Risk and risk prediction error signals in anterior insula

Most accounts of the function of anterior insula in the human brain refer to concepts that are difficult to formalize, such as feelings and awareness. The discovery of signals that reflect risk assessment and risk learning, however, opens the door to formal analysis. Hitherto, activations have been correlated with objective versions of risk and risk prediction error, but subjective versions (influenced by pessimism/optimism or risk aversion/tolerance) exist. Activation in closely related cortical structures has been found to be both objective (anterior cingulate cortex) and subjective (inferior frontal gyrus). For this quantitative analysis of uncertainty-induced neuronal activation to further understanding of insula’s role in feelings and awareness, however, formalization and documentation of the relation between uncertainty and feelings/awareness will be needed. One obvious starting point is the link with failure anxiety and error awareness.     

Role of the anterior insula in task-level control and focal attention

In humans, the anterior insula (aI) has been the topic of considerable research and ascribed a vast number of functional properties by way of neuroimaging and lesion studies. Here, we argue that the aI, at least in part, plays a role in domain-general attentional control and highlight studies (Dosenbach et al. 2006; Dosenbach et al. 2007) supporting this view. Additionally, we discuss a study (Ploran et al. 2007) that implicates aI in processes related to the capture of focal attention. Task-level control and focal attention may or may not reflect information processing supported by a single functional area (within the aI). Therefore, we apply a novel technique (Cohen et al. 2008) that utilizes resting state functional connectivity MRI (rs-fcMRI) to determine whether separable regions exist within the aI. rs-fcMRI mapping suggests that the ventral portion of the aI is distinguishable from more dorsal/anterior regions, which are themselves distinct from more posterior parts of the aI. When these regions are applied to functional MRI (fMRI) data, the ventral and dorsal/anterior regions support processes potentially related to both task-level control and focal attention, whereas the more posterior aI regions did not. These findings suggest that there exists some functional heterogeneity within aI that may subserve related but distinct types of higher-order cognitive processing.     

Conscious perception of errors and its relation to the anterior insula

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.     

Functional and effective connectivity of anterior insula in anorexia nervosa and bulimia nervosa

The anterior insula has been proposed to play a crucial role in eating disorders. However, it is still poorly understood how the anterior insula is involved in anorexia nervosa (AN) and bulimia nervosa (BN), which are characterized by opposite motivational responses to food. We applied a cue-reactivity paradigm using blood oxygen level-dependent functional magnetic resonance imaging in women with AN (N=18) and BN (N=20) and age-matched healthy controls (N=20). We defined the left anterior insula as a region-of-interest and performed seed-based functional connectivity and effective connectivity MRI analysis. In response to food images compared to non-food images, both the AN group and BN group demonstrated increased activity in the left anterior insula. In the AN group, the left anterior insula demonstrated significant interactions with the right insula and right inferior frontal gyrus. In the BN group, the left anterior insula demonstrated significant interactions with the medial orbitofrontal cortex. The distinct patterns of functional and effective connectivity of the anterior insula may contribute to the different clinical features of AN and BN.     

Electrophysiological evidence of sustained spatial attention effects over anterior cortex: Possible contribution of the anterior insula

Spatial attention can improve performance in terms of speed and accuracy; this advantage may be mediated by brain processes at both poststimulus (reactive) and prestimulus (proactive) stages. Here, we studied how visuospatial attention affects both proactive and reactive brain functions using event‐related potentials (ERPs). At reactive stage, effects of attention on parietal‐occipital components are well documented; little data are available on anterior components. Seventeen participants performed simple and discriminative response tasks, while voluntarily and steadily attending either the left or right visual hemifield throughout one block. Response speed was faster for the attended side. At ERP level, attending to one hemifield did not produce lateralization of proactive components—that is, the BP and the pN. As for poststimulus components, we confirmed the well‐known amplitude effects on the P1, N1, and P3. More interesting are results for the prefrontal components previously neglected in tasks modulating spatial attention. Previous studies suggest that these components reflect perceptual and sensory‐motor awareness (pN1 and pP1 components), and stimulus‐response mapping (pP2 component) associated to anterior insular activity. Spatial attention enhanced the pN1 and the pP1 amplitude but had no effect on the pP2. Overall, results extend knowledge on spatial attention, showing that sustained spatial attention affects the activity of anterior areas, such as the anterior insula, in addition to the known influence on occipital‐parietal areas. Top‐down spatial attention is likely mediated by increased sensory and sensory‐motor awareness for attended events; this effect is evident in reactive, not proactive, brain activity.     

