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.

Pituitary Adenylate Cyclase-Activating Polypeptide Modulates Dendritic Spine Maturation and Morphogenesis via MicroRNA-132 Upregulation.

Alterations in pituitary adenylate cyclase-activating polypeptide (PACAP), a multifunctional neuropeptide, and its receptors have been identified as risk factors for certain psychiatric disorders, including schizophrenia. Increasing evidence from human genetic and animal model studies suggest an association between various psychiatric disorders and altered dendritic spine morphology. In the present study, we investigated the role of exogenous and endogenous PACAP in spine formation and maturation. PACAP modified the density and morphology of PSD-95-positive spines in primary cultured hippocampal neurons. Notably, PACAP increased the levels of microRNA (miR)-132 and decreased expression of corresponding miR-132 target genes and protein expression of p250GAP, a miR-132 effector known to be involved in spine morphology regulation. In corroboration, PSD-95-positive spines were reduced in PACAP-deficient (PACAP-/-) mice versus WT mice. Golgi staining of hippocampal CA1 neurons revealed a reduced spine densities and atypical morphologies in the male PACAP-/- mice. Furthermore, viral miR-132 overexpression reversed the reduction in hippocampal spinal density in the male PACAP-/- mice. These results indicate that PACAP signaling plays a critical role in spine morphogenesis possibly via miR-132. We suggest that dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsychiatric disorders, at least partly through its effects on spine formation.SIGNIFICANCE STATEMENT Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling dysfunction and dendritic spine morphology alterations have recently been suggested as important pathophysiological mechanisms underlying several psychiatric and neurological disorders. In this study, we investigated whether PACAP regulates dendritic spine morphogenesis. In a combination of pharmacological and viral gain- and loss-of-function approaches in vitro and in vivo experiments, we found PACAP to increase the size and density of dendritic spines via miR-132 upregulation. Together, our data suggest that a dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsychiatric disorders, at least partly through abnormal spine formation.

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.

SNP Discrimination by Tolane-Modified Peptide Nucleic Acids: Application for the Detection of Drug Resistance in Pathogens.

During the treatment of viral or bacterial infections, it is important to evaluate any resistance to the therapeutic agents used. An amino acid substitution arising from a single base mutation in a particular gene often causes drug resistance in pathogens. Therefore, molecular tools that discriminate a single base mismatch in the target sequence are required for achieving therapeutic success. Here, we synthesized peptide nucleic acids (PNAs) derivatized with tolane via an amide linkage at the N-terminus and succeeded in improving the sequence specificity, even with a mismatched base pair located near the terminal region of the duplex. We assessed the sequence specificities of the tolane-PNAs for single-strand DNA and RNA by UV-melting temperature analysis, thermodynamic analysis, an in silico conformational search, and a gel mobility shift assay. As a result, all of the PNA-tolane derivatives stabilized duplex formation to the matched target sequence without inducing mismatch target binding. Among the different PNA-tolane derivatives, PNA that was modified with a naphthyl-type tolane could efficiently discriminate a mismatched base pair and be utilized for the detection of resistance to neuraminidase inhibitors of the influenza A/H1N1 virus. Therefore, our molecular tool can be used to discriminate single nucleotide polymorphisms that are related to drug resistance in pathogens.

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.

Higher postictal parasympathetic activity following greater ictal heart rate increase in right- than left-sided seizures.

OBJECTIVES: The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures. METHODS: Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincaré plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures. RESULTS: Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures. CONCLUSIONS: Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity.

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.

'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.

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.

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.

Unilateral cathodal transcranial direct current stimulation over the parietal area modulates postural control depending with eyes open and closed.

OBJECTIVE: Cathodal transcranial direct current stimulation (C-tDCS) is generally assumed to inhibit cortical excitability. The parietal cortex contributes to multisensory information processing in the postural control system, and this processing is proposed to be different between the right and left hemispheres and sensory modality. However, previous studies did not clarify whether the effects of unilateral C-tDCS of the parietal cortex on the postural control system differ depending on the hemisphere. We investigated the changes in static postural stability after unilateral C-tDCS of the parietal cortex. METHODS: Ten healthy right-handed participants were recruited for right- and left-hemisphere tDCS and sham stimulation, respectively. The cathodal electrode was placed on either the right or left parietal area, whereas the anodal electrode was placed over the contralateral orbit. tDCS was applied at 1.5 mA for 15 min. We evaluated static standing balance by measuring the sway path length (SPL), mediolateral sway path length (ML-SPL), anteroposterior sway path length (AP-SPL), sway area, and the SPL per unit area (L/A) after 15-minute C-tDCS under eyes open (EO) and closed (EC) conditions. To evaluate the effects of C-tDCS on pre- and post-offline trials, each parameter was compared using two-way repeated-measures analysis of variance (ANOVA) with factors of intervention and time. A post-hoc evaluation was performed using a paired t-test. The effect sizes were evaluated according to standardized size-effect indices of partial eta-squared (ηp2) and Cohen's d. The power analysis was calculated (1-ß). RESULTS: A significant interaction was observed between intervention and time for SPL (F (2, 27) = 4.740, p = 0.017, ηp2 = 0.260), ML-SPL (F (2, 27) = 4.926, p = 0.015, ηp2 = 0.267), and sway area (F (2, 27) = 9.624, p = 0.001, ηp2 = 0.416) in the EO condition. C-tDCS over the right hemisphere significantly increased the SPL (p < 0.01, d = 0.51), ML-SPL (p < 0.01, d = 0.52), and sway area (p < 0.05, d = 0.83) in the EO condition. In contrast, C-tDCS over the left hemisphere significantly increased the L/A in both the EC and EO condition (EO; p < 0.05, d = 0.67, EC; p < 0.05, d = 0.57). CONCLUSION: These results suggest that the right parietal region contributes to static standing balance through chiefly visual information processing during the EO condition. On the other hand, L/A increase during EC and EO by tDCS over the left parietal region depends more on somatosensory information to maintain static standing balance during the EC condition.

