Search

Background Functional connectivity abnormalities between Broca’s and Wernicke’s areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca’s and Wernicke’s areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca’s-Wernicke’s-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP. Methods White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI). Results FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different. Conclusions Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca’s and Wernicke’s areas. Other bilateral tracts’ gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.

An accumulating body of evidence suggests that transcranial direct current stimulation (tDCS) can be used to affect language processing, including word acquisition. There has been, however, no comprehensive study of effects of tDCS of the core language areas in relation to the main word-learning mechanisms. Two principal strategies have been posited as important for natural word acquisition: explicit encoding (EE) which relies on direct instructions and repetition of material, and fast mapping (FM) which operates implicitly, via context-based inference or deduction. We used anodal and cathodal tDCS of Broca's and Wernicke's areas to assess effects of stimulation site and polarity on novel word acquisition in both EE and FM regimes. 160 participants, divided into five groups, received 15 min of cathodal or anodal tDCS over one of the two areas or a sham (placebo) stimulation before learning eight novel words, presented ten times each in a short naturalistic audio-visual word-picture association session, fully counterbalanced across different learning regimes. The outcome of novel word acquisition was measured immediately after the training using a free recall task. The results showed elevated accuracy in all real stimulation groups in comparison with sham stimulation; however, this effect only reached full significance after anodal tDCS of Broca's area. Comparisons between the two learning modes indicated that Broca's anodal tDCS significantly improved both implicit and explicit acquisition of novel vocabulary in comparison with sham tDCS, without, however, any significant differences between EE and FM regimes as such. The results indicate involvement of the left inferior-frontal neocortex in the learning of novel vocabulary and suggest a possibility to promote different types of word acquisition using anodal tDCS of this area.

AIM: This investigation aims to advance the understanding of neural dynamics that underlies live and natural interactions during spoken dialogue between two individuals. INTRODUCTION: The underlying hypothesis is that functional connectivity between canonical speech areas in the human brain will be modulated by social interaction. METHODS: Granger causality was applied to compare directional connectivity across Broca's and Wernicke's areas during verbal conditions consisting of interactive and noninteractive communication. Thirty-three pairs of healthy adult participants alternately talked and listened to each other while performing an object naming and description task that was either interactive or not during hyperscanning with functional near-infrared spectroscopy (fNIRS). In the noninteractive condition, the speaker named and described a picture-object without reference to the partner's description. In the interactive condition, the speaker performed the same task but included an interactive response about the preceding comments of the partner. Causality measures of hemodynamic responses from Broca's and Wernicke's areas were compared between real, surrogate, and shuffled trials within dyads. RESULTS: The interactive communication was characterized by bidirectional connectivity between Wernicke's and Broca's areas of the listener's brain. Whereas this connectivity was unidirectional in the speaker's brain. In the case of the noninteractive condition, both speaker's and listener's brains showed unidirectional top-down (Broca's area to Wernicke's area) connectivity. CONCLUSION: Together, directional connectivity as determined by Granger analysis reveals bidirectional flow of neuronal information during dynamic two-person verbal interaction for processes that are active during listening (reception) and not during talking (production). Findings are consistent with prior contrast findings (general linear model) showing neural modulation of the receptive language system associated with Wernicke's area during a two-person live interaction. IMPACT STATEMENT: The neural dynamics that underlies real-life social interactions is an emergent topic of interest. Dynamically coupled cross-brain neural mechanisms between interacting partners during verbal dialogue have been shown within Wernicke's area. However, it is not known how within-brain long-range neural mechanisms operate during these live social functions. Using Granger causality analysis, we show bidirectional neural activity between Broca's and Wernicke's areas during interactive dialogue compared with a noninteractive control task showing only unidirectional activity. Findings are consistent with an Interactive Brain Model where long-range neural mechanisms process interactive processes associated with rapid and spontaneous spoken social cues.

