Neurocognitive and neurophysiological endophenotypes in Schizophrenia: an overview

Schizophrenia (SCZ) is a severe psychotic disorder that affects up to 1% of the US population and it is associated with progressive impairment in social functioning and cognition. Nonetheless, despite its high burden, the pathophysiology of SCZ, including the genetic and biological mechanisms underlying the development and manifestation of the disorder, remains largely elusive. Endophenotypes are subtypes of biological markers that are more closely related to the genetic vulnerability for a disorder (e.g., SCZ). Recently, research on endophenotypes has identified several parameters that may prove useful in shedding light over the underlying neurobiology of SCZ. In this article, we provide an overview of the most established SCZ endophenotypes in the domains of neurocognition (attention deficits, working and verbal declarative memory dysfunctions) and neurophysiology (pre-pulse inhibition, anti-saccade impairment, event-related potential deficits) along with some novel, sleep-based measures (reduced sleep spindles and sleep slow waves). We also discuss recent conceptual advances in the field that may lead to novel, personalized treatment interventions for patients affected by this devastating mental illness

Normalization Removes Differences in Contractile Properties and Corticospinal Excitability Between Single- and Multi-Joint Exercises

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Impact of Operational Stress on Motor Evoked Potentials in Military Personnel

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Complexity of multi-dimensional spontaneous EEG decreases during propofol induced general anaesthesia

Emerging neural theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, causal interactions between brain regions are both integrated (all regions are to a certain extent connected) and differentiated (there is inhomogeneity and variety in the interactions). In support of this, recent work by Casali et al (2013) has shown that Lempel-Ziv complexity correlates strongly with conscious level, when computed on the EEG response to transcranial magnetic stimulation. Here we investigated complexity of spontaneous high-density EEG data during propofol-induced general anaesthesia. We consider three distinct measures: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability in the constitution of the set of active channels; and (iii) the novel synchrony coalition entropy (SCE), which measures the variability in the constitution of the set of synchronous channels. After some simulations on Kuramoto oscillator models which demonstrate that these measures capture distinct ‘flavours’ of complexity, we show that there is a robustly measurable decrease in the complexity of spontaneous EEG during general anaesthesia

Colossal dielectric constants in transition-metal oxides

Many transition-metal oxides show very large ("colossal") magnitudes of the dielectric constant and thus have immense potential for applications in modern microelectronics and for the development of new capacitance-based energy-storage devices. In the present work, we thoroughly discuss the mechanisms that can lead to colossal values of the dielectric constant, especially emphasising effects generated by external and internal interfaces, including electronic phase separation. In addition, we provide a detailed overview and discussion of the dielectric properties of CaCu3Ti4O12 and related systems, which is today's most investigated material with colossal dielectric constant. Also a variety of further transition-metal oxides with large dielectric constants are treated in detail, among them the system La2-xSrxNiO4 where electronic phase separation may play a role in the generation of a colossal dielectric constant.Comment: 31 pages, 18 figures, submitted to Eur. Phys. J. for publication in the Special Topics volume "Cooperative Phenomena in Solids: Metal-Insulator Transitions and Ordering of Microscopic Degrees of Freedom

Sleep endophenotypes of schizophrenia: slow waves and sleep spindles in unaffected first-degree relatives

Sleep spindles and slow waves are the main brain oscillations occurring in non-REM sleep. Several lines of evidence suggest that spindles are initiated within the thalamus, whereas slow waves are generated and modulated in the cortex. A decrease in sleep spindle activity has been described in Schizophrenia (SCZ), including chronic, early course, and early onset patients. In contrast, slow waves have been inconsistently found to be reduced in SCZ, possibly due to confounds like duration of illness and antipsychotic medication exposure. Nontheless, the implication of sleep spindles and slow waves in the neurobiology of SCZ and related disorders, including their heritability, remains largely unknown. Unaffected first-degree relatives (FDRs) share a similar genetic background and several neurophysiological and cognitive deficits with SCZ patients, and allow testing whether some of these measures are candidate endophenotypes. In this study, we performed sleep high-density EEG recordings to characterise the spatiotemporal features of sleep spindles and slow waves in FDRs of SCZ probands and healthy subjects (HS) with no family history of SCZ. We found a significant reduction of integrated spindle activity (ISAs) in FDRs relative to HS, whereas spindle density and spindle duration were not different between groups. FDRs also had decreased slow wave amplitude and slopes. Altogether, our results suggest that ISAs deficits might represent a candidate endophenotype for SCZ. Furthermore, given the slow wave deficits observed in FDRs, we propose that disrupted cortical synchronisation increases the risk for SCZ, but thalamic dysfunction is necessary for the disorder to fully develop

Electrode Polarization Effects in Broadband Dielectric Spectroscopy

In the present work, we provide broadband dielectric spectra showing strong electrode polarization effects for various materials, belonging to very different material classes. This includes both ionic and electronic conductors as, e.g., salt solutions, ionic liquids, human blood, and colossal-dielectric-constant materials. These data are intended to provide a broad data base enabling a critical test of the validity of phenomenological and microscopic models for electrode polarization. In the present work, the results are analyzed using a simple phenomenological equivalent-circuit description, involving a distributed parallel RC circuit element for the modeling of the weakly conducting regions close to the electrodes. Excellent fits of the experimental data are achieved in this way, demonstrating the universal applicability of this approach. In the investigated ionically conducting materials, we find the universal appearance of a second dispersion region due to electrode polarization, which is only revealed if measuring down to sufficiently low frequencies. This indicates the presence of a second charge-transport process in ionic conductors with blocking electrodes.Comment: 9 pages, 6 figures, experimental data are provided in electronic form (see "Data Conservancy"

TMS-Induced Cortical Potentiation during Wakefulness Locally Increases Slow Wave Activity during Sleep

BACKGROUND: Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis directly, we used transcranial magnetic stimulation (TMS) in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1±17.4%, p<0.01, n = 10). Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep. CONCLUSIONS/SIGNIFICANCE: These results provide direct evidence for a link between plastic changes and the local regulation of sleep need

Daytime Naps, Motor Memory Consolidation and Regionally Specific Sleep Spindles

BACKGROUND: Increasing evidence demonstrates that motor-skill memories improve across a night of sleep, and that non-rapid eye movement (NREM) sleep commonly plays a role in orchestrating these consolidation enhancements. Here we show the benefit of a daytime nap on motor memory consolidation and its relationship not simply with global sleep-stage measures, but unique characteristics of sleep spindles at regionally specific locations; mapping to the corresponding memory representation. METHODOLOGY/PRINCIPAL FINDINGS: Two groups of subjects trained on a motor-skill task using their left hand – a paradigm known to result in overnight plastic changes in the contralateral, right motor cortex. Both groups trained in the morning and were tested 8 hr later, with one group obtaining a 60–90 minute intervening midday nap, while the other group remained awake. At testing, subjects that did not nap showed no significant performance improvement, yet those that did nap expressed a highly significant consolidation enhancement. Within the nap group, the amount of offline improvement showed a significant correlation with the global measure of stage-2 NREM sleep. However, topographical sleep spindle analysis revealed more precise correlations. Specifically, when spindle activity at the central electrode of the non-learning hemisphere (left) was subtracted from that in the learning hemisphere (right), representing the homeostatic difference following learning, strong positive relationships with offline memory improvement emerged–correlations that were not evident for either hemisphere alone. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that motor memories are dynamically facilitated across daytime naps, enhancements that are uniquely associated with electrophysiological events expressed at local, anatomically discrete locations of the brain

Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints

The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease