A characteristic of olfactory function in four types of dementia and non-dementia subjects using smell identification test.

BACKGROUND: For those outpatients who were consulted for memory loss, the Japanese version of University of Pennsylvania Smell Identification Test (UPSIT-J) was performed to examine olfactory function. In the same way, the revised version of Hasegawa Dementia Scale, Mini Mental State Examination, Clinical Dementia Rating and brain magnetic resonance imaging were used to investigate the cognitive function. In the present study, we evaluated the olfactory function of elderly subjects, including those with dementia, by means of UPSIT-J and we examined their characteristics. METHODS: The characteristics of dementia as Alzheimer type group (AD.G), mixed type group (MixD.G), vascular type group (VaD.G), dementia with Lewy bodies group (DLB.G) and the groups which had no dementia as low score group (LS.G), high score group (HS.G), and healthy group (H.G), were examined. RESULTS: The numbers of olfactory discriminating scores (nODS) were significantly lower in all the dementia groups than in all the LS.G, HS.G and the H.G. No significant difference was observed in nODS between AD.G and DLB.G. The rate of nODS with less than five scores were as follows: AD.G (80.1%), MixD.G (91.5%), VaD.G (63.1%), DLB.G (89.6%), LS.G (50.8%), HS.G (18.6%), H.G (15.6%). A significant positive correlation was found between nODS and Hasegawa Dementia Scale and Mini Mental State Examination scores (r = 0.567, r = 0.532, respectively), which was significant negatively correlated for Clinical Dementia Rating (r = -0.578). A significant negative correlation was observed between nODS and Z score of voxel-based specific regional analysis for Z score of Alzheimer's disease (VSRAD) (r = 0.463). CONCLUSION: nODS showed a significant correlation between cognitive function tests and brain atrophy level. These results indicate that UPSIT-J is considered a psycho-physiological index useful for the diagnosis and early detection of dementia.

Efficacy, Tolerability, and Safety of Blonanserin in Schizophrenia: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: We conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing blonanserin with other antipsychotics (amisulpride, aripiprazole, haloperidol, paliperidone, and risperidone). METHODS: Weighted mean difference (WMD), risk ratio, and number needed to harm (NNH) with 95% confidence intervals (95% CIs) were calculated using random-effects model. RESULTS: Ten RCTs (n=1521) were included in this study. Blonanserin was superior to aripiprazole in improvement of Positive and Negative Syndrome Scale total scores (WMD=-10.62, 95% CI=-17.67 to -3.560, p=0.003). Blonanserin was associated with a higher incidence of all-cause discontinuation (RR=1.373, 95% CI=1.088-1.734, p=0.008, NNH=11), akathisia, extrapyramidal disorder, and agitation/excitement and a lower risk of hyperprolactinemia compared with risperidone + paliperidone. DISCUSSION: The current meta-analytic study did not update the comparison of blonanserin vs. haloperidol because there were no new RCTs. Our results suggest that the efficacy of blonanserin for schizophrenia is comparable with that of other antipsychotics, and blonanserin seems to be well tolerated.

Comparison of changes in the oxygenated hemoglobin level during a 'modified rock-paper-scissors task' between healthy subjects and patients with schizophrenia.

AIM: The purpose of this study, using single-event-related near-infrared spectroscopy (NIRS), was to examine the psychophysiological and social function assessment of 30 schizophrenic patients during a modified rock-paper-scissors task. METHODS: We set up a screen in front of the subjects, on which pictures of hand-gestures for rock, paper, and scissors were randomly presented. Subjects were asked to give verbal answers under the conditions of win, lose, and draw, respectively. Using the 44-channel NIRS system, we evaluated the maximum amplitude of oxygenated hemoglobin, latency, and the area based on the arithmetic mean of resulting values after the task between 30 outpatients with schizophrenia and 30 healthy subjects, and analyzed the frontal pole area, dorsolateral prefrontal region, and parietal association area as regions of interest (ROI). RESULTS: In schizophrenic patients, oxygenated hemoglobin changes (Δoxy-Hb) when losing the task showed a significantly lower level of Δoxy-Hb in ROI than controls. In addition, a significant positive correlation was observed between the Global Assessment of Functioning Scale and Δoxy-Hb in ROI, and a significant negative correlation was observed between the Negative Syndrome scale of the Positive and Negative Syndrome Scale and Δoxy-Hb in ROI. CONCLUSION: From these results, we conclude that Δoxy-Hb levels when performing the modified rock-paper-scissors task assessed using NIRS may be a useful psychophysiological marker to evaluate the cognitive and social functions of schizophrenic patients.