Severe dose inaccuracies caused by an oxygen-antioxidant imbalance in normoxic polymer gel dosimeters

Two oxygen scavengers have been successfully tested to produce normoxic polymer gel dosimeters under normal atmospheric conditions. The first is ascorbic acid and the second is a chloride (also sulfate) salt of tetrakis (hydroxymethyl) phosphonium. These antioxidants, added to the dosimeter during gel preparation, chemically remove dissolved oxygen that otherwise inhibits propagation of the polymerization reaction during irradiation of the dosimeter. These gel dosimeters are radiosensitive after manufacture under normoxic conditions. However, we show herein that the accuracy of the dosimetric measurement is compromised due to chemical reactions of the antioxidant with radicals. In addition, we provide evidence that both antioxidant and oxygen act as radical scavengers that affect the amount of polymer formed in the gel dosimeter. This can result in important dose inaccuracies in both methacrylic acid-based and acrylamide-based normoxic dosimeter gels.     

Voxel-based morphometry reveals an association between aerobic capacity and grey matter density in the right anterior insula

This study investigated the effects of aerobic capacity on brain structure and memory performance. A sample of 33 healthy young subjects completed (i) assessment of aerobic capacity based on blood-lactate concentration, (ii) structural magnetic resonance imaging (MRI) scanning and analysis of grey matter density using voxel-based morphometry (VBM) and (iii) a range of memory tests. Memory performance was not significantly associated with aerobic capacity. After adjusting for effects of age, gender and total intracranial volume, cortical grey matter density in the right anterior insula was strongly correlated with aerobic capacity. These findings are in line with studies implicating the insula in the cortical control of cardiovascular processes during both exercise and autonomic arousal. Interindividual differences in aerobic capacity are thus reflected in structural differences in brain regions involved in cardiovascular control, resembling structural changes associated with certain cognitive or motor skills.     

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula,anterior cingulate,and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative “pain matrix” that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient’s expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a “pain matrix” and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient’s heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain’s conscious experience.     

Is coronary heart disease caused by an environmentally-induced chronic metabolic imbalance?

The hypothesis is put forward that coronary heart disease (CHD) arises from a chronic imbalance between anabolism and catabolism in the body, induced by the psychosocial environment and mediated through the central nervous system (CNS) and neuroendocrine system. Psychosocial demands increase periods of waking arousal and reduce the periods of rest necessary to compensate for the catabolic and degradative effects of activity. This prevents the complete healing of repeated arterial damage caused by haemodynamic stress, and enhances the accumulation of lipids into damaged areas in the arterial wall. This hypothesis can account for the significance of known CHD risk factors. A high-fat diet exacerbates the problem by increasing the rate of lipid accumulation into the arterial lesions. Cigarette smoking increases CHD risk by acting as a stimulant of the arousal-inducing neuroendocrine mechanisms, and moderate alcohol consumption reduces CHD risk by depressing CNS arousal. Physical activity enforces subsequent inactivity and compensatory anabolism through feedback mechanisms, which "overshoots" and produces a net anabolic effect that increases cardiovascular strength and general resistance to physical strain.     

Adenoma,adenocarcinoma and mixed carcinoid-adenocarcinoma arising in a small lesion of the colon

A unique tumor measuring 8 x 8 x 5 mm and composed of adenoma, adenocarcinoma and mixed carcinoid-adenocarcinoma arising in the ascending colon is reported. The mixed carcinoid-adenocarcinoma, in which adenocarcinomatous and carcinoid components intermingled, originated in the mucosa, penetrated the muscularis mucosa and extended into the submucosa. Immunohistochemically, carcinoid cells were positive for neuroendocrine markers and adenocarcinoma cells were intracytoplasmicly positive for carcinoembryonic antigen. Ultrastructurally, membrane-bound electron dense granules varying in shape, size and electron density were detected in the cytoplasm of carcinoid cells. No mutations of p53 and k-ras genes were detected in adenomatous, adenocarcinomatous or mixed carcinoid-adenocarcinoma components. The morphological appearances of the present case strongly suggests the histogenesis of this tumor in an adenoma-adenocarcinoma-carcinoid tumor sequence.     

