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Much remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding. Single-unit activity was recorded in the AIC from 15 male rats during alcohol-only and compulsion-like consumption. We found three sustained firing phenotypes, sustained-increase, sustained-decrease, and drinking-onset cells, as well as several firing patterns synchronized with licking. While many AIC neurons had session-long activity changes, only neurons with firing increases at drinking onset had greater activity under compulsion-like conditions. Further, only cells with persistent firing increases maintained activity during pauses in licking, suggesting roles in maintaining drive for alcohol during breaks. AIC firing was not elevated during saccharin drinking, similar to lack of effect of AIC inhibition on sweet fluid intake in many studies. In addition, we observed subsecond changes in AIC neural activity tightly entrained to licking. One lick-synched firing pattern (determined for all licks in a session) predicted compulsion-like drinking, while a separate lick-associated pattern correlated with greater consumption across alcohol intake conditions. Collectively, these data provide a more integrated model for the role of AIC firing in compulsion-like drinking, with important relevance for how the AIC promotes sustained motivated responding more generally. [ABSTRACT FROM AUTHOR]

Better understanding of breathlessness perception addresses an unmet clinical need for more effective treatments for intractable dyspnoea, a prevalent symptom of multiple medical conditions. The insular-cortex is predominantly activated in brain-imaging studies of dyspnoea, but its precise role remains unclear. We measured experimentally-induced hypercapnic air-hunger in three insular-glioma patients before and after surgical resection. Tests involved one- minute increments in inspired CO2, raising end-tidal PCO2 to 7.5 mmHg above baseline (38.5 ± 5.7 mmHg), whilst ventilation was constrained (10.7 ± 2.3 L/min). Patients rated air-hunger on a visual analogue scale (VAS). Patients had lower stimulus--response (2.8 ± 2 vs. 11 ± 4 %VAS/mmHg; p = 0.004), but similar threshold (40.5 ± 3.9 vs. 43.2 ± 5.1 mmHg), compared to healthy individuals. Volunteered comments implicated diminished affective valence. After surgical resection; sensitivity increased in one patient, decreased in another, and other was unable to tolerate the ventilatory limit before any increase in inspired CO2. We suggest that functional insular-cortex is essential to register breathlessness unpleasantness and could be targeted with neuromodulation in chronically- breathless patients. Neurological patients with insula involvement should be monitored for blunted breathlessness to inform clinical management. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has been approved by Health Canada for smoking cessation. It is a safe and well-tolerated procedure that offers an alternative treatment option for individuals who want to quit smoking. The treatment involves daily sessions over the course of 3 weeks, followed by weekly sessions for 3 weeks. Clinical trials have shown positive results, with higher abstinence rates compared to sham stimulation. However, rTMS is currently only available in a limited number of clinics in Canada, and further research is needed to analyze real-world patient outcomes and cost-effectiveness. [Extracted from the article]

Background: Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. Methods: This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters. Results: When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups. Conclusions: This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central–peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central–peripheral system interaction mechanisms involved in autoimmune diseases. [ABSTRACT FROM AUTHOR]

While functional brain imaging studies in humans suggest that chronic cocaine use alters functional connectivity (FC) within and between key large-scale brain networks, including the default mode network (DMN), the salience network (SN), and the central executive network (CEN), cross-sectional studies in humans are challenging to obtain brain FC prior to cocaine use. Such information is critical to reveal the relationship between individual's brain FC and the subsequent development of cocaine dependence and brain changes during abstinence. Here, we performed a longitudinal study examining functional magnetic resonance imaging (fMRI) data in male rats (n = 7), acquired before cocaine self-administration (baseline), on 1 d of abstinence following 10 d of cocaine self-administration, and again after 30 d of experimenter-imposed abstinence. Using repeated-measures analysis of variance (ANOVA) with network-based statistics (NBS), significant connectivity changes were found between anterior insular cortex (AI) of the SN, retrosplenial cortex (RSC) of the DMN, somatosensory cortex, and caudate–putamen (CPu), with AI–RSC FC showing the most robust changes between baseline and 1 d of abstinence. Additionally, the level of escalated cocaine intake is associated with AI–RSC and AI– CPu FC changes between 1 d and 30 d of abstinence; further, the subjects’ AI–RSC FC prior to cocaine intake is a significant moderator for the AI–RSC changes during abstinence. These results provide novel insights into the roles of AI–RSC FC before and after cocaine intake and suggest this circuit to be a potential target to modulate large-scale network and associated behavioral changes in cocaine use disorders. [ABSTRACT FROM AUTHOR]

• Our study explored the executive function deficits(EFD) after trauma exposed. • The adult who has lost their only child is a special type of trauma. • The results of the excessive connection between the anterior insula and DMN might contribute to EFD after trauma exposed. There is increasing evidence that major trauma can adversely affect the brain and cognition. In some cases, trauma may lead to deficits in executive function (EF). The anterior insula may be a causal outflow hub acting to coordinate EF-related brain networks. To clarify the neural underpinnings of EF deficits (EFD) after trauma, we performed a resting-state functional magnetic resonance imaging (rs-fMRI) study of anterior insular subnetworks in adults who have lost their only child. A total of 167 participants completed various psychological and cognitive assessments to assess EF-related deficits. Correlations were computed between abnormal connectivity and cognitive/post-traumatic stress symptoms. The results showed abnormal anterior insular subregion connectivity in the default mode network (DMN), prefrontal lobe, and cerebellum lobe in participants with EFD. No correlation was found between abnormal connectivity and cognitive/post-traumatic stress symptoms in participants with EFD. These results suggest that excessive connections between the insula and DMN could contribute to EFD after trauma. Overall, this study provides novel references into the neural mechanisms of EF status after trauma exposure. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that emotional reactivity changes with age, but the neural basis is still unclear. The insula may be critical for the emotional reactivity. The current study examined how ageing affects emotional reactivity using the emotional reactivity task data from a human sample (Cambridge Center for Age and Neuroscience, N = 243, age 18–88 years). The resting‐state magnetic resonance measurements from the same sample were used to investigate the potential mechanisms of the insula. In the initial analysis, we conducted partial correlation assessments to examine the associations between emotional reactivity and age, as well as between the gray matter volume (GMV) of the insula and age. Our results revealed that emotional reactivity, especially positive emotional reactivity, decreased with age and that the GMV of the insula was negatively correlated with age. Subsequently, the bilateral insula was divided into six subregions to calculate the whole brain resting‐state functional connectivity (rsFC). The mediating effect of the rsFC on age and emotional reactivity was then calculated. The results showed that the rsFC of the left anterior insula (AI) with the right hippocampus, and the rsFCs of the right AI with the striatum and the thalamus were mediated the relationship between positive emotional reactivity and age. Our findings suggest that attenuating emotional reactivity with age may be a strategic adaptation fostering emotional stability and diminishing emotional vulnerability. Meanwhile, the findings implicate a key role for the AI in the changes in positive emotional reactivity with age. [ABSTRACT FROM AUTHOR]

