Auditory neural oscillations and excitation/inhibition balance in emerging psychosis

BF Psychology;Q Science (General)

Thune, Hanna E.A. ; Uhlhaas, Peter

University:University of Glasgow

Department:Institute of Neuroscience and Psychology

关键词: Schizophrenia, Psychosis, GABA, glutamate, Glx, excitation, inhibition, E/I-balance, MEG, 1H-MRS, psychiatry, biomarker, Clinical High-Risk.;   

Others  :  http://theses.gla.ac.uk/75097/8/2019ThunePhD.pdf

来源: University of Glasgow

【 摘 要 】

Chronic schizophrenia (ScZ) is associated with impaired gamma oscillations, reflected by robust alterations in 40 Hz ASSR. Oscillatory deficits may arise from changes in the cortical E/I-balance. However, it is unclear whether aberrant oscillations and potential underlying mechanisms are present also in early and clinical high risk (CHR) stages of psychosis.In this thesis, data from a multimodal CHR study were used to explore auditory oscillatory alterations in CHR individuals, assessed using MEG-recorded 40 Hz Auditory Steady State Response (ASSR) measures, with the aim to establish how deficits may account for early alterations in neural circuits in emerging psychosis. To further map such changes, a group of first episode of psychosis (FEP) participants were also studied, and oscillatory measures were compared with H1-MRS measures of neurotransmitter levels as well as with clinical measures.The thesis first presents a meta-analysis of ASSR findings in ScZ so far, showing that the response is impaired in chronic patients. Each of the following four chapters respectively present separate data analyses, focusing on baseline ASSR data, connectivity analyses, proton magnetic resonance spectroscopy (1H-MRS) analyses, and data assessing longitudinal outcomes.Through these investigations, the thesis demonstrates impairments in RSMG 40 Hz spectral power and ITPC in CHR and FEP, with bidirectional connectivity impairments present between RSMG and primary auditory cortex in CHR participants. In addition, strong beta frequency reductions in power were observed in CHR and FEP participants relative to controls. No clear impairments were detected in 1H-MRS data, but a trend deficit in right auditory GABA levels was seen in FEP patients. Finally, investigations of longitudinal parameters revealed that RSMG oscillatory impairments are related to functioning at the time of scanning, but not to functioning at the one-year follow-up. Moreover, beta frequency power was found to be selectively impaired in individuals with sustained CHR symptoms and low GAF scores (at both baseline and 12 months).Combined, the results of this thesis provide evidence for complex, subtle neural circuit alterations in emerging psychosis, which can be captured non-invasively using the 40 Hz ASSR paradigm.