Stereotactic radiosurgery and stereotactic body radiation therapy cost-effectiveness results.

OBJECTIVE: To describe and synthesize the current stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) cost-effectiveness research to date across several common SRS and SBRT applications. METHODS: This review was limited to comparative economic evaluations of SRS, SBRT, and alternative treatments (e.g., other radiotherapy techniques or surgery). Based on PubMed searches using the terms, "stereotactic," "SRS," "stereotactic radiotherapy," "stereotactic body radiotherapy," "SBRT," "stereotactic ablative radiotherapy," "economic evaluation," "quality adjusted life year (QALY)," "cost," "cost-effectiveness," "cost-utility," and "cost analysis," published studies of cost-effectiveness and health economics were obtained. Included were articles in peer-reviewed journals that presented a comparison of costs between treatment alternatives from January 1997 to November 2012. Papers were excluded if they did not present cost calculations, therapeutic cost comparisons, or health economic endpoints. RESULTS: Clinical outcomes and costs of SRS and SBRT were compared to other therapies for treatment of cancer in the brain, spine, lung, prostate, and pancreas. Treatment outcomes for SRS and SBRT are usually superior or comparable, and cost-effective, relative to alternative techniques. CONCLUSION: Based on the review of current SRS and SBRT clinical and health economic literature, from a patient perspective, SRS and SBRT provide patients a clinically effective treatment option, while from the payer and provider perspective, SRS and SBRT demonstrate cost savings.

Image-guided radiosurgical ablation of intra- and extra-cranial lesions.

For decades since its introduction, stereotactic radiosurgery (SRS) was used only to treat intracranial lesions because intracranial targets could be immobilized and located relative to a rigid metal frame affixed to the patient's head. Lesions outside the head were generally not treated with SRS because it is difficult to immobilize extracranial lesions and to attach stereotactic frames elsewhere on the body. Advances in computerized image guidance and robotics allowed the development of systems, such as the CyberKnife SRS System (Accuray, Inc, Sunnyvale, CA), that could target intracranial lesions without the stereotactic frame. Enhancements have resulted in a radiation delivery system that can accurately deliver high-dose, focal radiation to lesions in the spine, chest, and abdomen, even if they move during respiration. In this review we will describe the technical features of frameless SRS systems and briefly review their application to treating intracranial and extracranial lesions, focusing in particular on spinal lesions.

Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats.

Activation of the Akt/protein kinase B (PKB) kinase pathway can be neuroprotective after stroke. Akt is activated by growth factors via a phosphorylation-dependent pathway involving the kinases phosphoinositide 3 (PI3) kinase and phosphoinositide-dependent protein kinase-1 (PDK1) and is negatively regulated by phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Akt kinase blocks apoptosis by phosphorylating the substrates forkhead transcription factor (FKHR) and glycogen synthase kinase 3beta (GSK3beta). We found that intra-ischemic hypothermia (30 degrees C) reduced infarct size and improved functional outcomes up to 2 months. Changes in phosphorylation levels of Akt, as measured by Western blots and immunostaining, differed from levels of Akt activity measured in an in vitro assay in normothermic animals. Hypothermia blocked most of these changes and maintained Akt activity. Inhibition of PI3/Akt enlarged infarct size in hypothermic animals. Hypothermia improved phosphorylation of PDK1, PTEN, and FKHR. Hypothermia did not improve GSK3beta (Ser9) phosphorylation but blocked the nuclear translocation of phosphorylated beta-catenin (Ser33/37/Thr41) downstream of GSK3beta. Phosphorylation levels of PTEN, Akt, and Akt substrate decreased before apoptotic cytochrome c release and degradation of microtubule-associated protein-2, a marker of neuronal survival. Hypothermia may protect from ischemic damage in part by preserving Akt activity and attenuating the apoptotic effects of PTEN, PDK1, and FKHR.

Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels.

Growing experimental and clinical evidence supports the notion that the cortico-basal ganglia-thalamo-cortical loops proceed along parallel circuits linking cortical and subcortical regions subserving the processing of sensorimotor, associative and affective tasks. In particular, there is evidence that a strict topographic segregation is maintained during the processing of sensorimotor information flowing from cortical motor areas to the sensorimotor areas of the basal ganglia. The output from the basal ganglia to the motor thalamus, which projects back to neocortical motor areas, is also organized into topographically segregated channels. This high degree of topographic segregation is demonstrated by the presence of a well-defined somatotopic organization in the sensorimotor areas of the basal ganglia. The presence of body maps in the basal ganglia has become clinically relevant with the increasing use of surgical procedures, such as lesioning or deep brain stimulation, which are selectively aimed at restricted subcortical targets in the sensorimotor loop such as the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). The ability to ameliorate the motor control dysfunction without producing side effects related to interference with non-motor circuits subserving associative or affective processing requires the ability to target subcortical areas particularly involved in sensorimotor processing (currently achieved only by careful intraoperative microelectrode mapping). The goal of this article is to review current knowledge about the somatotopic segregation of basal ganglia sensorimotor areas and outline in detail what is known about their body maps.

