Distinctive responses in anterior temporal lobe and ventrolateral prefrontal cortex during categorization of semantic information.

Semantic categorization is a fundamental ability in language as well as in interaction with the environment. However, it is unclear what cognitive and neural basis generates this flexible and context dependent categorization of semantic information. We performed behavioral and fMRI experiments with a semantic priming paradigm to clarify this. Participants conducted semantic decision tasks in which a prime word preceded target words, using names of animals (mammals, birds, or fish). We focused on the categorization of unique marine mammals, having characteristics of both mammals and fish. Behavioral experiments indicated that marine mammals were semantically closer to fish than terrestrial mammals, inconsistent with the category membership. The fMRI results showed that the left anterior temporal lobe was sensitive to the semantic distance between prime and target words rather than category membership, while the left ventrolateral prefrontal cortex was sensitive to the consistency of category membership of word pairs. We interpreted these results as evidence of existence of dual processes for semantic categorization. The combination of bottom-up processing based on semantic characteristics in the left anterior temporal lobe and top-down processing based on task and/or context specific information in the left ventrolateral prefrontal cortex is required for the flexible categorization of semantic information.

Facilitated lexical ambiguity processing by transcranial direct current stimulation over the left inferior frontal cortex.

Previous studies suggest that the left inferior frontal cortex is involved in the resolution of lexical ambiguities for language comprehension. In this study, we hypothesized that processing of lexical ambiguities is improved when the excitability of the left inferior frontal cortex is enhanced. To test the hypothesis, we conducted an experiment with transcranial direct current stimulation (tDCS). We investigated the effect of anodal tDCS over the left inferior frontal cortex on behavioral indexes for semantic judgment on lexically ambiguous and unambiguous words within a context. Supporting the hypothesis, the RT was shorter in the anodal tDCS session than in the sham session for ambiguous words. The results suggest that controlled semantic retrieval and contextual selection were facilitated by anodal tDCS over the left inferior frontal cortex.

Accuracy of estimating strengths of dipole moments from a small number of magnetoencephalographic trial data.

The conventional analysis estimates both the locations and strengths of neural source activations from event-related magnetoencephalography data that are averaged across about a hundred trials. In the present report, we propose a new method based on a minimum modified-l 1-norm to obtain the dependence of strengths on the presented stimuli from a limited number of trial data. It estimates the strengths from 10-trial average data and the locations from 100-trial average data. The method can be applied to neural activations whose strengths, but not locations, depend on the presented stimuli. For instance, it can be used in experiments in which the activation in the anterior temporal area (aT) is measured by varying semantic relatedness between stimuli in linguistic experiments. We conducted a realistic simulation, following previous experiments on lexico-semantic processing, in which five neural sources were simultaneously activated. The results showed that when the signal-to-noise ratio was one for non-averaged data, the proposed method had standard deviations of 13 % for the normalized strengths in the aT. It is inferred on the basis of the general linear model in which the strength has a linear dependence on the stimulus parameters that the proposed method can detect the dependence at a significance level of 1 % if the peak-to-peak change in normalized strength is more than 49 %. It is smaller than 66 % for the conventional method, which estimated locations and strengths from 10-trial data for each point. Thus, the proposed method can plot an activation-strength versus stimulus-parameter curve with better sensitivity.

Language comprehension dependent on emotional context: a magnetoencephalography study.

In communication, language can be interpreted differently depending upon the emotional context. To clarify the effect of emotional context on language processing, we performed experiments using a cross-modal priming paradigm with an auditorily presented prime and a visually presented target. The primes were the names of people that were spoken with a happy, sad, or neutral intonation; the targets were interrogative one-word sentences with emotionally neutral content. Using magnetoencephalography, we measured neural activities during silent reading of the targets presented in a happy, sad, or neutral context. We identified two conditional differences: the happy and sad conditions produced less activity than the neutral condition in the right posterior inferior and middle frontal cortices in the latency window from 300 to 400 ms; the happy and neutral conditions produced greater activity than the sad condition in the left posterior inferior frontal cortex in the latency window from 400 to 500 ms. These results suggest that the use of emotional context stored in the right frontal cortex starts at ∼300 ms, that integration of linguistic information with emotional context starts at ∼400 ms in the left frontal cortex, and that language comprehension dependent on emotional context is achieved by ∼500 ms.

Phase-interpolated averaging for analyzing electroencephalography and magnetoencephalography epochs.

