Studying synaptogenesis using [11C]UCB-J PET-fMRI
Research type
Research Study
Full title
Detecting synaptogenesis induced by Ketamine and motor learning using the PET tracer [11C]UCB-J in an integrated PET-fMRI paradigm
IRAS ID
286308
Contact name
David Nutt
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
4 years, 5 months, 1 days
Research summary
Research Summary
Both motor learning and the antidepressant effects of ketamine may be mediated by neuroplasticity, specifically, the formation of new synaptic connections between neurones. It has only very recently become possible to investigate where, when and how the brain forms new connections in the living human brain thanks to advancements in Positron Emission Tomography, also known as PET scanning. In this study, we propose to use such PET scanning techniques in combination with a magnetic brain scan (MRI) in order to investigate formation of new synaptic connections following two different interventions: Once after learning a new simple motor skill, and once after ketamine administration. To do this, we will be using a new radioligand that is detectable by PET scanning, called [11C]UCB-J, that binds exclusively to connections between brain cells. Using this, we will be able to detect changes in the number of connections before and after motor-skill learning and again, after ketamine administration. From this, we can find out where, and to what degree these neuroplasticity related changes in brain connections are taking place. Additionally, we will relate this information to electrophysiological recordings of participants brain activity during two tasks that respectively index the brains global ability to form new connections in response to sensory information (the human visual long-term potentiation task), and ability to adapt to novel information (the auditory mismatch negativity task), before and after ketamine. Both of these tasks provide indirect and complimentary measures of neuroplasticity. This may give us new insights into how ketamine works as an antidepressant, and how the brain forms new connections when learning new skills.
Summary of Results
Our study did not identify significant modulations in the resting-state fMRI profile post- ketamine exposure. Specifically, ketamine did not produce significant alterations in the integrity of the analysed functional networks nor the connectivity between them. We observed CBF increases in a few brain regions after ketamine exposure, especially within the right parahippocampal region.
However, some of the regions were localized within the white matter, while one cluster was localized outside the brain. There was a trend towards increased CBF within the 7 canonical functional brain networks following ketamine administration, but the effect did not reach statistical significance.We found significant lateralisation in [11C]-UCBJ binding between the left and right hemisphere in key brain regions of the motor network, hinting at dynamics in synaptic density mirroring induced alterations in sensorimotor representation.
No statistically significant alterations in synaptic density, as indexed by the VT of [11C]-UCBJ, were found post-ketamine administration in any analysed brain regions. Moreover, no statistically significant differences were detected in the change of [11C]-UCBJ before and after ketamine when comparing the Day1 and Day7 groups. There were no significant correlations between baseline or changes in VT of [11C]-UCBJ with variables such as age, ketamine dosage, or CADSS scores.
We observed a statistically significant positive correlation between the change in VT of [11C]- UCBJ and the change in fALFF after ketamine exposure within the anterior cingulate gyrus, precentral gyrus, supramarginal gyrus, insular cortex, and temporal lobe.
REC name
London - Brent Research Ethics Committee
REC reference
21/LO/0397
Date of REC Opinion
30 Sep 2021
REC opinion
Further Information Favourable Opinion