Borderline Personality Disorder (BPD) is a severe mental disorder, characterized by deficits in emotion regulation, interpersonal dysfunctions, dissociation and impulsivity. Brain abnormalities have been generally explored; however, the specific contribution of different limbic structures to BPD symptomatology is not described. The aim of this study is to cover this gap, exploring functional and structural alterations of amygdala and insula and to highlight their contribution to neuropsychiatric symptoms. Twenty-eight BPD patients (23.7 ± 3.42 years; 6 M/22F) and twenty-eight matched healthy controls underwent a brain MR protocol (1.5 T, including a 3D T1-weighted sequence and resting-state fMRI) and a complete neuropsychiatric assessment. Volumetry, cortical thickness and functional connectivity of amygdala and insula were evaluated, along with correlations with the neuropsychiatric scales. BPD patients showed a lower cortical thickness of the left insula (p = 0.027) that negatively correlated with the Anger Rumination Scale (p = 0.019; r = − 0.450). A focused analysis on female patients showed a significant reduction of right amygdala volumes in BPD (p = 0.037), that correlate with Difficulties in Emotion Regulation Scale (p = 0.031; r = − 0.415), Beck Depression Inventory (p = 0.009; r = − 0.50) and Ruminative Response Scale (p = 0.045; r = − 0.389). Reduced functional connectivity was found in BPD between amygdala and frontal pole, precuneus and temporal pole. This functional connectivity alterations correlated with Anger Rumination Scale (p =.009; r = − 0.491) and Barratt Impulsiveness Scale (p = 0.020; r = − 0.447). Amygdala and insula are altered in BPD patients, and these two limbic structures are implicated in specific neuropsychiatric symptoms, such as difficulty in emotion regulation, depression, anger and depressive rumination. [ABSTRACT FROM AUTHOR]

Objective: Atrial fibrillation (AF) detected after insular stroke might arise from autonomic and inflammatory mechanisms triggered by insular damage, and be associated with a low embolic risk. We assessed the association of the timing of AF detection and insular involvement with the risk of embolic events after acute ischemic stroke. Methods: Acute ischemic stroke patients with AF who underwent brain magnetic resonance imaging at baseline were enrolled. Patients were classified according to the timing of AF detection (AF detected after stroke [AFDAS] or known AF [KAF]) and insular involvement. The primary outcome was embolic events defined as recurrent ischemic stroke, transient ischemic attack, and systemic embolism within 90 days. Results: Of 1,548 patients, 360 had AFDAS with insular cortex lesions (+I), 409 had AFDAS without insular cortex lesions (−I), 349 had KAF+I, and 430 had KAF−I. Cumulative incidence rates of embolic events at 90 days in patients with AFDAS+I, AFDAS−I, KAF+I, and KAF−I were 0.8%, 3.5%, 4.9%, and 3.3%, respectively. Patients with AFDAS−I (adjusted hazard ratio 5.04, 95% confidence interval 1.43–17.75), KAF+I (6.18, 1.78–21.46), and KAF−I (5.26, 1.48–18.69) had a significantly higher risk of embolic events than those with AFDAS+I. Interpretation: Acute ischemic stroke patients with AFDAS and insular cortex lesions had a lower risk of embolic events than those who had AFDAS without insular cortex lesions or those with KAF, regardless of insular involvement. ANN NEUROL 2024;95:338–346 [ABSTRACT FROM AUTHOR]

Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. Compared with both control conditions, psychosocial stress elicited higher alcohol cue–induced activation in the left anterior insula (familywise error–corrected p <.05) and a stress- and cue-specific dynamic increase in insula activation over time (F 22,968 = 2.143, p =.007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate–corrected p =.016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate–corrected p =.032) and alcohol use during follow-up (r = 0.218, false discovery rate–corrected p =.046). Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients. Methods: A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel‐based morphometry (VBM) and surface‐based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one‐way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale‐17 (HAMD‐17) scores. Results: PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal–occipital–temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD‐17 scores in the PDD group tended to be significant (r = −0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth. Conclusion: Our research shows extensive cortical structural changes in the insular cortex, parietal–occipital–temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Aims: Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients. Discussion: We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic‐parasympathetic balance, would potentially improve clinical outcomes in ICH patients. Conclusion: The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes. [ABSTRACT FROM AUTHOR]

The Municipality of Venice, through Insula srl (Insula, 2024), started the RAMSES (Rilievo Altimetrico, Modellazione Spaziale E Scansione 3D) project in 2005 with the unprecedented intention of conducting a static laser scanner survey of an entire city. The authors of this paper, who have been involved in the project on behalf of the client, including drafting general contract technical specifications, wished to revisit the survey's findings nearly two decades later. This contribution illustrates the procedures implemented to guarantee the future accessibility of the surveyed data. It is interesting to highlight how the detailed technical specifications outlined in the general technical contract section have facilitated the retrieval of the historical three-dimensional laser scanner measurements archive. Tests have been conducted to determine how the existing mobile mapping technologies may be utilised to update the three-dimensional historical data obtained in the Ramses project efficiently. Furthermore, the paper describes the surveying approach that has never been adequately described in the literature. The surveying and geo-referencing methodologies continue to have several interesting and relevant aspects, especially regarding how the topographic network has been implemented. The Ramses three-dimensional model represents an extraordinary, valuable digital archive containing portraits of the city's conditions at the time of the mapping. Ramses 3D model, when enriched with field activities conducted using more updated technologies, can provide interesting and unique evaluations of the evolution of Venice's landscape. [ABSTRACT FROM AUTHOR]

Context: An existing major challenge in Parkinson's disease (PD) research is the identification of biomarkers of disease progression. While magnetic resonance imaging is a potential source of PD biomarkers, none of the magnetic resonance imaging measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations. Objective: This study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinson's Progression Markers Initiative (PPMI). Methods: Using 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between structural changes and cognitive decline. We compared our findings to the results in the original study. Results: (1) Similarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance. Conclusion: Despite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data is added to PPMI. [ABSTRACT FROM AUTHOR]

