Takefumi Ueno

Estimated cognitive decline in patients with schizophrenia: A multicenter study

Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning.

Differentiation between major depressive disorder and bipolar disorder by auditory steady-state responses.

BACKGROUNDnThe auditory steady-state response (ASSR) elicited by gamma band neural oscillations has received considerable interest as a biomarker of psychiatric disorders. Although recent ASSR studies have reported that patients with bipolar disorder (BD) show altered ASSRs, little is known about ASSRs in patients with major depressive disorder (MDD). The aim of this study was to evaluate whether ASSRs in MDD subjects differed from those in BD subjects or normal controls (NC).nnnMETHODnWe analyzed ASSRs in 14 MDD patients, 19 BD patients, and 29 normal control subjects. We used whole-head 306-channel magnetoencephalography to evaluate ASSR power and phase-locking factors (PLF) elicited by 20-, 30-, 40-, and 80-Hz click trains. We determined optimal sensitivity and specificity of ASSR power and PLF for the diagnosis of MDD or BD via receiver operating characteristic (ROC) curve analysis using a nonparametric approach.nnnRESULTSnMDD patients exhibited no significant differences in ASSR power or PLF compared with NC subjects, while BD patients showed deficits on the ASSR measures. MDD patients showed significantly larger ASSR power and PLF for 30-, 40-, and 80-Hz stimuli compared with BD patients. The area under the curve (AUC) for the ROC analysis (MDD vs. BD) was 0.81 [95% CI=0.66-0.96, p=0.003] concerning 40-Hz ASSR power.nnnLIMITATIONSnWe could not exclude the effect of medication and the sample size of the current study is relatively small.nnnCONCLUSIONSnWe could differentiate between MDD and BD subjects in terms of gamma band ASSR. Our data suggest that the 40-Hz ASSR may be a potential biomarker for differentiation between MDD and BD patients.

Cognitive insight and functional outcome in schizophrenia; a multi-center collaborative study with the specific level of functioning scale–Japanese version

The Specific Levels of Functioning Scale (SLOF) has been reported to provide a measure of social function in patients with schizophrenia. The aim of this multi-center study was to determine convergent validity of the Japanese version of SLOF, and if cognitive insight would be associated with social function. Fifty-eight patients with schizophrenia participated in the study. Social function, neurocognition, and daily activity skills were evaluated by the Social Functioning Scale (SFS), Brief Assessment of Cognition in Schizophrenia (BACS) and UCSD Performance-based Skills Assessment-Brief (UPSA-B), respectively. We also assessed cognitive insight with the Beck Cognitive Insight Scale (BCIS). Significant relationships were noted between scores on the SLOF vs. those of the SFS, BACS, UPSA-B, and BCIS. Specifically, the correlation between performance on the UPSA-B and SLOF scores was significantly more robust compared to the correlation between performance on the UPSA-B and scores on the SFS. Similarly, the correlation between scores on the BACS and SLOF tended to be more robust than that between the BACS and SFS. Importantly, while the correlation between scores on the BCIS and SLOF reached significance, it was not so between scores on the BCIS and SFS. The SLOF Japanese version was found to provide a measure of social consequences in patients with schizophrenia. Importantly, this study is the first to indicate the relationship between cognitive insight and social function evaluated by the SLOF. This finding is consistent with the observation that SLOF scores were considerably associated with performances on objective functional measures.

Preattentive dysfunction in patients with bipolar disorder as revealed by the pitch-mismatch negativity: A magnetoencephalography (MEG) study

Mismatch negativity (MMN) and its magnetic counterpart (MMNm) are thought to reflect an automatic process that detects a difference between an incoming stimulus and the sensory memory trace of preceding stimuli. In patients with schizophrenia, an attenuation of the MMN/MMNm amplitude has been repeatedly reported. Heschls gyrus (HG) is one of the major generators of MMN and the functional alteration of HG has been reported in patients with bipolar disorder. The present study investigated the pitch‐MMNm in patients with bipolar disorder using whole‐head 306‐ch magnetoencephalography (MEG).

Regional differences of repeatability on visual analogue scale with experimental mechanical pain stimuli.

