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Evaluation of language dominance is an essential step prior to epilepsy surgery. There is no consensus on an optimal methodology for determining language dominance using magnetoencephalography (MEG). Oscillatory dynamics are increasingly recognized as being of fundamental importance for brain function and dysfunction. Using task-related beta power modulations in MEG, we developed an analysis framework for localizing and lateralizing areas relevant to language processing in patients with focal epilepsy. We examined MEG responses from 29 patients (age 42 ​± ​13 years, 15M/14F) during auditory description naming (ADN) and visual picture naming (PN). MEG data were preprocessed using a combination of spatiotemporal filtering, signal thresholding, and ICA decomposition. Beta-band 17–25Hz power decrements were examined at both sensor and source levels. Volumetric grids of anatomical source space were constructed in MNI space at 8 ​mm isotropic resolution, and beta-band power changes were estimated using the dynamic imaging of coherent sources beamformer technique. A 600 ​ms temporal-window that ends 100 ​ms before speech onset was selected for analysis, to focus on later stages of word production such as phonologic selection and motor speech preparation. Cluster-based permutation testing was employed for patient- and group-level statistical inferences. Automated anatomic labeling atlas-driven laterality indices (LIs) were computed for 13 left and right language- and motor speech-related cortical regions. Group localization of ADN and PN consistently revealed significant task-related decrements of beta-power within language-related areas in the frontal, temporal and parietal lobes as well as motor-related regions of precentral/premotor and postcentral/somatomotor gyri. A region-of-interest analysis of ADN and PN suggested a strong correlation of r ​= ​0.74 (p ​ ​0.1) for most individuals (93% and 82% during ADN and PN, respectively), with average LIs of 0.40 ​± ​0.25 and 0.34 ​± ​0.20 for ADN and PN, respectively. Source analysis of task-related beta power decrements appears to be a reliable method for lateralizing and localizing brain activations associated with language processing in patients with epilepsy.

Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (

Neuroimaging studies suggest that categorical perception of speech phonemes in adults is primarily subserved by a pathway from bilateral primary auditory areas to association areas in the left middle superior temporal cortex, but the neural substrates underlying categorical speech perception in children are not yet known. Here, fMRI was used to examine the neural substrates associated with phoneme perception in 7- to 12-year-old children as well as the relationships among level of expertise in phoneme perception, the associated activation, and the development of reading and phonological processing abilities. While multiple regions in left frontal, temporal, and parietal cortex were found to be more responsive to phonemic than nonphonemic sounds, the extent of left lateralization in posterior temporal and parietal regions during phonemic relative to nonphonemic discrimination differed depending on the degree of categorical phoneme perception. In addition, an unexpected finding was that proficiency in categorical perception was strongly related to activation in the left ventral occipitotemporal cortex, an area frequently associated with orthographic processing. Furthermore, in children who showed lower proficiency in categorical perception, the level of categorical perception was positively correlated with reading ability and reading and reading-related abilities were inversely correlated with right mid-temporal activation in the phonemic relative to nonphonemic perception contrast. These results suggest that greater specialization of left hemisphere temporal and parietal regions for the categorical perception of phonemes, as well as activation of the region termed the visual word form area, may be important for the optimal developmental refinement of both phoneme perception and reading ability.

The idea that the conceptual system draws on sensory and motor systems has received considerable experimental support in recent years. Whether the tight coupling between sensory-motor and conceptual systems is modulated by factors such as context or task demands is a matter of controversy. Here, we tested the context sensitivity of this coupling by using action verbs in three different types of sentences in an fMRI study: literal action, apt but non-idiomatic action metaphors, and action idioms. Abstract sentences served as a baseline. The result showed involvement of sensory-motor areas for literal and metaphoric action sentences, but not for idiomatic ones. A trend of increasing sensory-motor activation from abstract to idiomatic to metaphoric to literal sentences was seen. These results support a gradual abstraction process whereby the reliance on sensory-motor systems is reduced as the abstractness of meaning as well as conventionalization is increased, highlighting the context sensitive nature of semantic processing.

