Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function.

The use of ultrasound to detect small-for-gestational-age infants in patients with elevated human chorionic gonadotropin on maternal serum screening.

We evaluated serial sonography for the antenatal detection of small-for-gestational-age (SGA) infants in pregnancies with elevated human chorionic gonadotropin (hCG) levels on midtrimester triple-marker screen. A retrospective cohort study was performed at Saddleback Memorial Medical Center where serial ultrasounds from 26 weeks to delivery are generally recommended for patients with hCG levels >2.0 Multiple of the Median (MoM). From 1999 to 2007, 659 subjects were identified for analysis. The incidence of intrauterine growth restriction (IUGR) and SGA were 5.2% and 7.3%, respectively. Antenatal ultrasound identified 31.3% of SGA infants. Compared with estimated fetal weight (EFW) <10th percentile alone, abdominal circumference (AC) <10th percentile improved the detection of SGA from 31.3% (95% confidence interval [CI], 18.7 to 46.3) to 35.4% (95% CI, 22.2 to 50.5). Using either EFW or AC further increased the sensitivity to 45.8% (95% CI, 31.4 to 60.8). The sensitivity for the detection of SGA was 100% when an EFW cutoff of 75% was used. Ultrasound can be used to detect SGA infants in patients with elevated hCG levels on midtrimester serum screening. A sonographic estimated fetal weight > or = 75th percentile appears to be a safe cutoff to rule out all fetuses at risk for SGA.

Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats.

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson's disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (1) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (2) emergence of the ventrolateral striatum as a new broadly connected network hub; and (3) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the parkinsonian rats, which could underlie recovery in motor functions observed in these animals.

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain.

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface "Cx-2D" allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex-changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies.