We aimed to characterise the association of pulmonary hypertension due to hypoventilation and exercise capacity, and the haemodynamic and functional changes under noninvasive ventilation.A retrospective analysis was carried out to assess haemodynamics and functional capacity in 18 patients with daytime pulmonary hypertension, due to hypoventilation, at baseline and after 3 months of noninvasive ventilation.Patients presented with a mean¡SD pulmonary artery pressure of 49¡13 mmHg, preserved cardiac index (3.2¡0.66 L?min -1 ?m -2 ), 6-min walking distance of 303¡134 m and severely elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Mean pulmonary artery pressure correlated negatively with maximum work rate (R5 -0.72; p50.03) and 6-min walking distance (R5 -0.62; p50.01). Following noninvasive ventilation we found a significant reduction of mean pulmonary artery pressure (-18 mmHg; p,0.001) and NT-proBNP levels (-2110 pg?mL -1 ; p50.001), and improvement in the 6-min walking distance (+66 m; p50.008) and maximum work rate (+18 W; p50.028). Changes in work rate correlated inversely with pulmonary artery pressure (R5 -0.75; p50.031).In this specific cohort with hypoventilation and severe pulmonary hypertension, pulmonary hypertension was associated with reduced exercise capacity. Following noninvasive ventilation, haemodynamics and exercise capacity improved significantly. @ERSpublications Pulmonary hypertension due to alveolar hypoventilation is associated with functional impairment and improved by NIPPV
SUMMARYObjective: Juvenile myoclonic epilepsy (JME) has been considered to be a frontal variant of thalamocortical network dysfunction in epilepsy. Changes of c-aminobutyric acid (GABA)ergic neurotransmission may play a key role in this dysfunction. Magnetic resonance spectroscopy (MRS) is the only noninvasive method to measure GABA concentrations in different brain regions. We measured GABA and other metabolite concentrations in the thalamus and frontal lobe of patients with JME. Methods: A specific protocol was used for determining GABA concentrations in the thalamus, frontal lobe, and motor cortex contralateral to the handedness in 15 patients with JME and 15 age-matched controls. In addition, we measured concentrations of glutamate and glutamine, N-acetyl-aspartate (NAA), myoinositol, creatine, and choline using MRS with short echo time. JME-related concentration changes were analyzed comparing patients to controls, also considering potential effects of antiepileptic drugs. Results: In patients with JME, GABA and NAA were reduced in the thalamus (p = 0.03 and p = 0.02), whereas frontal GABA and glutamine were elevated (p = 0.046 and p = 0.03). MRS revealed reduced NAA in the thalamic gray matter contralateral to the handedness (p = 0.04 each). These changes were found consistently in patients treated with new antiepileptic drugs and with valproate, although the extent of metabolic changes differed between these treatments. Significance: Decreased thalamic and increased frontal GABA suggest a dysfunction of GABAergic neurotransmission in these brain regions of patients with JME. The NAA decrease in the gray matter of the thalamus may hint to a damage of GABAergic neurons, whereas frontal increase of GABA and its precursor glutamine may reflect increased density in GABAergic neurons due to subtle cortical disorganization in the thalamofrontal network.
The relation of selective attention to understanding of natural scenes has been subject to intense behavioral research and computational modeling, and gaze is often used as a proxy for such attention. The probability of an image region to be fixated typically correlates with its contrast. However, this relation does not imply a causal role of contrast. Rather, contrast may relate to an object's “importance” for a scene, which in turn drives attention. Here we operationalize importance by the probability that an observer names the object as characteristic for a scene. We modify luminance contrast of either a frequently named (“common”/“important”) or a rarely named (“rare”/“unimportant”) object, track the observers' eye movements during scene viewing and ask them to provide keywords describing the scene immediately after. When no object is modified relative to the background, important objects draw more fixations than unimportant ones. Increases of contrast make an object more likely to be fixated, irrespective of whether it was important for the original scene, while decreases in contrast have little effect on fixations. Any contrast modification makes originally unimportant objects more important for the scene. Finally, important objects are fixated more centrally than unimportant objects, irrespective of contrast. Our data suggest a dissociation between object importance (relevance for the scene) and salience (relevance for attention). If an object obeys natural scene statistics, important objects are also salient. However, when natural scene statistics are violated, importance and salience are differentially affected. Object salience is modulated by the expectation about object properties (e.g., formed by context or gist), and importance by the violation of such expectations. In addition, the dependence of fixated locations within an object on the object's importance suggests an analogy to the effects of word frequency on landing positions in reading.
Emotional instability, difficulties in social adjustment, and disinhibited behavior are the most common symptoms of the psychiatric comorbidities in juvenile myoclonic epilepsy (JME). This psychopathology has been associated with dysfunctions of mesial-frontal brain circuits. The present work is a first direct test of this link and adapted a paradigm for probing frontal circuits during empathy for pain. Neural and psychophysiological parameters of pain empathy were assessed by combining functional magnetic resonance imaging (fMRI) with simultaneous pupillometry in 15 JME patients and 15 matched healthy controls. In JME patients, we observed reduced neural activation of the anterior cingulate cortex (ACC), the anterior insula (AI), and the ventrolateral prefrontal cortex (VLPFC). This modulation was paralleled by reduced pupil dilation during empathy for pain in patients. At the same time, pupil dilation was positively related to neural activity of the ACC, AI, and VLPFC. In JME patients, the ACC additionally showed reduced functional connectivity with the primary and secondary somatosensory cortex, areas fundamentally implicated in processing the somatic cause of another's pain. Our results provide first evidence that alterations of mesial-frontal circuits directly affect psychosocial functioning in JME patients and draw a link of pupil dynamics with brain activity during emotional processing. The findings of reduced pain empathy related activation of the ACC and AI and aberrant functional integration of the ACC with somatosensory cortex areas provide further evidence for this network's role in social behavior and helps explaining the JME psychopathology and patients' difficulties in social adjustment.
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