Naming our concerns about neuroscience: a review of Bennett and Hacker's philosophical foundations of neuroscience.

Bennett and Hacker use conceptual analysis to appraise the theoretical language of modern cognitive neuroscientists, and conclude that neuroscientific theory is largely dualistic despite the fact that neuroscientists equate mind with the operations of the brain. The central error of cognitive neuroscientists is to commit the mereological fallacy, the tendency to ascribe to the brain psychological concepts that only make sense when ascribed to whole animals. The authors review how the mereological fallacy is committed in theories of memory, perception, thinking, imagery, belief, consciousness, and other psychological processes studied by neuroscientists, and the consequences that fallacious reasoning have for our understanding of how the brain participates in cognition and behavior. Several behavior-analytic concepts may themselves be nonsense based on thorough conceptual analyses in which the criteria for sense and nonsense are found in the ways the concepts are used in ordinary language. Nevertheless, the authors' nondualistic approach and their consistent focus on behavioral criteria for the application of psychological concepts make Philosophical Foundations of Neuroscience an important contribution to cognitive neuroscience.

The functional organization of the sensorimotor region of the subthalamic nucleus.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is viewed by many as the ultimate therapy targeting severe advanced stages of Parkinson's disease (PD). A fundamental constituent of the mechanisms underlying the therapeutic effects of DBS is clearly the functional organization of the STN; however, there is limited understanding of the organization of this structure in humans. Data from primates suggest that different domains can be identified in the STN, including a sensorimotor area with a segregated body map, as well as nonmotor areas. Recent clinical studies have used microelectrode recording to investigate the presence of a body map in the sensorimotor STN of PD patients. This paper will review and compare experimental and clinical data regarding the functional organization of the STN and discuss the clinical implications for PD patients undergoing STN DBS.

Disruption of temporally organized behavior by morphine.

Four pigeons pecked keys in two different procedures commonly used in the study of timing, or temporal discrimination. Sessions consisted of 40 trials. During half of the trials, two keys were presented for 50 s. Left-key pecks were reinforced according to a variable-interval 67.86-s schedule during the first 25 s of the trial, and right-key pecks were not reinforced. During the second 25 s of the trial, right-key pecks were reinforced according to the same schedule, and left-key pecks were not reinforced. In the other half of the 40-trial session, the center key was presented. The majority of these trials arranged fixed-interval 2.5-s schedules. Occasionally a probe, or peak-interval, trial was presented. These trials were 100 s in duration and terminated without reinforcement. These two procedures were used to examine the effects of morphine on indexes of timing and on patterns of responding. Morphine altered behavior in a race-dependent manner in both procedures. Low baseline (saline) response rates were increased following morphine administration, and high baseline rates were either unaffected or decreased slightly. Rate-dependent effects appeared as leftward shifts in the timing index for two-key trials and decreases in the index of curvature for fixed-interval trials. Despite large changes in response rates, no consistent shift of the peak time was observed during peak-interval trials. These results are discussed primarily in terms of rate dependency; that is, rates of responding following drug administration tend to be determined in large part by rates of responding under baseline conditions.

Time of supplemental feeding alters the effects of cocaine on lever pressing of rats.

The present experiment assessed the effects of cocaine on the lever pressing of 4 rats maintained during 15-min sessions by a fixed-ratio 50 schedule of food reinforcement. Across phases, supplemental food was provided either immediately or 2 hr after sessions. Two rats began the experiment in the delayed-feeding condition, and 2 began the experiment in the immediate-feeding condition. Rates of lever pressing of 2 rats sometimes decreased to low levels near the ends of sessions when supplemental feeding was provided immediately, but were consistently high throughout sessions when supplemental feeding was delayed. Cocaine (1.0 to 17.0 or 30.0 mg/kg) was administered intraperitoneally 15 min prior to test sessions. In most cases, cocaine suppressed response rates at lower doses under immediate-feeding conditions. Decreases in overall response rates were correlated with dosedependent increases in the time rats spent not responding. It is suggested that delaying the time of postsession feeding increased response strength, as indicated by greater resistance to the rate-suppressive effects of cocaine.