Neuroimaging data in humans and neurobiological studies in rodents have suggested an involvement of the insular cortex (IC) in anxiety manifestations. However, the local neurochemical mechanisms involved are still poorly understood. Corticotropin-releasing factor (CRF) neurotransmission has been described as a prominent neurochemical mechanism involved in the expression of anxiety-like behaviors, but the brain sites related are poorly understood. Additionally, several findings indicate that control of physiological and behavioral responses by the IC occurs in a site-specific manner along its rostrocaudal axis. Thus, this study is aimed at evaluating the effect of CRF receptor agonism and antagonism within the anterior and posterior subregions of the IC in controlling anxiety-related behaviors in the elevated plus maze (EPM). For this, independent groups (six groups) of animals received bilateral microinjections of vehicle, the selective CRF1 receptor antagonist CP376395, or CRF into either the anterior or posterior subregions of the IC. Ten minutes later, the behavior in the EPM was evaluated for five minutes. Treatment of the anterior IC with CP376395, but not with CRF, increased the time and number of entries into the open arms of the EPM. CRF, but not the CRF1 receptor antagonist, microinjected into the posterior IC also increased exploration of the EPM open arms. Taken together, these data indicate that CRFergic neurotransmission in the anterior IC is involved in the expression of anxiety-related behaviors in the EPM. This neurochemical mechanism does not seem to be activated within the posterior IC during exposure to the EPM, but the effects caused by CRF microinjection indicate that activation of CRF receptors in this IC subregion might evoke anxiolytic-like effects. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common highly aggressive malignant brain tumor, with a very limited chance for survival post-diagnosis and post-treatment. Despite significant advancement in GBM genomics implicated in molecularly targeted chemotherapies, the prognosis remains poor and requires new drug discovery approaches. We used fluoropyrimidine 5-fluorouracil (5-FU), an antimetabolite anticancer drug conjugated or 'caged' within a lipophilic Ru(II)-diphosphine (dppe) core formulated as [RuII(dppe)2(5-FU)]PF6 (Ru-DPPE-5FU), where dppe = 1,2-bis(diphenylphosphino)ethane, and evaluated its in vitro cytotoxicity in depth with aggressive GBM cells (LN229). The hydrophilic nature of 5-FU limits its passage through the blood–brain barrier (BBB), which prevents its effective accumulation and efficacy for GBM tumors. Herein, we attempted to modulate the lipophilicity of 5-FU by inserting it within a well-designed lipophilic {Ru(dppe)2}-core with anticipated higher efficiency towards GBM. The physicochemical properties of [RuII(dppe)2(5-FU)]PF6 (Ru-DPPE-5FU) were studied using various spectroscopic and analytical techniques. The molecular structure was determined using X-ray crystallography, showing a distorted {RuP4NO} octahedral geometry with bidentate (N, O) binding of 5-FU and its aromatization in the Ru(II)-bound form. The 31P-NMR spectra of Ru-DPPE-5FU showed four closely spaced distinct 31P-signals, indicating four unique chemical environments around P, and the strong coupling constants between them make it a second-order spectrum. The RuII/RuIII redox potential in Ru-DPPE-5FU shifted by ∼0.91 V towards the anodic region as compared to its precursor complex cis-[Ru(dppe)2Cl2] (Ru-DPPE-Cl). DFT-based theoretical calculations have been performed to correlate the experimental electronic absorption spectra and redox behaviours of the complexes. The electrostatic potential (ESP) plots indicate the delocalization of the charge density on the O-/F-atom from the 5-FU ligand towards Ru(II) upon its complexation. The antioxidant properties of all the compounds were quantified by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The hyphenation of the 5-fluorouracil (5-FU) ligand to the lipophilic {Ru(dppe)2}-core endowed lipophilicity to Ru-DPPE-5FU with higher in vitro cytotoxicity (IC50 = 2.37 μM) against the LN229 GBM cells as compared to the hydrophilic 5-FU, suggesting efficient cellular uptake. Further biological assays indicated that the complex is highly potent in inhibiting significant proliferation and spheroid formation and restricting the migratory potentials of the GBM cells. Increased caspase 3/7 activity and the presence of apoptotic bodies at the center of 3-D GBM spheroids as revealed by AO/EB dual staining indicated a deeper penetration of the lipophilic complex. The Ru-DPPE-5FU complex displayed lower cytotoxicity in HaCaT normal cells (IC50 = 7.27 μM) in comparison to LN229 cancer cells with a selectivity index (S.I.) of ≥3. Overall, the synergism and caging of 5-FU within the hydrophobic {Ru(dppe)2}-core improves the pharmacokinetic profile of Ru-DPPE-5FU as a potent anticancer agent for glioblastoma. [ABSTRACT FROM AUTHOR]

The brain operates in a flexible dynamic regime, generating complex patterns of activity (i.e. neuronal avalanches). This study aimed at describing how brain dynamics change according to menstrual cycle (MC) phases. Brain activation patterns were estimated from resting-state magnetoencephalography (MEG) scans, acquired from women at early follicular (T1), peri-ovulatory (T2) and mid-luteal (T3) phases of the MC. We investigated the functional repertoire (number of brain configurations based on fast high-amplitude bursts of the brain signals) and the region-specific influence on large-scale dynamics across the MC. Finally, we assessed the relationship between sex hormones and changes in brain dynamics. A significantly larger number of visited configurations in T2 as compared to T1 was specifically observed in the beta frequency band. No relationship between changes in brain dynamics and sex hormones was evident. Finally, we showed that the left posterior cingulate gyrus and the right insula were recruited more often in the functional repertoire during T2 as compared to T1, while the right pallidum was more often part of the functional repertoires during T1 as compared to T2. In summary, we showed hormone-independent increased flexibility of the brain dynamics during the ovulatory phase. Moreover, we demonstrated that several specific brain regions play a key role in determining this change. [ABSTRACT FROM AUTHOR]

Background: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. Aim: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. Methods: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. Results: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. Conclusion: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary. [ABSTRACT FROM AUTHOR]

The insular cortex (IC) integrates sensory and interoceptive cues to inform downstream circuitry executing adaptive behavioral responses. The IC communicates with areas involved canonically in stress and motivation. IC projections govern stress and ethanol recruitment of bed nucleus of the stria terminalis (BNST) activity necessary for the emergence of negative affective behaviors during alcohol abstinence. Here, we assess the impact of the chronic drinking forced abstinence (CDFA) volitional home cage ethanol intake paradigm on synaptic and excitable properties of IC neurons that project to the BNST (IC→BNST). Using whole-cell patch-clamp electrophysiology, we investigated IC→BNST circuitry 24 h or 2 weeks following forced abstinence (FA) in female C57BL6/J mice. We find that IC→BNST cells are transiently more excitable following acute ethanol withdrawal. In contrast, in vivo ethanol exposure via intraperitoneal injection, ex vivo via ethanol wash, and acute FA from a natural reward (sucrose) all failed to alter excitability. In situ hybridization studies revealed that at 24 h post FA BK channel mRNA expression is reduced in IC. Further, pharmacological inhibition of BK channels mimicked the 24 h FA phenotype, while BK activation was able to decrease AP firing in control and 24 h FA subjects. All together these data suggest a novel mechanism of homeostatic plasticity that occurs in the IC→BNST circuitry following chronic drinking. [ABSTRACT FROM AUTHOR]

