Left Posterior Insula Research Articles

Lateralization of affective processing in the insula

Evidence from electrophysiological and functional neuroimaging studies has suggested strong lateralization of affective processing within the insular cortices; however, little is known about the spatial location of these processes in these regions. Using quantitative meta-analytic methods the laterality of: (1) emotional processing; (2) stimulus valence (positive vs. negative); (3) perception vs. experience of emotion; and (4) sex-differences were assessed using the data from 143 functional magnetic resonance imaging studies. Activation in response to all emotional stimuli occurred in bilateral anterior and mid-insula, and the left posterior insula. Positive emotional stimuli were associated with activation in the left anterior and mid-insula, while negative emotional stimuli activated bilateral anterior and mid-insula. Activation in response to the perception and experience of emotions was highest in bilateral anterior insula, and within the mid and posterior insula it was left lateralized. In males, emotional stimuli predominantly activated the left anterior/mid-insula and right posterior insula, whereas females activated bilateral anterior insula and the left mid and posterior insula. Spatial distinctions observed in emotional processing and its subcategories can provide a comprehensive account of the role of the insular cortices in affect processing, which could aid in understanding deficits seen in psychiatric or developmental disorders.

A preliminary fMRI study on the effects of burning perception on cognitive-related brain networks in burning mouth syndrome patients

Burning mouth syndrome (BMS) is a rare, idiopathic pain condition characterized by bilateral-burning sensations of tongue, lips, and oral mucosa. Most BMS patients are relatively pain free in the mornings, while pain and burning intensity increase substantially by late afternoon. We hypothesized that when BMS symptoms are strongest, patients activate more brain areas to a greater extent while performing a cognitive task, despite comparable performance levels. Seven women with BMS (mean age 54, range 40-67) underwent two sessions in one day (early morning and late afternoon). Participants performed the multi-source interference task (MSIT) with two levels of difficulty (low and high cognitive load) during an fMRI scan (3T Siemens Tim-Trio). Questionnaires completed at the two sessions included: short form McGill Pain Questionnaire; State-Trait Anxiety Inventory; Profile of Mood States. Patients also rated their BMS pain intensity and burning intensity on a numerical rating scale of 0-10. Patients had significantly higher burning intensity ratings in the afternoon sessions, but no significant change in pain intensity, anxiety, or mood, and there was no difference in MSIT performance between sessions. MSIT performance activated a cognitive network including bilateral premotor, midcingulate, posterior parietal, anterior insula, visual motion area (MT+), and cerebellum. In the high cognitive load condition, patients had increased activity in the afternoon in left caudate. Three additional clusters that were marginally significant included bilateral posterior/mid insula, and brainstem/periaqueductal gray (PAG). Increased activity in these regions was not correlated with changes in burning intensity or any other measured behavioral variable. Interestingly, we also found significantly increased activity during the afternoon session for the low cognitive load condition in left mid and posterior insula, left thalamus, and bilateral paracentral lobule. Our findings thus suggest that ongoing burning pain can influence cognitive networks, and do so differentially depending on the difficulty of the task. Burning mouth syndrome (BMS) is a rare, idiopathic pain condition characterized by bilateral-burning sensations of tongue, lips, and oral mucosa. Most BMS patients are relatively pain free in the mornings, while pain and burning intensity increase substantially by late afternoon. We hypothesized that when BMS symptoms are strongest, patients activate more brain areas to a greater extent while performing a cognitive task, despite comparable performance levels. Seven women with BMS (mean age 54, range 40-67) underwent two sessions in one day (early morning and late afternoon). Participants performed the multi-source interference task (MSIT) with two levels of difficulty (low and high cognitive load) during an fMRI scan (3T Siemens Tim-Trio). Questionnaires completed at the two sessions included: short form McGill Pain Questionnaire; State-Trait Anxiety Inventory; Profile of Mood States. Patients also rated their BMS pain intensity and burning intensity on a numerical rating scale of 0-10. Patients had significantly higher burning intensity ratings in the afternoon sessions, but no significant change in pain intensity, anxiety, or mood, and there was no difference in MSIT performance between sessions. MSIT performance activated a cognitive network including bilateral premotor, midcingulate, posterior parietal, anterior insula, visual motion area (MT+), and cerebellum. In the high cognitive load condition, patients had increased activity in the afternoon in left caudate. Three additional clusters that were marginally significant included bilateral posterior/mid insula, and brainstem/periaqueductal gray (PAG). Increased activity in these regions was not correlated with changes in burning intensity or any other measured behavioral variable. Interestingly, we also found significantly increased activity during the afternoon session for the low cognitive load condition in left mid and posterior insula, left thalamus, and bilateral paracentral lobule. Our findings thus suggest that ongoing burning pain can influence cognitive networks, and do so differentially depending on the difficulty of the task.

