The Characteristics of Power Spectral Density in Bipolar Disorder at the Resting State.

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks.

Detection of deviance in Japanese kanji compound words.

Reading fluency is based on the automatic visual recognition of words. As a manifestation of the automatic processing of words, an automatic deviance detection of visual word stimuli can be observed in the early stages of visual recognition. To clarify whether this phenomenon occurs with Japanese kanji compounds-since their lexicality is related to semantic association-we investigated the brain response by utilizing three types of deviants: differences in font type, lexically correct or incorrect Japanese kanji compound words and pseudo-kanji characters modified from correct and incorrect compounds. We employed magnetoencephalography (MEG) to evaluate the spatiotemporal profiles of the related brain regions. The study included 22 adult native Japanese speakers (16 females). The abovementioned three kinds of stimuli containing 20% deviants were presented during the MEG measurement. Activity in the occipital pole region of the brain was observed upon the detection of font-type deviance within 250 ms of stimulus onset. Although no significant activity upon detecting lexically correct/incorrect kanji compounds or pseudo-kanji character deviations was observed, the activity in the posterior transverse region of the collateral sulcus (pCoS)-which is a fusiform neighboring area-was larger when detecting lexically correct kanji compounds than when detecting pseudo-kanji characters. Taken together, these results support the notion that the automatic detection of deviance in kanji compounds may be limited to a low-level feature, such as the stimulus stroke thickness.

Large-scale cortico-cerebellar computations for horizontal and vertical vergence in humans.

Horizontal and vertical vergence eye movements play a central role in binocular coordination. Neurophysiological studies suggest that cortical and subcortical regions in animals and humans are involved in horizontal vergence. However, little is known about the extent to which the neural mechanism underlying vertical vergence overlaps with that of horizontal vergence. In this study, to explore neural computation for horizontal and vertical vergence, we simultaneously recorded electrooculography (EOG) and whole-head magnetoencephalography (MEG) while presenting large-field stereograms for 29 healthy human adults. The stereograms were designed to produce vergence responses by manipulating horizontal and vertical binocular disparities. A model-based approach was used to assess neural sensitivity to horizontal and vertical disparities via MEG source estimation and the theta-band (4 Hz) coherence between brain activity and EOG vergence velocity. We found similar time-locked neural responses to horizontal and vertical disparity in cortical and cerebellar areas at around 100-250 ms after stimulus onset. In contrast, the low-frequency oscillatory neural activity associated with the execution of vertical vergence differed from that of horizontal vergence. These findings indicate that horizontal and vertical vergence involve partially shared but distinct computations in large-scale cortico-cerebellar networks.

Disrupted local beta band networks in schizophrenia revealed through graph analysis: A magnetoencephalography study.

AIMS: Schizophrenia (SZ) is characterized by psychotic symptoms and cognitive impairment, and is hypothesized to be a 'dysconnection' syndrome due to abnormal neural network formation. Although numerous studies have helped elucidate the pathophysiology of SZ, many aspects of the mechanism underlying psychotic symptoms remain unknown. This study used graph theory analysis to evaluate the characteristics of the resting-state network (RSN) in terms of microscale and macroscale indices, and to identify candidates as potential biomarkers of SZ. Specifically, we discriminated topological characteristics in the frequency domain and investigated them in the context of psychotic symptoms in patients with SZ. METHODS: We performed graph theory analysis of electrophysiological RSN data using magnetoencephalography to compare topological characteristics represented by microscale (degree centrality and clustering coefficient) and macroscale (global efficiency, local efficiency, and small-worldness) indices in 29 patients with SZ and 38 healthy controls. In addition, we investigated the aberrant topological characteristics of the RSN in patients with SZ and their relationship with SZ symptoms. RESULTS: SZ was associated with a decreased clustering coefficient, local efficiency, and small-worldness, especially in the high beta band. In addition, macroscale changes in the low beta band are closely associated with negative symptoms. CONCLUSIONS: The local networks of patients with SZ may disintegrate at both the microscale and macroscale levels, mainly in the beta band. Adopting an electrophysiological perspective of SZ as a failure to form local networks in the beta band will provide deeper insights into the pathophysiology of SZ as a 'dysconnection' syndrome.

Late responses in the anterior insula reflect the cognitive component of pain: evidence of nonpain processing.