Introduction: Loss of control (LOC) eating is the perceived inability to control how much is eaten, regardless of actual amount consumed. Childhood LOCeating is a risk factor for the development of binge-eating disorder (BED), but its neurobiological basis is poorly understood. Studies in children with BED have shown both increased gray matter volume in regions related to top-down cognitive control (e.g., dorsolateral prefrontal cortex) and rewardrelated decision making (e.g., orbital frontal cortex) relative to healthy controls. However, no studies have examined brain structure in children with LOCeating. To identify potential neurobiological precursors of BED, we conducted secondary analysis of five studies that conducted T1 MPRAGE scans. Methods: A total of 143, 7-12-year-old children (M = 8.9 years, 70 boys) were included in the study, 26% of which (n = 37) reported LOC-eating (semi-structured interview). Age, sex, and obesity status did not differ by LOC-eating. Differences between children with and without LOC were examined for gray matter volume, cortical thickness, gyrification, sulci depth, and cortical complexity after adjusting for age, sex, total intercranial volume, weight status, and study. Results: Children with LOC, relative to those without, had greater gray matter volume in right orbital frontal cortex but lower gray matter volume in right parahippocampal gyrus, left CA4/dentate gyrus, and left cerebellar lobule VI. While there were no differences in cortical thickness or gyrification, children with LOC-eating had great sulci depth in left anterior cingulate cortex and cuneus and greater cortical complexity in right insular cortex. Discussion: Together, this indicates that children with LOC-eating have structural differences in regions related to cognitive control, reward-related decision-making, and regulation of eating behaviors. [ABSTRACT FROM AUTHOR]

Purpose: We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction. Methods: In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H- magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann--Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses. Results: Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P < 0.001) in the rAI. We did not observe any significant between-group di [ABSTRACT FROM AUTHOR]

The functional organization of the primate insula has been studied using a variety of techniques focussing on regional differences in either architecture, connectivity, or function. These complementary methods offered insights into the complex organization of the insula and proposed distinct parcellation schemes at varying levels of detail and complexity. The advent of imaging techniques that allow noninvasive assessment of structural and functional connectivity, has popularized data-driven connectivity-based parcellation methods to investigate the organization of the human insula. Yet, it remains unclear if the subdivisions derived from these data-driven clustering methods reflect meaningful descriptions of the functional specialization of the insula. In this study, we employed hierarchical clustering to examine the cluster parcellations of the macaque insula. As our aim was exploratory, we examined parcellations consisting of two up to ten clusters. Three different cluster validation methods (fingerprinting, silhouette, elbow) converged on a four-cluster solution as the most optimal representation of our data. Examining functional response properties of these clusters, in addition to their brain-wide functional connectivity suggested a functional specialization related to processing gustatory, somato-motor, vestibular and social visual cues. However, a more detailed functional differentiation aligning with previous functional investigations of insula subfields became evident at higher cluster numbers beyond the proposed optimal four clusters. Overall, our findings demonstrate that resting-state-based hierarchical clustering can provide a meaningful description of the insula's functional organization at some level of detail. Nonetheless, cluster parcellations derived from this method are best combined with data obtained through other modalities, to provide a more comprehensive and detailed account of the insula's complex functional organization. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). Methods: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. Results: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular–left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. Conclusions: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) is a chronic mental illness characterized by abnormal functional connectivity among distributed brain regions. Previous studies have primarily focused on undirected functional connectivity and rarely reported from network perspective. Methods: To better understand between or within-network connectivities of OCD, effective connectivity (EC) of a large-scale network is assessed by spectral dynamic causal modeling with eight key regions of interests from default mode (DMN), salience (SN), frontoparietal (FPN) and cerebellum networks, based on large sample size including 100 OCD patients and 120 healthy controls (HCs). Parametric empirical Bayes (PEB) framework was used to identify the difference between the two groups. We further analyzed the relationship between connections and Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: OCD and HCs shared some similarities of inter- and intra-network patterns in the resting state. Relative to HCs, patients showed increased ECs from left anterior insula (LAI) to medial prefrontal cortex, right anterior insula (RAI) to left dorsolateral prefrontal cortex (L-DLPFC), right dorsolateral prefrontal cortex (R-DLPFC) to cerebellum anterior lobe (CA), CA to posterior cingulate cortex (PCC) and to anterior cingulate cortex (ACC). Moreover, weaker from LAI to L-DLPFC, RAI to ACC, and the self-connection of R-DLPFC. Connections from ACC to CA and from L-DLPFC to PCC were positively correlated with compulsion and obsession scores (r = 0.209, p = 0.037; r = 0.199, p = 0.047, uncorrected). Conclusions: Our study revealed dysregulation among DMN, SN, FPN, and cerebellum in OCD, emphasizing the role of these four networks in achieving top-down control for goal-directed behavior. There existed a top-down disruption among these networks, constituting the pathophysiological and clinical basis. [ABSTRACT FROM AUTHOR]

Background: Social touch is an integral part of social relationships and has been associated with reward. Major depressive disorder (MDD) is characterized by severe impairments in reward processing, but the neural effects of social touch in MDD are still elusive. In this study, we aimed to determine whether the neural processing of social touch is altered in MDD and to assess the impact of antidepressant therapy. Methods: Before and after antidepressant treatment, 53 MDD patients and 41 healthy controls underwent functional magnetic resonance imaging (fMRI) while receiving social touch. We compared neural responses to social touch in the reward network, behavioral ratings of touch comfort and general aversion to interpersonal touch in patients to controls. Additionally, we examined the effect of treatment response on those measures. Results: Clinical symptoms decreased after treatment and 43.4% of patients were classified as responders. Patients reported higher aversion to interpersonal touch and lower comfort ratings during the fMRI paradigm than controls. Patients showed reduced responses to social touch in the nucleus accumbens, caudate nucleus and putamen than controls, both before and after treatment. Contrary to our hypotheses, these effects were independent of touch velocity. Non-responders exhibited blunted response in the caudate nucleus and the insula compared to responders, again irrespective of time. Conclusions: These findings suggest altered striatal processing of social touch in MDD. Persistent dysfunctional processing of social touch despite clinical improvements may constitute a latent risk factor for social withdrawal and isolation. [ABSTRACT FROM AUTHOR]

Background: Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure. Methods: We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled. Results: Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure. Conclusions: These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being. [ABSTRACT FROM AUTHOR]