Real-time imaging of brain areas involved in the generation of spontaneous skin sympathetic nerve activity at rest

In thermoneutral conditions resting skin sympathetic nerve activity (SSNA) is related to the level of arousal and emotional state. The brain regions responsible for the generation of spontaneous SSNA are not known. In the present study we used concurrent recordings of SSNA and brain activity in awake humans to identify cortical and subcortical areas involved in the generation of spontaneous SSNA in 13 healthy subjects. Blood oxygen level dependent signal intensity increases covaried with SSNA in the left thalamus in the region of the ventromedial nucleus, the left posterior and right anterior insula, the right orbitofrontal cortex, the right frontal cortex, and bilaterally in the mid-cingulate cortex and precuneus. Functional connectivity analysis revealed a strong positive coupling between the right orbitofrontal cortex and the right anterior insula. Furthermore, signal intensity changes within the precuneus were temporally coupled to the left anterior and posterior insula, cerebellum, cingulate cortex and thalamus. It has been hypothesized that these brain regions monitor the internal state of the body and may regulate emotional state changes. Our results show that the activities within these regions are also correlated to spontaneous fluctuations in SSNA.

Distinct illusory own-body perceptions caused by damage to posterior insula and extrastriate cortex

Recent research in cognitive neuroscience using virtual reality, robotic technology and brain imaging has linked self-consciousness to the processing and integration of multisensory bodily signals. This work on bodily self-consciousness has implicated the temporo-parietal, premotor and extrastriate cortex and partly originated in work on neurological patients with different disorders of bodily self-consciousness. One class of such disorders is autoscopic phenomena, which are defined as illusory own-body perceptions, during which patients experience the visual illusory reduplication of their own body in extrapersonal space. Three main forms of autoscopic phenomena have been defined. During autoscopic hallucinations, a second own body is seen without any changes in bodily self-consciousness. During out-of-body experiences, the second own body is seen from an elevated perspective and location associated with disembodiment. During heautoscopy, subjects report strong self-identification with the second own body, often associated with the experience of existing at and perceiving the world from two places at the same time. Although it has been proposed that each autoscopic phenomenon is associated with different impairments of bodily self-consciousness, past research on neurological patients and the development of experimental paradigms for the study of bodily self-consciousness has focused on out-of-body experiences and the association with temporo-parietal cortex. Here, we performed quantitative lesion analysis in the-to date-largest group of patients with autoscopic hallucination and heautoscopy and compared the location of brain damage with those of control patients suffering from complex visual hallucinations. We found that heautoscopy was associated with lesions to the left posterior insula, and that autoscopic hallucinations were associated with damage to the right occipital cortex. Autoscopic hallucination and heautoscopy were further associated with distinct symptoms and deficits. The present data suggest that the autoscopic hallucination is a visuo-somatosensory deficit implicating extrastriate cortex and is, despite the visual hallucination of the own body, not associated with major deficits in bodily self-consciousness. Based on the symptoms and deficits in patients with heautoscopy and the implication of the left posterior insula, we suggest that abnormal bodily self-consciousness during heautoscopy is caused by a breakdown of self-other discrimination regarding affective somatosensory experience due to a disintegration of visuo-somatosensory signals with emotional (and/or interoceptive) bodily signals. These brain mechanisms are distinct from those described for out-of-body experiences. The present data extend previous models of autoscopic phenomena and provide clinical evidence for the importance of emotional and interoceptive signal processing in the posterior insula in relation to bodily self-consciousness.