Language consists of sequences of words, but comprehending phrases involves more than concatenating meanings: A boat house is a shelter for boats, whereas a summer house is a house used during summer, and a ghost house is typically uninhabited. Little is known about the brain bases of combinatorial semantic processes. We performed two fMRI experiments using familiar, highly meaningful phrases (LAKE HOUSE) and unfamiliar phrases with minimal meaning created by reversing the word order of the familiar items (HOUSE LAKE). The first experiment used a 1-back matching task to assess implicit semantic processing, and the second used a classification task to engage explicit semantic processing. These conditions required processing of the same words, but with more effective combinatorial processing in the meaningful condition. The contrast of meaningful versus reversed phrases revealed activation primarily during the classification task, to a greater extent in the right hemisphere, including right angular gyrus, dorsomedial prefrontal cortex, and bilateral posterior cingulate/precuneus, areas previously implicated in semantic processing. Positive correlations of fMRI signal with lexical (word-level) frequency occurred exclusively with the 1-back task and to a greater spatial extent on the left, including left posterior middle temporal gyrus and bilateral parahippocampus. These results reveal strong effects of task demands on engagement of lexical versus combinatorial processing and suggest a hemispheric dissociation between these levels of semantic representation.

The ability to create new meanings from combinations of words is one important function of the language system. We investigated the neural correlates of combinatorial semantic processing using fMRI. During scanning, participants performed a rating task on auditory word or pseudoword strings that differed in the presence of combinatorial and word-level semantic information. Stimuli included normal sentences comprised of thematically related words that could be readily combined to produce a more complex meaning, semantically incongruent sentences in which content words were randomly replaced with other content words, pseudoword sentences, and versions of these three sentence types in which syntactic structure was removed by randomly re-ordering the words. Several regions showed greater BOLD signal for stimuli with words than for those with pseudowords, including the left angular gyrus, left superior temporal sulcus, and left inferior frontal gyrus, suggesting that these areas are involved in semantic access at the single word level. In the angular and inferior frontal gyri these differences emerged early in the course of the hemodynamic response. An effect of combinatorial semantic structure was observed in the left angular gyrus and left lateral temporal lobe, which showed greater activation for normal compared to semantically incongruent sentences. These effects appeared later in the time course of the hemodynamic response, beginning after the entire stimulus had been presented. The data indicate a complex spatiotemporal pattern of activity associated with computation of word and sentence-level semantic information, and suggest a particular role for the left angular gyrus in processing overall sentence meaning.

In functional neuroimaging, a local decrease in blood flow during an active task, relative to a “resting” baseline, is referred to as task-induced deactivation (TID). TID may occur when resources shift from ongoing, internally generated processing typical of “resting” states to processing required by an exogenous task. We previously found specific brain regions in which TID increased as task processing demands increased. When engaged in an exogenous cognitive task, reallocation of resources from areas involved in internal processing should result in suspension of that processing. Self-reported thought content has been used as an indicator of the extent of internal processing activity. We investigated the relationship between TID and task-unrelated thought (TUT) frequency using an auditory target detection task with seven levels of task difficulty. At varied intervals during task performance, subjects indicated whether they were experiencing a TUT. We expected TUT frequency to decrease as task demands increased and for this pattern to correlate with TID magnitude across conditions. Generally, fewer TUTs were reported during difficult task conditions than during easier conditions. As TID magnitude increased across task conditions, the frequency of TUTs declined (r = 0.90, P = 0.005). Four left hemisphere regions (posterior parieto-occipital cortex, anterior cingulate gyrus, fusiform gyrus, and middle frontal gyrus) showed strong relationships between TUTs and TID (r > 0.79, P < 0.05 corrected). As these regions have been implicated in semantic processing and self-referential thought, the findings support the suspension of internal cognitive processing as one mechanism for TID.

