Impact of Methods on Sensory Gating Indices

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SCHUBRING, David, 2017. Impact of Methods on Sensory Gating Indices [Dissertation]. Konstanz: University of Konstanz

@phdthesis{Schubring2017Impac-40641, title={Impact of Methods on Sensory Gating Indices}, year={2017}, author={Schubring, David}, address={Konstanz}, school={Universität Konstanz} }

Schubring, David Impact of Methods on Sensory Gating Indices 2017 eng The present dissertation addresses sensory gating in schizophrenia and the impact different methodological approaches can have on the assessment of it and related connectivity measures. The auditory P50/M50 event-related brain potential/field is one of the most prominent parameters subject to sensory gating. A classical paradigm for its measurement consists of two identical click sounds (S1 & S2) presented 500 ms apart (paired-click protocol). The P50/M50 following the second click S2 is typically partially suppressed compared to the first, which is denominated as gating. Schizophrenia patients have less gating, which is interpreted as a lack of filtering of irrelevant information. The sensory gating deficit has been proposed as an endophenotype for schizophrenia and a link between deficient frontal control with sensory gating has been suggested. However, used methods and associated effect sizes vary considerably across studies using first-admission and/or using chronic patients. Both as a potential endophenotype and as a node in a potential brain network, the sensory gating deficit should be able to be reliably quantified. Pilot study The first step of this dissertation was to investigate the consistency of abnormal sensory gating in chronic schizophrenia patients (CHR) compared to healthy controls (HC) across methods in a pilot study. Magnetoencephalography (MEG) was measured in 58 CHR and 28 HC during a paired-click protocol. Sensory gating was evaluated in a large number of common preprocessing and quantification methods through all possible combinations. As preprocessing methods different strategies for noise correction, trial exclusion, artifact correction and filter settings were compared. As quantification methods, different strategies for source projection, peak identification, peak scoring and calculating a sensory gating index were compared. The contrast between HC and CHR was used as a point of comparison. Depending on the combination of preprocessing methods, results showed either no HC vs CHR contrast at all, a tendency of a HC vs CHR contrast or significant HC vs CHR contrasts. Following the law of parsimony, only the minimum amount of preprocessing necessary to produce a HC vs CHR contrast was used in the later studies. Study 1 Study 1 evaluated the impact of several quantification methods with an additional patient group of 35 first-admission (FA) schizophrenia patients. This was done to both estimate the consistency of abnormal sensory gating across stage of disorder and to have an patient group independent from the comparisons of the pilot study. Sensory gating was quantified on sensor and source levels as a ratio (S2 / S1) and as a S1-minus-S2 difference, with M50 amplitude scored relative to baseline and relative to M100 and to M40. Independent of quantification method, patients showed less sensory gating than HC, with medium-to-large effect sizes, without differences between FA and CHR. Results indicate that the frequently reported sensory gating deficit in schizophrenia is robust to variations in quantification methods and stage of disorder. Study 2 Study 2 evaluated connectivity dynamics within auditory – frontal cortex networks in a sensory gating context and related them to the robust sensory gating measures from study 1. Background: Connectivity measures delineate the communication within and between neuronal cell assemblies that constitute large-scale default, functional, or salience networks in service of perceptual and cognitive function. Correspondingly, perceptual and cognitive dysfunction in schizophrenia has been related to dysfunctional communication within and between neuronal assemblies, hence, dysfunctional large-scale default and functional networks. Different connectivity measures verified dysfunctional connectivity, while dysfunctional communication by direction of information flow (top-down or bottom-up) remains to be specified. Here, we used Granger causality analysis of MEG data to delineate communication within a functional auditory-frontal network and test the hypothesis that the common auditory sensory gating deficit in schizophrenia patients is associated with altered communication within this network. Method: Auditory sensory gating, indexed by MEG M50, was assessed in 72 healthy participants (H) and 56 schizophrenia patients (SZ) in a binaural auditory paired-stimulus task. Sources of M50 S1-S2 differences were localized in bilateral auditory (Heschl’s gyri) and bilateral frontal (mid-cingulate) regions. Information flow, indexed by 7-30 Hz oscillations, was analyzed within this network prior to and in response to the stimulus onset of paired clicks using Granger causality algorithms with either auditory or frontal sources as predictor of activity in the respective other source. Results: H, but not SZ, exhibited pre-stimulus information flow (at 19 Hz) from right auditory to right frontal source, which varied with post-stimulus auditory gating. No significant frontal-to-auditory information flow and relationship with M50-gating was found in any group. Conclusion: Results indicate bottom-up rather than top-down information flow mediating auditory sensory gating in H. Stimulus-unrelated (pre-stimulus) information flow may reflect a preparatory process for the top-down modulation after stimulus onset. The lack of systematic pre-stimulus communication within an ‘auditory-frontal’ auditory-gating network might explain dysfunctional sensory gating in SZ. 2017-11-16T09:41:41Z terms-of-use 2017-11-16T09:41:41Z Schubring, David

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