Data-point-wise spatiotemporal mapping of human ventral visual areas: Use of spatial frequency/luminance-modulated chromatic faces.

Visual information involving facial identity and expression is crucial for social communication. Although the influence of facial features such as spatial frequency (SF) and luminance on face processing in visual areas has been studied extensively using grayscale stimuli, the combined effects of other features in this process have not been characterized. To determine the combined effects of different SFs and color, we created chromatic stimuli with low, high or no SF components, which bring distinct SF and color information into the ventral stream simultaneously. To obtain neural activity data with high spatiotemporal resolution we recorded face-selective responses (M170) using magnetoencephalography. We used a permutation test procedure with threshold-free cluster enhancement to assess statistical significance while resolving problems related to multiple comparisons and arbitrariness found in traditional statistical methods. We found that time windows with statistically significant threshold levels were distributed differently among the stimulus conditions. Face stimuli containing any SF components evoked M170 in the fusiform gyrus (FG), whereas a significant emotional effect on M170 was only observed with the original images. Low SF faces elicited larger activation of the FG and the inferior occipital gyrus than the original images, suggesting an interaction between low and high SF information processing. Interestingly, chromatic face stimuli without SF first activated color-selective regions and then the FG, indicating that facial color was processed according to a hierarchy in the ventral stream. These findings suggest complex effects of SFs in the presence of color information, reflected in M170, and unveil the detailed spatiotemporal dynamics of face processing in the human brain.

Rapidly spreading seizures arise from large-scale functional brain networks in focal epilepsy.

It remains unclear whether epileptogenic networks in focal epilepsy develop on physiological networks. This work aimed to explore the association between the rapid spread of ictal fast activity (IFA), a proposed biomarker for epileptogenic networks, and the functional connectivity or networks of healthy subjects. We reviewed 45 patients with focal epilepsy who underwent electrocorticographic (ECoG) recordings to identify the patients showing the rapid spread of IFA. IFA power was quantified as normalized beta-gamma band power. Using published resting-state functional magnetic resonance imaging databases, we estimated resting-state functional connectivity of healthy subjects (RSFC-HS) and resting-state networks of healthy subjects (RSNs-HS) at the locations corresponding to the patients' electrodes. We predicted the IFA power of each electrode based on RSFC-HS between electrode locations (RSFC-HS-based prediction) using a recently developed method, termed activity flow mapping. RSNs-HS were identified using seed-based and atlas-based methods. We compared IFA power with RSFC-HS-based prediction or RSNs-HS using non-parametric correlation coefficients. RSFC and seed-based RSNs of each patient (RSFC-PT and seed-based RSNs-PT) were also estimated using interictal ECoG data and compared with IFA power in the same way as RSFC-HS and seed-based RSNs-HS. Spatial autocorrelation-preserving randomization tests were performed for significance testing. Nine patients met the inclusion criteria. None of the patients had reflex seizures. Six patients showed pathological evidence of a structural etiology. In total, we analyzed 49 seizures (2-13 seizures per patient). We observed significant correlations between IFA power and RSFC-HS-based prediction, seed-based RSNs-HS, or atlas-based RSNs-HS in 28 (57.1%), 21 (42.9%), and 28 (57.1%) seizures, respectively. Thirty-two (65.3%) seizures showed a significant correlation with either seed-based or atlas-based RSNs-HS, but this ratio varied across patients: 27 (93.1%) of 29 seizures in six patients correlated with either of them. Among atlas-based RSNs-HS, correlated RSNs-HS with IFA power included the default mode, control, dorsal attention, somatomotor, and temporal-parietal networks. We could not obtain RSFC-PT and RSNs-PT in one patient due to frequent interictal epileptiform discharges. In the remaining eight patients, most of the seizures showed significant correlations between IFA power and RSFC-PT-based prediction or seed-based RSNs-PT. Our study provides evidence that the rapid spread of IFA in focal epilepsy can arise from physiological RSNs. This finding suggests an overlap between epileptogenic and functional networks, which may explain why functional networks in patients with focal epilepsy frequently disrupt.

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.

Modified ischaemic nerve block of the forearm: use for the induction of cortical plasticity in distal hand muscles.