Stimulus-locked averages of electroencephalography (EEG) and magnetoencephalography (MEG) epochs reveal characteristic waveforms. EEG/MEG generation models to have reconstruct such waveforms have been recently proposed. These models assume that evoked, phase-modulated, and amplitude-modulated activities occur solely or simultaneously. We propose a two-stage stimulus-locked averaging method, called phase-interpolated averaging, to investigate the EEG/MEG generation process. First, virtual EEG/MEG epochs, which would be obtained as if instantaneous phases for each time sampling point were on a phase-grid, are interpolated from actually measured EEG/MEG epochs. Then, the virtual EEG/MEG epochs are discrete Fourier transformed. A simulation revealed that the zeroth Fourier term revealed the evoked activity, the first Fourier term revealed the amplitude-modulated activity, and the condition number of the interpolation reflected the phase-modulated activity. On the basis of these facts, a preliminary EEG analysis implied that the evoked activity is much smaller than what would be expected by using conventional averaging, the evoked and phase-modulated activities simultaneously occur, and the amplitude-modulated activity occasionally associates with the evoked and phase-modulated activities. To the best of our knowledge, this is the first time that these three activities have been shown to coexist by actually separating them.

Masked immediate-repetition-priming effect on the early lexical process in the bilateral anterior temporal areas assessed by neuromagnetic responses.

A masked priming paradigm has been used to measure unconscious and automatic context effects on the processing of words. However, its spatiotemporal neural basis has not yet been clarified. To test the hypothesis that masked repetition priming causes enhancement of neural activation, we conducted a magnetoencephalography experiment in which a prime was visually presented for a short duration (50 ms), preceded by a mask pattern, and followed by a target word that was represented by a Japanese katakana syllabogram. The prime, which was identical to the target, was represented by another hiragana syllabogram in the "Repeated" condition, whereas it was a string of unreadable pseudocharacters in the "Unrepeated" condition. Subjects executed a categorical decision task on the target. Activation was significantly larger for the Repeated condition than for the Unrepeated condition at a time window of 150-250 ms in the right occipital area, 200-250 ms in the bilateral ventral occipitotemporal areas, and 200-250 ms and 200-300 ms in the left and right anterior temporal areas, respectively. These areas have been reported to be related to processing of visual-form/orthography and lexico-semantics, and the enhanced activation supports the hypothesis. However, the absence of the priming effect in the areas related to phonological processing implies that automatic phonological priming effect depends on task requirements.

Phase-compensated averaging for analyzing electroencephalography and magnetoencephalography epochs.

Stimulus-locked averaging for electroencephalography and/or megnetoencephalography (EEG/MEG) epochs cancels out ongoing spontaneous activities by treating them as noise. However, such spontaneous activities are the object of interest for EEG/MEG researchers who study phase-related phenomena, e.g., long-distance synchronization, phase-reset, and event-related synchronization/desynchronization (ERD/ERS). We propose a complex-weighted averaging method, called phase-compensated averaging, to investigate phase-related phenomena. In this method, any EEG/MEG channel is used as a trigger for averaging by setting the instantaneous phases at the trigger timings to 0 so that cross-channel averages are obtained. First, we evaluated the fundamental characteristics of this method by performing simulations. The results showed that this method could selectively average ongoing spontaneous activity phase-locked in each channel; that is, it evaluates the directional phase-synchronizing relationship between channels. We then analyzed flash evoked potentials. This method clarified the directional phase-synchronizing relationship from the frontal to occipital channels and recovered another piece of information, perhaps regarding the sequence of experiments, which is lost when using only conventional averaging. This method can also be used to reconstruct EEG/MEG time series to visualize long-distance synchronization and phase-reset directly, and on the basis of the potentials, ERS/ERD can be explained as a side effect of phase-reset.

Neuroimaging study on brain asymmetries in situs inversus totalis.

Situs inversus totalis (SI) is a rare condition in which all visceral organs are arranged as mirror images of the usual pattern. The objective of this study was to determine whether SI individuals have reversed brain asymmetries. We performed a neuroimaging study on 3 SI subjects and 11 control individuals with normally arranged visceral organs. The language-dominant hemisphere was determined by magnetoencephalography. Left-hemispheric dominance was observed in 1 SI subject and all controls, whereas right-hemispheric dominance was observed in the remaining 2 SI subjects. Statistical analysis revealed that language dominance patterns in SI subjects were different from those in the controls, suggesting that the developmental mechanisms underlying visceral organ asymmetries are related to those underlying functional brain asymmetry. Anatomical brain asymmetries were determined by magnetic resonance imaging. SI subjects had the same planum temporale (PT) asymmetry pattern as the controls, but a reversed petalia asymmetry pattern. The inferior frontal gyrus (IFG) asymmetry pattern varied within both groups, indicating a relationship between the rightward IFG and right-hemispheric language dominance. These results suggest that the developmental mechanisms underlying visceral organ asymmetries are related to those underlying petalia asymmetry but not to those underlying PT and IFG asymmetries, and that brain asymmetries might develop via multiple region-dependent mechanisms.

