Neuroimaging statistical approaches for determining neural correlates of Alzheimer's disease via positron emission tomography imaging.

Alzheimer's disease (AD) is a degenerative disorder involving significant memory loss and other cognitive deficits, manifesting as a progression from normal cognitive functioning to mild cognitive impairment to AD. The sooner an accurate diagnosis of probable AD is made, the easier it is to manage symptoms and plan for future therapy. Functional neuroimaging stands to be a useful tool in achieving early diagnosis.

Cast-Related Complications.

Despite advances in surgical techniques and technology, casting remains an important treatment modality in the armamentarium of orthopedic surgery. Opportunities for skill development and complication management are a decreasing commodity for the surgeon in training. Appropriate indications for casting and technical expertise of cast application are key to complication avoidance.

Multimodal Imaging Signatures of Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection. Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of functional and structural brain characteristics as biomarkers.

Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue.

Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation.

Chronic interferon-α decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behavior in nonhuman primates.

Neuroimaging studies in humans have demonstrated that inflammatory cytokines target basal ganglia function and presynaptic dopamine (DA), leading to symptoms of depression. Cytokine-treated nonhuman primates also exhibit evidence of altered DA metabolism in association with depressive-like behaviors. To further examine cytokine effects on striatal DA function, eight rhesus monkeys (four male, four female) were administered interferon (IFN)-α (20 MIU/m(2) s.

Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.

Context: Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function.

Objectives: To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior.

Design: Cross-sectional and longitudinal studies.

A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.

Context: Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants.

Objectives: To determine whether inhibition of the inflammatory cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), TNF, and its soluble receptors, predicts treatment response.

Design: Double-blind, placebo-controlled, randomized clinical trial.

Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression.

Background: Interferon (IFN)-alpha has been used to study the effects of innate immune cytokines on the brain and behavior in humans. The degree to which peripheral administration of IFN-alpha accesses the brain and is associated with a central nervous system (CNS) inflammatory response is unknown. Moreover, the relationship among IFN-alpha-associated CNS inflammatory responses, neurotransmitter metabolism, and behavior has yet to be established.