KEY POINTS: Ischaemic nerve block (INB) of the forearm rapidly reduces somatosensory input to a part of the body, which leads to the functional reorganization of the temporarily deafferented primary motor cortex (M1). We applied a novel modified INB (mINB) to the forearm, maintaining mean blood pressure, to assess cortical plasticity in the primary somatosensory cortex (S1) and the M1 regions associated with small hand muscles. S1 excitability was measured by median nerve somatosensory-evoked potentials (SEPs), while M1 excitability was evaluated by motor-evoked potentials (MEPS), using transcranial magnetic stimulation. The finding that S1 excitability increased and M1 excitability decreased after the mINB was removed reflects the differential short-term cortical plasticity of the S1 and M1 regions. These opposite effects observed for the S1 and M1 regions following the mINB may indicate a possible intra-hemispheric interaction between the S1 and M1 regions. ABSTRACT: Ischaemic nerve block (INB) causes short-term sensory deprivation, leading to functional reorganization in the deafferented motor cortex (M1). We used a modified INB (mINB) to evaluate cortical plasticity in the somatosensory cortex (S1) and M1 region associated with small hand muscles, because INB strongly inhibits muscles distal to the tourniquet. Thirty-three healthy adults participated in different combinations of four experiments. A pneumatic tourniquet was placed just below the right elbow and inflated to induce a mINB. We recorded the median nerve somatosensory- and motor-evoked potentials (SEPs and MEPs) before, during and after mINB placement and assessed spinal cord excitability using F-wave measurements. SEPs at Erb's point (N9) were abolished during the mINB; those at cortical N20 were suppressed. After removing the mINB, N20 amplitudes increased significantly, while those at N9 did not fully recover. P14 amplitudes after tourniquet deflation immediately recovered to baseline levels. M1-MEP amplitudes decreased during the mINB, and Erb-MEPs were suppressed. After the mINB was removed, M1-MEPs remained suppressed, while Erb-MEPs fully recovered. F-waves were not affected by the intervention. Therefore, sensory, but not motor, nerve function was affected by the mINB. S1 excitability was enhanced after the mINB was removed, indicating that S1 and M1 excitability were modulated in opposing directions after deflation. These after-effects may reflect isolated effects or interactions between the S1 and M1 regions. Our findings may facilitate improved understanding of the sensorimotor modulations that occur distal to the tourniquet due to temporal deafferentation and lead to development of novel neuromodulation protocols.

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.

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.

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.

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.

'Time-shrinking perception' in the visual system: a psychophysical and high-density ERP study.

'Time-shrinking perception (TSP)' is a unique perceptual phenomenon in which the duration of two successive intervals (T1 and T2) marked by three auditory stimuli is perceived as equal even when they are physically different. This phenomenon provides a link between time and working memory; however, previous studies have mainly been performed on the auditory modality but not the visual modality. To clarify the neural mechanism of visual TSP, we performed a psychophysical experiment and recorded event-related potentials (ERPs) under different T1/T2 combinations. Three successive black/white sinusoidal gratings (30 ms duration) were presented to the participants. In the psychophysical experiment, either T1 or T2 was varied from 240 to 560 ms in 40-ms steps, while T2 or T1 was fixed at 400 ms. Participants judged whether T1 and T2 were equal or not by pressing a button. ERPs were recorded from 128 scalp electrodes, while T1 was varied from 240, 320, and 400 ms with the 400 ms T2 duration, and vice versa. Behavioral data showed asymmetrical assimilation: When -80 ms ≤ (T1 - T2) ≤ +120 ms, TSP was observed in the T1-varied condition. When -120 ms ≤ (T1 - T2) ≤ +80 ms, it was also observed in the T2-varied condition. These asymmetric time ranges in vision were different from those in the auditory modality. ERP data showed that contingent negative variation (CNV) appeared in the fronto-central region at around 300-500 ms during T2 presentation in the T1 < T2 condition. In the /240/400/ pattern, the CNV amplitude was decreased at around 350 ms. In contrast, P3 appeared at the parietal region about 450-650 ms after T2 in the T1 > T2 condition. In the /400/240/ pattern, P3 amplitude was greater than those of other temporal patterns. These neural responses corresponded to participants' perception that T1 and T2 were not equal. The neural responses in the fronto-central region were involved with endogenous temporal attention for discrimination. Moreover, neural responses in the parietal region were engaged in exogenous temporal attention. Therefore, fronto-parietal neural responses underlie temporal perception in vision.

