Precise Discrimination for Multiple Etiologies of Dementia Cases Based on Deep Learning with Electroencephalography.

INTRODUCTION: It is critical to develop accurate and universally available biomarkers for dementia diseases to appropriately deal with the dementia problems under world-wide rapid increasing of patients with dementia. In this sense, electroencephalography (EEG) has been utilized as a promising examination to screen and assist in diagnosing dementia, with advantages of sensitiveness to neural functions, inexpensiveness, and high availability. Moreover, the algorithm-based deep learning can expand EEG applicability, yielding accurate and automatic classification easily applied even in general hospitals without any research specialist. METHODS: We utilized a novel deep neural network, with which high accuracy of discrimination was archived in neurological disorders in the previous study. Based on this network, we analyzed EEG data of healthy volunteers (HVs, N = 55), patients with Alzheimer's disease (AD, N = 101), dementia with Lewy bodies (DLB, N = 75), and idiopathic normal pressure hydrocephalus (iNPH, N = 60) to evaluate the discriminative accuracy of these diseases. RESULTS: High discriminative accuracies were archived between HV and patients with dementia, yielding 81.7% (vs. AD), 93.9% (vs. DLB), 93.1% (vs. iNPH), and 87.7% (vs. AD, DLB, and iNPH). CONCLUSION: This study revealed that the EEG data of patients with dementia were successfully discriminated from HVs based on a novel deep learning algorithm, which could be useful for automatic screening and assisting diagnosis of dementia diseases.

EEG Resting-State Networks in Dementia with Lewy Bodies Associated with Clinical Symptoms.

BACKGROUND: Dementia with Lewy bodies (DLB) is characterized by progressive cognitive decline, fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism. DLB is the second most common type of degenerative dementia of all dementia cases. However, DLB, particularly in the early stage, is underdiagnosed and sometimes misdiagnosed with other types of dementia. Thus, it is of great interest investigating neurophysiological markers of DLB. METHOD: We introduced exact low-resolution brain electromagnetic tomography (eLORETA)-independent component analysis (ICA) to assess activities of 5 electroencephalography (EEG) resting-state networks (RSNs) in 41 drug-free DLB patients. RESULTS: Compared to 80 healthy controls, DLB patients had significantly decreased activities in occipital visual and sensorimotor networks, where DLB patients and healthy controls showed no age dependences in all EEG-RSN activities. Also, we found correlations between all EEG-RSN activities and DLB symptoms. Specifically, decreased occipital α activity showed correlations with worse brain functions related to attention/concentration, visuospatial discrimination, and global cognition. Enhanced visual perception network activity correlated with milder levels of depression and anxiety. Enhanced self-referential network activity correlated with milder levels of depression. Enhanced memory perception network activity correlated with better semantic memory, visuospatial discrimination function, and global cognitive function as well as with severer visual hallucination. In addition, decreased sensorimotor network activity correlated with a better semantic memory. CONCLUSION: These results indicate that eLORETA-ICA can detect EEG-RSN activity alterations in DLB related to symptoms. Therefore, eLORETA-ICA with EEG data can be a useful noninvasive tool for sensitive detection of EEG-RSN activity changes characteristic of DLB and for understanding the neurophysiological mechanisms underlying this disease.

Alpha event-related synchronization after eye closing differs in Alzheimer's disease and dementia with Lewy bodies: a magnetoencephalography study.

BACKGROUND: The electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis. METHODS: Six patients with DLB, 11 patients with Alzheimer's disease, and 11 age-matched normal subjects were recruited. We investigated alterations in the ratio of event-related synchronization (ERS) in the alpha band after eye-closing. RESULTS: Although the averaged ratio change of alpha ERS after eye-closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto-occipital cortex compared to Alzheimer's disease patients or normal controls. CONCLUSION: Our findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye-closing is a brain electromagnetic feature of DLB.

Healthy and Pathological Brain Aging: From the Perspective of Oscillations, Functional Connectivity, and Signal Complexity.

