Bilateral Posterior Insula Research Articles

Decreased task‐evoked functional connectivity in the descending pain modulatory network in Alzheimer’s disease

AbstractBackgroundPeople with Alzheimer’s disease (AD) may suffer from alterations in the descending pain modulatory network (DPMN). Adults with AD receive fewer analgesic pain medications and report pain less frequently than healthy controls. This study examines possible alterations in task‐evoked functional connectivity (TEFC) in response to thermal pain in several structures comprising the DPMN. We hypothesize that adults with AD will demonstrate decreased TEFC between DPMN regions.MethodThe sample consisted of 61 adults, 31 people with Alzheimer’s disease (AD; Mage = 77) and 30 healthy controls (HC; Mage = 73). The groups did not differ on socioeconomic status, current or average pain, or state or trait anxiety scores. Age and depression scores differed between groups and were controlled. Participants completed 4 pseudorandomized fMRI sessions using a passive thermal pain induction task consisting of warmth, mild pain, and moderate pain temperature thresholds. Regions of interest were selected a priori: bilateral primary somatosensory cortex (S1), bilateral anterior insula (aINS), bilateral posterior insula (pINS), anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). Psychophysiological interactions (PPI) analysis was completed using CONN v18.b. Motion correction was performed using Artifact Detection Tools and fMRI sessions for which greater than 20% of the timeseries exceeded 2 mm normalized motion were excluded from the analysis. Age and AD‐related differences in cerebral tissue volume were controlled. Contrasts for this analysis were chosen to be mild pain > warmth and moderate pain > warmth to subtract innocuous stimulus from noxious stimuli.ResultCompared to healthy controls, adults with AD exhibited decreased TEFC between the R S1 and L S1 for mild pain > warmth (T = ‐2.03, p = 0.047), and decreased TEFC between the PAG and ACC for moderate pain > warmth (T = ‐2.18, p = 0.033).ConclusionFindings suggest that in people with AD, decreased connectivity between left and right S1 may indicate altered sensory processing of neural input. Evidence of decreased connectivity between the PAG and ACC in adults with AD may indicate an inability to modulate endogenous opioid systems within the brain and may lead to increased suffering from pain.

Tau pathology in posterior DMN is related to aberrant SN‐DMN network connectivity in atypical Alzheimer’s disease

AbstractBackgroundCircumscribed patterns of pathological tau propagation along functional networks have been observed in normal aging and amnestic Alzheimer’s disease (AD), including in two cognition‐relevant networks: the default mode network (DMN) and the salience network (SN). It remains unclear if atypical phenotypes of AD demonstrate a direct relationship between tau and functional connectivity within and between these networks.MethodTwenty‐six amyloid‐positive patients diagnosed with atypical phenotypes of AD (12 PCA, 10 lvPPA, and 4 dysexecutive; mean age = 66 years, 9M/17F) were examined with tau (18F‐AV‐1451) PET and resting state functional MRI (rs‐fMRI). Hub regions within the DMN and SN were defined from the literature within the bilateral posterior cingulate cortex (PCC) and anterior insula (aI), respectively. ROI‐to‐ROI connectivity was calculated to determine within‐ and between‐network connectivity. Bivariate correlation analyses were conducted to determine if the magnitude of partial volume corrected tau PET signal in each network’s hub region was related to the within‐network functional connectivity of the DMN and SN, as well as between the hub regions of the DMN and SN.ResultWe found that higher tau signal in bilateral PCC was associated with diminished DMN connectivity (PCC to posterior angular gyrus) in both hemispheres (left: r = ‐0.50, p = 0.009; right: r = ‐0.47, p = 0.01). We did not observe any relationship between tau and functional connectivity within the SN. Our novel observation was that higher tau signal in the PCC was associated with increased connectivity between the DMN and SN within both hemispheres (left: r = 0.55, p = 0.004; right: r = 0.47, p = 0.02), with some patients demonstrating pathologically positive functional connectivity between the DMN and SN.ConclusionOur findings support the posited relationship between tau pathology and aberrant functional network connectivity reported in aging and amnestic AD by demonstrating that higher tau burden within the PCC is related to fractured DMN connectivity and pathologically increased DMN‐SN connectivity in a group of non‐amnestic AD patients. These findings may help explain how tau deposition in key hub regions of the DMN bring about dysfunctional inter‐network connectivity with the SN, likely contributing to the cognitive and affective dysfunction observed across the clinical spectrum of AD.

