title: Auditory sensory attenuation effect in emerging psychosis
Creators: name: Hua, Lingling
Publisher: name: University of Glasgow
Year: 2021
Subjects: subject: Clinical high-risk psychosis, first-episode psychosis, sensory attenuation, magnetoencephalography, dynamic causal modeling.

description: Sensory consequences of one’s own voluntary action are perceived as less intense than externally initiated sensations. This process is referred to as sensory attenuation. This sensory attenuation has been identified in humans and animals across various modalities, including visual, auditory and somatosensory domains. The auditory sensory attenuation is explored by comparing the auditory N/M100 amplitude between self- and external-initiated conditions. The focus of auditory sensory attenuation is mainly on the primary auditory cortex and the superior temporal cortex, while emerging evidence indicates that the sensory attenuation is present in broader brain area. Moreover, the generation of sensory attenuation relies upon the precise coordination of the motor system with sensory areas. However, sensory attenuation across the whole brain and the underlying neural interaction between brain areas remain underexplored. Importantly, failure in sensory attenuation is considered to play a role in clinical psychotic symptoms, such as auditory hallucination and illusion. This has been confirmed in chronic schizophrenia (ScZ), possibly resulting from disrupted frontal-temporal coordination during generating sensory attenuation. However, it currently remains unclear whether deficits in sensory attenuation emerge before the prodromal phase of psychosis, as well as what aberrant neural mechanism underlie emerging psychosis. Given previous studies based on electroencephalogram(EEG) technology, the current thesis aimed to employ magnetoencephalography (MEG) to examine auditory M100 sensory attenuation. MEG-data were collected from 48 healthy controls (HC), 110 clinical high-risk psychosis (CHR), and 26 first-episode psychosis (FEP) participants during an auditory task in which pure tones were either elicited through a button press or passively presented. Auditory M100 event-related fields (ERFs) were recorded to assess auditory M100 sensory attenuation at the sensor- and source-level. The first aim was to map the sensory attenuation effect across the whole brain and further explore the association between motor-related activity and auditory sensory attenuation. Dynamic causal modelling (DCM) was also employed to determine the top-down and bottom-up modulation to determine the underpinning neural mechanism during sensory attenuation generation (Chapter 3). Subsequently, we focused on the auditory regions to address the sensory attenuation characteristics in emerging psychosis and its association with clinical features and cognitive functions. The goal was to address whether the sensory attenuation deficit could be regarded as a potential biomarker for early identification of psychosis (Chapter 4). Finally, DCM was employed to explore the alteration of neural interactions across the sensory attenuation network in emerging psychosis and investigate the aberrant neural mechanism of sensory attenuation (Chapter 5). The findings in Chapter 3 revealed that auditory M100 sensory attenuation was present in spatially distributed brain areas, involving various subcortical-cortical areas. In addition, the current results supported the modulation of motor-related activity with auditory sensory attenuation. The results from DCM further indicated the role of both top-down and bottom-up modulation of a thalamo-cortical network in generating auditory sensory attenuation. The results in Chapter 4 demonstrated impaired auditory M100 sensory attenuation in FEP and indicated that aberrant sensory attenuation emerged in the prodromal phase of psychosis. Moreover, the sensory attenuation effect in the auditory cortex was linearly associated with clinical symptom severity and cognitive performance. Finally, the DCM results in Chapter 5 suggested that the impaired sensory attenuation in FEP-participants originated from imprecise top-down control and subsequently enhanced bottom-up input (prediction error). The deficits in top-down control in CHR-individuals were not strong, while CHR participants were characterized by increased bottom-up inputs, which was intermediate between HC and FEP. Collectively, the results of this thesis suggested impaired auditory sensory attenuation in emerging psychosis, resulting from aberrant top-down and bottom-up interaction. This provides evidence that the auditory M100 sensory attenuation could be a potential candidate for the early detection of psychosis.