Modelling impairment of evoked gamma range oscillations in schizophrenia

© 2015 Metzner et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abnormal oscillatory activity in schizophrenia has been found in a wide range of experimental paradigms [1]. For example, schizophrenic patients show reduced evoked gamma activity, which has been associated with negative symptoms, and increased spontaneous gamma activity, which has been associated with positive symptoms [2]. However, the underlying mechanisms remain elusive. Here we investigated the impact of circuit abnormalities on oscillatory activity in the gamma range (> 30 Hz) by simulating auditory entrainment in an established computational model of the primary auditory cortex [3]. Auditory click entrainment experiments showed that for schizophrenic patients EEG/MEG power decreased at 40 Hz and increased at 20 Hz in response to 40 Hz drive but no differences between were visible in response to 30 Hz drive [4, 5]. Here we used the primary auditory cortex model from Beeman [3] and simulated click train stimulation at 40 Hz, to investigate gamma entrainment deficits, and at 30 Hz as a control condition. Without alterations the model entrained at the driving frequency of 30 and 40 Hz, respectively. Similar to previous approaches [6], however, focusing on evoked rather than spontaneous activity, we next explored the effects of (1) connectivity disturbances (reduced (a) recurrent excitation, (b) pyramidal cell input and (c) total connectivity), (2) prolonged GABAergic decay time constant, and (3) reduced inhibitory output. All three interventions in connectivity (1a-c) led to an increase in 40 Hz power for 40 Hz drive, contrary to human EEG/MEG experiments. A prolonged GABAergic decay time constant produced a reduction of power at 40 Hz and an increase in power at 20 Hz, for the 40 Hz drive, which concurs with [4, 5]. Furthermore, for the 30 Hz drive, no differences to the standard model were observed. Reduction of inhibitory output led to decreases in power at 40 Hz for 40 Hz drive but no increases at 20 Hz. In the 30 Hz drive condition, a decrease was visible, in contrast to experimental data [4, 5]. In conclusion, only prolonged GABAergic decay time constants (2), but not interventions (1) and (3) led to changes in entrainment comparable to experimental evidence in agreement with previous modeling approaches [5]. Our simulations suggest that prolonged time constants at GABAergic synapses might play a key role in abnormal evoked gamma rhythms in schizophrenia. However, since we only investigated one intervention at a time, further studies are needed to investigate the complex interactions of these circuit abnormalities. Furthermore, it remains unclear if the same mechanism also underlies increased spontaneous gamma activity in schizophrenia.Peer reviewe

Center-surround interactions in a network model of layer 4Cα of primary visual cortex

© 2013 Metzner et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedContext integration is an ubiquitious principle in cortical processing underlying many perceptual and cognitive functions. Several neuropsychiatric disorders have been associated with an impairment of integration of context information, particularly schizophrenia. One way to investigate the mechanisms underlying context processing and its impairments, is to look at context integration in the well-understood visual system. Center-surround interactions (CSI), i.e. the mutual influencing of stimuli presented in the center and in the surround of the visual or receptive field, respectively, are well established, both in animal neurophysiology and human psychophysical and neuroimaging studiesPeer reviewe

Spike-timing dependent plasticity facilitates excitatory/inhibitory disbalances in early phases of tinnitus manifestation

© 2012 Metzner et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedThe majority of tinnitus cases are related to cochlear dysfunction, leading to altered peripheral input to the central auditory system. These alterations are believed to diminish the difference in activation during on- and off-conditions of sound. As a compensatory means the affected region of primary auditory cortex tries to maximize the difference between basic level activity and sound-induced activity by changing the excitatory /inhibitory balance. In a previous model comprising ~3000 multi-compartment Hodgkin-Huxley-type neurons, we have shown that solely an increase of excitatory influences may be sufficient to achieve these maximization. This previous Hodgkin-Huxley-type model did not take into account synaptic plasticity, howeverPeer reviewedFinal Published versio

Cataglyphis ant navigation strategies solve the global localization problem in robots with binary sensors

Low cost robots, such as vacuum cleaners or lawn mowers, employ simplistic and often random navigation policies. Although a large number of sophisticated localization and planning approaches exist, they require additional sensors like LIDAR sensors, cameras or time of flight sensors. In this work, we propose a global localization method biologically inspired by simple insects, such as the ant Cataglyphis that is able to return from distant locations to its nest in the desert without any or with limited perceptual cues. Like in Cataglyphis, the underlying idea of our localization approach is to first compute a pose estimate from pro-prioceptual sensors only, using land navigation, and thereafter refine the estimate through a systematic search in a particle filter that integrates the rare visual feedback. In simulation experiments in multiple environments, we demonstrated that this bioinspired principle can be used to compute accurate pose estimates from binary visual cues only. Such intelligent localization strategies can improve the performance of any robot with limited sensing capabilities such as household robots or toys.Comment: Accepted to BIOSIGNALS 201

Computational multifactoriality in a detailed neural network model resembling centre-surround suppression deficits in schizophrenia

© 2014 Metzner et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedPeer reviewe

Context integration in visual processing: a computational model of center-surround suppression in the visual system

[Poster presentation]. A dysfunction of GABAergic neurotransmission is hypothesized to be an important factor in the pathophysiology of schizophrenia [1], depression and anxiety disorders. Findings of decreased center-surround suppression (CSS, i.e. the mutual inhibition of a focal visual stimulus and its surrounding) have been interpreted in terms of GABAergic dysfunction [2]. Consistently, strongly decreased CSS is reported in schizophrenic patients [3]. However, the underlying mechanisms of this decrease remain unclearPeer reviewe