The role of EphrinA for the retinotopic map formation in mouse visual cortex

The mammalian cortex is arranged into a number of areas that represent our sensory, motor and cognitive functions. A characteristic feature of many sensory areas is their precise topographic organisation: in the same way as the “homunculus” in the somatosensory cortex represents the entire body surface, in the visual system retinal inputs are mapped topographically; i.e. spatial relationships in the visual field are maintained all the way to the primary visual cortex (area 17). The formation of such maps has been shown to depend on specific guidance molecules that are recognised by outgrowing axons. One major family of molecules implicated in axonal guidance and map formation are the ephrin ligands and their Eph receptors. These molecules have been shown to contribute to topographic mapping in several mammalian brain systems including the retinotectal and retinogeniculate projection. Much less is known about mechanisms that are important for the formation of topographic maps in the cortex. This study has investigated the role of ephrin-A ligands for the formation of the retinotopic map in the primary visual cortex of mice with optical imaging of intrinsic signals. Using grating stimuli presented at adjacent but non-overlapping positions within the visual field, I was able to visualise the retinotopic map in area 17 and resolve the pattern of retinotopic activity with high precision and reliability. In order to examine the influence of ephrinA ligands on cortical map formation, I used transgenic mice with a functional ephrin-A deficiency. These mice have a cDNA inserted into their genome that codes for a receptor antibody, which blocks all ephrin-As. I found an ordered retinotopic map in both wild type and transgenic mice, suggesting that other molecules or mechanisms apart from ephrin-A ligands are responsible for guiding thalamic axons to their target in the primary visual cortex. However, I also detected some important differences between the two genotypes: in ephrin-A knockout mice, the cortical representation of the peripheral visual field is compressed while that of the central field is expanded. Moreover, I applied the same paradigms to mice of about two weeks of age showing similar but evidently stronger effects in the young ephrin-A deficient mice, implying that initial errors in map formation can be corrected later in development. This observation suggests that the formation of topographic maps is not only regulated by genes that are expressed early in development, but that activity dependent neuronal plasticity plays a fundamental role, too.Die Großhirnrinde der Säuger ist in eine große Zahl unterschiedlicher Areale unterteilt, die Sitz unserer sensorischen, motorischen und kognitiven Funktionen sind. Charakteristisch für viele sensorische Areale ist ihre sehr genaue topographische Organisation: So wie z.B. im somatosensorischen Kortex der „Homunculus“ die gesamte Körperoberfläche repräsentiert, sind auch im visuellen System die retinalen Eingänge topographisch organisiert, d.h. die räumlichen Beziehungen zwischen Punkten im visuellen Feld bleiben auf dem gesamten Weg von der Netzhaut bis zum primären visuellen Kortex (Area 17) erhalten. Es konnte gezeigt werden, dass die Entwicklung solcher Karten durch die räumliche Verteilung von Wegfindungsmolekülen gesteuert wird, die von auswachsenden Axonen gelesen werden. Eine für die Lenkung von Axonen und die Entstehung topographischer Karten wichtige Molekülfamilie ist die der Ephrin Liganden und ihrer Eph Rezeptoren. Ihre Rolle ist insbesondere für die retinalen Projektionen ins Mittel- und Zwischenhirn etabliert. Viel weniger wissen wir darüber, welche Mechanismen für die Entstehung topographischer Karten im Kortex wichtig sind. In der vorliegenden Arbeit habe ich die Rolle der EphrinA Liganden bei der Entstehung der retinotopen Karte im primären visuellen Kortex der Maus mit optischen Ableitungen von intrinsischen Signalen untersucht. Mit Hilfe visueller Stimuli, die an benachbarten aber nicht überlappenden Positionen im Gesichtsfeld präsentiert wurden, konnte ich die retinotope Karte in Area 17 mit hoher Auflösung sichtbar machen. Um den Einfluss der Ephrin-A Liganden zu untersuchen, verwendete ich eine transgene Maus mit einer funktionellen Ephrin-A Defizienz. Bei dieser Maus beruht die Blockade aller A-Ephrine auf der Insertion einer cDNA in das Genom, die für einen Rezeptor-Antikörper kodiert, der an alle A-Ephrine bindet. Sowohl in Wildtypmäusen als auch in diesen transgenen Mäusen konnte ich eine geordnete retinotope Karte ableiten, was zunächst darauf hinweist, dass neben den Ephrin-A Liganden auch andere Moleküle oder Mechanismen für die Lenkung der thalamischen Axone zu ihren Zielorten im visuellen Kortex verantwortlich sind. Ich habe jedoch auch einige wichtige Unterschiede zwischen den zwei Genotypen gefunden: die kortikale Repräsentation des peripheren Gesichtsfeldes ist bei den Ephrin-A defizienten Mäusen komprimiert, während die des zentralen Gesichtsfeldes vergrössert ist. Optische Ableitungen der retinotopen Karte im visuellen Kortex von jungen, etwa 2 Wochen alten Mäusen zeigten interessanterweise deutlich stärkere Effekte. Dies legt nahe, dass initiale Fehler in der Karte im späteren Verlauf der Entwicklung korrigiert werden können. Diese Beobachtung weist darauf hin dass die Entstehung topographischer Karten nicht nur durch früh in der Entwicklung exprimierte Gene reguliert wird, sondern dass aktivitätsabhängige neuronale Plastizität ebenfalls eine wichtige Rolle spielt

