Temporal and topographical characterization of language cortices using intraoperative optical intrinsic signals

We used intraoperative optical imaging of intrinsic signals (iOIS) and electrocortical stimulation mapping (ESM) to compare functionally active brain regions in 10 awake patients undergoing neurosurgical resection. Patients performed two to four tasks, including visual and auditory naming, word discrimination, and/or orofacial movements. All iOIS maps included areas identified by ESM mapping. However, iOIS also revealed topographical specificity dependent on language task. In Broca's area, naming paradigms activated both anterior and posterior inferior frontal gyrus (IFG), while the word discrimination paradigm activated only posterior IFG. In Wernicke's area, object naming produced activations localizing over the inferior and anterior/posterior regions, while the word discrimination task activated superior and anterior cortices. These results may suggest more posterior phonological activation and more anterior semantic activations in Broca's area, and more anterior/superior phonological activation and more posterior/inferior semantic activations in Wernicke's area. Although similar response onset was observed in Broca's and Wernicke's areas, temporal differences were revealed during block paradigm (20-s) activations. In Broca's area, block paradigms yielded a boxcar temporal activation profile (in all tasks) that resembled response profiles observed in motor cortex (with orofacial movements). In contrast, activations in Wernicke's area responded with a more dynamic profile (including early and late peaks) which varied with paradigm performance. Wernicke's area profiles were very similar to response profiles observed in sensory and visual cortex. The differing temporal patterns may therefore reflect unique processing performed by receptive (Wernicke's) and productive (Broca's) language centers. This study is consistent with task-specific semantic and phonologic regions within Broca's and Wernicke's areas and also is the first report of response profile differences dependent on cortical region and language task.     

The role of dominant premotor cortex in language: a study using intraoperative functional mapping in awake patients

Although the role of the premotor cortex (PMC) was widely studied in motor function, very few data are currently available about the participation of this structure in language. We report a series of 25 right-handed patients harboring a low-grade glioma near or within the left dominant PMC, operated on under local anesthesia with intraoperative real-time sensorimotor and language mappings using electrical stimulations all along the resection. Language tasks consisted of counting and picture naming (preceded by the reading of a short sentence). Stimulations of the left PMC induced transient speech disturbances in all patients, with disruption of both counting and reading/naming during stimulation of the ventral PMC--due to elicitation of an anarthria--while generating an anomia during stimulation of the dorsal PMC. Moreover, corresponding subcortical pathways generated the same language disorders as at the cortical level when stimulated. Eloquent structures were systematically preserved, allowing the avoidance of definitive postoperative deficit. These findings suggest first that the left dominant PMC seems to play a major role in language and second that this structure could have a well-ordered functional organization, namely with the ventral PMC, which might be involved in planification of articulation, and the dorsal PMC, which might be involved in the naming network.     

Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.     

不出声与出声图片命名任务神经激活机制差异的功能磁共振成像

目的 采用功能磁共振成像(fMRI)技术观察执行不出声和出声图片命名任务时大脑活动的差异.方法 在10名健康志愿者(24～27岁)分别进行不出声和出声图片命名时,同时采集其脑部的fMRI数据,通过分析处理获得执行不同任务时的头动结果及脑功能区统计激活图.结果 不出声任务的平均头动和最大头动低于出声任务,但差异无统计学意义(P=0.23).不出声图片命名的神经激活网络包括双侧枕回及小脑、双侧辅助运动区、中央后回、双侧额下回和前扣带回.出声图片命名时除在上述不出声时的激活区有更强激活外,还激活了双侧中央前回(BA4)、双侧后上颞回、左侧前上颞回、双侧丘脑及基底节区、左侧岛叶.结论 不出声和出声图片命名的神经处理网络及环节互不相同,两种任务不能相互替代.     

