Quadrupling the depairing current density in the iron-based superconductor SmFeAsO1-xHx.

Iron-based 1111-type superconductors display high critical temperatures and relatively high critical current densities Jc. The typical approach to increasing Jc is to introduce defects to control dissipative vortex motion. However, when optimized, this approach is theoretically predicted to be limited to achieving a maximum Jc of only ∼30% of the depairing current density Jd, which depends on the coherence length and the penetration depth. Here we dramatically boost Jc in SmFeAsO1-xHx films using a thermodynamic approach aimed at increasing Jd and incorporating vortex pinning centres. Specifically, we reduce the penetration depth, coherence length and critical field anisotropy by increasing the carrier density through high electron doping using H substitution. Remarkably, the quadrupled Jd reaches 415 MA cm-2, a value comparable to cuprates. Finally, by introducing defects using proton irradiation, we obtain high Jc values in fields up to 25 T. We apply this method to other iron-based superconductors and achieve a similar enhancement of current densities.

Characteristics of auditory steady-state responses to different click frequencies in awake intact macaques.

BACKGROUND: Auditory steady-state responses (ASSRs) are periodic evoked responses to constant periodic auditory stimuli, such as click trains, and are suggested to be associated with higher cognitive functions in humans. Since ASSRs are disturbed in human psychiatric disorders, recording ASSRs from awake intact macaques would be beneficial to translational research as well as an understanding of human brain function and its pathology. However, ASSR has not been reported in awake macaques. RESULTS: Electroencephalograms (EEGs) were recorded from awake intact macaques, while click trains at 20-83.3 Hz were binaurally presented. EEGs were quantified based on event-related spectral perturbation (ERSP) and inter-trial coherence (ITC), and ASSRs were significantly demonstrated in terms of ERSP and ITC in awake intact macaques. A comparison of ASSRs among different click train frequencies indicated that ASSRs were maximal at 83.3 Hz. Furthermore, analyses of laterality indices of ASSRs showed that no laterality dominance of ASSRs was observed. CONCLUSIONS: The present results demonstrated ASSRs, comparable to those in humans, in awake intact macaques. However, there were some differences in ASSRs between macaques and humans: macaques showed maximal ASSR responses to click frequencies higher than 40 Hz that has been reported to elicit maximal responses in humans, and showed no dominant laterality of ASSRs under the electrode montage in this study compared with humans with right hemisphere dominance. The future ASSR studies using awake intact macaques should be aware of these differences, and possible factors, to which these differences were ascribed, are discussed.

Acceleration of the Dehydrogenation of d-Glucose to 2-Keto-d-gluconate in Aqueous Amino Acid via Hydrated Stacked Clay Nanosheets.

The assembly of discrete active species to form periodical nanostructures is essential in realizing low-cost artificial enzymes that mimic natural enzymatic functions in extraordinary bio(chemo)selective reactions. In this study, we developed artificial bifunctional glucose/gluconic acid dehydrogenase from naturally abundant resources: l-aspartic acid (Asp) and montmorillonite (a subgroup of smectite natural clay minerals). ß-d-Glucose (Glc) was dehydrogenated to 2-keto-d-gluconate (2-KGA) at 25 and 30 °C in an aqueous acidic solution (pH = 3, 4, and 5). The reaction involved sequential steps that yielded d-gluconic acid (GA) as an intermediate. The second step of the dehydrogenation (GA to 2-KGA) occurred at a higher rate than the first (Glc to GA), which is comparable to the natural process. A negatively charged carboxylate in Asp was required for the dehydrogenation, which donates an electron pair (COO:-) to the hydroxyl group bonded to the C(1)-position of Glc. The acidic sites in clay served as coenzymatic sites (electron acceptor), promoting the Glc dehydrogenation as the Glc reduced by Asp approached the clay coenzymatic sites. The active coenzymatic structures were developed in 48 h (induction period) through the rearrangement of the adsorbed Asp and Glc molecules on montmorillonite in water (intermediate structure). The spontaneous assembling of the intermediate structures facilitated the one-pot dehydrogenation of Glc to 2-KGA via periodic "hydrated stacked layers" comprising clay nanosheets, Asp, and Glc. The facile synthetic route proposed here is inexpensive and would be beneficial without using both GDH and GADH enzymes bound to a cell membrane.

