Critical Language Areas Research Articles

Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities.

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

Feasibility of awake brain surgery in glioblastoma patients with severe aphasia: Five case illustrations

ABSTRACT Background Traditionally, surgical removal of glioblastoma is performed with general anaesthesia but a recent meta-analysis revealed that awake surgery in glioblastoma resulted in better surgical outcomes than non-awake surgery. Preoperative severe aphasia is one of the exclusion criteria for awake surgery because of difficulties in intraoperative interpretation of language deterioration and the distinction between preoperative vs. intraoperative induced paraphasias. As severe aphasia is common in glioblastoma patients, many potential patients who may benefit from awake surgery are excluded. Aims We aim to investigate the feasibility of awake surgery in glioblastoma patients with severe aphasia using a patient-tailored approach with adapted intraoperative language tasks. We also examined the effect of awake surgery on language outcomes. Methods & Procedures We discuss five case studies of patients elected for awake surgery with presumed glioblastoma in eloquent language areas and severe aphasia. Pre- and postoperatively, an extensive test-protocol was administered at different linguistic levels and modalities. A patient-tailored intraoperative language test-protocol was applied. Outcomes & Results Preoperatively, all patients had severe impairments on all language and cognitive tests. Intraoperative language tasks for direct electrical stimulation and resection were selected and adapted to patients’ preoperative level. Despite preoperative severe aphasia, functional boundaries for critical language areas could be identified in each patient. Postoperatively, all patients had stable or improved language outcome. One of the patients recovered to maximum scores on nearly all language tests. Conclusions Our cases demonstrate that awake surgery in severely aphasic glioblastoma patients is feasible and did not cause further deterioration of aphasia. An extensive preoperative neurolinguistic examination is necessary for adequate patient-tailored intraoperative monitoring with maximal tumour resection and to consequently increase the chance of language preservation and quality of life.

Language Neuroplasticity in Brain Tumor Patients Revealed by Magnetoencephalography.

Little is known about language impairment in brain tumor patients, especially in the presurgical phase. Impairment in this population may be missed because standardized tests fail to capture mild deficits. Additionally, neuroplasticity may also contribute to minimizing language impairments. We examined 14 presurgical patients with brain tumors in the language-dominant hemisphere using magnetoencephalography (MEG) while they performed a demanding picture-word interference task, that is, participants name pictures while ignoring distractor words. Brain tumor patients had behavioral picture-naming effects typically observed in healthy controls. The MEG responses also showed the expected pattern in its timing and amplitude modulation typical of controls, but with an altered spatial distribution of right hemisphere sources, in contrast to the classic left hemisphere source found in healthy individuals. This finding supports tumor-induced neural reorganization of language before surgery. Crucially, the use of electrophysiology allowed us to show the "same" neuronal response in terms of its timing and amplitude modulation in the right hemisphere, supporting the hypothesis that the processes performed by the right hemisphere following reorganization are similar in nature to those (previously) performed by the left hemisphere. We also identified one participant with a fast-growing tumor affecting large parts of critical language areas and underlying ventral and dorsal white matter tracts who showed a deviant pattern in behavior and in the MEG event-related responses. In conclusion, our results attest to the validity of using a demanding picture-naming task in presurgical patients and provide evidence for neuroplasticity, with the right hemisphere performing similar computations as the left hemisphere typically performs.

Is awake brain surgery in high-grade glioma patients and a severe aphasia feasible? A case study.

Is awake brain surgery in high-grade glioma patients and a severe aphasia feasible? A case study.

Leukoaraiosis is independently associated with naming outcome in poststroke aphasia.

