Search

The left posterior superior temporal gyrus (pSTG) is thought to be involved in the pathophysiology and core symptoms of schizophrenia, although its structural connectivity has not yet been systematically investigated. Here, we aimed to evaluate its white matter (WM) connectivity with Broca's area, the thalamus, and the right pSTG. Eighty-three patients with schizophrenia and 141 healthy controls underwent diffusion-weighted imaging and T1-weighted three-dimensional magnetic resonance imaging. Probabilistic tractography was performed from the left pSTG to the Broca area, the left thalamus, and the right pSTG. Group comparison of WM fractional anisotropy (FA) in these pathways, as well as its correlations with the pSTG volume and clinical characteristics in the patient group, were examined. Patients showed significantly lower FA in the left pSTG-Broca and left-right pSTG pathways, but not in the left pSTG-thalamus pathway. Patients also revealed a trend toward a smaller left pSTG volume. Significant negative correlations were found in patients between FA in the left-right pSTG pathway and the left pSTG volume, and between FA in the left pSTG-Broca pathway and positive symptom severity. The present results suggest fiber-specific alterations in structural connectivity linked to the left pSTG, possibly supporting the "inner speech" and "interhemispheric disconnection" hypotheses of schizophrenia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Transcranial direct current stimulation (tDCS) targeting Broca's area has shown promise for augmenting language production in post-stroke aphasia (PSA). However, previous research has been limited by small sample sizes and inconsistent outcomes. This study employed a double-blind, parallel, randomized, controlled design to evaluate the efficacy of anodal Broca's tDCS, paired with 20-minute speech and language therapy (SLT) focused primarily on expressive language, across 5 daily sessions in 45 chronic PSA patients. Utilizing the Western Aphasia Battery-Revised, which assesses a spectrum of linguistic abilities, we measured changes in both expressive and receptive language skills before and after intervention. The tDCS group demonstrated significant improvements over sham in aphasia quotient, auditory verbal comprehension, and spontaneous speech. Notably, tDCS improved both expressive and receptive domains, whereas sham only benefited expression. These results underscore the broader linguistic benefits of Broca's area stimulation and support the integration of tDCS with SLT to advance aphasia rehabilitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Functional MRI (fMRI) is gaining importance in the preoperative assessment of language for presurgical planning. However, inconsistencies with the Wada test might arise. This current case report describes a very rare case of an epileptic patient who exhibited bilateral distribution (right > left) in the inferior frontal gyrus (laterality index [LI] = -0.433) and completely right dominance in the superior temporal gyrus (LI = -1). However, the Wada test revealed a dissociation: his motor speech was located in the left hemisphere, while he could understand vocal instructions with his right hemisphere. A clinical implication is that the LIs obtained by fMRI should be cautiously used to determine Broca's area in atypical patients; for example, even when complete right dominance is found in the temporal cortex in right-handed patients. Theoretically, as the spatially separated functions of motor speech and language comprehension (by the combined results of fMRI and Wada) can be further temporally separated (by the intracarotid amobarbital procedure) in this case report, these findings might provide direct support to Broca's initial conclusions that Broca's area is associated with acquired motor speech impairment, but not language comprehension per se . Moreover, this current finding supports the idea that once produced, motor speech can be independent from language comprehension., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Objective: Subthreshold depression is an essential precursor and risk factor for major depressive disorder, and its accurate identification and timely intervention are important for reducing the prevalence of major depressive disorder. Therefore, we used functional near-infrared spectroscopic imaging (fNIRS) to explore the characteristics of the brain neural activity of college students with subthreshold depression in the verbal fluency task., Methods: A total of 72 subthreshold depressed college students (SDs) and 67 healthy college students (HCs) were recruited, and all subjects were subjected to a verbal fluency task (VFT) while a 53-channel fNIRS device was used to collect the subjects' cerebral blood oxygenation signals., Results: The results of the independent samples t-test showed that the mean oxyhemoglobin in the right dorsolateral prefrontal (ch34, ch42, ch45) and Broca's area (ch51, ch53) of SDs was lower than that of HCs. The peak oxygenated hemoglobin of SDs was lower in the right dorsolateral prefrontal (ch34) and Broca's area (ch51, ch53).The brain functional connectivity strength was lower than that of HCs. Correlation analysis showed that the left DLPFC and Broca's area were significantly negatively correlated with the depression level., Conclusion: SDs showed abnormally low, inadequate levels of brain activation and weak frontotemporal brain functional connectivity. The right DLPFC has a higher sensitivity for the differentiation of depressive symptoms and is suitable as a biomarker for the presence of depressive symptoms. Dysfunction in Broca's area can be used both as a marker of depressive symptoms and as a biomarker, indicating the severity of depressive symptoms., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oral automatism (OA) and manual automatism (MA) are common signs during initiation of temporal seizures. However, the precise symptomatogenic zones for OA and MA remains largely unclear. In this study, we presented a case of intractable frontal lobe epilepsy (FLE) in which the patient received intracranial EEG monitoring with subdural electrodes. During electrical stimulation of a grid contact located over the right pars opercularis cortex, OA and contralateral MA were observed unexpectedly without afterdischarges (ADs) or with brief ADs detected in the adjacent contacts. This case suggested that the pars opercularis cortex might play an important role in generating OA. In addition, our data implied that the symptomatogenic zone for MA might locate contralaterally to symptomatic hand., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Both hemispheres have role in post-stroke aphasia recovery but better recovery is expected with the restoration of function by the left hemisphere. Transcranial stimulation has been used to favor recruitment of left-hemispheric language networks and increase activity of the left hemisphere, thus helps aphasia recovery ., Objective: The aim of this study is to evaluate the effect of excitatory repetitive transcranial magnetic stimulation (rTMS) on recovery of post stroke aphasic patients ., Materials and Methods: Twenty patients with post stroke chronic aphasia were enrolled in the study. Aphasia severity was assessed using Aphasia Severity Rating Scale (ASRS). Linguistic deficits were assessed using Kasr Al-Aini Arabic Aphasia test (KAAT). Real rTMS was applied three for 10 sessions of 10-Hz stimulation, positioned over the left Broca's area of the affected hemisphere. All patients were evaluated before, after the end of treatment sessions and one month later ., Results: There was a significant improvement in the mean total score and mean scores of components of KAAT scale before, immediately after and after one month of rTMS (P< 0.05). Moreover, there was a significant improvement in mean scores of ASRS before, immediately after and after one month of rTMS (P= 0.000). There was a significant difference in mean scores of ASRS and KAAT before, immediately after the last session and after one month between small, medium and large brain infarcts. (P< 0.05)., Conclusion: Excitatory rTMS is a beneficial adjuvant therapy that improves language skills in patients with chronic post-stroke non-fluent aphasia in short and long term. The protocol of this observational study was registered in clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04708197., Competing Interests: Declaration of Competing Interest Authors have no competing interest, and the work was not supported by any organization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics., Methods: Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis., Results: We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems., Conclusions: Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Focal brain lesions, such as stroke and tumors, can lead to remote structural alterations across the whole-brain networks. Brain arteriovenous malformations (AVMs), usually presumed to be congenital, often result in tissue degeneration and functional displacement of the perifocal areas, but it remains unclear whether AVMs may produce long-range effects upon the whole-brain white matter organization. In this study, we used diffusion tensor imaging and graph theory methods to investigate the alterations of brain structural networks in 14 patients with AVMs in the presumed Broca's area, compared to 27 normal controls. Weighted brain structural networks were constructed based on deterministic tractography. We compared the topological properties and network connectivity between patients and normal controls. Functional magnetic resonance imaging revealed contralateral reorganization of Broca's area in five (35.7%) patients. Compared to normal controls, the patients exhibited preserved small-worldness of brain structural networks. However, AVM patients exhibited significantly decreased global efficiency ( p = 0.004) and clustering coefficient ( p = 0.014), along with decreased corresponding nodal properties in some remote brain regions ( p < 0.05, family-wise error corrected). Furthermore, structural connectivity was reduced in the right perisylvian regions but enhanced in the perifocal areas ( p < 0.05). The vulnerability of the left supramarginal gyrus was significantly increased ( p = 0.039, corrected), and the bilateral putamina were added as hubs in the AVM patients. These alterations provide evidence for the long-range effects of AVMs on brain white matter networks. Our preliminary findings contribute extra insights into the understanding of brain plasticity and pathological state in patients with AVMs., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Maogui Li et al.)

