Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a nonforensic sample

Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self‐Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. Hum Brain Mapp 36:1417–1428, 2015. © 2014 Wiley Periodicals, Inc .     

Insula‐based networks in professional musicians: Evidence for increased functional connectivity during resting state fMRI

Despite considerable research on experience‐dependent neuroplasticity in professional musicians, detailed understanding of an involvement of the insula is only now beginning to emerge. We investigated the effects of musical training on intrinsic insula‐based connectivity in professional classical musicians relative to nonmusicians using resting‐state functional MRI. Following a tripartite scheme of insula subdivisions, coactivation profiles were analyzed for the posterior, ventral anterior, and dorsal anterior insula in both hemispheres. While whole‐brain connectivity across all participants confirmed previously reported patterns, between‐group comparisons revealed increased insular connectivity in musicians relative to nonmusicians. Coactivated regions encompassed constituents of large‐scale networks involved in salience detection (e.g., anterior and middle cingulate cortex), affective processing (e.g., orbitofrontal cortex and temporal pole), and higher order cognition (e.g., dorsolateral prefrontal cortex and the temporoparietal junction), whereas no differences were found for the reversed group contrast. Importantly, these connectivity patterns were stronger in musicians who experienced more years of musical practice, including also sensorimotor regions involved in music performance (M1 hand area, S1, A1, and SMA). We conclude that musical training triggers significant reorganization in insula‐based networks, potentially facilitating high‐level cognitive and affective functions associated with the fast integration of multisensory information in the context of music performance. Hum Brain Mapp 38:4834–4849, 2017. © 2017 Wiley Periodicals, Inc.     

Processing of nociceptive input from posterior to anterior insula in humans

Previous brain imaging studies have shown robust activations in the insula during nociceptive stimulation. Most activations involve the posterior insular cortex but they can cover all insular gyri in some fMRI studies. However, little is known about the timing of activations across the different insular sub‐regions. We report on the distribution of intracerebrally recorded nociceptive laser evoked potentials (LEPs) acquired from the full extent of the insula in 44 epileptic patients. Our study shows that both posterior and anterior subdivisions of the insular cortex respond to a nociceptive heat stimulus within a 200–400 ms latency range. This nociceptive cortical potential occurs firstly, and is larger, in the posterior granular insular cortex. The presence of phase reversals in LEP components in both posterior and anterior insular regions suggests activation of distinct, presumably functionally separate, sources in the posterior and anterior parts of the insula. Our results suggest that nociceptive input is first processed in the posterior insula, where it is known to be coded in terms of intensity and anatomical location, and then conveyed to the anterior insula, where the emotional reaction to pain is elaborated. Hum Brain Mapp 35:5486–5499, 2014. © 2014 Wiley Periodicals, Inc.     

Thalamic connections of the insula in the rhesus monkey and comments on the paralimbic connectivity of the medial pulvinar nucleus

Thalamic connections of the insula in the rhesus monkey were studied with axonal transport methods. Tritiated amino acid injections limited to the insula revealed autoradiographic label in the principal and parvicellular components of the ventroposterior medial nucleus, the ventroposterior inferior nucleus, the oral and medial pulvinar nuclei, the nucleus reuniens, the parvicellular and magnocellular components of the medial dorsal nucleus, the centromedian-parafasicularis nuclei, and the reticular nucleus. In additional animals, tritiated amino acids and horseradish perioxidase injections were made within different regions of the insula. Although the injection sites in these additional cases may have included minor extensions into claustrum and adjacent structures, several tentative conclusions emerged with respect to the antero-posterior gradient in insulothalamic connectivity. The anterior insula appears to have a more extensive relationship with the ventroposterior medial complex, the medial dorsal nucleus, the centromedian-parafasicularis nuclei and with some midline nuclei. In contrast, the posterior insula is more extensively connected with the ventroposterior inferior nucleus, the oral and medial pulvinar nuclei, and the suprageniculate nucleus. The patterns of insulothalamic connections support conclusions derived from observations on the cortical connectivity of the primate insular cortex indicating that the anterior insula is related to olfactory, gustatory, and viscero-autonomic behavior, whereas the posterior insula is related to auditory-somesthetic-skeletomotor function (Mesulam and Mufson, '82b). The medial pulvinar nucleus has extensive connections with many paralimbic cortical regions including the insula as well as with high order polymodal association cortex. These findings suggest that the medial pulvinar may provide a region for the convergence of multisensory association input with limbic information.     