To test the hypothesis that severity of leukoaraiosis in the noninfarcted hemisphere at onset is associated with poorer language outcome after poststroke aphasia independently of volume of infarct, damage to 3 critical language areas (left inferior frontal gyrus, superior longitudinal fasciculus, and superior temporal gyrus), comorbid conditions, and time since stroke. In this cross-sectional study, we evaluated naming outcome (>3 months after stroke) in 42 individuals who initially had aphasia after stroke. We rated leukoaraiosis in the right hemisphere 1 to 4 weeks from onset of stroke using the Cardiovascular Health Study rating scale. We evaluated associations between severity of leukoaraiosis and each measure of naming using Spearman correlations and evaluated the independent contributions of leukoaraiosis, lesion volume, months since onset, comorbid conditions, and damage to critical nodes of the language network on language outcomes using logistic regression. We also evaluated associations between dichotomously defined leukoaraiosis and language outcomes using χ2 tests. Severity of leukoaraiosis at onset correlated with object naming (ρ = -0.56, p = 0.0008) and word fluency (ρ = -0.37, p = 0.01) outcomes. Severe leukoaraiosis was associated with failure to achieve the highest quartile of object naming and word fluency. Severity of leukoaraiosis was associated with degree of naming outcome with the use of both measures after controlling for lesion volume, months since stroke, comorbid conditions, and damage to specific locations. Naming outcome after poststroke aphasia is influenced by the initial severity of right hemisphere leukoaraiosis independently of other variables. Degree of recovery from aphasia may depend on the integrity of the noninfarcted brain tissue.

Critical Language Areas Show Increased Functional Connectivity in Human Cortex.

Electrocortical stimulation (ECS) mapping is routinely used to identify critical language sites before resective neurosurgery. The precise locations of these sites are highly variable across patients, occurring in the frontal, temporal, and parietal lobes-it is this variability that necessitates individual patient mapping. But why these particular anatomical sites are so privileged in each patient is unknown. We hypothesized that critical language sites have greater functional connectivity with nearby cortex than sites without critical functions, since they serve as central nodes within the language network. Functional connectivity across language, motor, and cleared sites was measured in 15 patients undergoing electrocortiographic (ECoG) mapping for epilepsy surgery. Critical language sites had significantly higher connectivity than sites without critical functions (P = 0.001), and this also held for motor sites (P = 0.022). These data support the hypothesis that critical language sites are highly connected within the local cortical network, perhaps explaining why their disruption with ECS leads to transient disturbances in language function. It is our hope that improved understanding of the mechanisms of ECS will permit improved surgical planning and perhaps contribute to the understanding of normal language physiology.

Functional activation independently contributes to naming ability and relates to lesion site in post-stroke aphasia.

Language network reorganization in aphasia may depend on the degree of damage in critical language areas, making it difficult to determine how reorganization impacts performance. Prior studies on remapping of function in aphasia have not accounted for the location of the lesion relative to critical language areas. They rectified this problem by using a multimodal approach, combining multivariate lesion-symptom mapping and fMRI in chronic aphasia to understand the independent contributions to naming performance of the lesion and the activity in both hemispheres. Activity was examined during two stages of naming: covert retrieval, and overt articulation. Regions of interest were drawn based on over- and under-activation, and in areas where activity had a bivariate relationship with naming. Regressions then tested whether activation of these regions predicted naming ability, while controlling for lesion size and damage in critical left hemisphere naming areas, as determined by lesion-symptom mapping. Engagement of the right superior temporal sulcus (STS) and disengagement of the left dorsal pars opercularis (dPOp) during overt naming was associated with better than predicted naming performance. Lesions in the left STS prevented right STS engagement and resulted in persistent left dPOp activation. In summary, changes in activity during overt articulation independently relate to naming outcomes, controlling for stroke severity. Successful remapping relates to network disruptions that depend on the location of the lesion in the left hemisphere. Hum Brain Mapp 38:2051-2066, 2017. © 2017 Wiley Periodicals, Inc.

Bilingualism Influences Structural Indices of Interhemispheric Organization.

Bilingualism represents an interesting model of possible experience-dependent alterations in brain structure. The current study examines whether interhemispheric adaptations in brain structure are associated with bilingualism. Corpus callosum volume and cortical thickness asymmetry across 13 regions of interest (selected to include critical language and bilingual cognitive control areas) were measured in a sample of Spanish-English bilinguals and age- and gender-matched monolingual individuals (N = 39 per group). Cortical thickness asymmetry of the anterior cingulate region differed across groups, with thicker right than left cortex for bilinguals and the reverse for monolinguals. In addition, two adjacent regions of the corpus callosum (mid-anterior and central) had greater volume in bilinguals. The findings suggest that structural indices of interhemispheric organization in a critical cognitive control region are sensitive to variations in language experience.

Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke.

