: We compared the effect of anodal tDCS at an intensity of 0.5 mA and 1.5 mA with sham tDCS, separately in different groups, on performance in a word learning and recall task. RESULTS: The results show that 1.5 mA anodal tDCS improved performance. The number of words learned in this condition was higher compared with stimulation at 0.5 mA current strength and sham stimulation. Furthermore, stimulation with 1.5 mA specifically prevented the interference effect over word learning, compared to the other two tDCS conditions. CONCLUSIONS: These results show an intensity-dependent effect of anodal tDCS on verbal memory formation. These findings are discussed in the context of the various functions of Wernicke's area and the ability of tDCS to modulate the activity and functionality of this cortical area at different intensities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Single Word Auditory Comprehension (SWAC) test: A simple method to identify receptive language areas with electrical stimulation.

OBJECTIVES: Resective surgery for medically refractory epilepsy in proximity to speech receptive areas requires balancing adequate resection of the epileptogenic zone for optimal seizure control with preservation of function. We develop a simple test (Single Word Auditory Comprehension or SWAC) to localize speech receptive areas by evaluating patients' ability to comprehend a single word. METHODS: Patients were studied during presurgical or intraoperative assessment for epilepsy with intracranial electrodes. They were asked to listen to a common word (target word) and to describe what it meant without saying the target word. Electrical stimulation (trains of biphasic 2-ms pulses, 50 Hz for 3 s) was delivered while the patient listened to the target word, not while the patient explained the meaning of the word. In six patients, SWAC test was carried out during extraoperative chronic recordings, and in one patient in the operating theater under local anesthesia. RESULTS: Among the 7 patients where the test identified deficits, 6 underwent resection (4 temporal, 1 supramarginal, and 1 occipital). Two patients showed temporary minor speech deficits after resection. No patient showed permanent speech deficits after resection. CONCLUSION/SIGNIFICANCE: The SWAC test is reliable, simple and fast to implement, and suitable for intraoperating mapping. It could be used as a simple initial test to identify receptive language areas where more complex additional tests can be performed.

Multiclass Classification of Word Imagination Speech with Hybrid Connectivity Features.

OBJECTIVE: In this study, electroencephalography data of imagined words were classified using four different feature extraction approaches. Eight subjects were recruited for the recording of imagination with five different words, namely; 'go', 'back', 'left', 'right', and 'stop'.

Silent Sentence Completion Shows Superiority Localizing Wernicke's Area and Activation Patterns of Distinct Language Paradigms Correlate with Genomics: Prospective Study.

Preoperative mapping of language areas using fMRI greatly depends on the paradigms used, as different tasks harness distinct capabilities to activate speech processing areas. In this study, we compared the ability of 3 covert speech paradigms: Silent Sentence Completion (SSC), category naming (CAT) and verbal fluency (FAS), in localizing the Wernicke's area and studied the association between genomic markers and functional activation. Fifteen right-handed healthy volunteers and 35 mixed-handed patients were included. We focused on the anatomical areas of posterosuperior, middle temporal and angular gyri corresponding to Wernicke's area. Activity was deemed significant in a region of interest if P < 0.05. Association between fMRI activation and genomic mutation status was obtained. Results demonstrated SSC's superiority at localizing Wernicke's area. SSC demonstrated functional activity in 100% of cancer patients and healthy volunteers; which was significantly higher than those for FAS and CAT. Patients with 1p/19q non-co-deleted had higher extent of activation on SSC (P < 0.02). Those with IDH-1 wild-type were more likely to show no activity on CAT (P < 0.05). SSC is a robust paradigm for localizing Wernicke's area, making it an important clinical tool for function-preserving surgeries. We also found a correlation between tumor genomics and functional activation, which deserves more comprehensive study.

Current Controversies on Wernicke's Area and its Role in Language.

PURPOSE OF REVIEW: The aim of the study is to assess historical anatomical and functional definitions of Wernicke's area in light of modern lesion and neuroimaging data. RECENT FINDINGS: "Wernicke's area" has become an anatomical label usually applied to the left posterior superior temporal gyrus and adjacent supramarginal gyrus. Recent evidence shows that this region is not critical for speech perception or for word comprehension. Rather, it supports retrieval of phonological forms (mental representations of phoneme sequences), which are used for speech output and short-term memory tasks. Focal damage to this region produces phonemic paraphasia without impairing word comprehension, i.e., conduction aphasia. Neuroimaging studies in recent decades provide evidence for a widely distributed temporal, parietal, and frontal network supporting language comprehension, which does not include the anatomically defined Wernicke area. The term Wernicke's area, if used at all, should not be used to refer to a zone critical for speech comprehension.

