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The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset. Here we present another method using a Convolutional Neural Network for Estimating synaptic Connectivity from spike trains. After adaptation to huge amounts of simulated data, this method robustly captures the specific feature of monosynaptic impact in a noisy cross-correlogram. There are no user-adjustable parameters. With this new method, we have constructed diagrams of neuronal circuits recorded in several cortical areas of monkeys.

Perception of a stable visual world despite eye motion requires integration of visual information across saccadic eye movements. To investigate how the visual system deals with localization of moving visual stimuli across saccades, we observed spatiotemporal changes of receptive fields (RFs) of motion-sensitive neurons across periods of saccades in the middle temporal (MT) and medial superior temporal (MST) areas. We found that the location of the RFs moved with shifts of eye position due to saccades, indicating that motion-sensitive neurons in both areas have retinotopic RFs across saccades. Different characteristic responses emerged when the moving visual stimulus was turned off before the saccades. For MT neurons, virtually no response was observed after the saccade, suggesting that the responses of these neurons simply reflect the reafferent visual information. In contrast, most MST neurons increased their firing rates when a saccade brought the location of the visual stimulus into their RFs, where the visual stimulus itself no longer existed. These findings suggest that the responses of such MST neurons after saccades were evoked by a memory of the stimulus that had preexisted in the postsaccadic RFs (“memory remapping”). A delayed-saccade paradigm further revealed that memory remapping in MST was linked to the saccade itself, rather than to a shift in attention. Thus, the visual motion information across saccades was integrated in spatiotopic coordinates and represented in the activity of MST neurons. This is likely to contribute to the perception of a stable visual world in the presence of eye movements.

Forward head posture (FHP) is a serious problem causing head and neck disability, but the characteristics of muscle activity during long-term postural maintenance are unclear. This study aimed to investigate a comparison of electromyography (EMG) activation properties and subjective fatigue between young adults with and without habitual FHP. In this study, we examined the changes in the spatial and temporal distribution patterns of muscle activity using high-density surface EMG (HD-SEMG) in addition to mean frequency, a conventional measure of muscle fatigue. Nineteen male participants were included in the study (FHP group (n = 9; age = 22.3 ± 1.5 years) and normal group (n = 10; age = 22.5 ± 1.4 years)). Participants held three head positions (e.g., forward, backward, and neutral positions) for a total of 30 min each, and the EMG activity of the trapezius pars descendens muscle during posture maintenance was measured by HD-SEMG. The root mean square (RMS), the modified entropy, and the correlation coefficient were calculated. Additionally, the visual analogue scale (VAS) was evaluated to assess subjective fatigue. The RMS, VAS, modified entropy, and correlation coefficients were significantly higher in the FHP group than in the normal group ( p  < 0.001). With increasing postural maintenance time, the modified entropy and correlation coefficient values significantly decreased, and the mean frequency and VAS values significantly increased ( p  < 0.001). Furthermore, the forward position had significantly higher RMS, correlation coefficient, modified entropy, and VAS values than in the neutral position ( p  < 0.001). The HD-SEMG potential distribution patterns in the FHP group showed less heterogeneity and greater muscle activity in the entire muscle and subjective fatigue than those in the normal group. Excess muscle activity even in the neutral/comfortable position in the FHP group could potentially be a mechanism of neuromuscular conditions in this population.

When two-frame apparent motion stimuli are presented with an appropriate inter-stimulus interval (ISI), motion is perceived in the direction opposite to the actual image shift. Herein, we measured a simple eye movement, ocular following responses (OFRs), in macaque monkeys to examine the ISI reversal effect on oculomotor. Two-frame movies with an ISI induced reversed OFRs. Without ISI, the OFRs to the two-frame movie were induced in the direction of the stimulus shift. However, with ISIs ≥10 ms, OFRs in the direction opposite to the phase shift were observed. This directional reversal persisted for ISIs up to 160 ms; for longer ISIs virtually no ocular response was observed. Furthermore, longer exposure to the initial image (Motion onset delay: MOD) reduced OFRs. We show that these dependences on ISIs/MODs can be explained by the motion energy model. Furthermore, we examined the dependence on ISI reversal using various spatial frequencies. To account for our findings, the optimal frequency of the temporal filters of the energy model must decrease between 0.5 and 1 cycles/°, suggesting that there are at least two channels with different temporal characteristics. These results are consistent with those from humans, suggesting that the temporal filters embedded in human and macaque visual systems are similar. Thus, the macaque monkey is a good animal model for the early visual processing of humans to understand the neural substrates underlying the visual motion detectors that elicit OFRs.