Anorexia nervosa and the insula

Anorexia nervosa is a serious illness with major physical and psychological morbidity. It has largely been understood in terms of cultural and environmental explanations. However these are insufficient to explain the diverse clinical features of the illness, nor its rarity given the universality of sociocultural factors. Over the last 20 years, there has been a steady accumulation of neurobiological evidence requiring a re-formulation of current causal models. We now offer a new empirically-derived hypothesis implicating underlying rate-limiting dysfunction of insula cortex as a crucial risk factor for the development of anorexia nervosa. Supporting evidence for this hypothesis is drawn from anatomical and clinical research of insula cortex damage in humans and neuroscientific studies of relevant clinical features including taste, pain perception and reward processing. This hypothesis, if sustainable, would be the first fully to explain the disorder and predicts promising novel treatment possibilities including Cognitive Remediation and Motivation Enhancement Therapies. The knowledge that the challenging behaviours, so characteristic of AN, are the result of underlying cerebral dysfunction, rather than being purely volitional, could help to reduce the stigma patients experience and improve the therapeutic alliance in this poorly understood and difficult to treat disorder.     

Cerebrovascular lesion caused by activation of platelets and leukocytes and their correction by neurotropin

Department of Pharmacology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR K. V. Sudakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 10, pp. 391–393, October, 1991.     

Who is honest and why: Baseline activation in anterior insula predicts inter-individual differences in deceptive behavior

Humans engage in deceptive behavior that negatively affects others. The propensity to deceive is, however, characterized by vast inter-individual heterogeneity that is poorly understood. Attempts to investigate the origins of this heterogeneity have so far mainly relied on subjective measures and have shown little predictive power. Here, we used resting electroencephalography to measure objective and stable individual differences in neural baseline activation in combination with an ecologically valid deception paradigm. Results showed that task-independent baseline activation in the anterior insula, a brain area implicated in mapping internal bodily states and in representing emotional arousal and conscious feelings, predicts individuals’ propensity for deceptive behavior. The higher the neural baseline activation in this area is, the lower individuals’ propensity to deceive. Moreover, results provide evidence that high baseline activation in the anterior insula is associated with negative affect and dispositional tendencies to avoid aversive emotional situations. These results provide converging neural and psychological evidence that individuals might avoid a deceptive act due to a highly active negative emotional system which would make a deceptive act too stressful and bothersome.     

Natural genetic variation caused by small insertions and deletions in the human genome

Human genetic variation is expected to play a central role in personalized medicine. Yet only a fraction of the natural genetic variation that is harbored by humans has been discovered to date. Here we report almost 2 million small insertions and deletions (INDELs) that range from 1 bp to 10,000 bp in length in the genomes of 79 diverse humans. These variants include 819,363 small INDELs that map to human genes. Small INDELs frequently were found in the coding exons of these genes, and several lines of evidence indicate that such variation is a major determinant of human biological diversity. Microarray-based genotyping experiments revealed several interesting observations regarding the population genetics of small INDEL variation. For example, we found that many of our INDELs had high levels of linkage disequilibrium (LD) with both HapMap SNPs and with high-scoring SNPs from genome-wide association studies. Overall, our study indicates that small INDEL variation is likely to be a key factor underlying inherited traits and diseases in humans.     

Pancreatic lesion in newborn mice caused by Coxsackie B1 virus]

Changes in the pancreatic gland manifested by necrosis of excretory cells and marked atrophy of insulae with the loss of beta-cells producing insulin were observed experimentally in suckling mice infected with Coxsackie B1 virus. It is suggested that the above changes of the pancreas may be a model of human diseases caused by Coxsackie viruses, including a model of development of some cases of diabetes.