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.

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.

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 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.

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.

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.

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.

Single event-related changes in cerebral oxygenated hemoglobin using word game in schizophrenia.

Neuroimaging studies have been conducted using word generation tasks and have shown greater hypofrontality in patients with schizophrenia compared with healthy subjects. In this study, we compared the characteristics of oxygenated hemoglobin changes involved in both phonological and categorical verbal fluency between 35 outpatients with schizophrenia and 35 healthy subjects during a Japanese "shiritori" task using single-event-related near-infrared spectroscopy. During this task, the schizophrenic patients showed significantly smaller activation in the prefrontal cortex area than the controls. In addition, a significant positive correlation was obtained between oxygenated hemoglobin changes (prefrontal cortex area, inferior parietal area) and the severity of positive psychiatric symptoms. It is possible that hypofrontality of patients may be a diagnostic assistance tool for schizophrenia, and that the relationship between activation and positive syndrome scores may be of help in predicting functional outcome in patients.

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.

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.

[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.

Reduced prefrontal cortex activation using the Trail Making Test in schizophrenia.

Schizophrenia has been associated with a deficit of the prefrontal cortex, which is involved in attention, executive processes, and working memory. The Trail Making Test (TMT) is administered in two parts, TMT-A and TMT-B. It is suggested that the difference in performance between part A and part B reflects executive processes. In this study, we compared the characteristics of hemodynamic changes during TMT tasks between 14 outpatients with schizophrenia and 14 age- and gender-matched healthy control subjects. Using multichannel near-infrared spectroscopy, we measured relative changes in oxygenated hemoglobin concentration, which reflects brain activity of the prefrontal cortex during this task. In both tasks, patients showed significantly smaller activation than controls and, in an assessment of executive functions, a subtraction of oxygenated hemoglobin (oxy-Hb) changes during TMT-A from those of TMT-B showed a decrease in cerebral lateralization and hypoactivity in patients. There was a significant negative correlation between oxy-Hb changes and the severity of psychiatric symptoms. These findings may characterize disease-related features, suggesting the usefulness of oxy-Hb change measurement during TMT tasks for assessing functional outcomes in schizophrenic patients.

Left eye scanning deficit in schizophrenia patients under emotional loading task: comparison with healthy controls.

The aim of the present study was to evaluate and characterize visual cognitive function and the effect of emotion in patients with schizophrenia.We recorded exploratory eye movements as biologic markers in 40 schizophrenic patients and 40 age-matched healthy controls. Total eye scanning length (TESL), total number of gaze points (TNGP), and TNGP in right (right TNGP) and left (left TNGP) visual fields on screen were calculated as subjects viewed affectively charged pictures (smiling and crying babies) with fitting sounds.TESL of patients was shorter than that of controls when viewing pictures of smiling babies while recalling pleasurable events, and significantly decreased under negative emotional loading when viewing crying babies while recalling sad events. TESL recovered to the original values after loading positive emotion again in the controls. However, TESL did not recover to the original values in schizophrenic patients. TNGP showed similar alterations in the emotional loading task. When TNGP was evaluated in left and right fields, in patients, the non-recovery of TNGP was only observed in the left side. TESL and left TNGP were negatively correlated with negative symptom scores on PANSS.Schizophrenic patients'eye movements in the left visual field screen during the emotional loading task were different from those of controls, which suggests that visual cognitive function is impaired in the right brain in schizophrenic patients. Exploratory eye movements are a useful marker of visual cognitive function, and are a useful tool to evaluate the influence of emotion in schizophrenic patients.

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.

Characteristics of cortical activation in schizophrenia during the card game "concentration".

Various functional imaging studies have demonstrated reduced lateralization of cortical activation during neurocognitive tasks in schizophrenia. -A well-known card game, "concentration", reflects working memory (WM). We compared characteristics of hemodynamic changes in the prefrontal to temporo-parietal areas of the brain during this card game between 24 outpatients with schizophrenia and 24 age- and gender-matched healthy control subjects. Using multi-channel near-infrared spectroscopy, we measured relative changes in oxygenated hemoglobin concentration (oxy-Hb changes), which reflects brain activity during this task. Patients showed reduced lateralization in the midfrontal area, which is involved in executive functions, and in the inferior parietal area, involved in WM subcomponents. We also found a significant negative correlation between left midfrontal region oxy-Hb changes and severity of negative symptoms of schizophrenia. Our results characterized disease-related features, suggesting the usefulness of oxy-Hb change measurement during this card game for assessing functional outcome in schizophrenic patients.

Effects of emotionally affect adult and baby' photographs in healthy controls and schizophrenic patients evaluating by exploratory eye movements.

The relationship between mother and baby is of fundamental importance in the development of cognitive function and emotion. In this study we investigated the effects of affective photographs of a mother and baby (crying or smiling faces) and other stimuli (neutral mother or baby faces) on visual cognitive function in schizophrenic patents. We recorded exploratory eye movements in 22 healthy controls and 22 age-matched schizophrenic patients. Total number of right and left field gaze points (right TNGP, left TNGP) in the visual fields were determined using an eye-mark recorder as subjects viewed affectively charged or neutral photographs (crying, smiling or neutral faces). Left TNGP for all mother photographs (crying, smiling or neutral) were significantly larger in controls than patients, and right TNGP for neutral mother photographs were significantly larger in controls than in patients. Right TNGP for photographs of smiling babies were significantly larger in controls than patients, and left TNGP for photographs of both smiling and crying babies were significantly larger in controls than patients. Within the patient group, right TNGP were significantly larger than left TNGP for all mother photographs (crying, smiling or neutral). Left TNGP for photographs of mothers and babies correlated negatively with negative symptom scores. These results suggest that exploratory eye movements when viewing emotionally laded twin stimuli such as photographs of a mother and baby are a useful marker of visual cognitive function in both healthy controls and schizophrenic patients.

Brain activities on fMRI using the shiritori task in normal subjects.

Shiritori is a popular Japanese word chain game that resembles verbal fluency tasks used in Western countries. Recently, shiritori has been used to determine the dominant hemisphere for language and as a rehabilitation tool. However, there are few reports of neuroimaging during shiritori. We used functional magnetic resonance imaging (fMRI) to conduct a detailed study of brain activities during shiritori and observed activation not only of the left inferior frontal gyrus (including the pars opecularis, the pars triangularis and the pars orbitalis), which is a language-related area, but also of the left superior and middle frontal gyri, the right pars orbitalis (inferior frontal gyrus), and the right cerebellar hemisphere. Shiritori is a useful tool for psychological study and rehabilitation.