Autonomic responses and efferent pathways from the insular cortex in the rat

The anatomical distribution of autonomic, particularly cardiovascular, responses originating in the insular cortex was examined by using systematic electrical microstimulation. The localization of these responses to cell bodies in the insular cortex was demonstrated by using microinjection of the excitatory amino acid, D,L-homocysteic acid. The efferents from the cardiovascular responsive sites were traced by iontophoretic injection of the anterograde axonal tracer Phaseoleus vulgaris leucoagglutinin (PHA-L). Two distinct patterns of cardiovascular response were elicited from the insular cortex: an increase in arterial pressure accompanied by tachycardia or a decrease in arterial pressure with bradycardia. The pressor responses were obtained by stimulation of the rostral half of the posterior insular cortex while depressor sites were located in the caudal part of the posterior insular area. Both types of site were primarily located in the dysgranular and agranular insular cortex. Gastric motility changes originated from a separate but adjacent region immediately rostral to the cardiovascular responsive sites in the anterior insular cortex. Tracing of efferents with PHA-L indicated a number of differences in connectivity between the pressor and depressor sites. Pressor sites had substantially more intense connections with other limbic regions including the infralimbic cortex, the amygdala, the bed nucleus of the stria terminalis and the medial dorsal and intralaminar nuclei of the thalamus. Alternatively, the depressor region of the insular cortex more heavily innervated sensory areas of the brain including layer I of the primary somatosensory cortex, a peripheral region of the sensory relay nuclei of the thalamus and the caudal spinal trigeminal nucleus. In addition, there were topographical differences in the projection to the lateral hypothalamic area, the primary site of autonomic outflow for these responses from the insular cortex. These differences in connectivity may provide the anatomic substrate for the specific cardiovascular responses and behaviors integrated in the insular cortex.     

Processing of affective and emotionally neutral tactile stimuli in the insular cortex

The insula is important for the processing of pleasant aspects of touch whereas its role in the processing of emotionally neutral touch has been less explored. Here, we used a network approach to investigate the insular processing of pleasant stroking touch and emotionally neutral vibratory touch, analysing functional magnetic resonance imaging data from 23 healthy adult participants. Vibration and skin stroking activated areas in the posterior, middle and anterior insula. Psychophysiological interaction analyses suggested that skin stroking increased functional connectivity between the posterior and ventral anterior insula. Vibration instead increased functional connectivity between the posterior and dorsal anterior insula, and induced a stronger decrease of the default mode network activity compared to stroking. These results confirmed findings from previous studies showing that the posterior insula processes affective touch information. We suggest that this is accomplished by relaying tactile information from the posterior insula to ventral anterior insula, an area tightly connected to the emotional parts of the brain. However, our results also suggested that the insula processes tactile information with less emotional valence. A central hub in this processing seemed to be the right dorsal anterior insula.     

Intrinsic functional connectivity of the central extended amygdala

The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a critical role in triggering fear and anxiety and is implicated in the development of a range of debilitating neuropsychiatric disorders. Although it is widely believed that these disorders reflect the coordinated activity of distributed neural circuits, the functional architecture of the EAc network and the degree to which the BST and the Ce show distinct patterns of functional connectivity is unclear. Here, we used a novel combination of imaging approaches to trace the connectivity of the BST and the Ce in 130 healthy, racially diverse, community‐dwelling adults. Multiband imaging, high‐precision registration techniques, and spatially unsmoothed data maximized anatomical specificity. Using newly developed seed regions, whole‐brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala, the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed stronger connectivity with the thalamus, striatum, periaqueductal gray, and several prefrontal territories. The only regions showing stronger functional connectivity with the Ce were neighboring regions of the dorsal amygdala, amygdalohippocampal area, and anterior hippocampus. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and showcase image registration techniques that are likely to be useful for researchers working with “deidentified” neuroimaging data.     

