The effects of acute dopamine depletion on resting-state functional connectivity in healthy humans

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 ob-served. (C) 2022 Elsevier B.V. and ECNP. All rights reserved.