Temporal dynamics of the knowledge-mediated visual disambiguation process in humans: a magnetoencephalography study.

Disambiguation of a noisy visual scene with prior knowledge is an indispensable task of the visual system. To adequately adapt to a dynamically changing visual environment full of noisy visual scenes, the implementation of knowledge-mediated disambiguation in the brain is imperative and essential for proceeding as fast as possible under the limited capacity of visual image processing. However, the temporal profile of the disambiguation process has not yet been fully elucidated in the brain. The present study attempted to determine how quickly knowledge-mediated disambiguation began to proceed along visual areas after the onset of a two-tone ambiguous image using magnetoencephalography with high temporal resolution. Using the predictive coding framework, we focused on activity reduction for the two-tone ambiguous image as an index of the implementation of disambiguation. Source analysis revealed that a significant activity reduction was observed in the lateral occipital area at approximately 120 ms after the onset of the ambiguous image, but not in preceding activity (about 115 ms) in the cuneus when participants perceptually disambiguated the ambiguous image with prior knowledge. These results suggested that knowledge-mediated disambiguation may be implemented as early as approximately 120 ms following an ambiguous visual scene, at least in the lateral occipital area, and provided an insight into the temporal profile of the disambiguation process of a noisy visual scene with prior knowledge.

Efficiency of a "small-world" brain network depends on consciousness level: a resting-state FMRI study.

It has been revealed that spontaneous coherent brain activity during rest, measured by functional magnetic resonance imaging (fMRI), self-organizes a "small-world" network by which the human brain could sustain higher communication efficiency across global brain regions with lower energy consumption. However, the state-dependent dynamics of the network, especially the dependency on the conscious state, remain poorly understood. In this study, we conducted simultaneous electroencephalographic recording with resting-state fMRI to explore whether functional network organization reflects differences in the conscious state between an awake state and stage 1 sleep. We then evaluated whole-brain functional network properties with fine spatial resolution (3781 regions of interest) using graph theoretical analysis. We found that the efficiency of the functional network evaluated by path length decreased not only at the global level, but also in several specific regions depending on the conscious state. Furthermore, almost two-thirds of nodes that showed a significant decrease in nodal efficiency during stage 1 sleep were categorized as the default-mode network. These results suggest that brain functional network organizations are dynamically optimized for a higher level of information integration in the fully conscious awake state, and that the default-mode network plays a pivotal role in information integration for maintaining conscious awareness.

Neuromagnetic detection of the laryngeal area: Sensory-evoked fields to air-puff stimulation.

The sensory projections from the oral cavity, pharynx, and larynx are crucial in assuring safe deglutition, coughing, breathing, and voice production/speaking. Although several studies using neuroimaging techniques have demonstrated cortical activation related to pharyngeal and laryngeal functions, little is known regarding sensory projections from the laryngeal area to the somatosensory cortex. The purpose of this study was to establish the cortical activity evoked by somatic air-puff stimulation at the laryngeal mucosa using magnetoencephalography. Twelve healthy volunteers were trained to inhibit swallowing in response to air stimuli delivered to the larynx. Minimum norm estimates was performed on the laryngeal somatosensory evoked fields (LSEFs) to best differentiate the target activations from non-task-related activations. Evoked magnetic fields were recorded with acceptable reproducibility in the left hemisphere, with a peak latency of approximately 100ms in 10 subjects. Peak activation was estimated at the caudolateral region of the primary somatosensory area (S1). These results establish the ability to detect LSEFs with an acceptable reproducibility within a single subject and among subjects. These results also suggest the existence of laryngeal somatic afferent input to the caudolateral region of S1 in human. Our findings indicate that further investigation in this area is needed, and should focus on laryngeal lateralization, swallowing, and speech processing.

[Electrophysiological diagnosis of multiple sclerosis].

Evoked potentials (EPs) in a daily practice consist of somatosensory evoked potentials (SEP), visual evoked potentials (VEP), auditory brainstem response (ABR) and motor evoked potentials (MEP). EPs can confirm the presence of lesions in patients with suspected involvement, and document the presence of clinically unsuspected lesions in multiple sclerosis (MS) patients. MEP has the highest sensitivity while VEP is the second sensitive. Furthermore, we are able to obtain an increase in sensitivity by using multimodality evoked potentials (MuEP). By doing so, there is a significant correlation between EP abnormalities and Expanded Disability Status Scale. Thus, EPs are useful for the diagnosis or evaluation of MS and predicting neurological disabilities.