Feed-forward deep neural networks have better performance in object categorization tasks than other models of computer vision. To understand the relationship between feed-forward deep networks and the primate brain, we investigated representations of upright and inverted faces in a convolutional deep neural network model and compared them with representations by neurons in the monkey anterior inferior-temporal cortex, area TE. We applied principal component analysis to feature vectors in each model layer to visualize the relationship between the vectors of the upright and inverted faces. The vectors of the upright and inverted monkey faces were more separated through the convolution layers. In the fully-connected layers, the separation among human individuals for upright faces was larger than for inverted faces. The Spearman correlation between each model layer and TE neurons reached a maximum at the fully-connected layers. These results indicate that the processing of faces in the fully-connected layers might resemble the asymmetric representation of upright and inverted faces by the TE neurons. The separation of upright and inverted faces might take place by feed-forward processing in the visual cortex, and separations among human individuals for upright faces, which were larger than those for inverted faces, might occur in area TE.

It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

When we see a person's face, we can easily recognize their species, individual identity and emotional state. How does the brain represent such complex information? A substantial number of neurons in the macaque temporal cortex respond to faces 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . However, the neuronal mechanisms underlying the processing ofcomplex information are not yet clear. Here we recorded the activity of single neurons in the temporal cortex of macaque monkeys while presenting visual stimuli consisting of geometric shapes, and monkey and human faces with various expressions. Information theory was used to investigate how well the neuronal responses could categorize the stimuli. We found that single neurons conveyed two different scales of facial information intheir firing patterns, starting at different latencies. Global information, categorizing stimuli as monkey faces, human faces or shapes, was conveyed in the earliest part of the responses. Fineinformation about identity or expression was conveyed later,beginning on average 51 ms after global information. We speculate that global information could be used as a ‘header’ to prepare destination areas for receiving more detailed information.

Macroglossia is a common feature in patients with Beckwith-Wiedemann syndrome (BWS). The underlying cause of macroglossia in BWS remains unknown, and further histological studies are required to uncover its etiology. We present the case of a 5-year-old girl who was diagnosed with BWS and underwent partial tongue resection for difficulties in articulation and aesthetics. The keyhole-shaped partial resection revealed a harder posterior side than the anterior. Microscopically, the posterior side consisted of dense subepithelial eosinophilic areas composed of an abundance of tightly packed skeletal muscle fibers that were arranged in a fascicular or storiform pattern. BWS-associated macroglossia results from skeletal muscle hyperplasia, consistent with true macroglossia. Therefore, tongue resection may be beneficial for such patients. Further studies are required to develop personalized surgical interventions for each patient with BWS.

The ribbon synapse is a specialized synaptic structure in the retinal outer plexiform layer where visual signals are transmitted from photoreceptors to the bipolar and horizontal cells. This structure is considered important in high-efficiency signal transmission; however, its role in visual signal processing is unclear. In order to understand its role in visual processing, the present study utilized Pikachurin-null mutant mice that show improper formation of the photoreceptor ribbon synapse. We examined the initial and late phases of the optokinetic responses (OKRs). The initial phase was examined by measuring the open-loop eye velocity of the OKRs to sinusoidal grating patterns of various spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant mice showed significant initial OKRs with a spatiotemporal frequency tuning (spatial frequency, 0.09 ± 0.01 cycles/°; temporal frequency, 1.87 ± 0.12 Hz) that was slightly different from the wild-type mice (spatial frequency, 0.11 ± 0.01 cycles/°; temporal frequency, 1.66 ± 0.12 Hz). The late phase of the OKRs was examined by measuring the slow phase eye velocity of the optokinetic nystagmus induced by the sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and temporal frequencies of the mutant mice (spatial frequency, 0.11 ± 0.02 cycles/°; temporal frequency, 0.81 ± 0.24 Hz) were both lower than those in the wild-type mice (spatial frequency, 0.15 ± 0.02 cycles/°; temporal frequency, 1.93 ± 0.62 Hz). These results suggest that the ribbon synapse modulates the spatiotemporal frequency tuning of visual processing along the ON pathway by which the late phase of OKRs is mediated.

We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.