Concurrent Statistical Learning of Ignored and Attended Sound Sequences: An MEG Study

In an auditory environment, humans are frequently exposed to overlapping sound sequences such as those made by human voices and musical instruments, and we can acquire information embedded in these sequences via attentional and nonattentional accesses. Whether the knowledge acquired by attentional accesses interacts with that acquired by nonattentional accesses is unknown, however. The present study examined how the statistical learning (SL) of two overlapping sound sequences is reflected in neurophysiological and behavioral responses, and how the learning effects are modulated by attention to each sequence. SL in this experimental paradigm was reflected in a neuromagnetic response predominantly in the right hemisphere, and the learning effects were not retained when attention to the tone streams was switched during the learning session. These results suggest that attentional and nonattentional learning scarcely interact with each other and that there may be a specific system for nonattentional learning, which is independent of attentional learning

CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme

AbstractDNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic component (p460) and a DNA-binding component Ku protein. Immunoblot analysis after treatment of Jurkat cells with anti-Fas antibody demonstrated the cleavage of p460 concomitantly with an increase in CPP32/Yama/apopain activity. Recombinant CPP32/Yama/apopain specifically cleaved p460 in the DNA-PK preparation that had been purified from Raji cells into 230- and 160-kDa polypeptides, the latter of which was detected in anti-Fas-treated Jurkat cells. The regulatory component Ku protein was not significantly affected by CPP32/Yama/apopain. DNA-PK activity was decreased with the disappearance of p460 in the incubation of DNA-PK with CPP32/Yama/apopain. These results suggest that the catalytic component of DNA-PK is one of the target proteins for CPP32/Yama/apopain in Fas-mediated apoptosis

Correlation of motor-auditory cross-modal and auditory unimodal N1 and mismatch responses of schizophrenic patients and normal subjects: an MEG study

IntroductionIt has been suggested that the positive symptoms of schizophrenic patients (hallucinations, delusions, and passivity experience) are caused by dysfunction of their internal and external sensory prediction errors. This is often discussed as related to dysfunction of the forward model that executes self-monitoring. Several reports have suggested that dysfunction of the forward model in schizophrenia causes misattributions of self-generated thoughts and actions to external sources. There is some evidence that the forward model can be measured using the electroencephalography (EEG) and magnetoencephalography (MEG) components such as N1 (m) and mismatch negativity (MMN) (m). The objective in this MEG study is to investigate differences in the N1m and MMNm-like activity generated in motor-auditory cross-modal tasks in normal control (NC) subjects and schizophrenic (SC) patients, and compared that activity with N1m and MMNm in the auditory unimodal task.MethodsThe N1m and MMNm/MMNm-like activity were recorded in 15 SC patients and 12 matched NC subjects. The N1m-attenuation effects and peak amplitude of MMNm/MMNm-like activity of the NC and SC groups were compared. Additionally, correlations between MEG measures (N1m suppression rate, MMNm, and MMNm-like activity) and clinical variables (Positive and Negative Syndrome Scale (PANSS) scores and antipsychotic drug (APD) dosages) in SC patients were investigated.ResultsIt was found that (i) there was no significant difference in N1m-attenuation for the NC and SC groups, and that (ii) MMNm in the unimodal task in the SC group was significantly smaller than that in the NC group. Further, the MMNm-like activity in the cross-modal task was smaller than that of the MMNm in the unimodal task in the NC group, but there was no significant difference in the SC group. The PANSS positive symptoms and general psychopathology score were moderately negatively correlated with the amplitudes of the MMNm-like activity, and the APD dosage was moderately negatively correlated with the N1m suppression rate. However, none of these correlations reached statistical significance.DiscussionThe findings suggest that schizophrenic patients perform altered predictive processes differently from healthy subjects in latencies reflecting MMNm, depending on whether they are under forward model generation or not. This may support the hypothesis that schizophrenic patients tend to misattribute their inner experience to external agents, thus leading to the characteristic schizophrenia symptoms

Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity

BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men. METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped. RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects. CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia

Strontium isotope evidence of migration and diet in relation to ritual tooth ablation: a case study from the Inariyama Jomon site, Japan