Consecutive TMS-fMRI reveals remote effects of neural noise to the "occipital face area".

The human cortical system for face perception comprises a network of connected regions including the middle fusiform gyrus ("fusiform face area" or FFA), the inferior occipital gyrus ("occipital face area" or OFA), and the posterior superior temporal sulcus (pSTS). Here, we sought to investigate how transcranial magnetic stimulation (TMS) to the OFA affects activity within the face processing network. We used offline repetitive TMS to temporarily introduce neural noise in the right OFA in healthy subjects. We then immediately performed functional magnetic resonance imaging (fMRI) to measure changes in blood oxygenation level dependent (BOLD) signal across the face network using an fMR-adaptation (fMR-A) paradigm. We hypothesized that TMS to the right OFA would induce abnormal face identity coding throughout the face processing network in regions to which it has direct or indirect connections. Indeed, BOLD signal for face identity, but not non-face (butterfly) identity, decreased in the right OFA and FFA following TMS to the right OFA compared to both sham TMS and TMS to a control site, the nearby object-related lateral occipital area (LO). Further, TMS to the right OFA decreased face-related activation in the left FFA, without any effect in the left OFA. Our findings indicate that TMS to the right OFA selectively disrupts face coding at both the stimulation site and bilateral FFA. TMS to the right OFA also decreased BOLD signal for different identity stimuli in the right pSTS. Together with mounting evidence from patient studies, we demonstrate connectivity of the OFA within the face network and that its activity modulates face processing in bilateral FFA as well as the right pSTS. Moreover, this study shows that deep regions within the face network can be remotely probed by stimulating structures closer to the cortical surface.

Broca and Wernicke are dead, or moving past the classic model of language neurobiology.

With the advancement of cognitive neuroscience and neuropsychological research, the field of language neurobiology is at a cross-roads with respect to its framing theories. The central thesis of this article is that the major historical framing model, the Classic "Wernicke-Lichtheim-Geschwind" model, and associated terminology, is no longer adequate for contemporary investigations into the neurobiology of language. We argue that the Classic model (1) is based on an outdated brain anatomy; (2) does not adequately represent the distributed connectivity relevant for language, (3) offers a modular and "language centric" perspective, and (4) focuses on cortical structures, for the most part leaving out subcortical regions and relevant connections. To make our case, we discuss the issue of anatomical specificity with a focus on the contemporary usage of the terms "Broca's and Wernicke's area", including results of a survey that was conducted within the language neurobiology community. We demonstrate that there is no consistent anatomical definition of "Broca's and Wernicke's Areas", and propose to replace these terms with more precise anatomical definitions. We illustrate the distributed nature of the language connectome, which extends far beyond the single-pathway notion of arcuate fasciculus connectivity established in Geschwind's version of the Classic Model. By illustrating the definitional confusion surrounding "Broca's and Wernicke's areas", and by illustrating the difficulty integrating the emerging literature on perisylvian white matter connectivity into this model, we hope to expose the limits of the model, argue for its obsolescence, and suggest a path forward in defining a replacement.

Cortico-cortical evoked hemodynamic responses in human language systems using intraoperative near-infrared spectroscopy during direct cortical stimulation.

BACKGROUND: Understanding of cortico-cortical activity in eloquent areas intraoperatively is crucial for neurosurgical procedures. Here, we used intraoperative near-infrared spectroscopy (iNIRS) during direct cortical stimulation as a robust tool to better understand the cortico-cortical connectivity in language systems. METHODS: We applied iNIRS to 3 patients who underwent epilepsy surgery due to lesions (cavernous angioma, epidermoid cyst, and low-grade glioma) located in language areas. Using iNIRS, we measured the blood concentration changes of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) in the lateral temporal cortex during direct cortical stimulation (50Hz) at the inferior frontal area where Broca's area was probabilistically located. RESULTS: In all patients, 50Hz stimulation elicited hemodynamic changes in the superior temporal gyrus (STG). During 0.8-4.8s after stimulation, HbO2 increased and HbR decreased in the posterior part of the STG (Wernicke's area). Similar responses were observed in the anterior part of the STG 1.3-8.0s after stimulation. Finally, these changes were disappeared in the middle temporal gyrus. CONCLUSIONS: Our results suggest that cortical stimulation of Broca's area elicits hemodynamic responses in Wernicke's area via cortico-cortical connectivity. We demonstrated cortico-cortical evoked responses in language systems using iNIRS during direct cortical stimulation. Our iNIRS data will provide useful information about cortico-cortical networks underlying human brain functions intraoperatively and will contribute to neurosurgical treatment in eloquent areas.

