Volume 16 Supplement 1

24th Annual Computational Neuroscience Meeting: CNS*2015

Open Access

Modelling impairment of evoked gamma range oscillations in schizophrenia

BMC Neuroscience201516(Suppl 1):P305

https://doi.org/10.1186/1471-2202-16-S1-P305

Published: 18 December 2015

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.

Authors’ Affiliations

(1)
Institute for Robotics and Cognitive Systems, University of Luebeck
(2)
Department of Psychiatry, University of Luebeck

References

  1. Gonzalez-Burgos G, Lewis DA: GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophrenia Bulletin. 2008, 34 (5): 944-961.PubMedPubMed CentralView ArticleGoogle Scholar
  2. Gordon E, Williams L, Haig AR, Wright J, Meares RA: Symptom profile and "gamma" processing in schizophrenia. Cognitive Neuropsychiatry. 2001, 6: 7-19,2001.View ArticleGoogle Scholar
  3. Beeman D: A modeling study of cortical waves in primary auditory cortex. BMC Neuroscience. 2013, 14 (Suppl 1): P23-PubMed CentralGoogle Scholar
  4. Kwon JS, O'Donnell BF, Wallenstein GV, Greene RW, Hirayasu Y, Nestor PG, Hasselmo ME, Potts GF, Shenton ME, McCarley RW.: Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. Archives of General Psychiatry. 1999, 56 (11): 1001-1005.PubMedPubMed CentralView ArticleGoogle Scholar
  5. Vierling-Claassen D, Siekmeier P, Stufflebeam S, Kopell N: Modeling gaba alterations in schizophrenia: a link between impaired inhibition and altered gamma and beta range auditory entrainment. Journal of Neurophysiology. 2008, 99 (5): 2656-2671.PubMedPubMed CentralView ArticleGoogle Scholar
  6. Spencer KM: The functional consequences of cortical circuit abnormalities on gamma oscillations in schizophrenia: insights from computational modeling. Frontiers in Human Neuroscience. 2009, 3:Google Scholar

Copyright

© Metzner et al. 2015

This article is published under license to 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 stated.

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