Background: There are very limited reports on anti-metabolic glutamate receptor5 (mGluR5) encephalitis, especially lacking of pediatric research. The disease was mostly accompanied by tumors, mainly Hodgkin's lymphoma. No reports of other tumors, such as gangliocytoma have been reported to associate with anti-mGluR5 encephalitis so far. Case presentation and literature reviews: We reported a case of a 12-year-old boy with anti-mGluR5 encephalitis complicated with gangliocytoma. The patient suffered from mental disorders including auditory hallucination, and sleep disorders. His cranial magnetic resonance imaging (MRI) showed an abnormality in the right insular lobe. Autoimmune encephalitis antibodies testing was positive for mGluR5 IgG antibody both in cerebrospinal fluid and serum (1:3.2, 1:100 respectively). Abdominal CT indicated a mass in left retroperitoneal confirmed with gangliocytoma via pathology. The patient underwent resection of gangliocytoma. After first-line immunotherapy (glucocorticoid, gamma globulin), his condition was improved. Furthermore, we provide a summary of 6 pediatric cases of Anti-mGluR5 encephalitis. Most of them complicated with Hodgkin's lymphoma, except the case currently reported comorbid with gangliocytoma. The curative effect is satisfactory. Conclusions: We report the first patient with anti-mGlur5 encephalitis complicated with gangliocytoma. It suggests that in addition to paying attention to the common lymphoma associated with anti-mGlur5 encephalitis, we should also screen the possibility of other tumors for early detection of the cause, active treatment and prevention of recurrence. [ABSTRACT FROM AUTHOR]

Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants - half of whom were put under acute stress - made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n = 45), participants in the stress group (n = 46) chose to exert effort more often for self-than for other-benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms. [ABSTRACT FROM AUTHOR]

Regional differences in synaptic degeneration may underlie differences in clinical presentation and neuropathological disease progression in Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Here, we mapped and quantified synaptic degeneration in cortical brain regions in PD, PD with dementia (PDD) and DLB, and assessed whether regional differences in synaptic loss are linked to axonal degeneration and neuropathological burden. We included a total of 47 brain donors, 9 PD, 12 PDD, 6 DLB and 20 non-neurological controls. Synaptophysin+ and SV2A+ puncta were quantified in eight cortical regions using a high throughput microscopy approach. Neurofilament light chain (NfL) immunoreactivity, Lewy body (LB) density, phosphorylated-tau and amyloid-β load were also quantified. Group differences in synaptic density, and associations with neuropathological markers and Clinical Dementia Rating (CDR) scores, were investigated using linear mixed models. We found significantly decreased synaptophysin and SV2A densities in the cortex of PD, PDD and DLB cases compared to controls. Specifically, synaptic density was decreased in cortical regions affected at Braak α-synuclein stage 5 in PD (middle temporal gyrus, anterior cingulate and insula), and was additionally decreased in cortical regions affected at Braak α-synuclein stage 4 in PDD and DLB compared to controls (entorhinal cortex, parahippocampal gyrus and fusiform gyrus). Synaptic loss associated with higher NfL immunoreactivity and LB density. Global synaptophysin loss associated with longer disease duration and higher CDR scores. Synaptic neurodegeneration occurred in temporal, cingulate and insular cortices in PD, as well as in parahippocampal regions in PDD and DLB. In addition, synaptic loss was linked to axonal damage and severe α-synuclein burden. These results, together with the association between synaptic loss and disease progression and cognitive impairment, indicate that regional synaptic loss may underlie clinical differences between PD and PDD/DLB. Our results might provide useful information for the interpretation of synaptic biomarkers in vivo. [ABSTRACT FROM AUTHOR]

Social scientists are increasingly interested in studying the psychological bases of political preferences. Research at the interface of neuroscience and political psychology is uniquely positioned to test theories that link political attitudes to cognitive, affective, perceptual, and motivational processes in the brain. In this article, we review existing theories and evaluate findings from the growing field of political neuroscience with an emphasis on four brain regions that have emerged as important neural substrates of political ideology: the amygdala, the insular cortex, the anterior cingulate cortex, and the prefrontal cortex. We conclude by discussing current methodological and theoretical limitations before setting out an agenda for future research. [ABSTRACT FROM AUTHOR]

[Display omitted] • The functional anatomy of the P3 is still unclear. • This study applied an auditory oddball paradigm in M/EEG and fMRI. • M/EEG and fMRI independently suggest a major P3 source in retro-splenial cortex. The P3 is an event-related response observed in relation to task-relevant sensory events. Despite its ubiquitous presence, the neural generators of the P3 are controversial and not well identified. We compared source analysis of combined magneto- and electroencephalography (M/EEG) data with functional magnetic resonance imaging (fMRI) and simulation studies to better understand the sources of the P3 in an auditory oddball paradigm. Our results suggest that the dominant source of the classical, postero-central P3 lies in the retro-splenial cortex of the ventral cingulate gyrus. A second P3 source in the anterior insular cortex contributes little to the postero-central maximum. Multiple other sources in the auditory, somatosensory, and anterior midcingulate cortex are active in an overlapping time window but can be functionally dissociated based on their activation time courses. The retro-splenial cortex is a dominant source of the parietal P3 maximum in EEG. These results provide a new perspective for the interpretation of the extensive research based on the P3 response. [ABSTRACT FROM AUTHOR]

In this study we present the results of an interdisciplinary analysis applied to four pictoric sets from three domus (Domus 1, Domus 2 –belonging to Insula I- and House of the Lararium) of the roman site of Municipium Augusta Bilbilis (Calatayud, Spain). The main objective is to find out if the analytical techniques applied to the pigments (archaeometry) and the study of the mortars (petrology) allow us to find our own craft recipes and there-fore conclude that these decorations were made by the same workshop. The aim is also to establish a working methodology to identify this type of workshop beyond the traditional one based on the observation of certain iconographic or technical aspects. The four pictoric sets fall stylistically within the so-called II style and all of them come from representation rooms within the three most important dwellings in this town. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether insula network connectivity modulates the relationship between apolipoprotein E (APOE) ε4 genotype, cerebrospinal fluid (CSF) biomarkers (Aβ, Tau, and pTau) and cognition across Alzheimer's disease (AD) spectrum. Methods: Forty‐six cognitive normal (CN), 35 subjective memory complaint (SMC), 41 mild cognitive impairment (MCI), and 32 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were obtained. Multivariable linear regression analyses were conducted to investigate the main effects and interaction of the APOE genotype and disease status on the insula functional connectivity (IFC) network. Mediation and moderation analysis were performed to investigate whether IFC strengths regulate the association between APOE genotype, CSF biomarkers and cognition. Additionally, the support vector machine (SVM) model integrating APOE genotype, CSF biomarkers, and neuroimaging biomarkers (insula volumes and altered regional IFCs) was used to classify the AD spectrum. Results: The interactive effect of the APOE genotype and disease on the insula network was found in the left medial superior frontal gyrus (SFGmed.L), right anterior medial prefrontal cortex (aMPFC.R), and bilateral thalamus (THA.B). The functional connectivities (FCs) in the left insula (LIns) connecting with the left posterior middle temporal gyrus (pMTG.L), SFGmed.L, and right lingual gyrus (LING.R) were correlated with cognition. LIns‐SFGmed.L and LIns‐pMTG.L FCs could moderate the effects of Tau on cognition. Furthermore, LIns‐SFGmed.L FC may suppress the association between APOE genotype and cognition. More importantly, the integrated biomarkers from the SVM model yielded strong powers for classifying the AD spectrum. Conclusions: Insula functional connectivity regulated the association between APOE genotype, CSF Tau and cognition and provided stage‐dependent biomarkers for early differentiation of the AD spectrum. The present study used a cross‐sectional design. Follow‐up studies are needed to validate the relationship. [ABSTRACT FROM AUTHOR]

