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Every decision that we make involves a conflict between exploiting our current knowledge of an action’s value or exploring alternative courses of action that might lead to a better, or worse outcome. The sub-cortical nuclei that make up the basal ganglia have been proposed as a neural circuit that may contribute to resolving this explore-exploit ‘dilemma’. To test this hypothesis, we examined the effects of neuromodulating the basal ganglia’s output nucleus, the globus pallidus interna, in patients who had undergone deep brain stimulation (DBS) for isolated dystonia. Neuromodulation enhanced the number of exploratory choices to the lower value option in a 2-armed bandit probabilistic reversal-learning task. Enhanced exploration was explained by a reduction in the rate of evidence accumulation (drift rate) in a reinforcement learning drift diffusion model. We estimated the functional connectivity profile between the stimulating DBS electrode and the rest of the brain using a normative functional connectome derived from heathy controls. Variation in the extent of neuromodulation induced exploration between patients was associated with functional connectivity from the stimulation electrode site to a distributed brain functional network. We conclude that the basal ganglia’s output nucleus, the globus pallidus interna, can adaptively modify decision choice when faced with the dilemma to explore or exploit.

To demonstrate the computed tomography, conformal irradiation, and treatment planning capabilities of a small animal radiation research platform (SARRP).The SARRP uses a dual-focal spot, constant voltage X-ray source mounted on a gantry with a source-to-isocenter distance of 35 cm. Gantry rotation is limited to 120 degrees from vertical. X-rays of 80-100 kVp from the smaller 0.4-mm focal spot are used for imaging. Both 0.4-mm and 3.0-mm focal spots operate at 225 kVp for irradiation. Robotic translate/rotate stages are used to position the animal. Cone-beam computed tomography is achieved by rotating the horizontal animal between the stationary X-ray source and a flat-panel detector. The radiation beams range from 0.5 mm in diameter to 60 x 60 mm(2). Dosimetry is measured with radiochromic films. Monte Carlo dose calculations are used for treatment planning. The combination of gantry and robotic stage motions facilitate conformal irradiation.The SARRP spans 3 ft x 4 ft x 6 ft (width x length x height). Depending on the filtration, the isocenter dose outputs at a 1-cm depth in water were 22-375 cGy/min from the smallest to the largest radiation fields. The 20-80% dose falloff spanned 0.16 mm. Cone-beam computed tomography with 0.6 x 0.6 x 0.6 mm(3) voxel resolution was acquired with a dose of1 cGy. Treatment planning was performed at submillimeter resolution.The capability of the SARRP to deliver highly focal beams to multiple animal model systems provides new research opportunities that more realistically bridge laboratory research and clinical translation.

In cancer research, well characterized small animal models of human cancer, such as transgenic mice, have greatly accelerated the pace of development of cancer treatments. The goal of the Small Animal Radiation Research Platform (SARRP) is to make those same models available for the development and evaluation of novel radiation therapies. In combination with advanced imaging methods, small animal research allows detailed study of biological processes, disease progression, and response to therapy, with the potential to provide a natural bridge to the clinical environment. The SARRP will realistically model human radiation treatment methods in standard animal models. In this paper, we describe the mechanical and control structure of the system. This system requires accurate calibration of the x-ray beam for both imaging and radiation treatment, which is presented in detail in the paper.