TY - JOUR
T1 - The effects of acute dopamine depletion on resting-state functional connectivity in healthy humans
AU - Caravaggio, Fernando
AU - Barnett, Alexander J.
AU - Nakajima, Shinichiro
AU - Iwata, Yusuke
AU - Kim, Julia
AU - Borlido, Carol
AU - Mar, Wanna
AU - Gerretsen, Philip
AU - Remington, Gary
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
This study was funded by the Canadian Institutes of Health Research (CIHR) (MOP-114,989) and US National Institutes of Health (NIH) (RO1MH084886–01A2). The CIHR and the NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
© 2022 Elsevier B.V. and ECNP
PY - 2022/4
Y1 - 2022/4
N2 - Alpha-methyl-para-tyrosine (AMPT), a competitive inhibitor of tyrosine hydroxylase, can be used to deplete endogenous dopamine in humans. We examined how AMPT-induced dopamine depletion alters resting-state functional connectivity of the basal ganglia, and canonical resting-state networks, in healthy humans. Fourteen healthy participants (8 females; age [mean ± SD] = 27.93 ± 9.86) completed the study. Following dopamine depletion, the caudate showed reduced connectivity with the medial prefrontal cortex (mPFC) (Cohen's d = 1.89, p<.0001). Moreover, the caudate, putamen, globus pallidus, and midbrain all showed reduced connectivity with the occipital cortex (Cohen's d = 1.48–1.90; p<.0001–0.001). Notably, the dorsal caudate showed increased connectivity with the sensorimotor network (Cohen's d = 2.03, p=.002). AMPT significantly decreased self-reported motivation (t(13)=4.19, p=.001) and increased fatigue (t(13)=4.79, p=.0004). A greater increase in fatigue was associated with a greater reduction in connectivity between the substantia nigra and the mPFC (Cohen's d = 3.02, p<.00001), while decreased motivation was correlated with decreased connectivity between the VTA and left sensorimotor cortex (Cohen's d = 2.03, p=.00004). These findings help us to better understand the role of dopamine in basal ganglia function and may help us better understand neuropsychiatric diseases where abnormal dopamine levels are observed.
AB - Alpha-methyl-para-tyrosine (AMPT), a competitive inhibitor of tyrosine hydroxylase, can be used to deplete endogenous dopamine in humans. We examined how AMPT-induced dopamine depletion alters resting-state functional connectivity of the basal ganglia, and canonical resting-state networks, in healthy humans. Fourteen healthy participants (8 females; age [mean ± SD] = 27.93 ± 9.86) completed the study. Following dopamine depletion, the caudate showed reduced connectivity with the medial prefrontal cortex (mPFC) (Cohen's d = 1.89, p<.0001). Moreover, the caudate, putamen, globus pallidus, and midbrain all showed reduced connectivity with the occipital cortex (Cohen's d = 1.48–1.90; p<.0001–0.001). Notably, the dorsal caudate showed increased connectivity with the sensorimotor network (Cohen's d = 2.03, p=.002). AMPT significantly decreased self-reported motivation (t(13)=4.19, p=.001) and increased fatigue (t(13)=4.79, p=.0004). A greater increase in fatigue was associated with a greater reduction in connectivity between the substantia nigra and the mPFC (Cohen's d = 3.02, p<.00001), while decreased motivation was correlated with decreased connectivity between the VTA and left sensorimotor cortex (Cohen's d = 2.03, p=.00004). These findings help us to better understand the role of dopamine in basal ganglia function and may help us better understand neuropsychiatric diseases where abnormal dopamine levels are observed.
KW - dopamine
KW - fMRI
KW - striatum
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U2 - 10.1016/j.euroneuro.2022.01.003
DO - 10.1016/j.euroneuro.2022.01.003
M3 - Article
C2 - 35091322
AN - SCOPUS:85123736623
SN - 0924-977X
VL - 57
SP - 39
EP - 49
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -
