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.

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.

Development of information sharing in language neocortex in childhood-onset drug-resistant epilepsy.

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.

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.

Reorganization of language centers in patients with brain tumors located in eloquent speech areas - A pre- and postoperative preliminary fMRI study.

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.

Neural adaptation in pSTS correlates with perceptual aftereffects to biological motion and with autistic traits.

The adaptive nature of biological motion perception has been documented in behavioral studies, with research showing that prolonged viewing of an action can bias judgments of subsequent actions towards the opposite of its attributes. However, the neural mechanisms underlying action adaptation aftereffects remain unknown. We examined adaptation-induced changes in brain responses to an ambiguous action after adapting to walking or running actions within two bilateral regions of interest: 1) human middle temporal area (hMT+), a lower-level motion-sensitive region of cortex, and 2) posterior superior temporal sulcus (pSTS), a higher-level action-selective area. We found a significant correlation between neural adaptation strength in right pSTS and perceptual aftereffects to biological motion measured behaviorally, but not in hMT+. The magnitude of neural adaptation in right pSTS was also strongly correlated with individual differences in the degree of autistic traits. Participants with more autistic traits exhibited less adaptation-induced modulations of brain responses in right pSTS and correspondingly weaker perceptual aftereffects. These results suggest a direct link between perceptual aftereffects and adaptation of neural populations in right pSTS after prolonged viewing of a biological motion stimulus, and highlight the potential importance of this brain region for understanding differences in social-cognitive processing along the autistic spectrum.

Early-onset hearing loss reorganizes the visual and auditory network in children without cochlear implantation.

The present study investigates the effect of early-onset hearing loss on the reorganization of visual and auditory networks in children without cochlear implants. Eleven congenitally deaf children and 12 age-matched hearing children were included in the study. Bilateral transverse temporal cortices and bilateral lateral occipital cortices were defined as auditory and visual seeds, respectively (as verified using an independent component analysis). The four seed-based connectivity maps were computed for each participant. As a result, group analysis showed that the primary auditory cortex was less connected with the motor cortex, whereas the visual cortex showed strengthened connectivity with motor and speech cortices in congenitally deaf children compared with the controls. Moreover, we found that the differences in functional connectivity between deaf and control children were not because of morphometric changes. Our results provide neural evidence for the sensorimotor coupling model of speech development.

Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study.

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.

Outcome of bipolar electrocoagulation with lesionectomy in the treatment of epilepsy involving eloquent areas.

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.

Primary progressive aphasia and the evolving neurology of the language network.

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke's area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations.

BACKGROUND: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). METHODS: Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically. RESULTS: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range: 4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p=0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p=0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p=0.03) and negative (p=0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p=0.008). CONCLUSION: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.

Neurocognitive brain response to transient impairment of Wernicke's area.

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure.