Independent circuits in the basal ganglia for the evaluation and selection of actions

The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (GPh) neurons, exists within the basal ganglia. The GPh neurons are glutamatergic and can drive the activity of the lateral habenula, which, in turn, provides an indirect inhibitory influence on midbrain dopamine neurons. We show that GPh neurons receive inhibitory input from the striosomal compartment of the striatum. The striosomal input can reduce the excitatory drive to the lateral habenula and, consequently, decrease the inhibition onto the dopaminergic system. Dopaminergic neurons, in turn, provide feedback that inhibits the GPh. In addition, GPh neurons receive direct projections from the pallium (cortex in mammals), which can increase the GPh activity to drive the lateral habenula to increase the inhibition of the neuromodulatory systems. This circuitry, thus, differs markedly from the "direct" and "indirect" pathways that regulate the pallidal (e.g., globus pallidus) output nuclei involved in the control of motion. Our results show that a distinct reward-evaluation circuit exists within the basal ganglia, in parallel to the direct and indirect pathways, which select actions. Our results suggest that these circuits are part of the fundamental blueprint that all vertebrates use to select actions and evaluate their outcome

Οι εξουσίες του δικαστηρίου στη πρωτοβάθμια δίκη

Η εργασία μελετά τη φύση, το σκοπό, το εύρος, τη lege latta (με βαρύνουσα έμφαση στη νομολογία), αλλά και τη lege ferenda εφαρμογή των εξουσιών του δικαστηρίου στη πρωτοβάθμια δίκη. Διαρθρώνεται σε πέντε κεφάλαια. Αρχικά, εξετάζεται το κοινό υπόβαθρο όλων των εξουσιών του πρωτοβάθμιου δικαστηρίου: ποια είναι η σημασία τους για τη πολιτική δίκη, πώς και πότε πρέπει να ασκούνται (υπό [II]). Στη συνέχεια, επιχειρείται η συστηματική καταγραφή και η έρευνα των επιμέρους εξουσιών, όπως αυτές ασκούνται αφενός, στη πρωτοβάθμια δίκη της αμφισβητούμενης δικαιοδοσίας (υπό [III]) και αφετέρου, σε εκείνη της εκούσιας δικαιοδοσίας (υπό [IV]). Ακολουθεί η εξέταση μιας ιδιαίτερης κατηγορίας εξουσιών, ήτοι, όσων συνέχονται με το νομικό και το νοητικό υλικό της δίκης (υπό [V]). Τέλος, στο Επίμετρο (υπό [VI]) εξάγονται ορισμένα συμπεράσματα και συνάμα, διατυπώνονται συγκεκριμένες προτάσεις, με στόχο την αποτελεσματικότερη άσκηση των εξουσιών.This thesis studies the nature, purpose, scope, the lege latta (with a special focus on case law), as well as the lege ferenda application of the court's powers in the first instance. It is structured in five chapters. First, the common background of all the powers of the trial court is examined: what is their relevance to civil proceedings, how and when they should be exercised (under [II]). Following that analysis, an attempt is made to systematically list and investigate the individual powers as they are exercised, on the one hand, in the first instance of contested jurisdiction (under [III]) and, on the other, in that of voluntary jurisdiction (under [IV]). Next, a particular category of powers is examined, namely those which are inherent in the legal material of the proceedings (under [V]). Finally, the Epilogue (under [VI]) draws a number of conclusions and, at the same time, makes specific proposals aiming at the more effective exercise of powers

Peripheral doses in patients undergoing Cyberknife treatment for intracranial lesions. A single centre experience

<p>Abstract</p> <p>Background</p> <p>Stereotactic radiosurgery/radiotherapy procedures are known to deliver a very high dose per fraction, and thus, the corresponding peripheral dose could be a limiting factor for the long term surviving patients. The aim of this clinical study was to measure the peripheral dose delivered to patients undergoing intracranial Cyberknife treatment, using the MOSFET dosimeters. The influence of the supplemental shielding, the number of monitor units and the collimator size to the peripheral dose were investigated.</p> <p>Methods</p> <p>MOSFET dosimeters were placed in preselected anatomical regions of the patient undergoing Cyberknife treatment, namely the thyroid gland, the nipple, the umbilicus and the pubic symphysis.</p> <p>Results</p> <p>The mean peripheral doses before the supplemental shielding was added to the Cyberknife unit were 51.79 cGy, 13.31 cGy and 10.07 cGy while after the shielding upgrade they were 38.40 cGy, 10.94 cGy, and 8.69 cGy, in the thyroid gland, the umbilicus and the pubic symphysis, respectively. The increase of the collimator size corresponds to an increase of the PD and becomes less significant at larger distances, indicating that at these distances the PD is predominate due to the head leakage and collimator scatter.</p> <p>Conclusion</p> <p>Weighting the effect of the number of monitor units and the collimator size can be effectively used during the optimization procedure in order to choose the most suitable treatment plan that will deliver the maximum dose to the tumor, while being compatible with the dose constraints for the surrounding organs at risk. Attention is required in defining the thyroid gland as a structure of avoidance in the treatment plan especially in patients with benign diseases.</p

Implications of interrupted eye–head gaze shifts for resettable integrator reset.

