Ayumu Matani

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-/sup 18/F-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//spl ap/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 /sup 15/O-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.

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.

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.

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.

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. Hum Brain Mapp, 2010.

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.

Doppler Signal Processing of Blood Flow Using a Wavelet Transform

In medical echography, Doppler signal analysis is one of the most important diagnostic techniques. In Doppler signal analysis, time-frequency localization techniques are necessary. Many techniques have been proposed for the analysis. Short-time Fourier transform (STFT) is one of the most popular techniques. STFT has a fixed time-frequency window making it inappropriate for analysis of signals having a wide bandwidth. On the other hand, recently, wavelet transform (WT) has received much attention. WT has a flexible time-frequency window adaptable to any time-frequency range. In this paper, we describe an application of STFT and WT to Doppler signal processing. The STFT in this study had a rectangular window and required fast Fourier transform (FFT). On the other hand, the WT with the Morlet function as the mother wavelet was modified to reduce the amount of calculation. Then, we compared the suitability of STFT and WT for application to Doppler signal processing of a simulation and an actual blood flow. In the simulation, a flow having fast and slow velocity changes was assumed. The simulation revealed that the WT could reproduce the fast change of flow velocity, while the STFT could not. Then, a blood flow Doppler signal was measured at a point near the mitral valve in the left ventriculus. Only the WT was capable of reproducing the fast change of flow velocity in the heart. The WT is expected to be useful for analyzing blood flow disorders such as regurgitation.

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.

Phase-Interpolated 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.

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.