Configural Cues Associated with Reward Elicit Theta Oscillations of Rat Retrosplenial Cortical Neurons Phase-Locked to LFP Theta Cycles.

Previous behavioral studies implicated the retrosplenial cortex (RSC) in stimulus-stimulus associations, and also in the retrieval of remote associative memory based on EEG theta oscillations. However, neural mechanisms involved in the retrieval of stored information of such associations and memory in the RSC remain unclear. To investigate the neural mechanisms underlying these processes, RSC neurons and local field potentials (LFPs) were simultaneously recorded from well-trained rats performing a cue-reward association task. In the task, simultaneous presentation of two multimodal conditioned stimuli (configural CSs) predicted a reward outcome opposite to that associated with the individual presentation of each elemental CS. Here, we show neurophysiological evidence that the RSC is involved in stimulus-stimulus association where configural CSs are discriminated from each elementary CS that is a constituent of the configural CSs, and that memory retrieval of rewarding CSs is associated with theta oscillation of RSC neurons during CS presentation, which is phase-locked to LFP theta cycles. The results suggest that cue (elementary and configural CSs)-reinforcement associations are stored in the RSC neural circuits, and are retrieved in synchronization with LFP theta rhythm.

Rat Retrosplenial Cortical Involvement in Wayfinding Using Visual and Locomotor Cues.

The retrosplenial cortex (RSC) has been implicated in wayfinding using different sensory cues. However, the neural mechanisms of how the RSC constructs spatial representations to code an appropriate route under different sensory cues are unknown. In this study, rat RSC neurons were recorded while rats ran on a treadmill affixed to a motion stage that was displaced along a figure-8-shaped track. The activity of some RSC neurons increased during specific directional displacements, while the activity of other neurons correlated with the running speed on the treadmill regardless of the displacement directions. Elimination of visual cues by turning off the room lights and/or locomotor cues by turning off the treadmill decreased the activity of both groups of neurons. The ensemble activity of the former group of neurons discriminated displacements along the common central path of different routes in the track, even when visual or locomotor cues were eliminated where different spatial representations must be created based on different sensory cues. The present results provide neurophysiological evidence of an RSC involvement in wayfinding under different spatial representations with different sensory cues.

Superior Neuronal Detection of Snakes and Conspecific Faces in the Macaque Medial Prefrontal Cortex.

Snakes and conspecific faces are quickly and efficiently detected in primates. Because the medial prefrontal cortex (mPFC) has been implicated in attentional allocation to biologically relevant stimuli, we hypothesized that it might also be highly responsive to snakes and conspecific faces. In this study, neuronal responses in the monkey mPFC were recorded, while monkeys discriminated 8 categories of visual stimuli. Here, we show that the monkey mPFC neuronal responses to snakes and conspecific faces were unique. First, the ratios of the neurons that responded strongly to snakes and monkey faces were greater than those of the neurons that responded strongly to the other stimuli. Second, mPFC neurons responded stronger and faster to snakes and monkey faces than the other categories of stimuli. Third, neuronal responses to snakes were unaffected by low-pass filtering of the images. Finally, activity patterns of responsive mPFC neurons discriminated snakes from the other stimuli in the second 50 ms period and monkey faces in the third period after stimulus onset. These response features indicate that the mPFC processes fast and coarse visual information of snakes and monkey faces, and support the hypothesis that snakes and social environments have shaped the primate visual system over evolutionary time.

Ingestion of dried-bonito broth (dashi) facilitates PV-parvalbumin-immunoreactive neurons in the brain, and affects emotional behaviors in mice.