Einleitung: Die repetitive transkranielle Magnetstimulation (rTMS) ist ein nicht-invasives, schmerzarmes Stimulationsverfahren, welches die Erregbarkeit des stimulierten Hirnareals auch nach der Stimulation verändern kann. Die Eigenschaft, auch nach der Stimulation anhaltend zu wirken, macht die rTMS interessant in der Neurologie und Psychiatrie. Es gibt hier vielversprechende Therapieansätze, allerdings ist grundlegend noch weiter zu erforschen, welche Stimulationsprotokolle welche Wirkung haben und ob sie auf alle Areale so anwendbar sind. Ein Großteil der Studien wurde am motorischen Kortex durchgeführt. Hier konnte eine Inhibierung durch niedrige Frequenzen (≤1Hz) sowie kontinuierliche Theta Burst Stimulation (cTBS) und eine Fazilitierung durch höhere Frequenzen (≥3Hz) und intermittierende Theta Burst Stimulation (iTBS) gesehen werden. Weitere Studien geben Hinweise daraufhin, dass eine Wirksamkeit an anderen Hirnarealen ähnlich ist. So konnte eine Vorgängerstudie zeigen, dass die inhibierende Wirkung durch cTBS und 1Hz rTMS auf das Wernickeareal übertragbar war. In der vorliegenden Studie erfolgte schließlich der Vergleich der am motorischen Kortex fazilitierenden Protokolle iTBS und 20Hz rTMS am Wernickeareal. Material und Methoden: Teilnehmer des Experiments waren je Gruppe zehn weibliche und zehn männliche Probanden zwischen 18 und 30 Jahren, die entweder studierten oder den Abschluss der allgemeinen Hochschulreife erlangt hatten. Zusätzlich zu der iTBS und 20Hz rTMS wurden zwei Kontrollgruppen untersucht, eine ohne Stimulation und eine mit Stimulation eines Kontrollareals (Brodmannareal 9). Vor der Stimulation wurde eine Magnetresonanztomographie (MRT) des Schädels der Probanden angefertigt, um so mit dem Navigationsgerät spezifisch stimulieren zu können. Im Anschluss an die rTMS erfolgte die lexikalische Entscheidungsaufgabe, bei welcher die Probanden so schnell und so korrekt wie möglich mittels Tastendruck entscheiden sollten, ob es sich beim angezeigten Wort um ein echtes Wort oder ein Pseudowort handelte. Ergebnisse: Es zeigte sich ein signifikanter Unterschied zwischen den Reaktionszeiten der iTBS-Gruppe und den anderen Gruppen. Die Probanden, die mit iTBS am Wernickeareal stimuliert wurden, waren bei der Wortentscheidungsaufgabe also signifikant schneller als die aller anderen Gruppen. Zusätzlich wurde ein Haupteffekt für „Wortart“ gefunden, welcher zeigte, dass die Reaktionszeiten der Pseudoworte signifikant länger waren. Außerdem waren die Probanden unabhängig von Gruppe und Wortart in der zweiten Hälfte der lexikalischen Entscheidungsaufgabe signifikant schneller als in der Ersten. Diskussion: Der Effekt der iTBS auf die Reaktionszeiten legt nahe, dass es durch dieses Stimulationsprotokoll zu einer Fazilitierung des Wernickeareals gekommen sein könnte. Es scheint also, dass die im Motorkortex beobachtete Wirkung der iTBS auch auf höhere kognitive Funktionen übertragbar und anwendbar ist. Fraglich ist jedoch, warum die 20Hz Stimulation nicht ebenfalls wie erwartet zu einer Fazilitierung geführt hat. Möglichkeiten wären eine Voraktivität des stimulierten Areals aufgrund von verbalen Äußerungen, welche es in dieser Gruppe während der Stimulation gegeben hat, oder die Monotonie der 20Hz Stimulation in Gegensatz zur kurzen iTBS und die dadurch größere mögliche Müdigkeit der Probanden in der 20Hz rTMS Gruppe. Um dieser Frage weiter nachzugehen, sind Änderungen im Versuchsaufbau sicherlich hilfreich. Schlussfolgerung: Es kann davon ausgegangen werden, dass die iTBS zur Fazilitierung des Wernickeareals geführt hat und damit zur Erhöhung der Erregbarkeit auch nicht-motorischer Areale appliziert werden kann. So scheint es plausibel, die im Motorkortex charakterisierten inhibierenden (cTBS) und fazilitierenden (iTBS) Protokolle gleichsinnig auch in Arealen im Zusammenhang mit höheren kognitiven Funktionen einzusetzen. Die TBS, welche im Vergleich zur konventionellen rTMS kürzer und weniger unangenehm ist, wird so sicherlich weiter an Bedeutung auch als Therapieverfahren gewinnen.