Regional cerebral changes and functional connectivity during the observation of negative emotional stimuli in subjects with post-traumatic stress disorder

Patients with post-traumatic stress disorder (PTSD) exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional dysfunction. The aim of this study was to investigate the functional connectivity between the areas activated during emotional processing of negative stimuli in a sample of individuals affected by PTSD compared to a group of healthy subjects. Ten subjects with PTSD (who survived the L'Aquila 2009 earthquake) and ten healthy controls underwent fMRI during which the participants observed 80 images: 40 pictures with negative emotional valence and 40 neutral (scrambled) stimuli. A higher activation was found in the left posterior (LP) insula for PTSD group and in the ventromedial prefrontal cortex (vmPFC) for the healthy group. Two sets of Granger causality modeling analyses were performed to examine the directed influence from LP-insula and vmPFC to other brain regions. Activity in the vmPFC in the healthy group while observing negative stimuli predicted activity in several subcortical regions and insula, while in the PTSD group the LP-insula exerted a positive directed influence on several cortical regions. The hyperactivation in PTSD subjects of subcortical areas such as the insula would underlie the emotional, social, and relational difficulties of PTSD patients.

Altered Cognitive Function of Prefrontal Cortex During Error Feedback in Patients With Irritable Bowel Syndrome, Based on fMRI and Dynamic Causal Modeling

Patients with irritable bowel syndrome (IBS) have increased activity in the insula and reduced activation of the dorsolateral prefrontal cortex (DLPFC) in response to visceral stimulation. We investigated whether they have latent impairments in cognitive flexibility because of dysfunction in the DLPFC and insula and altered connectivity between brain regions. We analyzed data from 30 individuals with IBS (15 men; age, 21.7 ± 3.0 y) diagnosed based on Rome III criteria, along with 30 individuals matched for age, sex, and education level (controls). Event-related functional magnetic resonance imaging of the brain was performed to evaluate cognitive flexibility and was assessed by the Wisconsin Card Sorting Test, in which subjects are allowed to change choice criteria, defined as set-shifting in response to error feedback. Brain images were analyzed with statistical parametric mapping 5 and 8 software and dynamic causal modeling. Subjects with IBS had significantly more Nelson perseverative errors (P < .05) and set-maintenance difficulties (P < .05) than controls. They also showed significantly decreased activity of the right DLPFC (Brodmann's area 9; P < .001) and right hippocampus (P < .001), and significantly increased activity of the left posterior insula (P < .001) at error feedback during set-shifting. Dynamic causal modeling analysis during set-shifting revealed significantly less connectivity from the DLPFC to pre-supplementary motor area in subjects with IBS, compared with controls (P = .012). Individuals with IBS have latent impairments in cognitive flexibility as a result of altered activity of the DLPFC, insula, and hippocampus, and impaired connectivity between the DLPFC and pre-supplementary motor area.

Insular dysfunction and descending pain inhibition in anorexia nervosa

Reduced perception of pain is a well-established phenomenon in patients with anorexia nervosa (AN). We tested the hypothesis that altered processing of pain within the insula might account for reduced perception of pain. Heat pain thresholds were obtained in nineteen patients with AN and matched controls. Thereafter, a thermode was used to deliver thermal painful stimuli to the right arm during functional magnetic resonance imaging (fMRI) measurements. Stimuli were initiated for 10 s from a baseline resting temperature (32°C) to three different levels (37, 42, 45°C). Significantly increased heat pain thresholds were observed in patients. A stronger activation during heat pain perception was found in the left posterior insula in controls. In contrast, higher levels of activity were shown in the ipsilateral pons in patients when compared to controls. In patients, we found a significant interrelation between the depression score (Beck depression inventory) and heat pain activations. We suggest that reduced activity in the left posterior insula might contribute to increased pain thresholds in patients, while increased activations in the right anterior insula and pons mirror augmented sympathetic modulation putatively related to amplification of adrenergic descending pain inhibition. In addition, pain thresholds and brain activations were influenced by disease-inherent depressed mood.

