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

Birn, Rasmus M.; Converse, Alexander K.; Rajala, Abigail Z.; Alexander, Andrew L.; Block, Walter F.; McMillan, A.; Christian, Bradley T.; Filla, Caitlynn; Murali, Dhanabalan; Jenison, Rick L.; Populin, Luis C.

doi:10.1523/jneurosci.2513-18.2018

Cited by 28 publications

(22 citation statements)

References 56 publications

(28 reference statements)

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“…While the precuneus is a central hub of the DMN (Cunningham, Tomasi, & Volkow, ), the cluster of our study was located above a standard DMN‐mask and was not significant in this DMN‐ROI. Nevertheless, a recent study independently shows the influence of DA modulation of FC between striatum‐precuneus (Birn et al, ). The functional role of the balance between striatum and precuneus FC during DA modulation remains unclear and more studies are warranted.…”

Section: Discussionmentioning

confidence: 99%

Amisulpride and l‐DOPA modulate subcortical brain nuclei connectivity in resting‐state pharmacologic magnetic resonance imaging

Grimm

Kopfer

Küpper-Tetzel

et al. 2019

Human Brain Mapping

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The precise understanding of the dopaminergic (DA) system and its pharmacological modifications is crucial for diagnosis and treatment of neuropsychiatric disorders, as well as for understanding basic processes, such as motivation and reward. We probed the functional connectivity (FC) of subcortical nuclei related to the DA system according to seed regions defined according to an atlas of subcortical nuclei. We conducted a large pharmaco‐fMRI study using a double‐blind, placebo‐controlled design, where we examined the effect of l ‐DOPA, a dopamine precursor, and amisulpride, a D2/D3‐receptor antagonist on resting‐state FC in 45 healthy young adults using a cross‐over design. We examined the FC of subcortical nuclei with connection to the reward system and their reaction to opposing pharmacological probing. Amisulpride increased FC from the putamen to the precuneus and from ventral striatum to precentral gyrus. l ‐DOPA increased FC from the ventral tegmental area (VTA) to the insula/operculum and between ventral striatum and ventrolateral prefrontal cortex and it disrupted ventral striatal and dorsal caudate FC with the medial prefrontal cortex. In an exploratory analysis, we demonstrated that higher self‐rated impulsivity goes together with a significant increase in VTA‐mid‐cingulate gyrus FC during l ‐DOPA‐challenge. Therefore, our DA challenge modulated distinct large‐scale subcortical connectivity networks. A dopamine‐boost can increase midbrain DA nuclei connectivity to the cortex. The involvement of the VTA‐cingulum connectivity in dependence of impulsivity has implications for diagnosis and therapy in disorders like ADHD.

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Section: Discussionmentioning

confidence: 99%

Amisulpride and l‐DOPA modulate subcortical brain nuclei connectivity in resting‐state pharmacologic magnetic resonance imaging

Grimm

Kopfer

Küpper-Tetzel

et al. 2019

Human Brain Mapping

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“…The effects of oral methylphenidate, which blocks the dopamine transporter, were investigated with the high affinity D 2 /D 3 receptor radiotracer [ 18 F]fallypride and functional connectivity in non-human primates. 91 Methylphenidate decreased [ 18 F]fallypride binding potential in the head of caudate, which was then shown to negatively correlate with dorsolateral prefrontal cortex, precuneus and hippocampus using functional connectivity. A similar negative relationship between dopamine release and functional connectivity was also demonstrated in healthy human volunteers after oral methylphenidate administration.…”