Healthy aging is associated with impairment in cognitive information processing. Several neuroimaging methods such as functional magnetic resonance imaging, positron emission tomography and near-infrared spectroscopy have been used to explore healthy and pathological aging by relying on hemodynamic or metabolic changes that occur in response to brain activity. Since electroencephalography (EEG) and magnetoencephalography (MEG) are able to measure neural activity directly with a high temporal resolution of milliseconds, these neurophysiological techniques are particularly important to investigate the dynamics of brain activity underlying neurocognitive aging. It is well known that age is a major risk factor for Alzheimer's disease (AD), and that synaptic dysfunction represents an early sign of this disease associated with hallmark neuropathological findings. However, the neurophysiological mechanisms underlying AD are not fully elucidated. This review addresses healthy and pathological brain aging from a neurophysiological perspective, focusing on oscillatory activity changes during the resting state, event-related potentials and stimulus-induced oscillatory responses during cognitive or motor tasks, functional connectivity between brain regions, and changes in signal complexity. We also highlight the accumulating evidence on age-related EEG/MEG changes and biological markers of brain neurodegeneration, including genetic factors, structural abnormalities on magnetic resonance images, and the biochemical changes associated with Aß deposition and tau pathology.

Eye movement as a biomarker of schizophrenia: Using an integrated eye movement score.

AIM: Studies have shown that eye movement abnormalities are possible neurophysiological biomarkers for schizophrenia. The aim of this study was to investigate the utility of eye movement abnormalities in identifying patients with schizophrenia from healthy controls. METHODS: Eighty-five patients with schizophrenia and 252 healthy controls participated in this study. Eye movement measures were collected from free viewing, fixation stability, and smooth pursuit tests. In an objective and stepwise method, eye movement measures were extracted to create an integrated eye movement score. RESULTS: The discriminant analysis resulted in three eye movement measures; the scanpath length during the free viewing test, the horizontal position gain during the fast Lissajous paradigm of the smooth pursuit test, and the duration of fixations during the far distractor paradigm of the fixation stability test. An integrated score using these variables can distinguish patients with schizophrenia from healthy controls with 82% accuracy. The integrated score was correlated with Wechsler Adult Intelligence Scale-Third Edition full scale IQ, Positive and Negative Syndrome Scale scores, and chlorpromazine equivalents, with different correlation patterns in the three eye movement measures used. The discriminant analysis in subgroups matched for age, sex, years of education, and premorbid IQ revealed a sustained classification rate. CONCLUSION: We established an integrated eye movement score with high classification accuracy between patients with schizophrenia and healthy controls, although there was a significant effect of medication. This study provides further evidence of the utility of eye movement abnormalities in schizophrenia pathology and treatment.

Emotion Regulation of Neuroticism: Emotional Information Processing Related to Psychosomatic State Evaluated by Electroencephalography and Exact Low-Resolution Brain Electromagnetic Tomography.

Emotion regulation is the process that adjusts the type or amount of emotion when we experience an emotional situation. The aim of this study was to reveal quantitative changes in brain activity during emotional information processing related to psychosomatic states and to determine electrophysiological features of neuroticism. Twenty-two healthy subjects (mean age 25 years, 14 males and 8 females) were registered. Electroencephalography (EEG) was measured during an emotional audiovisual memory task under three conditions (neutral, pleasant and unpleasant sessions). We divided the subjects into two groups using the Cornell Medical Index (CMI): (CMI-I: control group, n = 10: CMI-II, III or IV: neuroticism group, n = 12). We analyzed the digital EEG data using exact low-resolution brain electromagnetic tomography (eLORETA) current source density (CSD) and functional connectivity analysis in several frequency bands (δ, θ, α, ß, γ and whole band). In all subjects, bilateral frontal α CSD in the unpleasant session increased compared to the pleasant session, especially in the control group (p < 0.05). CSD of the neuroticism group was significantly higher than that of the control group in the full band at the amygdala and inferior temporal gyrus, and in the α band at the right temporal lobe (p < 0.05). Additionally, we found an increase in functional connectivity between the left insular cortex and right superior temporal gyrus in all subjects during the unpleasant session compared to the pleasant session (p < 0.05). In this study, using EEG analysis, we could find a novel cortical network related to brain mechanisms underlying emotion regulation. Overall findings indicate that it is possible to characterize neuroticism electrophysiologically, which may serve as a neurophysiological marker of this personality trait. © 2015 S. Karger AG, Basel.

Association of cerebrospinal fluid tap-related oscillatory activity and shunt outcome in idiopathic normal-pressure hydrocephalus.