Frontiers in neuroscience 15, 680762 (2021). doi:10.3389/fnins.2021.680762 special issue: "Shared Genetic Risk Factors among Psychiatric Diseases and other Medical Diseases and Traits", Published by Frontiers Research Foundation, Lausanne

BACKGROUND AND PURPOSE: Temporal lobe epilepsy, structural or nonlesional, may negatively affect language function. However, little is known about the lesion-specific influence on language networks. We hypothesized that different epileptogenic lesions are related to distinct alterations in the functional language connectome detected by fMRI. MATERIALS AND METHODS: One hundred one patients with epilepsy due to mesiotemporal sclerosis (21 left, 22 right), low-grade mesiotemporal tumors (12 left), or nonlesional temporal lobe epilepsy (22 left, 24 right) and 22 healthy subjects performed 3T task-based language fMRI. Task-based activation maps (laterality indices) and functional connectivity analysis (global and connectivity strengths between language areas) were correlated with language scores. RESULTS: Laterality indices based on fMRI activation maps failed to discriminate among patient groups. Functional connectivity analysis revealed the most extended language network alterations in left mesiotemporal sclerosis (involving the left temporal pole, left inferior frontal gyrus, and bilateral premotor areas). The other patient groups showed less extended but also predominantly ipsilesional network changes compared with healthy controls. Left-to-right hippocampal connectivity strength correlated positively with naming function (P = .01), and connectivity strength between the left Wernicke area and the left hippocampus was linked to verbal fluency scores (P = .01) across all groups. CONCLUSIONS: Different pathologies underlying temporal lobe epilepsy are related to distinct alterations of the functional language connectome visualized by fMRI functional connectivity analysis. Network analysis allows new insights into language organization and provides possible imaging biomarkers for language function. These imaging findings emphasize the importance of a personalized treatment strategy in patients with epilepsy.

Rationale: We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT). Patient concerns: The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset. Diagnosis: A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory. Intervention: Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset). Outcomes: On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker. Lessons: We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.

Perinatal stroke affects child's language development and can change language lateralization. Language generation and comprehension tasks in functional magnetic resonance imaging were used to determine language lateralization in term born children with perinatal left-side arterial ischemic stroke (AIS) (n = 9, mean age (SD) 13.4 (3.1) y.) and periventricular venous infarction (PVI) (n = 12, 11.8 (2.8) y.), and in healthy right-handed controls (n = 30, 11.6 (2.6) y.). Lateralization index was calculated for the Broca and Wernicke areas and correlated with language and cognitive outcomes measured by the Kaufman Assessment Battery for Children II ed. Language outcome in children with perinatal stroke is poorer compared to healthy controls. Children with small AIS lesions and most children with PVI showed left-side language activation. Most children with large AIS lesions and one child with large PVI had language activation reorganized to the right hemisphere. Language reorganization to the unlesioned right hemisphere did not ensure normal language outcome.

Determining the impact that the KIAA0319 gene has on primate brain morphology can provide insight into the evolution of human cognition and language systems. Here, we tested whether polymorphisms in KIAA0319 in chimpanzees account for gray matter volumetric variation in brain regions implicated in language and communication (particularly within the posterior superior temporal gyrus and inferior frontal gyrus). First, we identified the nature and frequencies of single nucleotide variants (SNVs) in KIAA0319 in a sample of unrelated chimpanzees (Pan troglodytes spp.). Next, we genotyped a subset of SNVs (those important for gene regulation or likely to alter protein structure/function) in a sample of chimpanzees for which in vivo T1-structural magnetic resonance imaging scans had been obtained. We then used source-based morphometry (SBM) to test for whole-brain gray matter covariation differences between chimpanzees with different KIAA0319 alleles. Finally, using histologic sections of 15 postmortem chimpanzee brains, we analyzed microstructural variation related to KIAA0319 polymorphisms in the posterior superior temporal cortex. We found that the SNVs were associated with variation in gray matter within several brain regions, including the posterior superior temporal gyrus (a region associated with language comprehension and production in humans). The microstructure analysis further revealed hemispheric differences in neuropil fraction, indicating that KIAA0319 expression may be involved in regulation of processes related to the formation and maintenance of synapses, dendrites, or axons within regions associated with communication.