How reading differs from object naming at the neuronal level

This paper uses whole brain functional neuroimaging in neurologically normal participants to explore how reading aloud differs from object naming in terms of neuronal implementation. In the first experiment, we directly compared brain activation during reading aloud and object naming. This revealed greater activation for reading in bilateral premotor, left posterior superior temporal and precuneus regions. In a second experiment, we segregated the object-naming system into object recognition and speech production areas by factorially manipulating the presence or absence of objects (pictures of objects or their meaningless scrambled counterparts) with the presence or absence of speech production (vocal vs. finger press responses). This demonstrated that the areas associated with speech production (object naming and repetitively saying "OK" to meaningless scrambled pictures) corresponded exactly to the areas where responses were higher for reading aloud than object naming in Experiment 1. Collectively the results suggest that, relative to object naming, reading increases the demands on shared speech production processes. At a cognitive level, enhanced activation for reading in speech production areas may reflect the multiple and competing phonological codes that are generated from the sublexical parts of written words. At a neuronal level, it may reflect differences in the speed with which different areas are activated and integrate with one another.     

Contribution of the left and right inferior frontal gyrus in recovery from aphasia. A functional MRI study in stroke patients with preserved hemodynamic responsiveness

The relative contribution of dominant and non-dominant language networks to recovery from aphasia is a matter of debate. We assessed with functional magnetic resonance imaging (fMRI) to what extent the left and right hemispheres are associated with recovery from aphasia after stroke. fMRI with three language tasks was performed in 13 aphasic stroke patients and in 13 healthy subjects. Severity of aphasia was examined within 2 months after stroke and after at least 1 year. Recovery of naming ability and scores on the Token Test were correlated with data from fMRI in the chronic phase. A breath-hold paradigm was used to investigate hemodynamic responsiveness.Overall language performance in the chronic phase correlated with higher relative activation of left compared to right perisylvian areas. Recovery of naming ability was positively correlated with activation in the left inferior frontal gyrus (IFG) for semantic decision and verb generation. Recovery on the Token Test was positively correlated with activation in both left and right IFG during semantic decision and verb generation. Hemodynamic response to the breath-hold task was similar in patients and controls.Our study suggests that in the chronic stage after stroke left IFG activity is associated with improvement of picture naming and sentence comprehension, whereas activity in the right IFG may reflect up-regulation of non-linguistic cognitive processing. Altered hemodynamic responsiveness seems an unlikely confounder in the interpretations of fMRI results.     

Neural substrates of spoken language rehabilitation in an aphasic patient: an fMRI study

Little is known about the neural counterparts of speech therapy in aphasic patients. An fMRI experiment was performed before and after a specific and intensive speech output therapy in RC, a patient with long-lasting speech output deficit following a left-sided ischemic lesion. Overt picture naming and picture/word rhyming were used as activation tasks in RC and 6 control subjects. The naming task concerned the output lexicon deficit to be rehabilitated while rhyming referred to preserved levels of processing and was used to control for repetition effect. The speech therapy program improved naming performance. By comparison to the pattern observed before therapy, the naming task after therapy induced a pattern of activation close to that observed in control subjects, involving left-sided language areas surrounding the lesion. Speech therapy effect was associated with activations in Broca's area and the left supra-marginal gyrus, which might reflect a therapy-induced phonological compensatory strategy for naming.     

A new verbal reports fMRI dichotic listening paradigm for studies of hemispheric asymmetry

Dichotic listening (DL) is one of the most frequently used paradigms to study hemispheric asymmetry and has been employed in several neuroimaging studies. The classic behavioral DL paradigm requires the subject to give a verbal response on each trial, which may cause image artifacts due to head movements when applied to an imaging environment. In order to avoid such artifacts most studies have used modified versions of the classic DL paradigm, where no verbal response is required. The purpose of the present study was to test a new DL paradigm, specifically developed for the fMRI environment, which is based on collecting verbal responses and thus being as close as possible to the classic DL behavioral task. By employing a sparse-sampling EPI acquisition schema we attempted to limit the negative impact of overt speech on image quality. A 5-s 'silent gap' allowed for stimulus presentation and collection of a verbal response to occur between subsequent image acquisitions and served as a high-pass filter that was optimized to detect activations of interest. Hence, the contribution of response-related activations to the measured signal was reduced. Twelve healthy volunteers (six males and six females) participated in the study. In order to obtain a measure of reliability, all participants went through the classic DL paradigm three times. The results, based on the estimation of the intraclass correlation coefficient, functional probability maps as well as on laterality maps, showed consistent activation in the right and left superior temporal gyrus, left middle temporal gyrus, and right inferior temporal gyrus, thus replicating previous results with visual display and motor response DL paradigms. It is concluded that an fMRI DL paradigm based on overt verbal responses is feasible and could have general implications for future fMRI studies of speech perception and product in general.     

