Multifactorial modeling of impairment of evoked gamma range oscillations in schizophrenia

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Despite a significant increase in efforts to identify biomarkers and endophenotypic measures of psychiatric illnesses, only a very limited amount of computational models of these markers and measures has been implemented so far. Moreover, existing computational models dealing with biomarkers typically only examine one possible mechanism in isolation, disregarding the possibility that other combinations of model parameters might produce the same network behavior (what has been termed “multifactoriality”). In this study we describe a step toward a computational instantiation of an endophenotypic finding for schizophrenia, namely the impairment of evoked auditory gamma and beta oscillations in schizophrenia. We explore the multifactorial nature of this impairment using an established model of primary auditory cortex, by performing an extensive search of the parameter space. We find that single network parameters contain only little information about whether the network will show impaired gamma entrainment and that different regions in the parameter space yield similar network level oscillation abnormalities. These regions in the parameter space, however, show strong differences in the underlying network dynamics. To sum up, we present a first step toward an in silico instantiation of an important biomarker of schizophrenia, which has great potential for the identification and study of disease mechanisms and for understanding of existing treatments and development of novel ones.Peer reviewedFinal Published versio

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

Dynamics of Dynamics within a Single Data Acquisition Session: Variation in Neocortical Alpha Oscillations in Human MEG

Background Behavioral paradigms applied during human recordings in electro- and magneto- encephalography (EEG and MEG) typically require 1–2 hours of data collection. Over this time scale, the natural fluctuations in brain state or rapid learning effects could impact measured signals, but are seldom analyzed. Methods and Findings We investigated within-session dynamics of neocortical alpha (7–14 Hz) rhythms and their allocation with cued-attention using MEG recorded from primary somatosensory neocortex (SI) in humans. We found that there were significant and systematic changes across a single ~1 hour recording session in several dimensions, including increased alpha power, increased differentiation in attention-induced alpha allocation, increased distinction in immediate time-locked post-cue evoked responses in SI to different visual cues, and enhanced power in the immediate cue-locked alpha band frequency response. Further, comparison of two commonly used baseline methods showed that conclusions on the evolution of alpha dynamics across a session were dependent on the normalization method used. Conclusions These findings are important not only as they relate to studies of oscillations in SI, they also provide a robust example of the type of dynamic changes in brain measures within a single session that are overlooked in most human brain imaging/recording studies.National Institutes of Health (U.S.) (P41RR14075)National Institutes of Health (U.S.) (K25MH072941)National Institutes of Health (U.S.) (K01AT003459)National Institutes of Health (U.S.) (1RO1-NS045130-01)National Institutes of Health (U.S.) (T32GM007484)National Science Foundation (U.S.) (0316933)Osher Lifelong Learning Institute

State of the art on stylized fabrication

© 2019 Copyright held by the owner/author(s). Digital fabrication devices are powerful tools for creating tangible reproductions of 3D digital models. Most available printing technologies aim at producing an accurate copy of a tridimensional shape. However, fabrication technologies can also be used to create a stylistic representation of a digital shape. We refer to this class of methods as stylized fabrication methods. These methods abstract geometric and physical features of a given shape to create an unconventional representation, to produce an optical illusion, or to devise a particular interaction with the fabricated model. In this course, we classify and overview this broad and emerging class of approaches and also propose possible directions for future research

Computational modeling of distinct neocortical oscillations driven by cell-type selective optogenetic drive: separable resonant circuits controlled by low-threshold spiking and fast-spiking interneurons

Selective optogenetic drive of fast-spiking (FS) interneurons (INs) leads to enhanced local field potential (LFP) power across the traditional “gamma” frequency band (20–80 Hz; Cardin et al., 2009). In contrast, drive to regular-spiking (RS) pyramidal cells enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABAA synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS, and low-threshold spiking (LTS) INs. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time constant of GABAA inhibition induced by synchronous FS activity. Lower-frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.National Institutes of Health (U.S.) (NIH grant K25MH07294)National Institutes of Health (U.S.) (NIH grant F32NS063694)Massachusetts General Hospital (Claflin Distinguished Scholar Award