More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

White Matter Microstructural Abnormalities in the Broca's-Wernicke's-Putamen "Hoffman Hallucination Circuit" and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations.

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.

Are language skills related to structural features in Broca's and Wernicke's area?

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 expertize. 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.

3D Printing of Diffuse Low-Grade Gliomas Involving Eloquent Cortical Areas and Subcortical Functional Pathways: Technical Note.

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.

Hallucinating schizophrenia patients have longer left arcuate fasciculus fiber tracks: a DTI tractography study.

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.

Plasticity in language cortex and white matter tracts after resection of dominant inferior parietal lobule arteriovenous malformations: a combined fMRI and DTI study.

OBJECTIVE: The 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. METHODS: A 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. RESULTS: Of 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. CONCLUSIONS: The 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 importance of the fibre tracts connecting the planum temporale in absolute pitch possessors.

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.

Anatomical evidence of an indirect pathway for word repetition.

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.

Age associated decline in the arcuate fasciculus and IQ.

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.

Impact of AVM location on language cortex right-hemisphere reorganization: A voxel-based lesion-symptom mapping study.

OBJECTIVES: Cerebral arteriovenous malformations (AVMs) are congenital malformations, and right-sided dominance of the language cortex is not a rare phenomenon for patients with AVM involving language area. We tried to use voxel-based lesion-symptom mapping (VLSM) method to depict the location of AVM nidus and to demonstrate the relationship between AVM location and the pattern of language cortex reorganization. PATIENTS AND METHODS: The authors retrospectively reviewed clinical and imaging data of 70 adult patients with unruptured cerebral AVMs who underwent blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of language task. All patients were right handed, and all lesions were located in the left cerebral hemisphere. Lateralization indexes (LI) of the BOLD signals were calculated for Broca and Wernicke areas separately and were used to reflect the degree of right-sided dominance of the two language areas. VLSM method was applied to study the relationship between AVM location and LI of language task activations. RESULTS: Statistical analysis revealed that the change of LI of Broca area was significantly associated with lesions located in the inferior frontal gyrus, pre- and post-central gyrus, supramarginal gyrus and middle frontal gyrus. The change of LI of Wernicke area was significantly associated with lesions located in the left superior, middle, inferior and transverse temporal gyrus. CONCLUSION: These findings provide new evidence that the language cortex reorganization patterns in AVM patients have anatomic specificity.

Repeatability of language fMRI lateralization and localization metrics in brain tumor patients.

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.

Normal voice processing after posterior superior temporal sulcus lesion.

The right posterior superior temporal sulcus (pSTS) shows a strong response to voices, but the cognitive processes generating this response are unclear. One possibility is that this activity reflects basic voice processing. However, several fMRI and magnetoencephalography findings suggest instead that pSTS serves as an integrative hub that combines voice and face information. Here we investigate whether right pSTS contributes to basic voice processing by testing Faith, a patient whose right pSTS was resected, with eight behavioral tasks assessing voice identity perception and recognition, voice sex perception, and voice expression perception. Faith performed normally on all the tasks. Her normal performance indicates right pSTS is not necessary for intact voice recognition and suggests that pSTS activations to voices reflect higher-level processes.

Applicability of genetic polymorphism analysis for the diagnosis of Angelman syndrome and the correlation between language difficulties and disease phenotype.

Angelman syndrome (AS) is a neurogenetic disorder caused by a defect in the expression of the maternally inherited ubiquitin protein ligase E3A (UBE3A) gene in chromosome 15. The most common genetic defects include maternal deletions in chromosome 15q11-13; however, paternal uniparental disomy and imprinting defects allow for the identification of mutations in UBE3A in 10% of patients with AS. The aim of this study was to validate the clinical features and genetic polymorphisms of AS, and to discuss the relationship between functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas. Six children with AS (mean age = 32.57 months) presenting characteristic behavioral patterns of AS (frequent laughter and happy demeanor, hand flapping, and hypermotor behavior) were recruited to this study. The patients underwent a clinical evaluation (clinical history, dysmorphological and neurological examinations, and psychological evaluations) and paraclinical investigations [genetic tests (fluorescence in situ hybridization and methylation polymerase chain reaction), electroencephalogram, and magnetic resonance imaging]. We conclude that AS diagnosis cannot rely solely on genetic testing for polymorphisms in UBE3A and must consider its clinical characteristics. Moreover, functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas were found to be closely correlated. Therefore, UBE3A gene mutation analysis combined with comprehensive clinical evaluations may be suitable for the diagnosis of AS.

Testosterone affects language areas of the adult human brain.

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