Background: In Cri du Chat (CdC), cancer as comorbidity is extremely rare. In databases from Denmark, Spain, Australia, New Zealand, and Japan, no cancer was reported; in Italy and Germany, four cancers were identified out of 321 CdCs. Methods: In a 29-year-old CdC patient, clinical investigations following hematemesis led to the diagnosis of esophageal adenocarcinoma (EAC). A high pain threshold was also observed. Conventional and molecular cytogenetic defined the size of the deletion, and exome analysis on the trio completed the molecular work. Results: Cytogenetic analysis showed a de novo chromosomal alteration: 46,XY,ishdel(5)(p14.3)(D5S28-) and arr[GRCh37] 5p15.33p14.3(1498180_19955760)x1. A quantitative sensory test demonstrated a high heat threshold. A 18f-fluorodeoxyglucose PET/TC scan of the brain failed to detect reduction of metabolism in the somatosensory area or insular cortex. Exome analysis in the trio (patient and parents) failed to identify variants to be interpreted as a likely risk factor for EAC. Conclusion: We conclude that the presence of well-known risk factors (maleness, obesity, gastroesophageal reflux, and Barrett's metaplasia) in a patient with very limited capability of expressing discomfort or referring clinical symptoms have been the main risk factors for developing EAC. At present, based on the available data, there is no evidence of any increased risk of developing cancer in CdC patients. [ABSTRACT FROM AUTHOR]

The signed value and unsigned salience of reward prediction errors (RPEs) are critical to understanding reinforcement learning (RL) and cognitive control. Dorsomedial prefrontal cortex (dMPFC) and insula (INS) are key regions for integrating reward and surprise information, but conflicting evidence for both signed and unsigned activity has led to multiple proposals for the nature of RPE representations in these brain areas. Recently developed RL models allow neurons to respond differently to positive and negative RPEs. Here, we use intracranially recorded high frequency activity (HFA) to test whether this flexible asymmetric coding strategy captures RPE coding diversity in human INS and dMPFC. At the region level, we found a bias towards positive RPEs in both areas which paralleled behavioral adaptation. At the local level, we found spatially interleaved neural populations responding to unsigned RPE salience and valence-specific positive and negative RPEs. Furthermore, directional connectivity estimates revealed a leading role of INS in communicating positive and unsigned RPEs to dMPFC. These findings support asymmetric coding across distinct but intermingled neural populations as a core principle of RPE processing and inform theories of the role of dMPFC and INS in RL and cognitive control. It is unclear how dorsomedial prefrontal cortex and insula represent reward prediction errors. Here, the authors analyze human intracranial data to reveal spatially mixed, asymmetric coding of valence-specific and unsigned reward prediction errors, with insula leading dorsomedial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Background: Isocitrate dehydrogenase-wildtype glioblastoma (IDH-wildtype GBM) and IDH-mutant astrocytoma have distinct biological behaviors and clinical outcomes. The location of brain tumors is closely associated not only with clinical symptoms and prognosis but also with key molecular alterations such as IDH. Therefore, we hypothesize that the key brain regions influencing the prognosis of glioblastoma and astrocytoma are likely to dier. This study aims to (1) identify specific regions that are associated with the Karnofsky Performance Scale (KPS) or overall survival (OS) in IDH-wildtype GBM and IDH-mutant astrocytoma and (2) test whether the involvement of these regions could act as a prognostic indicator. Methods: A total of 111 patients with IDH-wildtype GBM and 78 patients with IDHmutant astrocytoma from the Cancer Imaging Archive database were included in the study. Voxel-based lesion-symptom mapping (VLSM) was used to identify key brain areas for lower KPS and shorter OS. Next, we analyzed the structural and cognitive dysfunction associated with these regions. The survival analysis was carried out using Kaplan–Meier survival curves. Another 72 GBM patients and 48 astrocytoma patients from Harbin Medical University Cancer Hospital were used as a validation cohort. Results: Tumors located in the insular cortex, parahippocampal gyrus, and middle and superior temporal gyrus of the left hemisphere tended to lead to lower KPS and shorter OS in IDH-wildtype GBM. The regions that were significantly correlated with lower KPS in IDH-mutant astrocytoma included the subcallosal cortex and cingulate gyrus. These regions were associated with diverse structural and cognitive impairments. The involvement of these regions was an independent predictor for shorter survival in both GBM and astrocytoma. Conclusion: This study identified the specific regions that were significantly associated with OS or KPS in glioma. The results may help neurosurgeons evaluate patient survival before surgery and understand the pathogenic mechanisms of glioma in depth. [ABSTRACT FROM AUTHOR]

Cannabis is the most widely used recreational drug in the United States and regular use has been linked to deficits in attention and memory. However, the effects of regular use on motor control are less understood, with some studies showing deficits and others indicating normal performance. Eighteen users and 23 nonusers performed a motor sequencing task during high‐density magnetoencephalography (MEG). The MEG data was transformed into the time‐frequency domain and beta responses (16–24 Hz) during motor planning and execution phases were imaged separately using a beamformer approach. Whole‐brain maps were examined for group (cannabis user/nonuser) and time window (planning/execution) effects. As expected, there were no group differences in task performance (e.g., reaction time, accuracy, etc.). Regular cannabis users exhibited stronger beta oscillations in the contralateral primary motor cortex compared to nonusers during the execution phase of the motor sequences, but not during the motor planning phase. Similar group‐by‐time window interactions were observed in the left superior parietal, right inferior frontal cortices, right posterior insular cortex, and the bilateral motor cortex. We observed differences in the neural dynamics serving motor control in regular cannabis users compared to nonusers, suggesting regular users may employ compensatory processing in both primary motor and higher‐order motor cortices to maintain adequate task performance. Future studies will need to examine more complex motor control tasks to ascertain whether this putative compensatory activity eventually becomes exhausted and behavioral differences emerge. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate morphological changes in cortical and subcortical regions and their asymmetrical dierences in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). These morphological changes may provide valuable insights into the early diagnosis and treatment of Alzheimer’s disease (AD). Methods: We conducted structural MRI scans on a cohort comprising 62 SCD patients, 97 MCI patients, and 70 age-, sex-, and years of education-matched healthy controls (HC). Using Freesurfer, we quantified surface area, thickness, the local gyrification index (LGI) of cortical regions, and the volume of subcortical nuclei. Asymmetry measures were also calculated. Additionally, we explored the correlation between morphological changes and clinical variables related to cognitive decline. Results: Compared to HC, patients with MCI exhibited predominantly left-sided surface morphological changes in various brain regions, including the transverse temporal gyrus, superior temporal gyrus, insula, and pars opercularis. SCD patients showed relatively minor surface morphological changes, primarily in the insula and pars triangularis. Furthermore, MCI patients demonstrated reduced volumes in the anterior-superior region of the right hypothalamus, the fimbria of the bilateral hippocampus, and the anterior region of the left thalamus. These observed morphological changes were significantly associated with clinical ratings of cognitive decline. Conclusion: The findings of this study suggest that cortical and subcortical morphometric changes may contribute to cognitive impairment in MCI, while compensatory mechanisms may be at play in SCD to preserve cognitive function. These insights have the potential to aid in the early diagnosis and treatment of AD. [ABSTRACT FROM AUTHOR]