This study used structural magnetic resonance imaging to examine whether specific anatomical features of Broca's and Wernicke's areas are related to language functions in typically developing older subjects with no specific language expertise. Data from 231 subjects from the Zurich LHAB-study are used for this study. For these subjects, we obtained several psychometric measures from which we calculated performance measures reflecting specific psychological functions (language comprehension, verbal fluency, perceptual speed, visual memory, recognition of regularities, and logical thinking). From the MRI measurements, we calculated the cortical thickness and cortical surface of Broca's and Wernicke's areas. Applying multiple regression analyses, we identified a moderately strong relationship between language comprehension and the brain metrics from Broca's and Wernicke's areas and showed that approximately 10% of the variance in language comprehension performance is explained by the linear combination of all perisylvian brain metrics. The other psychological functions (verbal fluency, perceptual speed, visual memory, recognition of regularities, and logical thinking) are not related to these brain metrics. Subsequent detailed analyses revealed that the cortical thickness of Wernicke's area, in particular, contributed most to this structure-function relationship. The better performance in the language comprehension tests was related to a thicker cortex in Wernicke's area. Thus, this study demonstrates a structure-function relationship between the anatomical features of the perisylvian language areas and language comprehension, suggesting that particular anatomical features are associated with better language performance.

Objective Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere. Methods Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study. Cognitive performances were analyzed regarding an influence of patient characteristics and tumor localization. Results Severe impairment in at least one neurocognitive domain was found in 36 (83.7%) patients. Anxiety and depression were observed most frequently, followed by verbal memory impairments. Verbal memory was more strongly affected in patients with ATL or pST/SMG tumors compared to IFG tumors (p = 0.004 and p = 0.013, resp.). Overall, patients suffering from tumors in the ATL were most frequently and severely impaired. Conclusion Patients suffering from gliomas involving different regions within the language dominant hemisphere frequently present impairments in neurocognitive domains also other than language. Considering individual functions at risk may help in better advising patients prior to treatment and in tailoring the individual therapeutic strategy to preserve patients' quality of life.

[Background] Surgical resection of diffuse low-grade gliomas (DLGGs) involving cortical eloquent areas and subcortical functional pathways represents a challenge in neurosurgery. Patient-specific, 3-dimensional (3D)-printed models of head and brain structures have emerged in recent years as an educational and clinical tool for patients, doctors, and surgical residents., [Methods] Using multimodal high-definition magnetic resonance imaging data, which incorporates information from specific task-based functional neuroimaging and diffusion tensor imaging tractography and rapid prototyping technologies with specialized software and “in-house” 3D printing, we were able to generate 3D-printed head models that were used for preoperative patient education and consultation, surgical planning, and resident training in 2 complicated DLGG surgeries., [Results] This 3D-printed model is rapid prototyped and shows a means to model individualized, diffuse, low-level glioma in 3D space with respect to cortical eloquent areas and subcortical pathways. Survey results from 8 surgeons with different levels of expertise strongly support the use of this model for surgical planning, intraoperative surgical guidance, doctor-patient communication, and surgical training (>95% acceptance)., [Conclusions] Spatial proximity of DLGG to cortical eloquent areas and subcortical tracts can be readily assessed in patient-specific 3D printed models with high fidelity. 3D-printed multimodal models could be helpful in preoperative patient consultation, surgical planning, and resident training., Funding for this technical paper was received from the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (PI14/01823, PI16/01575, PI18/01898, PI19/01576), Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526, CTS-7685), Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0471–2013, PE-0210–2018, PI-0459–2018, PE-0186–2019), the Fundación Alicia Koplowitz and the Spanish Ministry of Science and Innovation “Retos Colaboración” 2019 program (TC2019–007150–1). Jose Gomez-Feria Ferreiro is supported by the Spanish Ministry of Education, Culture and Sports (FPU16/03550). The Hospital Virgen del Rocío Fabrication Laboratory is partially funded by (PIN-0213–2018) 3D printing Laboratory for Andalusian Public Health Service. Juan F Martín-Rodríguez is supported by the VI-PPIT-US from the University of Seville (USE-18817-A).

Objective We studied age-related dynamics of information sharing among cortical language regions with electrocorticographic high-gamma modulation during picture-naming and story-listening tasks. Methods Seventeen epilepsy patients aged 4-19 years, undergoing extraoperative monitoring with left-hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial-averaged 70-150 Hz power modulations during language tasks. Impact of age on pairwise MI between language regions and their determinants were ascertained with regression analysis. Results During picture naming, significant increase in MI with age was seen between pairwise combinations of Broca's area, inferior precentral gyrus (iPreC), and frontal association cortex (FAC); Wernicke's area and posterior association cortex (PAC); and Broca's and Wernicke's areas. During story listening, significant age-related increase in MI was seen between Wernicke's area and either Broca's area, FAC, or PAC; and between Broca's area and FAC. Significant impact of baseline intelligence quotient was seen on the relationship between age and MI for all pairs, except between Broca's area and iPreC. The mean MI was higher during naming compared to listening for pairs including iPreC with Broca's area, FAC, or PAC and was lower for pairs of Wernicke's area or PAC with anterior language regions. Significance Information sharing matures with age "within" frontal and temporoparietal language cortices, and "between" Broca's and Wernicke's areas. This study provides evidence for distinct patterns of developmental plasticity within perisylvian language cortex and has implications for planning epilepsy surgery.

