Treatment of depression with deep brain stimulation works by altering in specific ways the conscious perception of the core symptoms of sadness or anhedonia,not by modulating network circuitry

An important advance in the management of treatment-resistant depression has recently been reported: deep brain stimulation (DBS) of the subgenual cingulate (Brodmann area 25 or Cg 25) or the nucleus accumbens (NAcc). These treatments produce a response rate, meaning significant clinical improvement, of about 50%, but only a few patients are returned completely to normal. The authors of these papers generally attribute the therapeutic response to restoration of an altered or perturbed neural network. In contrast, the idea advanced here is that DBS works by altering conscious perception of the core symptoms of sadness and anhedonia, not by modulating network circuitry. In the case of Cg25, the crucial thing about this site is that it is where conscious perception of sadness localizes. However, the stimulus frequency of DBS (130 Hz) was too fast to support consciousness, which is associated with gamma frequencies (35–85 Hz). Therefore, the imposed rapid frequency instantaneously blocked the subjective experience of sadness. In the case of the NAcc, the treatment worked by stimulating hot zones in the NAcc, which, in animal models, are known to intensify the perception of pleasure. This magnifier effect on the perception of pleasure was able to alleviate anhedonia. The response was not instantaneous but could begin within hours. In both cases, patients’ realization that a core symptom had been relieved led to a moderate overall improvement in other symptoms.     

Superior temporal metabolic changes related to auditory hallucinations: a 31P-MR spectroscopy study in antipsychotic-free schizophrenia patients

Structural deficits in the superior temporal cortex and transverse temporal gyri appear to be related to auditory hallucinations in schizophrenia, which are a key symptom of this disorder. However, the cellular and neurochemical underpinnings are poorly understood and hardly studied in vivo. We used ³¹P-MRS (magnetic resonance spectroscopy) with chemical shift imaging to assess the association between left superior temporal cortex metabolism and severity of auditory hallucinations in 29 schizophrenia patients off antipsychotics. Hallucinations scores derived from the Scale for the Assessment of Positive Symptoms showed significant positive correlations with both measures of phospholipids (phosphomonoesters and phosphodiesters), and energy (inorganic phosphate and phosphocreatine, but not adenosine tri-phosphate) metabolism in left superior temporal gyrus/Heschl gyrus voxels. There was no correlation of metabolites in these regions with formal thought disorder, a symptom also linked to superior temporal pathology, thus suggesting symptom specificity. Our findings provide a link between established structural deficits and neurochemical pathology related to membrane pathology and markers of general metabolic turnover.     

Guidelines for Best Practice in the Audiological Management of Adults with Severe and Profound Hearing Loss

Individuals with severe to profound hearing loss are likely to present with complex listening needs that require evidence-based solutions. This document is intended to inform the practice of hearing care professionals who are involved in the audiological management of adults with a severe to profound degree of hearing loss and will highlight the special considerations and practices required to optimize outcomes for these individuals.     

Do they teach what they need to? An analysis of the impact of curriculum mapping on the learning objectives taught in a lecture series in surgery

Abstract

Introduction: Curriculum mapping shows concordances and differences between the intended and the taught curriculum. To our knowledge, no previous studies describe the effects that this mapping has on the curriculum. The aim of the present study is to map the content of a lecture series in surgery to the National Catalogue of Learning Objectives in Surgery and analyze the effects this mapping has on the content of the following lecture series.

Methods: All lecturers in the lecture series were directly observed by a minimum of two reviewers and learning objectives and the level of competence were documented. After the lecture series, the results were visualized within the catalog of learning objectives and were sent to the lecturers. In the following lecture series, learning objectives were documented correspondingly.

Results: In the first lecture series, 47% of the learning objectives were taught. After the mapping, the number of learning objectives that were taught increased to 59% (p?<?0.001). The increase was found in all surgical disciplines and in all levels of competences without any changes in the average duration of the lectures.

Conclusions: The presented method for mapping a curriculum effectively increased the number of taught learning objectives without requiring longer lecture durations.     

Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study

The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.     

Catestatin-like immunoreactivity in the rat eye

The aim of the study was to investigate the presence and distribution of the chromogranin A-derived peptide catestatin in the rat eye and trigeminal ganglion by immunofluorescence using an antibody which recognizes not only free catestatin but also larger fragments containing the sequence of catestatin. Western blots were performed in an attempt to characterize the immunoreactivities detected by the catestatin antiserum. Sparse immunoreactive nerve fibers were visualized in the corneal stroma, in the chamber angle, in the sphincter muscle but also in association with the dilator muscle, in the stroma of the ciliary body and processes, but dense in the irideal stroma, around blood vessels at the limbus and in the choroid and in cells of the innermost retina representing amacrine cells as identified by colocalization with substance P. Furthermore, catestatin-immunoreactivity was detected in the trigeminal ganglion in small to medium-sized cells and there were abundant catestatin-positive nerve fibers stained throughout the stroma of the ganglion. Double immunofluorescence of catestatin with substance P revealed colocalization both in cells of the trigeminal ganglion as well as in nerve fibers in the choroid. The immunoreactivities are present obviously as free catestatin and/or small-sized catestatin-containing fragments in the retina and ocular nerves but as large processed fragments as well, weak in the retina and more prominent in remaining ocular tissues, possibly in endothelial cells. This indicates that this peptide is a constituent of sensory neurons innervating the rat eye and the presence in amacrine cells in the retina is typical for neuropeptides. Catestatin is biologically highly active and might be of significance in the pathophysiology of the eye.