Objective: To 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)., Methods: The 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., Results: Compared 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., Conclusions: The 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., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Social anxiety disorder is characterized by a marked fear and avoidance of social situations or a fear of being evaluated by others. Although training for top-down attentional control has been an effective treatment for social anxiety disorder, few studies have demonstrated that individuals with social anxiety have top-down attentional dysfunction. This study used dichotic listening (DL) tasks to investigate the relationship between social anxiety and top-down attentional control over relevant brain activities. We also investigated relationships between both social situation-dependent self-focused attention and external attention bias and situation-independent attentional control. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing top-down selective and divided attention DL tasks. Then, they undertook a speech task and completed a questionnaire to assess the degrees of their self-focused attention and external attention bias. The results showed that the degree of social fear and self-focused attention during the speech task were negatively correlated with scores on the selective attention task and with the activity of the left pars opercularis during the selective DL task, which were related to each other. These results suggest that a relationship exists between social fear, self-focused attention in a social situation, and top-down selective attentional dysfunction as assessed both behaviorally and by brain activity changes.

A large body of evidence indicates that both the altered cytokines that mediate the immune-inflammatory process and abnormal gray matter are associated with schizophrenia. Whether peripheral cytokines are related to cerebral structural abnormality remains unclear. Therefore, we aimed to investigate the association of peripheral cytokine levels with gray matter abnormalities at the whole brain level in schizophrenia. Forty-four outpatients with schizophrenia and 44 controls were recruited. The serum levels of interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), and IL-10 were measured using a quantitative chemiluminescence assay. High-resolution T1 weighted images were acquired from all subjects and processed using FreeSurfer software to obtain the cortical thickness, surface area, and cortical and subcortical gray matter volumes. The cytokines and cerebral structures were compared between patients and controls using analysis of covariance (ANCOVA). The association between the cytokines and whole cerebral structures was performed using stepwise linear regression. Patients had higher levels of IL-2, IL-6, IL-8, and IL-10 than controls. In patients, the IL-6 level was significantly associated with the cortical thickness in the left pars opercularis, right pars triangularis, left superior temporal gyrus, and right middle temporal gyrus, which showed structural differences between the two groups. Altered cytokine levels may be associated with particular but not all cortical abnormalities in schizophrenia, especially IL-6, which was significantly associated with the abnormal cortical thickness of the bilateral Broca's area and temporal gyrus, which provided neuroimaging evidence to support the relationship between peripheral cytokines and the cerebral cortex in schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Previous research associated the left inferior frontal cortex with implicit structure learning. The present study tested patients with lesions encompassing the left inferior frontal gyrus (LIFG; including Brodmann areas 44 and 45) to further investigate this cognitive function, notably by using non-verbal material, implicit investigation methods, and by enhancing potential remaining function via dynamic attending. Patients and healthy matched controls were exposed to an artificial pitch grammar in an implicit learning paradigm to circumvent the potential influence of impaired language processing., Methods: Patients and healthy controls listened to pitch sequences generated within a finite-state grammar (exposure phase) and then performed a categorization task on new pitch sequences (test phase). Participants were not informed about the underlying grammar in either the exposure phase or the test phase. Furthermore, the pitch structures were presented in a highly regular temporal context as the beneficial impact of temporal regularity (e.g. meter) in learning and perception has been previously reported. Based on the Dynamic Attending Theory (DAT), we hypothesized that a temporally regular context helps developing temporal expectations that, in turn, facilitate event perception, and thus benefit artificial grammar learning., Results: Electroencephalography results suggest preserved artificial grammar learning of pitch structures in patients and healthy controls. For both groups, analyses of event-related potentials revealed a larger early negativity (100-200 msec post-stimulus onset) in response to ungrammatical than grammatical pitch sequence events., Conclusions: These findings suggest that (i) the LIFG does not play an exclusive role in the implicit learning of artificial pitch grammars, and (ii) the use of non-verbal material and an implicit task reveals cognitive capacities that remain intact despite lesions to the LIFG. These results provide grounds for training and rehabilitation, that is, learning of non-verbal grammars that may impact the relearning of verbal grammars., Competing Interests: The authors have declared that no competing interests exist.