Section: Pet/mri Of Endogenous Neurotransmitter Release By Pharmacolomentioning

confidence: 99%

Advances in simultaneous PET/MR for imaging neuroreceptor function

Sander

Hansen

Wey

2020

J Cereb Blood Flow Metab

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Hybrid imaging using PET/MRI has emerged as a platform for elucidating novel neurobiology, molecular and functional changes in disease, and responses to physiological or pharmacological interventions. For the central nervous system, PET/MRI has provided insights into biochemical processes, linking selective molecular targets and distributed brain function. This review highlights several examples that leverage the strengths of simultaneous PET/MRI, which includes measuring the perturbation of multi-modal imaging signals on dynamic timescales during pharmacological challenges, physiological interventions or behavioral tasks. We discuss important considerations for the experimental design of dynamic PET/MRI studies and data analysis approaches for comparing and quantifying simultaneous PET/MRI data. The primary focus of this review is on functional PET/MRI studies of neurotransmitter and receptor systems, with an emphasis on the dopamine, opioid, serotonin and glutamate systems as molecular neuromodulators. In this context, we provide an overview of studies that employ interventions to alter the activity of neuroreceptors or the release of neurotransmitters. Overall, we emphasize how the synergistic use of simultaneous PET/MRI with appropriate study design and interventions has the potential to expand our knowledge about the molecular and functional dynamics of the living human brain. Finally, we give an outlook on the future opportunities for simultaneous PET/MRI.

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“…Encoding of the Go‐response, in turn, critically involves auditory‐cortical NMDA receptor signalling (Schicknick & Tischmeyer, ) and was selectively affected in opposite directions when β 1 ‐adrenergic antagonists and agonists were previously applied to naive animals in the present study. Given that catecholamines in the brain in general (Birn et al., ; van den Brink et al., ; Devilbiss, ; Guedj, Meunier, Meunier, & Hadj‐Bouziane, ; Helbing, Tischmeyer, & Angenstein, ) and in the auditory cortex (Happel, ; Happel et al., ; Reichenbach et al., ) shape the functional connectivity of local as well as global circuits, the present findings can be explained by postulating a critical role of β‐adrenergic activity in the auditory cortex for NMDA receptor‐dependent mechanisms of FM discrimination learning that support the strengthening of functional connections required for goal‐directed behaviour.…”

Section: Discussionmentioning

confidence: 61%

β‐adrenergic modulation of discrimination learning and memory in the auditory cortex

Schicknick

Henschke

Budinger

et al. 2019

Eur J of Neuroscience

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Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long‐term memory formation is scarce. Our previous pharmacological studies on cortex‐dependent frequency‐modulated tone‐sweep discrimination learning of Mongolian gerbils showed that auditory‐cortical D1/5‐dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D1/5‐dopamine receptors and β‐adrenoceptors, we hypothesised a role of β‐adrenergic signalling in the auditory cortex for sweep discrimination learning and memory. Supporting this hypothesis, the β1/2‐adrenoceptor antagonist propranolol bilaterally applied to the gerbil auditory cortex after task acquisition prevented the discrimination increment that was normally monitored 1 day later. The increment in the total number of hurdle crossings performed in response to the sweeps per se was normal. Propranolol infusion after the seventh training session suppressed the previously established sweep discrimination. The suppressive effect required antagonist injection in a narrow post‐session time window. When applied to the auditory cortex 1 day before initial conditioning, β1‐adrenoceptor‐antagonising and β1‐adrenoceptor‐stimulating agents retarded and facilitated, respectively, sweep discrimination learning, whereas β2‐selective drugs were ineffective. In contrast, single‐sweep detection learning was normal after propranolol infusion. By immunohistochemistry, β1‐ and β2‐adrenoceptors were identified on the neuropil and somata of pyramidal and non‐pyramidal neurons of the gerbil auditory cortex. The present findings suggest that β‐adrenergic signalling in the auditory cortex has task‐related importance for discrimination learning of complex sounds: as previously shown for D1/5‐dopamine receptor signalling, β‐adrenoceptor activity supports long‐term memory consolidation and reconsolidation; additionally, tonic input through β1‐adrenoceptors may control mechanisms permissive for memory acquisition.

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

Cited by 28 publications

References 56 publications

Amisulpride and l‐DOPA modulate subcortical brain nuclei connectivity in resting‐state pharmacologic magnetic resonance imaging

Amisulpride and l‐DOPA modulate subcortical brain nuclei connectivity in resting‐state pharmacologic magnetic resonance imaging

Advances in simultaneous PET/MR for imaging neuroreceptor function

β‐adrenergic modulation of discrimination learning and memory in the auditory cortex

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