Working Memory and Neurofeedback.

Impairments in working memory are typically associated with impairments in other cognitive faculties such as attentional processes and short-term memory. This paper briefly introduces neurofeedback as a treatment modality in general, and, more specifically, we review several of the current modalities successfully used in neurofeedback (NF) for the treatment of working memory deficits. Two case studies are presented to illustrate how neurofeedback is applied in treatment. The development of Low Resolution Electromagnetic Tomography (LORETA) and its application in neurofeedback now makes it possible to specifically target deep cortical/subcortical brain structures. Developments in neuroscience concerning neural networks, combined with highly specific yet practical NF technologies, makes neurofeedback of particular interest to neuropsychological practice, including the emergence of specific methodologies for treating very difficult working memory (WM) problems.

RANKL:osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis.

OBJECTIVE: To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL:osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease. METHODS: Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects. RESULTS: At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL:OPG ratio compared with that in healthy children (mean +/- SD 2.19 +/- 3.03 and 0.13 +/- 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of -1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than -1.5 (P = 0.038). Lumbar spine BMD Z scores (mean +/- SD -0.13 +/- 1.19 [range -2.10 to 2.85]) were inversely associated with the duration of untreated disease (R = -0.50, P = 0.003). CONCLUSION: Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.

Composition of calcifications in children with juvenile dermatomyositis: association with chronic cutaneous inflammation.

OBJECTIVE: Calcific deposits develop in 20-40% of children with juvenile dermatomyositis (juvenile DM), contributing to disease morbidity and mortality. This study was undertaken to define the structure and composition of these deposits and to characterize their association with chronic inflammation. METHODS: We examined calcific deposits from 5 children with juvenile DM (2 boys and 3 girls). The crystal structure and mineral content of the deposits was analyzed by x-ray diffraction, Fourier transform infrared spectroscopy, and imaging. The protein content of the deposits, following solubilization, was assayed by Western blotting. RESULTS: All 5 children had both a young age at disease onset (mean +/- SD 3.3 +/- 1.9 years) and, despite therapy, persistent cutaneous inflammation (mean +/- SD duration 81.3 +/- 58.7 months). The bone proteins, osteopontin, osteonectin, and bone sialoprotein, were identified in the protein extracts; the only mineral detected was hydroxyapatite, but the tissue was distinct from bone, with an extremely high mineral content and an irregular distribution of mineral. CONCLUSION: These results indicate that chronic cutaneous inflammation may contribute to the formation of hydroxyapatite-containing pathologic calcifications in children with juvenile DM.

MxA gene expression in juvenile dermatomyositis peripheral blood mononuclear cells: association with muscle involvement.

Juvenile dermatomyositis (JDM), a systemic vasculopathy, is characterized by inflammation of skin and muscle. Muscle biopsies from untreated JDM patients show upregulation of type I interferon (IFN)-inducible genes, including myxovirus resistance protein A (MxA). The present study examines whether MxA mRNA expression in peripheral blood mononuclear cells (PBMC) from JDM patients: (1) is elevated compared to healthy controls, (2) reflects disease activity, and (3) changes with the onset of clinically effective treatment. MxA mRNA expression in JDM PBMC obtained at the initial clinic visit was elevated compared to controls and was positively correlated with Disease Activity Score (DAS) for muscle, but not with DAS for skin, suggesting that damage to skin and muscle in JDM may each have a discrete pathophysiology. During the course of clinically effective treatment, decrease in muscle symptoms was associated with a decrease in PBMC MxA mRNA expression.

Duration of illness is an important variable for untreated children with juvenile dermatomyositis.

OBJECTIVE: To evaluate the impact of duration of untreated symptoms in children with juvenile dermatomyositis (JDM) on clinical and laboratory status at diagnosis. STUDY DESIGN: We examined physical and laboratory data from the first physician visit for 166 untreated children with JDM. Disease activity scores (DASs) assessed skin and muscle involvement. Height and weight were compared with the National Health and Nutrition Examination Survey III dataset. Duration of untreated illness was designated as the time from first sign of rash or weakness to diagnostic visit. RESULTS: Boys and girls with untreated JDM were shorter and lighter than national norms (P > .0005 for both), and nonwhite children were weaker than white children (P > .0005). Older children had more dysphagia (P = .017) and arthritis (P > .001). Duration of untreated JDM was negatively associated with DAS weakness (P > .0005), unrelated to DAS skin, and positively associated with pathological calcifications (P = .006). With untreated disease > or = 4.7 months, serum levels of 4 muscle enzymes (aldolase, lactic dehydrogenase, creatine kinase, serum glutamic-oxaloacetic transaminase/aspartate aminotransferase) tended toward normal (P > .01 for each). CONCLUSIONS: Duration of untreated symptoms is an important variable and should be included in decisions concerning both diagnostic criteria and intensity of therapy for children with JDM.

History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry.

OBJECTIVE: To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM). METHODS: Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis. RESULTS: Children for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were < or =4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics. CONCLUSION: This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.