Dataset Information

The periaqueductal gray and Bayesian integration in placebo analgesia.

ABSTRACT: In placebo hypoalgesia research, the strength of treatment expectations and experiences are key components. However, the reliability or precision of expectations had been mostly ignored although being a likely source for interindividual differences. In the present study, we adopted a Bayesian framework, naturally combining expectation magnitudes and precisions. This postulates that expectations (prior) are integrated with incoming nociceptive information (likelihood) and both are weighted by their relative precision to form the pain percept and placebo effect. Sixty-two healthy subjects received heat pain during fMRI. Placebo effects were more pronounced in subjects with more precise treatment expectations and correlated positively with the relative precision of the prior expectation. Neural correlates of this precision were observed in the periaqueductal gray and the rostral ventromedial medulla, indicating that already at the level of the brainstem the precision of an expectation can influence pain perception presenting strong evidence for Bayesian integration in placebo hypoalgesia.

SUBMITTER: Grahl A

PROVIDER: S-EPMC5860873 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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The periaqueductal gray and Bayesian integration in placebo analgesia.

Grahl Arvina A Onat Selim S Büchel Christian C

eLife 20180320

In placebo hypoalgesia research, the strength of treatment expectations and experiences are key components. However, the reliability or precision of expectations had been mostly ignored although being a likely source for interindividual differences. In the present study, we adopted a Bayesian framework, naturally combining expectation magnitudes and precisions. This postulates that expectations (prior) are integrated with incoming nociceptive information (likelihood) and both are weighted by the ...[more]

PMID: 29555019

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Project description:Background: Parkinson’s disease (PD) is a progressive, degenerative disease with early-stage pathology hypothesized to manifest in brainstem regions. Vocal deficits, including soft monotone speech, result in significant clinical and quality of life issues and are present in 90% of PD patients; yet, the underlying pathology mediating these significant voice deficits is unknown. The Pink1-/- rat is a valid model of early-onset PD that presents with analogous vocal communication deficits (e.g. reduced loudness). Previous work shows abnormal α-synuclein protein aggregation in the periaqueductal gray (PAG), a brain region critical and necessary to the modulation of mammalian vocal behavior. In this study, we used high-throughput RNA sequencing to examine gene expression within the PAG of both male and female Pink1-/- rats as compared to age-matched wildtype controls. We used a bioinformatic approach to (1) test the hypothesis that loss of Pink1 in the PAG will influence expression of genes that interact with Pink1, (2) highlight other key genes that relate to Mendelian PD, and (3) catalog molecular targets important for the production of rat vocalizations. Results: Knockout of the Pink1 gene resulted in differentially expressed genes for both male and female rats. Pathway analysis highlighted several significant metabolic pathways. Weighted gene co-expression network analysis (WGCNA) was used to identify gene nodes and their interactions in (A) males, (B) females, and (C) combined-sexes datasets. For each analysis, within the module containing the Pink1 gene, Pink1 itself was the central node with the highest number of interactions with other genes including solute carriers, glutamate metabotropic receptors, and genes associated with protein localization. Strong connections between Pink1 and Krt2 and Hfe were found in both males and female datasets. In females a number of modules were significantly correlated with vocalization traits. Of interest, gene enrichment of the key vocal Cyan module in females showed a significant number of neuromodulatory genes including Nts, Slc6a4, Slc10a4, Ndnf, and Gpr160, that may be responsible for the modulation of rat vocalizations. The top biological pathways within the female Cyan vocal module included the regulation of membrane depolarization, indolalkylamine metabolic process, and monoamine transport. Conclusions: Overall, this work supports the premise that gene expression changes in the PAG may contribute to the vocal behavioral and deficits observed in this PD rat model. Additionally, this dataset identifies genes that represent new therapeutic targets for PD voice disorders.

Dataset Information

The periaqueductal gray and Bayesian integration in placebo analgesia.

Publications

The periaqueductal gray and Bayesian integration in placebo analgesia.

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