Shigeyuki Kan

Human brain activity time-locked to rapid eye movements during REM sleep.

To identify the neural substrate of rapid eye movements (REMs) during REM sleep in humans, we conducted simultaneous functional magnetic resonance imaging (fMRI) and polysomnographic recording during REM sleep. Event-related fMRI analysis time-locked to the occurrence of REMs revealed that the pontine tegmentum, ventroposterior thalamus, primary visual cortex, putamen and limbic areas (the anterior cingulate, parahippocampal gyrus and amygdala) were activated in association with REMs. A control experiment during which subjects made self-paced saccades in total darkness showed no activation in the visual cortex. The REM-related activation of the primary visual cortex without visual input from the retina provides neural evidence for the existence of human ponto-geniculo-occipital waves (PGO waves) and a link between REMs and dreaming. Furthermore, the time-course analysis of blood oxygenation level-dependent responses indicated that the activation of the pontine tegmentum, ventroposterior thalamus and primary visual cortex started before the occurrence of REMs. On the other hand, the activation of the putamen and limbic areas accompanied REMs. The activation of the parahippocampal gyrus and amygdala simultaneously with REMs suggests that REMs and/or their generating mechanism are not merely an epiphenomenon of PGO waves, but may be linked to the triggering activation of these areas.

Connectivity pattern changes in default-mode network with deep non-REM and REM sleep

Recent studies have compared default-mode network (DMN) connectivity in different arousal levels to investigate the relationship between consciousness and DMN. The comparison between the DMN in rapid eye movement (REM) sleep with that in non-REM (NREM) sleep is useful for revealing the relationship between arousal level and DMN, because the arousal level is at its lowest during deep NREM, while during REM sleep it is as high as wakefulness. Functional magnetic resonance imaging (fMRI) and polysomnogram data were acquired from participants in REM, deep NREM, and light NREM sleep, and the DMN was compared using functional connectivity analysis. Our analysis revealed that functional connectivity among the DMN core regions - the posterior cingulate cortex, rostral anterior cingulate cortex, and inferior parietal lobule - remained consistent across sleep states. In contrast, connectivity involving the DMN subsystems of REM sleep differs from that of NREM sleep, and the change well accounts for the characteristics of REM sleep. Our results suggest that both the DMN core region and subsystems may not relate to the maintenance of arousal. The DMN core network and subsystems may respectively serve to integrate brain regions and perform function specific to each level of arousal.

Network-dependent modulation of brain activity during sleep

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks.

Distinct role of spatial frequency in dissociative reading of ideograms and phonograms: An fMRI study

It has been proposed that distinct neural circuits are activated by reading Japanese ideograms (Kanji) and phonograms (Kana). By measuring high-density event-related potentials, we recently reported that spatial frequency (SF) information is responsible for the dissociation between Kanji and Kana reading. In particular, we found close links between Kana and low SF (LSF) information and between Kanji and high SF (HSF) information. However, it remains unclear which brain regions contribute to this dissociation. To determine this, we performed functional magnetic resonance imaging while presenting unfiltered or spatially filtered Kanji and Kana word stimuli to healthy native Japanese subjects. Fourier analysis revealed that Kanji and Kana stimuli were characterized by HSF and LSF information, respectively. When presented with either type of unfiltered stimulus (Kanji or Kana), the bilateral inferior temporal (IT, BA 37) regions were activated compared to the resting condition. Kana but not Kanji reading also activated the bilateral inferior parietal lobules (IPL, BA 40). When we compared Kanji and Kana reading directly, the left IT region was significantly activated by Kanji reading, while significant activation of the left IPL was observed during Kana reading. In response to filtered HSF stimuli, the Kanji reading minus Kana reading comparison revealed significant activation of the left IT region but not the left IPL. Conversely, significant activation of the left IPL but not the left IT region occurred in the Kana reading minus Kanji reading comparison for filtered LSF stimuli. These results suggest that Kanji and Kana engage a relatively overlapping network, within which the left IT is more involved in Kanji processing, while the left IPL contributes more to Kana processing. The preferential engagements of these brain regions could reflect the close links between Kana and LSF information, and between Kanji and HSF information. Therefore, this study provides further evidence that SF contributes to the dissociation between Kanji and Kana reading.

Different modulation of medial superior temporal activity across saccades: a functional magnetic resonance imaging study.

Studies on saccadic eye movements in humans and animals reported decreased cortical activation accompanying saccades in visual motion sensitive area MT+/V5, implying that the region is the neural basis of saccadic suppression. This, however, conflicts with findings that MT+/V5 is activated by saccades. As MT+/V5 can be subdivided into middle temporal (MT) and medial superior temporal (MST), these regions may have distinct functional roles that cause the discrepancy. To test this hypothesis, we compared the activation of MT with that of MST during exploratory saccades and visually guided saccades. MST was activated only during visually guided saccades, whereas MT was not activated by either. These findings support our hypothesis and suggest that the activity of these regions is differentially modulated depending on extraretinal information.

