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Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naïve schizophrenia subjects pre-and post-treatment with antipsychotics in comparison with traditional EEG analysis. We recorded eyes-closed resting state EEG from frontal, temporal, parietal and occipital regions in drug-naïve 22 schizophrenia and 24 age-matched healthy control subjects. Fifteen patients were re-evaluated within 2-8 weeks after the initiation of antipsychotic treatment. For each participant, MSE was calculated on one continuous 60 second epoch for each experimental session. Schizophrenia subjects showed significantly higher complexity at higher time scales (lower frequencies), than that of healthy controls in fronto-centrotemporal, but not in parieto-occipital regions. Post-treatment, this higher complexity decreased to healthy control subject levels selectively in fronto-central regions, while the increased complexity in temporal sites remained higher. Comparative power analysis identified spectral slowing in frontal regions in pre-treatment schizophrenia subjects, consistent with previous findings, whereas no antipsychotic treatment effect was observed. In summary, multiscale entropy measures identified abnormal dynamical EEG signal complexity in anterior brain areas in schizophrenia that normalized selectively in fronto-central areas with antipsychotic treatment. These findings show that entropybased analytic methods may serve as a novel approach for characterizing and understanding abnormal cortical dynamics in schizophrenia, and elucidating the therapeutic mechanisms of antipsychotics.

Objective Multiscale entropy (MSE) is a recently proposed entropy-based index of physiological complexity, evaluating signals at multiple temporal scales. To test this method as an aid to elucidating the pathophysiology of Alzheimer’s disease (AD), we examined MSE in resting state EEG activity in comparison with traditional EEG analysis. Methods We recorded EEG in medication-free 15 presenile AD patients and 18 age- and sex-matched healthy control (HC) subjects. MSE was calculated for continuous 60-second epochs for each group, concurrently with power analysis. Results The MSE results from smaller and larger scales were associated with higher and lower frequencies of relative power, respectively. Group analysis demonstrated that the AD group had less complexity at smaller scales in more frontal areas, consistent with previous findings. In contrast, higher complexity at larger scales was observed across brain areas in AD group and this higher complexity was significantly correlated with cognitive decline. Conclusions MSE measures identified an abnormal complexity profile across different temporal scales and their relation to the severity of AD. Significance These findings indicate that entropy-based analytic methods with applied at temporal scales may serve as a complementary approach for characterizing and understanding abnormal cortical dynamics in AD.

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Age-related differences involved in the neural substrates of emotional face perception were investigated in young and old healthy volunteers. The subjects were scanned using functional magnetic resonance imaging while they were judging the gender of faces with negative, positive, or neutral emotional valence. The results showed that both the predominant activation in young subjects and reduced activity in old subjects contributed to a significant age difference in the left amygdala during the perception of negative faces. Activity in the right parahippocampal gyrus during the perception of positive faces diminished with advancing age. Neural activity in the angular gyrus and lingual gyrus of the right hemisphere was reduced in the old subjects during the perception of positive faces. There was no region where old subjects had greater activity than young subjects during the task. In old subjects, the overall activity in the right hippocampus during the task correlated negatively with age, whereas the activity in the right parahippocampal gyrus correlated positively with neuropsychological performance. There was no significant correlation between subjects' characteristics and signal change in young subjects. These results indicate the age-associated vulnerability of the medial temporal lobe structures including the amygdala, hippocampus, and parahippocampal gyrus during face perception. The dissociation with reduced activity in the left amygdala and the right parahippocampal gyrus may suggest that aging differentially affects neural responses to faces with negative or positive emotional valence. The parieto-occipital lobe, which has been found to be involved in face processing, also showed a functional decline associated with aging.

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Some involvement of the human amygdala in the processing of facial expressions has been investigated in neuroimaging studies, although the neural mechanisms underlying motivated or emotional behavior in response to facial stimuli are not yet fully understood. We investigated, using functional magnetic resonance imaging (fMRI) and healthy volunteers, how the amygdala interacts with other cortical regions while subjects are judging the sex of faces with negative, positive, or neutral emotion. The data were analyzed by a subtractive method, then, to clarify possible interaction among regions within the brain, several kinds of analysis (i.e., a correlation analysis, a psychophysiological interaction analysis and a structural equation modeling) were performed. Overall, significant activation was observed in the bilateral fusiform gyrus, medial temporal lobe, prefrontal cortex, and the right parietal lobe during the task. The results of subtraction between the conditions showed that the left amygdala, right orbitofrontal cortex, and temporal cortices were predominantly involved in the processing of the negative expressions. The right angular gyrus was involved in the processing of the positive expressions when the negative condition was subtracted from the positive condition. The correlation analysis showed that activity in the left amygdala positively correlated with activity in the left prefrontal cortex under the negative minus neutral subtraction condition. The psychophysiological interaction revealed that the neural responses in the left amygdala and the right prefrontal cortex underwent the condition-specific changes between the negative and positive face conditions. The right amygdaloid activity also had an interactive effect with activity in the right hippocampus and middle temporal gyrus. These results may suggest that the left and right amygdalae play a differential role in effective processing of facial expressions in collaboration with other cortical or subcortical regions, with the left being related with the bilateral prefrontal cortex, and the right with the right temporal lobe.

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