Investigation of sensorimotor dysfunction in Parkinson disease by resting-state fMRI

PurposeFunctional MRI has played a fundamental role in Parkinson's disease(PD) study. In this paper, we performed an independent component analysis (ICA) based on functional networks to reveal the intricate variations on the morphology and functional properties of brain. Our analysis aims at discovering the differences between PD patients with sensorimotor function impairment and normal controls(NC), thus helping to understand the coordination neurological function degeneration in PD objectively. MethodWe investigated the blood oxygen level dependent(BOLD) functional MRI obtained at a 3.0 T MRI scanner. 30 PD patients and 28 NC subjects underwent the scan in resting state. The signals of sensory and motor coordinative control areas in the sensorimotor, insula and cerebellum networks acquired by ICA(Independent Component Analysis)were applied to analyze the functional alterations. Specifically, intra-network analysis was performed with signals in local networks, and inter-network analysis was conducted by functional network connectivity (FNC) with signals across different networks. Two sample T test was carried out to detect the significant (p < 0.05, FDR p < 0.05) functional abnormality in PD patients. ConclusionWe identified an obvious increase in bilateral posterior insula, but decrease in bilateral cerebellum hemisphere, supplementary motor area(SMA) and precentral gyrus paracentral lobule of left postcentral gyrus. Besides, we found a significantly increased connection between independent component (IC) 13 which was located in right postcentral gyrus and cerebellum. Decreased connections were detected between sensory and motor cortex in sensorimotor network and between cerebellum and insula network by FNC analysis in PD patients as well. DiscussionParkinson's disease derives from the degeneration of the dopaminergic neurons in substantia nigra, and results in decreased secretion of inhibitory neurotransmitter. The significant differences between PD and NC groups in our research maybe explain the clinical manifestations of prominent bradykinesia and multiple extrapyramidal symptoms.

Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder

BackgroundSystemic inflammation and immune dysregulation have been considered as risk factors in the pathophysiology of mood disorders including bipolar disorder (BD). Previous neuroimaging studies have demonstrated metabolic, structural and functional abnormalities in the insula in BD, proposed that the insula played an important role in BD. We herein aimed to explore neural mechanisms underlying inflammation-induced in the insular subregions functional connectivity (FC) in patients with BD. MethodsBrain resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 41 patients with unmedicated BD II (current episode depressed), 68 healthy controls (HCs). Three pairs of insular seed regions were selected: the bilateral anterior insula (AI), the bilateral middle insula (MI) and the bilateral posterior insula (PI), and calculated the whole-brain FC for each subregion. Additionally, the serum levels of pro-inflammatory cytokines in patients and HCs, including IL-6 and TNF-α, were detected. Then the partial correlation coefficients between the abnormal insular subregions FC values and pro-inflammatory cytokines levels in patients with BD II depression were calculated. ResultsThe BD II depression group exhibited decreased FC between the right PI and the left postcentral gyrus, and increased FC between the left AI and the bilateral insula (extended to the right putamen) when compared with the HC group. Moreover, the patients with BD II depression showed higher IL-6 and TNF-α levels than HCs, and IL-6 level was negatively correlated with FC of the right PI to the left postcentral gyrus. ConclusionsOur results demonstrated that abnormal FC between the bilateral insula, and between the insula and sensorimotor areas in BD. Moreover, disrupted FC between the insula and sensorimotor areas was associated with elevated pro-inflammatory cytokine levels of IL-6 in BD.

Shared and distinct functional networks for empathy and pain processing: a systematic review and meta-analysis of fMRI studies.

BackgroundEmpathy for pain is a complex phenomenon incorporating sensory, cognitive and affective processes. Functional neuroimaging studies indicate a rich network of brain activations for empathic processing. However, previous research focused on core activations in bilateral anterior insula (AI) and anterior cingulate/anterior midcingulate cortex (ACC/aMCC) which are also typically present during nociceptive (pain) processing. Theoretical understanding of empathy would benefit from empirical investigation of shared and contrasting brain activations for empathic and nociceptive processing.MethodThirty-nine empathy for observed pain studies (1112 participants; 527 foci) were selected by systematic review. Coordinate based meta-analysis (activation likelihood estimation) was performed and novel contrast analyses compared neurobiological processing of empathy with a comprehensive meta-analysis of 180 studies of nociceptive processing (Tanasescu et al., 2016).ResultsConjunction analysis indicated overlapping activations for empathy and nociception in AI, aMCC, somatosensory and inferior frontal regions. Contrast analysis revealed increased likelihood of activation for empathy, relative to nociception, in bilateral supramarginal, inferior frontal and occipitotemporal regions. Nociception preferentially activated bilateral posterior insula, somatosensory cortex and aMCC.ConclusionOur findings support the likelihood of shared and distinct neural networks for empathic, relative to nociceptive, processing. This offers succinct empirical support for recent tiered or modular theoretical accounts of empathy.

