Modulators in concert for cognition: modulator interactions in the prefrontal cortex

Research on the regulation and function of ascending noradrenergic, dopaminergic, serotonergic, and cholinergic systems has focused on the organization and function of individual systems. In contrast, evidence describing co-activation and interactions between multiple neuromodulatory systems has remained scarce. However, commonalities in the anatomical organization of these systems and overlapping evidence concerning the post-synaptic effects of neuromodulators strongly suggest that these systems are recruited in concert; they influence each other and simultaneously modulate their target circuits. Therefore, evidence on the regulatory and functional interactions between these systems is considered essential for revealing the role of neuromodulators. This postulate extends to contemporary neurobiological hypotheses of major neuropsychiatric disorders. These hypotheses have focused largely on aberrations in the integrity or regulation of individual ascending modulatory systems, with little regard for the likely possibility that dysregulation in multiple ascending neuromodulatory systems and their interactions contribute essentially to the symptoms of these disorders. This review will paradigmatically focus on neuromodulator interactions in the PFC and be further constrained by an additional focus on their role in cognitive functions. Recent evidence indicates that individual neuromodulators, in addition to their general state-setting or gating functions, encode specific cognitive operations, further substantiating the importance of research concerning the parallel recruitment of neuromodulator systems and interactions between these systems.     

Programs for Preventing Depression in Adolescence: Who Benefits and Who Does Not? An Introduction to the Supplemental Issue

We introduce this supplemental issue of Prevention Science, which brings together a set of papers from leading investigators who have conducted trials testing whether intervention programs prevent adolescent depression. Using data from these trials, these papers explore a series of factors that might account for variation in intervention benefit, employing several novel methods for assessing effect heterogeneity. These studies follow two general paradigms: three papers report findings from single randomized preventive intervention trials, while the remaining papers develop and apply new methods for combining data from multiple studies to evaluate effect heterogeneity more broadly. Colleagues from NIMH and SAMHSA also provide commentaries on these studies. They conclude that synthesis of findings from multiple trials holds great promise for advancing the field, and progress will be accelerated if collaborative data sharing becomes the norm rather than the exception.     

Neuromuscular choristoma of the sciatic nerve and lumbosacral plexus: an association with nerve-territory undergrowth in the pelvis affecting soft tissue and bone

Background

Neuromuscular choristomas (NMC) are rare congenital lesions with differentiated muscle found within peripheral nerves. Patients often present with progressive neuropathy, undergrowth of the affected limb, and limb length discrepancy. In the sciatic nerve (the most common location of NMC), this may lead to specific manifestations in the distal limb, including progressive neuropathy, a shortened atrophic limb and a cavus foot. We hypothesized that the presence of NMC of the sciatic nerve (proximal to the sciatic notch) extending to the lumbosacral plexus could lead to abnormalities in proximal nerve territories (i.e., nerve, muscle and bone) within the hemipelvis.

Methods

A retrospective review of all cases of sciatic nerve NMCs diagnosed at the Mayo Clinic was performed.

Results

Seven patients were identified with sciatic nerve NMCs extending proximal and distal to the sciatic notch. Four patients with NMCs had denervation of muscles within the pelvis and ipsilateral undergrowth of bone which resulted in three cases of hip dysplasia. To our knowledge, the finding of proximal nerve-territory soft tissue and bony undergrowth (including hip dysplasia) in patients with NMCs involving the sciatic nerve and lumbosacral plexus has not previously been recognized.

Conclusion

This finding will aid in both the diagnosis of the disease and an understanding of associated conditions.     

Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators

Uterine leiomyoma is the most frequent gynecologic neoplasm in women. By using a panel of cell lines derived from spontaneous Eker rat leiomyomas, we examined the estrogen-responsive phenotype of these tumor cells. Leiomyoma-derived ELT cell lines proliferated in response to estrogen, and estrogen-induced cell proliferation could be inhibited by the estrogen antagonist ICI 182780 and the selective estrogen-receptor modulators (SERMs) raloxifene and tamoxifen. In addition to inhibiting cell growth, these antagonists also inhibited estrogen-induced increases in progesterone-receptor expression. These data indicate that SERMs such as raloxifene and tamoxifen act as estrogen antagonists in uterine myometrial cells and suggest that this class of compounds may be effective for treatment of this important gynecologic neoplasm. © 1996 Wiley-Liss, Inc.     

The reliability of measuring quadriceps cross-sectional area with compound B ultrasound scanning

Many therapists use thigh circumference as a measure of quadriceps size to evaluate the effect of an injury or effectiveness of an intervention. However, this technique has been shown to be unreliable, thus more accurate methods of measuring muscle size are required. The purpose of this study was to investigate the validity and reliability of measuring quadriceps cross-sectional area (CSA) with static compound B ultrasound scanning at the level of the mid-thigh. Repeated measures of known linear distances and CSAs were made with a planimetry device. Both face and criterion validity were demonstrated indicating that the device is reliable when measuring CSAs. A single rater located quadriceps muscle borders and measured CSAs on a series of ultrasound scans. A mean coefficient of variation (%CV = 1.7) was observed, signifying high intra-rater reliability. Two raters performed six scans on each of 15 subjects. Initial observation of these results suggest that the measurement of quadriceps CSA with compound B ultrasound scanning is reliable, mean %CVs = 2.8 and 1.9 for the two raters and 2.4 when their results were combined. When raters performed scans on 18 subjects on two occasions on the same day intra-class correlation coefficients (ICC) were high, 0.991 and 0.980 for raters A and B, respectively. Paired Student's t-tests revealed a significant difference (p<0.05) for Rater B between CSAs measured for initial and relocated scans. However, this difference was calculated as 1.4–2.9% and was not of clinical importance. A significant difference (p<.0.05) was observed between measurements of CSAs made by both raters on the same subject. A calibration factor was calculated for transforming the measurements of Rater B, the use of which gave comparable values. ICCs using a fixed model for inter-rater reliability were 0.963 and 0.974 for actual and trans' formed values, respectively. This study observed differences between measures obtained by different raters and recommends that the calculation and employment of a calibration factor may be useful when comparing sequential measures made by different raters.     

Co-storage of enkephalins and adrenaline in the bovine adrenal medulla

Fluorescence histochemical and immunohistochemical techniques have been used to examine the distribution of catecholamine-containing and enkephalin-containing cells in sections of adult bovine adrenal medulla. Noradrenaline-containing cells were identified by fluorescence microscopy following perfusion fixation with 4% paraformaldehyde (formaldehyde-induced fluorescence, technique of Era¨nko¨⁸). Adrenaline-containing cells did not fluoresce under these conditions. Adrenaline-synthesizing cells were identified by immunofluorescence with an antiserum to bovinephenyl-N-methyl transferase. An antiserum to bovine dopamine-β-hydroxylase was used to identify noradrenaline plus adrenaline cells in the same section. Leu- and met-enkephalin-containing cells were identified immunohistochemically with their respective antisera. To determine whether there was a preferential association of leu- or met-enkephalin with adrenaline or noradrenaline cells, these various antisera were used singly or sequentially on sections treated with formaldehyde in which the localization of endogenous noradrenaline fluorescence had been recorded and then the fluorescence removed by washing overnight.Immunoreactive leu- and met-enkephalin were found to be associated exclusively with adrenaline-synthesizing cells. The finding that both enkephalins are localized in the one cell type (adrenaline cells) in the bovine adrenal medulla is consistent with the proposed common precursor model for synthesis of the two opioid pentapeptides. These findings on co-storage of enkephalins with adrenaline in the adrenal medulla may have implications for other areas of the peripheral and central nervous system where co-storage of catecholamines and enkephalins is known to occur.