Resting-state abnormal baseline brain activity in unipolar and bipolar depression

In the present study, we investigated differences in resting-state brain activity in patients with bipolar depression (BD) and unipolar depression (UD) by measuring the amplitude of low-frequency fluctuation (ALFF) of functional magnetic resonance imaging (fMRI) signals. Twenty-one BD and 21 gender-, age-, and education-matched UD patients participated in the fMRI analysis. We compared the differences in the ALFF between the two groups and investigated the correlation between clinical measurements and ALFF in the regions displaying significant group differences. BD subjects displayed significantly decreased ALFF in the left superior parietal lobule and the left posterior insula (l-PI). They also displayed increased ALFF in the right dorsal anterior insula (r-dAI) when compared to the UD group. Moderate negative correlations were found between the Hamilton Depression Rating Scale score (HAMD) and the ALFF in the l-PI for the BD (r=−0.44, P=0.02) and UD (r=−0.45, P=0.02) groups. Our results support the notion that insular subregions may contribute to the precise differentiation between BD and UD.

The Neuronal Correlates of Digits Backward Are Revealed by Voxel-Based Morphometry and Resting-State Functional Connectivity Analyses

Digits backward (DB) is a widely used neuropsychological measure that is believed to be a simple and effective index of the capacity of the verbal working memory. However, its neural correlates remain elusive. The aim of this study is to investigate the neural correlates of DB in 299 healthy young adults by combining voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analyses. The VBM analysis showed positive correlations between the DB scores and the gray matter volumes in the right anterior superior temporal gyrus (STG), the right posterior STG, the left inferior frontal gyrus and the left Rolandic operculum, which are four critical areas in the auditory phonological loop of the verbal working memory. Voxel-based correlation analysis was then performed between the positive rsFCs of these four clusters and the DB scores. We found that the DB scores were positively correlated with the rsFCs within the salience network (SN), that is, between the right anterior STG, the dorsal anterior cingulate cortex and the right fronto-insular cortex. We also found that the DB scores were negatively correlated with the rsFC within an anti-correlation network of the SN, between the right posterior STG and the left posterior insula. Our findings suggest that DB performance is related to the structural and functional organizations of the brain areas that are involved in the auditory phonological loop and the SN.

Cue-Elicited Craving in Heroin Addicts at Different Abstinent Time: An fMRI Pilot Study

Objective: We evaluated the effect of short-term and long-term heroin abstinence on brain responses to heroin-related cues using functional magnetic resonance imaging (fMRI). Methods: Eighteen male heroin addicts following short-term abstinence and 19 male heroin addicts following long-term abstinence underwent fMRI scanning while viewing heroin-related and neutral images. Cue-elicited craving and withdrawal symptoms in the subjects were measured. Results: Following short-term abstinence, greater activation was found in response to heroin cues compared to neutral cues in bilateral temporal, occipital, posterior cingulate, anterior cingulate, thalamus, cerebellum, and left hippocampus. In contrast, activations in bilateral temporal and occipital and deactivations in bilateral frontal, bilateral parietal, left posterior cingulate, insula, thalamus, dorsal striatum, and bilateral cerebellum were observed following long-term abstinence. Direct comparisons between conditions showed greater brain reactivity in response to smoking cues following short-term abstinence. In addition, short-term abstinence had more serious withdrawal symptoms than the long-term. Conclusion: The present findings indicate that compared to short-term, long-term abstinence manifests less serious withdrawal symptoms and significantly decreases neural responses to heroin-related cues in brain regions subserving visual sensory processing, attention, memory, and action planning. These findings suggest that long-term abstinence can decrease the salience of conditioned cues, thereby reducing the risk of relapses. The study's limitations are noted.

