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Journal of Clinical Neurophysiology :... Jul 2017The insular cortex, or "Island of Reil," is hidden deep within the lateral sulcus of the brain. Subdivisions within the insula have been identified on the basis of... (Meta-Analysis)
Meta-Analysis Review
The insular cortex, or "Island of Reil," is hidden deep within the lateral sulcus of the brain. Subdivisions within the insula have been identified on the basis of cytoarchitectonics, sulcal landmarks, and connectivity. Depending on the parcellation technique used, the insula can be divided into anywhere between 2 and 13 distinct subdivisions. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognition. Here, we provide a concise summary of known structural and functional features of the human insular cortex with a focus on lesion case studies and recent neuroimaging evidence for considerable functional heterogeneity of this brain region.
Topics: Cerebral Cortex; Humans
PubMed: 28644199
DOI: 10.1097/WNP.0000000000000377 -
Current Biology : CB Jun 2017Whether you see the person you are in love with, try to listen to your own heartbeat, suffer from a headache, or crave for a chocolate cookie, one part of your brain is...
Whether you see the person you are in love with, try to listen to your own heartbeat, suffer from a headache, or crave for a chocolate cookie, one part of your brain is sure to increase its activity strongly: the insular cortex. The insular cortex, or 'insula' for short, is part of the cerebral cortex. J.C. Reil, a German neurologist, first named this brain structure in the early 19 century. Subsequent research findings have implicated the insula in an overwhelming variety of functions ranging from sensory processing to representing feelings and emotions, autonomical and motor control, risk prediction and decision-making, bodily- and self-awareness, and complex social functions like empathy. How is one single brain area involved in so many different tasks? Is the insula comprised of several functional regions? How are these related? And, are there any common themes underlying the apparently so heterogeneous roles of the insula?
Topics: Cerebral Cortex; Humans; Mental Disorders; Neural Pathways
PubMed: 28633023
DOI: 10.1016/j.cub.2017.05.010 -
Cell Nov 2021Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear....
Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear. Here, we show that the brain's insular cortex (InsCtx) stores immune-related information. Using activity-dependent cell labeling in mice (Fos), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.
Topics: Animals; Colitis; Colon; Dextran Sulfate; Female; Immunity; Inflammation; Insular Cortex; Male; Mice; Mice, Inbred C57BL; Neurons; Peritoneum; Peritonitis; Synapses; Zymosan
PubMed: 34752731
DOI: 10.1016/j.cell.2021.10.013 -
Nature Mar 2023Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart. However, whether an increased...
Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.
Topics: Animals; Mice; Anxiety; Brain; Brain Mapping; Emotions; Heart; Behavior, Animal; Electrophysiology; Optogenetics; Insular Cortex; Heart Rate; Channelrhodopsins; Tachycardia; Pacemaker, Artificial
PubMed: 36859543
DOI: 10.1038/s41586-023-05748-8 -
Neuron Jun 2022Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience...
Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.
Topics: Animals; Basolateral Nuclear Complex; Cerebral Cortex; Glutamic Acid; Insular Cortex; Mice; Pain; Synapses
PubMed: 35443154
DOI: 10.1016/j.neuron.2022.03.030 -
Cell Dec 2021The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we...
The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aIC), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aIC neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC → NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aIC neurons do not represent taste or valence. Moreover, aIC → NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC → NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC's top-down regulation of dopamine signaling.
Topics: Animals; Behavior, Animal; Brain Stem; Dopamine; Female; Insular Cortex; Learning; Male; Mice, Inbred C57BL; Motivation; Neural Pathways; Neurons; Nucleus Accumbens; Time Factors; Mice
PubMed: 34890577
DOI: 10.1016/j.cell.2021.11.019 -
Frontiers in Molecular Neuroscience 2017The sense of taste is a key component of the sensory machinery, enabling the evaluation of both the safety as well as forming associations regarding the nutritional... (Review)
Review
The sense of taste is a key component of the sensory machinery, enabling the evaluation of both the safety as well as forming associations regarding the nutritional value of ingestible substances. Indicative of the salience of the modality, taste conditioning can be achieved in rodents upon a single pairing of a tastant with a chemical stimulus inducing malaise. This robust associative learning paradigm has been heavily linked with activity within the insular cortex (IC), among other regions, such as the amygdala and medial prefrontal cortex. A number of studies have demonstrated taste memory formation to be dependent on protein synthesis at the IC and to correlate with the induction of signaling cascades involved in synaptic plasticity. Taste learning has been shown to require the differential involvement of dopaminergic GABAergic, glutamatergic, muscarinic neurotransmission across an extended taste learning circuit. The subsequent activation of downstream protein kinases (ERK, CaMKII), transcription factors (CREB, Elk-1) and immediate early genes (c-fos, Arc), has been implicated in the regulation of the different phases of taste learning. This review discusses the relevant neurotransmission, molecular signaling pathways and genetic markers involved in novel and aversive taste learning, with a particular focus on the IC. Imaging and other studies in humans have implicated the IC in the pathophysiology of a number of cognitive disorders. We conclude that the IC participates in circuit-wide computations that modulate the interception and encoding of sensory information, as well as the formation of subjective internal representations that control the expression of motivated behaviors.
PubMed: 29163022
DOI: 10.3389/fnmol.2017.00335 -
Biology Apr 2023The insula is a multiconnected brain region that centralizes a wide range of information, from the most internal bodily states, such as interoception, to high-order... (Review)
Review
The insula is a multiconnected brain region that centralizes a wide range of information, from the most internal bodily states, such as interoception, to high-order processes, such as knowledge about oneself. Therefore, the insula would be a core region involved in the self networks. Over the past decades, the question of the self has been extensively explored, highlighting differences in the descriptions of the various components but also similarities in the global structure of the self. Indeed, most of the researchers consider that the self comprises a phenomenological part and a conceptual part, in the present moment or extending over time. However, the anatomical substrates of the self, and more specifically the link between the insula and the self, remain unclear. We conducted a narrative review to better understand the relationship between the insula and the self and how anatomical and functional damages to the insular cortex can impact the self in various conditions. Our work revealed that the insula is involved in the most primitive levels of the present self and could consequently impact the self extended in time, namely autobiographical memory. Across different pathologies, we propose that insular damage could engender a global collapse of the self.
PubMed: 37106799
DOI: 10.3390/biology12040599 -
Nature Communications Aug 2023Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, neural coding of...
Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, neural coding of both anxiety and valence by IC neurons remains unknown. Using fiber photometry recordings in mice, we uncover a selective increase of activity in IC projection neurons of the anterior (aIC), but not posterior (pIC) section, when animals are exploring anxiogenic spaces, and this activity is proportional to the level of anxiety of mice. Neurons in aIC also respond to stimuli of positive and negative valence, and the strength of response to strong negative stimuli is proportional to mice levels of anxiety. Using ex vivo electrophysiology, we characterized the IC connection to the basolateral amygdala (BLA), and employed projection-specific optogenetics to reveal anxiogenic properties of aIC-BLA neurons. Finally, we identified that aIC-BLA neurons are activated in anxiogenic spaces, as well as in response to aversive stimuli, and that both activities are positively correlated. Altogether, we identified a common neurobiological substrate linking negative valence with anxiety-related information and behaviors, which provides a starting point to understand how alterations of these neural populations contribute to psychiatric disorders.
Topics: Animals; Mice; Insular Cortex; Anxiety; Emotions; Anxiety Disorders; Amygdala
PubMed: 37604802
DOI: 10.1038/s41467-023-40517-1