Characteristics of oxygenated hemoglobin concentration change during pleasant and unpleasant image-recall tasks in patients with depression: Comparison with healthy subjects.

AIM: Patients with major depressive disorder (MDD) have been reported to show cognitive impairment in attention, cognition control, and motivation. The prefrontal cortex plays an important role in the pathophysiology of depression. Neurophysiological abnormalities have been examined in MDD patients by several neuroimaging studies. However, the underlying neural mechanism is still unclear. We evaluated brain function during pleasant and unpleasant image-recall tasks using multichannel near-infrared spectroscopy (NIRS) in MDD patients. METHODS: The subjects were 25 MDD patients and 25 age- and sex-matched healthy controls. Patients were classified according to DSM-IV-TR criteria. We measured the oxygenated hemoglobin concentration change (δoxyHb) in the forehead and temporal lobe during image-recall task with pleasant (e.g., puppy) and unpleasant (e.g., snake) images using NIRS. To check whether all subjects understood the task, they were asked to draw pictures of both image tasks after NIRS measurement. RESULTS: The δoxyHb in the healthy group was significantly higher than that in the MDD group in the bilateral frontal region during the unpleasant condition. A significant negative correlation between the Hamilton Rating Scale for Depression score and δoxyHb was observed in the left frontal region during the unpleasant condition. CONCLUSION: We suggest that image-recall tasks related to emotion measured by NIRS might be a visually useful psychophysiological marker to understand the decrease in the frontal lobe function in MDD patients. In particular, we suggest that the decrease in δoxyHb in the left frontal lobe is related to the severity of depression.

Evaluation of changes in oxyhemoglobin during Shiritori task in elderly subjects including those with Alzheimer‧s disease.

BACKGROUND: In recent years, as the prevalence of Alzheimer‧s disease (AD) has increased rapidly, demand has increased for early detection and treatment. Therefore, discovery and treatment intervention at the mild cognitive impairment stage are important. Dysfunction of the working memory is known to be conspicuously present in AD patients or mild cognitive impairment subjects from an early stage. Near-infrared spectroscopy (NIRS) is a method to measure hemoglobin concentration changes during an activation task. In the present study, we evaluated the cognitive function of elderly subjects, including those with AD, by means of NIRS. METHODS: The subjects were divided into three groups-the AD group, the intermediate group, and the healthy group (HG)-based on assement of dementia using the Hasegawa‧s Dementia Scale-Revised, Mini-Mental State Examination, and Clinical Dementia Rating. The intermediate group was divided into two groups-the high score group (HSMG) and the low score group (LSMG)-based on Hasegawa‧s Dementia Scale-Revised and Mini-Mental State Examination scores. In this study, during Shiritori tasks using single-event-related NIRS, we analyzed oxyhemoglobin changes in an area, the peak amplitude, and latency, and compared them among four groups: AD group, HSMG, LSMG, and HG. RESULT: In the AD group, the area at left channel (Ch)9, 11, and 19, the area at right Ch22, and the peak ampulitude at left Ch11 and 19 and right Ch5,12, and 22 were significantly smaller than those in HSMG and HG. Furthermore, the latency of the AD group was significantly longer than that of HSMG and HG at all region of interests. However, no significant difference was observed between the AD group and LSMG. CONCLUSION: These findings suggest that analysis of changes in oxyhemoglobin during Shiritori tasks may be a useful neuropsychological index for the early diagnosis of AD. Detailed studies will be conducted in LSMG to facilitate the early introduction of NIRS as a screening tool for cognitive impairment.