OBJECTIVES: Emerging evidence suggests that traditional diets and nutrition have a significant impact on brain development, and could contribute to the promotion of mental health and prevention of psychiatric disorders in children and adolescents. Moreover, deficits in parvalbumin (PV)-immunoreactive and/or GABAergic neurons are closely associated with various psychiatric disorders in children and adolescents. To investigate the possible neural mechanisms of diet involvement in mental health, we analyzed the effects of dried-bonito dashi (Japanese fish broth) (DBD) on PV-immunoreactive neurons and emotional behaviors in young mice. METHODS: Male mice after weaning were fed DBD for 60 days, and tested with a resident-intruder test for aggressiveness and a forced swimming test for depression-like symptoms. After the behavioral testing, PV-immunoreactive neurons in the brain were immunohistochemically analyzed. RESULTS: The results indicated that DBD intake decreased aggressiveness and depression-like symptoms, and increased the densities of PV-immunoreactive neurons in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and superior colliculus. These behavioral changes were correlated with the densities of PV-immunoreactive neurons in the mPFC, amygdala, and hippocampus. However, subdiaphragmatic vagotomy did not affect the effects of DBD on emotional behaviors, although it nonspecifically decreased the densities of PV-immunoreactive neurons. DISCUSSION: The results suggest that DBD might modulate emotional behaviors by promoting PV-immunoreactive and/or GABAergic neuronal activity through parallel routes. The present results highlight a new mechanism for diet involvement in brain functions, and suggest that DBD might have therapeutic potential for the promotion of mental health.

Effects of high fat diet and perinatal dioxin exposure on development of body size and expression of platelet-derived growth factor receptor ß in the rat brain.

Environmental exposure to dioxins, consumption of a high fat diet, and platelet-derived growth factor receptor ß signaling in the brain affect feeding behavior, which is an important determinant of body growth. In the present study, we investigated the effects of prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fact diet after weaning on body growth and expression of platelet-derived growth factor receptor ß in the brain in rat pups. Subjects from the control and dioxin exposure groups were assigned to 1 of 3 different diet groups: standard diet, high fat diet in the juvenile period, or high fat diet in adulthood. Body weight gain rate in the juvenile high fat diet group and the length gain rate in the adult high fat diet group were greater than the corresponding values in the standard diet group only in male offspring, although the effects of dioxin exposure on growth were not significant. Consumption of a high fat diet decreased platelet-derived growth factor receptor ß levels in the amygdala and hippocampus in both sexes compared to control groups, while 2,3,7,8-tetrachlorodibenzo-p-dioxin decreased platelet-derived growth factor receptor platelet-derived growth factor receptor ß levels in the amygdala and striatum only in females receiving an high fat diet. Furthermore, platelet-derived growth factor receptor ß levels in the hippocampus and platelet-derived growth factor receptor ß striatum were inversely correlated with increases in body length, while changes in platelet-derived growth factor receptor ß in the amygdala and nucleus accumbens were significantly correlated to body weight gain or body mass index. In conclusion, these findings suggest that these 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fat diet-induced changes in body growth and feeding behaviors might be partially mediated by changes in brain platelet-derived growth factor receptor ß levels.

Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes.

Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates' heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

Place-related neuronal activity in the monkey parahippocampal gyrus and hippocampal formation during virtual navigation.

Neuropsychological data in primates demonstrated a pivotal role of the hippocampal formation (HF) and parahippocampal gyrus (PH) in navigation and episodic memory. To investigate the role of HF and PH neurons in environmental scaling in primates, we recorded neuronal activities in the monkey HF and PH during virtual navigation (VN) and pointer translocation (PT) tasks. The monkeys had to navigate within three differently sized virtual spaces with the same spatial cues (VN task) or move a pointer on a screen (PT task) by manipulating a joystick to receive a reward. Of the 234 recorded neurons, 170 and 61 neurons displayed place-related activities in the VN and PT tasks, respectively. Significant differences were observed between the HF and PH neurons. The spatial similarity of place fields between the two different virtual spaces was lower in PH than in HF, while specificities of the neuronal responses to distal spatial cues were higher in PH than in HF. Spatial view information was predominately processed in posterior PH. The spatial scales (place field sizes) of the HF and PH neurons were reduced in the reduced virtual space, as shown in rodent place cells. These results suggest the complementary roles of HF (allocentric representation of landmarks) and PH (representation of the spatial layout of landmarks) in the recognition of a location during navigation.

