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Heiss W.-D.,Max Planck Institute for Neurological Research
Neuroscience Bulletin | Year: 2014

Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large (“malignant”) infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases. © 2014, Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg. Source

Thiel A.,McGill University | Heiss W.-D.,Max Planck Institute for Neurological Research
Stroke | Year: 2011

Activated microglia is one of the most important cellular components of poststroke neuroinflammation, which occurs early in the area of the infarct but also in remote regions with fiber tract connections to the site of the primary lesion. The development of different radioligands for the translocator protein, a mitochondrial membrane protein expressed in microglial cells when they transform from the resting to the activated state, allows to study the temporal dynamics of this cellular neuroinflammatory component in vivo in animal models and human stroke using positron emission tomography. In this article, we review the advantage and limitations of current and future methods for microglia imaging as well as new results of multimodal imaging approaches in clinical stroke, which try to combine microglia imaging with diffusion tensor imaging to investigate the clinical relevance of remote microglia activation along fiber tracts for poststroke recovery. © 2011 American Heart Association, Inc. Source

Heiss W.-D.,Max Planck Institute for Neurological Research
International Journal of Stroke | Year: 2010

The 'penumbra' is a concept coined in animal experiments suggesting that functionally impaired tissue can survive and recover if sufficient reperfusion is re-established within a limited time period, which depends on the level of residual flow. In an ischaemic territory, irreversible damage progresses over time from the centre of the most severe flow reduction to the periphery with less disturbed perfusion. This centrifugal progression of irreversible tissue damage is characterised by a complex cascade of interconnected electrophysiological, molecular, metabolic and perfusion disturbances. Waves of depolarisations, the peri infarct spreading depressions, inducing activation of ion pumps and liberation of excitatory transmitters play an important role in the drastically increased metabolic demand during reduced oxygen supply causing hypoxic tissue changes and lactacidosis, which further damage the tissue. Positron emission tomography allows the quantification of regional cerebral blood flow, the regional metabolic rate for oxygen and the regional oxygen extraction fraction, which can be used to identify regions with a critical reduction in these physiologic variables as indicators of penumbra and irreversible damage within ischaemic territories in animal models and patients with stroke. These positron emission tomography methods require arterial blood sampling and due to the complex logistics involved, are limited for routine application. Therefore, newer tracers were developed for the noninvasive detection of irreversible tissue damage (flumazenil) and of hypoxic tissue changes (fluoromisonidazole). As a widely applicable clinical tool, diffusion/perfusion-weighted magnetic resonance imaging is used; the 'mismatch' between perfusion and diffusion changes serves as a surrogate marker of the penumbra. However, in comparative studies of magnetic resonance imaging and positron emission tomography, diffusion-weighted imaging showed a high false-positive rate of irreversible damage, and the perfusion-weighted-diffusion-weighted mismatch overestimated the penumbra as defined by positron emission tomography. Advanced analytical procedures of magnetic resonance imaging data may improve the reliability of these surrogate markers but should be validated with quantitative procedures. © 2010 The Authors. Journal compilation © 2010 World Stroke Organization. Source

Ullsperger M.,Max Planck Institute for Neurological Research
Brain structure & function | Year: 2010

To detect erroneous action outcomes is necessary for flexible adjustments and therefore a prerequisite of adaptive, goal-directed behavior. While performance monitoring has been studied intensively over two decades and a vast amount of knowledge on its functional neuroanatomy has been gathered, much less is known about conscious error perception, often referred to as error awareness. Here, we review and discuss the conditions under which error awareness occurs, its neural correlates and underlying functional neuroanatomy. We focus specifically on the anterior insula, which has been shown to be (a) reliably activated during performance monitoring and (b) modulated by error awareness. Anterior insular activity appears to be closely related to autonomic responses associated with consciously perceived errors, although the causality and directions of these relationships still needs to be unraveled. We discuss the role of the anterior insula in generating versus perceiving autonomic responses and as a key player in balancing effortful task-related and resting-state activity. We suggest that errors elicit reactions highly reminiscent of an orienting response and may thus induce the autonomic arousal needed to recruit the required mental and physical resources. We discuss the role of norepinephrine activity in eliciting sufficiently strong central and autonomic nervous responses enabling the necessary adaptation as well as conscious error perception. Source

Wessel J.R.,University of California at San Diego | Wessel J.R.,Max Planck Institute for Neurological Research
Frontiers in Human Neuroscience | Year: 2012

From its discovery in the early 1990s until this day, the error-related negativity (ERN) remains the most widely investigated electrophysiological index of cortical error processing. When researchers began addressing the electrophysiology of subjective error awareness more than a decade ago, the role of the ERN, alongside the subsequently occurring error positivity (Pe), was an obvious locus of attention. However, the first two studies explicitly addressing the role of error-related event-related brain potentials (ERPs) would already set the tone for what still remains a controversy today: in contrast to the clear-cut findings that link the amplitude of the Pe to error awareness, the association between ERN amplitude and error awareness is vastly unclear. An initial study reported significant differences in ERN amplitude with respect to subjective error awareness, whereas the second failed to report this result, leading to a myriad of follow-up studies that seemed to back up or contradict either view. Here, I review those studies that explicitly dealt with the role of the error-related ERPs in subjective error awareness, and try to explain the differences in reported effects of error awareness on ERN amplitude. From the point of view presented here, different findings between studies can be explained by disparities in experimental design and data analysis, specifically with respect to the quantification of subjective error awareness. Based on the review of these results, I will then try to embed the error-related negativity into a widely known model of the implementation of access consciousness in the brain, the global neuronal workspace (GNW) model, and speculate as the ERN's potential role in such a framework. At last, I will outline future challenges in the investigation of the cortical electrophysiology of error awareness, and offer some suggestions on how they could potentially be addressed. © 2012 Wessel. Source

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