Neural activations correlated with reading speed during reading novels.

Functional magnetic resonance imaging was used to measure neural activations in subjects instructed to silently read novels at ordinary and rapid speeds. Among the 19 subjects, 8 were experts in a rapid reading technique. Subjects pressed a button to turn pages during reading, and the interval between turning pages was recorded to evaluate the reading speed. For each subject, we evaluated activations in 14 areas and at 2 instructed reading speeds. Neural activations decreased with increasing reading speed in the left middle and posterior superior temporal area, left inferior frontal area, left precentral area, and the anterior temporal areas of both hemispheres, which have been reported to be active for linguistic processes, while neural activation increased with increasing reading speed in the right intraparietal sulcus, which is considered to reflect visuo-spatial processes. Despite the considerable reading speed differences, correlation analysis showed no significant difference in activation dependence on reading speed with respect to the subject groups and instructed reading speeds. The activation reduction with speed increase in language-related areas was opposite to the previous reports for low reading speeds. The present results suggest that subjects reduced linguistic processes with reading speed increase from ordinary to rapid speed.

Early neural activation for lexico-semantic access in the left anterior temporal area analyzed by an fMRI-assisted MEG multidipole method.

To determine the time and location of lexico-semantic access, we measured neural activations by magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) and estimated the neural sources by fMRI-assisted MEG multidipole analysis. Since the activations for phonological processing and lexico-semantic access were reported to overlap in many brain areas, we compared the activations in lexical and phonological decision tasks. The former task required visual form processing, phonological processing, and lexico-semantic access, while the latter task required only visual form and phonological processing, with similar phonological task demands for both tasks. The activation areas observed among 9 or 10 subjects out of 10 were the superior temporal and inferior parietal areas, anterior temporal area, and inferior frontal area of both hemispheres, and the left ventral occipitotemporal area. The activations showed a significant difference between the 2 tasks in the left anterior temporal area in all 50-ms time windows between 200-400 ms from the onset of visual stimulus presentation. Previous studies on semantic dementia and neuroimaging studies on normal subjects have shown that this area plays a key role in accessing semantic knowledge. The difference between the tasks appeared in common to all areas in the time windows of 100-150 ms and 400-450 ms, suggesting early differences in visual form processing and late differences in the decision process, respectively. The present results demonstrate that the activations for lexico-semantic access in the left anterior temporal area start in the time window of 200-250 ms, after early visual form processing.

Phonological influences on lexicosemantic processing of kanji words.

To investigate the phonological influences on the lexicosemantic process with a strong orthographic constraint, we used kanji (morphogram) homophone words and measured, using magnetoencephalography, the neural activities during the silent reading of prime-target pairs. The primes were phonologically the same as or different from the targets or pseudocharacters. The neural activities in the left posterior temporal and inferior parietal areas became weaker with phonological repetition. Furthermore, stronger activities for the different condition in the left anterior temporal area and for the same condition in the left inferior frontal cortex, respectively, suggest the roles of these areas of the brain in the semantic processing of words and in the selection of appropriate meanings. We conclude that phonological information affects the lexicosemantic process even with a strong orthographic constraint.

Lexical access and selection of contextually appropriate meaning for ambiguous words.

To clarify the neural mechanisms of lexical access and selection of contextually appropriate meanings for ambiguous words, we investigated the spatio-temporal characteristics of neural activities during silent reading and semantic judgment of lexically ambiguous or unambiguous target words that were preceded by semantically related or unrelated words by using magnetoencephalography. The left posterior superior temporal/inferior parietal area and the left anterior middle/inferior temporal area consistently showed a clear context effect, regardless of the ambiguity: the activities for related words were weaker than those for unrelated words. The activities in the left inferior frontal cortex, in contrast, were influenced by ambiguities. From approximately 200 to 300 ms, the activities in the left anterior inferior frontal cortex (aIFC) were stronger for ambiguous words than for unambiguous words, regardless of context. The stronger activities in the left aIFC, reflecting an increase in controlled semantic retrieval, indicate that multiple meanings for lexically ambiguous words are accessed irrespective of context. At approximately 400 ms, the left posterior inferior frontal cortex (pIFC) showed a clear context effect for unambiguous words but not for ambiguous ones. In addition, the activation in the left pIFC was stronger for related ambiguous words than for related unambiguous ones. These results suggest that in ambiguous words, not only contextually appropriate meanings but also two or more inappropriate meanings would be semantically integrated with a context. We conclude that the left IFC plays an important role in selecting an appropriate meaning from multiple alternatives after the integration of contextual information.

Temporal characteristics of neural activity related to target detection during visual search.

A previous MEG study on neural activities during the orientation singleton search showed that both efficient and inefficient searches shared a common neural network and the search efficiency was determined by a neural process executed in the temporal and parietal areas. The target segmentation stage, however, remains to be elucidated. In the present study, MEG and fMRI experiments were conducted, and moment-magnitudes of equivalent current dipoles were estimated with an fMRI-constrained MEG multi-dipole method to obtain differences between target-present and -absent conditions in each brain region for the whole time course. The dipole moments around the calcarine sulcus (CaS) and posterior fusiform gyrus (pFuG) increased at latencies around 70-350 ms. Activity around the CaS consisted of a prominent and a subsequent smaller but still obvious peak (117, 215 ms); the first peak showed no difference between conditions, while the second peak was significantly larger in the target-present condition. Activity around the pFuG had a prominent peak (125 ms) and subsequent small activity (237 ms), whereas the target's presence or not had no influence on either activity. The activity of the right intraparietal sulcus (IPS) was significantly larger than that for the left IPS at latencies around 196 ms irrespective of the target's presence or not. The activity of the other brain regions such as the posterior superior temporal sulcus, cingulate sulcus and central sulcus showed no difference between target conditions. The results demonstrate that neural activities of multiple regions had different temporal characteristics, and the later activity around the CaS was related to the target segregation from its surroundings during the orientation contrast search.

Influence of seamlessness between pre- and poststimulus alpha rhythms on visual evoked potential.

The influence of seamlessness between the prestimulus alpha rhythm and poststimulus alpha ringing on the visual evoked potentials (VEPs) was investigated. Subjects passively viewed a series of 1000 flash stimuli with their eyelids closed, and their VEPs were recorded. The instantaneous phase angle of the alpha rhythm in each subject was calculated by using a two-cycle complex exponential sequence. VEPs were classified into four subsets according to seamlessness: how well the phase angle of the prestimulus alpha rhythm and the backward-extrapolated phase angle from poststimulus alpha ringing were synchronized. VEPs of each subset were averaged. A one-way repeated measures analysis of variance revealed that seamlessness significantly affected the amplitude of P100. Moreover, the level of seamlessness significantly affected the phase locking index. Two models for the generating evoked potentials have been proposed; one is the phase resetting model (Makeig, S., Westerfield, M., Jung, T.P., Enghoff, S., Townsend, J., Courchesne, E., Sejnowski, T.J., 2002. Dynamic brain sources of visual evoked responses. Science 295, 690-694) and the other is the evoked model (Mäkinen, V., Tiitinen, H., May, P., 2005. Auditory event-related responses are generated independently of ongoing brain activity. Neuroimage 24, 961-968). These results suggest that alpha ringing is possibly generated by the phase-resetting alpha rhythm and support the phase resetting model.

Anatomically constrained dipole adjustment (ANACONDA) for accurate MEG/EEG focal source localizations.

This paper proposes an alternative approach to enhance localization accuracy of MEG and EEG focal sources. The proposed approach assumes anatomically constrained spatio-temporal dipoles, initial positions of which are estimated from local peak positions of distributed sources obtained from a pre-execution of distributed source reconstruction. The positions of the dipoles are then adjusted on the cortical surface using a novel updating scheme named cortical surface scanning. The proposed approach has many advantages over the conventional ones: (1) as the cortical surface scanning algorithm uses spatio-temporal dipoles, it is robust with respect to noise; (2) it requires no a priori information on the numbers and initial locations of the activations; (3) as the locations of dipoles are restricted only on a tessellated cortical surface, it is physiologically more plausible than the conventional ECD model. To verify the proposed approach, it was applied to several realistic MEG/EEG simulations and practical experiments. From the several case studies, it is concluded that the anatomically constrained dipole adjustment (ANACONDA) approach will be a very promising technique to enhance accuracy of focal source localization which is essential in many clinical and neurological applications of MEG and EEG.

fMRI-constrained MEG source imaging and consideration of fMRI invisible sources.