Reduced cortical thickness in non-medicated patients with obsessive-compulsive disorder

Increasing evidence suggests the presence of grey matter volume abnormalities in patients with obsessive-compulsive disorder (OCD) and the mediation of the expression of different OCD symptoms by discrete neural systems of the brain. However, limited studies have investigated the abnormalities of cortical thickness, and their results are comparatively inconsistent, possibly owing to the inclusion of medicated patients. Therefore, this study investigated cortical thickness abnormalities using surface-based analysis to identify distinct neural correlates of each symptom dimension in non-medicated patients with OCD. Thirty non-medicated patients with OCD and 30 age- and gender-matched healthy controls underwent magnetic resonance imaging. Group comparison of cortical thickness was performed using surface-based analysis. We also conducted correlation analysis between cortical thickness and each symptom dimension score. Compared to the healthy controls, the OCD patients had statistically significant reduction in cortical thickness in the cluster that contained the left superior temporal gyrus and posterior insular cortex (p<.05, corrected); no areas of the brain had significantly greater cortical thickness. Negative correlation was also found between cortical thickness and "cleaning" dimension scores in the left postcentral and right superior parietal gyri. The present results suggest that cortical thinning in the region that contains the left superior temporal gyrus and posterior insula may underlie pathophysiology of OCD and that discrete neural systems may mediate the "cleaning" symptom dimension.

The neural predictors of choice preference in intertemporal choice

Intertemporal choice may involve two processing stages: a valuation stage and a choice stage. Decision makers must integrate the various dimensions of an option (e.g., money, time) into a single measure of its subjective value (the valuation stage) and then choose the option that is the most valuable (the choice stage). Although previous studies have implicated that subjective values are represented by a diverse set of brain regions (e.g., vmPFC, VStr, and PCC) in intertemporal choice, it is not yet known which of these regions contain information that directly predicts subsequent choice. To address this question, we measured brain activity using functional MRI while participants performed a simple intertemporal choice task. The results found that participants' decision could be encoded by three specific brain areas (vmPFC, ACC, and PCC) even before they were required to make a choice, while the left posterior insula showed positively active in the choice stage when individuals selected the delayed rewards compared to the immediate rewards. These findings suggest that activation patterns in the vmPFC, ACC, and PCC were able to predict the subsequent choice preference; however, left posterior insula may play an important role for choice preference in the choice stage.

Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data

A meta-analysis of 140 neuroimaging studies was performed using the activation-likelihood-estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus-specific likelihood of being activated.

Activation likelihood estimation meta‐analysis of brain correlates of placebo analgesia in human experimental pain

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which areas consistently contribute to placebo analgesia-related networks. In the present study, we used activation likelihood estimation (ALE) meta-analysis, a state-of-the-art approach, to search for the cortical areas involved in PA in human experimental pain models. Nine fMRI studies and two PET studies investigating cerebral hemodynamic changes were included in the analysis. During expectation of analgesia, activated foci were found in the left anterior cingulate, right precentral, and lateral prefrontal cortex and in the left periaqueductal gray (PAG). During noxious stimulation, placebo-related activations were detected in the anterior cingulate and medial and lateral prefrontal cortices, in the left inferior parietal lobule and postcentral gyrus, anterior insula, thalamus, hypothalamus, PAG, and pons; deactivations were found in the left mid- and posterior cingulate cortex, superior temporal and precentral gyri, in the left anterior and right posterior insula, in the claustrum and putamen, and in the right thalamus and caudate body. Our results suggest on one hand that the modulatory cortical networks involved in PA largely overlap those involved in the regulation of emotional processes, on the other that brain nociceptive networks are downregulated in parallel with behavioral analgesia.

