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Changes in Endogenous Dopamine Induced by Methylphenidate Predict Functional Connectivity in Nonhuman Primates.

Rasmus M Birn^1,2, Alexander K Converse³, Abigail Z Rajala⁴

¹Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience

|December 12, 2018

Summary

Methylphenidate increases dopamine in the brain

Keywords:

PET/MR dopamine fallypride methylphenidate

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Area of Science:

Neuroscience
Pharmacology
Radiology

Background:

Dopamine (DA) is crucial for cognitive functions and is modulated by drugs like methylphenidate (MPH).
MPH increases extracellular DA by blocking the dopamine transporter, but its effects on brain connectivity are not fully understood.
Understanding the link between DA levels and brain network organization is key for treating conditions like ADHD.

Purpose of the Study:

To investigate the relationship between methylphenidate-induced dopamine changes and functional brain connectivity.
To elucidate the neural mechanisms underlying methylphenidate's effects on cognitive functions.

Main Methods:

Simultaneous positron emission tomography (PET) with [18F]fallypride and resting-state functional magnetic resonance imaging (fMRI) in awake rhesus monkeys.
Oral administration of various doses of methylphenidate (MPH).
Analysis of dopamine levels (BPND) and functional connectivity (FC) in brain regions including the striatum and prefrontal cortex.

Main Results:

Methylphenidate administration dose-dependently increased extracellular dopamine in the head of the caudate (hCd).
Decreased dopamine binding potential (BPND) in the hCd correlated negatively with functional connectivity between the hCd and the prefrontal cortex (PFC).
Voxelwise analyses showed negative correlations between hCd dopamine levels and FC with the dorsolateral PFC, hippocampus, and precuneus.

Conclusions:

Methylphenidate-induced changes in striatal dopamine levels predict alterations in resting-state functional connectivity.
These findings reveal a mechanism by which dopamine modulation in the striatum influences prefrontal cortex function.
This research provides insights into how drugs like methylphenidate affect brain networks underlying cognitive processes.