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).

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.

ObjectiveTo explore atrophy–deficit correlations of word comprehension and repetition in temporoparietal cortices encompassing the Wernicke area, based on patients with primary progressive aphasia (PPA).MethodsCortical thickness in regions within and outside the classical Wernicke area, measured by FreeSurfer, was correlated with repetition and single word comprehension scores in 73 right-handed patients at mild to moderate stages of PPA.ResultsAtrophy in the Wernicke area was correlated with repetition (r = 0.42, p = 0.001) but not single word comprehension (r = −0.072, p = 0.553). Correlations with word comprehension were confined to more anterior parts of the temporal lobe, especially its anterior third (r = 0.60, p < 0.001). A single case with postmortem autopsy illustrated preservation of word comprehension but not repetition 6 months prior to death despite nearly 50% loss of cortical volume and severe neurofibrillary degeneration in core components of the Wernicke area.ConclusionsTemporoparietal cortices containing the Wernicke area are critical for language repetition. Contrary to the formulations of classic aphasiology, their role in word and sentence comprehension is ancillary rather than critical. Thus, the Wernicke area is not sufficient to sustain word comprehension if the anterior temporal lobe is damaged. Traditional models of the role of the Wernicke area in comprehension are based almost entirely on patients with cerebrovascular lesions. Such lesions also cause deep white matter destruction and acute network diaschisis, whereas progressive neurodegenerative diseases associated with PPA do not. Conceptualizations of the Wernicke area that appear to conflict, therefore, can be reconciled by considering the hodologic and physiologic differences of the underlying lesions.

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

Introduction The aim of this study was to determine in pre- and postsurgical fMRI studies the rearrangement of the Broca's and Wernicke's areas and the lateralization index for these areas in patients with brain tumors located near speech centers. Impact of the surgical treatment on the brain plasticity was evaluated. Materials and methods Pre- and postoperative fMRI examinations were performed in 10 patients with low grade glial, left-sided brain tumors located close to the Broca's (5 patients) or Wernicke's area (5 patients). BOLD signal was recorded in regions of interest: Broca's and Wernicke's areas, and their anatomic right-sided homologues. Results In the preoperative fMRI study the left Broca's area was activated in all cases. The right Broca's area was activated in all the patients with no speech disorders. In the postoperative fMRI the activation of both Broca's areas increased in two cases. In other two cases activation of one of the Broca's area increased along with the decrease in the contralateral hemisphere. In all patients with temporal lobe tumors, the right Wernicke's area was activated in the pre- and postsurgical fMRI. After the operation, in two patients with speech disorder, the activation of both Broca's areas decreased and the activation of one of the Wernicke's areas increased. Conclusions In the cases of tumors localized near the left Broca's area, a transfer of the function to the healthy hemisphere seems to take place. Resection of tumors located near Broca's or Wernicke's areas may lead to relocation of the brain language centers.

ObjectiveTo combine MRI-based cortical morphometry and diffusion white matter tractography to describe the anatomical correlates of repetition deficits in patients with primary progressive aphasia (PPA).MethodsThe traditional anatomical model of language identifies a network for word repetition that includes Wernicke and Broca regions directly connected via the arcuate fasciculus. Recent tractography findings of an indirect pathway between Wernicke and Broca regions suggest a critical role of the inferior parietal lobe for repetition. To test whether repetition deficits are associated with damage to the direct or indirect pathway between both regions, tractography analysis was performed in 30 patients with PPA (64.27 ± 8.51 years) and 22 healthy controls. Cortical volume measurements were also extracted from 8 perisylvian language areas connected by the direct and indirect pathways.ResultsCompared to healthy controls, patients with PPA presented with reduced performance in repetition tasks and increased damage to most of the perisylvian cortical regions and their connections through the indirect pathway. Repetition deficits were prominent in patients with cortical atrophy of the temporo-parietal region with volumetric reductions of the indirect pathway.ConclusionsThe results suggest that in PPA, deficits in repetition are due to damage to the temporo-parietal cortex and its connections to Wernicke and Broca regions. We therefore propose a revised language model that also includes an indirect pathway for repetition, which has important clinical implications for the functional mapping and treatment of neurologic patients.

