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The insular cortex and anterior cingulate cortex together comprise the salience or midcingulo‐insular network, involved in detecting salient events and initiating control signals to mediate brain network dynamics. The extent to which functional coupling between the salience network and the rest of the brain undergoes changes due to development and aging is at present largely unexplored. Here, we examine dynamic functional connectivity (dFC) of the salience network in a large life span sample (n = 601; 6–85 years old). A sliding‐window analysis and k‐means clustering revealed five states of dFC formed with the salience network, characterized by either widespread asynchrony or different patterns of synchrony between the salience network and other brain regions. We determined the frequency, dwell time, total transitions, and specific state‐to‐state transitions for each state and subject, regressing the metrics with subjects' age to identify life span trends. A dynamic state characterized by low connectivity between the salience network and the rest of the brain had a strong positive quadratic relationship between age and both frequency and dwell time. Additional frequency, dwell time, total transitions, and state‐to‐state transition trends were observed with other salience network states. Our results highlight the metastable dynamics of the salience network and its role in the maturation of brain regions critical for cognition. Here, we examine dynamic functional connectivity (dFC) of the salience network in a large life span sample (n = 601). A sliding‐window analysis and k‐means clustering revealed five states of dFC formed with the salience network, characterized by either widespread asynchrony or different patterns of synchrony between the salience network and other brain regions. Life span trends in the frequency, dwell time, and transitions of these states highlight the role of metastability maturation in cognitively important brain regions.

Purpose Evidence from animal and human studies demonstrates that cortical regions play a key role in autonomic modulation with a differential role for some brain regions located in the left and right brain hemispheres. Known as autonomic asymmetry, this phenomenon has been demonstrated by clinical observations, by experimental models, and currently by combined neuroimaging and direct recordings of sympathetic nerve activity. Previous studies report peculiar autonomic-mediated cardiovascular alterations following unilateral damage to the left or right insula, a multifunctional key cortical region involved in emotional processing linked to autonomic cardiovascular control and featuring asymmetric characteristics. Methods Based on clinical studies reporting specific damage to the insular cortex, this review aims to provide an overview of the prognostic significance of unilateral (left or right hemisphere) post-insular stroke cardiac alterations. In addition, we review experimental data aiming to unravel the central mechanisms involved in post-insular stroke cardiovascular complications. Results and Conclusion Current clinical and experimental data suggest that stroke of the right insula  can present a worse cardiovascular prognosis.

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart 1 – 3 . However, whether an increased heart rate might itself induce anxiety or fear responses is unclear 3 – 8 . 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 9 . 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. Direct elevation of heart rate using noninvasive optogenetics in mice influences anxiety-like behaviours in specific environmental contexts, and the posterior insular cortex is implicated in this integration of signals from the heart with environmental risk information.

Trigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) is thought to involve several neuroplastic changes in multiple brain regions, resulting in distorted pain perception and associated comorbidities. While the functional changes in the insula are recognized contributors to TNP, the intricate mechanisms underlying the involvement of the insula in TNP processing remain subjects of ongoing investigation. Here, we have overviewed the most recent advancements regarding the functional role of IC in regulating TNP alongside insights into the IC’s connectivity with other brain regions implicated in trigeminal pain pathways. In addition, the review examines diverse modulation strategies that target the different parts of the IC, thereby suggesting novel diagnostic and therapeutic management of chronic TNP in the future.

Noradrenergic activation of the basolateral amygdala (BLA) by emotional arousal enhances different forms of recognition memory via functional interactions with the insular cortex (IC). Human neuroimaging studies have revealed that the anterior IC (aIC), as part of the salience network, is dynamically regulated during arousing situations. Emotional stimulation first rapidly increases aIC activity but suppresses it in a delayed fashion. Here, we investigated in male Sprague-Dawley rats whether the BLA influence on recognition memory is associated with an increase or suppression of aIC activity during the postlearning consolidation period. We first employed anterograde and retrograde viral tracing and found that the BLA sends dense monosynaptic projections to the aIC. Memory-enhancing norepinephrine administration into the BLA following an object training experience suppressed aIC activity 1 h later, as determined by a reduced expression of the phosphorylated form of the transcription factor cAMP response element-binding (pCREB) protein and neuronal activity marker c-Fos. In contrast, the number of perisomatic γ-aminobutyric acid (GABA)ergic inhibitory synapses per pCREB-positive neuron was significantly increased, suggesting a dynamic up-regulation of GABAergic tone. In support of this possibility, pharmacological inhibition of aIC activity with a GABAergic agonist during consolidation enhanced object recognition memory. Norepinephrine administration into the BLA did not affect neuronal activity within the posterior IC, which receives sparse innervation from the BLA. The evidence that noradrenergic activation of the BLA enhances the consolidation of object recognition memory via a mechanism involving a suppression of aIC activity provides insight into the broader brain network dynamics underlying emotional regulation of memory.

