This study also shows an association between hypo-activation and lower CM in the cerebellum for cocaine subjects compared to controls. The locus coeruleus, a homeostatic gray matter nucleus in the brainstem (lower midbrain/pons), is the main source of norepinephrinergic innervation to the thalamus and cerebellum [44] and is closely located to our midbrain seed (22 mm; 7 imaging voxels apart from midbrain; Fig. 7). These results are therefore consistent with altered norepinephrinergic regulation in cocaine addiction. Since most cocaine subjects had a positive urine for cocaine on the day of the study, the cocaine subjects' lower cerebellar BOLD and CM signals may reflect in part activation of norepinephrinergic pathways during short-term/acute withdrawal [45]. However, it could also reflect serotonergic dysfunction since there is increasing evidence of serotonergic regulation of cerebellar activity [46].
