Dataset Information

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

ABSTRACT:

Background

Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.

Methods

We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study.

Results

Kisspeptin's modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin's DMN modulation was greater in men with less reward drive (r = -0.489, P = 0.008) and predicted reduced sexual aversion (r = -0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus-globus pallidus (all P < 0.05). Consistent with this, kisspeptin's enhancement of hippocampus-globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]).

Conclusion

Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind.

Funding

NIHR, MRC, and Wellcome Trust.

SUBMITTER: Comninos AN

PROVIDER: S-EPMC6237465 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

Comninos Alexander N AN Demetriou Lysia L Wall Matthew B MB Shah Amar J AJ Clarke Sophie A SA Narayanaswamy Shakunthala S Nesbitt Alexander A Izzi-Engbeaya Chioma C Prague Julia K JK Abbara Ali A Ratnasabapathy Risheka R Yang Lisa L Salem Victoria V Nijher Gurjinder M GM Jayasena Channa N CN Tanner Mark M Bassett Paul P Mehta Amrish A McGonigle John J Rabiner Eugenii A EA Bloom Stephen R SR Dhillo Waljit S WS

JCI insight 20181018 20

<h4>Background</h4>Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.<h4>Methods</h4>We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometr ...[more]

PMID: 30333302

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Project description:Numerous studies have used functional magnetic resonance imaging (fMRI) to characterize functional connectivity between cortical regions by analyzing correlations in blood oxygenation level dependent (BOLD) signals in a resting state. However, to date, there have been only a handful of studies reporting resting state BOLD signals in white matter. Nonetheless, a growing number of reports has emerged in recent years suggesting white matter BOLD signals can be reliably detected, though their biophysical origins remain unclear. Moreover, recent studies have identified robust correlations in a resting state between signals from cortex and specific white matter tracts. In order to further validate and interpret these findings, we studied a non-human primate model to investigate resting-state connectivity patterns between parcellated cortical volumes and specific white matter bundles. Our results show that resting-state connectivity patterns between white and gray matter structures are not randomly distributed but share notable similarities with diffusion- and histology-derived anatomic connectivities. This suggests that resting-state BOLD correlations between white matter fiber tracts and the gray matter regions to which they connect are directly related to the anatomic arrangement and density of WM fibers. We also measured how different levels of baseline neural activity, induced by varying levels of anesthesia, modulate these patterns. As anesthesia levels were raised, we observed weakened correlation coefficients between specific white matter tracts and gray matter regions while key features of the connectivity pattern remained similar. Overall, results from this study provide further evidence that neural activity is detectable by BOLD fMRI in both gray and white matter throughout the resting brain. The combined use of gray and white matter functional connectivity could also offer refined full-scale functional parcellation of the entire brain to characterize its functional architecture.

Dataset Information

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

Background

Methods

Results

Conclusion

Funding

Publications

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

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