Objective: To examine gray (GM) and white matter (WM) structural changes in regions of the speech network (SpN) in ALS patients with varying degree of bulbar disease. Methods: T1 and DTI images were obtained for 19 ALS participants and 13 neurologically-intact controls. Surface-based, volumetric, and DTI metrics were obtained for 6 regions-of-interest (ROIs) including the primary motor cortex (PMC), pars triangularis (parsT), pars opercularis (ParsO), posterior superior temporal gyrus (pSTG), and transverse temporal (TT). Disease-effects and brain-behavioral correlates between neuroanatomy and clinical measures of bulbar, limb, and overall disability were examined using linear models. Results: Structural changes were observed in the right oral and limb PMC and left ParsT, TT, and pSTG in ALS. Bulbar motor dysfunction was associated with WM abnormalities in the right oral PMC and left pSTG, and GM changes in bilateral TT. In contrast, symptom progression rate predicted GM and WM changes in bilateral pars opercularis (part of Broca's area). Grip strength and disease duration models were non-significant. Conclusions: The findings suggested that regions of the left-dominant SpN may be implicated in ALS and degeneration of these areas are related to bulbar disease severity. Involvement of regions that overlap across multiple connectomes such as Broca's area, however, may be dependent on the rate of disease progression. The work contributes to our understanding of bulbar ALS subtype, which is crucial for predicting disease progression, delivering targeted clinical care, and appropriate recruitment into clinical trials.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been used experimentally to facilitate naming abilities in individuals with chronic post-stroke aphasia. However, little is known about how rTMS confers clinical improvement, hampering its therapeutic value. The present study investigated the characteristics of naming failure that improve following administration of continuous theta burst stimulation (cTBS)-an inhibitory form of rTMS-to the right pars triangularis (rPTr) in persons with chronic aphasia., Methods: Eleven participants with chronic aphasia following left hemisphere stroke named pictures prior to and immediately following cTBS of the rPTr and a control site (vertex) in separate sessions. Prior to stimulation, we obtained two baseline measurements of picture naming ability to determine the extent and type (i.e., phonological vs. semantic) of naming impairment. Items presented for naming during stimulation were those that were named incorrectly in one or both of the baseline sessions (i.e., inconsistent vs. wrong items, respectively). Analyses assessed whether cTBS effects differed depending on the severity and/or type of naming impairment., Results: Relative to vertex, cTBS of the rPTr improved naming of inconsistent, but not wrong, items for individuals with more severe baseline naming impairment. Critically, baseline phonological but not semantic naming impairment severity marginally correlated with improved accuracy overall, and significantly correlated with decreased phonological errors following rPTr stimulation., Conclusion: CTBS of the rPTr enhances naming by facilitating phonological access during word retrieval, indicating that individuals whose naming impairment is localized to this stage of processing may be most likely to benefit from this rTMS approach., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Connectivity modeling in functional neuroimaging has become widely used method of analysis for understanding functional architecture. One method for deriving directed connectivity models is Group Iterative Multiple Model Estimation (GIMME; Gates and Molenaar, 2012). GIMME looks for commonalities across the sample to detect signal from noise and arrive at edges that exist across the majority in the group ("group-level edges") and individual-level edges. In this way, GIMME obtains generalizable results via the group-level edges while also allowing for between subject heterogeneity in connectivity, moving the field closer to obtaining reliable personalized connectivity maps. In this article, we present a novel extension of GIMME, confirmatory subgrouping GIMME, which estimates subgroup-level edges for a priori known groups (e.g. typically developing controls vs. clinical group). Detecting edges that consistently exist for individuals within predefined subgroups aids in interpretation of the heterogeneity in connectivity maps and allows for subgroup-specific inferences. We describe this algorithm, as well as several methods to examine the results. We present an empirical example that finds similarities and differences in resting state functional connectivity among four groups of children: typically developing controls (TDC), children with autism spectrum disorder (ASD), children with Inattentive (ADHD-I) and Combined (ADHD-C) Type ADHD. Findings from this study suggest common involvement of the left Broca's area in all the clinical groups, as well as several unique patterns of functional connectivity specific to a given disorder. Overall, the current approach and proof of principle findings highlight a novel and reliable tool for capturing heterogeneity in complex mental health disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stroke is the third leading cause of death in the developed world and the primary cause of adult disability. The most common site of stroke is the middle cerebral artery (MCA), an artery that supplies a range of areas involved in both language and motor function. As a consequence, many stroke patients experience a combination of language and motor deficits. Indeed, those suffering from Broca's aphasia have an 80% chance of also suffering hemiplegia. Despite the prevalence of multifaceted disability in patients, the current trend in both clinical trials and clinical practice is toward compartmentalization of dysfunction. In this article, we review evidence that aphasia and hemiplegia do not just coexist, but that they interact. We review a number of clinical reports describing how therapies for one type of deficit can improve recovery in the other and vice versa. We go on to describe how language deficits should be seen as a warning to clinicians that the patient is likely to experience motor impairment and slower motor recovery, aiding clinicians to optimize their choice of therapy. We explore these findings and offer a tentative link between language and arm function through their shared need for sequential action, which we term fluency. We propose that area BA44 (part of Broca's area) acts as a hub for fluency in both movement and language, both in terms of production and comprehension.