Evaluation of P300 components for emotion-loaded visual event-related potential in elderly subjects, including those with dementia.

AIM: In the present study, the P300 component of the emotion-loaded visual event-related potential in response to photographs of babies crying or smiling was measured to evaluate cognitive function in elderly subjects, including those with dementia. METHODS: The subjects were 48 elderly people who consulted a memory disorder clinic. The visual event-related potential was measured using oddball tasks. Brain waves were recorded from four sites. We analyzed the P300 amplitude and latency. Subjects were divided into three groups (the dementia with Alzheimer's disease group [ADG]; the intermediate group [MG], and the healthy group [HG]) based on the Revised Hasegawa Dementia Scale, Mini-mental State Examination scores and the Clinical Dementia Rating. RESULTS: For all subjects, there was a significant positive correlation between P300 latency and Z-score of voxel-based specific regional analysis for Alzheimer's disease for crying or smiling faces. There was a negative correlation between P300 amplitude and Z-score for the crying face. MG subjects were divided into two groups (high risk: HRMG, low risk: LRMG) based on Z-scores (HRMG ≥ 2.0). The P300 amplitude of ADG was significantly smaller than that of HG, and the P300 latency of ADG was significantly longer than those of other groups for crying or smiling faces. The P300 latency of HRMG was significantly longer than that of LRMG for the smiling face. Furthermore, the P300 latency for the crying face was significantly shorter than that for the smiling face in HG and ADG. CONCLUSION: These findings suggest that analysis of P300 components of the emotion-loaded visual event-related potential may be a useful neuropsychological index for the diagnosis of Alzheimer's disease and high-risk subjects.

[Characteristics of single event-related cerebral hemodynamics during verbal task in emotionally charged state measured by multi-channel near-infrared spectroscopy (NIRS) in patients with schizophrenia: comparison with healthy subjects].

Neared infrared spectroscopy (NIRS) is one of the recently developed methodologies which can measure cerebral blood volumes to determine the blood hemoglobin (Hb) concentration simultaneously at multiple points with marked time resolution. Monitoring the changes in the Hb concentration yields site-specific readings on blood flow and, thus, on neural activities. The aim of this study was to examine the characteristics of a single event-related oxyhemoglobin concentration [oxy-Hb] changes in patients with schizophrenia using multi-channel NIRS during a word generation task, Japanese 'Shiritori', and single-word generation task in an emotionally charged state induced by three facial expressions of "crying", "neutral", and "smiling" babies' photographs. Thirty-four patients with schizophrenia and 34 age-matched healthy controls participated in the present study after giving consent. In healthy controls, [oxy-Hb] changes when viewing the "crying" baby's photograph were significantly larger than when viewing the "smiling" baby's photograph. On the other hand, in patients with schizophrenia, [oxy-Hb] changes when viewing the "smiling" baby's photograph were significantly larger than when viewing the "crying" baby's photograph. These results suggest that cautions/execution functions in patients with schizophrenia during the single event word "Shiritori" task measured by multi-channel NIRS were impaired. It was also suggested that, in patients with schizophrenia, the affective reaction influenced by each photograph may be different from healthy controls (mismatch). Multi-channel NIRS can be a useful tool for research and clinical purposes in psychiatry.

State and trait markers of emotionally charged visual event-related potentials (P300) in drug-naïve schizophrenia.

AIM: In the present study, we investigated the changes in P3 component in the emotionally charged visual event-related potentials (ERP) in 30 drug-naïve schizophrenic patients for up to 1 year. METHODS: Visual oddball event-related potential was recorded from six recording sites for crying baby or smiling baby photographs. ERP were recorded before the treatment (session 1 [S1]), after 3 months (session 2 [S2]), and after 12 months (session 3 [S3]), as well as in 30 healthy subjects. RESULTS: Before taking medicine, there were no significant differences in the P300 amplitude between viewing photographs of a crying and a smiling baby. The P300 amplitude was significantly larger at S2 and S3 than at S1 for a crying baby, while there was no significant difference among sessions for a smiling baby after medication. A significant difference of the P300 amplitude was only observed between S3 and healthy subjects for a smiling baby. The P300 latency only when viewing a smiling face became significantly longer at S3 than those at S1 and S2. A significant negative correlation was obtained between the P300 amplitude changes upon viewing crying faces and negative syndrome score changes at the Pz site. CONCLUSION: The P300 amplitude induced by crying-face stimuli may be a state marker and the P300 amplitude caused by smiling-face stimuli may be a trait marker during recovery in schizophrenic patients. Atypical antipsychotic medications may be useful and may recover cognitive function reflected by the emotionally charged visual P300 components in schizophrenic patients.

