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

Rasmus M Birn | Alexander K Converse | Abigail Z Rajala | Andrew L Alexander | Walter F Block | Alan B McMillan | Bradley T Christian | Caitlynn N Filla | Dhanabalan Murali | Samuel A Hurley | Rick L Jenison | Luis C Populin
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2019

Dopamine (DA) levels in the striatum are increased by many therapeutic drugs, such as methylphenidate (MPH), which also alters behavioral and cognitive functions thought to be controlled by the PFC dose-dependently. We linked DA changes and functional connectivity (FC) using simultaneous [18F]fallypride PET and resting-state fMRI in awake male rhesus monkeys after oral administration of various doses of MPH. We found a negative correlation between [18F]fallypride nondisplaceable binding potential (BPND) and MPH dose in the head of the caudate (hCd), demonstrating increased extracellular DA resulting from MPH administration. The decreased BPND was negatively correlated with FC between the hCd and the PFC. Subsequent voxelwise analyses revealed negative correlations with FC between the hCd and the dorsolateral PFC, hippocampus, and precuneus. These results, showing that MPH-induced changes in DA levels in the hCd predict resting-state FC, shed light on a mechanism by which changes in striatal DA could influence function in the PFC.SIGNIFICANCE STATEMENT Dopamine transmission is thought to play an essential role in shaping large scale-neural networks that underlie cognitive functions. It is the target of therapeutic drugs, such as methylphenidate (Ritalin), which blocks the dopamine transporter, thereby increasing extracellular dopamine levels. Methylphenidate is used extensively to treat attention deficit hyperactivity disorder, even though its effects on cognitive functions and their underlying neural mechanisms are not well understood. To date, little is known about the link between changes in dopamine levels and changes in functional brain organization. Using simultaneous PET/MR imaging, we show that methylphenidate-induced changes in endogenous dopamine levels in the head of the caudate predict changes in resting-state functional connectivity between this structure and the prefrontal cortex, precuneus, and hippocampus.

Pubmed ID: 30530859

Associated grants

  • Agency: NCRR NIH HHS, United States
    Id: C06 RR015459
  • Agency: NCRR NIH HHS, United States
    Id: C06 RR020141
  • Agency: NIH HHS, United States
    Id: P51 OD011106
  • Agency: NICHD NIH HHS, United States
    Id: U54 HD090256

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Analysis of Functional NeuroImages (software resource)

RRID:SCR_005927

Set of (mostly) C programs that run on X11+Unix-based platforms (Linux, Mac OS X, Solaris, etc.) for processing, analyzing, and displaying functional MRI (FMRI) data defined over 3D volumes and over 2D cortical surface meshes. AFNI is freely distributed as source code plus some precompiled binaries.

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SR Research EyeLink Eye Trackers (material resource)

RRID:SCR_009602

THIS RESOURCE IS NO LONGER AVAILABLE,documented on February 1st, 2022. Instrument supplier providing eye tracking capabilities for behavioral labs as well as for MRI, MEG, and EEG research environments.

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SR Research EyeLink Eye Trackers (material resource)

RRID:SCR_009602

THIS RESOURCE IS NO LONGER AVAILABLE,documented on February 1st, 2022. Instrument supplier providing eye tracking capabilities for behavioral labs as well as for MRI, MEG, and EEG research environments.

View all literature mentions

Analysis of Functional NeuroImages (software resource)

RRID:SCR_005927

Set of (mostly) C programs that run on X11+Unix-based platforms (Linux, Mac OS X, Solaris, etc.) for processing, analyzing, and displaying functional MRI (FMRI) data defined over 3D volumes and over 2D cortical surface meshes. AFNI is freely distributed as source code plus some precompiled binaries.

View all literature mentions

MATLAB (software resource)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

View all literature mentions

MATLAB (software resource)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

View all literature mentions