Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation

Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks) that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks) were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli. © 2014 Balaban et al

Light-Induced Responses of Slow Oscillatory Neurons of the Rat Olivary Pretectal Nucleus

Background: The olivary pretectal nucleus (OPN) is a small midbrain structure responsible for pupil constriction in response to eye illumination. Previous electrophysiological studies have shown that OPN neurons code light intensity levels and therefore are called luminance detectors. Recently, we described an additional population of OPN neurons, characterized by a slow rhythmic pattern of action potentials in light-on conditions. Rhythmic patterns generated by these cells last for a period of approximately 2 minutes. Methodology: To answer whether oscillatory OPN cells are light responsive and whether oscillatory activity depends on retinal afferents, we performed in vivo electrophysiology experiments on urethane anaesthetized Wistar rats. Extracellular recordings were combined with changes in light conditions (light-dark-light transitions), brief light stimulations of the contralateral eye (diverse illuminances) or intraocular injections of tetrodotoxin (TTX). Conclusions: We found that oscillatory neurons were able to fire rhythmically in darkness and were responsive to eye illumination in a manner resembling that of luminance detectors. Their firing rate increased together with the strength of the light stimulation. In addition, during the train of light pulses, we observed two profiles of responses: oscillationpreserving and oscillation-disrupting, which occurred during low- and high-illuminance stimuli presentation respectively. Moreover, we have shown that contralateral retina inactivation eliminated oscillation and significantly reduced the firin

Psychological symptoms

Psychological symptoms are highly prevalent in people requiring palliative care. They are much more challenging to elicit, and more controversy exists about what is normal and what might require intervention than physical symptoms. There are significant issues in determining what is normal and what is not. Sadness, distress, anxiety, and depression can coexist and require careful assessment. Management of psychological symptoms and conditions can broadly be considered in terms of non-pharmacological and pharmacological therapies, “the talking and the drug therapies.” These are not mutually exclusive, and for people with limited energy, failing cognition, and limited time, some pragmatic decisions may be necessary. To be distressed and immobilized by emotion is not normal. Depression is not a normal part of dying. There should be discussion about the nature of psychological issues and conditions, explanation of common somatic symptoms, and a plan for intervention and support. The burden on the carer, both professional and personal, in such situations should not be underestimated.Gregory B. Crawfor

Quantitative Response Characteristics of Thermoreceptive and Nociceptive Lamina I Spinothalamic Neurons in the Cat

The physiological characteristics of antidromically identified lamina I spinothalamic (STT) neurons in the lumbosacral spinal cord were examined using quantitative thermal and mechanical stimuli in barbiturate-anesthetized cats. Cells belonging to the three main recognized classes were included based on categorization with natural cutaneous stimulation of the hindpaw: nociceptive-specific (NS), polymodal nociceptive (HPC), or thermoreceptive-specific (COOL) cells. The mean central conduction latencies of these classes differed significantly; NS = 130.8 ± 55.5 (SD) ms ( n= 100), HPC = 72.1 ± 28.0 ms ( n = 128), and COOL = 58.6 ± 25.3 ms ( n = 136), which correspond to conduction velocities of 2.5, 4.6, and 5.6 m/s. Based on recordings made prior to any noxious stimulation, the mean spontaneous discharge rates of these classes also differed: NS = 0.5 ± 0.7 imp/s ( n = 47), HPC = 0.9 ± 0.7 imp/s ( n = 59), and COOL = 3.3 ± 2.6 imp/s ( n = 107). Standard, quantitative, thermal stimulus sequences applied with a Peltier thermode were used to characterize the stimulus-response functions of 76 COOL cells, 47 HPC cells, and 37 NS cells. The COOL cells showed a very linear output from 34°C down to ∼15°C and a maintained plateau thereafter. The HPC cells showed a fairly linear but accelerating response to cold below a median threshold of ∼24°C and down to 9°C (measured at the skin-thermode interface with a thermode temperature of 2°C). The HPC cells and the NS cells both showed rapidly increasing, sigmoidal response functions to noxious heat with a fairly linear response between 45 and 53°C, but they had significantly different thresholds; half of the HPC cells were activated at ∼45.5°C and half of the NS cells at ∼43°C. The 20 HPC lamina I STT cells and 10 NS cells tested with quantitative pinch stimuli showed fairly linear responses above a threshold of ∼130 g/mm2 for HPC cells and a threshold of ∼100 g/mm2 for NS cells. All of these response functions compare well (across species) with the available data on the characteristics of thermoreceptive and nociceptive primary afferent fibers and the appropriate psychophysics in humans. Together these results support the concept that these classes of lamina I STT cells provide discrete sensory channels for the sensations of temperature and pain. </jats:p