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., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Aim: Previous functional imaging studies demonstrate that people who stutter (PWS) exhibit over- and under-activation of Broca's and Wernicke's areas and their right hemisphere homologues when speaking. However, it is unclear whether this altered activation represents the neural cause of speech dysfluency or a secondary compensatory activation in PWS. To clarify the functional significance of the altered activation pattern in classic language areas and their right homologues, we examined whether the severity of stuttering was affected when the activation of these areas was modulated by brain stimulation., Methods: While PWS read passages aloud, we applied transcranial direct current stimulation (tDCS) using electrode montages that included an anodal or cathodal electrode placed over one of the language areas and its right hemisphere homologue, with the second electrode placed over the contralateral supraorbital region. Each participant underwent both anodal and cathodal tDCS sessions, each of which included a sham stimulation. Effects of stimulation polarity and electrode location on the frequency of stuttering were analyzed., Results: We observed a significant interaction between polarity and location on the frequency of stuttering. Follow-up analyses revealed that a tDCS montage including the cathodal electrode over right Broca's area (RB) significantly reduced the frequency of stuttering., Conclusion: The results indicated that stuttering severity was ameliorated when overactivation in RB was reduced by tDCS. This observation further suggests that speech dysfluency in PWS may be caused either by functional alteration in RB or by abnormal activation in speech motor control areas that are connected with RB., (© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.)

To assess the within-subject intra-scan session repeatability of language functional MRI (fMRI) activation maps in patients with brain tumors who were undergoing presurgical fMRI as part of their preoperative clinical workup. Sentence completion (SC) and silent word generation (SWG) tasks were used for language localization and hemispheric lateralization for identifying the primary language cortex. Within-subject repeatability for each of these paradigms was assessed in right-handed patients-37 for SC and 78 for SWG. Repeatability of activation maps between consecutive runs of the same task within the same scan session was evaluated by comparing lateralization indexes in holohemispheric and regional language areas. Displacement of center of activation between consecutive runs was also used to assess the repeatability of activation maps. Holohemispheric and regional language lateralization results demonstrated high intra-subject intra-scan repeatability when lateralization indices were calculated using threshold-dependent and threshold-independent approaches. The high repeatability is demonstrated both when centers of mass of activation are considered within key eloquent regions of the brain, such as Broca's area and Wernicke's area, as well as in larger more inclusive expressive and receptive language regions. We examined two well-known and widely accepted language tasks that are known to activate eloquent language cortex. We have demonstrated very high degree of repeatability at a single-subject level within single scan sessions of language mapping in a large cohort of brain tumor patients undergoing presurgical fMRI across several years at our institution., (© 2018 Wiley Periodicals, Inc.)

Despite the frequent suggestion in the literature that Broca's area is a common link between vocal and gestural models of the origins of language, this has never been established within a single motor-production study. In the present functional MRI experiment, participants were asked to describe the spatial properties of objects (e.g. a motorcycle) using speech, pantomime, and drawing. Pairwise conjunction analyses revealed that the left inferior gyrus - in combination with the left basal ganglia and ventral anterior thalamus - was jointly activated for the production of speech and pantomime but not for the conjunctions with drawing. Drawing and pantomime instead showed strong overlap in the intraparietal sulcus and superior parietal region bilaterally. These results provide the first demonstration in a production study that Broca's area is jointly activated by speech and gesture when depicting the same semantic content.

Background: Intraoperative functional cortical mapping using direct electrical stimulation may show a wider individual variability than suggested by noninvasive imaging data of healthy subjects., Methods: We assessed intraoperative variability of the frontal eye fields and the speech arrest sites in adult patients who underwent awake craniotomy with direct electrostimulation for treatment of diffuse gliomas located within eloquent regions, and we compared findings with human cortical parcellation of the Human Connectome Project., Results: The frontal eye fields were defined by intraoperative direct electrostimulations (14.3% of patients) projected on the superior subdivision of the premotor cortex covering the areas defined as frontal eye fields (parcel index 10), area 55b (parcel index 12), and premotor eye field (parcel index 11) and in the posterior part of the dorsolateral prefrontal cortex covering the areas defined as inferior 6-8 transitional area (parcel index 97), area 8Av (parcel index 67), and area 8C (parcel index 73). The speech arrest sites were defined by intraoperative direct electrostimulations (100% of patients) projected predominantly posteriorly to the inferior frontal gyrus in the inferior subdivision of the premotor cortex, that is, rostral area 6 (parcel index 78), ventral area 6 (parcel index 54), and area 43 (parcel index 99)., Conclusions: Intraoperative functional cortical mapping using direct electrostimulation highlights that actual individual variability is wider than suggested by analyses of healthy subjects and results in atypical patterns of functional organization and structural and functional changes of the human cerebral cortex under pathologic conditions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations (AVHs) in schizophrenia (SZ) remains unclear. In this study, we used stochastic dynamic causal modeling (sDCM) to quantify connections among the left dorsolateral prefrontal cortex (inner speech monitoring), auditory cortex (auditory processing), hippocampus (memory retrieval), thalamus (information filtering), and Broca's area (language production) in 17 first-episode drug-naïve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging. Finally, we performed receiver operating characteristic (ROC) analysis and correlation analysis between image measures and symptoms. sDCM revealed an increased sensitivity of auditory cortex to its thalamic afferents and a decrease in hippocampal sensitivity to auditory inputs in SZ patients with AVHs. The area under the ROC curve showed the diagnostic value of these two connections to distinguish SZ patients with AVHs from those without AVHs. Furthermore, we found a positive correlation between the strength of the connectivity from Broca's area to the auditory cortex and the severity of AVHs. These findings demonstrate, for the first time, augmented AVH-specific excitatory afferents from the thalamus to the auditory cortex in SZ patients, resulting in auditory perception without external auditory stimuli. Our results provide insights into the neural mechanisms underlying AVHs in SZ. This thalamic-auditory cortical-hippocampal dysconnectivity may also serve as a diagnostic biomarker of AVHs in SZ and a therapeutic target based on direct in vivo evidence.

