The relationship between pupil diameter and other measures of opioid withdrawal during naloxone precipitated withdrawal

AbstractAdult attention-deficit/hyperactivity disorder (ADHD) frequently leads to psychological/social dysfunction if unaddressed. Identifying a reliable biomarker would assist the diagnosis of adult ADHD and ensure that adults with ADHD receive treatment. Pupil diameter can reflect inherent neural activity and deficits of attention or arousal characteristic of ADHD. Furthermore, distinct profiles of the complexity and symmetricity of neural activity are associated with some psychiatric disorders. We hypothesized that analysing the relationship between the size, complexity of temporal patterns, and asymmetricity of pupil diameters will help characterize the nervous systems of adults with ADHD and that an identification method combining these features would ease the diagnosis of adult ADHD. To validate this hypothesis, we evaluated the resting state hippus in adult participants with or without ADHD by examining the pupil diameter and its temporal complexity using sample entropy and the asymmetricity of the left and right pupils using transfer entropy. We found that large pupil diameters and low temporal complexity and symmetry were associated with ADHD. Moreover, the combination of these factors by the classifier enhanced the accuracy of ADHD identification. These findings may contribute to the development of tools to diagnose adult ADHD.

Download Full-text

Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

10.1101/2020.11.16.384818 ◽

2020 ◽

Author(s):

Olivia Uddin ◽

Carleigh Jenne ◽

Megan E. Fox ◽

Keiko Arakawa ◽

Asaf Keller ◽

...

Keyword(s):

Thermal Hyperalgesia ◽

Opioid Withdrawal ◽

Human Condition ◽

Model Systems ◽

Preclinical Models ◽

Precipitated Withdrawal ◽

Withdrawal Behaviors ◽

Illicit Use ◽

Ongoing Pain ◽

Rats And Mice

AbstractOpioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species’ strengths as model systems and can inform experimental design in studies of opioid withdrawal.

Download Full-text

Inter-and intra-individual coupling between pupillary, electrophysiological, and behavioral responses in a visual oddball task

10.31234/osf.io/nu6fe ◽

2020 ◽

Author(s):

Sara LoTemplio ◽

Jack Silcox ◽

Brennan Payne ◽

Kara D. Federmeier

Keyword(s):

Pupil Diameter ◽

Strong Relationship ◽

Individual Variability ◽

Pupil Dilation ◽

Pupillary Dilation ◽

Strong Correlations ◽

Control Center ◽

The Relationship ◽

Visual Oddball ◽

Phasic Activation

Although the P3b component of the event-related brain potential is one of the most widely-studied components, its underlying generators are not currently well understood. Recent theories have suggested that the P3b is triggered by phasic activation of the locus-coeruleus norepinephrine (LC-NE) system, an important control center implicated in facilitating optimal task-relevant behavior. Previous research has reported strong correlations between pupil dilation and LC activity, suggesting that pupil diameter is a useful indicator for ongoing LC-NE activity. Given the strong relationship between LC activity and pupil dilation, if the P3b is driven by phasic LC activity, there should be a robust trial-to-trial relationship with the phasic pupillary dilation response (PDR). However, previous work examining relationships between concurrently recorded pupillary and P3b responses has not supported this. One possibility is that the relationship between the measures might be carried primarily by either inter-individual (i.e., between-participant) or intra-individual (i.e., within-participant) contributions to coupling, and prior work has not systematically delineated these relationships. Doing so in the current study, we do not find evidence for either inter-individual or intra-individual relationships between the PDR and P3b responses. However, baseline pupil dilation did predict the P3b. Interestingly, both the PDR and P3b independently predicted inter-individual and intra-individual variability in decision response time. Implications for the LC-P3b hypothesis are discussed.

Download Full-text