Magnetoencephalographic signatures of insular epileptic spikes based on functional connectivity

Failure to recognize insular cortex seizures has recently been identified as a cause of epilepsy surgeries targeting the temporal, parietal, or frontal lobe. Such failures are partly due to the fact that current noninvasive localization techniques fare poorly in recognizing insular epileptic foci. Our group recently demonstrated that magnetoencephalography (MEG) is sensitive to epileptiform spikes generated by the insula. In this study, we assessed the potential of distributed source imaging and functional connectivity analyses to distinguish insular networks underlying the generation of spikes. Nineteen patients with operculo‐insular epilepsy were investigated. Each patient underwent MEG as well as T1‐weighted magnetic resonance imaging (MRI) as part of their standard presurgical evaluation. Cortical sources of MEG spikes were reconstructed with the maximum entropy on the mean algorithm, and their time courses served to analyze source functional connectivity. The results indicate that the anterior and posterior subregions of the insula have specific patterns of functional connectivity mainly involving frontal and parietal regions, respectively. In addition, while their connectivity patterns are qualitatively similar during rest and during spikes, couplings within these networks are much stronger during spikes. These results show that MEG can establish functional connectivity‐based signatures that could help in the diagnosis of different subtypes of insular cortex epilepsy. Hum Brain Mapp 37:3250–3261, 2016. © 2016 Wiley Periodicals, Inc .     

Connectivity of the subthalamic nucleus and globus pallidus pars interna to regions within the speech network: A meta‐analytic connectivity study

Cortico‐basal ganglia connections are involved in a range of behaviors within motor, cognitive, and emotional domains; however, the whole‐brain functional connections of individual nuclei are poorly understood in humans. The first aim of this study was to characterize and compare the connectivity of the subthalamic nucleus (STN) and globus pallidus pars interna (GPi) using meta‐analytic connectivity modeling. Structure‐based activation likelihood estimation meta‐analyses were performed for STN and GPi seeds using archived functional imaging coordinates from the BrainMap database. Both regions coactivated with caudate, putamen, thalamus, STN, GPi, and GPe, SMA, IFG, and insula. Contrast analyses also revealed coactivation differences within SMA, IFG, insula, and premotor cortex. The second aim of this study was to examine the degree of overlap between the connectivity maps derived for STN and GPi and a functional activation map representing the speech network. To do this, we examined the intersection of coactivation maps and their respective contrasts (STN > GPi and GPi > STN) with a coordinate‐based meta‐analysis of speech function. In conjunction with the speech map, both STN and GPi coactivation maps revealed overlap in the anterior insula with GPi map additionally showing overlap in the supplementary motor area (SMA). Among cortical regions activated by speech tasks, STN was found to have stronger connectivity than GPi with regions involved in cognitive linguistic processes (pre‐SMA, dorsal anterior insula, and inferior frontal gyrus), while GPi demonstrated stronger connectivity to regions involved in motor speech processes (middle insula, SMA, and premotor cortex). Hum Brain Mapp 35:3499–3516, 2014. © 2013 Wiley Periodicals, Inc .     

The role of the dorsal anterior insula in ecstatic sensation revealed by direct electrical brain stimulation