Placebo-induced pain reduction is associated with negative coupling between brain networks at rest

Placebos can reduce pain by inducing beliefs in the effectiveness of an actually inert treatment. Such top-down effects on pain typically engage lateral and medial prefrontal regions, the insula, somatosensory cortex, as well as the thalamus and brainstem during pain anticipation or perception. Considering the level of large-scale brain networks, these regions spatially align with fronto-parietal/executive control, salience, and sensory-motor networks, but it is unclear if and how placebos alter interactions between them during rest. Here, we investigated how placebo analgesia affected intrinsic network coupling. Ninety-nine human participants were randomly assigned to a placebo or control group and underwent resting-state fMRI after pain processing. Results revealed inverse coupling between two resting-state networks in placebo but not control participants. Specifically, networks comprised the bilateral somatosensory cortex and posterior insula, as well as the brainstem, thalamus, striatal regions, dorsal and rostral anterior cingulate cortex, and the anterior insula, respectively. Across participants, more negative between-network coupling was associated with lower individual pain intensity as assessed during a preceding pain task, and there was no significant relation with expectations of medication effectiveness in the placebo group. Altogether, these findings provide initial evidence that placebo analgesia affects the intrinsic communication between large-scale brain networks, even in the absence of pain. We suggest a theoretical model where placebo analgesia might affect processing within a descending pain-modulatory network, potentially segregating it from somatosensory regions that may code for painful experiences.

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning.

Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n=84), PTSD+DS (n=49), and age-matched healthy controls (n=51). Ascompared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, ascompared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.

Social anxiety, posterior insula activation, and autonomic response during self-initiated action in a Cyberball game

BackgroundAn earlier study characterized the neural correlates of self-initiated actions in a Cyberball game in healthy individuals. It remains unclear how social anxiety may influence these neural processes. MethodsWe examined regional activations to self-initiated actions in 25 adults with low and 25 with high social anxiety (LA and HA, respectively). Skin conductance was recorded concurrently with fMRI. We followed published routines in the analyses of imaging and skin conductance data. ResultsWe hypothesized that HA as compared to LA individuals would demonstrate increased cortical limbic activations during self-initiated actions (tossing or T > receiving or R trials, to control for motor activities) in social exclusion (EX) vs. fair game (FG) scenario. At a corrected threshold, HA as compared with LA group showed increases in bilateral posterior insula activation during T vs. R trials in EX as compared to FG. Further, HA as compared to LA showed higher skin conductance response to tossing trials during EX as compared to FG. LimitationsWith a limited sample size, we did not examine potential sex effects. Further, we cannot rule out the effects of depression on the findings. ConclusionsTogether, the results suggest that individuals with more severe social anxiety engaged the somatosensory insula to a greater extent and exhibited higher physiological arousal when initiating ball toss during social exclusion in the Cyberball game. Posterior insula response to self-initiated action may represent a biomarker of social anxiety. It remains to be investigated whether interventions to decrease physiological arousal may alleviate social anxiety.

Decreased interhemispheric functional connectivity rather than corpus callosum volume as a potential biomarker for autism spectrum disorder

Previous studies have implicated both structural and interhemispheric functional connectivity alterations in autism spectrum disorder (ASD) although findings are inconsistent. There is evidence that connectivity between corresponding regions in each hemisphere (homotopic) may be of particular importance and therefore the present study used the Autism Brain Imaging Data Exchange data to investigate ASD-related resting-state and structural alterations as well as associations with symptom severity (Autism Diagnostic Observation Schedule – ADOS). We employed a voxel-mirrored homotopic connectivity analysis to compare interhemispheric functional connectivity in 409 ASD and 455 typically developing subjects. Additionally, voxel-based morphology was used to investigate volumetric differences in the corpus callosum, the major commissure for interhemispheric communication. ASD subjects demonstrated significant reductions in interhemispheric functional connections between regions in the default mode network (medial prefrontal, posterior cingulate and precuneus), salience network (anterior cingulate and insula), mirror neuron/motor systems (inferior frontal gyrus, inferior parietal lobule, precentral gyrus, supplementary motor area), thalamus and auditory (superior temporal gyrus) and visual systems (lingual, fusiform and inferior occipital gyri). A support vector machine analysis based on interhemispheric connectivity (but not all homotopic) revealed an average classification accuracy of 88.70% for distinguishing ASD from controls across different sites. In ASD subjects symptom severity as measured by ADOS was negatively associated with posterior cingulate, insula and superior temporal gyrus homotopic functional connectivity. While ASD subjects displayed reduced anterior and posterior callosal volumes they were not associated with either ADOS scores or functional connectivity changes. Our findings suggest that reduced interhemispheric connectivity involving homotopic regions may be a potential biomarker for ASD with bilateral posterior cingulate, insula and superior temporal gyrus connections being associated with symptom severity.

Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder

ObjectiveSome individuals with functional neurological disorder (FND) exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. Given that the multimodal integration network (insula, dorsal cingulate, temporoparietal...

Insular changes induced by electroconvulsive therapy response to symptom improvements in schizophrenia

Although modified electroconvulsive therapy (MECT) has been employed as a treatment strategy and to resolve medication resistant symptoms in schizophrenia (SZ), its action mechanisms remain unclear. The insula has been demonstrated to associate with clinical symptoms and neuropathology in SZ. This study examined whether insular changes response to MECT outcomes in SZ. Forty-two SZ were divided into two groups according to their treatment strategies. One group (MSZ, n = 21) received 4-weeks MECT together with antipsychotics; another group (DSZ, n = 21) was treated only with antipsychotics. Twenty-three healthy controls (HC) were also included. Structural and functional MRI were scanned twice (baseline and after 4-week treatment) for SZ and once for HC. Firstly, the insula was divided into three subregions based on resting-state functional connectivity (FC). Subsequently, gray matter volume (GMV) and voxel-wise FC were assessed in each subregion. Finally, the relationship between insular changes and symptom improvements was also investigated. Compared with baseline, the DSZ group showed reduced GMV in insular subregions. In contrast, the MSZ group exhibited increased GMV in bilateral posterior insula (PIns); furthermore, the increase in the PIns was correlated with symptom improvements. Second, the decreased FC between right PIns and left orbitofrontal cortex, and left PIns and middle occipital gyrus was observed only in the MSZ group; moreover, these FC changes were associated with symptom improvements. The present study demonstrated that MECT induced insular changes, which may contribute to the mechanisms of MECT.

The Sound of Words Evokes Affective Brain Responses.

The long history of poetry and the arts, as well as recent empirical results suggest that the way a word sounds (e.g., soft vs. harsh) can convey affective information related to emotional responses (e.g., pleasantness vs. harshness). However, the neural correlates of the affective potential of the sound of words remain unknown. In an fMRI study involving passive listening, we focused on the affective dimension of arousal and presented words organized in two discrete groups of sublexical (i.e., sound) arousal (high vs. low), while controlling for lexical (i.e., semantic) arousal. Words sounding high arousing, compared to their low arousing counterparts, resulted in an enhanced BOLD signal in bilateral posterior insula, the right auditory and premotor cortex, and the right supramarginal gyrus. This finding provides first evidence on the neural correlates of affectivity in the sound of words. Given the similarity of this neural network to that of nonverbal emotional expressions and affective prosody, our results support a unifying view that suggests a core neural network underlying any type of affective sound processing.

Delay discounting mediates the association between posterior insular cortex volume and social media addiction symptoms.

Addiction-like symptoms in relation to excessive and compulsive social media use are common in the general population. Because they can lead to various adverse effects, there is a growing need to understand the brain systems and processes that are involved in potential social media addiction. We focus on the morphology of the posterior subdivision of the insular cortex (i.e., the insula), because it has been shown to be instrumental to supporting the maintenance of substance addictions and problematic behaviors. Assuming that social media addiction shares neural similarities with more established ones and consistent with evidence from the neuroeconomics domain, we further examine one possible reason for this association-namely that insular morphology influences one's delay discounting and that this delay discounting contributes to exaggerated preference for immediate social media rewards and consequent addiction-like symptoms. Based on voxel-based morphometry techniques applied to MRI scans of 32 social media users, we show that the gray matter volumes of the bilateral posterior insula are negatively associated with social media addiction symptoms. We further show that this association is mediated by delay discounting. This provides initial evidence that insular morphology can be associated with potential social media addiction, in part, through its contribution to poor foresight and impulsivity as captured by delay discounting.

Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease.

ObjectiveSevere hyposmia is a risk factor of dementia in Parkinson’s disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients with severe hyposmia (PD-SH) are unclear.MethodsWe examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH), and 15 healthy controls (HCs).ResultsDecreased gray matter volume (GMV) was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke’s Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH.ConclusionPD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

Motor-related brain abnormalities in HIV-infected patients: a multimodal MRI study.