Testosterone affects language areas of the adult human brain.

Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.

[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.

The Wernicke area: Modern evidence and a reinterpretation.

The term "Wernicke's area" is most often used as an anatomical label for the gyri forming the lower posterior left sylvian fissure. Although traditionally this region was held to support language comprehension, modern imaging and neuropsychological studies converge on the conclusion that this region plays a much larger role in speech production. This evidence is briefly reviewed, and a simple schematic model of posterior cortical language processing is described.

Age-Related Differences and Heritability of the Perisylvian Language Networks.

Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and their lateralization remains stable throughout adolescence and early adulthood. Conversely, the posterior segment shows right lateralization in childhood but becomes progressively bilateral during adolescence, driven by a reduction in volume in the right hemisphere. Analysis of the twin sample showed that genetic and shared environmental factors influence the anatomy of those segments that lateralize earlier, whereas specific environmental effects drive the variability in the volume of the posterior segment that continues to change in adolescence and adulthood. Our results suggest that the age-related differences in the lateralization of the language perisylvian pathways are related to the relative contribution of genetic and environmental effects specific to each segment. SIGNIFICANCE STATEMENT: Our study shows that, by early childhood, frontotemporal (long segment) and frontoparietal (anterior segment) connections of the arcuate fasciculus are left and right lateralized, respectively, and remain lateralized throughout adolescence and early adulthood. In contrast, temporoparietal (posterior segment) connections are right lateralized in childhood, but become progressively bilateral during adolescence. Preliminary twin analysis suggested that lateralization of the arcuate fasciculus is a heterogeneous process that depends on the interplay between genetic and environment factors specific to each segment. Tracts that exhibit higher age effects later in life (i.e., posterior segment) appear to be influenced more by specific environmental factors.

Use of Computational Modeling to Inform tDCS Electrode Montages for the Promotion of Language Recovery in Post-stroke Aphasia.

BACKGROUND: Although pilot trials of transcranial direct current stimulation (tDCS) in aphasia are encouraging, protocol optimization is needed. Notably, it has not yet been clarified which of the varied electrode montages investigated is the most effective in enhancing language recovery. OBJECTIVE: To consider and contrast the predicted brain current flow patterns (electric field distribution) produced by varied 1×1 tDCS (1 anode, 1 cathode, 5 × 7 cm pad electrodes) montages used in aphasia clinical trials. METHODS: A finite element model of the head of a single left frontal stroke patient was developed in order to study the pattern of the cortical EF magnitude and inward/outward radial EF under five different electrode montages: Anodal-tDCS (A-tDCS) over the left Wernicke's area (Montage A) and over the left Broca's area (Montage B); Cathodal tDCS (C-tDCS) over the right homologue of Wernicke's area (Montage C), and of Broca's area (Montage D), where for all montages A-D the "return" electrode was placed over the supraorbital contralateral forehead; bilateral stimulation with A-tDCS over the left Broca's and CtDCS over the right Broca's homologue (Montage E). RESULTS: In all cases, the "return" electrode over the contralesional supraorbital forehead was not inert and influenced the current path through the entire brain. Montage B, although similar to montage D in focusing the current in the perilesional area, exerted the greatest effect over the left perilesional cortex, which was even stronger in montage E. CONCLUSIONS: The position and influence of both electrodes must be considered in the design and interpretation of tDCS clinical trials for aphasia.

The right hemisphere contribution to semantic categorization: a TMS study.

A large amount of evidence suggests an involvement of the right hemisphere in lexical-semantic processing, but its specific contribution compared to the left hemisphere is not entirely clear. The present study investigated the contribution of both hemispheres to the semantic categorization process of words referring to typical and atypical exemplars. Transcranial Magnetic Stimulation (TMS) was used to interfere with the online activity of Wernicke's area and its right homologue during a verbal category membership task. The TMS delayed the responses to typical member nouns compared to the control condition, over both areas of interest. On the contrary, a delay in the responses to atypical member nouns was observed only when the right Wernicke's area was stimulated. Overall, these results indicate that while both hemispheres are involved in the categorization of typical exemplars, the right hemisphere specifically contributes to semantic categorization of atypical ones.