Brodmann areas 44 and 45 are known as Broca's area; however, their true functional roles are still unknown. Recent developments in neuroimaging techniques revealed the structures and functions of Broca's area in detail. More specifically regarding language functions, sufficient evidence has been accumulated that this region subserves the center of syntactic processing, not necessarily motor functions. Here, we review a role of Broca's area as the grammar center, including other roles in nonlinguistic functions.

Background: Under 'cocktail party' listening conditions, healthy listeners and listeners with schizophrenia can use temporally pre-presented auditory speech-priming (ASP) stimuli to improve target-speech recognition, even though listeners with schizophrenia are more vulnerable to informational speech masking., Method: Using functional magnetic resonance imaging, this study searched for both brain substrates underlying the unmasking effect of ASP in 16 healthy controls and 22 patients with schizophrenia, and brain substrates underlying schizophrenia-related speech-recognition deficits under speech-masking conditions., Results: In both controls and patients, introducing the ASP condition (against the auditory non-speech-priming condition) not only activated the left superior temporal gyrus (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced functional connectivity of the left STG/pMTG with the left caudate. It also enhanced functional connectivity of the left STG/pMTG with the left pars triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the left Rolandic operculum in patients. The strength of functional connectivity between the left STG and left TriIFG was correlated with target-speech recognition under the speech-masking condition in both controls and patients, but reduced in patients., Conclusions: The left STG/pMTG and their ASP-related functional connectivity with both the left caudate and some frontal regions (the left TriIFG in healthy listeners and the left Rolandic operculum in listeners with schizophrenia) are involved in the unmasking effect of ASP, possibly through facilitating the following processes: masker-signal inhibition, target-speech encoding, and speech production. The schizophrenia-related reduction of functional connectivity between the left STG and left TriIFG augments the vulnerability of speech recognition to speech masking.

Objective: To study resting cerebral blood flow in children and adults with developmental stuttering., Methods: We acquired pulsed arterial spin labeling magnetic resonance imaging data in 26 participants with stuttering and 36 healthy, fluent controls. While covarying for age, sex, and IQ, we compared perfusion values voxel-wise across diagnostic groups and assessed correlations of perfusion with stuttering severity within the stuttering group and with measures of motor speed in both groups., Results: We detected lower regional Cerebral Blood Flow (rCBF) at rest in the stuttering group compared with healthy controls in Broca's area bilaterally and the superior frontal gyrus. rCBF values in Broca's area bilaterally correlated inversely with the severity of stuttering and extended posteriorly into other portions of the language loop. We also found increased rCBF in cerebellar nuclei and parietal cortex in the stuttering group compared with healthy controls. Findings were unchanged in child-only analyses and when excluding participants with comorbid illnesses or those taking medication., Conclusions: rCBF is reduced in Broca's region in persons who stutter. More severe stuttering is associated with even greater reductions in rCBF to Broca's region, additive to the underlying putative trait reduction in rCBF relative to control values. Moreover, a greater abnormality in rCBF in the posterior language loop is associated with more severe symptoms, suggesting that a common pathophysiology throughout the language loop likely contributes to stuttering severity. Hum Brain Mapp 38:1865-1874, 2017. © 2017 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Neurocognitive models of language comprehension have proposed different mechanisms with different neural substrates mediating human language processing. Whether the left inferior frontal gyrus (LIFG) is engaged in morpho-syntactic information processing is currently still controversially debated. The present study addresses this issue by examining the processing of irregular verb inflection in real words (e.g., swim > swum > swam) and pseudowords (e.g., frim > frum > fram) by using event-related brain potentials (ERPs) in neurological patients with lesions in the LIFG involving Broca's area as well as healthy controls. Different ERP patterns in response to the grammatical violations were observed in both groups. Controls showed a biphasic negativity-P600 pattern in response to incorrect verb inflections whereas patients with LIFG lesions displayed a N400. For incorrect pseudoword inflections, a late positivity was found in controls, while no ERP effects were obtained in patients. These findings of different ERP patterns in the two groups strongly indicate an involvement of LIFG in morphosyntactic processing, thereby suggesting brain regions' specialization for different language functions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Area 44 is a cytoarchitectonically distinct portion of Broca's region. Parallel and overlapping large-scale networks couple with this region thereby orchestrating heterogeneous language, cognitive, and motor functions. In the context of stuttering, area 44 frequently comes into focus because structural and physiological irregularities affect developmental trajectories, stuttering severity, persistency, and etiology. A remarkable phenomenon accompanying stuttering is the preserved ability to sing. Speaking and singing are connatural behaviours recruiting largely overlapping brain networks including left and right area 44. Analysing which potential subregions of area 44 are malfunctioning in adults who stutter, and what effectively suppresses stuttering during singing, may provide a better understanding of the coordination and reorganization of large-scale brain networks dedicated to speaking and singing in general. We used fMRI to investigate functionally distinct subregions of area 44 during imagery of speaking and imaginary of humming a melody in 15 dextral males who stutter and 17 matched control participants. Our results are fourfold. First, stuttering was specifically linked to a reduced activation of left posterior-dorsal area 44, a subregion that is involved in speech production, including phonological word processing, pitch processing, working memory processes, sequencing, motor planning, pseudoword learning, and action inhibition. Second, functional coupling between left posterior area 44 and left inferior parietal lobule was deficient in stuttering. Third, despite the preserved ability to sing, males who stutter showed bilaterally a reduced activation of area 44 when imagine humming a melody, suggesting that this fluency-enhancing condition seems to bypass posterior-dorsal area 44 to achieve fluency. Fourth, time courses of the posterior subregions in area 44 showed delayed peak activations in the right hemisphere in both groups, possibly signaling the offset response. Because these offset response-related activations in the right hemisphere were comparably large in males who stutter, our data suggest a hyperactive mechanism to stop speech motor responses and thus possibly reflect a pathomechanism, which, until now, has been neglected. Overall, the current results confirmed a recently described co-activation based parcellation supporting the idea of functionally distinct subregions of left area 44., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies on schizophrenia have detected elevated cytokines in both brain and blood, suggesting neuroinflammation may contribute to the pathophysiology in some cases. We aimed to determine the extent to which elevated peripheral cytokine messenger RNA (mRNA) expression: (1) characterizes a subgroup of people with schizophrenia and (2) shows a relationship to cognition, brain volume and/or symptoms. Forty-three outpatients with schizophrenia or schizoaffective disorder and matched healthy controls were assessed for peripheral cytokine mRNAs (interleukin (IL)-1β, IL-2, IL-6, IL-8 and IL-18), intelligence quotient, memory and verbal fluency, symptom severity and cortical brain volumes integral to language (that is, Broca's and Wernicke's areas). IL-1β mRNA levels were 28% increased in schizophrenia compared with controls (t(82)=2.64, P<0.01). Using a two-step clustering procedure, we identified a subgroup of people displaying relatively elevated cytokine mRNA levels (17/43 people with schizophrenia and 9/42 controls). Individuals with schizophrenia in the elevated cytokine subgroup performed significantly worse than the low-cytokine subgroup on verbal fluency (F(1,40)=15.7, P<0.001). There was a 17% volume reduction of the left pars opercularis (POp) (Broca's area) in patients with elevated cytokines compared with patients with lower cytokines (F(1,29)=9.41, P=0.005). Negative linear relationships between IL-1β mRNA levels and both verbal fluency and left POp volume were found in schizophrenia. This study is among the first to link blood biomarkers of inflammation with both cognitive deficits and brain volume reductions in people with schizophrenia, supporting that those with elevated cytokines represent a neurobiologically meaningful subgroup. These findings raise the possibility that targeted anti-inflammatory treatments may ameliorate cognitive and brain morphological abnormalities in some people with schizophrenia.