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND.

Changes in Resting-State Cerebral Activity in Patients with Hyperthyroidism: A Short-Term Follow-Up Functional MR Imaging Study

To investigate the brain functional abnormality of hyperthyroid patients before and after treatment for one month using resting-state functional magnetic resonance imaging (rs-fMRI). Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analysis were performed in 27 new-onset untreated hyperthyroid patients relative to 30 healthy controls. In addition, follow-up data were available for 19 patients treated with methimazole for one month. Compared with healthy controls, patients exhibited lower ALFF in the right posterior cingulate cortex (PCC); increased FC in the bilateral anterior insula (AI), bilateral posterior insula (PI) and left anterior lobe of the cerebellum (ALC); and decreased FC in the bilateral lateral prefrontal cortex (LPFC), the right medial temporal gyrus (MTG) and the bilateral PCC. Compared with the hyperthyroid status, patients with improved thyroid function showed increased FC in the right LPFC and right dorsolateral prefrontal cortex (DLPFC). Subsequently, Pearson’s correlation analyses were performed between abnormal ALFF, FC, neuropsychological assessment and serum free triiodothyronine (FT3) levels. The results indicated that the alterations in regional and network-level brain functions, which might underlie different psychiatric complications were dynamic and interactional processes in hyperthyroidism. Moreover, the improvement in regional brain FC was correlated with the efficacy of anti-thyroid medication.

High Frequency Migraine Is Associated with Lower Acute Pain Sensitivity and Abnormal Insula Activity Related to Migraine Pain Intensity, Attack Frequency, and Pain Catastrophizing.

Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful), we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds nor in pre-scan pain ratings to mildly painful thermal stimuli, patients did have aberrant suprathreshold nociceptive processing. Brain imaging showed that, compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain vs. mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS); bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA) and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula, associated with indices of disease severity in migraine.

Reduced insula habituation associated with amplification of trigeminal brainstem input in migraine.

Background Impaired sensory processing in migraine can reflect diminished habituation, increased activation, or even increased gain or amplification of activity from the primary synapse in the brainstem to higher cortical/subcortical brain regions. Methods We scanned 16 episodic migraine (interictal) and 16 healthy controls (cross-sectional study), and evaluated brain response to innocuous air-puff stimulation over the right forehead in the ophthalmic nerve (V1) trigeminal territory. We further evaluated habituation, and cortical/subcortical amplification relative to spinal trigeminal nucleus (Sp5) activation. Results Migraine subjects showed greater amplification from Sp5 to the posterior insula and hypothalamus. In addition, while controls showed habituation to repetitive sensory stimulation in all activated cortical regions (e.g. the bilateral posterior insula and secondary somatosensory cortices), for migraine subjects, habituation was not found in the posterior insula. Moreover, in migraine, the habituation slope was correlated with the amplification ratio in the posterior insula and secondary somatosensory cortex, i.e. greater amplification was associated with reduced habituation in these regions. Conclusions These findings suggest that in episodic migraine, amplified information processing from spinal trigeminal relay nuclei is linked to an impaired habituation response. This phenomenon was localized in the posterior insula, highlighting the important role of this structure in mechanisms supporting altered sensory processing in episodic migraine.

Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms

Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the “hyperarousal theory” of insomnia symptoms, which could serve as a biomarker for insomnia.

Adolescent development of insula-dependent interoceptive regulation.

Adolescence is hypothesized to be a critical period for the maturation of self-regulatory capacities, including those that depend on interoceptive sensitivity, but the neural basis of interoceptive regulation in adolescence is unknown. We used functional magnetic resonance imaging and psychophysiology to study interoceptive regulation in healthy adolescent females. Participants regulated their gut activities in response to a virtual roller coaster by deep breathing aided by visually monitoring their online electrogastrogram (EGG) activity through a virtual thermometer (i.e. gut biofeedback), or without biofeedback. Analyses focused on the insula, given its putative role in interoception. The bilateral posterior insula showed increased activation in the no-biofeedback compared to biofeedback condition, suggesting that the participants relied more on interoceptive input when exteroceptive feedback was unavailable. The bilateral dorsal anterior insula showed activation linearly associated with age during both induction and regulation, and its activation during regulation correlated positively with change of EGG in the tachygastria frequency band from induction to regulation. Induction-related activation in the bilateral ventral anterior insula was nonlinearly associated with age and peaked at mid-adolescence. These results implicate different developmental trajectories of distinct sub-regions of the insula in interoceptive processes, with implications for competing neurobiological theories of female adolescent development.