A practical clinical method to quantify language lateralization in fMRI using whole-brain analysis

Surgery is often the only effective treatment for intractable epilepsy, but its benefits must be balanced by potential disruption of eloquent cortical functions. Wada test is the standard technique to lateralize language before surgery; however, it is invasive and associated with complications. fMRI provides an attractive noninvasive alternative, which has been previously shown to correlate with Wada results. However this correlation is imperfect since standard fMRI laterality indices are dependent on a particular arbitrary statistical threshold used in the data processing. We report a novel automated, threshold-independent fMRI methodology to assess language lateralization, which we hypothesize provides a robust and unbiased pre-operative assessment. This hemispheric histogram analysis method can accurately interrogate language lateralization, as validated against the Wada test. Fifty-nine subjects with intractable epilepsy received preoperative evaluation for language lateralization using fMRI. fMRI data then were analyzed using a novel automated threshold-independent method for determining language lateralization. The methodology generated a lateralization score based on hemispheric activation of language areas and a quality index based on multiple factors, including patient motion and signal-to-noise characteristics. Lateralization scores were compared to Wada test results (51 patients), direct cortical stimulation (3 patients), and subdural grid stimulation (5 patients). Data sets were used to generate a probability score for language lateralization for each subject. The lateralization scores correlated well with the objective measures of language lateralization (r(2)=0.46). Cumulative historical data were utilized to prospectively determine probabilities of language lateralization for individual patients. In conclusion, hemispheric language lateralization can be accurately determined using a novel objective and automated methodology that calculates language lateralization in a threshold-independent manner and can be used to determine the probability of language dominance in individual patients.     

"What" versus "where" in the audiovisual domain: an fMRI study

Similar "what/where" functional segregations have been proposed for both visual and auditory cortical processing. In this fMRI study, we investigated if the same segregation exists in the crossmodal domain, when visual and auditory stimuli have to be matched in order to perform either a recognition or a localization task. Recent neuroimaging research highlighted the contribution of different heteromodal cortical regions during various forms of crossmodal binding. Interestingly, crossmodal effects during audiovisual speech and object recognition have been found in the superior temporal sulcus, while crossmodal effects during the execution of spatial tasks have been found over the intraparietal sulcus, suggesting an underlying "what/where" segregation. In order to directly compare the specific involvement of these two heteromodal regions, we scanned ten male right-handed subjects during the execution of two crossmodal matching tasks. Participants were simultaneously presented with a picture and an environmental sound, coming from either the same or the opposite hemifield and representing either the same or a different object. The two tasks required a manual YES/NO response respectively about location or semantic matching of the presented stimuli. Both group and individual subject analysis were performed. Task-related differences in BOLD response were observed in the right intraparietal sulcus and in the left superior temporal sulcus, providing a direct confirmation of the "what-where" functional segregation in the crossmodal audiovisual domain.     

Neural recruitment associated with anomia treatment in aphasia

The purpose of this study was to investigate changes in the spatial distribution of cortical activity associated with anomia treatment in three persons with aphasia. Participants underwent three fMRI sessions before and after a period of intensive language treatment focused on object naming. The results revealed bilateral hemispheric recruitment associated with improved ability to name items targeted in treatment. This is the first study to employ multiple pre- and post-treatment fMRI sessions in the study of treatment-induced recovery from aphasia and has implications for future studies of brain plasticity in stroke.     

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space--the roles of Brodmann areas 44 and 45

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Broca's speech region (Brodmann's areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.     