BackgroundAn ecstatic phenomenon is an altered state of consciousness with a sense of “hyper-reality”, and a complete present-moment awareness with a feeling of union with the Universe. A better understanding of the network mechanisms underlying this fascinating subjective experience may help to unravel some mysteries of human consciousness. Insula has been recently proposed to be a key region to elicit these symptoms.Objective/HypothesisWe studied functional connectivity changes in several brain areas during the induction of ecstatic auras by direct electrical stimulation of the dorsal anterior insular cortex in patients with refractory focal epilepsy implanted with intracerebral electrodes (stereotactic-EEG, SEEG) in the context of their pre-surgical evaluation.MethodsThree patients were selected on the basis of the occurrence of ecstatic symptoms triggered by direct intracerebral electrical stimulation (ES) of the antero-dorsal part of the insula. ES was performed (50 Hz, 1.5–2.1 mA, in a bipolar fashion to each contact in the gray matter during a 3 s period) to map functional cortices and trigger habitual seizures. One stimulation inducing ecstatic changes in each patient was analyzed. Functional connectivity analysis was performed by measuring interdependencies (nonlinear regression analysis based on the h² coefficient) between SEEG signals before and after stimulations.ResultsIn all patients, only the stimulation of dorsal anterior insula was able to reproduce an ecstatic aura. We observed a significant increase of functional connectivity values between several brain regions in the immediate period following stimulations. The most commonly implicated region was the dorsal anterior insula. Out-degrees (a measure intended to identify leading structures in a network) identified the dorsal anterior insula as the most common leading region in the induced networks.Conclusion(s)Our findings bring additional support in favor of a major role played by the dorsal anterior insula in ecstatic experiences.     

Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

The insular cortex is one of the brain regions that show consistent abnormalities in both structural and functional neuroimaging studies of schizophrenia. In healthy individuals, the insula has been implicated in a myriad of physiologic functions. The anterior cingulate cortex (ACC) and insula together constitute the salience network, an intrinsic large-scale network showing strong functional connectivity. Considering the insula as a functional unit along with the ACC provides an integrated understanding of the role of the insula in information processing. In this review, we bring together evidence from imaging studies to understand the role of the salience network in schizophrenia and propose a model of insular dysfunction in psychosis.     

Functional organization of the human posterior cingulate cortex,revealed by multiple connectivity‐based parcellation methods

Based on cytoarchitecture, the posterior cingulate cortex (PCC) is thought to be comprised of two distinct functional subregions: the dorsal and ventral PCC (dPCC and vPCC). However, functional subregions do not completely match anatomical boundaries in the human brain. To understand the relationship between the functional organization of regions and anatomical features, it is necessary to apply parcellation algorithms based on functional properties. We therefore defined functionally informed subregions in the human PCC by parcellation of regions with similar patterns of functional connectivity in the resting brain. We used various patterns of functional connectivity, namely local, whole‐brain and diffuse functional connections of the PCC, and various clustering methods, namely hierarchical, spectral, and k‐means clustering to investigate the subregions of the PCC. Overall, the approximate anatomical boundaries and predicted functional regions were highly overlapped to each other. Using hierarchical clustering, the PCC could be clearly separated into two anatomical subregions, namely the dPCC and vPCC, and further divided into four subregions segregated by local functional connectivity patterns. We show that the PCC could be separated into two (dPCC and vPCC) or four subregions based on local functional connections and hierarchical clustering, and that subregions of PCC display differential global functional connectivity, particularly along the dorsal‐ventral axis. These results suggest that differences in functional connectivity between dPCC and vPCC may be due to differences in local connectivity between these functionally hierarchical subregions of the PCC. Hum Brain Mapp 38:2808–2818, 2017. © 2017 Wiley Periodicals, Inc.     

Altered insula-prefrontal functional connectivity correlates to decreased vigilant attention after total sleep deprivation

BackgroundSleep deprivation can robustly affect vigilant attention. The insula is a key hub of the salience network that mediates shifting attention between endogenous and exogenous states. However, little is known regarding the involvement of insular functional connectivity in impaired vigilant attention after total sleep deprivation (TSD). The purpose of this study is to explore the alterations in insular functional connectivity and its association with vigilant attention performance following TSD.MethodsTwenty-six adult men were enrolled in the study. Participants underwent two counterbalanced resting-state functional magnetic resonance imaging (rs-fMRI) scans, once in rested wakefulness (RW) and once after 36 h of TSD. Seed-based functional connectivity analysis was performed using rs-fMRI data for the left and right insula. The vigilant attention was measured using a psychomotor vigilance test (PVT). Furthermore, Pearson correlation analysis was conducted to investigate the relationship between altered insular functional connectivity and PVT performance.ResultsCompared to RW, enhanced functional connectivity was observed between the insula and prefrontal cortex and anterior cingulate cortex, while reduced functional connectivity was observed between the insula and temporal, parietal, and occipital regions following TSD. Moreover, altered insular functional connectivity with the prefrontal cortex, ie superior frontal gyrus and middle frontal gyrus, and inferior temporal gyrus was correlated with PVT performance after TSD.ConclusionOur results suggest that insular coupling with the prefrontal cortex and inferior temporal gyrus may act as neural indicators for vigilant attention impairment, which further reveals the critical role of the salience network in cognitive decline following TSD.     