Neuronal mechanism of innate rapid processing of threating animacy cue in primates: insights from the neuronal responses to snake images.

To survive in nature, it is crucial for animals to promptly and appropriately respond to visual information, specifically to animacy cues that pose a threat. The subcortical visual pathway is thought to be implicated in the processing of visual information necessary for these responses. In primates, this pathway consists of retina-superior colliculus-pulvinar-amygdala, functioning as a visual pathway that bypasses the geniculo-striate system (retina-lateral geniculate nucleus-primary visual cortex). In this mini review, we summarize recent neurophysiological studies that have revealed neural responses to threatening animacy cues, namely snake images, in different parts of the subcortical visual pathway and closely related brain regions in primates. The results of these studies provide new insights on (1) the role of the subcortical visual pathway in innate cognitive mechanisms for predator recognition that are evolutionarily conserved, and (2) the possible role of the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) in the development of fear conditioning to cues that should be instinctively avoided based on signals from the subcortical visual pathway, as well as their function in excessive aversive responses to animacy cues observed in conditions such as ophidiophobia (snake phobia).

Characterization of Ultrasonic Vocalization-Modulated Neurons in Rat Motor Cortex Based on Their Activity Modulation and Axonal Projection to the Periaqueductal Gray.

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the motor cortex. The neural activity patterns around the emission of USVs differed between the anterior and posterior regions, which were divided based on the distribution of PAG-projecting neurons in the motor cortex. Furthermore, using optogenetic tagging, we recorded the USV modulation of PAG-projecting neurons in the posterior part of the motor cortex and found that they showed predominantly sustained excitatory responses during USVs. These results contribute to our understanding of the involvement of the motor cortex in the generation of USV at the neuronal and circuit levels.

Unsupervised decomposition of natural monkey behavior into a sequence of motion motifs.

Nonhuman primates (NHPs) exhibit complex and diverse behavior that typifies advanced cognitive function and social communication, but quantitative and systematical measure of this natural nonverbal processing has been a technical challenge. Specifically, a method is required to automatically segment time series of behavior into elemental motion motifs, much like finding meaningful words in character strings. Here, we propose a solution called SyntacticMotionParser (SMP), a general-purpose unsupervised behavior parsing algorithm using a nonparametric Bayesian model. Using three-dimensional posture-tracking data from NHPs, SMP automatically outputs an optimized sequence of latent motion motifs classified into the most likely number of states. When applied to behavioral datasets from common marmosets and rhesus monkeys, SMP outperformed conventional posture-clustering models and detected a set of behavioral ethograms from publicly available data. SMP also quantified and visualized the behavioral effects of chemogenetic neural manipulations. SMP thus has the potential to dramatically improve our understanding of natural NHP behavior in a variety of contexts.

Deciphering social traits and pathophysiological conditions from natural behaviors in common marmosets.

