1. Large-scale brain networks in the awake, truly resting marmoset monkey. Resting-state functional MRI is a powerful tool that is increasingly used as a noninvasive method for investigating whole-brain circuitry and holds great potential as a possible diagnostic for disease;yet few resting-state studies have incorporated animal models. Here we present results from a small New World monkey that allows for the characterization of resting-state networks in the awake state. Six adult common marmosets (Callithrix jacchus) were acclimated to light, comfortable restraint using individualized helmets. Following behavioral training, resting BOLD data were acquired during eight consecutive 10 min scans for each conscious subject. Group independent component analysis revealed 12 brain networks that overlap substantially with known anatomically constrained circuits seen in the awake human. Specifically, we found eight sensory and lower order networks (four visual, two somatomotor, one cerebellar, and one caudateputamen network), and four higher-order association networks (one default mode-like network, one orbitofrontal, one frontopolar, and one network resembling the human salience network). In addition to their functional relevance, these network patterns bear great correspondence to those previously described in awake humans. This first-of-its-kind report in an awake New World nonhuman primate provides a platform for mechanistic neurobiological examination for existing disease models established in the marmoset. 2. Abstinence from Cocaine and Sucrose Self-administration Reveals Altered Mesocorticolimbic Circuit Connectivity. Previous preclinical studies have emphasized that drugs of abuse, through actions within and between Mesocorticolimbic (MCL) regions, usurp learning and memory processes normally involved in the pursuit of naturally rewarding stimuli. To distinguish MCL circuit pathobiological neuroadaptations that accompany addiction from general learning processes associated with natural reward goal-directed behavior, we trained two groups of rats to self-administer either cocaine (IV) or sucrose (orally) followed by an identically enforced 30 day abstinence period previously shown to induce behavioral self-administration (SA) plasticity. A third group of sedentary animals served as a negative control group for general handling effects. We examined low-frequency spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) signal, known as resting-state functional connectivity (rsFC), as a measure of intrinsic neurobiological interactions between brain regions. Our data provide evidence of fronto-striatal plasticity across the addiction trajectory, which are consistent with Acb-PFC hypoactivity seen in abstinent human drug addicts, suggesting potential circuit level biomarkers that may inform therapeutic interventions.
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