INTRODUCTION: Pain is a complex experience influenced by sensory and psychological factors. The insula is considered to be a core part of the pain network in the brain. Previous studies have suggested a relationship between the posterior insula (PI) and sensory processing, and between the anterior insula (AI) and cognitive-affective factors. OBJECTIVES: Our aim was to distinguish sensory and cognitive responses in pain-related insular activities. METHODS: We recorded spatiotemporal insular activation patterns of healthy participants (n = 20) during pain or tactile processing with painful or nonpainful movie stimuli, using a magnetoencephalography. We compared the peak latency between PI and AI activities in each stimulus condition, and between pain and tactile processing in each response. The peak latency and amplitude between different movies were then examined to explore the effects of cognitive influence. A visual analogue scale was used to assess subjective perception. RESULTS: The results revealed one clear PI activity and 2 AI activities (early and late) in insular responses induced by pain/tactile stimulation. The early response transmitted from the PI to AI was observed during sensory-associated brain activity, whereas the late AI response was observed during cognitive-associated activity. In addition, we found that painful movie stimuli had a significant influence on both late AI activity and subjective perception, caused by nonpainful actual stimulation. CONCLUSIONS: The current findings suggested that late AI activation reflects the processing of cognitive pain information, whereas the PI and early AI responses reflect sensory processing.

Prospects for Future Methodological Development and Application of Magnetoencephalography Devices in Psychiatry.

Magnetoencephalography (MEG) is a functional neuroimaging tool that can record activity from the entire cortex on the order of milliseconds. MEG has been used to investigate numerous psychiatric disorders, such as schizophrenia, bipolar disorder, major depression, dementia, and autism spectrum disorder. Although several review papers on the subject have been published, perspectives and opinions regarding the use of MEG in psychiatric research have primarily been discussed from a psychiatric research point of view. Owing to a newly developed MEG sensor, the use of MEG devices will soon enter a critical period, and now is a good time to discuss the future of MEG use in psychiatric research. In this paper, we will discuss MEG devices from a methodological point of view. We will first introduce the utilization of MEG in psychiatric research and the development of its technology. Then, we will describe the principle theory of MEG and common algorithms, which are useful for applying MEG tools to psychiatric research. Next, we will consider three topics-child psychiatry, resting-state networks, and cortico-subcortical networks-and address the future use of MEG in psychiatry from a broader perspective. Finally, we will introduce the newly developed device, the optically-pumped magnetometer, and discuss its future use in MEG systems in psychiatric research from a methodological point of view. We believe that state-of-the-art electrophysiological tools, such as this new MEG system, will further contribute to our understanding of the core pathology in various psychiatric disorders and translational research.

Frequency-Specific Resting Connectome in Bipolar Disorder: An MEG Study.

BACKGROUND: Bipolar disorder (BD) is a serious psychiatric disorder that is associated with a high suicide rate, and for which no clinical biomarker has yet been identified. To address this issue, we investigated the use of magnetoencephalography (MEG) as a new prospective tool. MEG has been used to evaluate frequency-specific connectivity between brain regions; however, no previous study has investigated the frequency-specific resting-state connectome in patients with BD. This resting-state MEG study explored the oscillatory representations of clinical symptoms of BD via graph analysis. METHODS: In this prospective case-control study, 17 patients with BD and 22 healthy controls (HCs) underwent resting-state MEG and evaluations for depressive and manic symptoms. After estimating the source current distribution, orthogonalized envelope correlations between multiple brain regions were evaluated for each frequency band. We separated regions-of-interest into seven left and right network modules, including the frontoparietal network (FPN), limbic network (LM), salience network (SAL), and default mode network (DMN), to compare the intra- and inter-community edges between the two groups. RESULTS: In the BD group, we found significantly increased inter-community edges of the right LM-right DMN at the gamma band, and decreased inter-community edges of the right SAL-right FPN at the delta band and the left SAL-right SAL at the theta band. Intra-community edges in the left LM at the high beta band were significantly higher in the BD group than in the HC group. The number of connections in the left LM at the high beta band showed positive correlations with the subjective and objective depressive symptoms in the BD group. CONCLUSION: We introduced graph theory into resting-state MEG studies to investigate the functional connectivity in patients with BD. To the best of our knowledge, this is a novel approach that may be beneficial in the diagnosis of BD. This study describes the spontaneous oscillatory brain networks that compensate for the time-domain issues associated with functional magnetic resonance imaging. These findings suggest that the connectivity of the LM at the beta band may be a good objective biological biomarker of the depressive symptoms associated with BD.