Temperature is a fundamental sensory modality separate from touch, with dedicated receptor channels and primary afferent neurons for cool and warm 1 – 3 . Unlike for other modalities, however, the cortical encoding of temperature remains unknown, with very few cortical neurons reported that respond to non-painful temperature, and the presence of a ‘thermal cortex’ is debated 4 – 8 . Here, using widefield and two-photon calcium imaging in the mouse forepaw system, we identify cortical neurons that respond to cooling and/or warming with distinct spatial and temporal response properties. We observed a representation of cool, but not warm, in the primary somatosensory cortex, but cool and warm in the posterior insular cortex (pIC). The representation of thermal information in pIC is robust and somatotopically arranged, and reversible manipulations show a profound impact on thermal perception. Despite being positioned along the same one-dimensional sensory axis, the encoding of cool and that of warm are distinct, both in highly and broadly tuned neurons. Together, our results show that pIC contains the primary cortical representation of skin temperature and may help explain how the thermal system generates sensations of cool and warm. A study using calcium imaging in the mouse forepaw system identifies neurons in the posterior insular cortex that respond to cooling and/or warming with distinct response dynamics.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303 .

Inhibiting prepotent responses in the face of external stop signals requires complex information processing, from perceptual to control processing. However, the cerebral circuits underlying these processes remain elusive. In this study, we used neuroimaging and brain stimulation to investigate the interplay between human brain regions during response inhibition at the whole-brain level. Magnetic resonance imaging suggested a sequential four-step processing pathway: initiating from the primary visual cortex (V1), progressing to the dorsal anterior insula (daINS), then involving two essential regions in the inferior frontal cortex (IFC), namely the ventral posterior IFC (vpIFC) and anterior IFC (aIFC), and reaching the basal ganglia (BG)/primary motor cortex (M1). A combination of ultrasound stimulation and time-resolved magnetic stimulation elucidated the causal influence of daINS on vpIFC and the unidirectional dependence of aIFC on vpIFC. These results unveil asymmetric pathways in the insular - prefrontal cortex and outline the macroscopic cerebral circuits for response inhibition: V1→daINS→vpIFC/aIFC→BG/M1. Osada et al. used MRI and brain stimulation to outline the macroscopic cerebral circuits for response inhibition: visual cortex→dorsal anterior insula→inferior frontal cortex→basal ganglia/motor cortex, confirming the insula’s critical bridging role.

Motor BCIs, with the help of Artificial Intelligence (AI) and machine learning, have shown promise in decoding neural signals for restoring motor function. Structures beyond motor cortex have provided additional sources for movement signals. New evidence points to the role of the insula in motor control, specifically directional hand-movements. In this study, we applied AI and machine learning techniques to decode directional hand-movements from high-gamma band (70–200 Hz) activity in the insular cortex. Seven participants with medication-resistant epilepsy underwent stereo electroencephalographic (SEEG) implantation of depth electrodes for seizure monitoring in the insula. SEEG data were sampled throughout a cued motor task involving three conditions: left-hand movement, right-hand movement, or no movement. Neural signal processing focused on high-gamma band activity. Demixed Principal Component Analysis (dPCA) was used for dimension reduction (d = 10) and feature extraction from the time-frequency analysis. For movement classification, we implemented a bidirectional Long Short-Term Memory (LSTM) architecture with a single layer, utilizing the capacity to process temporal sequences in forward and back directions for optimal decoding of movement direction. Our findings revealed robust directional-specific high-gamma modulation within the insular cortex during motor execution. Temporal decomposition through dPCA demonstrated distinct spatiotemporal patterns of high-gamma activity across movement conditions. Subsequently, LSTM networks successfully decoded these condition-specific neural signatures, achieving a classification accuracy of 72.6% ± 13.0% (mean ± SD), which significantly exceeded chance-level performance of 33.3% ( p  < 0.0001, n  = 16 sessions). Furthermore, we identified a strong negative correlation between temporal distance of training-testing sessions and decoding performance ( r = -0.868, p  < 0.0001), indicating temporal difference of the neural representations. Our study highlights the potential role of deep brain structures, such as the insula, in conditional movement discrimination. We demonstrate that LSTM networks and high-gamma band analysis can advance the understanding of neural mechanisms underlying movement. These insights may pave the way for improvements in SEEG-based BCI.

•We delineate fundamental neurophysiological mechanisms for how people can act intentionally.•We show that the ability to foresee the effects of action is a role of a theta activity.•There is bi-directional communication between temporo-frontal cortices is essential.•The results conceptually broaden the relevance of theta band activity. The ability to plan and carry out goal-directed behavior presupposes knowledge about the contingencies between movements and their effects. Ideomotor accounts of action control assume that agents integrate action-effect contingencies by creating action-effect bindings, which associate movement patterns with their sensory consequences. However, the neurophysiological underpinnings of action-effect binding are not yet well understood. Given that theta band activity has been linked to information integration, we thus studied action-effect integration in an electrophysiological study with N = 31 healthy individuals with a strong focus on theta band activity. We examined how information between functional neuroanatomical structures is exchanged to enable action planning. We show that theta band activity in a network encompassing the insular cortex (IC), the anterior temporal lobe (ATL), and the inferior frontal cortex (IFC) supports the establishment of action-effect bindings. All regions revealed bi-directional effective connectivities, indicating information transfer between these regions. The IC and ATL create a loop for information integration and the conceptual abstraction of it. The involvement of anterior regions of the IFC, particularly during the acquisition phase of the action-effect, likely reflects episodic control mechanisms in which a past event defines a “template” of what action-effect is to be expected. Taken together, the current findings connect well with major cognitive concepts. Our study suggests a functional relevance of theta band activity in an IC-ATL-IFC network, which in turn implies that basic ideomotor action-effect integration is implemented through theta band activity and effective connectivities between temporo-frontal structures.