Reliability of fMRI for studies of language in post-stroke aphasia subjects

Quantifying change in brain activation patterns associated with post-stroke recovery and reorganization of language function over time requires accurate understanding of inter-scan and inter-subject variability. Here we report inter-scan variability measures for fMRI activation patterns associated with verb generation (VG) and semantic decision/tone decision (SDTD) tasks in 4 healthy controls and 4 aphasic left middle cerebral artery (LMCA) stroke subjects. A series of 10 fMRI scans was completed on a 4T Varian scanner for each task for each subject, except for one stroke subject who completed 5 and 6 scans for SDTD and VG, thus yielding 35 and 36 total stroke subject scans for SDTD and VG, respectively. Group composite and intraclass correlation coefficient (ICC) maps were computed across all subjects and trials for each task. The patterns of reliable activation for the VG and SDTD tasks correspond well to those regions typically activated by these tasks in healthy and aphasic subjects. ICCs for activation were consistently high (R(0.05) approximately 0.8) for individual tasks among both control and aphasic subjects. These voxel-wise measures of reliability highlight regions of low inter-scan variability within language circuitry for control and post-recovery stroke subjects. ICCs computed from the combination of the SDTD/VG data were markedly reduced for both control and aphasic subjects as compared with the ICCs for the individual tasks. These quantitative measures of inter-scan variability support the proposed use of these fMRI paradigms for longitudinal mapping of neural reorganization of language processing following left hemispheric insult.     

Connectivity constraints on cortical reorganization of neural circuits involved in object naming

The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function.     

Independent component analysis applied to self-paced functional MR imaging paradigms

Self-paced functional MR imaging (fMRI) paradigms, in which the task timing is determined by the subject's performance, can offer several advantages over commonly applied paradigms with predetermined stimulus timing. Independent component analysis (ICA) does not require specification of a timed response function, and could be an advantageous method of deriving results from fMRI data sets with varying response timings and durations. In this study normal volunteers (N = 10) each performed two self-paced fMRI motor and arithmetic paradigms. Individual data sets were analyzed with the Infomax spatial ICA algorithm. Conventional regression analysis was performed for comparison purposes. Spatial ICA effectively produced task-related components from each of the self-paced data sets, even in a few cases where regression analysis yielded non-specific functional maps. For the motor paradigm, these components consistently mapped to primary motor areas. ICA of the arithmetic paradigm yielded multiple task-related components that variably mapped to regions of parietal and frontal lobes. Regression analysis generally yielded similar spatial maps. The multiple task-related ICA components that were sometimes produced from each self-paced data set can be challenging to identify and evaluate for significance. These preliminary results indicate that ICA is useful as an exploratory and complementary method to conventional regression analysis for fMRI of self-paced paradigms.     

Local and global inhibition in bilingual word production: fMRI evidence from Chinese-English bilinguals

The current study examined the neural correlates associated with local and global inhibitory processes used by bilinguals to resolve interference between competing responses. Two groups of participants completed both blocked and mixed picture naming tasks while undergoing functional magnetic resonance imaging (fMRI). One group first named a set of pictures in L1, and then named the same pictures in L2. The other group first named pictures in L2, and then in L1. After the blocked naming tasks, both groups performed a mixed language naming task (i.e., naming pictures in either language according to a cue). The comparison between the blocked and mixed naming tasks, collapsed across groups, was defined as the local switching effect, while the comparison between blocked naming in each language was defined as the global switching effect. Distinct patterns of neural activation were found for local inhibition as compared to global inhibition in bilingual word production. Specifically, the results suggest that the dorsal anterior cingulate cortex (ACC) and the supplementary motor area (SMA) play important roles in local inhibition, while the dorsal left frontal gyrus and parietal cortex are important for global inhibition.     