Secondary somatosensory area is involved in vibrotactile temporal-structure processing: MEG analysis of slow cortical potential shifts in humans.

Purpose: Temporal-structure discrimination is an essential dimension of tactile processing. Exploring object surface by touch generates vibrotactile input with various temporal dynamics, which gives diversity to tactile percepts. Here, we examined whether slow cortical potential shifts (SCPs) (<1 Hz) evoked by long vibrotactile stimuli can reflect active temporal-structure processing.Materials and methods: Vibrotactile-evoked magnetic brain responses were recorded in 10 right-handed healthy volunteers using a piezoelectric-based stimulator and whole-head magnetoencephalography. A series of vibrotactile train stimuli with various temporal structures were delivered to the right index finger. While all trains consisted of identical number (15) of stimuli delivered within a fixed duration (1500 ms), temporal structures were varied by modulating inter-stimulus intervals (ISIs). Participants judged regularity/irregularity of ISI for each train in the active condition, whereas they ignored the stimuli while performing a visual distraction task in the passive condition. We analysed the spatiotemporal features of SCPs and their behaviour using the minimum norm estimates with the dynamic statistical parametric mapping.Results: SCPs were localized to contralateral primary somatosensory area (S1), contralateral superior temporal gyrus, and contralateral as well as ipsilateral secondary somatosensory areas (S2). A significant enhancement of SCPs was observed in the ipsilateral S2 (S2i) in the active condition, whereas such effects were absent in the other regions. We also found a significant larger amplitude difference between the regular- and irregular-stimulus evoked S2i responses during the active condition than during the passive condition.Conclusions: This study suggests that S2 subserves the temporal dimension of vibrotactile processing.

A novel method for extracting interictal epileptiform discharges in multi-channel MEG: Use of fractional type of blind source separation.

OBJECTIVE: Visual inspection of interictal epileptiform discharges (IEDs) in multi-channel MEG requires a time-consuming evaluation process and often leads to inconsistent results due to variability of IED waveforms. Here, we propose a novel extraction method for IEDs using a T/k type of blind source separation (BSST/k). METHODS: We applied BSST/k with seven patients with focal epilepsy to test the accuracy of identification of IEDs. We conducted comparisons of the results of BSS components with those obtained by visual inspection in sensor-space analysis. RESULTS: BSST/k provided better signal estimation of IEDs compared with sensor-space analysis. Importantly, BSST/k was able to uncover IEDs that could not be detected by visual inspection. Furthermore, IED components were clearly extracted while preserving spike and wave morphology. Variable IED waveforms were decomposed into one dominant component. CONCLUSIONS: BSST/k was able to visualize the spreading signals over multiple channels into a single component from a single epileptogenic zone. BSST/k can be applied to focal epilepsy with a simple parameter setting. SIGNIFICANCE: Our novel method was able to highlight IEDs with increased accuracy for identification of IEDs from multi-channel MEG data.

Vertical size disparity induces enhanced neural responses in good stereo observers.

Stereoscopic three-dimensional vision requires cortical processing for horizontal binocular disparity between the two eyes' retinal images. Behavioral and theoretical studies suggest that vertical size disparity is used to recover the viewing geometry and to generate the slant of a large surface. However, unlike horizontal disparity, the relation between stereopsis and neural responses to vertical disparity remains controversial. To determine the role of cortical processing for vertical size disparity in stereopsis, we measured neuromagnetic responses to disparities in people with good and poor stereopsis, using magnetoencephalography (MEG). Healthy adult participants viewed stereograms with a horizontal or vertical size disparity, and judged the perceived slant of the pattern. We assessed neural activity in response to disparities in the visual cortex and the phase locking of oscillatory responses including the alpha frequency range using MEG. For participants with good stereopsis, activity in the visual areas was significantly higher in response to vertical size disparity than to horizontal size disparity. The time-frequency analysis revealed that early neural responses to vertical size disparity were more phase-locked in good stereo participants than in poor stereo participants. These results provide neuromagnetic evidence that vertical-size disparity processing plays a role in good stereo vision.