In the present study we investigated 90 musicians of both sexes who possess different degrees of absolute pitch (AP) using diffusion tensor imaging in association with a correlational approach and evaluated whether there are differences in perisylvian connections depending on the proficiency level of AP. We expected higher fractional anisotropy with increasing AP ability in the white matter underlying perisylvian brain areas. Results revealed a significant positive correlation between the proficiency level of AP and fractional anisotropy values in the left-sided white matter underlying the planum temporale. We interpret this result as an indicator of auditory processing differences between musicians possessing different degrees of AP, reflecting early auditory encoding and categorization processes. The present study provides further evidence for the substantial importance of the left-sided planum temporale for the ability of AP.

OBJECTIVEThe dominant inferior parietal lobe (IPL) contains cortical and subcortical structures that serve language processing. A high incidence of postoperative short-term aphasia and good potential for language reorganization have been observed. The authors’ goal was to study the plasticity of the language cortex and language-related fibers in patients with brain arteriovenous malformations (BAVMs) located in the IPL.METHODSA total of 6 patients who underwent microsurgical treatment of an IPL BAVM were prospectively recruited between September 2016 and May 2018. Blood oxygen level–dependent functional MRI (BOLD-fMRI) and diffusion tensor imaging (DTI) were performed within 1 week before and 6 months after microsurgery. Language-related white matter (WM) eloquent fiber tracts and their contralateral homologous fiber tracts were tracked. The Western Aphasia Battery was administered to assess language function. The authors determined the total number of fibers and mean fractional anisotropy (FA) indices for each individual tract. In addition, they calculated the laterality index (LI) between the activated language cortex voxels in the lesional and contralesional hemispheres and compared these indices between the preoperative and postoperative fMR and DT images.RESULTSOf the 6 patients with IPL BAVMs, all experienced postoperative short-term language deficits, and 5 (83.3%) recovered completely at 6 months after surgery. Five patients (83.3%) had right homologous reorganization of BOLD signal activations in both Broca’s and Wernicke’s areas. More fibers were observed in the arcuate fasciculus (AF) in the lesional hemisphere than in the contralesional hemisphere (1905 vs 254 fibers, p = 0.035). Six months after surgery, a significantly increased number of fibers was seen in the right hemispheric AF (249 fibers preoperatively vs 485 postoperatively, p = 0.026). There were significantly more nerve fibers in the postoperative left inferior frontooccipital fasciculus (IFOF) (874 fibers preoperatively vs 1186 postoperatively, p = 0.010). A statistically significant increase in right hemispheric dominance of Wernicke’s area was observed. The overall functional LI showed functional lateralization of Wernicke’s area in the right hemisphere (LI ≤ −0.20) in all patients.CONCLUSIONSThe authors’ findings provide evidence for the functional reorganization by recruiting the right hemispheric homologous region of Broca’s and Wernicke’s areas, right hemispheric AFs, and left hemispheric IFOFs following resection of IPL BAVMs.Clinical trial registration no.: NCT02868008 (clinicaltrials.gov)

The arcuate fasciculus (AF) has been implicated in its association with intelligence. Probabilistic tractography on diffusion tensor imaging (DTI) data provides isolation of white matter tracts between two distant cortical structures. In this study, we performed probabilistic tractography between Wernicke’s and Broca’s area in the left and right hemisphere, to examine the association of the arcuate fasciculus’s integrity with age and intelligence, using DTI data from 488 individuals whose age ranges between 6 to 85 years. The left, but not right, AF showed significant decline with age. Both left and right AF showed significant association with the full-scale IQ measured by the Wechsler Abbreviated Intelligence Scale. Both fasciculi showed significant association with the subscale verbal IQ, but only the left showed performance IQ. This study demonstrates that the bilateral arcuate fasciculi are associated with IQ; left vs. right asymmetry is present in its aging and function.