Transcranial modulation of brain oscillatory responses: A concurrent tDCS–MEG investigation

The physiological mechanisms underlying the effects of transcranial direct current stimulation (tDCS) are still largely unknown. To provide novel insight into the neurobiology of tDCS, stimulation was applied concurrently with Magnetoencephalography (MEG). This occurred while participants completed a visuomotor task before, during and after stimulation. Motor beta band (15–30 Hz) and visual gamma band (30–80 Hz) responses were localised using Synthetic Aperture Magnetometry (SAM). The resulting evoked and induced brain oscillatory responses were analysed. A significant reduction of average power was observed in the visual gamma band for anodal compared to sham stimulation. The magnitude of motor evoked responses was also demonstrated to be modulated by anodal tDCS. These results highlight that MEG can be used to draw inferences on the cortical mechanisms of DC stimulation

Stimulating somatosensory psychophysics: a double-blind, sham-controlled study of the neurobiological mechanisms of tDCS

In this study, the influence of tDCS on vibrotactile adaptation is investigated. Double-blind tDCS (Anodal/Sham) of 1 mA was delivered for 600 s to electrodes positioned in a somatosensory/contralateral orbit montage. Stimulation was applied between blocks of the implemented amplitude discrimination tasks. Amplitude discrimination thresholds were significantly degraded during adaptation trials, compared to those achieved at baseline but tDCS failed to modify task performance. Using Bayesian statistics, this finding was revealed to constitute substantial evidence for the null hypothesis. The failure of DC stimulation to alter performance is discussed in the context of several factors that may have confounded the induction of changes in cortical plasticity

Inpatients with neurologic disease referred for palliative care consultation.

OBJECTIVES: To compare characteristics and needs of inpatients with neurologic disease to those with cancer referred for palliative care (PC) consultation. METHODS: This prospective cohort study used data collected by the Palliative Care Quality Network from January 2013 until December 2016. We compared demographics, reasons for consultation, discharge disposition, Palliative Performance Scale (PPS) score, and outcomes of care among patients with a primary diagnosis of neurologic disease vs cancer. RESULTS: The most common reason for PC consultation in all patients was assistance with goals of care and advanced care planning. PC consultation was less often requested for pain and symptom management in patients with neurologic disease compared to patients with cancer (13.7% vs 43%, odds ratio 0.3) and more often for assistance with transition to comfort measures only and withdrawal of life-sustaining treatment (19.1% vs 7.1%, odds ratio 1.3). Patients with cancer had higher PPS scores (42.1% vs 23.4%) and were more likely to be discharged home from the hospital, while patients with neurologic disease were more likely to die in hospital. CONCLUSIONS: Patients with neurologic disease as a reason for PC consultation are more in need of end-of-life care planning and more likely to die in the hospital than those with cancer, suggesting that targeted approaches may best address the needs of each patient population. Our results can direct further research and education in neuropalliative care

Clinical Use of Surface Electromyography to Track Acute Upper Extremity Muscle Recovery after Stroke: A Descriptive Case Study of a Single Patient

Arm recovery varies greatly among stroke survivors. Wearable surface electromyography (sEMG) sensors have been used to track recovery in research; however, sEMG is rarely used within acute and subacute clinical settings. The purpose of this case study was to describe the use of wireless sEMG sensors to examine changes in muscle activity during acute and subacute phases of stroke recovery, and understand the participant’s perceptions of sEMG monitoring. Beginning three days post-stroke, one stroke survivor wore five wireless sEMG sensors on his involved arm for three to four hours, every one to three days. Muscle activity was tracked during routine care in the acute setting through discharge from inpatient rehabilitation. Three- and eight-month follow-up sessions were completed in the community. Activity logs were completed each session, and a semi-structured interview occurred at the final session. The longitudinal monitoring of muscle and movement recovery in the clinic and community was feasible using sEMG sensors. The participant and medical team felt monitoring was unobtrusive, interesting, and motivating for recovery, but desired greater in-session feedback to inform rehabilitation. While barriers in equipment and signal quality still exist, capitalizing on wearable sensing technology in the clinic holds promise for enabling personalized stroke recovery