Monaural 40-Hz auditory steady-state magnetic responses can be useful for identifying epileptic focus in mesial temporal lobe epilepsy.

OBJECTIVE: Patients with mesial temporal lobe epilepsy (mTLE) often exhibit central auditory processing (CAP) dysfunction. Monaural 40-Hz auditory steady-state magnetic responses (ASSRs) were recorded to explore the pathophysiology of mTLE. METHODS: Eighteen left mTLE patients, 11 right mTLE patients and 16 healthy controls (HCs) were examined. Monaural clicks were presented at a rate of 40 Hz. Phase-locking factor (PLF) and power values were analyzed within bilateral Heschl's gyri. RESULTS: Monaural 40-Hz ASSR demonstrated temporal frequency dynamics in both PLF and power data. Symmetrical hemispheric contralaterality was revealed in HCs. However, predominant contralaterality was absent in mTLE patients. Specifically, right mTLE patients exhibited a lack of contralaterality in response to left ear but not right ear stimulation, and vice versa in left mTLE patients. CONCLUSION: This is the first study to use monaural 40-Hz ASSR with unilateral mTLE patients to clarify the relationship between CAP and epileptic focus. CAP dysfunction was characterized by a lack of contralaterality corresponding to epileptic focus. SIGNIFICANCE: Monaural 40-Hz ASSR can provide useful information for localizing epileptic focus in mTLE patients.

Proposal for an accurate TMS-MRI co-registration process via 3D laser scanning.

An important technical issue in transcranial magnetic stimulation (TMS) usage is how accurately the specific brain areas activated by TMS are assessed. However, in practice, electric field induced in TMS is dispersed and therefore actual estimation is still difficult. As a preliminary step, the projection line which is perpendicular to the TMS stimulation coil beneath the center of the coil must be accurately estimated into the brain. Therefore, we have developed a new TMS-MRI co-registration procedure that employs a 3D laser-scanner system that is very useful for general hand-manipulated TMS, and which easily estimates the TMS projection point onto the brain. The proposed system accurately captures the positional relationship between the TMS coil and anatomical images. The results of 3D image processing revealed that the registration error at each stage was kept within the submillimeter level. In addition, a motor evoked potential experiment examining the right finger motor area revealed that understandable responses were obtained when stimulation was targeted to the three different motor areas according to Penfield's map. 3D laser scanning is a technique of substantial recent interest for anatomical co-registration. The proposed method demonstrated submillimeter level accuracy of TMS-MRI co-registration.

Altered neural synchronization to pure tone stimulation in patients with mesial temporal lobe epilepsy: An MEG study.

OBJECTIVE: Our previous study of monaural auditory evoked magnetic fields (AEFs) demonstrated that hippocampal sclerosis significantly modulated auditory processing in patients with mesial temporal lobe epilepsy (mTLE). However, the small sample size (n = 17) and focus on the M100 response were insufficient to elucidate the lateralization of the epileptic focus. Therefore, we increased the number of patients with mTLE (n = 39) to examine whether neural synchronization induced by monaural pure tone stimulation provides useful diagnostic information about epileptic foci in patients with unilateral mTLE. METHODS: Twenty-five patients with left mTLE, 14 patients with right mTLE, and 32 healthy controls (HCs) were recruited. Auditory stimuli of 500-Hz tone burst were monaurally presented to subjects. The AEF data were analyzed with source estimation of M100 responses in bilateral auditory cortices (ACs). Neural synchronization within ACs and between ACs was evaluated with phase-locking factor (PLF) and phase-locking value (PLV), respectively. Linear discriminant analysis was performed for diagnosis and lateralization of epileptic focus. RESULTS: The M100 amplitude revealed that patients with right mTLE exhibited smaller M100 amplitude than patients with left mTLE and HCs. Interestingly, PLF was able to differentiate the groups with mTLE, with decreased PLFs in the alpha band observed in patients with right mTLE compared with those (PLFs) in patients with left mTLE. Right hemispheric predominance was confirmed in both HCs and patients with left mTLE while patients with right mTLE showed a lack of right hemispheric predominance. Functional connectivity between bilateral ACs (PLV) was reduced in both patients with right and left mTLE compared with that of HCs. The accuracy of diagnosis and lateralization was 80%-90%. CONCLUSION: Auditory cortex subnormal function was more pronounced in patients with right mTLE compared with that in patients with left mTLE as well as HCs. Monaural AEFs can be used to reveal the pathophysiology of mTLE. Overall, our results indicate that altered neural synchronization may provide useful information about possible functional deterioration in patients with unilateral mTLE.

