Abstract
Here, we present an approach for identifying brainstem dopaminergic pathways using resting state functional MRI. In a group of healthy individuals, we searched for significant functional connectivity between dopamine-rich midbrain areas (substantia nigra; ventral tegmental area) and a striatal region (caudate) that was modulated by both a pharmacological challenge (the administration of the dopaminergic agonist bromocriptine) and a dopamine-sensitive cognitive trait (an individual’s working memory capacity). A significant inverted-U shaped connectivity pattern was found in a subset of midbrain-striatal connections, demonstrating that resting state fMRI data is sufficiently powerful to identify brainstem neuromodulatory brain networks.
Highlights
Dopamine is critical for a myriad of different functions ranging from motor control to high-level cognition [1], and is implicated in the pathology of neurological and psychiatric disorders such as Parkinson’s disease and schizophrenia
In a group of healthy individuals, we searched for significant functional connectivity between dopamine-rich midbrain areas and a striatal region that was modulated by both a pharmacological challenge and a dopamine-sensitive cognitive trait
We sought to further investigate whether the observed midbrain connectivity with other brain regions reflected dopaminergic projections by assessing whether connectivity was modulated by both the administration of the dopaminergic agonist bromocriptine and an individual’s working memory capacity
Summary
Dopamine is critical for a myriad of different functions ranging from motor control to high-level cognition [1], and is implicated in the pathology of neurological and psychiatric disorders such as Parkinson’s disease and schizophrenia. Numerous studies using resting state fMRI data have shown that neuronal activity is characterized by temporal correlations in blood oxygen level-dependent (BOLD) signal across disparate brain regions [3]. These fluctuations seem highly consistent over time and reflect the presence of intrinsic functional [4] and structural [5] connectivity. In a group of healthy individuals, we searched for significant functional connectivity between dopamine-rich midbrain areas (substantia nigra; ventral tegmental area) and a striatal region (caudate) that was modulated by both a pharmacological challenge (the administration of the dopaminergic agonist bromocriptine) and a dopamine-sensitive cognitive trait (an individual’s working memory capacity). Given the strong evidence that the relationship between cognitive performance and dopamine levels follows an inverted-U shaped function [6], and that working memory capacity can be linked to dopamine synthesis capacity in the caudate [7], we reasoned that voxels of the midbrain and caudate that varied in this manner would likely reflect dopaminergic pathways
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