Input and output gain modulation by the lateral interhemispheric network in early visual cortex.

Neurons in the cerebral cortex are constantly integrating different types of inputs. Dependent on their origin, these inputs can be modulatory in many ways and, for example, change the neuron's responsiveness, sensitivity, or selectivity. To investigate the modulatory role of lateral input from the same level of cortical hierarchy, we recorded in the primary visual cortex of cats while controlling synaptic input from the corresponding contralateral hemisphere by reversible deactivation. Most neurons showed a pronounced decrease in their response to a visual stimulus of different contrasts and orientations. This indicates that the lateral network acts via an unspecific gain-setting mechanism, scaling the output of a neuron. However, the interhemispheric input also changed the contrast sensitivity of many neurons, thereby acting on the input. Such a contrast gain mechanism has important implications because it extends the role of the lateral network from pure response amplification to the modulation of a specific feature. Interestingly, for many neurons, we found a mixture of input and output gain modulation. Based on these findings and the known physiology of callosal connections in the visual system, we developed a simple model of lateral interhemispheric interactions. We conclude that the lateral network can act directly on its target, leading to a sensitivity change of a specific feature, while at the same time it also can act indirectly, leading to an unspecific gain setting. The relative contribution of these direct and indirect network effects determines the outcome for a particular neuron.

Dual atrioventricular nodal non-re-entrant tachycardia.

Dual atrioventricular nodal non-re-entrant tachycardia (DAVNNT), also known as 'double fire', has recently received more attention since it was demonstrated to mimic more common arrhythmias such as atrial premature beats, atrial fibrillation, and ventricular tachycardia. This is important, since mistaken differential diagnoses and the resulting therapeutic decisions have severe consequences for affected patients. DAVNNT is characterized by conduction characteristics of the atrioventricular (AV) node that leads to a double antegrade conduction of one sinoatrial nodal activity via the slow and fast AV nodal pathways. As a result, the most significant hint from an electrocardiogram (ECG) is a P wave followed by two narrow QRS complexes. Although DAVNNT is rather a rare arrhythmia, it now appears to be more common than previously thought. To date, 68 cases including 3 small single-centre observational studies accumulated over the last 5 years have demonstrated the feasibility and safety of radiofrequency catheter ablation for DAVNNT. Catheter ablation treats this arrhythmia effectively by modifying or eliminating slow pathway function. Here, we review the current state of DAVNNT knowledge systematically and address current challenges presented by this 'ECG chameleon from the AV node'.

An updated midline rule: visual callosal connections anticipate shape and motion in ongoing activity across the hemispheres.

It is generally thought that callosal connections (CCs) in primary visual cortices serve to unify the visual scenery parted in two at the vertical midline (VM). Here, we present evidence that this applies also to visual features that do not cross yet but might cross the VM in the future. During reversible deactivation of the contralateral visual cortex in cats, we observed that ipsilaterally recorded neurons close to the border between areas 17 and 18 receive selective excitatory callosal input on both ongoing and evoked activity. In detail, neurons responding well to a vertical Gabor patch moving away from the deactivated hemifield decreased prestimulus and stimulus-driven activity much more than those preferring motion toward the cooled hemifield. Further, activity of neurons responding to horizontal lines decreased more than the response to vertical lines. Embedding a single Gabor into a collinear line context selectively stabilized responses, especially when the context was limited to the intact hemifield. These findings indicate that CCs interconnect not only neurons coding for similar orientations but also for similar directions of motion. We conclude that CCs anticipate stimulus features that are potentially relevant for both hemifields (i.e., coherent motion but also collinear shape) because already prestimulus activity and activity to stimuli not crossing the VM revealed feature specificity. Finally, we hypothesize that intrinsic and callosal networks processing different orientations and directions are anisotropic close to the VM facilitating perceptual grouping along likely future motion or (shape) trajectories before the visual stimulus arrives.

Pulse detection with a single accelerometer placed at the carotid artery: Performance in a real-life diagnostic test during acute hypotension.

Pulse detection via palpation is a basic and essential procedure in daily medical practice. We have been investigating the performance of a single accelerometer placed above the carotid artery, which is one of the recommended locations for manual palpation. A low-cost sensor attached by an adhesive measures accelerations due to carotid dilatations and whole body vibrations. A real-time demonstrator has been developed to classify 10 second- windows in "Pulse", "Motion" and "No Pulse" and to infer pulse rate. Data were obtained during a scheduled head-up tilt table test (HUTT). Our results show for a subgroup of 10 patients with acute hypotension a wide spread of "good" signal coverage ranging from as low as 37% up to 100%. Key factors compromising the performance in HUTT are motion artifacts, arrhythmias, sensor placement and sensor-skin coupling. In conclusion, pulse detection with a single accelerometer is sufficiently accurate, if good signal coverage can be achieved.

[Dual AV nodal nonreentry tachycardia (DAVNNT): unrecognized differential diagnosis with far-reaching consequences]. / Duale AV-nodale Nicht-Reentry-Tachykardie: Verkannte Differenzialdiagnose mit weitreichenden Konsequenzen?

BACKGROUND: The dual atrioventricular nodal nonreentry tachycardia (DAVNNT) is a rare form of tachycardia which occurs due to a time delayed double antegrade conduction via the slow and fast atrioventricular nodal pathways. Its epidemiology is not known so far. The aim of this article is to present the clinical findings in a series of patients with DAVNNT. MATERIALS AND METHODS: We retrospectively analyzed our database of patients who successfully underwent radiofrequency catheter ablation between January 2012 and March 2013 due to diagnosed supraventricular tachycardia. RESULTS: In 3 out of 231 patients DAVNNT could be successfully treated by slow pathway modulation/ablation. Patients presented with widely varying symptoms including syncope, palpitations which had been mistaken as atrial fibrillation, and inappropriate defibrillator shocks due to suspected ventricular tachycardia. CONCLUSIONS: The DAVNNT seems to be more common than previously thought. This important differential diagnosis needs to be taken into consideration as slow pathway modulation can be curative while a misdiagnosis, such as atrial fibrillation or ventricular tachycardia might result in over-treatment in patients with this arrhythmia.

Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based phenotypic assay.

Stem cells, through their ability to both self-renew and differentiate, can produce a virtually limitless supply of specialized cells that behave comparably to primary cells. We took advantage of this property to develop an assay for small-molecule-based neuroprotection using stem-cell-derived motor neurons and astrocytes, together with activated microglia as a stress paradigm. Here, we report on the discovery of hit compounds from a screen of more than 10,000 small molecules. These compounds act through diverse pathways, including the inhibition of nitric oxide production by microglia, activation of the Nrf2 pathway in microglia and astrocytes, and direct protection of neurons from nitric-oxide-induced degeneration. We confirm the activity of these compounds using human neurons. Because microglial cells are activated in many neurological disorders, our hit compounds could be ideal starting points for the development of new drugs to treat various neurodegenerative and neurological diseases.