We describe frontal language reorganization in a 50-60 year-old right-handed patient with a low-grade left frontotemporal insular glioma. Pre-operative fMRI revealed robust activation in the left superior temporal gyrus (Wernicke Area, WA) and in the right inferior frontal gyrus (right anatomical homologue of Broca Area, BA). Intra-operative cortical stimulation of the left inferior frontal gyrus and adjacent cortices elicited no speech deficits, and gross total resection including the expected location of BA resulted in no speech impairment. We employed statistical inference methods to reconstruct the functional brain network and determined how different brain areas connect with one another. We found that the right homologue of the BA in this patient functionally connected to the same areas as the left BA in a typical healthy control. As opposed to the functional connection of the left BA in a healthy brain, the right BA did not connect directly with the left WA, but connected indirectly, mediated by the pre-Supplementary Motor Area and the Middle Frontal Gyrus. This case illustrates that pre-surgical fMRI may be used to identify atypical hemispheric language reorganization in the presence of brain tumor and that network theory opens the possibility for future insight into the neural mechanism underlying the language reorganization.

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.

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 ± 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.

A 24-year-old woman was referred to us for an intracranial haemorrhage in the left temporal lobe caused by a ruptured cavernous malformation; the bleeding extended over the left Heschl’s gyrus and Wernicke area. On admission, the patient had global aphasia. A few days later, she spontaneously improved but remained with mild residual comprehensive dysphasia. She reported hearing, in her right ear, recently heard words, which is consistent with palinacousis. Auditory acuity testing was normal. EEG showed focal slowing in the left temporal region with no epileptiform activity. During awake surgery for resection of the cavernous malformation, stimulation of the superior temporal gyrus did not provoke palinacousis. The patient made good recovery with complete resolution of the aphasia and no recurrence of palinacousis. We aimed to review this phenomenon and to provide a systematic review of the current literature.

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.

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on the constrains for interaction between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer reconstructed tracks along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer tracks in the left compared to the right side. In addition, there were significant positive correlations between PANSS scores and track length, track volume, and number of track streamlines for the posterior AF segment on the left side. It is concluded that the present DTI results may have implications for interpretations of functional imaging results. publishedVersion

Objective We aimed to predict language deficits after epilepsy surgery. In addition to evaluating surgical factors examined previously, we determined the impact of the extent of functional magnetic resonance imaging (fMRI) activation that was resected on naming ability. Method Thirty-five adults (mean age 37.5 ± 10.9 years, 13 male) with temporal lobe epilepsy completed a preoperative fMRI auditory description decision task, which reliably activates frontal and temporal language networks. Patients underwent temporal lobe resections (20 left resection). The Boston Naming Test (BNT) was used to determine language functioning before and after surgery. Language dominance was determined for Broca and Wernicke area (WA) by calculating a laterality index following statistical parametric mapping processing. We used an innovative method to generate anatomic resection masks automatically from pre- and postoperative MRI tissue map comparison. This mask provided the following: (a) resection volume; (b) overlap between resection and preoperative activation; and (c) overlap between resection and WA. We examined postoperative language change predictors using stepwise linear regression. Predictors included parameters described above as well as age at seizure onset (ASO), preoperative BNT score, and resection side and its relationship to language dominance. Results Seven of 35 adults had significant naming decline (6 dominant-side resections). The final regression model predicted 38% of the naming score change variance (adjusted r2 = 0.28, P = 0.012). The percentage of top 10% fMRI activation resected (P = 0.017) was the most significant contributor. Other factors in the model included WA LI, ASO, volume of WA resected, and WA LI absolute value (extent of laterality). Significance Resection of fMRI activation during a word-definition decision task is an important factor for postoperative change in naming ability, along with other previously reported predictors. Currently, many centers establish language dominance using fMRI. Our results suggest that the amount of the top 10% of language fMRI activation in the intended resection area provides additional predictive power and should be considered when planning surgical resection.

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.” Methods: One hundred trials for each word were recorded for both imagination and perception, although this study utilized only imagination data. Two different connectivity methods were applied, namely; a covariance-based and a maximum linear cross-correlation-based connectivity measure. These connectivity measures were further computed to extract the phase-only data as an additional method of feature extraction. In addition, four different channel selections were used. The final connectivity matrix from each of the four methods was vectorized and used as the feature vector for the classifier. To classify EEG data, a sigmoid activation function-based linear extreme learning machine was used. Result and Significance: We achieved a maximum classification rate of 40.30% ( p $ 0.007) and 87.90% ( p $ 0.003) in multiclass (five classes) and binary settings, respectively. Thus, our results suggested that EEG responses to imagined speech could be successfully classified using an extreme learning machine. Conclusion: This study involving the classification of imagined words can be a milestone contribution toward the development of practical brain–computer interface systems using silent speech.