In the congenitally blind, language processing involves visual areas. In the case of normal visual development however, it remains unclear whether later visual loss induces interactions between the language and visual areas. This study compared the resting-state functional connectivity (FC) of retinotopic and language areas in two unique groups of late visually deprived subjects: (1) blind individuals suffering from retinitis pigmentosa (RP), (2) RP subjects without a visual periphery but with preserved central "tunnel vision", both of whom were contrasted with sighted controls. The results showed increased FC between Broca's area and the visually deprived areas in the peripheral V1 for individuals with tunnel vision, and both the peripheral and central V1 for blind individuals. These findings suggest that FC can develop in the adult brain between the visual and language systems in the completely and partially blind. These changes start in the deprived areas and increase in size (involving both foveal and peripheral V1) and strength (from negative to positive FC) as the disease and sensory deprivation progress. These observations support the claim that functional connectivity between remote systems that perform completely different tasks can change in the adult brain in cases of total and even partial visual deprivation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Expressive dysphasia accompanies left inferior frontal gyrus (IFG/Broca) injury. Recovery may relate to interhemispheric balance with homologous, contralesional IFG but is unexplored in children. We evaluated effects of inhibitory rTMS to contralesional IFG combined with intensive speech therapy (SLT). A 15year-old, right-handed male incurred a left middle cerebral artery stroke. After 30months, severe non-fluent dysphasia impacted quality of life. Language networks, neuronal metabolism and white matter pathways were explored using MRI. Language function was measured longitudinally. An intensive SLT program was combined with contralesional inhibitory rTMS of right pars triangularis. Procedures were well tolerated. Language function improved persisting to four months. Post-treatment fMRI demonstrated increased left perilesional IFG activations and connectivity at rest. Bilateral changes in inositol and glutamate metabolism were observed. Contralesional, inhibitory rTMS appears safe in childhood stroke-induced dysphasia. We observed clinically significant improvements after SLT coupled with rTMS. Advanced neuroimaging can evaluate intervention-induced plasticity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Retardation of thought is a crucial clinical feature in patients with bipolar depression, characterized by dysfunctional semantic processing and language communication. However, the underlying neuropathological mechanisms remain largely unknown. The objective of this study was to evaluate the disruption in resting-state functional connectivity in 90 different brain regions during the depressive episodes of bipolar disorder and during disease remission., Methods: Applying the whole brain and language regions of interest methods to the resting-state functional magnetic resonance imaging data, we explored the discrepancies in 90 brain regions' functional connectivity in 42 patients with bipolar disorder - 23 experiencing a depressive episode and 19 in remission - and 28 healthy controls matched for gender, age, and education., Results: Bipolar depressive patients had significantly reduced connectivity strength in the language regions relative to healthy controls. Specifically, the affected regions included the left triangular part of the inferior frontal gyrus, left opercular part of the inferior frontal gyrus, left middle temporal gyrus, and left angular gyrus. However, no significant differences in these regions were observed between bipolar patients in remission and healthy controls. Furthermore, the decreased connectivity strength between the left middle temporal gyrus and right lingual gyrus showed significant positive correlation with the scores on the Hamilton Depression Rating Scale., Limitations: Bipolar depressive patients received treatment of benzodiazepines, which may confound the findings., Conclusions: Our results illustrated that connectivity disturbances in the language regions may change depending on the disease phase of bipolar disorder., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Functional MRI (fMRI) can assess language lateralization in brain tumor patients; however, this can be limited if the primary language area-Broca's area (BA)-is affected by the tumor. We hypothesized that the middle frontal gyrus (MFG) can be used as a clinical indicator of hemispheric dominance for language during presurgical workup., Methods: Fifty-two right-handed subjects with solitary left-hemispheric primary brain tumors were retrospectively studied. Subjects performed a verbal fluency task during fMRI. The MFG was compared to BA for fMRI voxel activation, language laterality index (LI), and the effect of tumor grade on the LI., Results: Language fMRI (verbal fluency) activated more voxels in MFG than in BA (MFG = 315, BA = 216, p < 0.001). Voxel activations in the left-hemispheric MFG and BA were positively correlated (r = 0.69, p < 0.001). Mean LI in the MFG was comparable to that in BA (MFG = 0.48, BA = 0.39, p = 0.06). LIs in MFG and BA were positively correlated (r = 0.62, p < 0.001). Subjects with high-grade tumors demonstrate lower language lateralization than those with low-grade tumors in both BA and MFG (p = 0.02, p = 0.02, respectively)., Conclusion: MFG is comparable to BA in its ability to indicate hemispheric dominance for language using a measure of verbal fluency and may be an adjunct measure in the clinical determination of language laterality for presurgical planning.