The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical language areas in the left hemisphere and then to quantify each stroke survivor's lesion burden in these areas. After controlling for these direct effects of the stroke on language, voxel-based morphometry was then used to determine whether local grey matter volumes in the right hemisphere explained additional variance in language outcomes. In brain areas in which grey matter volumes related to language outcomes, we then compared grey matter volumes in patients and healthy controls to assess post-stroke plasticity. Lesion-symptom mapping showed that specific left hemisphere regions related to different language abilities. After controlling for lesion burden in these areas, lesion size, and demographic factors, grey matter volumes in parts of the right temporoparietal cortex positively related to spontaneous speech, naming, and repetition scores. Examining whether domain general cognitive functions might explain these relationships, partial correlations demonstrated that grey matter volumes in these clusters related to verbal working memory capacity, but not other cognitive functions. Further, grey matter volumes in these areas were greater in stroke survivors than healthy control subjects. To confirm this result, 10 chronic left hemisphere stroke survivors with no history of aphasia were identified. Grey matter volumes in right temporoparietal clusters were greater in stroke survivors with aphasia compared to those without history of aphasia. These findings suggest that the grey matter structure of right hemisphere posterior dorsal stream language homologues independently contributes to language production abilities in chronic left hemisphere stroke, and that these areas may undergo hypertrophy after a stroke causing aphasia.

Electrocorticographic language mapping with a listening task consisting of alternating speech and music phrases

ObjectiveElectrocorticographic (ECoG) mapping of high gamma activity induced by language tasks has been proposed as a more patient friendly alternative for electrocortical stimulation mapping (ESM), the gold standard in pre-surgical language mapping of epilepsy patients. However, ECoG mapping often reveals more language areas than considered critical with ESM. We investigated if critical language areas can be identified with a listening task consisting of speech and music phrases. MethodsNine patients with implanted subdural grid electrodes listened to an audio fragment in which music and speech alternated. We analysed ECoG power in the 65–95Hz band and obtained task-related activity patterns in electrodes over language areas. We compared the spatial distribution of sites that discriminated between listening to speech and music to ESM results using sensitivity and specificity calculations. ResultsOur listening task of alternating speech and music phrases had a low sensitivity (0.32) but a high specificity (0.95). ConclusionsThe high specificity indicates that this test does indeed point to areas that are critical to language processing. SignificanceOur test cannot replace ESM, but this short and simple task can give a reliable indication where to find critical language areas, better than ECoG mapping using language tasks alone.

Cognitive outcome after awake surgery for left and right hemisphere tumours

Cognitive outcome after awake surgery for left and right hemisphere tumours

Comparison of blocked and event-related fMRI designs for pre-surgical language mapping

Language functional magnetic resonance imaging (fMRI) is a promising non-invasive technique for pre-surgical planning in patients whose lesions are adjacent to or within critical language areas. Most language fMRI studies in patients use blocked experimental design. In this study, we compared a blocked design and a rapid event-related design with a jittered inter-stimulus-interval (ISI) (or stochastic design) for language fMRI in six healthy controls, and eight brain tumor patients, using a vocalized antonym generation task. Comparisons were based on visual inspection of fMRI activation maps and degree of language lateralization, both of which were assessed at a constant statistical threshold for each design. The results indicated a relatively high degree of discordance between the two task designs. In general, the event-related design provided maps with more robust activations in the putative language areas than the blocked design, especially for brain tumor patients. Our results suggest that the rapid event-related design has potential for providing comparable or even higher detection power over the blocked design for localizing language function in brain tumor patients, and therefore may be able to generate more sensitive language maps. More patient studies, and further investigation and optimization of language fMRI paradigms will be needed to determine the utility and validity of this approach for pre-surgical planning.

Age-Related Changes in the Anatomy of Language Regions in Autism Spectrum Disorder

Impairments in language and communication are core features of autism spectrum disorder (ASD). The anatomy of critical language areas has been studied in ASD with inconsistent findings. We used MRI to measure gray matter volume and asymmetry of Heschl's gyrus, planum temporale, pars triangularis, and pars opercularis in 40 children and adolescents with ASD and 40 typically developing individuals, each divided into younger (7-11 years) and older (12-19 years) cohorts. The older group had larger left planum temporale volume and stronger leftward asymmetry than the younger group, regardless of diagnosis. The pars triangularis and opercularis together were larger in ASD than controls. Correlations between frontal language areas with language and symptom severity scores were significant in younger ASD children. Results suggest similar developmental changes in planum temporale anatomy in both groups, but group differences in pars triangularis and opercularis that may be related to language abilities and autism symptom severity.

