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Simultaneous pupillometry and functional Magnetic Resonance Imaging (fMRI) for the detection of stress-related endophenotypes
Simultaneous pupillometry and functional Magnetic Resonance Imaging (fMRI) for the detection of stress-related endophenotypes
Mental diseases constitute a core health challenge of the 21st century. To date, diagnostics in psychiatry have been primarily based on subjective self-reports, largely bypassing the biological underpinnings and phenotypic heterogeneity of psychiatric disorders. As an effort to implement a more biologically valid classification of mental disorders, recent initiatives like the Research Domain Criteria (RDoC) project aim to identify endophenotypes that reflect transdiagnostic core mechanisms of psychiatric disorders. Stress is known to play a fundamental role in the development of mood and anxiety disorders. One key system involved in the physiological response to stress is the brainstem’s noradrenergic (NA) arousal center located in the locus coeruleus (LC), and previous studies indicate that pupil size provides an indirect index for activity of the LC-NA system. In order to investigate the relationship between spontaneous drifts in autonomic arousal and global brain activity in healthy human subjects, we first determined the fMRI correlates of spontaneous pupil fluctuations during the resting state. We found that pupil dilations are strongly coupled to activation of the dorsal anterior cingulate cortex (dACC) and bilateral insula (salience network [SN]). To assess whether this link between the pupil and the SN would also extend to emotional arousal, we next investigated the neural correlates of reward anticipation-induced pupil dilations in healthy subjects. Here, we could show that a cue signaling the possibility to receive a monetary reward evoked strong pupil dilations, the magnitude of which predicted response time to a target cue. Again, pupil dilations were strongly linked to SN activation. Furthermore, our results suggest that pupillometry is helpful to dissect different phases of reward anticipation and associated brain activity, disentangling reward prediction, arousal modulation and attentionrelated processes. These observations led us to the conclusion that the SN modulates arousal levels to optimize task performance, that is, to counteract drowsiness/ transitions to sleep during the resting state and to facilitate reward-directed behaviors in the reward anticipation task. Taken together, pupillometry appears to provide a reliable index for activity of the SN, a core network related to psychiatric disorders, making it a promising tool for the detection of stress-related endophenotypes.
neuroscience, psychiatry, pupil, arousal, salience network
Schneider, Maximilian
2018
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Schneider, Maximilian (2018): Simultaneous pupillometry and functional Magnetic Resonance Imaging (fMRI) for the detection of stress-related endophenotypes. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)
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Abstract

Mental diseases constitute a core health challenge of the 21st century. To date, diagnostics in psychiatry have been primarily based on subjective self-reports, largely bypassing the biological underpinnings and phenotypic heterogeneity of psychiatric disorders. As an effort to implement a more biologically valid classification of mental disorders, recent initiatives like the Research Domain Criteria (RDoC) project aim to identify endophenotypes that reflect transdiagnostic core mechanisms of psychiatric disorders. Stress is known to play a fundamental role in the development of mood and anxiety disorders. One key system involved in the physiological response to stress is the brainstem’s noradrenergic (NA) arousal center located in the locus coeruleus (LC), and previous studies indicate that pupil size provides an indirect index for activity of the LC-NA system. In order to investigate the relationship between spontaneous drifts in autonomic arousal and global brain activity in healthy human subjects, we first determined the fMRI correlates of spontaneous pupil fluctuations during the resting state. We found that pupil dilations are strongly coupled to activation of the dorsal anterior cingulate cortex (dACC) and bilateral insula (salience network [SN]). To assess whether this link between the pupil and the SN would also extend to emotional arousal, we next investigated the neural correlates of reward anticipation-induced pupil dilations in healthy subjects. Here, we could show that a cue signaling the possibility to receive a monetary reward evoked strong pupil dilations, the magnitude of which predicted response time to a target cue. Again, pupil dilations were strongly linked to SN activation. Furthermore, our results suggest that pupillometry is helpful to dissect different phases of reward anticipation and associated brain activity, disentangling reward prediction, arousal modulation and attentionrelated processes. These observations led us to the conclusion that the SN modulates arousal levels to optimize task performance, that is, to counteract drowsiness/ transitions to sleep during the resting state and to facilitate reward-directed behaviors in the reward anticipation task. Taken together, pupillometry appears to provide a reliable index for activity of the SN, a core network related to psychiatric disorders, making it a promising tool for the detection of stress-related endophenotypes.