Relationships between exploratory eye movement dysfunction and clinical symptoms in schizophrenia.

AIM: Many psychophysiological tests have been widely researched in the search for a biological marker of schizophrenia. The exploratory eye movement (EEM) test involves the monitoring of eye movements while subjects freely view geometric figures. Suzuki et al. (2009) performed discriminant analysis between schizophrenia and non-schizophrenia subjects using EEM test data; consequently, clinically diagnosed schizophrenia patients were identified as having schizophrenia with high probability (73.3%). The aim of the present study was to investigate the characteristics of schizophrenia patients who were identified as having schizophrenia on EEM discriminant analysis (SPDSE) or schizophrenia patients who were identified as not having schizophrenia on EEM discriminant analysis (SPDNSE). METHODS: The data for the 251 schizophrenia subjects used in the previous discriminant-analytic study were analyzed, and the demographic or symptomatic characteristics of SPDSE and SPDNSE were investigated. As for the symptomatic features, a factor analysis of the Brief Psychiatric Rating Scale (BPRS) rating from the schizophrenia subjects was carried out. RESULTS: Five factors were found for schizophrenia symptoms: excitement/hostility; negative symptoms; depression/anxiety; positive symptoms; and disorganization. SPDSE had significantly higher factor scores for excitement/hostility, negative symptoms and disorganization than SPDNSE. Furthermore, the BPRS total score for the SPDSE was significantly higher than that for the SPDNSE. CONCLUSION: SPDSE may be a disease subtype of schizophrenia with severe symptoms related to excitement/hostility, negative symptoms and disorganization, and EEM parameters may detect this subtype. Therefore, the EEM test may be one of the contributors to the simplification of the heterogeneity of schizophrenia.

The Changes in Concentration of Cerebral Oxygenated Hemoglobin During Single Event-Related Japanese Shiritori Task in Patients With Major Depression Disorder: Comparison With Healthy Subjects.

Patients with major depressive disorder (MDD) have been reported to show cognitive impairments in attention, cognition control, and motivation. The purpose of this study is to compare and examine the characteristics of frontal and temporal cortical activity in outpatients with MDD during the word production task (Shiritori) using a single event-related Near-Infrared Spectroscopy (NIRS) measurement method that was originally devised. The subjects were 29 MDD patients and 29 age matched healthy controls. In this task, one session consisted of two contrasting conditions (word production task, control condition), and all subjects alternated between these conditions. Each word was visually presented by a monitor for 0.3 s as an activation task and a fixed circle was presented for 12 s. In the activation task, subjects had to immediately generate a noun that starts with the last syllable of the presented word and they were required to say only creatures. From the data obtained at each measurement point during the 20 trials, and averaged waveform during activation task (20 trials) was calculated for each channel. During the word production task, the MDD patients showed significantly smaller activation than the controls in the prefrontal cortex area and inferior parietal area, especially in the left area. In addition, there was a significant negative correlation between Δoxy-Hb at the bilateral temporal lobe area and HAM-D total score in the MDD patients. These findings suggest that a single event-related NIRS measurement during Japanese shiritori tasks may be useful tool for evaluating psychophysiological indices in MDD patients, that relationship between activation and symptom may be of help in predicting functional outcome in patients.

Effects of emotionally charged sounds in schizophrenia patients using exploratory eye movements: comparison with healthy subjects.