BACKGROUND: Idiopathic normal-pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by the clinical triad of gait disturbance, urinary dysfunction, and cognitive impairment. The aim of the present study was to find specific EEG patterns associated with shunt response in iNPH. METHODS: Twenty five iNPH patients (10 shunt responders and 15 non-responders) were enrolled in this study. We performed current source density (CSD) analysis in several frequency bands (delta: 2-4 Hz, theta: 4-8 Hz, alpha: 8-13 Hz, beta: 13-30 Hz, gamma: 30-60 Hz) using exact Low Resolution Brain Electromagnetic Tomography (eLORETA). CSD distribution was compared between shunt responders and non-responders for each frequency band before and after CSF tap test. RESULTS: Shunt responders showed increased gamma CSD in the left temporal cortex before CSF tapping relative to non-responders. However, after CSF tapping, shunt response was associated with significantly higher CSDs in several frequency bands, specifically theta, alpha, beta and gamma, involving mainly the frontal and temporal areas. Using eLORETA analysis, we were able to identify cortical oscillatory activity before and after CSF tap test related to clinical recovery due to shunt operation in iNPH. CONCLUSION: Our findings support and extend the results of previous studies examining the effects of CSF tap test and shunt operation in patients with iNPH, possibly indicating electrophysiological features of shunt response in this disease. These findings warrant future studies to use EEG for prediction of shunt response in iNPH.

Relation between remission status and attention in patients with schizophrenia.

AIM: Patients with schizophrenia in remission have shown significantly higher levels of neurocognitive function than patients not in remission. However, previous studies have mainly examined the association between neurocognitive function and the remission status of schizophrenia without considering the time component of the definition for remission using cross-sectional methods. The purpose of this study was to investigate the relations between remission status with considering time components and three cognitive functions of intellectual ability, memory and attention, which were examined before fulfilling the remission criteria, using longitudinal methods. METHODS: We assessed the remission status using the Positive and Negative Syndrome Scale (PANSS) on the same patients twice: at recruitment and at 6 months after the first PANSS assessment. Cognitive tests were performed within 3 months after recruitment. At recruitment, 337 patients were enrolled. Of the patients, 63 patients were followed up and completedthe first and second PANSS assessments and three cognitive tests at the end of study. RESULTS: Of the patients, 33 patients fulfilled the remission criteria, while 30 patients did not fulfill the criteria. Patients in remission showed significantly higher levels of 2-digit (P = 0.020) and 3-digit (P = 0.015) Continuous Performance Test scores, attention/concentration in the Wechsler Memory Scale-Revised (P = 0.034) and processing speeds in the Wechsler Adult Intelligence Scale-III (P = 0.047) than patients not in remission. Additionally, these cognitive scores were positively correlated with each other (P < 0.05). CONCLUSION: Our findings suggest that patients who achieve remission may demonstrate a pre-existing higher level of attention than patients who do not achieve remission.

Visual salience is affected in participants with schizophrenia during free-viewing.

Abnormalities in visual exploration affect the daily lives of patients with schizophrenia. For example, scanpath length during free-viewing is shorter in schizophrenia. However, its origin and its relevance to symptoms are unknown. Here we investigate the possibility that abnormalities in eye movements result from abnormalities in visual or visuo-cognitive processing. More specifically, we examined whether such abnormalities reflect visual salience in schizophrenia. Eye movements of 82 patients and 252 healthy individuals viewing natural and/or complex images were examined using saliency maps for static images to determine the contributions of low-level visual features to salience-guided eye movements. The results showed that the mean value for orientation salience at the gazes of the participants with schizophrenia were higher than that of the healthy control subjects. Further analyses revealed that orientation salience defined by the L + M channel of the DKL color space is specifically affected in schizophrenia, suggesting abnormalities in the magnocellular visual pathway. By looking into the computational stages of the visual salience, we found that the difference between schizophrenia and healthy control emerges at the earlier stage, suggesting functional decline in early visual processing. These results suggest that visual salience is affected in schizophrenia, thereby expanding the concept of the aberrant salience hypothesis of psychosis to the visual domain.

Influence of the NRGN gene on intellectual ability in schizophrenia.

Genome-wide association studies have reported an association between schizophrenia and rs12807809 of the neurogranin (NRGN) gene. We have recently found that an rs12807809-rs12278912 haplotype of the gene is associated with schizophrenia in a Japanese population and that the NRGN expression of the high-risk TG haplotype is lower than that of the protective TA haplotype in immortalized lymphoblasts. In this study, we investigated the influences of neurogranin genotypes (rs12807809 and rs12278912), haplotypes and diplotypes and genetic variant-diagnosis interactions on intellectual ability in 414 Japanese patients with schizophrenia and healthy subjects. We detected possible effects of the genome-wide screen-supported rs12807809, haplotypes, diplotypes and their genetic variant-diagnosis interactions on intellectual abilities at the threshold level of P<0.05. After applying Bonferroni correction for 13 genotype measures and setting P-values for significance (P<0.0039; 0.05/13), three effects remained significant: the rs12807809-rs12278912 diplotype-diagnosis interactions on performance intelligence quotient (CG/CG: P=3.9 × 10(-13); TA/TA: P=1.1 × 10(-7)) and TA/TA diplotype on performance intelligence quotient in patients with schizophrenia (P=8.2 × 10(-8)) remained significant. The intellectual abilities of the high-risk TG/TG diplotype of the neurogranin gene were lower compared to those with the non-risk TA/TA diplotype. Our findings suggest that the genetic risk variant in the neurogranin gene may be related to reduced intellectual ability.