Phase-dependent modulation of the vestibular-cerebellar network via combined alternating current stimulation influences human locomotion and posture.

Background: Human locomotion induces rhythmic movements of the trunk and head. Vestibular signaling is relayed to multiple regions in the brainstem and cerebellum, and plays an essential role in maintaining head stability. However, how the vestibular-cerebellar network contributes to the rhythmic locomotor pattern in humans is unclear. Transcranial alternating current stimulation (tACS) has been used to investigate the effects of the task-related network between stimulation regions in a phase-dependent manner. Here, we investigated the relationship between the vestibular system and the cerebellum during walking imagery using combined tACS over the left cerebellum and alternating current galvanic vestibular stimulation (AC-GVS). Methods: In Experiment 1, we tested the effects of AC-GVS alone at around individual gait stride frequencies. In Experiment 2, we then determined the phase-specificity of combined stimulation at the gait frequency. Combined stimulation was applied at in-phase (0° phase lag) or anti-phase (180° phase lag) between the left vestibular and left cerebellar stimulation, and the sham stimulation. We evaluated the AC-GVS-induced periodic postural response during walking imagery or no-imagery using the peak oscillatory power on the angular velocity signals of the head in both experiments. In Experiment 2, we also examined the phase-locking value (PLV) between the periodic postural responses and the left AC-GVS signals to estimate entrainment of the postural response by AC-GVS. Results: AC-GVS alone induced the periodic postural response in the yaw and roll axes, but no interactions with imagery walking were observed in Experiment 1 (p > 0.05). By contrast, combined in-phase stimulation increased yaw motion (0.345 ± 0.23) compared with sham (-0.044 ± 0.19) and anti-phase stimulation (-0.066 ± 0.18) during imaginary walking (in-phase vs. other conditions, imagery: p < 0.05; no-imagery: p ≥ 0.125). Furthermore, there was a positive correlation between the yaw peak power of actual locomotion and in-phase stimulation in the imagery session (imagery: p = 0.041; no-imagery: p = 0.177). Meanwhile, we found no imagery-dependent effects in roll peak power or PLV, although in-phase stimulation enhanced roll motion and PLV in Experiment 2. Conclusion: These findings suggest that combined stimulation can influence vestibular-cerebellar network activity, and modulate postural control and locomotion systems in a temporally sensitive manner. This novel combined tACS/AC-GVS stimulation approach may advance development of therapeutic applications.

The effect of interictal epileptic discharges and following spindles on motor sequence learning in epilepsy patients.

Purpose: Interictal epileptic discharges (IEDs) are known to affect cognitive function in patients with epilepsy, but the mechanism has not been elucidated. Sleep spindles appearing in synchronization with IEDs were recently demonstrated to impair memory consolidation in rat, but this has not been investigated in humans. On the other hand, the increase of sleep spindles at night after learning is positively correlated with amplified learning effects during sleep for motor sequence learning. In this study, we examined the effects of IEDs and IED-coupled spindles on motor sequence learning in patients with epilepsy, and clarified their pathological significance. Materials and methods: Patients undergoing long-term video-electroencephalography (LT-VEEG) at our hospital from June 2019 to November 2021 and age-matched healthy subjects were recruited. Motor sequence learning consisting of a finger-tapping task was performed before bedtime and the next morning, and the improvement rate of performance was defined as the sleep-dependent learning effect. We searched for factors associated with the changes in learning effect observed between the periods of when antiseizure medications (ASMs) were withdrawn for LT-VEEG and when they were returned to usual doses after LT-VEEG. Results: Excluding six patients who had epileptic seizures at night after learning, nine patients and 11 healthy subjects were included in the study. In the patient group, there was no significant learning effect when ASMs were withdrawn. The changes in learning effect of the patient group during ASM withdrawal were not correlated with changes in sleep duration or IED density; however, they were significantly negatively correlated with changes in IED-coupled spindle density. Conclusion: We found that the increase of IED-coupled spindles correlated with the decrease of sleep-dependent learning effects of procedural memory. Pathological IED-coupled sleep spindles could hinder memory consolidation, that is dependent on physiological sleep spindles, resulting in cognitive dysfunction in patients with epilepsy.