Pain-VAS is quite subjective as a scale, but has a tendency to assume differences in repeatability in accordance with perceived pain intensity. The aim of the present study was to investigate the repeatability of regional differences with ratings of pain-VAS. Three experimental mechanical stimuli were applied to twenty seven healthy volunteers across four sessions over four weeks within individuals. The same stimuli were also simultaneously measured in the same manner with an electric balance. The magnitude of mechanical stimuli was determined by 100 g, 300 g, and 600 g monofilaments. Standard deviations (SDs) across measurements with an electric balance showed a regular increase with stimulus magnitude, while coefficient variations (CVs) were constant in each stimulus. On the other hand, although SDs across pain-VAS measurements were significantly greater with the 300 g filament than with the 100 g and 600 g filaments, CVs showed a regular decrease in magnitude of stimulus. These results showed that the CVs of repeated measurement with electric balance were consistent regardless of stimulus intensity, in contrast, CVs of pain-VAS decreased with greater pain rating averaged by repeated measurement. These results suggest that a low rating in pain-VAS is inherently less objective, indicating poor repeatability. In contrast, a high rating in pain-VAS is more objective with better repeatability for experimental pain perception.

Higher pain rating results in lower variability of somatosensory cortex activation by painful mechanical stimuli: An fMRI study

OBJECTIVEnThe aim of this study was to find pain-related brain activity which corresponds to self-report pain ratings based on degree of response and repeatability.nnnMETHODSnThree painful mechanical stimuli were applied to the right hands of 25 healthy volunteers using monofilaments (forces of 0.98N, 2.94N, and 5.88N). Simultaneously, brain activities were evaluated using functional MRI for a constant stimulus conducted three times in a session. In first assessment, the average percent signal change (PSC) of neuronal response was measured for each region of interest (ROI), secondary repeatability of PSC conducted three times over the session was evaluated for each ROI.nnnRESULTSnAlthough the average PSCs for trice stimuli conducted in one session increased in accordance with pain ratings in the somatosensory cortex (S1) and anterior cingulate cortex (ACC), there was a different response between S1 and ACC when subjects rated intense pain; a stable response in S1 against a variable response in ACC.nnnCONCLUSIONSnThese results imply that there are different cognitive responses between sensory discrimination and affective component to constant painful stimulus each time.nnnSIGNIFICANCEnConsistency of brain activity based on PSC may be an important biomarker which, along with its neuronal activity, gauges self-report pain ratings.

Early Integration Processing between Faces and Vowel Sounds in Human Brain: An MEG Investigation

Objective: Unconscious fast integration of face and voice information is a crucial brain function necessary for communicating effectively with others. Here, we investigated for evidence of rapid face-voice integration in the auditory cortex. Methods: Magnetic fields (P50m and N100m) evoked by visual stimuli (V), auditory stimuli (A) and audiovisual stimuli (VA), i.e. by face, vowel and simultaneous vowel-face stimuli, were recorded in 22 healthy subjects. Magnetoencephalographic data from 28 channels around bilateral auditory cortices were analyzed. Results: In both hemispheres, AV - V showed significantly larger P50m amplitudes than A. Additionally, compared with A, the N100m amplitudes and dipole moments of AV - V were significantly smaller in the left hemisphere, but not in the right hemisphere. Conclusions: Differential changes in P50m (bilateral) and N100m (left hemisphere) that occur when V (faces) are associated with A (vowel sounds) indicate that AV (face-voice) integration occurs in early processing, likely enabling us to communicate effectively in our lives.

Development of a hematocrit-insensitive device to collect accurate volumes of dried blood spots without specialized skills for measuring clozapine and its metabolites as model analytes

Dried blood spots have been used as alternatives to traditional plasma and serum samples. We have now developed new devices, named volumetric absorptive paper disc (VAPD) and mini-disc (VAPDmini), to collect accurate volumes of dried blood spots in a simple manner and without the need for additional instruments. VAPD consists of a filter paper disc and a filter paper sheet with holes slightly larger than the disc. The disc is fixed in one such hole without direct contact with the filter sheet. VAPDmini is a scaled-down version of the same device. When several drops of whole blood are applied, the disc becomes saturated and any excess sample is absorbed by the surrounding filter sheet. Accuracy and precision of sampling were assessed by determining the levels of clozapine and its metabolites as target analytes by liquid-liquid extraction and high-performance liquid chromatography with coulometric detection. In addition, differences in analyte recovery were within ±15% for all analytes in samples with 30-60% hematocrit, suggesting that VAPD and VAPDmini are insensitive to hematocrit for the analytes tested. The devices were also validated for analyte concentrations in the range 50-1000u202fng/mL, and the limit of detection and lower limit of quantification were 5-17u202fng/mL and 15-51u202fng/mL, respectively. Intra- and inter-day precision ranged from 3% to 13%, whereas accuracy ranged from a -14% to 12% bias. Analytes were stable in the devices for at least 2u202fweeks at room temperature. Collectively, these results indicate that sampling using VAPD and VAPDmini is comparable to conventional hole punch sampling of entire dried blood spots, even for samples obtained from patients treated with clozapine. Importantly, the devices were also found to be suitable for sample self-collection.