Mice fed a single meal daily at a fixed time display food anticipatory activity (FAA). It has been reported that the insular cortex (IC) plays an essential role in food anticipation, and lateral hypothalamus (LH) regulates the expression of FAA. However, how these areas contribute to FAA production is still unclear. Thus, we examined the temporal and spatial activation pattern of neurons in the IC and LH during the food anticipation period to determine their role in FAA establishment. We observed an increase of c-Fos-positive neurons in the IC and LH, including orexin neurons of male adult C57BL/6 mice. These neurons were gradually activated from the 1st day to 15th day of restricted feeding. The activation of these brain regions, however, peaked at a distinct point in the food restriction procedure. These results suggest that the IC and LH are differently involved in the neural network for FAA production. [ABSTRACT FROM AUTHOR]

For centuries, the brain has been considered a single organ from an anatomical and functional perspective. However, while the cerebral cortex, consisting of many lobes and lobules, generally creates voluntary actions, autonomous parts of the brain also carry out vital activities such as survival, reproduction, and nutrition. The functions of the group of organs that carry out basic vital activities are modulated by autonomous ganglia that work like the deep intelligence networks of the brain. Information and energy packets produced as different molecules in vital organs and sent to the autonomous ganglia are decoded. These packages are then made available for use by cells, tissues, and organs. This deep information, purified and summarized by the autonomic ganglia, is presented to the cerebral cortex after passing through the control of the brainstem and insula. As a result, the entire brain and all the organs under its control decide together what to do. From this conceptual perspective, the brain is a united states group with different states under its management; the autonomic ganglia can also be thought of as the brain's deep intelligence networks. [ABSTRACT FROM AUTHOR]

The vestibular apparatus provides spatial information on the position of the head in space and with respect to gravity. Low-frequency sinusoidal galvanic vestibular stimulation (sGVS), a means of selectively changing the firing of vestibular afferents, induces a frequency-dependent perception of sway and, in some individuals, induces nausea. Given that vestibular afferents project to the insular cortex—which forms part of the vestibular cortex—and that the insula receives inputs from the dorsolateral prefrontal cortex (dlPFC), we tested the hypothesis that electrical stimulation of the dlPFC can modulate vestibular inputs. Sinusoidal electrical stimulation (± 2 mA, 0.08 Hz, 100 cycles) was delivered via surface electrodes over (1) the mastoid processes alone (sGVS), (2) electroencephalogram (EEG) site F4 (right dlPFC) and the nasion or (3) to each site concurrently (sGVS + dlPFC) in 23 participants. The same stimulation protocol was used in a separate study to investigate EEG site F3 (left dlPFC) instead of F4 in 13 participants. During sGVS, all participants reported perceptions of sway and 13 participants also reported nausea, neither sensation of which occurred as a result of dlPFC stimulation. Interestingly, when sGVS and dlPFC stimulations were delivered concurrently, vestibular perceptions and sensations of nausea were almost completely abolished. We conclude that the dlPFC provides top-down control of vestibular inputs and further suggests that dlPFC stimulation may provide a novel means of controlling nausea. [ABSTRACT FROM AUTHOR]

Raised Intra-Cranial Pressure causes hypertension. We report a 75 years old lady with large Middle Cerebral Artery bifurcation aneurysm that was operated on. Post-operatively she had a progressive hypotension that was refractory to inotropes and became life threatening. There was subgaleal, extradural and subdural collection of Cerebro-Spinal Fluid. Drainage of this collection led to immediate complete recovery from hypotension, normalization of tachycardia and improvement in sensorium within 4 hours. Raised Intra-Cranial Pressure can manifest with hypotension and tachycardia if the right insula has been exposed. Removal of the irritant can lead to rapid and complete recovery. [ABSTRACT FROM AUTHOR]

Medical students and professional healthcare providers often underestimate patients' pain, together with decreased neural responses to pain information in the anterior insula (AI), a brain region implicated in self‐pain processing and negative affect. However, the functional significance and specificity of these neural changes remains debated. Across two experiments, we recruited university medical students and emergency nurses to test the role of healthcare experience on the brain reactivity to other's pain, emotions, and beliefs, using both pictorial and verbal cues. Brain responses to self‐pain was also assessed and compared with those to observed pain. Our results confirmed that healthcare experience decreased the activity in AI in response to others' suffering. This effect was independent from stimulus modality (pictures or texts), but specific for pain, as it did not generalize to inferences about other mental or affective states. Furthermore, representational similarity and multivariate pattern analysis revealed that healthcare experience impacted specifically a component of the neural representation of others' pain that is shared with that of first‐hand nociception, and related more to AI than to other pain‐responsive regions. Taken together, our study suggests a decreased propensity to appraise others' suffering as one's own, associated with a reduced recruitment of pain‐specific information in AI. These findings provide new insights into neural mechanisms leading to pain underestimation by caregivers in clinical settings. [ABSTRACT FROM AUTHOR]

