Modeling GABA Alterations in Schizophrenia: A Link Between Impaired Inhibition and Altered Gamma and Beta Range Auditory Entrainment

• Published in: Journal of neurophysiology Vol. 99; no. 5; pp. 2656 - 2671
• Main Authors: Vierling-Claassen, Dorea, Siekmeier, Peter, Stufflebeam, Steven, Kopell, Nancy
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.05.2008
• Subjects: Acoustic Stimulation; Adolescent; Adult; Algorithms; Auditory Cortex - physiopathology; Auditory Perception - physiology; Beta Rhythm; Computer Simulation; Electroencephalography; Evoked Potentials - physiology; Excitatory Postsynaptic Potentials - physiology; GABA Plasma Membrane Transport Proteins - genetics; GABA Plasma Membrane Transport Proteins - metabolism; gamma-Aminobutyric Acid - physiology; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Humans; Interneurons - physiology; Magnetoencephalography; Male; Middle Aged; Models, Neurological; Neural Networks, Computer; Psychiatric Status Rating Scales; Schizophrenia - genetics; Schizophrenia - metabolism; Schizophrenia - physiopathology; Schizophrenic Psychology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00870.2007

1 Department of Mathematics and Statistics, 2 Center for BioDynamics, Boston University, Boston; 3 McLean Hospital, Harvard Medical School, Belmont; and 4 Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts Submitted 6 August 2007; accepted in final form 20 February 2008 The disorganized symptoms of schizophrenia, including severely disordered thought patterns, may be indicative of a problem with the construction and maintenance of cell assemblies during sensory processing and attention. The gamma and beta frequency bands (15–70 Hz) are believed relevant to such processing. This paper addresses the results of an experimental examination of the cortical response of 12 schizophrenia patients and 12 control subjects when presented with auditory click-train stimuli in the gamma/beta frequency band during measurement using magnetoencephalography (MEG), as well as earlier work by Kwon et al. These data indicate that control subjects show an increased 40-Hz response to both 20- and 40-Hz stimulation as compared with patients, whereas schizophrenic subjects show a preference for 20-Hz response to the same driving frequencies. In this work, two computational models of the auditory cortex are constructed based on postmortem studies that indicate cortical interneurons in schizophrenic subjects have decreased GAT-1 (a GABA transporter) and GAD 67 (1 of 2 enzymes responsible for GABA synthesis). The models transition from control to schizophrenic frequency response when an extended inhibitory decay time is introduced; this change captures a possible effect of these GABA alterations. Modeling gamma/beta range auditory entrainment in schizophrenia provides insight into how biophysical mechanisms can impact cognitive function. In addition, the study of dynamics that underlie auditory entrainment in schizophrenia may contribute to the understanding of how gamma and beta rhythms impact cognition in general. Address for reprint requests and other correspondence: D. Vierling-Claassen, Boston University Math Dept. (E-mail: dorea{at}math.bu.edu )