Leftward interhemispheric asymmetry of macaque monkey temporal lobe language area homolog is evident at the cytoarchitectural, but not gross anatomic level

The most marked leftward interhemispheric asymmetry of the human and great ape brain is present in a multisensory association area of the superior temporal gyrus. This cortical region, the planum temporale (part of Brodmann's area 22), has a cytoarchitectural homolog, area Tpt, in Old World monkeys. Reports in non-human primates vary widely in descriptions of area Tpt-associated indices of asymmetry at the gross anatomic level, but such asymmetry has not yet been considered at the cellular level. Here we assessed a mixed sex sample of perfusion-fixed adult macaque monkey brains to determine whether purported interhemispheric asymmetry of Tpt is manifested at the gross anatomic level by consideration of the length of the lateral sulcus. A separate sample was used to consider interhemispheric asymmetry by volumetric assessment of the cytoarchitectural profile of area Tpt. There was no significant hemispheric asymmetry of lateral sulcus length at the gross anatomic level. Previous studies that used endocasts may not have factored in opercularization of the sylvian point, shown here as being pronounced. Conversely, there was a significant leftward volumetric asymmetry of area Tpt at the cytoarchitectural level. Furthermore, the intrahemispheric profile of area Tpt topography was more varied than expected. These results indicate that leftward hemispheric asymmetry of these critical human language areas may have been based on a functional substrate with a long evolutionary history. The leftward cytoarchitectural asymmetry and highly varied topography of Tpt should be factored into investigative approaches that consider this region of the cerebral cortex.

Functional MR Imaging of Language Processing: An Overview of Easy-to-Implement Paradigms for Patient Care and Clinical Research

Functional magnetic resonance (MR) imaging is one of the most commonly used functional neuroimaging techniques for studying the cerebral representation of language processing and is increasingly being used for both patient care and clinical research. In patient care, functional MR imaging is primarily used in the preoperative evaluation of (a) the relationship of a lesion to critical language areas and (b) hemispheric dominance. In clinical research, this modality is used to study language disorders due to neurologic disease and is generally aimed at language function recovery. A variety of language paradigms (verbal fluency, passive listening, comprehension) have been developed for the study of language processing and its separate components. All of the tasks are easy to implement, analyze, and perform. Silent gap acquisition is preferable for the imaging of specific language processing components because auditory stimuli are not degraded by imager noise. On the other hand, continuous acquisition allows more data to be acquired in less time, thereby increasing statistical power and decreasing the effects of motion artifacts. Although functional MR imaging cannot yet replace intraoperative electrocortical stimulation in patients undergoing neurosurgery, it may be useful for guiding surgical planning and mapping, thereby reducing the extent and duration of craniotomy.

Characterization of displaced white matter by brain tumors using combined DTI and fMRI

In vivo white matter tractography by diffusion tensor imaging (DTI) has become a popular tool for investigation of white matter architecture in the normal brain. Despite some unresolved issues regarding the accuracy of DTI, recent studies applied DTI for delineating white matter organization in the vicinity of brain lesions and especially brain tumors. Apart from the intrinsic limitations of DTI, the tracking of fibers in the vicinity or within lesions is further complicated due to changes in diseased tissue such as elevated water content (edema), tissue compression and degeneration. These changes deform the architecture of the white matter and in some cases prevent definite selection of the seed region of interest (ROI) from which fiber tracking begins. We show here that for displaced fiber systems, the use of anatomical approach for seed ROI selection yields insufficient results. Alternatively, we propose to select the seed points based on functional MRI activations which constrain the subjective seed ROI selection. The results are demonstrated on two major fiber systems: the pyramidal tract and the superior longitudinal fasciculus that connect critical motor and language areas, respectively. The fMRI based seed ROI selection approach enabled a more comprehensive mapping of these fiber systems. Furthermore, this procedure enabled the characterization of displaced white matter using the eigenvalue decomposition of DTI. We show that along the compressed fiber system, the diffusivity parallel to the fiber increases, while that perpendicular to the fibers decreases, leading to an overall increase in the fractional anisotropy index reflecting the compression of the fiber bundle. We conclude that definition of the functional network of a subject with deformed white matter should be done carefully. With fMRI, one can more accurately define the seed ROI for DTI based tractography and to provide a more comprehensive, functionally related, white matter mapping, a very important tool used in pre-surgical mapping.

