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• Talamocortical dysrhythmia (TCD) and reward deficiency syndrome (RDS) group several brain disorders. • Both disorders are proposed to be uncertainty disorders. • Both TCD and RDS are characterized by abnormal beta activity in the dorsal anterior cingulate cortex. • RDS has additional theta activity in the ventromedial prefrontal cortex and pregenual anterior cingulate cortex. • TCD and RDS share a neurophysiological core but exhibit regional differences in brain activity. A common anatomical core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common neurophysiological core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common genetic core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC. [ABSTRACT FROM AUTHOR]

With the spread of smartphones and computer games, concerns have escalated regarding the rising prevalence of gaming disorder. Patients often display attentional biases, unconsciously turning their attention towards gaming-related stimuli. However, attempts to discover and ameliorate these attentional deficits have yielded inconsistent outcomes, potentially due to the dynamic nature of attentional bias. This study investigated neural mechanisms underlying attentional bias state by combining neuroimaging (functional magnetic resonance imaging -fMRI) with an approach-avoidance task tailored to an individual's gaming preference. We conducted a multivariate pattern analysis of endogenous brain activity in 21 participants with probable gaming disorder. Our analyses revealed that activity patterns in the insula tracked temporal attentional bias states specific to gaming stimuli. A broad network of frontal and parietal regions instead appeared to predict a general temporal attentional bias state. Finally, we conducted a proof-of-concept study for 'just-in-time' attentional bias training through fMRI-decoded neurofeedback of insula activity patterns, named decoded attentional bias training (DecABT). Our preliminary results suggest that DecABT may help to decrease the attractiveness of gaming stimuli via a insula- and precuneus-based neural mechanism. This work provides new evidence for the insula as an endogenous regulator of attentional bias states in gaming disorder and a starting point to develop novel, individualized therapeutic approaches to treat addiction. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context: Olfactory dysfunction (OD) is a common early symptom of Parkinson's disease (PD). However, OD is not specific to PD, as approximatively 20% of the general population exhibit different forms of OD. To use olfactory measures for early Parkinson screening, it is crucial to distinguish PD-related OD from Non-Parkinsonian OD (NPOD). Objectives and hypothesis: This study aimed to compare the structural changes associated with PD-related OD (n = 15) with NPOD (n = 15), focusing on gray matter volumes and white matter fiber integrity in chemosensory regions. We hypothesized that PD-related OD presents specific structural alterations in these regions. Methods: Participants underwent a 3 T MRI scan, which included anatomical T1 and diffusion-weighted imaging. Gray and white matter integrity were assessed using both whole-brain analyses (voxel-based morphometry—VBM and tract-based spatial statistics—TBSS, respectively) and localized approaches, including regions of interest and tractography. Results: PD patients exhibited significantly higher gray matter volume in the left insula using restricted regions-of-interest analyses, while no other significant gray or white matter differences were found between groups. Conclusion: Structural imaging of the gray matter, particularly the insula, but not of white matter, differentiates PD-related OD from NPOD. [ABSTRACT FROM AUTHOR]

Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered functional neuroimaging study of 46 individuals with anxiety, depression, and/or eating disorders (ADE) and 46 propensity-matched healthy comparisons (HC), comparing their neural activity across two interoceptive tasks differentially recruiting top-down or bottom-up processing within the same scan session. During an interoceptive attention task, top-down attention was voluntarily directed towards cardiorespiratory or visual signals. In contrast, during an interoceptive perturbation task, intravenous infusions of isoproterenol (a peripherally-acting beta-adrenergic receptor agonist) were administered in a double-blinded and placebo-controlled fashion to drive bottom-up cardiorespiratory sensations. Across both tasks, neural activation converged upon the insular cortex, localizing within the granular and ventral dysgranular subregions bilaterally. However, contrasting hemispheric differences emerged, with the ADE group exhibiting (relative to HCs) an asymmetric pattern of overlap in the left insula, with increased or decreased proportions of co-activated voxels within the left or right dysgranular insula, respectively. The ADE group also showed less agranular anterior insula activation during periods of bodily uncertainty (i.e. when anticipating possible isoproterenol-induced changes that never arrived). Finally, post-task changes in insula functional connectivity were associated with anxiety and depression severity. These findings confirm the dysgranular mid-insula as a key cortical interface where attention and prediction meet real-time bodily inputs, especially during heightened awareness of interoceptive states. Furthermore, the dysgranular mid-insula may indeed be a ‘locus of disruption’ for psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Studies in experimental animals revealed that acute and chronic treatment with small‐molecule immunosuppressive drugs lead to neurobehavioral alterations in rodents. Methods: Against this background, this study investigated behavioral alterations in rats after repeated administration of FTY720, an immunosuppressive drug used for the treatment of multiple sclerosis, employing the open field, elevated plus maze, and dark/light tests. Results: Compared to controls, repeated FTY720 treatment affected behavior in rats, reflected by a reduction in distance traveled as well as increased time engaged in freezing in the open field and elevated plus maze. Furthermore, the time spent freezing in the elevated plus maze test positively correlated with FTY720 concentrations in the amygdala and insular cortex, two brain regions involved in regulation of emotionality. Since no changes in plasma corticosterone levels were observed, stress effects due to treatment, behavioral testing, or handling can be ruled out. Conclusion: The present findings indicate that treatment with FTY720 did not induce typical anxiety‐like behavioral patterns in otherwise healthy rats as seen following treatment with other immunosuppressive drugs. Nevertheless, it remains of great importance to evaluate behavioral effects in clinical practice to shed more light onto possible detrimental side effects emerging during treatment with small‐molecule immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

• Low-intensity focused ultrasound (LIFU) can target insular and cingulate cortex subregions. • Modulation of the anterior and posterior insula differentially decreased the heartbeat evoked potential (HEP). • The effects on the HEP were partially explained by LIFU pressure. The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing that may be generated in the insula and dorsal anterior cingulate cortex (dACC). Low-intensity focused ultrasound (LIFU) can selectively modulate sub-regions of the insula and dACC to better understand their contributions to the HEP. Healthy participants (n = 16) received stereotaxically targeted LIFU to the anterior insula (AI), posterior insula (PI), dACC, or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was HEP amplitudes. Relationships between LIFU pressure and HEP changes and effects of LIFU on heart rate and heart rate variability (HRV) were also explored. Relative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; PI effects were partially explained by increased LIFU pressure. LIFU did not affect heart rate or HRV. These results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. Our findings have implications for the causal role of these areas in bottom-up heart-brain communication that could guide future work investigating the HEP as a marker of interoceptive processing in healthy and clinical populations. [ABSTRACT FROM AUTHOR]

Purpose: A relevant aspect of listening is the effort required during speech processing, which can be assessed by pupillometry. Here, we assessed the pupil dilation response of normal-hearing (NH) and hard of hearing (HH) individuals during listening to clear sentences and masked or degraded sentences. We combined this assessment with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of the pupil dilation response. Method: Seventeen NH participants (Mage = 46 years) were compared to 17 HH participants (Mage = 45 years) who were individually matched in age and educational level. Participants repeated sentences that were presented clearly, that were distorted, or that were masked. The sentence intelligibility level of masked and distorted sentences was 50% correct. Silent baseline trials were presented as well. Performance measures, pupil dilation responses, and fMRI data were acquired. Results: HH individuals had overall poorer speech reception than the NH participants, but not for noise-vocoded speech. In addition, an interaction effect was observed with smaller pupil dilation responses in HH than in NH listeners for the degraded speech conditions. Hearing impairment was associated with higher activation across conditions in the left superior temporal gyrus, as compared to the silent baseline. However, the region of interest analysis indicated lower activation during degraded speech relative to clear speech in bilateral frontal regions and the insular cortex, for HH compared to NH listeners. Hearing impairment was also associated with a weaker relation between the pupil response and activation in the right inferior frontal gyrus. Overall, degraded speech evoked higher frontal activation than clear speech. Conclusion: Brain areas associated with attentional and cognitive-control processes may be increasingly recruited when speech is degraded and are related to the pupil dilation response, but this relationship is weaker in HH listeners. [ABSTRACT FROM AUTHOR]

