Poster No:
1765
Submission Type:
Abstract Submission
Authors:
Megan McClintick1, Dara Ghahremani2, Jean Baptiste Pochon1, Andy Dean1, Robert Kessler1, Mark Mandelkern3, Edythe London1
Institutions:
1UCLA, Los Angeles, CA, 2UCLA, Irvine, CA, 3Veterans Administration of Greater Los Angeles, Los Angeles, CA
First Author:
Co-Author(s):
Mark Mandelkern
Veterans Administration of Greater Los Angeles
Los Angeles, CA
Introduction:
The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in impulse control and addictive behavior in humans and animals. We previously reported a significant effect of tobacco but not methamphetamine use on mGlu5 volumes of distribution and an association between cortical mGlu5 and verbal learning (McClintick et al., 2024). Here we test the association of mGlu5 receptors with impulsivity, risk-taking, and novelty seeking in human subjects.
Methods:
Fourteen individuals with methamphetamine use disorder (MUD; 10 men and 4 women) and fourteen individuals with no history of illicit drug use (9 men and 5 women) completed Positron Emission Tomography (PET) and questionnaires assessing self-reported impulsivity (Barratt Impulsiveness Scale [BIS]; UPPS-P Impulsive Behavior Scale [UPPS-P]), risk-taking (Domain-Specific Risk-Taking Scale [DOSPERT]), and novelty seeking (Cloninger Temperament and Character Inventory [TCI]). All fourteen individuals with MUD participated in outpatient (n = 2) or residential (n = 12) treatment programs and were abstinent from substances for less than 2 months (mean 41.5 days).
Total mGlu5 glutamate receptor volumes of distribution (VT) were measured with [18F]-FPEB PET (5 mCi bolus/infusion [kbol 205 min]). PET data, acquired as three contiguous 10-minute frames on a Siemens Biograph mCT were reconstructed with TrueX creating 30 one-minute volumes (400 × 400 × 109). Relative scatter and measured attenuation corrections and 2.0-mm Gaussian smoothing were applied. Within each frame, the 10 one-minute volumes were realigned to the averaged volume for that frame using FSL FLIRT (normalized correlation cost function). FSL FLIRT was used to co-register and resample the realigned averaged volumes for all three PET frames to the structural MPRAGE image with mutual information as the cost function. The MPRAGE image underwent segmentation via Freesurfer and was normalized to MNI space using linear (FSL FLIRT) and nonlinear (FSL FNIRT) registration. Volumes of interest (VOIs) from the FreeSurfer-based Desikan-Killiany Atlas in MNI space transformed to native space.
Total VT was calculated as the ratio of activity in brain tissue in each 10-minute frame to the mean activity in venous samples measured immediately before and after the frame. VT was averaged within each VOI in native space.
Group (MUD versus control) differences in self-reported impulsivity and risk-taking were tested with unpaired t tests. Associations of self-reported impulsivity and risk-taking with VT in bilateral cortical, striatal and thalamic VOIs were tested with partial correlational analyses controlling for smoking status, stimulant use and sex.
Results:
Self-reported impulsivity, assessed by the BIS (total score) and UPPS-P (negative and positive urgency subscale dimension scores), was significantly higher in the MUD group (t = 3.25, p = 0.0033; t = 4.95, p < 0.0001; t = 3.51, p = 0.0016 respectively). The TCI novelty seeking and UPPS-P premeditation scores were positively correlated (rs = 0.48, p = 0.018). BIS, DOSPERT, and UPPS-P scores were not associated with each other.
BIS total score correlated positively with thalamic VT (r = 0.44, p = 0.0342). UPPS-P negative urgency subscale dimension score correlated positively with striatal VT (r = 0.44, p = 0.0329). Risk-taking measured by the DOSPERT and novelty seeking measured by the TCI did not correlate with VT.
Conclusions:
The positive association between the mGlu5 VT and self-reported impulsivity in this sample further supports the role of mGlu5 in executive function in populations at higher risk for impaired inhibitory control. The mGlu5 may be a useful therapeutic target for neuropsychiatric disorders associated with deficits in impulse control.
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Transmitter Receptors 1
Keywords:
Addictions
Glutamate
Neurotransmitter
Positron Emission Tomography (PET)
Thalamus
1|2Indicates the priority used for review
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
I accept
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information.
Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
I do not want to participate in the reproducibility challenge.
Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Yes, I have IRB or AUCC approval
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
PET
Structural MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
FSL
Free Surfer
Provide references using APA citation style.
McClintick, M. N., Kessler, R. M., Mandelkern, M. A., Mahmoudie, T., Allen, D. C., Lachoff, H., Pochon, J. F., Ghahremani, D. G., Farahi, J. B., Partiai, E., Casillas, R. A., Mooney, L. J., Dean, A. C., & London, E. D. (2024). Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use. The international journal of neuropsychopharmacology, 27(8), pyae031. https://doi.org/10.1093/ijnp/pyae031
No