Atrophy related to multiple sclerosis (MS) has been found at the early stages of the disease. However, the archetype dynamic trajectories of the neurodegenerative process, even prior to clinical diagnosis, remain unknown. We modeled the volumetric trajectories of brain structures across the entire lifespan using 40,944 subjects (38,295 healthy controls and 2649 MS patients). Then, we estimated the chronological progression of MS by assessing the divergence of lifespan trajectories between normal brain charts and MS brain charts. Chronologically, the first affected structure was the thalamus, then the putamen and the pallidum (around 4 years later), followed by the ventral diencephalon (around 7 years after thalamus) and finally the brainstem (around 9 years after thalamus). To a lesser extent, the anterior cingulate gyrus, insular cortex, occipital pole, caudate and hippocampus were impacted. Finally, the precuneus and accumbens nuclei exhibited a limited atrophy pattern. Subcortical atrophy was more pronounced than cortical atrophy. The thalamus was the most impacted structure with a very early divergence in life. Our experiments showed that lifespan models of most impacted structures could be an important tool for future preclinical/prodromal prognosis and monitoring of MS. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effectiveness of mindfulness‐based interventions (MBIs) on mental and cognitive outcomes including, anxiety, depression, attention, memory, global cognition and neuroplastic changes in older adults with mild cognitive impairment (MCI). Design: Systematic review and meta‐analysis. Data source: A three‐step search strategy was conducted on eight electronic databases, grey literature and reference lists from inception to February 2022. Review methods: Randomized controlled trials (RCTs) examining MBIs on older adults with MCI were screened and assessed for risk of bias using the Cochrane Risk of Bias Tool. Meta‐analysis was conducted using RevMan using a random‐effect model. Narrative synthesis was performed for studies where results could not be pooled statistically. Results: Ten RCTs were included in the review. Results suggested that right frontal parietal and left inferior temporal gyrus of the brain showed increased cortical thickness after receiving MBIs. There were significant interaction effects for global efficiency and significant interactions in the insular and gyrus regions. Functional connectivity between the posterior cingulate cortex, bilateral medial prefrontal cortex and left hippocampus were increased in participants undergoing MBIs. Nevertheless, meta‐analysis showed non‐significant pooled effects, favouring control groups on anxiety, depression, attention, memory and global cognition. Conclusion: This review suggested the potential effects of MBIs in improving cortical thickness and connectivity in regions associated with memory and attention. Nevertheless, the effects of MBIs compared to active control groups on depression, anxiety, attention, memory and global cognition are inconclusive due to the lack of studies and non‐significant results. Impact: The review advocates for more rigorous studies with larger sample size and utilizing wait‐list controls to evaluate the effects of MBIs. MBIs can be considered as an adjunct with other therapies to further enhance the effect on psychological and cognitive outcomes for older adults with MCI. No Patient or Public Contribution as this is a meta‐analysis. [ABSTRACT FROM AUTHOR]

The distance effect states that the closer two compared magnitudes (e.g., two numbers, physical attractiveness in two faces), the more difficult the comparison, and the greater the activity of the frontoparietal control network. However, it is unclear whether this network is also recruited to the same extent when we perform ingroup and outgroup beauty comparisons and whether the activation of these networks is tracked by interindividual variation in the perceptions we hold about an outgroup. We recorded brain activity with fMRI, where participants compared the beauty of two women ostensibly either from their ingroup or from an outgroup. Low-distance conditions produced longer response times than the high-distance conditions, and this was found in both the ingroup and outgroup conditions. However, our neuroimaging analyses revealed that the left IFG/anterior insula showed the classic distance effect only during ingroup processing but not during outgroup processing. Notably, interaction-specific activity within the left IFG/anterior insula was related to perceptions of outgroup homogeneity assessed via a questionnaire. This set of findings reveals the dynamic role of the prefrontal cortex and its interplay with perceptions of outgroup homogeneity in shaping ingroup and outgroup decision-making. [ABSTRACT FROM AUTHOR]

This text discusses the groundbreaking contributions of Bud Craig, a neuroscientist, in understanding the pathways and mechanisms of pain and temperature sensations in the brain. Bud's research revealed that the insular cortex is the primary sensory cortex for pain and temperature, resolving a long-standing paradox in the field. His work also highlighted the interoceptive nature of pain and temperature sensations, which are closely related to other bodily sensations such as taste and visceral sensations. Despite facing opposition and criticism, Bud's findings have had a significant impact on the study of interoception and the role of the insula in various conditions. Unfortunately, Bud's illness prevented him from continuing his research, leaving some of his important data unpublished. The author emphasizes the importance of recognizing Bud's contributions and hopes that his work will receive the recognition it deserves. [Extracted from the article]

Objective: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post‐operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. Results: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591–0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5–12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu1 cohort onward, receding post the Hu4 cohort. Conclusion: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH. [ABSTRACT FROM AUTHOR]

Musical training has been linked to enhanced interoceptive abilities and increased resting‐state (RS) functional connectivity (FC) within the interoceptive brain network. We aimed to replicate and extend these findings with a unique cross‐sectional and longitudinal study design. Professional musicians and matched individuals with no prior musical experience (training group) were recruited. Participants underwent RS fMRI scans and completed heartbeat counting and discrimination tasks outside of the scanner (time point 1). The training group additionally had RS scans and interoception tests repeated after a 6‐month‐long keyboard course training (time point 2). We found no evidence for increased interoceptive abilities in professional musicians relative to non‐musicians, nor did we observe any improvements in interoception over the course of musical training. RS FC analysis revealed increased FC within the sensorimotor network in professional musicians compared to the training group at the first time point with no change in FC over time in the Training group. These findings challenge the view that musical training may improve interoceptive abilities. Yet, the results suggest that musical training is related to increased communication within the sensorimotor RS network, which consists of some hubs important for interoceptive processing (namely pre‐ and postcentral gyri and supplementary motor area). Using a unique cross‐sectional and longitudinal study design, we challenge the view that musical training may improve interoceptive processing. Yet, our findings suggest that professional musicians show increased communication within the sensorimotor resting state network, which consists of some hubs important for interoceptive processing. [ABSTRACT FROM AUTHOR]

Objectives: In physiological situations, the anterior cingulate cortex (ACC) and anterior insular cortex (AIC) are prone to coactivation. The functional connectivity and interaction between ACC and AIC in the context of epilepsy remain unclear. This study aimed to investigate the dynamic coupling between these two brain regions during seizures. Methods: Patients who underwent stereoelectroencephalography (SEEG) recording were included in this study. The SEEG data were visually inspected and quantitatively analyzed. The narrowband oscillations and aperiodic components at seizure onset were parameterized. The frequency‐specific non‐linear correlation analysis was applied to the functional connectivity. The excitation/inhibition ratio (E:I ratio) reflected by the aperiodic slope was performed to evaluate the excitability. Results: Twenty patients were included in the study, with 10 diagnosed with anterior cingulate epilepsy and 10 with anterior insular epilepsy. In both types of epilepsy, the correlation coefficient (h2) between the ACC and AIC at seizure onset exhibited a significantly higher value than that during interictal and preictal periods (p < 0.05). The direction index (D) showed a significant increase at seizure onset, serving as an indicator for the direction of information flow between these two brain regions with up to 90% accuracy. The E:I ratio increased significantly at seizure onset, with the seizure‐onset zone (SOZ) demonstrating a more pronounced increase compared to non‐SOZ (p < 0.05). For seizures originating from AIC, the E:I ratio was significantly higher in the AIC than in the ACC (p = 0.0364). Conclusions: In the context of epilepsy, the ACC and AIC are dynamically coupled during seizures. The functional connectivity and excitability exhibit a significant increase at seizure onset. By analyzing connectivity and excitability, the SOZ in ACC and AIC can be identified. The direction index (D) serves as an indicator for the direction of information flow from SOZ to non‐SOZ. Notably, the excitability of SOZ changes more significantly than that of non‐SOZ. [ABSTRACT FROM AUTHOR]