Changes in cortical activation in craniomandibular disorders during splint therapy – A single subject fMRI study

There is some controversial discussion within the therapy of craniomandibular disorders (CMDs) about the mode of action of occlusal splints. Here we present a case report on one CMD-patient measuring cerebral activation changes with functional magnetic resonance imaging (fMRI) before and after therapy with a stabilization splint. Wearing the Michigan splint for 11 nights and partially days resulted in substantial pain relief and changes in occlusal movement performance. Cerebral activation during occlusion was decreased after therapy (PRE-POST) in bilateral sensorimotor regions but also additional areas such as left posterior insula, right superior temporal cortex and bilateral occipital lobe. During the first usage of the splint in the scanner (PRE) increased activation in the left dorsolateral prefrontal lobe (BA 9) was observed. After splint training occlusion with the splint compared to without a splint increasingly involved the left superior parietal lobe (BA 7, POST). Whereas BA 9 might be associated with increasing working memory load due to the manipulation with an unusual object, the BA 7 activation in the POST session might document increased sensorimotor interaction after getting used to the splint. Our findings indicate that wearing an occlusion splint triggers activation in parietal sensorimotor integration areas, also observed after long periods of sensorimotor training. These additional recourses might improve coordination and physiological handling of the masticatory system.

Altered brain activity during emotional empathy in somatoform disorder.

Somatoform disorder patients suffer from impaired emotion recognition and other emotional deficits. Emotional empathy refers to the understanding and sharing of emotions of others in social contexts. It is likely that the emotional deficits of somatoform disorder patients are linked to disturbed empathic abilities; however, little is known so far about empathic deficits of somatoform patients and the underlying neural mechanisms. We used fMRI and an empathy paradigm to investigate 20 somatoform disorder patients and 20 healthy controls. The empathy paradigm contained facial pictures expressing anger, joy, disgust, and a neutral emotional state; a control condition contained unrecognizable stimuli. In addition, questionnaires testing for somatization, alexithymia, depression, empathy, and emotion recognition were applied. Behavioral results confirmed impaired emotion recognition in somatoform disorder and indicated a rather distinct pattern of empathic deficits of somatoform patients with specific difficulties in "empathic distress." In addition, somatoform patients revealed brain areas with diminished activity in the contrasts "all emotions"-"control," "anger"-"control," and "joy"-"control," whereas we did not find brain areas with altered activity in the contrasts "disgust"-"control" and "neutral"-"control." Significant clusters with less activity in somatoform patients included the bilateral parahippocampal gyrus, the left amygdala, the left postcentral gyrus, the left superior temporal gyrus, the left posterior insula, and the bilateral cerebellum. These findings indicate that disturbed emotional empathy of somatoform disorder patients is linked to impaired emotion recognition and abnormal activity of brain regions responsible for emotional evaluation, emotional memory, and emotion generation.

Self-rating scales assessing subjective well-being and distress correlate with rCBF in PTSD-sensitive regions

The aim of this study was to investigate the distribution of the regional cerebral blood flow (rCBF) in occupational-related post-traumatic stress disorder (PTSD) subjects and to seek possible correlations between brain perfusion and self-rating scales (SRS) in order to cross-check their diagnostic value and to look for their neural correlates. A total of 13 traumatized underground and long-distance train drivers developing (S) and 17 not developing (NS) PTSD who had experienced a 'person under train' accident or who had been assaulted at work underwent clinical assessment and 99mTc-HMPAO SPECT imaging during autobiographical trauma scripts. Statistical parametric mapping was applied to analyse rCBF changes in S as compared with NS and to search for correlations between rCBF and the administered SRS scores, modelling age, months to SPECT and the ratio 'grey matter/intra-cranial volume' as nuisance variables. Significantly higher activity was observed during trauma script in left posterior and anterior insula, posterior cingulate, inferior parietal lobule, precuneus, caudate and putamen in PTSD subjects as compared with the trauma-exposed control group. Impact of Event Scale and World Health Organisation (10) Well-Being Index scores highly correlated with tracer uptake to a great extent in the same regions in which rCBF differences between S and NS were found. These findings support the involvement of insular, cingulate and parietal cortices (as well as the basal ganglia) in the pathogenesis of PTSD and in the processing of related subjective well-being and distress.

