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.

Diazepam treatment blocks the elevation of hippocampal activity and the accelerated proliferation of hippocampal neural stem cells after focal cerebral ischemia in mice.

Hippocampal neurogenesis is accelerated during the elevation of hippocampal neural activities under both physiological and pathophysiological conditions. One of these conditions, middle cerebral artery occlusion (MCAO), induces both the hyperactivities of hippocampal network and the elevation of neural stem cell (NSC) proliferation. However, the causal relationship between the elevated activity and the elevation of NSC proliferation is still unclear. In this study, to block the elevation of hippocampal activity after MCAO in mice, we utilized a typical γ-aminobutyric acid type A (GABAA ) receptor active modulator, diazepam. With MCAO mice treated with diazepam, we observed complete disappearance of the elevation of hippocampal activity. Additionally, the diazepam treatment blocked the elevation of NSC proliferation after MCAO. From this result, it is speculated that the increased NSC proliferation is blocked by the suppression of elevated neural activity. However, diazepam might have effects other than the suppression of hippocampal activity, so we performed additional experiment and found that diazepam did not affect the number of bromodeoxyuridine-positive cells under the normal condition, whereas the GABA agonist pentobarbital stimulated NSC/neural progenitor cell proliferation and differentiation. Next, we evaluated the expression of the diazepam-binding inhibitor (DBI) protein and found that the cells expressed DBI in soma and on the surface of cell membrane. From these observations, we can propose that diazepam blocks the elevation of hippocampal activity and also NSC proliferation after MCAO.

Involvement of metabotropic glutamate receptor 5 signaling in activity-related proliferation of adult hippocampal neural stem cells.

Adult hippocampal neural stem cells can be activated by hippocampal neural activities. When focal cerebral ischemia, known as middle cerebral artery occlusion (MCAO), occurs, neural stem cells are activated to promote their proliferation. However, the mechanism by which these cells are activated is still unclear. Here, we indicate the involvement of metabotropic glutamate receptor 5 (mGluR5) signaling in neural stem cells in their activity-related proliferation after MCAO. We found mGluR5 molecules on neural stem cells by using calcium imaging. We detected the activation of neural stem cells by adding the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine. On a hippocampal slice, the activation of neural stem cells to promote their proliferation was initiated by theta-burst electrical stimulation at the perforant pathway, and this activation was significantly blocked by an mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP). In addition to this, the injection of the blood-brain barrier-permeable mGluR5 agonist 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide into live mice promoted the proliferation of neural stem cells. Moreover, in vivo theta-burst electrical stimulation induced proliferation of neural stem cells. A chronic field recording study showed that the activity of the hippocampal formation was elevated after MCAO. Finally, we observed that the mGluR5 antagonist MPEP significantly blocked the stimulated proliferation of neural stem cells induced by MCAO, by blocking mGluR5 signaling. Our results suggest that glutamates released by the elevated neural activities after MCAO may trigger mGluR5 signaling in neural stem cells to promote their proliferation.

The neuroanatomy of social trust predicts depression vulnerability.

Trust attitude is a social personality trait linked with the estimation of others' trustworthiness. Trusting others, however, can have substantial negative effects on mental health, such as the development of depression. Despite significant progress in understanding the neurobiology of trust, whether the neuroanatomy of trust is linked with depression vulnerability remains unknown. To investigate a link between the neuroanatomy of trust and depression vulnerability, we assessed trust and depressive symptoms and employed neuroimaging to acquire brain structure data of healthy participants. A high depressive symptom score was used as an indicator of depression vulnerability. The neuroanatomical results observed with the healthy sample were validated in a sample of clinically diagnosed depressive patients. We found significantly higher depressive symptoms among low trusters than among high trusters. Neuroanatomically, low trusters and depressive patients showed similar volume reduction in brain regions implicated in social cognition, including the dorsolateral prefrontal cortex (DLPFC), dorsomedial PFC, posterior cingulate, precuneus, and angular gyrus. Furthermore, the reduced volume of the DLPFC and precuneus mediated the relationship between trust and depressive symptoms. These findings contribute to understanding social- and neural-markers of depression vulnerability and may inform the development of social interventions to prevent pathological depression.

Influence of coherence between multiple cortical columns on alpha rhythm: a computational modeling study.

In electroencephalographic (EEG) and magnetoencephalographic (MEG) signals, stimulus-induced amplitude increase and decrease in the alpha rhythm, known as event-related synchronization and desynchronization (ERS/ERD), emerge after a task onset. ERS/ERD is assumed to reflect neural processes relevant to cognitive tasks. Previous studies suggest that several sources of alpha rhythm, each of which can serve as an alpha rhythm generator, exist in the cortex. Since EEG/MEG signals represent spatially summed neural activities, ERS/ERD of the alpha rhythm may reflect the consequence of the interactions between multiple alpha rhythm generators. Two candidates modulate the magnitude of ERS/ERD: (1) coherence between the activities of the alpha rhythm generators and (2) mean amplitude of the activities of the alpha rhythm generators. In this study, we use a computational model of multiple alpha rhythm generators to determine the factor that dominantly causes ERS/ERD. Each alpha rhythm generator is modeled based on local column circuits in the primary visual cortex and made to interact with the neighboring generators through excitatory connections. We observe that the model consistently reproduces spontaneous alpha rhythms, event-related potentials, phase-locked alpha rhythms, and ERS/ERD in a specific range of connectivity coefficients. Independent analyses of the coherence and amplitude of multiple alpha rhythm generators reveal that the ERS/ERD in the simulated data is dominantly caused by stimulus-induced changes in the coherence between multiple alpha rhythm generators. Nonlinear phenomena such as phase-resetting and entrainment of the alpha rhythm are related to the neural mechanism underlying ERS/ERD.

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.

Transduction of the Geomagnetic Field as Evidenced from alpha-Band Activity in the Human Brain.

Magnetoreception, the perception of the geomagnetic field, is a sensory modality well-established across all major groups of vertebrates and some invertebrates, but its presence in humans has been tested rarely, yielding inconclusive results. We report here a strong, specific human brain response to ecologically-relevant rotations of Earth-strength magnetic fields. Following geomagnetic stimulation, a drop in amplitude of electroencephalography (EEG) alpha-oscillations (8-13 Hz) occurred in a repeatable manner. Termed alpha-event-related desynchronization (alpha-ERD), such a response has been associated previously with sensory and cognitive processing of external stimuli including vision, auditory and somatosensory cues. Alpha-ERD in response to the geomagnetic field was triggered only by horizontal rotations when the static vertical magnetic field was directed downwards, as it is in the Northern Hemisphere; no brain responses were elicited by the same horizontal rotations when the static vertical component was directed upwards. This implicates a biological response tuned to the ecology of the local human population, rather than a generic physical effect. Biophysical tests showed that the neural response was sensitive to static components of the magnetic field. This rules out all forms of electrical induction (including artifacts from the electrodes) which are determined solely on dynamic components of the field. The neural response was also sensitive to the polarity of the magnetic field. This rules out free-radical "quantum compass" mechanisms like the cryptochrome hypothesis, which can detect only axial alignment. Ferromagnetism remains a viable biophysical mechanism for sensory transduction and provides a basis to start the behavioral exploration of human magnetoreception.

Speech comprehension assessed by electroencephalography: a new method using m-sequence modulation.

Electroencephalograms (EEGs) were recorded from eight Japanese speakers while they listened to Japanese and Spanish sentences (approximately 51s each). The sentences were modulated in amplitude by a binary m-sequence and played forward or backward. A circular cross-correlation function was computed between the EEG signals and the m-sequence and averaged across subjects. Independent component analysis of the averaged function revealed a component source response which was obtained only for the comprehensible Japanese and not for the incomprehensible sentences. The present study has thus shown that a 1-min long EEG signal is sufficient for the assessment of speech comprehension.

Phase series echography with prior waveform distortion for evaluating posterior waveform distortion.

We describe a pulse-echo ultrasound method for measuring nonlinear waveform distortion. First, two artificially distorted ultrasound pulses, one of which is transformed into the other by using a linear transform, are prepared prior to the measurement. The linear relationship does not hold for nonlinear propagation. Second, different initial-phase versions of the two pulses are separately transmitted to a specimen one after another, then the echoes with the same turnaround time are placed in order of the initial phase. The placed echoes, called a phase series, have complete information on the posterior waveform distortion. We formulate a waveform distortion index by using these two techniques. The waveform distortion index has a monotonic increasing relationship with the nonlinear parameter B/A. As an example application, we performed tissue characterization of boiled eggs. As a result, egg whites and yolks were clearly distinguished. This method should be useful for biological tissue characterization.

Extraction of a plasma time-activity curve from dynamic brain PET images based on independent component analysis.

A compartment model has been used for kinetic analysis of dynamic positron emission tomography (PET) data [e.g., 2-deoxy-2-18F-fluoro-D-glucose (FDG)]. The input function of the model [the plasma time-activity curve (pTAC)] was obtained by serial arterial blood sampling. It is of clinical interest to develop a method for PET studies that estimates the pTAC without needing serial arterial blood sampling. For this purpose, we propose a new method to extract the pTAC from the dynamic brain PET images using a modified independent component analysis [extraction of the pTAC using independent component analysis (EPICA). Source codes of EPICA are freely available at http://www5f.biglobe.ne.jp/ukimura/Software/top.html]. EPICA performs the appropriate preprocessing and independent component analysis (ICA) using an objective function that takes the various properties of the pTAC into account. After validation of EPICA by computer simulation, EPICA was applied to human brain FDG-PET studies. The results imply that the EPICA-estimated pTAC was similar to the actual measured pTAC, and that the estimated blood volume image was highly correlated with the blood volume image measured using 15O-CO inhalation. These results demonstrated that EPICA is useful for extracting the pTAC from dynamic PET images without the necessity of serial arterial blood sampling.

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.

Transcranial extracellular impedance control (tEIC) modulates behavioral performances.

Electric brain stimulations such as transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and transcranial alternating current stimulation (tACS) electrophysiologically modulate brain activity and as a result sometimes modulate behavioral performances. These stimulations can be viewed from an engineering standpoint as involving an artificial electric source (DC, noise, or AC) attached to an impedance branch of a distributed parameter circuit. The distributed parameter circuit is an approximation of the brain and includes electric sources (neurons) and impedances (volume conductors). Such a brain model is linear, as is often the case with the electroencephalogram (EEG) forward model. Thus, the above-mentioned current stimulations change the current distribution in the brain depending on the locations of the electric sources in the brain. Now, if the attached artificial electric source were to be replaced with a resistor, or even a negative resistor, the resistor would also change the current distribution in the brain. In light of the superposition theorem, which holds for any linear electric circuit, attaching an electric source is different from attaching a resistor; the resistor affects each active electric source in the brain so as to increase (or decrease in some cases of a negative resistor) the current flowing out from each source. From an electrophysiological standpoint, the attached resistor can only control the extracellular impedance and never causes forced stimulation; we call this technique transcranial extracellular impedance control (tEIC). We conducted a behavioral experiment to evaluate tEIC and found evidence that it had real-time enhancement and depression effects on EEGs and a real-time facilitation effect on reaction times. Thus, tEIC could be another technique to modulate behavioral performance.

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.

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.

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.

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.

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.