Functional differentiation in the human ventromedial frontal lobe: A data‐driven parcellation

Ventromedial regions of the frontal lobe (vmFL) are thought to play a key role in decision‐making and emotional regulation. However, aspects of this area's functional organization, including the presence of a multiple subregions, their functional and anatomical connectivity, and the cross‐species homologies of these subregions with those of other species, remain poorly understood. To address this uncertainty, we employed a two‐stage parcellation of the region to identify six distinct structures within the region on the basis of data‐driven classification of functional connectivity patterns obtained using the meta‐analytic connectivity modeling (MACM) approach. From anterior to posterior, the derived subregions included two lateralized posterior regions, an intermediate posterior region, a dorsal and ventral central region, and a single anterior region. The regions were characterized further by functional connectivity derived using resting‐state fMRI and functional decoding using the Brain Map database. In general, the regions could be differentiated on the basis of different patterns of functional connectivity with canonical “default mode network” regions and/or subcortical regions such as the striatum. Together, the findings suggest the presence of functionally distinct neural structures within vmFL, consistent with data from experimental animals as well prior demonstrations of anatomical differences within the region. Detailed correspondence with the anterior cingulate, medial orbitofrontal cortex, and rostroventral prefrontal cortex, as well as specific animal homologs are discussed. The findings may suggest future directions for resolving potential functional and structural correspondence of subregions within the frontal lobe across behavioral contexts, and across mammalian species.     

Resting-state connectivity in the default mode network and insula during experimental low back pain简

Functional magnetic resonance imaging studies have shown that the insular cortex has a significant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the default mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy subjects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the importance of the interaction between these regions in pain processing.     

Reduced corticostriatal functional connectivity in temporomandibular disorders

Although temporomandibular disorders (TMD) have been associated with abnormal gray matter volumes in cortical areas and in the striatum, the corticostriatal functional connectivity (FC) of patients with TMD has not been studied. Here, we studied 30 patients with TMD and 20 healthy controls that underwent clinical evaluations, including Helkimo indices, pain assessments, and resting‐state functional magnetic resonance imaging scans. The FCs of the striatal regions with the other brain areas were examined with a seed‐based approach. As seeds, we used the dorsal caudate, ventral caudate/nucleus accumbens, dorsal caudal putamen, and ventral rostral putamen regions. Voxel‐wise comparisons with controls revealed that the patients with TMD exhibited reduced FCs in the ventral corticostriatal circuitry, between the ventral striatum and ventral frontal cortices, including the anterior cingulate cortex and anterior insula; in the dorsal corticostriatal circuitry, between the dorsal striatum and the dorsal cortices, including the precentral gyrus and supramarginal gyrus; and also within the striatum. Additionally, we explored correlations between the reduced corticostriatal FCs and clinical measurements. These results directly supported the hypothesis that TMD is associated with reduced FCs in brain corticostriatal networks and that these reduced FCs may underlie the deficits in motor control, pain processing, and cognition in TMD. Our findings may contribute to the understanding of the etiologies and pathologies of TMD.     