The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia.

BACKGROUND: Genome-wide significant associations of schizophrenia with eight SNPs in the CNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear. METHODS: After performing quality control for minor-allele frequency > 5% using a JPT HapMap sample and our sample, a genotyping call rate > 95% and Hardy-Weinberg equilibrium testing (p > 0.01), five of eight SNPs were eligible for analysis. We used a comprehensive voxel-based morphometry (VBM) technique to investigate the effects of these five SNPs on GM volumes between major-allele homozygotes and minor-allele carriers in Japanese patients with schizophrenia (n = 173) and healthy subjects (n = 449). RESULTS: The rs7914558 risk variant at CNNM2 was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T = 4.96, p = 0.0088, left T = 4.66, p = 0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWE-correction for multiple tests (p > 0.05). CONCLUSIONS: Our findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the GM volumetric vulnerability of the orbital regions in the inferior frontal gyri.

Frequency diversity of posterior oscillatory activity in human revealed by spatial filtered MEG.

The posterior EEG alpha rhythm is a distinctive feature of the normal brain in the waking state, consisting of oscillations within the 8-15 Hz frequency range over posterior cortical regions. This activity appears in resting, eyes-closed condition and is typically suppressed by eyes-opening. Other physiological rhythms in the alpha band, in particular the Rolandic mu rhythm, are proposed to include a fast component in the beta range. In this study we used spatial filtering techniques and permutation analysis to explore cortical source-power changes related to the magnetoencephalography (MEG) counterpart of the posterior alpha rhythm. We also aimed at determining a possible implication of components outside the alpha frequency range in the posterior rhythm reactivity to eye closure. We recorded resting brain activity using a whole-head MEG system in fifteen normal subjects. We applied an eyes-open/eyes-closed paradigm. A significant increase in alpha oscillations after eyes closing, representing the posterior alpha rhythm, was observed bilaterally in the occipital and parietal cortex, including the calcarine fissure and the parieto-occipital sulcus. We also found significant increase in beta (15-30 Hz) and low gamma (30-60 Hz) oscillations. This fast components and the classical alpha rhythm had similar topographic distribution in posterior brain regions, although with different strength and spatial extension. These features were highest for alpha synchronized oscillations, intermediate for beta, and lowest for gamma activity. These results suggest that, like the Rolandic mu rhythm, the MEG posterior dominant rhythm may be impure, with a mixture of predominant alpha oscillations and high-frequency components.

Normalized Power Variance: A new Field Orthogonal to Power in EEG Analysis.

To date, electroencephalogram (EEG) has been used in the diagnosis of epilepsy, dementia, and disturbance of consciousness via the inspection of EEG waves and identification of abnormal electrical discharges and slowing of basic waves. In addition, EEG power analysis combined with a source estimation method like exact-low-resolution-brain-electromagnetic-tomography (eLORETA), which calculates the power of cortical electrical activity from EEG data, has been widely used to investigate cortical electrical activity in neuropsychiatric diseases. However, the recently developed field of mathematics "information geometry" indicates that EEG has another dimension orthogonal to power dimension - that of normalized power variance (NPV). In addition, by introducing the idea of information geometry, a significantly faster convergent estimator of NPV was obtained. Research into this NPV coordinate has been limited thus far. In this study, we applied this NPV analysis of eLORETA to idiopathic normal pressure hydrocephalus (iNPH) patients prior to a cerebrospinal fluid (CSF) shunt operation, where traditional power analysis could not detect any difference associated with CSF shunt operation outcome. Our NPV analysis of eLORETA detected significantly higher NPV values at the high convexity area in the beta frequency band between 17 shunt responders and 19 non-responders. Considering our present and past research findings about NPV, we also discuss the advantage of this application of NPV representing a sensitive early warning signal of cortical impairment. Overall, our findings demonstrated that EEG has another dimension - that of NPV, which contains a lot of information about cortical electrical activity that can be useful in clinical practice.