Effects of spatially filtered fearful faces and awareness on amygdala activity in adults with autism spectrum disorder: A magnetoencephalography study.

BACKGROUND: The amygdala is pivotal in emotional face processing. Spatial frequencies (SFs) of visual images are divided and processed via two visual pathways: low spatial frequency (LSF) information is conveyed by the magnocellular pathway, while the parvocellular pathway carries high spatial frequency information. We hypothesized that altered amygdala activity might underlie atypical social communication caused by changes in both conscious and non-conscious emotional face processing in the brain in individuals with autism spectrum disorder (ASD). METHOD: Eighteen adults with ASD and 18 typically developing (TD) peers participated in this study. Spatially filtered fearful- and neutral-expression faces and object stimuli were presented under supraliminal or subliminal conditions, and neuromagnetic responses in the amygdala were measured using 306-channel whole-head magnetoencephalography. RESULTS: The latency of the evoked responses at approximately 200 ms to unfiltered neutral face stimuli and object stimuli in the ASD group was shorter than that in the TD group in the unaware condition. Regarding emotional face processing, the evoked responses in the ASD group were larger than those in the TD group under the aware condition. The later positive shift during 200-500 ms (ARV) was larger than that in the TD group, regardless of awareness. Moreover, ARV to HSF face stimuli was larger than that to the other spatial filtered face stimuli in the aware condition. CONCLUSION: Regardless of awareness, ARV might reflect atypical face information processing in the ASD brain.

Scalp EEG-recorded high-frequency oscillations can predict seizure activity in Panayiotopoulos syndrome.

OBJECTIVE: We studied the relationship between the clinical course of Panayiotopoulos syndrome (PS) and high-frequency oscillations (HFOs) captured during interictal scalp electroencephalography (EEG) to determine the feasibility of using HFOs to detect seizure activity in PS. METHODS: We analyzed the interictal scalp EEGs of 18 children with PS. Age parameters, seizure frequencies, and antiepileptic drugs were compared between the HFO-positive (HFOPG) and HFO-negative (HFONG) groups. RESULTS: Thirteen patients (72.2%) had HFOs while five patients (27.8%) had no HFOs in 194 interictal EEG records. We found no statistically significant differences in the mean age of epilepsy onset and last seizure, seizure frequency, or frequency of status epilepticus. However, the seizure activity period of the HFOPG was significantly longer than that of the HFONG. Patients with an HFO duration longer than 2 years were intractable to treatment. In most cases, seizures did not occur in the absence of HFOs, even when the spikes remained. CONCLUSIONS: HFOs are related to the seizure activity period in patients with PS. SIGNIFICANCE: We propose that HFOs are a biomarker of epileptogenicity and an indicator for drug reduction because seizures did not occur if HFOs disappeared even if the spikes remained.

Single-trial neuromagnetic analysis reveals somatosensory dysfunction in chronic Minamata disease.

Methylmercury pollution is a global problem, and Minamata disease (MD) is a stark reminder that exposure to methylmercury can cause irreversible neurological damage. A "glove and stocking type" sensory disturbance due to injured primary sensory cortex (SI) (central somatosensory disturbance) is the most common neurologic sign in MD. As this sign is also prevalent in those with polyneuropathy, we aimed to develop an objective assessment for detecting central somatosensory disturbances in cases of chronic MD. We selected 289 healthy volunteers and 42 patients with MD. We recorded the sensory nerve action potentials (SNAPs) and somatosensory evoked magnetic fields (SEFs) to median nerve stimulation with magnetoencephalography. Single-trial epochs were classified into three categories (N20m, non-response, and P20m epochs) based on the cross-correlation between averaged sensor SEFs and individual epochs. We assessed SI responses (the appearance rate of P20m [P20m rate] and non-response epochs [non-response rate]) and early somatosensory cortical processing (N20m amplitude, reproducibility of N20m in single-trial responses [cross-correlation value], and induced gamma-band oscillations of the SI [gamma response] of single epochs excluding non-response epochs). Receiver operating characteristic curve analyses were used to examine the diagnostic accuracy of each parameter. We found that SNAPs exerted a marginal effect on the N20m. The N20m amplitude, cross-correlation value, and gamma response were significantly reduced in the MD group on either side (p < 0.0001), suggestive of altered early somatosensory cortical processing. Interestingly, the P20m rate and non-response rate were significantly increased in the MD group on either side (p < 0.0001), thereby suggesting impaired SI responses. Notably, P20m and absent N20m peaks were observed in 6 and 11 patients with MD, respectively, which may be attributed to increased numbers of P20m epochs. The cross-correlation value exhibited the highest correlation with the P20m rate or non-response rate. Thus, reduced reproducibility of N20m may play an important role in chronic MD. The cross-correlation value exhibited the highest correlation with the gamma response for both SI parameters in early somatosensory cortical processing. The area under the curve was > 0.77 (range: 0.77-0.79) for all parameters. Their confidence intervals overlapped with each other; thus, each SEF parameter likely had an approximately equivalent discrimination ability. In conclusion, chronic MD is characterized by impaired SI responses and alterations in early somatosensory cortical processing. Thus, single-trial neuromagnetic analysis of somatosensory function may be useful for detecting central somatosensory disturbance and elucidating the relevant pathophysiological mechanisms even in the context of chronic MD.

