ABSTRACT
Advances in functional magnetic resonance imaging (fMRI) have significantly enhanced our understanding of the striatal system of both humans and non-human primates (NHP) over the last few decades. However, its circuit-level functional anatomy remains poorly understood, partly because in-vivo fMRI cannot directly perturb a brain system and map its casual input-output relationship. Also, routine 3T fMRI has an insufficient spatial resolution. We performed electrical microstimulation (EM) of the striatum in lightly-anesthetized NHPs while simultaneously mapping whole-brain activation, using contrast-enhanced fMRI at ultra-high-field 7T. By stimulating multiple positions along the striatum's main (dorsal-to-ventral) axis, we revealed its complex functional circuit concerning mutually connected subsystems in both cortical and subcortical areas. Indeed, within the striatum, there were distinct brain activation patterns across different stimulation sites. Specifically, dorsal stimulation revealed a medial-to-lateral elongated shape of activation in upper caudate and putamen areas, whereas ventral stimulation evoked areas confined to the medial and lower caudate. Such dorsoventral gradients also appeared in neocortical and thalamic activations, indicating consistent embedding profiles of the striatal system across the whole brain. These findings reflect different forms of within-circuit and inter-regional neuronal connectivity between the dorsal and ventromedial striatum. These patterns both shared and contrasted with previous anatomical tract-tracing and in-vivo resting-state fMRI studies. Our approach of combining microstimulation and whole-brain fMRI mapping in NHPs provides a unique opportunity to integrate our understanding of a targeted brain area's meso- and macro-scale functional systems.