Spatiotemporal brain dynamics of auditory temporal assimilation.

Time is a fundamental dimension, but millisecond-level judgments sometimes lead to perceptual illusions. We previously introduced a "time-shrinking illusion" using a psychological paradigm that induces auditory temporal assimilation (ATA). In ATA, the duration of two successive intervals (T1 and T2), marked by three auditory stimuli, can be perceived as equal when they are not. Here, we investigate the spatiotemporal profile of human temporal judgments using magnetoencephalography (MEG). Behavioural results showed typical ATA: participants judged T1 and T2 as equal when T2 - T1 ≤ +80 ms. MEG source-localisation analysis demonstrated that regional activity differences between judgment and no-judgment conditions emerged in the temporoparietal junction (TPJ) during T2. This observation in the TPJ may indicate its involvement in the encoding process when T1 ≠ T2. Activation in the inferior frontal gyrus (IFG) was enhanced irrespective of the stimulus patterns when participants engaged in temporal judgment. Furthermore, just after the final marker, activity in the IFG was enhanced specifically for the time-shrinking pattern. This indicates that activity in the IFG is also related to the illusory perception of time-interval equality. Based on these observations, we propose neural signatures for judgments of temporal equality in the human brain.

Neural oscillations in the temporal pole for a temporally congruent audio-visual speech detection task.

Though recent studies have elucidated the earliest mechanisms of processing in multisensory integration, our understanding of how multisensory integration of more sustained and complicated stimuli is implemented in higher-level association cortices is lacking. In this study, we used magnetoencephalography (MEG) to determine how neural oscillations alter local and global connectivity during multisensory integration processing. We acquired MEG data from 15 healthy volunteers performing an audio-visual speech matching task. We selected regions of interest (ROIs) using whole brain time-frequency analyses (power spectrum density and wavelet transform), then applied phase amplitude coupling (PAC) and imaginary coherence measurements to them. We identified prominent delta band power in the temporal pole (TP), and a remarkable PAC between delta band phase and beta band amplitude. Furthermore, imaginary coherence analysis demonstrated that the temporal pole and well-known multisensory areas (e.g., posterior parietal cortex and post-central areas) are coordinated through delta-phase coherence. Thus, our results suggest that modulation of connectivity within the local network, and of that between the local and global network, is important for audio-visual speech integration. In short, these neural oscillatory mechanisms within and between higher-level association cortices provide new insights into the brain mechanism underlying audio-visual integration.

Neuromagnetic evidence that the right fusiform face area is essential for human face awareness: An intermittent binocular rivalry study.

When and where the awareness of faces is consciously initiated is unclear. We used magnetoencephalography to probe the brain responses associated with face awareness under intermittent pseudo-rivalry (PR) and binocular rivalry (BR) conditions. The stimuli comprised three pictures: a human face, a monkey face and a house. In the PR condition, we detected the M130 component, which has been minimally characterized in previous research. We obtained a clear recording of the M170 component in the fusiform face area (FFA), and found that this component had an earlier response time to faces compared with other objects. The M170 occurred predominantly in the right hemisphere in both conditions. In the BR condition, the amplitude of the M130 significantly increased in the right hemisphere irrespective of the physical characteristics of the visual stimuli. Conversely, we did not detect the M170 when the face image was suppressed in the BR condition, although this component was clearly present when awareness for the face was initiated. We also found a significant difference in the latency of the M170 (human

A spatiotemporal signature of cortical pain relief by tactile stimulation: An MEG study.