Cascade of Neural Events Leading from Error Commission to Subsequent Awareness Revealed Using EEG Source Imaging

The goal of the present study was to shed light on the respective contributions of three important action monitoring brain regions (i.e. cingulate cortex, insula, and orbitofrontal cortex) during the conscious detection of response errors. To this end, fourteen healthy adults performed a speeded Go/Nogo task comprising Nogo trials of varying levels of difficulty, designed to elicit aware and unaware errors. Error awareness was indicated by participants with a second key press after the target key press. Meanwhile, electromyogram (EMG) from the response hand was recorded in addition to high-density scalp electroencephalogram (EEG). In the EMG-locked grand averages, aware errors clearly elicited an error-related negativity (ERN) reflecting error detection, and a later error positivity (Pe) reflecting conscious error awareness. However, no Pe was recorded after unaware errors or hits. These results are in line with previous studies suggesting that error awareness is associated with generation of the Pe. Source localisation results confirmed that the posterior cingulate motor area was the main generator of the ERN. However, inverse solution results also point to the involvement of the left posterior insula during the time interval of the Pe, and hence error awareness. Moreover, consecutive to this insular activity, the right orbitofrontal cortex (OFC) was activated in response to aware and unaware errors but not in response to hits, consistent with the implication of this area in the evaluation of the value of an error. These results reveal a precise sequence of activations in these three non-overlapping brain regions following error commission, enabling a progressive differentiation between aware and unaware errors as a function of time elapsed, thanks to the involvement first of interoceptive or proprioceptive processes (left insula), later leading to the detection of a breach in the prepotent response mode (right OFC).

White matter abnormalities in irritable bowel syndrome and relation to individual factors

Patients with irritable bowel syndrome (IBS) have abnormal cortical responses to rectal distension and grey matter thinning in brain areas associated with nociception. These abnormalities may be driven by white matter changes and individual factors. Therefore, we tested the hypothesis that WM subserving the pain system is compromised in IBS, and that disease characteristics and personality contribute to these abnormalities. MRI diffusion tensor imaging (DTI) images were obtained from 10 female IBS patients (20–54 years old, mean ± SD 32.8 ± 10.4), and 16 female healthy controls (20–44 years old, mean ± SD 29.1 ± 7.9). Mean fractional anisotropy (FA) was extracted from WM regions associated with nociception. The IBS group had higher FA in the fornix and external capsule adjacent to the right posterior insula. IBS chronic pain severity correlated with FA of the bilateral anterior insula and lateral thalamus and left anterior insula FA correlated with pain unpleasantness. IBS duration correlated with FA in the external capsule adjacent to the left posterior insula. Neuroticism correlated with FA in the left medial thalamus in IBS patients only. Pain catastrophizing correlated negatively to cingulum FA in IBS, whereas controls showed correlation between pain catastrophizing and FA of the external capsule adjacent to the left anterior and posterior insula. Thus, fornix and insular white matter is related to IBS symptoms. These data suggest that dysregulation of brain–gut communication via the neuroendocrine pathway or via abnormal visceral sensory and homeostatic input has a role in the pathology of IBS chronic pain.

Appreciating symptoms and deficits in schizophrenia: Right posterior insula and poor insight

Poor insight is one of the most prominent clinical features of psychosis. Loss of insight in schizophrenia is characterised by abnormalities in awareness and attribution of the origin of pathological mental phenomena. Converging lines of investigations suggest that in healthy individuals, right posterior insula plays an important role in awareness and self-attribution of mental phenomena, contributing to the emergence of a sense of self (Craig, 2002; Farrer et al., 2003). In addition, neuroimaging studies investigating brain morphometry in schizophrenia have consistently reported deficits in the structure of insula (Glahn et al., 2008; Ellison-Wright and Bullmore, 2010). In the present study, we investigated the relationship between the morphometry of posterior insula and degree of insight in a sample of 57 patients in a stable phase of illness using high resolution Magnetic Resonance Imaging. We measured the cortical surface area and local white matter volume of posterior insula. A significant inverse relationship was found between right posterior insular structure and degree of insight in schizophrenia. No such relationship was noted for left posterior insula. Our results highlight the importance of a predominantly right-sided network that includes posterior insula as the neural basis of insight. Abnormalities in interoceptive awareness and self-appraisal of emotional states may contribute to the loss of insight seen in schizophrenia.