Perceiving and naming actions and objects

Neuropsychological studies have suggested differences in the cortical representations of verbs and nouns. Assessment of word-class specific deficits often relies on picture naming with different sets of images used for action and object naming. Such a setup may be problematic in neuroimaging studies, as the perception of the image and the actual differences in retrieving verbs or nouns become intertwined. To address this issue, we investigated how different sets of images affect the pattern of activation in action and object naming. In the present fMRI experiment, healthy volunteers silently performed both action and object naming from action images, and object naming from object-only images. A similar network of cortical areas was activated in all three conditions, including bilateral occipitotemporal and parietal regions, and left frontal cortex. With action images, noun retrieval enhanced activation in bilateral parietal and right frontal cortex, areas previously associated with visual search and attention. Increased activation in the left posterior parietal cortex during this condition also suggests that naming an object in the context of action emphasizes motor-based properties of objects. Action images, regardless of whether verbs or nouns were named, evoked stronger activation than object-only images in the posterior middle temporal cortex bilaterally, the left temporo-parietal junction, and the left frontal cortex, a network previously identified in processing of action knowledge. The strong influence of perceptual input on neural activation associated with noun vs. verb naming can in part explain discrepancies in previous lesion and functional neuroimaging studies on the processing of nouns and verbs.     

Probing overtly spoken language at sentential level: a comprehensive high-field BOLD-fMRI protocol reflecting everyday language demands

Regarding the application of functional magnetic resonance imaging (fMRI) to preoperative mapping of language, the majority of previous studies applied silent vocalization at word level. Since mapping of language targets the protection of overt communication, the selection of the stimulation paradigm is a crucial issue. Typically, everyday language demands overt speech with construction of syntactically and semantically complete sentences. Here, 23 healthy right-handed subjects performed overt vocalization of complete german sentences. Subjects produced these sentences based on visually presented semantic choices. Special efforts were undertaken to minimize motion artifacts and maximize signal gain on a 3-T MR unit. Compared to previous studies, results showed a larger amount of highly reliable fMRI activations over the whole brain. Particularly, high sensitivity was found for Broca's and Wernicke's regions, as well as anterior and inferior temporal areas. Regarding the left hemisphere, simultaneous "Broca" and "Wernicke" activities were found in 95% of all subjects. When including atypical lateralizations, "Broca" and "Wernicke" activations were found in every subject. Overt vocalization at sentential level represents a new comprehensive language task with the potential to generate reliable activation maps that reflect brain activity associated with everyday language demands.     

Laser Doppler imaging for intraoperative human brain mapping

The identification and accurate location of centers of brain activity are vital both in neuro-surgery and brain research. This study aimed to provide a non-invasive, non-contact, accurate, rapid and user-friendly means of producing functional images intraoperatively. To this end a full field Laser Doppler imager was developed and integrated within the surgical microscope and perfusion images of the cortical surface were acquired during awake surgery whilst the patient performed a predetermined task. The regions of brain activity showed a clear signal (10–20% with respect to the baseline) related to the stimulation protocol which lead to intraoperative functional brain maps of strong statistical significance and which correlate well with the preoperative fMRI and intraoperative cortical electro-stimulation. These initial results achieved with a prototype device and wavelet based regressor analysis (the hemodynamic response function being derived from MRI applications) demonstrate the feasibility of LDI as an appropriate technique for intraoperative functional brain imaging.     

Functional re-recruitment of dysfunctional brain areas predicts language recovery in chronic aphasia

Functional recovery in response to a brain lesion, such as a stroke, can even occur years after the incident and may be accelerated by effective rehabilitation strategies. In eleven chronic aphasia patients, we administered a short-term intensive language training to improve language functions and to induce cortical reorganization under rigorously controlled conditions. Overt naming performance was assessed during functional magnetic resonance imaging (fMRI) prior to and immediately after the language training. Regions of interest (ROIs) for statistical analyses were constituted by areas with individually determined abnormally high densities of slow wave generators (identified by magnetoencephalography prior to the language intervention) that clustered mainly in left perilesional areas. Three additional individually defined regions served to control for the specificity of the results for the selected respective target region: the homologue area of the individual patient's lesion, the mirror image of the delta ROI in the right hemisphere and left hemispheric regions that did not produce a significant amount of slow wave activity. Treatment-induced changes of fMRI brain activation were highly correlated with improved naming of the trained pictures, but selectively within the pre-training dysfunctional perilesional brain areas. Our results suggest that remodeling of cortical functions is possible even years after a stroke. The behavioral gain seems to be mediated by brain regions that had been partially deprived from input after the initial stroke. We therefore provide first time direct evidence for the importance of treatment-induced functional reintegration of perilesional areas in a heterogeneous sample of chronic aphasia patients.