A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt) neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP) can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT) can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools has greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

Background/Aims: The clinical diagnosis of degenerative forms of parkinsonism is imperfect, with past studies reporting a high rate of misdiagnosis by neurologists and movement disorder specialists, particularly early in the disease course. ¹²³I-ioflupane SPECT (DaTscan) is a diagnostic neuroimaging tool used to distinguish essential tremor from tremor due to degenerative parkinsonisms. The present study expands upon prior studies of the clinical impact of DaTscan imaging in movement disorder centers by assessing quantitative estimates of diagnostic certainty, the impact on subsequent clinical decisions, and the degree to which the asymmetry in the results corresponds to laterality by clinical history and examination. Methods: In a prospective, observational study of the impact of DaTscan imaging in a movement disorder center over the course of 18 months, 4 specialists completed a questionnaire at the time they ordered imaging and again within 1 month after imaging. Results: Twenty-seven patients underwent DaTscan imaging; the result was normal in 4 cases (14.8%), abnormal in 22 cases (81.4%), and equivocal in 1 case (3.7%). In all cases of a normal result, the post-scan-predicted chance of degenerative parkinsonism decreased compared to the pre-scan prediction (p < 0.05), and in all cases of abnormal scan, the post-scan chance of degenerative parkinsonism increased or remained high (p < 0.0001). Clinical impacts were observed following imaging in a total of 24 patients (88.9%), including changes in medications for 18 patients and psychological impacts for 11 patients. Asymmetric clinical symptoms were corroborated based on the expected asymmetry of dopamine uptake deficits in 57.1% of the cases, were not present in 23.8%, and were opposite of expectations in 19.0% of the scans. Conclusion: DaTscan imaging results have an impact on physician's confidence in the diagnosis of parkinsonism and may also have a psychological impact on patients. DaTscan imaging may be a useful adjunct to clinical history and examination in selected patients.

Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson’s disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD.