Conceptual flexibility in the human brain: dynamic recruitment of semantic maps from visual, motor, and motion-related areas

Abstract Traditionally, concepts are assumed to be situational invariant mental knowledge entities (conceptual stability), which are represented in a unitary brain system distinct from sensory and motor areas (amodality). However, accumulating evidence suggests that concepts are embodied in perception and action in that their conceptual features are stored within modality-specific semantic maps in the sensory and motor cortex. Nonetheless, the first traditional assumption of conceptual stability largely remains unquestioned. Here, we tested the notion of flexible concepts using functional magnetic resonance imaging and event-related potentials (ERPs) during the verification of two attribute types (visual, action-related) for words denoting artifactual and natural objects. Functional imaging predominantly revealed crossover interactions between category and attribute type in visual, motor, and motion-related brain areas, indicating that access to conceptual knowledge is strongly modulated by attribute type: Activity in these areas was highest when nondominant conceptual attributes had to be verified. ERPs indicated that these category-attribute interactions emerged as early as 116 msec after stimulus onset, suggesting that they reflect rapid access to conceptual features rather than postconceptual processing. Our results suggest that concepts are situational-dependent mental entities. They are composed of semantic features which are flexibly recruited from distributed, yet localized, semantic maps in modality-specific brain regions depending on contextual constraints.     

Production and characterisation of monoclonal antibodies against RAI3 and its expression in human breast cancer

Background  

RAI3 is an orphan G-protein coupled receptor (GPCR) that has been associated with malignancy and may play a role in the proliferation of breast cancer cells. Although its exact function in normal and malignant cells remains unclear and evidence supporting its role in oncogenesis is controversial, its abundant expression on the surface of cancer cells would make it an interesting target for the development of antibody-based therapeutics. To investigate the link with cancer and provide more evidence for its role, we carried out a systematic analysis of RAI3 expression in a large set of human breast cancer specimens.     

Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories

Rationale  In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. Objectives  The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. Methods  For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Results  Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Conclusions  Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction. C. von der Goltz and V. Vengeliene contributed equally to this work.     

A grading system for chronic hydrocephalus

A generally accepted grading system for patients suffering from chronic hydrocephalus has not been established yet. Therefore we designed a new grading system, which focuses on five symptom categories: gait disturbances, mental disorder, incontinence, headache, dizziness. For each category clearly circumscribed degrees of handicaps are defined. For each degree a value between 0-6 points is assigned in concordance to the severity of handicap. To get a generally accepted validation of the obstruction, the assigned values were oriented on the values provided in Germany to evaluate the degree of obstruction for insurances.[nl]In contrast to the established gradings of Stein and Langfitt and the Black Rating Scale our grading allows a more exact acquisition of the clinical presentation of a patient. Our experiences with the grading seemingly indicate also, that it is reliable. Because the grading allows an incorporation of measurable data such as psychometric analysis or gait analysis, our grading is useful as well for everydays' practice as for scientific purpose.     

Diffusion and perfusion MRI for the localisation of epileptogenic foci in drug-resistant epilepsy

Drug-resistant epilepsy is an important clinical challenge, both diagnostically and therapeutically. More and more surgical options are being considered, but precise presurgical assessment is necessary. We prospectively studied eight patients with drug-resistant epilepsy, who underwent clinical examination, single photon emission computed tomography (SPECT) and interictal MRI, including diffusion- and perfusion-weighted echoplanar sequences. Lesions suspected on SPECT of being epileptogenic showed mild hypoperfusion, while the diffusion-weighted MRI (DWI) revealed increased apparent diffusion coefficients relative to the other side. However, these abnormalities were not visible on the corresponding maps. We showed that DWI and perfusion-weighted MRI could be used confirm the characteristics and site of an epileptogenic area in patients with drug-resistant epilepsy.     

Lesion response of long-term and recently immigrated resident endoneurial macrophages in peripheral nerve explant cultures from bone marrow chimeric mice

Resident macrophages of the peripheral nervous system have recently been shown to respond rapidly to Wallerian degeneration before the influx of blood-derived macrophages. Because resident endoneurial macrophages are slowly but incompletely exchanged from the blood within 3 months, they could potentially comprise a heterogenous cell population consisting of long-term resident cells and more mobile cells undergoing turnover. We used bone marrow chimeric mice created by transplanting bone marrow from green fluorescent protein-transgenic mice into irradiated wildtype recipients to selectively analyse the response of these two resident macrophage populations to Wallerian degeneration in sciatic nerve explant cultures. In such nerves, recently immigrated macrophages exhibit green fluorescence whereas long-term resident macrophages do not. Studies in cultures from wildtype controls revealed rapid morphological changes of resident macrophages towards a bloated phenotype, a proliferative response resulting in a 3.7-fold increase of macrophage numbers over 2 weeks, and phagocytosis of myelin basic protein-immunoreactive myelin debris. When chimeric mice were analysed, both populations of resident endoneurial macrophages participated in morphological transformation, proliferation and phagocytosis. Quantitative studies revealed a stronger proliferative and phagocytic response in long-term resident endoneurial macrophages compared with recently immigrated macrophages. Our results point towards subtle, but not principal, differences between the two macrophage populations, which might indicate different stages of macrophage differentiation rather than the existence of entirely distinct endoneurial macrophage populations. The results further underline the versatility of resident endoneurial macrophages following peripheral nerve injury, which is reminiscent of the lesion response of microglial cells within the brain.     

A new method of ultrasonic guidance of neuroendoscopic procedures. Technical note

The authors present a newly designed device for ultrasonic guidance of neuroendoscopic procedures. It consists of a puncture adapter that attaches to a rigid endoscope having an outer diameter of 6 mm and is mounted on a small, bayonet-shaped ultrasound probe. This adapter directs the movement of the endoscope precisely within the ultrasonic field of view. The targeted region is identified by transdural insonation via an enlarged single burr-hole approach, and the endoscope is tracked in real time throughout its approach to the target. The procedure has been performed in 10 patients: endoscopic ventriculocystostomy in four cases; removal of a colloid cyst of the third ventricle in two cases; and intraventricular tumor biopsy, intraventricular tumor resection, third ventriculostomy, and removal of an intraventricular hematoma in one case each. The endoscope was depicted on ultrasonograms as a hyperechoic line without disturbing echoes and, consequently, the target (cyst, ventricle, or tumor) was safely identified in all but one case, in which intraventricular air hid a colloid cyst in the foramen of Monro. The method presented by the authors proved to be very effective in the guidance and control of neuroendoscopic procedures. Combining this method with image guidance is recommended to define the entry point of the endoscope precisely.