ABSTRACT
Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between the midbrain and striatum, orbitofrontal cortex and insula in methamphetamine-dependent participants, but a positive relationship in the control group. In Study 2, an interaction of the group with RSFC on impulsivity was observed. Methamphetamine-dependent users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect the system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals.
Subject(s)
Impulsive Behavior/drug effects , Mesencephalon/drug effects , Receptors, Dopamine D2/metabolism , Adult , Amphetamine-Related Disorders/metabolism , Central Nervous System Stimulants , Dopamine/metabolism , Female , Humans , Impulsive Behavior/physiology , Magnetic Resonance Imaging , Male , Methamphetamine/adverse effects , Methamphetamine/metabolism , Middle Aged , Positron-Emission Tomography/methods , Prefrontal Cortex/metabolism , Receptors, Dopamine D2/physiology , Ventral Striatum/drug effects , Ventral Striatum/physiopathologyABSTRACT
Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.