Abstract The neural circuit responsible for saccadic eye movements is generally thought to resemble a closed loop controller. Several models of the saccadic system assume that the feedback signal of such a controller is an efference copy of &quot;eye displacement&quot;, a neural estimate of the distance already travelled by the eyes, provided by the so-called &quot;resettable integrator&quot; (RI). The speed, with which the RI is reset, is thought to be fast or instantaneous by some authors and gradual by others. To examine this issue, psychophysicists have taken advantage of the target-distractor paradigm. Subjects engaged in it, are asked to look to only one of two stimuli (the &quot;target&quot;) and not to a distractor presented in the diametrically opposite location and they often generate movement sequences in which a gaze shift towards the &quot;distractor&quot; is followed by a second gaze shift to the &quot;target&quot;. The fact that the second movement is not systematically erroneous even when very short time intervals (about 5 ms) separate it from the first movement has been used to question the verisimilitude of gradual RI reset. To explore this matter we used a saccade-generating network that relies on a RI coupled to a head controller and a model of the rotational vestibulo-ocular reflex. An analysis of the activation functions of model units provides disproof by counterexample: &quot;targets&quot; can be accurately acquired even when the RI of the saccadic burst generator is not reset at all after the end of the first, interrupted eye-head gaze shift to the distractor and prior to the second, complete eye-head gaze shift to the &quot;target&quot;

The Lamprey Pallium Provides a Blueprint of the Mammalian Motor Projections from Cortex

SummaryBackgroundThe frontal lobe control of movement in mammals has been thought to be a specific function primarily related to the layered neocortex with its efferent connections. In contrast, we now show that the same basic organization is present even in one of the phylogenetically oldest vertebrates, the lamprey.ResultsStimulation of specific sites in the pallium/cortex evokes eye, trunk, locomotor, or oral movements. The pallial projection neurons target brainstem motor centers and basal ganglia subnuclei and have prominent dendrites extending into the outer molecular layer. They exhibit the characteristic features of pyramidal neurons and elicit monosynaptic glutamatergic excitatory postsynaptic potentials in output neurons of the optic tectum, reticulospinal neurons, and, as shown earlier, basal ganglia neurons.ConclusionsOur results demonstrate marked similarities in the efferent functional connectivity and control of motor behavior between the lamprey pallium and mammalian neocortex. Thus, the lamprey motor pallium/cortex represents an evolutionary blueprint of the corresponding mammalian system

Evaluation of quality of life outcomes following palliative radiotherapy in bone metastases : a literature review

Purpose: To assess the quality of life (QoL) following palliative radiotherapy (RT) in patients with painful bone metastases. Methods: A literature search limited to English-written publications was carried out, through the Cochrane Central Register of Controlled Trials (November 2018), OvidSP and PubMedCentral (1940-November 2018) databases. Subject headings and keywords included "quality of life"(QoL), "bone metastases", "palliative therapy", "pain" and "radiotherapy". Original articles, literature reviews, trials and meta-analyses revealing alterations in QoL post-RT using ratified measuring tools were examined. Studies referring to other types of metastases (e.g. brain metastases), or to other types of palliative therapy (e.g. the use of bisphosphonates alone), or focusing only on pain, or even reporting QoL only before or only after the use of RT were excluded. Results: Twenty four articles were selected from a total of 1360 articles. Seven trials proceeded to patients' randomization. The most commonly used tool to evaluate QoL was EORTC, followed by Brief Pain Inventory (BPI) and Edmonton Symptom Assessment System (ESAS) questionnaires. All studies showed improvement in symptoms and functional interference scores after RT. The QoL between responders (Rs) and non-responders (NRs) has been juxtaposed in 10 studies. Rs had a significant benefit in QoL in comparison with the NRs. Discussion: Palliative radiotherapy in painful bone metastases improves Rs' QoL

Two Novel Methods For The Determination Of The Number Of Components In Independent Components Analysis Models

Independent Components Analysis is a Blind Source Separation method that aims to find the pure source signals mixed together in unknown proportions in the observed signals under study. It does this by searching for factors which are mutually statistically independent. It can thus be classified among the latent-variable based methods. Like other methods based on latent variables, a careful investigation has to be carried out to find out which factors are significant and which are not. Therefore, it is important to dispose of a validation procedure to decide on the optimal number of independent components to include in the final model. This can be made complicated by the fact that two consecutive models may differ in the order and signs of similarly-indexed ICs. As well, the structure of the extracted sources can change as a function of the number of factors calculated. Two methods for determining the optimal number of ICs are proposed in this article and applied to simulated and real datasets to demonstrate their performance

Learning the Optimal Control of Coordinated Eye and Head Movements

Various optimality principles have been proposed to explain the characteristics of coordinated eye and head movements during visual orienting behavior. At the same time, researchers have suggested several neural models to underly the generation of saccades, but these do not include online learning as a mechanism of optimization. Here, we suggest an open-loop neural controller with a local adaptation mechanism that minimizes a proposed cost function. Simulations show that the characteristics of coordinated eye and head movements generated by this model match the experimental data in many aspects, including the relationship between amplitude, duration and peak velocity in head-restrained and the relative contribution of eye and head to the total gaze shift in head-free conditions. Our model is a first step towards bringing together an optimality principle and an incremental local learning mechanism into a unified control scheme for coordinated eye and head movements