Right hemispheric hyperfrontality in schizophrenia during a Shiritori task: An fMRI study

N UMEROUS STUDIES HAVE reported that, in righthanded people, healthy subjects demonstrate leftlateralized language dominance, but patients with schizophrenia show reduced language dominance. However, the mechanism of reduced lateralization in schizophrenia is unclear as to whether brain activity of schizophrenia patients is significantly greater or lesser than that of healthy subjects. Clarifying this question, in the present study, we investigated language dominance in the frontal lobe during a Shiritori task by functional magnetic resonance imaging (fMRI). Shiritori is one of the most popular Japanese games, and this game mainly includes a verbal fluency task. Kurume University approved the present study (10086). Written informed consent was obtained from all subjects prior to participation in this study. Our previous study has demonstrated that brain activity of the frontal lobe (mainly including the inferior frontal gyrus) during a Shiritori task is left hemispheric dominant. Fourteen schizophrenia patients (10 men; aged 26.6 4.8 years) and 18 normal control subjects (nine men; aged 25.9 3.9 years) participated in the present study. The Shiritori task was a block design. In this task, two conditions were used: (i) the rest condition (the subjects relaxed without thinking about anything as much as possible during 51 s); and (ii) the Shiritori condition (the subjects performed Shiritori by themselves without moving their mouths or vocalizing). Data preprocessing was performed with Statistical Parametric Mapping (SPM8) software (Wellcome Department of Cognitive Neurology, London, UK). Before scanning, we checked the number of words during the vocal Shiritori for each participant (test trial). The average number ( SD) of the test trial was 25.3 4.0 in healthy subjects, whereas it was 17.2 2.4 in schizophrenia patients. This number for healthy subjects was significantly greater than that for schizophrenia patients (t = 7.1, P < 0.01). In the results of fMRI, although frontal activation in healthy subjects shows left hemispheric dominance, that in schizophrenia patients was observed bilaterally (at the pars opercularis of the inferior frontal gyrus) (t = 3.85, P < 0.001, uncorrected). In addition, compared with healthy subjects, brain activation in schizophrenia patients was significantly greater in the right frontal lobes

Right hemisphere pitch-mismatch negativity reduction in patients with major depression: An MEG study

BACKGROUNDnThe mismatch negativity (MMN) component of the event-related potential and its magnetic counterpart, the MMNm, are generated by a mismatch between the physical features of a deviant stimulus and a neuronal sensory-memory trace produced by repetitive standard stimuli. Deficits in the MMN/MMNm have been reported in patients with major depression; however, the results are inconsistent. The present study investigated the pitch-MMNm in patients with major depression using whole-head 306-channel magnetoencephalography (MEG).nnnMETHODSnTwenty patients with major depression and 36 healthy subjects participated in this study. Subjects were presented with two sequences of auditory stimuli. One consisted of 1000Hz standard signals (probability=90%) and 1200Hz deviant signals (probability=10%), while the other consisted of 1200Hz standard (90%) and 1000Hz deviant signals (10%). Event-related brain responses to standard tones were subtracted from responses to deviant tones.nnnRESULTSnMajor depressive patients showed significantly reduced magnetic global field power (GFP) of MMNm in the right hemisphere (p=0.02), although no significant MMNm reduction was observed in the left hemisphere (p=0.81). Additionally, patients with major depression showed significantly earlier bilateral MMNm peak latencies (p=0.004). No significant associations were observed between MMNm variables and demographic data/clinical variables within the patients.nnnLIMITATIONSnWe could not exclude the effects of antidepressants, mood stabilizers, or neuroleptics on the MMNm abnormalities found in patients with major depression. Sample size was also insufficient to permit subgroup analyses.nnnCONCLUSIONSnPatients with major depression exhibited reduced GFP of MMNm in the right hemisphere. The present study suggested that patients with major depression may have right hemispheric dominant preattentive dysfunction.