EEG resting-state networks in Alzheimer's disease associated with clinical symptoms.

Alzheimer's disease (AD) is a progressive neuropsychiatric disease affecting many elderly people and is characterized by progressive cognitive impairment of memory, visuospatial, and executive functions. As the elderly population is growing, the number of AD patients is increasing considerably. There is currently growing interest in determining AD's cognitive dysfunction markers. We used exact low-resolution-brain-electromagnetic-tomography independent-component-analysis (eLORETA-ICA) to assess activities of five electroencephalography resting-state-networks (EEG-RSNs) in 90 drug-free AD patients and 11 drug-free patients with mild-cognitive-impairment due to AD (ADMCI). Compared to 147 healthy subjects, the AD/ADMCI patients showed significantly decreased activities in the memory network and occipital alpha activity, where the age difference between the AD/ADMCI and healthy groups was corrected by linear regression analysis. Furthermore, the age-corrected EEG-RSN activities showed correlations with cognitive function test scores in AD/ADMCI. In particular, decreased memory network activity showed correlations with worse total cognitive scores for both Mini-Mental-State-Examination (MMSE) and Alzheimer's Disease-Assessment-Scale-cognitive-component-Japanese version (ADAS-J cog) including worse sub-scores for orientation, registration, repetition, word recognition and ideational praxis. Our results indicate that AD affects specific EEG-RSNs and deteriorated network activity causes symptoms. Overall, eLORETA-ICA is a useful, non-invasive tool for assessing EEG-functional-network activities and provides better understanding of the neurophysiological mechanisms underlying the disease.

Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment.

In this study we used magnetoencephalography during a modified version of the Sternberg's memory recognition task performed by patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event-related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline.

Functional genetic variation at the NRGN gene and schizophrenia: evidence from a gene-based case-control study and gene expression analysis.

Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P = 0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR = 1.14, P = 0.0019) and lower (OR = 0.85, P = 0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR = 1.10, P = 0.057) and rs2075713 (OR = 1.10, P = 0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z = 2.69, P = 0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z = 3.09, P = 0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia.

[Endophenotypes in schizophrenia: a review of electrophysiological studies].

Schizophrenia patients consistently show some deficiency in electrophysiological measures, such as PPI (Prepulse Inhibition), ERP (Event-Related Potential) components (mismatch negativity, P50, P300), EEG (Electroencephalography), and MEG (Magnetoencephalography). These components have been intensively studied as quantitative biological markers (i.e., endophenotypes) for psychiatric disorders. Recently brain oscillations, especially gamma (30-80 Hz) band activity (GBA), are being increasingly investigated as new candidate endophenotypes. In this review, we summarize the current status, perspective, and limitations of representative paradigms for investigating abnormal electrophysiological components of schizophrenia, along with relevant genetic polymorphism.

The effect of ketamine on eye movement characteristics during free-viewing of natural images in common marmosets.

Various eye movement abnormalities and impairments in visual information processing have been reported in patients with schizophrenia. Therefore, dysfunction of saccadic eye movements is a potential biological marker for schizophrenia. In the present study, we used a pharmacological model of schizophrenia symptoms in marmosets and compared the eye movement characteristics of marmosets during free-viewing, using an image set identical to those used for human studies. It contains natural and complex images that were randomly presented for 8 s. As a pharmacological model of schizophrenia symptoms, a subanesthetic dose of ketamine was injected intramuscularly for transient and reversible manipulation. Eye movements were recorded and compared under a ketamine condition and a saline condition as a control. The results showed that ketamine affected eye movement characteristics during free-viewing. Saccades amplitude and scanpath length were significantly reduced in the ketamine condition. In addition, the duration of saccades was longer under the ketamine condition than under the saline condition. A similar tendency was observed for the duration of fixations. The number of saccades and fixations tended to decrease in the ketamine condition. The peak saccades velocity also decreased after ketamine injection whereas there was no difference in the main sequence relationship between saccades amplitude and peak velocity. These results suggest that ketamine affected visual exploration but did not affect the oculomotor aspect of saccades in marmosets, consistent with studies in patients with schizophrenia. Therefore, we conclude that the subanesthetic dose of ketamine is a promising pharmacological model of schizophrenia symptoms in common marmosets and can be used in combination with free-viewing paradigms to establish "translatable markers" for schizophrenia in primates.