Header

UZH-Logo

Maintenance Infos

Modulation of midbrain neurocircuitry by intranasal insulin


Edwin Thanarajah, Sharmili; Iglesias, Sandra; Kuzmanovic, Bojana; Rigoux, Lionel; Stephan, Klaas E; Brüning, Jens C; Tittgemeyer, Marc (2019). Modulation of midbrain neurocircuitry by intranasal insulin. NeuroImage, 194:120-127.

Abstract

Insulin modulates dopamine neuron activity in midbrain and affects processes underlying food intake behaviour, including impulsivity and reward processing. Here, we used intranasal administration and task-free functional MRI in humans to assess time- and dose-dependent effects of insulin on functional connectivity of the dopaminergic midbrain – and how these effects varied depending on systemic insulin sensitivity as measured by HOMA-IR. Specifically, we used a repeated-measures design with factors dose (placebo, 40 IU, 100 IU, 160 IU), time (7 time points during a 90 min post-intervention interval), and group (low vs. high HOMA-IR).
A factorial analysis identified a three-way interaction (with whole-brain significance) with regard to functional connectivity between midbrain and the ventromedial prefrontal cortex. This interaction demonstrates that systemic insulin sensitivity modulates the temporal course and dose-dependent effects of intranasal insulin on midbrain functional connectivity. It suggests that altered insulin sensitivity may impact on dopaminergic projections of the midbrain and might underlie the dysregulation of reward-related and motivational behaviour in obesity and diabetes. Perhaps most importantly, the time courses of midbrain functional connectivity we present may provide useful guidance for the design of future human studies that utilize intranasal insulin administration.

Abstract

Insulin modulates dopamine neuron activity in midbrain and affects processes underlying food intake behaviour, including impulsivity and reward processing. Here, we used intranasal administration and task-free functional MRI in humans to assess time- and dose-dependent effects of insulin on functional connectivity of the dopaminergic midbrain – and how these effects varied depending on systemic insulin sensitivity as measured by HOMA-IR. Specifically, we used a repeated-measures design with factors dose (placebo, 40 IU, 100 IU, 160 IU), time (7 time points during a 90 min post-intervention interval), and group (low vs. high HOMA-IR).
A factorial analysis identified a three-way interaction (with whole-brain significance) with regard to functional connectivity between midbrain and the ventromedial prefrontal cortex. This interaction demonstrates that systemic insulin sensitivity modulates the temporal course and dose-dependent effects of intranasal insulin on midbrain functional connectivity. It suggests that altered insulin sensitivity may impact on dopaminergic projections of the midbrain and might underlie the dysregulation of reward-related and motivational behaviour in obesity and diabetes. Perhaps most importantly, the time courses of midbrain functional connectivity we present may provide useful guidance for the design of future human studies that utilize intranasal insulin administration.

Statistics

Citations

Dimensions.ai Metrics
12 citations in Web of Science®
11 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 04 Jun 2019
8 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Scopus Subject Areas:Life Sciences > Neurology
Life Sciences > Cognitive Neuroscience
Uncontrolled Keywords:Cognitive Neuroscience, Neurology
Language:English
Date:1 July 2019
Deposited On:04 Jun 2019 14:20
Last Modified:29 Jul 2020 10:47
Publisher:Elsevier
ISSN:1053-8119
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1016/j.neuroimage.2019.03.050
PubMed ID:30914385

Download

Hybrid Open Access

Download PDF  'Modulation of midbrain neurocircuitry by intranasal insulin'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)