Nonhuman primates (NHPs) are indispensable animal models by virtue of the continuity of behavioral repertoires across primates, including humans. However, behavioral assessment at the laboratory level has so far been limited. Employing the application of three-dimensional (3D) pose estimation and the optimal integration of subsequent analytic methodologies, we demonstrate that our artificial intelligence (AI)-based approach has successfully deciphered the ethological, cognitive, and pathological traits of common marmosets from their natural behaviors. By applying multiple deep neural networks trained with large-scale datasets, we established an evaluation system that could reconstruct and estimate the 3D poses of the marmosets, a small NHP that is suitable for analyzing complex natural behaviors in laboratory setups. We further developed downstream analytic methodologies to quantify a variety of behavioral parameters beyond motion kinematics. We revealed the distinct parental roles of male and female marmosets through automated detections of food-sharing behaviors using a spatial-temporal filter on 3D poses. Employing a recurrent neural network to analyze 3D pose time series data during social interactions, we additionally discovered that marmosets adjusted their behaviors based on others' internal state, which is not directly observable but can be inferred from the sequence of others' actions. Moreover, a fully unsupervised approach enabled us to detect progressively appearing symptomatic behaviors over a year in a Parkinson's disease model. The high-throughput and versatile nature of an AI-driven approach to analyze natural behaviors will open a new avenue for neuroscience research dealing with big-data analyses of social and pathophysiological behaviors in NHPs.

Neuronal responses in the nucleus accumbens shell during sexual behavior in male rats.

Previous behavioral studies have indicated that the nucleus accumbens (NAc) shell of a male rat is involved in its sexual behavior; however, no previous studies have investigated neuronal activities in the male rat NAc shell during sexual behavior. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. Of 123 NAc shell neurons studied, 53, 47, and 40 neurons exhibited significantly changed firing rates at various times during intromission, genital auto-grooming, and sniffing of females, respectively. The two types of NAc shell neurons [putative fast spiking interneurons (pFSIs) and medium spiny neurons (pMSNs)] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females. Second, both pFSIs and pMSNs responded differently to thrusting with and without intromission. Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation. Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward-related processing, and the inhibition of sexual behavior after ejaculation.

Neuronal responses to face-like stimuli in the monkey pulvinar.

The pulvinar nuclei appear to function as the subcortical visual pathway that bypasses the striate cortex, rapidly processing coarse facial information. We investigated responses from monkey pulvinar neurons during a delayed non-matching-to-sample task, in which monkeys were required to discriminate five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face-like patterns (three dark blobs on a bright oval), eye-like patterns and simple geometric patterns]. Of 401 neurons recorded, 165 neurons responded differentially to the visual stimuli. These visual responses were suppressed by scrambling the images. Although these neurons exhibited a broad response latency distribution, face-like patterns elicited responses with the shortest latencies (approximately 50 ms). Multidimensional scaling analysis indicated that the pulvinar neurons could specifically encode face-like patterns during the first 50-ms period after stimulus onset and classify the stimuli into one of the five different categories during the next 50-ms period. The amount of stimulus information conveyed by the pulvinar neurons and the number of stimulus-differentiating neurons were consistently higher during the second 50-ms period than during the first 50-ms period. These results suggest that responsiveness to face-like patterns during the first 50-ms period might be attributed to ascending inputs from the superior colliculus or the retina, while responsiveness to the five different stimulus categories during the second 50-ms period might be mediated by descending inputs from cortical regions. These findings provide neurophysiological evidence for pulvinar involvement in social cognition and, specifically, rapid coarse facial information processing.

Alpha- and theta-range cortical synchronization and corticomuscular coherence during joystick manipulation in a virtual navigation task.

Previous studies have reported that multiple brain regions are activated during spatial navigation, but it remains unclear how this activation is converted to motor commands for navigation. This study was aimed to investigate synchronization across different brain regions and between cortical areas and muscles during spatial navigation. This synchronization has been suggested to be essential for integrating activity in the multiple brain areas to support higher cognitive functions and for conversion of cortical activity to motor commands. In the present study, the subjects were required to sequentially trace ten checkpoints in a virtual town by manipulating a joystick and to perform this three times while electroencephalograms and electromyograms from the right arm were monitored. Time spent on the task in the third trial was significantly lesser than that in the first trial indicating an improvement in task performance. This repeated learning was associated with an increase in alpha power at the electrodes over the contralateral sensorimotor region and in theta power at the electrodes over the bilateral premotor and frontotemporal regions. Alpha- and theta-range corticocortical coherences between these regions and other brain areas were also increased in the third trial compared to the first trial. Furthermore, alpha- and theta-range corticomuscular coherence was significantly increased in the second and third trials compared to the first trial. These results suggest that alpha- and theta-range synchronous activity across multiple systems is essential for the integrated brain activity required in spatial navigation and for the conversion of this activity to motor commands.