The pronunciation of irregular words in deep orthographies like English cannot be specified by simple rules. On the other hand, the fact that novel letter strings can be pronounced seems to imply the existence of such rules. These facts motivate dual-route models of word naming, which postulate separate lexical (whole-word) and non-lexical (rule-based) mechanisms for accessing phonology. We used fMRI during oral naming of irregular words, regular words, and nonwords, to test this theory against a competing single-mechanism account known as the triangle model, which proposes that all words are handled by a single system containing distributed orthographic, phonological, and semantic codes rather than word codes. Two versions of the dual-route model were distinguished: an 'exclusive' version in which activation of one processing route predominates over the other, and a 'parallel' version in which both routes are equally activated by all words. The fMRI results provide no support for the exclusive dual-route model. Several frontal, insular, anterior cingulate, and parietal regions showed responses that increased with naming difficulty (nonword > irregular word > regular word) and were correlated with response time, but there was no activation consistent with the predicted response of a non-lexical, rule-based mechanism (i.e., nonword > regular word > irregular word). Several regions, including the angular gyrus and dorsal prefrontal cortex bilaterally, left ventromedial temporal lobe, and posterior cingulate gyrus, were activated more by words than nonwords, but these 'lexical route' regions were equally active for irregular and regular words. The results are compatible with both the parallel dual-route model and the triangle model. 'Lexical route' regions also showed effects of word imageability. Together with previous imaging studies using semantic task contrasts, the imageability effects are consistent with semantic processing in these brain regions, suggesting that word naming is partly semantically-mediated.

A prevailing neurobiological theory of semantic memory proposes that part of our knowledge about concrete, highly imageable concepts is stored in the form of sensory-motor representations. While this theory predicts differential activation of the semantic system by concrete and abstract words, previous functional imaging studies employing this contrast have provided relatively little supporting evidence. We acquired event-related functional magnetic resonance imaging (fMRI) data while participants performed a semantic similarity judgment task on a large number of concrete and abstract noun triads. Task difficulty was manipulated by varying the degree to which the words in the triad were similar in meaning. Concrete nouns, relative to abstract nouns, produced greater activation in a bilateral network of multimodal and heteromodal association areas, including ventral and medial temporal, posterior-inferior parietal, dorsal prefrontal, and posterior cingulate cortex. In contrast, abstract nouns produced greater activation almost exclusively in the left hemisphere in superior temporal and inferior frontal cortex. Increasing task difficulty modulated activation mainly in attention, working memory, and response monitoring systems, with almost no effect on areas that were modulated by imageability. These data provide critical support for the hypothesis that concrete, imageable concepts activate perceptually based representations not available to abstract concepts. In contrast, processing abstract concepts makes greater demands on left perisylvian phonological and lexical retrieval systems. The findings are compatible with dual coding theory and less consistent with single-code models of conceptual representation. The lack of overlap between imageability and task difficulty effects suggests that once the neural representation of a concept is activated, further maintenance and manipulation of that information in working memory does not further increase neural activation in the conceptual store.

Infrequent occurrences of a deviant sound within a sequence of repetitive standard sounds elicit the automatic mismatch negativity (MMN) event-related potential (ERP). The main MMN generators are located in the superior temporal cortex, but their number, precise location, and temporal sequence of activation remain unclear. In this study, ERP and functional magnetic resonance imaging (fMRI) data were obtained simultaneously during a passive frequency oddball paradigm. There were three conditions, a STANDARD, a SMALL deviant, and a LARGE deviant. A clustered image acquisition technique was applied to prevent contamination of the fMRI data by the acoustic noise of the scanner and to limit contamination of the electroencephalogram (EEG) by the gradient-switching artifact. The ERP data were used to identify areas in which the blood oxygenation (BOLD) signal varied with the magnitude of the negativity in each condition. A significant ERP MMN was obtained, with larger peaks to LARGE deviants and with frontocentral scalp distribution, consistent with the MMN reported outside the magnetic field. This result validates the experimental procedures for simultaneous ERP/fMRI of the auditory cortex. Main foci of increased BOLD signal were observed in the right superior temporal gyrus [STG; Brodmann area (BA) 22] and right superior temporal plane (STP; BA 41 and 42). The imaging results provide new information supporting the idea that generators in the right lateral aspect of the STG are implicated in processes of frequency deviant detection, in addition to generators in the right and left STP.

Current methods for thresholding functional magnetic resonance imaging (fMRI) maps are based on the well-known hypothesis-test framework, optimal for addressing novel theoretical claims. However, these methods as typically practiced have a strong bias toward protecting the null hypothesis, and thus may not provide an optimal balance between specificity and sensitivity in forming activation maps for surgical planning. Maps based on hypothesis-test thresholds are also highly sensitive to sample size and signal-to-noise ratio, whereas many clinical applications require methods that are robust to these effects. We propose a new thresholding method, optimized for surgical planning, based on normalized amplitude thresholding. We show that this method produces activation maps that are more reproducible and more predictive of postoperative cognitive outcome than maps produced with current standard thresholding methods.