Modular organization of intrinsic brain networks: A graph theoretical analysis of resting-state fMRI

Recently, modular organization of intrinsic brain networks has been revealed by the graph theoretical analysis of resting-state functional MRI (rs-fMRI). In this paper, we introduce the concept of the graph theoretical analysis and modular organization. Then, we present the results of our analysis. In the graph theoretical analysis, intrinsic brain networks measured by rs-fMRI are modeled as the graphs (nodes linked by edges). Then, a module is defined as a group of highly inter-connected nodes which have relatively sparse connections to nodes in other modules. Recently, effective module detection methods have been proposed, and applied to rs-fMRI. In our study, rs-fMRI data were collected from 18 healthy young participants, and we detected the modules from a group level graph with fine spatial resolution. As a result, we found 6 dominant modules (default-mode, fronto-parietal, cingulo-opercular, sensorimotor, visual, and auditory). These modules were also detected when another module detection method was applied. Then, nodes were classified according to their roles based on their intra-module and inter-module connections. We found that majority of brain regions were classified as peripheral nodes which mostly connect with nodes within their modules. Interestingly, fronto-parietal module which consists of transmodal higher-order brain regions had more connector nodes (connecting with other modules) than unimodal visual and sensorimotor modules. This suggested that modular organization in intrinsic brain networks can reflect functional properties of brain systems.

Training Artificial Neural Network using MR images for Visual Axes Estimation during Sleep

Estimation of visual axis during sleep has been attracting a considerable attention. A simultaneous measurement system composed of functional MRI and infrared-video has been developed to investigate a relationship between eye-movement and brain function during sleep. Although there are some methods for measuring visual axis of opening eyes from video images, they cannot be applied to estimate visual axis of closing eyes during sleep. This paper proposes a method based on artificial neural network (ANN) for estimating visual axes during sleep from infrared-video images. Also, this paper introduces a novel calibration method using MRI. The method takes structural MR images of the eyeball and detects the visual axes from the MR images. And, using the detected visual axes and the simultaneously taken infrared-video image, the ANN is trained. The experimental results showed that the proposed method detected visual axes of the right and the left eyes with errors of 1.32plusmn4.24 (RMSEplusmnSD) deg and 1.26plusmn4.20 deg, respectively.

fMRI evidence of improved visual function in patients with progressive retinitis pigmentosa by eye-movement training.

To evaluate changes in the visual processing of patients with progressive retinitis pigmentosa (RP) who acquired improved reading capability by eye-movement training (EMT), we performed functional magnetic resonance imaging (fMRI) before and after EMT. Six patients with bilateral concentric contraction caused by pigmentary degeneration of the retina and 6 normal volunteers were recruited. Patients were given EMT for 5 min every day for 8–10 months. fMRI data were acquired on a 3.0-Tesla scanner while subjects were performing reading tasks. In separate experiments (before fMRI scanning), visual performances for readings were measured by the number of letters read correctly in 5 min. Before EMT, activation areas of the primary visual cortex of patients were 48.8% of those of the controls. The number of letters read correctly in 5 min was 36.6% of those by the normal volunteers. After EMT, the activation areas of patients were not changed or slightly decreased; however, reading performance increased in 5 of 6 patients, which was 46.6% of that of the normal volunteers (p< 0.05). After EMT, increased activity was observed in the frontal eye fields (FEFs) of all patients; however, increases in the activity of the parietal eye fields (PEFs) were observed only in patients who showed greater improvement in reading capability. The improvement in reading ability of the patients after EMT is regarded as an effect of the increased activity of FEF and PEF, which play important roles in attention and working memory as well as the regulation of eye movements.

Activation in left primary visual cortex representing parafoveal visual field during reading Japanese texts.

Activation in the left primary visual cortex (V1) representing the parafoveal field during text reading has been interpreted as attentional modulation in the process of deciding saccadic target for reading ahead. Kanji words serve the main cue to decide the goal of saccades in Japanese. We aimed to determine the exact location of this modulation in the V1 and to determine whether the area of the modulation changes according to the location where the next Kanji word appears or it is fixed on a certain region in V1. Using functional magnetic resonance imaging, we determined the area in V1 representing each eccentricity on the horizontal meridian of the visual field for each participant. Then we investigated brain activation while they were reading two sets of Japanese texts that scrolled leftward as the participants. In set 1, the distance between the heads of adjacent Kanji words was about 3°. In set 2, the distance was about 5°. From the results of these experiments, we obtained activation amplitude of the area corresponding to each eccentricity. We recorded eye movements simultaneously with the acquisition of fMRI data. The maximum peak of the activation was found in the region representing about 4.5° of eccentricity on the horizontal meridian in the left V1 for each participant. The activation pattern did not essentially differ between the two text conditions, although the location of the saccades made for reading next section of the text corresponds to the head of the next Kanji word. The activation modulation during reading Japanese texts occurs in the parafoveal V1 of the left hemisphere. The attentional modulation did not change with the distance to the next goal of saccade but was fixed on the area representing about 4.5° of eccentricity.

P18-6 Dynamic brain networks depend on arousal level: An fMRI study using a graph theory

used with facial stimuli. However, normal day-to-day images always have a background. Moreover, background images are considered important in art forms (painting, photography, and movies, etc.) for eliciting effective expressions. In recent years, the background images are often used in computer screen for expecting emotional effects. We assessed the effect of background images on brain activation by using functional magnetic resonance imaging (fMRI). In this study, we implemented two types of experiments. In the first experiment, during fMRI scanning, face images with background images were presented repeatedly to 8 healthy righthanded males. Facial stimuli comprised 5 photographs of a face image expressing fear. The background images comprised 2 photographs one is lightning and the other is a flower garden. It is thought that face images expressing fear coincide with lightning background image on the point of situation. In the second experiment, we used background image of fire instead of lighting of first experiment. After scanning, the subjects rated the impression created by the images on the Plutchik scale. In the first experiment, significant effects of the image of the face against the lighting background minus that against the flower garden were assessed using a t-test. In the second experiment, significant effects of the image of the face against the fire background minus that against the flower garden were assessed. The activation of the amygdale and hippocampus was detected in the first experiment, but not detected in the second experiment. This difference of activation was thought to be occurred by the difference of effect of empathy.