Objective: Localizing expressive language function has been challenging using the conventional magnetoencephalography (MEG) source modeling methods. The present MEG study presents a new accurate and precise approach in localizing the language areas using a high-resolution MEG source imaging method., Methods: In 32 patients with brain tumors and/or epilepsies, an object-naming task was used to evoke MEG responses. Our Fast-VESTAL source imaging method was then applied to the MEG data in order to localize the brain areas evoked by the object-naming task., Results: The Fast-VESTAL results showed that Broca's area was accurately localized to the pars opercularis (BA 44) and/or the pars triangularis (BA 45) in all patients. Fast-VESTAL also accurately localized Wernicke's area to the posterior aspect of the superior temporal gyri in BA 22, as well as several additional brain areas. Furthermore, we found that the latency of the main peak of the response in Wernicke's area was significantly earlier than that of Broca's area., Conclusion: In all patients, Fast-VESTAL analysis established accurate and precise localizations of Broca's area, as well as other language areas. The responses in Wernicke's area were also shown to significantly precede those of Broca's area., Significance: The present study demonstrates that using Fast-VESTAL, MEG can serve as an accurate and reliable functional imaging tool for presurgical mapping of language functions in patients with brain tumors and/or epilepsies., (Published by Elsevier Ireland Ltd.)

Recent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=-0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Since the discovery of mirror neurons, there has been a great deal of interest in understanding the relationship between perception and action, and the role of the human mirror system in language comprehension and production. Two questions have dominated research. One concerns the role of Broca's area in speech perception. The other concerns the role of the motor system more broadly in understanding action-related language. The current study investigates both of these questions in a way that bridges research on language with research on manual actions. We studied the neural basis of observing and executing American Sign Language (ASL) object and action signs. In an fMRI experiment, deaf signers produced signs depicting actions and objects as well as observed/comprehended signs of actions and objects. Different patterns of activation were found for observation and execution although with overlap in Broca's area, providing prima facie support for the claim that the motor system participates in language perception. In contrast, we found no evidence that action related signs differentially involved the motor system compared to object related signs. These findings are discussed in the context of lesion studies of sign language execution and observation. In this broader context, we conclude that the activation in Broca's area during ASL observation is not causally related to sign language understanding., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca's region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24% (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4%). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.

The authors report the first case of a strikingly unusual speech impairment evoked by intraoperative electrostimulation in a 36-year-old right-handed patient, a well-trained singer, who underwent awake surgery for a right fronto-temporo-insular low-grade glioma. Functionally disrupting the pars opercularis of the right inferior frontal gyrus led the patient to automatically switch from a speaking to a singing mode of language production. Given the central role of the right pars opercularis in the inhibitory control network, the authors propose that this finding may be interpreted as possible evidence for a competitive and independent neurocognitive subnetwork devoted to the melodically intoned articulation of words (normal language-based vs singing-based) in subjects with high expertise. From a more clinical perspective, such data may have implications for awake neurosurgery, especially to preserve the quality of life for singers.

Research on (hand-)writing has revealed that Exner's area subserves transferring linguistic impulses into writing programmes. We report on a patient with a lesion affecting Broca's and Exner's area suffering from severe peripheral agraphia for letters but not for Arabic digits. Analogous to semantic (magnitude) information in numbers, we developed a specifically tailored writing training: additional mental imagery based semantic information was attached to letters. The training resulted in significant improvements. Imaging data revealed stronger fronto-parietal network activity including perilesional activation around Exner's area and precuneus for writing letters to dictation than for writing letters corresponding to their mental image expressions. Follow-up testing showed not only stable training effects but also an activation shift into the left angular gyrus. Results document neuronal correlates of a successful intervention by attaching additional meanings to letters in order to retrieve their grapho-motor patterns. These findings contribute to understanding the impact of Exner's area., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Dyslexia, or reading difficulty, is characterized by slow, inaccurate reading accompanied by executive dysfunction. Reading training using the Reading Acceleration Program improves reading and executive functions in both children with dyslexia and typical readers. This improvement is associated with increased activation in and functional connectivity between the anterior cingulate cortex, part of the cingulo-opercular cognitive-control network, and the fusiform gyrus during a reading task after training. The objective of the current study was to determine whether the training also has an effect on functional connectivity of the cingulo-opercular and fronto-parietal cognitive-control networks during rest in children with dyslexia and typical readers. Fifteen children with reading difficulty and 17 typical readers (8-12 years old) were included in the study. Reading and executive functions behavioral measures and resting-state functional magnetic resonance imaging data were collected before and after reading training. Imaging data were analyzed using a graphical network-modeling tool. Both reading groups had increased reading and executive-functions scores after training, with greater gains among the dyslexia group. Training may have less effect on cognitive control in typical readers and a more direct effect on the visual area, as previously reported. Statistical analysis revealed that compared to typical readers, children with reading difficulty had significantly greater functional connectivity in the cingulo-opercular network after training, which may demonstrate the importance of cognitive control during reading in this population. These results support previous findings of increased error-monitoring activation after reading training in children with dyslexia and confirm greater gains with training in this group.

