Improving sensitivity, specificity, and reproducibility of individual brainstem activation

Eva Matt,Elke R. Gizewski,Florian Ph. S. Fischmeister,Ahmad Amini,Thomas Foki,Alexandra Weber,Roland Beisteiner,Simon D. Robinson

doi:10.1007/s00429-019-01936-3

Abstract

Functional imaging of the brainstem may open new avenues for clinical diagnostics. However, for reliable assessments of brainstem activation, further efforts improving signal quality are needed. Six healthy subjects performed four repeated functional magnetic resonance imaging (fMRI) sessions on different days with jaw clenching as a motor task to elicit activation in the trigeminal motor nucleus. Functional images were acquired with a 7 T MR scanner using an optimized multiband EPI sequence. Activation measures in the trigeminal nucleus and a control region were assessed using different physiological noise correction methods (aCompCor and RETROICOR-based approaches with variable numbers of regressors) combined with cerebrospinal fluid or brainstem masking. Receiver-operating characteristic analyses accounting for sensitivity and specificity, activation overlap analyses to estimate the reproducibility between sessions, and intraclass correlation analyses (ICC) for testing reliability between subjects and sessions were used to systematically compare the physiological noise correction approaches. Masking the brainstem led to increased activation in the target ROI and resulted in higher values for the area under the curve (AUC) as a combined measure for sensitivity and specificity. With the highest values for AUC, activation overlap, and ICC, the most favorable physiological noise correction method was to control for the cerebrospinal fluid time series (aCompCor with one regressor). Brainstem motor nuclei activation can be reliably identified using high-field fMRI with optimized acquisition and processing strategies—even on single-subject level. Applying specific physiological noise correction methods improves reproducibility and reliability of brainstem activation encouraging future clinical applications.

Highlights

The brainstem is a complex anatomical structure which is densely packed with functionally specialized nuclei involved in the propagation of sensory and motor signals, pain modulation, and autonomic processes
We systematically investigated the impact of the differential physiological noise correction methods on measures of sensitivity and specificity of brainstem nuclei activation
The masking procedures increased the sensitivity to trigeminal activation, whereas the mean T values and the percentage of activated voxels in the high pons were relatively unaffected by the masking

Summary

Introduction

The brainstem is a complex anatomical structure which is densely packed with functionally specialized nuclei involved in the propagation of sensory and motor signals, pain modulation, and autonomic processes. Further research targets encompass the vestibular system (Wildenberg et al 2011), respiratory control (Faull et al 2015; Pattinson et al 2009), emotion processing (Satpute et al 2013), reward prediction (D’Ardenne et al 2008), and consciousness (Gili et al 2013) Motor tasks such as finger tapping and facial muscle contractions have been used as functional localizers (Faull et al 2015), to systematically test the impact of different preprocessing methods (Beissner et al 2011), or to evaluate the impact of physiological noise correction (Harvey et al 2008). Resting-state approaches have identified brainstem networks and their associations with cortical regions, resulting in descriptions of the vestibular circuitry (Kirsch et al 2016), motor and autonomic networks (Bianciardi et al 2016), the connectivity of the dopaminergic system (Vytlacil et al 2014), as well as a potential pontine portion of the default mode network (Beissner et al 2014)

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