Neuronal structures controlling locomotor behavior during active and inactive motor states.

Animal behaviors can be divided into two states according to their motor activity: the active motor state, which involves significant body movements, and the inactive motor state, which refers to when the animal is stationary. The timing and duration of these states are determined by the activity of the neuronal circuits involved in motor control. Among these motor circuits, those that generate locomotion are some of the most studied neuronal networks and are widely distributed from the spinal cord to the cerebral cortex. In this review, we discuss recent discoveries, mainly in rodents using state-of-the-art experimental approaches, of the neuronal mechanisms underlying the initiation and termination of locomotion in the brainstem, basal ganglia, and prefrontal cortex. These findings is discussed with reference to studies on the neuronal mechanism of motor control during sleep and the modulation of cortical states in these structures. Accumulating evidence has unraveled the complex yet highly structured network that controls the transition between motor states.

Electroencephalographic Effective Connectivity Analysis of the Neural Networks during Gesture and Speech Production Planning in Young Adults.

Gestures and speech, as linked communicative expressions, form an integrated system. Previous functional magnetic resonance imaging studies have suggested that neural networks for gesture and spoken word production share similar brain regions consisting of fronto-temporo-parietal brain regions. However, information flow within the neural network may dynamically change during the planning of two communicative expressions and also differ between them. To investigate dynamic information flow in the neural network during the planning of gesture and spoken word generation in this study, participants were presented with spatial images and were required to plan the generation of gestures or spoken words to represent the same spatial situations. The evoked potentials in response to spatial images were recorded to analyze the effective connectivity within the neural network. An independent component analysis of the evoked potentials indicated 12 clusters of independent components, the dipoles of which were located in the bilateral fronto-temporo-parietal brain regions and on the medial wall of the frontal and parietal lobes. Comparison of effective connectivity indicated that information flow from the right middle cingulate gyrus (MCG) to the left supplementary motor area (SMA) and from the left SMA to the left precentral area increased during gesture planning compared with that of word planning. Furthermore, information flow from the right MCG to the left superior frontal gyrus also increased during gesture planning compared with that of word planning. These results suggest that information flow to the brain regions for hand praxis is more strongly activated during gesture planning than during word planning.

Suppressive effects of ketamine on auditory steady-state responses in intact, awake macaques: A non-human primate model of schizophrenia.

Auditory steady-state responses (ASSRs) are recurrent neural activities entrained to regular cyclic auditory stimulation. ASSRs are altered in individuals with schizophrenia, and may be related to hypofunction of the N-methyl-D-aspartate (NMDA) glutamate receptor. Noncompetitive NMDA receptor antagonists, including ketamine, have been used in ASSR studies of rodent models of schizophrenia. Although animal studies using non-human primates are required to complement rodent studies, the effects of ketamine on ASSRs are unknown in intact awake non-human primates. In this study, after administration of vehicle or ketamine, click trains at 20-83.3 Hz were presented to elicit ASSRs during recording of electroencephalograms in intact, awake macaque monkeys. The results indicated that ASSRs quantified by event-related spectral perturbation and inter-trial coherence were maximal at 83.3 Hz after vehicle administration, and that ketamine reduced ASSRs at 58.8 and 83.3 Hz, but not at 20 and 40 Hz. The present results demonstrated a reduction of ASSRs by the NMDA receptor antagonist at optimal frequencies with maximal responses in intact, awake macaques, comparable to ASSR reduction in patients with schizophrenia. These findings suggest that ASSR can be used as a neurophysiological biomarker of the disturbance of gamma-oscillatory neural circuits in this ketamine model of schizophrenia using intact, awake macaques. Thus, this model with ASSRs would be useful in the investigation of human brain pathophysiology as well as in preclinical translational research.