The Food and Drug Administration has approved a medical device using the electroencephalogram (EEG) theta/beta ratio (tbr) to help assess pediatric attention deficit/hyperactivity disorder (ADHD). Tbr is reported to be higher in ADHD, with increased theta and decreased beta. This study examined theta and beta-1 power differences between ADHD and normal children, during tasks of selective attention, and elucidated topographical differences. EEGs were collected from 28 normal and 58 ADHD children, aged 6 to 14 years, using 31 scalp electrodes during auditory and visual tasks requiring selective attention. Spectral analysis was performed. Tbr was higher in ADHD than in normal children (2.60 vs 2.25, P = .007), with lower beta-1 (3.66 vs 4.22, P = .01), but no difference in theta power. There was lower beta-1 (P < .001) and higher tbr (P = .002) over Broca's area (electrode locations F7 and FC5). Beta-1 power over Broca's area was the best diagnostic test, with sensitivity 0.86 and specificity 0.57. Tbr is higher and beta-1 power lower in ADHD than in normal children, especially over Broca's area. Beta-1 power and tbr assist in confirming the diagnosis of ADHD in a sample with moderate pretest probability of ADHD., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits., (© 2015 Wiley Periodicals, Inc.)

Object: The deep frontal pathway connecting the superior frontal gyrus to Broca's area, recently named the frontal aslant tract (FAT), is assumed to be associated with language functions, especially speech initiation and spontaneity. Injury to the deep frontal lobe is known to cause aphasia that mimics the aphasia caused by damage to the supplementary motor area. Although fiber dissection and tractography have revealed the existence of the tract, little is known about its function. The aim of this study was to determine the function of the FAT via electrical stimulation in patients with glioma who underwent awake surgery., Methods: The authors analyzed the data from subcortical mapping with electrical stimulation in 5 consecutive cases (3 males and 2 females, age range 40-54 years) with gliomas in the left frontal lobe. Diffusion tensor imaging (DTI) and tractography of the FAT were performed in all cases. A navigation system and intraoperative MRI were used in all cases. During the awake phase of the surgery, cortical mapping was performed to find the precentral gyrus and Broca's area, followed by tumor resection. After the cortical layer was removed, subcortical mapping was performed to assess language-associated fibers in the white matter., Results: In all 5 cases, positive responses were obtained at the stimulation sites in the subcortical area adjacent to the FAT, which was visualized by the navigation system. Speech arrest was observed in 4 cases, and remarkably slow speech and conversation was observed in 1 case. The location of these sites was also determined on intraoperative MR images and estimated on preoperative MR images with DTI tractography, confirming the spatial relationships among the stimulation sites and white matter tracts. Tumor removal was successfully performed without damage to this tract, and language function did not deteriorate in any of the cases postoperatively., Conclusions: The authors identified the left FAT and confirmed that it was associated with language functions. This tract should be recognized by clinicians to preserve language function during brain tumor surgery, especially for tumors located in the deep frontal lobe on the language-dominant side.

Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multimodal imaging to better inform on the neural characteristics most relevant to the disorder., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.

Objective: We summarize our experiences on intraoperative electrophysiological monitoring during neurosurgical procedures on eloquent neuronal structures., Patients, Methods: Sixty patients were enrolled retrospectively in our study with pathologies involving eloquent neuronal structures. They were operated between May 2011. and March 2012. at the University of Debrecen, Department of Neurosurgery and at the National Institute of Neurosciences. Patients underwent standard preoperative examinations due to the primary pathology. In all cases we used intraoperative electrophysiological monitoring. We had 22 cases with cranial nerve monitoring, 10 cases with cauda monitoring, 16 cases with motor system monitoring, six cases with complex spinal cord monitoring, three degenerative spine reconstructions and 3 awake surgeries., Results: We found that with the use of intraoperative electrophysiology we could make these neurosurgical procedures safer, and were able to optimize the extent of resection in the cases of oncological pathologies., Conclusions: Our experiences as well as the international literature suggests that in certain high risk neurosurgical procedures intraoperative electrophysiology is indispensible for safe and optimally extended operation.

Background/aims: We have demonstrated previously that bipolar electrocoagulation on functional cortex (BCFC) is a safe and effective approach for epilepsy involving eloquent areas. Here, we report the results of BCFC with lesionectomy for patients with epileptogenic foci partially overlapping eloquent areas., Methods: Forty patients who had been treated with lesionectomy with BCFC were retrospectively reviewed with regard to seizure outcome and neurological deficits. Ten similar patients who had received lesionectomy with multiple subpial transections (MST) were examined as a control group., Results: In the lesionectomy group with BCFC, Engel class I was achieved in 18 (45%) patients, class II in 8 (20%) patients, class III in 8 (20%) patients and class IV in 6 (15%) patients. Five (12.5%) patients developed mild hemiparesis and 1 (2.5%) patient mild sensory dysphasia. In the lesionectomy group with MST, Engel class I was achieved in 3 (30%) patients, class II in 2 (20%) patients, class III in 3 (30%) patients and class IV in 2 (20%) patients. Two (20%) patients developed mild hemiparesis and 1 (10%) patient moderate hemiparesis. All these complications recovered within 1-12 months., Conclusions: Compared with MST, the outcome of BCFC with lesionectomy is similar. But since MST leads to mechanical injury, while BCFC causes thermal injury, the complications of BCFC seem less severe., (© 2014 S. Karger AG, Basel.)