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

The organization of tonotopic fields in human auditory cortex was investigated using functional magnetic resonance imaging. Subjects were presented with stochastically alternating multi-tone sequences in six different frequency bands, centered at 200, 400, 800, 1600, 3200, and 6400 Hz. Two mirror-symmetric frequency gradients were found extending along an anterior-posterior axis from a zone on the lateral aspect of Heschl's gyrus (HG), which responds preferentially to lower frequencies, toward zones posterior and anterior to HG that are sensitive to higher frequencies. The orientation of these two principal gradients is thus roughly perpendicular to HG, rather than parallel as previously assumed. A third, smaller gradient was observed in the lateral posterior aspect of the superior temporal gyrus. The results suggest close homologies between the tonotopic organization of human and nonhuman primate auditory cortex.

Neuropsychological and neurophysiological evidence point to a role for the left fusiform gyrus in visual word recognition, but the specific nature of this role remains a topic of debate. The aim of this study was to measure the sensitivity of this region to sublexical orthographic structure. We measured blood oxygenation (BOLD) changes in the brain with functional magnetic resonance imaging while fluent readers of English viewed meaningless letter strings. The stimuli varied systematically in their approximation to English orthography, as measured by the probability of occurrence of letters and sequential letter pairs (bigrams) comprising the string. A whole-brain analysis showed a single region in the lateral left fusiform gyrus where BOLD signal increased with letter sequence probability; no other brain region showed this response pattern. The results suggest tuning of this cortical area to letter probabilities as a result of perceptual experience and provide a possible neural correlate for the ‘word superiority effect’ observed in letter perception research.

The high degree of intersubject structural variability in the human brain is an obstacle in combining data across subjects in functional neuroimaging experiments. A common method for aligning individual data is normalization into standard 3D stereotaxic space. Since the inherent geometry of the cortex is that of a 2D sheet, higher precision can potentially be achieved if the intersubject alignment is based on landmarks in this 2D space. To examine the potential advantage of surface-based alignment for localization of auditory cortex activation, and to obtain high-resolution maps of areas activated by speech sounds, fMRI data were analyzed from the left hemisphere of subjects tested with phoneme and tone discrimination tasks. We compared Talairach stereotaxic normalization with two surface-based methods: Landmark Based Warping, in which landmarks in the auditory cortex were chosen manually, and Automated Spherical Warping, in which hemispheres were aligned automatically based on spherical representations of individual and average brains. Examination of group maps generated with these alignment methods revealed superiority of the surface-based alignment in providing precise localization of functional foci and in avoiding mis-registration due to intersubject anatomical variability. Human left hemisphere cortical areas engaged in complex auditory perception appear to lie on the superior temporal gyrus, the dorsal bank of the superior temporal sulcus, and the lateral third of Heschl's gyrus.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are now being combined to analyze brain function. Confounding the EEG signal acquired in the MR environment is a ballistocardiogram artifact (BA), which is predominantly caused by cardiac-related body movement. The objective of this study was to develop and evaluate a method for reducing these MR-induced artifacts to retrieve small auditory event-related potentials (ERPs) from EEG recorded during fMRI. An algorithm for BA reduction was developed that relies on timing information obtained from simultaneous electrocardiogram (ECG) recordings and subsequent creation of an adaptive BA template. The BA template is formed by median-filtering 10 consecutive BA events in the EEG signal. The continuously updated template is then subtracted from each BA in the EEG. The auditory ERPs are obtained through signal averaging of the remaining EEG signal. Experimental and simulated ERP data were estimated to assess effectiveness of the BA reduction. Simulation showed that the algorithm reduced BA without significantly altering the morphology of a signal periodically inserted in the EEG. Auditory ERP data, obtained in a 1.5-T scanner during a passive auditory oddball paradigm and processed with the BA reduction algorithm, were comparable to data recorded in a mock scanner outside the magnetic field with the same experimental paradigm. It is concluded that through adequate reduction of the BA, relatively small auditory ERPs can be acquired in the MR environment.