Free Communications: Neuroimages MEG and EEG

Abstract Functional Magnetic Resonance Imaging- and Magnetoencephalography-based Brain Mapping for Identifying Language Functions and Its Validation by Electrocortical Stimulation. 1 Kyousuke Kamada, 1 Kensuke Kawai, 2 Yoshitaka Masutani, 2 Shigeki Aoki, and 1 Takaaki Kirino ( 1 Department of Neurosurgery, the University of Tokyo, Tokyo, Japan 2 Radiology, the University of Tokyo, Tokyo, Japan ). Purpose: Functional magnetic resonance imaging (fMRI) detects changes in cerebral blood flow and has been applied to the identification of the dominant hemisphere in language functions. Most of the fMRI-language studies disclose frontal activation by various lexico-semantic tasks. Magnetoencephalography (MEG) directly detects neuronal activity and records intracellular electric current flow in the brain. It localizes semantic responses peaking at approximately 400 msec after word presentation (late responses) in the temporoparietal regions, and the MEG responses are suspected to be strongly related to the receptive language function. We have, therefore, utilized these two modalities to independently visualize the expressive- and receptive-language functions. The successful mapping results by noninvasive techniques were verified by electrocortical stimulation. Methods: We investigated two patients with intractable epilepsy; a right-handed patient with left frontal epilepsy (Patient 1) and a left-handed patient with bilateral temporal lobe epilepsy (Patient 2). Neurological examinations disclosed no language deficits in both patients. They were asked to generate verbs related to acoustically presented nouns (verb generation) and to categorize visually presented words as abstract or concrete (A/C categorization) for fMRI and MEG investigations, respectively. The averaged magnetic signals were digitally filtered between 0.1 and 30 Hz. Significant MEG deflections were visually identified on the basis of the root mean squared fields of more than 10 sensors in the fronto-temporal (FT) or temporo-occipital (TO) regions. Locations and dipole moments of equivalent current dipoles were calculated every 2 msec from 250 to 600 msec after the stimulus was started, using the single equivalent dipole model. After subdural electrodes were placed over the hemisphere, the results of fMRI and MEG, and postoperative CT scan demonstrating the electrode positions were co-registered and superimposed on the anatomical MRI by maximizing the mutual information of all data sets with Affine transformation. The noninvasive functional mapping results were validated by 60Hz bipolar stimulation with the subdural electrodes. During the stimulation, patients were instructed to keep reading words, naming pictures, or generating verbs. Results: FMRI demonstrated activations in the inferior (IFG) and middle frontal gyri (MFG) of the suspected dominant hemisphere. While MEG disclosed highly concentrated semantic dipoles in the superior temporal (STG), supramarginal (SmG) and fusiform gyri (FuG) of the dominant hemisphere, FMRI and MEG clearly indicated language dominancy on the left hemisphere in Patient 1 and on the right in Patient 2. During locus validations, the electrocortical stimulation to the IFG and STG consistently induced speech arrest and sensory aphasia including dyslexia, respectively. In addition, the stimulation to the right FuG in Patient 2 revealed pure dyslexia with no suppression in the picture-naming task. Since the cortical stimulation to the MFG caused no neurological symptom, the MFG activation on fMRI did not correspond to the results of the stimulation. These findings suggest that the MFG might play roles in speech association or working memory and might be outside the critical language area compared to the other activated areas on fMRI and MEG. Conclusion: Noninvasive functional mapping techniques are powerful tools to identify language dominancy. IFG activation on fMRI, as well as STG, SmG, and FuG dipole clusters on MEG, are highly reliable for the detection of the critical language areas. MFG activation on fMRI, however, needs more careful validation and interpretation. It is necessary to modify and improve the lexico-semantic tasks of functional brain mapping for appropriate visualization of the critical language areas.