Asynchronous neural oscillations associated with subliminal affective face priming in autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by social communicative disturbance. Social communication requires rapid processing and accurate cognition regarding others' emotional expressions. Previous electrophysiological studies have attempted to elucidate the processes underlying atypical face-specific N170 responses to emotional faces in ASD. The present study explored subliminal affective priming effects (SAPEs) on the N170 response and time-frequency analysis of intertrial phase coherence (ITPC) for the N170 in ASD. Fifteen participants [seven participants with ASD and eight typically developing (TD) controls] were recruited for the experiment. Event-related potentials were recorded with a 128-channel electroencephalography device while participants performed an emotional face judgment task. The results revealed enhanced N170 amplitude for supraliminal target-face stimuli when they were preceded by subliminal fearful-face stimuli, in both the ASD and TD groups. Interestingly, TD participants exhibited higher alpha-ITPC in the subliminal fearful-face priming condition in the right face-specific area in the N170 time window. In contrast, there were no significant differences in ITPC in any frequency bands between the subliminal fearful and neutral priming conditions in the ASD group. Asynchronous phase-locking neural activities in the face-specific area may underlie impaired nonconscious face processing in ASD, despite the presence of common features of SAPEs for the N170 component in both the ASD and TD groups.

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.

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.

Long-Term Effect of Acetylcholinesterase Inhibitors on the Dorsal Attention Network of Alzheimer's Disease Patients: A Pilot Study Using Resting-State Functional Magnetic Resonance Imaging.

Background: Alzheimer's disease (AD) is the most common condition of all neurodegenerative diseases and is characterized by various cognitive dysfunctions. Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed the physiological dynamics of functionally connected brain networks, which are called resting-state networks (RSNs). Associations between impairments of RSNs and various neuropsychiatric diseases, such as AD, have been reported. Acetylcholinesterase inhibitors (AChEIs) have been used as a pharmacological treatment for mild-to-moderate moderate AD, and short-term improvements in cognitive functions and RSNs in restricted areas have been reported. Objective: We aimed to characterize AChEI-related RSN changes by acquiring two sets of rs-fMRI data separated by approximately 3 to 6 months. Methods: Seventeen patients with AD and nine healthy subjects participated in this study. Independent component analysis was performed on the rs-fMRI data of AChEI-responsive and non-responsive AD patients, stratified according to change in Mini-Mental State Examination (MMSE) scores after 3 to 6 months of AChEI therapy. In addition, a region of interest-based analysis of the rs-fMRI data before therapy was performed to explore the functional connectivity (FC) changes associated with AchEI therapy. Results: Responders showed a significantly greater increase in MMSE scores, especially for orientation for time, than that of non-responders following AChEI therapy. A subtraction map of MMSE score differences (responders minus non-responders) in the independent component analysis revealed higher FC of the dorsal attention network in responders compared with that in non-responders. Moreover, in the region of interest analysis of untreated status data, the dorsal attention network showed significant negative FC with the right planum temporale, which belongs to the ventral attention network, proportional to MMSE score change. Conclusion: The negative correlation of the FC of the dorsal attention network and right planum temporale before AChEI therapy and MMSE score change may be a biomarker of the therapeutic effect of AChEIs for AD.