Aberrant Dependence of Default Mode/Central Executive Network Interactions on Anterior Insular Salience Network Activity in Schizophrenia

In schizophrenia, consistent structural and functional changes have been demonstrated for the insula including aberrant salience processing, which is critical for psychosis. Interactions within and across default mode and central executive network (DMN, CEN) are impaired in schizophrenia. The question arises whether these 2 types of changes are related. Recently, the anterior insula has been demonstrated to control DMN/CEN interactions. We hypothesized that aberrant insula and DMN/CEN activity in schizophrenia is associated with an impaired dependence of DMN/CEN interactions on anterior insular salience network (SN) activity. Eighteen patients with schizophrenia during psychosis and 20 healthy controls were studied by resting-state-fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed spatiotemporal patterns of synchronized ongoing blood-oxygenation-level-dependent (BOLD) activity including SN, DMN, and CEN. Scores of functional and time-lagged connectivity across networks’ time courses were calculated. Connectivity scores and spatial network maps were compared between groups and related with patients’ hallucination and delusion severity. Spatial BOLD-synchronicity was altered in patients’ SN, DMN, and CEN, including decreased activity in the right anterior insula (rAI). Patients’ functional connectivity between DMN and CEN was increased and related with hallucinations severity. Importantly, patients’ time-lagged connectivity between SN and DMN/CEN was reduced, and decreased rAI activity of the SN was associated with both hallucinations and increased functional connectivity between DMN and CEN. Data provide evidence for an aberrant dependence of DMN/CEN interactions on anterior insular SN activity, linking impaired insula, DMN, CEN activity, and psychosis in schizophrenia.Key words: schizophrenia, psychosis, anterior insula, salience network, default mode network, central executive network     

Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation

Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2 h 45 min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.     

Development of insula connectivity between ages 12 and 30 revealed by high angular resolution diffusion imaging

The insula, hidden deep within the Sylvian fissures, has proven difficult to study from a connectivity perspective. Most of our current information on the anatomical connectivity of the insula comes from studies of nonhuman primates and post mortem human dissections. To date, only two neuroimaging studies have successfully examined the connectivity of the insula. Here we examine how the connectivity of the insula develops between ages 12 and 30, in 307 young adolescent and adult subjects scanned with 4‐Tesla high angular resolution diffusion imaging (HARDI). The density of fiber connections between the insula and the frontal and parietal cortex decreased with age, but the connection density between the insula and the temporal cortex generally increased with age. This trajectory is in line with well‐known patterns of cortical development in these regions. In addition, males and females showed different developmental trajectories for the connection between the left insula and the left precentral gyrus. The insula plays many different roles, some of them affected in neuropsychiatric disorders; this information on the insula's connectivity may help efforts to elucidate mechanisms of brain disorders in which it is implicated. Hum Brain Mapp 35:1790–1800, 2014. © 2013 Wiley Periodicals, Inc.     

Dispositional use of emotion regulation strategies and resting-state cortico-limbic functional connectivity

Neuroimaging functional connectivity (FC) analyses have shown that the negative coupling between the amygdala and cortical regions is linked to better emotion regulation in experimental settings. Nevertheless, no studies have examined the association between resting-state cortico-amygdalar FC and the dispositional use of emotion regulation strategies. We aim at assessing the relationship between the resting-state FC patterns of two different amygdala territories, with different functions in the emotion response process, and trait-like measures of cognitive reappraisal and expressive suppression. Forty-eight healthy controls completed the Emotion Regulation Questionnaire (ERQ) and underwent a resting-state functional magnetic resonance imaging acquisition. FC maps of basolateral and centromedial amygdala (BLA/CMA) with different cortical areas were estimated with a seed-based approach, and were then correlated with reappraisal and suppression scores from the ERQ. FC between left BLA and left insula and right BLA and the supplementary motor area (SMA) correlated inversely with reappraisal scores. Conversely, FC between left BLA and the dorsal anterior cingulate cortex correlated directly with suppression scores. Finally, FC between left CMA and the SMA was inversely correlated with suppression. Top-down regulation from the SMA seems to account for the dispositional use of both reappraisal and suppression depending on the specific amygdala nucleus being modulated. In addition, modulation of amygdala activity from cingulate and insular cortices seem to also account for the habitual use of the different emotion regulation strategies.