image: Figure 3. PET results. (A) 18F-fallypride displacement in vmPFC. Single-sample t test of γ-maps yielded significant voxels in vmPFC (Tmax = 13.8; cluster size, 528 voxels; peak voxel coordinates, 4, 36, −10; familywise error rate–corrected P < 0.001) and amplitudes of 18F-fallypride displacement in this cluster of voxels of γ = 0.022 ± 0.006 min−1 for all included participants. (B) Negative correlation between 18F-fallypride displacement γ in vmPFC and response time–based switch costs from behavioral analyses (cluster 1: Tmax = 3.25; cluster size, 9; peak voxel coordinates, −8, 28, −8; P < 0.005) (cluster 2: Tmax = 3.11; cluster size, 5; peak voxel coordinates, −12, 20, −16; P < 0.005). (C) Negative correlation between 18F-fallypride displacement γ in vmPFC and error rate–based switch costs from behavioral analyses (Tmax = 3.08; cluster size, 18; peak voxel coordinates, 8, 26, −14; P < 0.005). Color scales show T-values.
Credit: Images created by Isabelle Miederer, Hans-Georg Buchholz, Mathias Schreckenberger, Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Reston, VA (March 16, 2025)—For the first time, scientists have confirmed a neurobiochemical link between dopamine and cognitive flexibility, according to new research published in the March issue of The Journal of Nuclear Medicine. PET imaging shows that the brain increases dopamine production when completing cognitively demanding tasks, and that the more dopamine released, the more efficiently the tasks are completed. Armed with this information, physicians may soon be able to develop more precise treatment strategies for neurological and psychiatric disorders.
Cognitive flexibility is the ability to adapt one’s thinking and behavior appropriately to a changing environment and is considered an aspect of executive function. Cognitive flexibility differs among people and is reported to be impaired in several psychiatric and neurologic disorders, such as depression, posttraumatic stress disorder, addiction, anxiety disorder, schizophrenia, Parkinson’s disease, and attention-deficit/hyperactivity disorder.
“At the neurotransmitter level, the dopamine system has been linked to cognitive flexibility. A direct neurochemical response to cognitive flexibility, however, has yet to be shown,” said Isabelle Miederer, PhD, associate professor in experimental nuclear medicine in the department of nuclear medicine at University Medical Center Mainz, Germany. “In our study, we sought to examine the release of dopamine in real-time by performing PET scans while individuals completed behavioral flexibility tasks.”
Eighteen participants were scanned with the D2/3 receptor ligand 18F-fallypride in a two-part block study design. In the first part, participants performed two tasks consecutively on a computer screen without rule switching while undergoing PET imaging. In the second part of the PET scan, participants had to switch flexibly between two task rules. Dopamine release was calculated using the linearized simplified reference region model which compares the two task blocks with each other.
PET imaging analysis showed a displacement of 18F-fallypride in the ventromedial prefrontal cortex during the task switching (higher cognitive demand) part of the study, which is assumed to be the release of dopamine. Results also showed that the greater dopamine release, the more efficient participants were in switching between tasks.
“The present findings emphasize the significance of dopamine in cognitive flexibility,” said Mathias Schreckenberger, MD, head of the department of nuclear medicine at University Medical Center Mainz. “They are consistent with the results of previous clinical studies indicating that dopamine deficiency in disorders such as Parkinson’s disease may cause behavioral deficits in cognitive flexibility.”
“Looking forward, it is expected that the results of the study will contribute to a better understanding of the neurochemical mechanisms underlying cognitive flexibility and thus facilitate the development of treatment strategies to improve flexibility in neurological and psychiatric disorders,” he continued.
The authors of “Dopaminergic Mechanisms of Cognitive Flexibility: An [18F]Fallypride PET Study” include Isabelle Miederer, Hans-Georg Buchholz, Mathias Schreckenberger, Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Lena Rademacher, Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany, and Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany; Cindy Eckart, Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany; Dominik Kraft, Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany, and Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health, University of Tübingen, Tübingen, Germany; Markus Piel, Department of Nuclear Chemistry, Johannes Gutenberg University Mainz, Mainz, Germany; and Christian J. Fiebach, Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany and Brain Imaging Center, Goethe University Frankfurt, Frankfurt am Main, Germany.
Visit the JNM website for the latest research, and follow our new Twitter and Facebook pages @JournalofNucMed or follow us on LinkedIn.
###
Please visit the SNMMI Media Centerfor more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or rmaxey@snmmi.org.
About JNM and the Society of Nuclear Medicine and Molecular Imaging
The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed 15 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.
JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine, molecular imaging, and theranostics—precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit www.snmmi.org.
Journal
Journal of Nuclear Medicine
Article Title
Dopaminergic Mechanisms of Cognitive Flexibility: An [18F]Fallypride PET Study
Article Publication Date
1-Mar-2025