We investigated the use of manganese-enhanced magnetic resonance imaging (MEMRI) with fractionated doses as a way to retain the unique properties of manganese as a neuronal contrast agent while lessening its toxic effects in animals. First, we followed the signal enhancement on T 1 -weighted images of the brains of rats receiving 30 mg/kg fractions of MnCl 2 ·4H 2 O every 48 hours and found that the signal increased in regions with consecutive fractionated doses up to about six injections, then saturated. Second, we used T 1 mapping to test whether the amount of MRI-visible manganese that accumulated depended on the driving concentration of manganese in the fractions. For a fixed cumulative dose of 180 mg/kg MnCl 2 ·4H 2 O, increasing fraction doses of 6 × 30 mg/kg, 3 × 60 mg/kg, 2 × 90 mg/kg and 1 × 180 mg/kg produced progressively shorter T 1 values. The adverse health effects, however, also rose with the fraction dose. Thus, fractionated MEMRI can be used to balance the properties of manganese as a contrast agent in animals against its toxic effects.

Comparative studies have established that a number of structures within the rostromedial basal forebrain are critical for affiliative behaviors and social attachment. Lesion and neuroimaging studies concur with the importance of these regions for attachment and the experience of affiliation in humans as well. Yet it remains obscure whether the neural bases of affiliative experiences can be differentiated from the emotional valence with which they are inextricably associated at the experiential level. Here we show, using functional MRI, that kinship-related social scenarios evocative of affiliative emotion induce septal-preoptic-anterior hypothalamic activity that cannot be explained by positive or negative emotional valence alone. Our findings suggest that a phylogenetically conserved ensemble of basal forebrain structures, especially the septohypothalamic area, may play a key role in enabling human affiliative emotion. Our finding of a neural signature of human affiliative experience bears direct implications for the neurobiological mechanisms underpinning impaired affiliative experiences and behaviors in neuropsychiatric conditions.

Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of manganese in regions of the brain of a non-human primate (the common marmoset, Callithrix jacchus) following four systemic injections of 30 mg/kg MnCl 2 ·H 2 0 in the tail vein using T 1 -weighted magnetic resonance imaging (MRI) and compare these to changes in the rat following the same exposure route and dose. The doses were spaced 48 hours apart and we imaged the animals 48 hours after the final dose. We find that marmosets have significantly larger T 1 -weighted image enhancements in regions of the brain compared to rats, notably in the basal ganglia and the visual cortex. To confirm this difference across species reflects actual differences in manganese concentrations and not variations in the MRI properties of manganese, we measured the longitudinal relaxivity of manganese (χ 1 ) in the in vivo brain and found no significant species' difference. The high manganese uptake in the marmoset basal ganglia and visual cortex can be explained by CSF-brain transport from the large lateral ventricles and we confirm this route of uptake with time-course MRI during a tail-vein infusion of manganese. There is also high uptake in the substructures of the hippocampus that are adjacent to the ventricles. The large manganese accumulation in these structures on overexposure may be common to all primates, including humans.