A Dynamic Model of Multilingualism

Bilingualism represents an interesting model of possible experience-dependent alterations in brain structure. The current study examines whether interhemispheric adaptations in brain structure are associated with bilingualism. Corpus callosum volume and cortical thickness asymmetry across 13 regions of interest (selected to include critical language and bilingual cognitive control areas) were measured in a sample of Spanish-English bilinguals and age- and gender-matched monolingual individuals (N = 39 per group). Cortical thickness asymmetry of the anterior cingulate region differed across groups, with thicker right than left cortex for bilinguals and the reverse for monolinguals. In addition, two adjacent regions of the corpus callosum (mid-anterior and central) had greater volume in bilinguals. The findings suggest that structural indices of interhemispheric organization in a critical cognitive control region are sensitive to variations in language experience.

Development of a functional magnetic resonance imaging protocol for intraoperative localization of critical temporoparietal language areas.

The aim of this study was to evaluate the use of functional magnetic resonance imaging as an alternative to intraoperative electrocortical stimulation mapping for the localization of critical language areas in the temporoparietal region. We investigated several requirements that functional magnetic resonance imaging must fulfill for clinical implementation: high predictive power for the presence as well as the absence of critical language function in regions of the brain, user-independent statistical methodology, and high spatial accuracy. Thirteen patients with temporal lobe epilepsy performed four different functional magnetic resonance imaging language tasks (ie, verb generation, picture naming, verbal fluency, and sentence comprehension) before epilepsy surgery that included intraoperative electrocortical stimulation mapping. To assess the optimal statistical threshold for functional magnetic resonance imaging, images were analyzed with three different statistical thresholds. Functional magnetic resonance imaging information was read into a surgical guidance system for identification of cortical areas of interest. Intraoperative electrocortical stimulation mapping was recorded by video camera, and stimulation sites were digitized. Next, a computer algorithm indicated whether significant functional magnetic resonance imaging activation was present or absent within the immediate vicinity (<6.4mm) of intraoperative electrocortical stimulation mapping sites. In 2 patients, intraoperative electrocortical stimulation mapping failed during surgery. Intraoperative electrocortical stimulation mapping detected critical language areas in 8 of the remaining 11 patients. Correspondence between functional magnetic resonance imaging and intraoperative electrocortical stimulation mapping depended heavily on statistical threshold and varied between patients and tasks. In 7 of 8 patients, sensitivity of functional magnetic resonance imaging was 100% with a combination of 3 functional magnetic resonance imaging tasks (ie, functional magnetic resonance imaging correctly detected all critical language areas with high spatial accuracy). In 1 patient, sensitivity was 38%; in this patient, functional magnetic resonance imaging was included in a larger area found with intraoperative electrocortical stimulation mapping. Overall, specificity was 61%. Functional magnetic resonance imaging reliably predicted the absence of critical language areas within the region exposed during surgery, indicating that such areas can be safely resected without the need for intraoperative electrocortical stimulation mapping. The presence of functional magnetic resonance imaging activity at noncritical language sites limited the predictive value of functional magnetic resonance imaging for the presence of critical language areas to 51%. Although this precludes current replacement of intraoperative electrocortical stimulation mapping, functional magnetic resonance imaging can at present be used to speed up intraoperative electrocortical stimulation mapping procedures and to guide the extent of the craniotomy.

The Critical Relationship between the Timing of Stimulus Presentation and Data Acquisition in Blocked Designs with fMRI

This paper concerns the experimental design and statistical models employed by fMRI activation studies which block presentation of linguistic stimuli. In particular, we note that the relationship between the timing of stimulus presentation and data acquisition can have a substantial impact on the ability to detect activations in critical language areas, even when the stimuli are presented in blocks. Using a blocked word rhyming paradigm and repeated investigations on a single subject, activation was observed in Broca's area (left inferior frontal cortex) and Wernicke's area (left posterior temporoparietal cortex) when (i) the timing of data acquisition was distributed throughout the peristimulus time and (ii) an event-related analysis was used to model the phasic nature of the hemodynamic response within each block of repeated word stimuli. In contrast, when the timing of data acquisition relative to stimulus presentation was fixed, activation was detected in Broca's area but not consistently in Wernicke's area. Our results indicate that phasic responses to stimuli occur even in a blocked design and that the sampling and proper modeling of these responses can have profound effects on their detection. Specifically, distributed sampling over peristimulus time is essential in order to detect small activations particularly when they are transient. These findings are likely to generalize to the detection of transient signals in any cognitive paradigm.