Background: Gamma oscillations (30-80 Hz) in the dorsolateral prefrontal cortex (DLPFC) are associated with working memory; a process involving the maintenance and manipulation of information on line (Baddeley, 1986). Gamma oscillations are supported by gamma-aminobutyric acid (GABA) inhibitory interneurons in the DLPFC. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method in which to stimulate the cortex that has been shown to modify oscillations, cognition and GABAergic mechanisms. Patients with schizophrenia have severe deficits in working memory that may be related to impairments in GABAergic inhibitory neurotransmission underlying gamma oscillations in the DLPFC. Objective: First, to evaluate gamma oscillatory activity in patients with schizophrenia during working memory compared to healthy subjects. Second, to examine the effect of rTMS applied over the DLPFC on gamma oscillations generated during working memory in healthy subjects. Third, to examine the effect of rTMS applied to the DLPFC on gamma oscillations in patients with schizophrenia compared to healthy subjects. Hypotheses: First, it was hypothesized that patients with schizophrenia would exhibit an alteration in gamma oscillatory activity. Second, it was hypothesized that rTMS would be effective in enhancing gamma oscillations in healthy subjects. Third, it was hypothesized that rTMS would be effective in inhibiting gamma oscillations in patients with schizophrenia. Results: The first study found that patients with schizophrenia generate excessive gamma oscillations during working memory compared to healthy subjects. The second experiment found that rTMS over the DLPFC resulted in the potentiation of gamma oscillations in healthy subjects during working memory. The third experiment demonstrated that rTMS inhibited excessive gamma oscillations in patients with schizophrenia while an opposite effect was found in healthy subjects. Conclusions: rTMS applied over the DLPFC modulates frontal gamma oscillatory in healthy subjects and in patients with schizophrenia depending on baseline levels of activity, a finding that may ultimately translate into a better understanding of the mechanisms leading to cognitive improvement in this disorder.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/29662 |
| Date | 29 August 2011 |
| Creators | Barr, Mera |
| Contributors | Daskalakis, Zafiris Jeff |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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