Anatomical studies in animals have described multiple striatal circuits and suggested that subcomponents of the striatum, although functionally related, project to distinct cortical areas. To date, anatomical investigations in humans have been limited by methodological constraints such that most of our knowledge of fronto-striatal networks relies on nonhuman primate studies. To better identify the fronto-striatal pathways in the human brain, we used Diffusion Tensor Imaging (DTI) tractography to reconstruct neural connections between the frontal cortex and the caudate nucleus and putamen in vivo. We demonstrate that the human caudate nucleus is interconnected with the prefrontal cortex, inferior and middle temporal gyrus, frontal eye fields, cerebellum and thalamus; the putamen is interconnected with the prefrontal cortex, primary motor area, primary somatosensory cortex, supplementary motor area, premotor area, cerebellum and thalamus. A connectivity-based seed classification analysis identified connections between the dorsolateral prefrontal areas (DLPFC) and the dorsal-posterior caudate nucleus and between the ventrolateral prefrontal areas (VLPFC) and the ventral-anterior caudate nucleus. For the putamen, connections exist between the supplementary motor area (SMA) and dorsal-posterior putamen while the premotor area projects to medial putamen, and the primary motor area to the lateral putamen. Identifying the anatomical organization of the fronto-striatal network has important implications for understanding basal ganglia function and associated disease processes. KeywordsCaudate; Putamen; Frontal connectivity; Motor connectivity; Diffusion tensor imaging (DTI) tractography; HumansThe striatum is the main entry point of cortical information to the basal ganglia and it receives afferents from anatomically and functionally different areas of the cerebral cortex.According to the current model of basal ganglia function, cortical information is processed in the basal ganglia nuclei, which in turn send projections back via the thalamus to the cortex ('cortico-basal ganglia loop') [2,1]. To date, there are two opposing views regarding

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aβ) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aβ-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aβ-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aβ-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aβ-plaques.