Ritual tooth ablation was extensively practiced among Jomon (Japanese Neolithic) societies in their final phase (ca. 3000-2300 BP). This tradition includes two different tooth ablation patterns, type 4I and type 2C, referring to extraction of the mandibular incisors and canines, respectively. However, the reason for this difference is unclear. Previous carbon and nitrogen stable isotope analysis of human remains from the Inariyama shell mound revealed that type 4I individuals were more dependent on terrestrial resources and type 2C individuals on marine resources. To test this hypothesis, we performed strontium (Sr) isotope (87Sr/86Sr) analyses on the same skeletal remains and on modern plants around the site. Because Sr isotope ratios of plants differ according to the local geology and seawater has a consistent Sr isotope ratio, the Sr isotope ratios of tooth enamel can reveal both migration and diet. Comparing Sr isotope ratios in plants and seawater with those of tooth enamel, we identified four possible immigrants. Type 4I locals had significantly higher Sr isotope ratios than type 2C locals. The ratios of the type 4I and type 2C locals were close to those of terrestrial plants and seawater, respectively, suggesting that type 4I locals had incorporated much Sr from terrestrial resources and type 2C locals from marine resources. These results support the hypothesis that ritual tooth ablation reflects dietary differences throughout an individual’s life, and they suggest possible occupational differentiation among the Jomon people

Carbon and nitrogen stable isotope analysis on the diet of Jomon populations from two coastal regions of Japan

We report on a stable isotope paleodietary reconstruction of Jomon populations in Japan during the Middle to Final Jomon period (ca. 5000–2300 years BP), focusing on dietary differences within and among populations and between regions. Carbon and nitrogen isotope analysis was performed on human and faunal bone collagen from six coastal sites along the Inland Sea in the Sanyo (Ota, Funamoto, and Tsukumo) region and along Mikawa Bay and the Pacific Ocean in the Tokai (Kawaji, Yoshigo, and Inariyama) region. We found that carbon and nitrogen isotope ratios were positively correlated, indicating that the Jomon people consumed a mixed diet of marine (shellfish and marine fish) and terrestrial (C3 plants and terrestrial mammals) protein. In the Ota samples (n = 25, during the Middle Jomon period, 5000–4000 years BP), sex was one of the main reasons for the intra-population dietary variation. Ota males consumed greater amounts of marine food, while Ota females consumed greater amounts of terrestrial food; these dissimilar diets may have been related to the sexual division of labor. Significant inter-population dietary differences were found, which may have been related to differences in age or site location. Notably, the two coastal regions showed clear isotopic differences. Nitrogen isotope ratios of individuals from the Sanyo region were significantly higher than ratios of individuals from the Tokai region. The individuals in the Sanyo region might have consumed a diet high in aquatic foods, particularly high trophic level marine fish, whereas the individuals in the Tokai region might have consumed a lot of marine shellfish. Another possible reason for the regional isotopic difference might have been different baseline of nitrogen isotope ratios of the marine ecosystems

Order of statistical learning depends on perceptive uncertainty

Statistical learning (SL) is an innate mechanism by which the brain automatically encodes the n-th order transition probability (TP) of a sequence and grasps the uncertainty of the TP distribution. Through SL, the brain predicts a subsequent event (en+1) based on the preceding events (en) that have a length of “n”. It is now known that uncertainty modulates prediction in top-down processing by the human predictive brain. However, the manner in which the human brain modulates the order of SL strategies based on the degree of uncertainty remains an open question. The present study examined how uncertainty modulates the neural effects of SL and whether differences in uncertainty alter the order of SL strategies. It used auditory sequences in which the uncertainty of sequential information is manipulated based on the conditional entropy. Three sequences with different TP ratios of 90:10, 80:20, and 67:33 were prepared as low-, intermediate, and high-uncertainty sequences, respectively (conditional entropy: 0.47, 0.72, and 0.92 bit, respectively). Neural responses were recorded when the participants listened to the three sequences. The results showed that stimuli with lower TPs elicited a stronger neural response than those with higher TPs, as demonstrated by a number of previous studies. Furthermore, we found that participants adopted higher-order SL strategies in the high uncertainty sequence. These results may indicate that the human brain has an ability to flexibly alter the order based on the uncertainty. This uncertainty may be an important factor that determines the order of SL strategies. Particularly, considering that a higher-order SL strategy mathematically allows the reduction of uncertainty in information, we assumed that the brain may take higher-order SL strategies when encountering high uncertain information in order to reduce the uncertainty. The present study may shed new light on understanding individual differences in SL performance across different uncertain situations