Convergent data from various scientific approaches strongly implicate cerebellar systems in nonmotor functions. The functional anatomy of these systems has been pieced together from disparate sources, such as animal studies, lesion studies in humans, and structural and functional imaging studies in humans. To better define this distinct functional anatomy, in the current study we delineate the role of the cerebellum in several nonmotor systems simultaneously and in the same subjects using resting state functional connectivity MRI. Independent component analysis was applied to resting state data from two independent datasets to identify common cerebellar contributions to several previously identified intrinsic connectivity networks (ICNs) involved in executive control, episodic memory/selfreflection, salience detection, and sensorimotor function. We found distinct cerebellar contributions to each of these ICNs. The neocerebellum participates in (1) the right and left executive control networks (especially crus I and II), (2) the salience network (lobule VI), and (3) the default-mode network (lobule IX). Little to no overlap was detected between these cerebellar regions and the sensorimotor cerebellum (lobules V-VI). Clusters were also located in pontine and dentate nuclei, prominent points of convergence for cerebellar input and output, respectively. The results suggest that the most phylogenetically recent part of the cerebellum, particularly crus I and II, make contributions to parallel cortico-cerebellar loops involved in executive control, salience detection, and episodic memory/self-reflection. The largest portions of the neocerebellum take part in the executive control network implicated in higher cognitive functions such as working memory.

The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus-regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition.

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This study evaluated the effect of local vanadyl acetylacetonate (VAC), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, and radiographic scoring were performed, as well as histomorphometry, including percent bone, percent cartilage, and osteoclast numbers. Fractures treated with local 1.5 mg/kg VAC possessed significantly increased mechanical properties compared to controls at 6 weeks post-fracture, including increased torque to failure (15%; p = 0.046), shear modulus (89%; p = 0.043), and shear stress (81%; p = 0.009). The radiographic scoring analysis showed increased cortical bridging at 4 weeks and 6 weeks (119%; p = 0.036 and 209%; p = 0.002) in 1.5 mg/kg VAC treated groups. Histomorphometry of the fracture callus at days 10 and 14 showed increased percent cartilage (121%; p = 0.009 and 45%; p = 0.035) and percent mineralized tissue (66%; p = 0.035 and 58%; p = 0.006) with local VAC treated groups compared to control. Additionally, fewer osteoclasts were observed in the local VAC treated animals as compared to controls at day 14 (0.45% ± 0.29% vs. 0.83% ± 0.36% of callus area; p = 0.032). The results suggest local administration of VAC acts to modulate osteoclast activity and increase percentage of early callus cartilage, ultimately enhancing mechanical properties comparably to non-diabetic animals treated with local VAC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2174-2180, 2017.

This study investigated the effects of local delivery of manganese chloride (MnCl 2 ), an insulin-mimetic compound, upon fracture healing using a rat femoral fracture model. Mechanical testing, histomorphometry, and immunohistochemistry were performed to assess early and late parameters of fracture healing. At 4 weeks post-fracture, maximum torque to failure was 70% higher (P < 0.05) and maximum torsional rigidity increased 133% (P < 0.05) in animals treated with 0.125 mg/kg MnCl 2 compared to saline controls. Histological analysis of the fracture callus revealed percent new mineralized tissue was 17% higher (P < 0.05) at day 10. Immunohistochemical analysis of the 0.125 mg/kg MnCl 2 treated group, compared to saline controls, showed a 379% increase in the density of VEGF-Cþ cells. In addition, compared to saline controls, the 0.125 mg/kg MnCl 2 treated group showed a 233% and 150% increase in blood vessel density in the subperiosteal region at day 10 post-fracture as assessed by detection of PECAM and smooth muscle a actin, respectively. The results suggest that local MnCl 2 treatment accelerates fracture healing by increasing mechanical parameters via a potential mechanism of amplified early angiogenesis leading to increased osteogenesis. Therefore, local administration of MnCl 2 is a potential therapeutic adjunct for fracture healing. ß