The authors attempted to demonstrate the difference in language cortex reorganization between cerebral malformations (AVMs), cavernous malformations (CMs), and gliomas by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Clinical and imaging data of 27 AVM patients (AVM-L group), 29 CM patients (CM-L group), and 20 glioma patients (Glioma-L group) were retrospectively reviewed, with lesions overlying the left inferior frontal gyrus (Broca area). As a control, patients with lesions involving the right inferior frontal gyrus were also enrolled, including 14 AVM patients (AVM-R group), 20 CM patients (CM-R group), and 14 glioma patients (Glioma-R group). All patients were right-handed. Lateralization indices (LI) of BOLD signal activations were calculated separately for Broca and Wernicke areas. In AVM-L group, right-sided lateralization of BOLD signals was observed in 10 patients (37.0 %), including 6 in the Broca area alone, 1 in the Wernicke area alone, and 3 in both areas. Three patients (10.3 %) of CM-L group showed right-sided lateralization in both Broca and Wernicke areas, and 1 patient (5.0 %) of Glioma-L group had right-sided lateralization in the Wernicke area alone. A significant difference of right-sided lateralization was observed between the AVM-L group and CM-L group (P = 0.018) and also between the AVM-L group and Glioma-L group (P = 0.027). No patient in AVM-R, CM-R, or Glioma-R groups showed right-sided lateralization. Language cortex reorganization may occur in AVM, CM, and glioma patients when the traditional language cortex was involved by lesions, but the potential of reorganization for CM and glioma patients seems to be insufficient compared with AVM patients.

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.

OBJECT Cerebral arteriovenous malformations (AVMs) are congenital malformations that may grow in the language cortex but usually do not lead to aphasia. In contrast, language dysfunction is a common presentation for patients with a glioma that involves language areas. The authors attempted to demonstrate the difference in patterns of language cortex reorganization between cerebral AVMs and gliomas by blood oxygen level–dependent (BOLD) functional MRI (fMRI) evaluation. METHODS The authors retrospectively reviewed clinical and imaging data of 63 patients with an unruptured cerebral AVM (AVM group) and 38 patients with a glioma (glioma group) who underwent fMRI. All the patients were right handed, and all their lesions were located in the left cerebral hemisphere. Patients were further categorized into 1 of the 2 following subgroups according to their lesion location: the BA subgroup (overlying or adjacent to the inferior frontal or the middle frontal gyri [the Broca area]) and the WA subgroup (overlying or adjacent to the supramarginal, angular, or superior temporal gyri [the Wernicke area]). Lateralization indices of BOLD signal activations were calculated separately for the Broca and Wernicke areas. Statistical analysis was performed to identify the difference in patterns of language cortex reorganization between the 2 groups. RESULTS In the AVM group, right-sided lateralization of BOLD signal activations was observed in 23 patients (36.5%), including 6 with right-sided lateralization in the Broca area alone, 12 in the Wernicke area alone, and 5 in both areas. More specifically, in the 34 patients in the AVM-BA subgroup, right-sided lateralization of the Broca area was detected in 9 patients (26.5%), and right-sided lateralization of the Wernicke area was detected in 4 (11.8%); in the 29 patients in the AVM-WA subgroup, 2 (6.9%) had right-sided lateralization of the Broca area, and 13 (44.8%) had right-sided lateralization of the Wernicke area. In the glioma group, 6 patients (15.8%) showed right-sided lateralization of the Wernicke area, including 2 patients in the glioma-BA subgroup and 4 patients in the glioma-WA subgroup. No patient showed right-sided lateralization of the Broca area. Moreover, although the incidence of right-sided lateralization was higher in cases of low-grade gliomas (5 in 26 [19.2%]) than in high-grade gliomas (1 in 12 [8.3%]), no significant difference was detected between them (p = 0.643). Compared with the AVM group, the incidence of aphasia was significantly higher (p < 0.001), and right-sided lateralization of language areas was significantly rarer (p = 0.026) in the glioma group. CONCLUSIONS Right-sided lateralization of BOLD signal activations was observed in patients with a cerebral AVM and in those with a glioma, suggesting that language cortex reorganization may occur with both diseases. However, the potential of reorganization in patients with gliomas seems to be insufficient compared with patients AVMs, which is suggested by clinical manifestations and the fMRI findings. Moreover, this study seems to indicate that in patients with an AVM, a nidus near the Broca area mainly leads to right-sided lateralization of the Broca area, and a nidus near the Wernicke area mainly leads to right-sided lateralization of the Wernicke area.