AIMS: Emotion-associated sounds have been suggested to exert important effects upon human personal relationships. The present study was aimed to characterize the effects of the sounds of crying or laughing on visual cognitive function in schizophrenia patients. METHODS: We recorded exploratory eye movements in 24 schizophrenia patients (mean age, 27.0 +/- 6.1 years; 14 male, 10 female) and age-matched controls. The total eye scanning length (TESL) and total number of gaze points in the left (left TNGP) and right (right TNGP) visual fields of the screen and the number of researching areas (NRA) were determined using eye-mark recording in the presence/absence of emotionally charged sounds. RESULTS: Controls' TESL for smiling pictures was longer than that for crying pictures irrespective of sounds. Patients' TESL for smiling pictures, however, was shorter than for crying pictures irrespective of the sounds. The left TNGP for smiling pictures was lower in patients than controls independent of sound. Importantly, the right TNGP was significantly larger with laughing sounds than in the absence of sound. In controls, the NRA for smiling pictures was significantly greater than for crying pictures irrespective of sound. Patient NRA did not significantly differ between smiling and crying pictures irrespective of sound. CONCLUSION: Eye movements in schizophrenia patients' left field for smiling pictures associated with laughing sounds particularly differed from those in controls, suggesting impaired visual cognitive function associated with positive emotion, also involving pleasure-related sounds, in schizophrenia.

Characteristics of exploratory eye movements in elderly people: possibility of early diagnosis of dementia.

BACKGROUND: Visual cognitive dysfunction is one of the most important signs indicating the early stage of dementia. Thus, visual testing could be used as an aid to the clinical diagnosis of dementia. In the present study, exploratory eye movement was measured to evaluate visual cognitive function in elderly subjects, including those with dementia. METHODS: We analyzed responsive search scores (RSS) from exploratory eye movements of 300 subjects who were examined with an eye mark recorder while viewing S shaped figures. Subjects were divided into three groups (dementia, intermediate, healthy) from the values of the Revised Hasegawa Dementia Scale (HDS-R), the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating. We further divided the intermediate groups into two subgroups, the high score and low score groups, based on RSS. In 202 subjects, Z-scores of voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) were obtained from magnetic resonance imaging (MRI). RESULTS: RSS of the dementia group were significantly lower than those in the intermediate and healthy groups, in order: dementia < intermediate < healthy groups. RSS of the low score intermediate group was significantly lower than that of the high score intermediate group. There was no significant difference between the low score intermediate and dementia groups, or between the high score intermediate and healthy groups. No significant differences of either HSD-R or MMSE were observed between the low score and the high score intermediate groups. The Z-score of VSRAD using MRI in the low score intermediate group was significantly higher than that in the high score intermediate group. CONCLUSIONS: These findings suggest that RSS using an eye mark recorder is a useful psychophysiological marker to evaluate the early stage of dementia as well as at-risk elderly people.

[Development of human visual cognitive function in childhood: evaluation by exploratory eye movements to a picture of a smiling face].

To evaluate the development of human visual cognitive function in childhood, we examined exploratory eye movements in 78 healthy subjects using affective pictures. We divided them into six groups, each of which comprised 14 subjects (7 boys or men, 7 girls or women) at the indicated ages. Exploratory eye movements were recorded via gazing points using an eye-mark recorder. The total eye scanning length (TESL) of gaze points increased significantly with age, and the mean eye scanning length, in 4-6-year-olds was significantly shorter than in the others groups. The total number of gaze points (TNGP) on the left half of the screen increased significantly with age. The left TNGP in 4-6-year-olds was significantly smaller than in the other groups. The response search score (RSS) measured in 8 areas of the screen increased significantly with age. It was concluded that exploratory eye movements are useful markers to estimate the development of human visual cognitive function in childhood.

Exploratory eye movement dysfunction as a discriminator for schizophrenia : a large sample study using a newly developed digital computerized system.