Recent studies on multimodal brain source imaging have shown that the use of functional MRI (fMRI) prior information could enhance spatial resolution of magnetoencephalography (MEG), while MEG could compensate poor temporal resolution of fMRI. This article deals with a multimodal imaging method, which combines fMRI and MEG for enhancing both spatial and temporal resolutions. Recent studies on the combination of fMRI and MEG have suggested that the fMRI prior information could be very easily implemented by just giving different weighting factors to the diagonal terms of source covariance matrix in linear inverse operator. We applied the fMRI constrained imaging method to several simulation data and experimental data (Japanese language lexical judgment experiment), and found that some MEG sources may be eliminated by the introduction of the fMRI weighting and the eliminated sources may affect source estimation in fMRI activation regions. In this article, in order to check whether the eliminated sources were fMRI invisible ones or just spurious ones, we placed small numbers of regional sources (rotating dipoles) around all possible activation regions and investigated their temporal changes. By investigating the results carefully, we could evaluate whether the missed sources were real or not.

Neural activation dependent on reading speed during covert reading of novels.

We measured the dependence of activation on reading speed with fMRI in a wide range that spanned two orders of magnitude. We used four trained subjects who were capable of a technique of rapid reading, and another four who were untrained, to investigate the neural mechanism during the covert reading of novels. This revealed that activation decreased for trained subjects during extremely rapid reading in the left superior and middle temporal gyri or near Wernicke's area, and in Broca's area. These results suggest that the trained subjects read sentences with fewer phonological processes. The decrease in activation might also be due to fewer semantic and syntactic processes, although the subjects understood the story lines in the novels.

Right-lateralized neural activity during inner speech repeated by cues.

Neural activity during inner speech of meaningless syllable sequences was measured with MEG and fMRI from eight right-handed subjects who executed a delayed-response task. An fMRI-constrained MEG multi-dipole analysis showed that active neural sources were detected at latencies of about 200-300 ms after cues near the posterior superior temporal sulcus and were more numerous in the right hemisphere than in the left hemisphere. Since the subjects were cued to repeat inner speech of meaningless sequences stored in verbal working memory, the activity in the right (language-nondominant) hemisphere suggested that the task required processing of more prosodic features such as pitch and rhythm than phonemic features.

Information flow related to visual search assessed using magnetoencephalography.

The sequence of neural activation during a visual search task was investigated using magnetoencephalography and the source locations for the activations were analyzed using a single-dipole algorithm. Five components (M1-5) were detected at mean latencies of 110, 146, 196, 250 and 333 ms in both of two different stimulus conditions; a target popped out in one stimulus condition (pop-out), while it did not in the other condition (non-pop-out). Statistical analysis showed that the M3 amplitude was larger and the M5 latency was shorter in the pop-out condition than in the non-pop-out condition, while there was no difference in the other components between the conditions. Neural sources were localized in the calcarine sulcus (M1) and the posterior fusiform gyrus (M2) of the hemisphere contralateral to the stimuli, the intraparietal sulcus and the posterior superior temporal sulcus (M3) in either of the hemispheres, and the calcarine sulcus (M4) of the same hemisphere in which the early processing (M1 and M2) occurred. The criteria for source localization were not satisfied for M5. The results suggest that the processing for pop-out and non-pop-out stimuli share a common mechanism; after early feature processing in the occipital cortex (M1 and M2), visual information is processed in the parietal and temporal regions (M3) and then some of this information is fed back to the occipital cortex (M4).

An fMRI-constrained MEG source analysis with procedures for dividing and grouping activation.

To analyze neural activity using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), we developed a method for fixing equivalent current dipoles of MEG in activation areas of fMRI. It includes a procedure for dividing large fMRI activation volumes into subvolumes in each of which a dipole is placed and another procedure for grouping neighboring dipoles whose temporal changes are inseparable based on MEG data. To optimize the procedures' parameters, we carried out simulations and found that (1) any single dipole within 10 mm from a true source can explain MEG data with a correlation of 94% on average for the low signal-to-noise ratio of 3 and (2) a neighboring dipole within a few tens of millimeters from the dipole nearest to the true source tends to be highly incorporated in explaining MEG data. We applied the method to data measured in a language experiment and detected 13 significant sources. The results show that the present method is promising for detecting neural activity originating from a number of separate neural sources.