Recently, the cortical mechanisms of tactile-induced analgesia have been investigated; however, spatiotemporal characteristics have not been fully elucidated. The insular-opercular region integrates multiple sensory inputs, and nociceptive modulation by other sensory inputs occurs in this area. In this study, we focused on the insular-opercular region to characterize the spatiotemporal signature of tactile-induced analgesia using magnetoencephalography in 11 healthy subjects. Aδ (intra-epidermal electrical stimulation) inputs were modified by Aß (mechanical tactile stimulation) selective stimulation, either independently or concurrently, to the right forearm. The optimal inter-stimulus interval (ISI) for cortical level modulation was determined after comparing the 40-, 60-, and 80-ms ISI conditions, and the calculated cortical arrival time difference between Aδ and Aß inputs. Subsequently, we adopted a 60-ms ISI for cortical modulation and a 0-ms ISI for spinal level modulation. Source localization using minimum norm estimates demonstrated that pain-related activity was located in the posterior insula, whereas tactile-related activity was estimated in the parietal operculum. We also found significant inhibition of pain-related activity in the posterior insula due to cortical modulation. In contrast, spinal modulation was observed both in the posterior insula and parietal operculum. Subjective pain, as evaluated by the visual analog scale, also showed significant reduction in both conditions. Therefore, our results demonstrated that the multisensory integration within the posterior insula plays a key role in tactile-induced analgesia.

The inhibition/excitation ratio related to task-induced oscillatory modulations during a working memory task: A multtimodal-imaging study using MEG and MRS.

Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro. In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM0B) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM2B-0B) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance.

Neuromagnetic evidence for hippocampal modulation of auditory processing.

The hippocampus is well known to be involved in memory, as well as in perceptual processing. To date, the electrophysiological process by which unilateral hippocampal lesions, such as hippocampal sclerosis (HS), modulate the auditory processing remains unknown. Auditory-evoked magnetic fields (AEFs) are valuable for evaluating auditory functions, because M100, a major component of AEFs, originates from auditory areas. Therefore, AEFs of mesial temporal lobe epilepsy (mTLE, n=17) with unilateral HS were compared with those of healthy (HC, n=17) and disease controls (n=9), thereby determining whether AEFs were indicative of hippocampal influences on the auditory processing. Monaural tone-burst stimuli were presented for each side, followed by analysis of M100 and a previously less characterized exogenous component (M400: 300-500ms). The frequency of acceptable M100 dipoles was significantly decreased in the HS side. Beam-forming-based source localization analysis also showed decreased activity of the auditory area, which corresponded to the inadequately estimated dipoles. M400 was found to be related to the medial temporal structure on the HS side. Volumetric analysis was also performed, focusing on the auditory-related areas (planum temporale, Heschl's gyrus, and superior temporal gyrus), as well as the hippocampus. M100 amplitudes positively correlated with hippocampal and planum temporale volumes in the HC group, whereas they negatively correlated with Heschl's gyrus volume in the mTLE group. Interestingly, significantly enhanced M400 component was observed in the HS side of the mTLE patients. In addition, the M400 component positively correlated with Heschl's gyrus volume and tended to positively correlate with disease duration. M400 was markedly diminished after hippocampal resection. Although volumetric analysis showed decreased hippocampal volume in the HS side, the planum temporale and Heschl's gyrus, the two major sources of M100, were preserved. These results suggested that HS significantly influenced AEFs. Therefore, we concluded that the hippocampus modulates auditory processing differently under normal conditions and in HS.

Cortical activity associated with the detection of temporal gaps in tones: a magnetoencephalography study.

We used magnetoencephalogram (MEG) in two experiments to investigate spatio-temporal profiles of brain responses to gaps in tones. Stimuli consisted of leading and trailing markers with gaps between the two markers of 0, 30, or 80 ms. Leading and trailing markers were 300 ms pure tones at 800 or 3200 Hz.Two conditions were examined: the within-frequency (WF) condition in which the leading and trailing markers had identical frequencies, and the between-frequency (BF) condition in which they had different frequencies. Using minimum norm estimates (MNE), we localized the source activations at the time of the peak response to the trailing markers. Results showed that MEG signals in response to 800 and 3200 Hz tones were localized in different regions within the auditory cortex, indicating that the frequency pathways activated by the two markers were spatially represented.The time course of regional activity (RA) was extracted from each localized region for each condition. In Experiment 1, which used a continuous tone for the WF 0-ms stimulus, the N1m amplitude for the trailing marker in the WF condition differed depending on gap duration but not tonal frequency. In contrast, N1m amplitude in BF conditions differed depending on the frequency of the trailing marker. In Experiment 2, in which the 0-ms gap stimulus in the WF condition was made from two markers and included an amplitude reduction in the middle, the amplitude in WF and BF conditions changed depending on frequency, but not gap duration.The difference in temporal characteristics betweenWF and BF conditions could be observed in the RA.