In our previous studies, we identified that exploratory eye movement (EEM) dysfunction appears to be specific to schizophrenia. The availability of a biological marker specific to schizophrenia would be useful for clinical diagnosis of schizophrenia. Consequently, we performed the discriminant analysis between schizophrenics and non-schizophrenics on a large sample using the EEM test data and examined an application of the EEM for clinical diagnosis of schizophrenia. EEM performances were recorded in 251 schizophrenics and 389 non-schizophrenics (111 patients with mood disorders, 28 patients with neurotic disorders and 250 normal controls). The patients were recruited from eight university hospitals and three affiliated hospitals. For this study with a large sample, we developed a new digital computerized version of the EEM test, which automatically handled large amounts of data. We measured four parameters: number of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning length (MESL) and responsive search score (RSS). These parameters of schizophrenics differed significantly from those of the other three groups. The stepwise regression analysis selected the TESL and the RSS as the valid parameters for discriminating between schizophrenics and non-schizophrenics. In the discriminant analysis using the RSS and TESL as prediction parameters, 184 of the 251 clinically diagnosed schizophrenics were discriminated as having schizophrenia (sensitivity 73.3%); and 308 of the 389 clinically diagnosed non-schizophrenic subjects were discriminated as non-schizophrenics (specificity 79.2%). Based on our findings we believe that the EEM measures may be useful for the clinical diagnosis of schizophrenia.

Comparison of changes in oxygenated hemoglobin during the tree-drawing task between patients with schizophrenia and healthy controls.

BACKGROUND: Tree-drawing test is used as a projective psychological test that expresses the abnormal internal experience in patients with schizophrenia (SZ). Despite the widely accepted view that the cognitive function is involved in characteristic tree-drawing in patients with SZ, no study has psychophysiologically examined it. The present study aimed to investigate the involvement of cognitive function during tree-drawing in patients with SZ. For that purpose, we evaluated the brain function in patients with SZ during a tree-drawing task by using near-infrared spectroscopy (NIRS) and compared them with those in healthy controls. PATIENTS AND METHODS: The subjects were 28 healthy controls and 28 patients with SZ. Changes in the oxygenated hemoglobin ([oxy-Hb]) concentration in both the groups during the task of drawing a tree imagined freely (free-drawing task) and the task of copying an illustration of a tree (copying task) were measured by using NIRS. RESULTS: Because of the difference between the task conditions, [oxy-Hb] levels in controls during the free-drawing task were higher than that during the copying task at the bilateral frontal pole regions and left inferior frontal region. Because of the difference between the groups, [oxy-Hb] levels at the left middle frontal region, bilateral inferior frontal regions, bilateral inferior parietal regions, and left superior temporal region during the free-drawing task in patients were lower than that in controls. CONCLUSION: [oxy-Hb] during the tree-drawing task in patients with SZ was lower than that in healthy controls. Our results suggest that brain dysfunction in patients with SZ might be associated with their tree-drawing.

Impaired exploratory eye movements in children with Asperger's syndrome.

OBJECTIVE: Previous eye-tracking studies using an eye mark recorder have reported that disturbances in exploratory eye movements in adult schizophrenic patients are associated with social functioning. The current study sought to determine whether exploratory eye-movement disturbances are present in children with Asperger's syndrome (AS) compared with typically developing (TD) children. MATERIALS/PARTICIPANTS: The participants were 23 children with AS and 23 age-matched TD children. We measured exploratory eye movements using an EMR-8B eye mark recorder and an exploratory eye movement-measuring device. METHOD: Eye movements were recorded while participants freely observed a geometric figure (free viewing task), and while they complied with the instructions of an experimenter (repeat-comparison task). We assessed eye fixation points (EFPs) and total eye scanning length (TESL) in all tasks, and measured the responsive search score (RSS) in the repeat-comparison task. RESULTS: In the free viewing task, children with AS exhibited significantly shorter TESL compared with TD children. In the repeat-comparison task, children with AS exhibited significantly lower RSS. Autism Spectrum Screening Questionnaire scores were negatively correlated with both EFP and TESL, but not RSS. CONCLUSION: The current results revealed that children with AS exhibited dysfunction in exploratory eye movements. Thus, assessing exploratory eye movements in a repeat-comparison task may be useful for detecting social impairment among children with AS.