The tendency of falsely remembering events that did not happen in the past increases with age. This is particularly evident in cases in which features presented at study are re-presented at test in a recombined constellation (termed rearranged pairs). Interestingly, older adults also express high confidence in such false memories, a tendency that may indicate reduced metacognitive efficiency. Within an existing cohort study, we aimed at investigating age-related differences in memory metacognitive efficiency (as measured by meta d' ratio) in a sample of 1522 older adults and 397 young adults. The analysis showed an age-related deficit in metacognition which was more pronounced for rearranged pairs than for new pairs. We then explored associations between cortical thickness and memory metacognitive efficiency for rearranged pairs in a subsample of 231 older adults. By using partial least square analysis, we found that a multivariate profile composed by ventromedial prefrontal cortex, insula, and parahippocampal cortex was uniquely associated with between-person differences in memory metacognitive efficiency. These results suggest that the impairment in memory metacognitive efficiency for false alarms is a distinct age-related deficit, above and beyond a general age-related decline in memory discrimination, and that it is associated with brain regions involved in metacognitive processes. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid‐contacting neurons (CSF‐cNS) are considered mechanoreceptors and chemoreceptors involved in detecting changes in CSF circulation. However, considering that recent data suggest that this type of cell could exert an active response when an external stimulus is sensed, identification of CSF‐cNS may be relevant. In this regard, some data suggest that a neuronal connection exists between the ventral region of the hypothalamic paraventricular nucleus (PVN) and rostral agranular insular cortex (RAIC); indeed, a potential CSF‐cNS is hypothesized. However, a detailed analysis of this connection has not been conducted. Thus, using neuronal tracers (Fluoro‐Gold® (FG) and cholera toxin (ChT)) coupled with transmission electron microscopy and immunofluorescence assays against Fluoro‐Gold®, oxytocin (OXT), vasopressin (AVP) and oxytocin receptors (OTR), we describe an oxytocinergic or vasopressinergic CSF‐cNS between the PVN and RAIC. Our results showed that CSF‐cNS along the PVN labelled with oxytocin and/or AVP were present in dendritic projections near the third ventricle. This CSF‐cNS in the PVN seems to project to the RAIC. Inside the RAIC, ultrastructural analysis showed that axons immunopositive for oxytocin from the PVN sustained synaptic connections with neurons that expressed OTR. These findings show that the CSF‐cNS from the PVN sends projections to the RAIC. To the best of our knowledge, the relevance of CSF‐cNS has not been elucidated; however, we hypothesized that the activation of cells could concomitantly release neuropeptides (i.e., oxytocin and AVP) in the CSF and RAIC. Thus, further analysis of the impact of neuropeptides released into the third ventricle and RAIC is warranted. [ABSTRACT FROM AUTHOR]

Adolescent food insecurity is a salient adversity hypothesized to affect neural systems associated with increased impulsive behavior. Family environments shape how adverse experiences influence development. In this study, hypotheses were tested regarding the conjoint effects of food insecurity and family flexibility on impulsivity via alterations in connectivity between regions within the salience and central executive networks. Such alterations are reflected in resting‐state functional connectivity (rsFC) metrics between the anterior insula (AI) and the middle frontal gyrus (MFG). Hypotheses were tested in a longitudinal moderated mediation model with two waves of data from 142 adolescents (Time 1 [T1] Mage = 12.89, SD = 0.85; Time 2 [T2] Mage = 15.01, SD = 1.07). Data on past‐year household food insecurity, family flexibility, and rsFC were obtained at T1. Impulsivity was self‐reported by the adolescent at T1 and T2. Findings revealed that high T1 left‐to‐left rsFC between the AI and MFG was associated with increased impulsivity at T2. The interaction of family flexibility and food insecurity was associated with AI and MFG rsFC. In the context of low family flexibility, food insecurity was linked to high levels of AI and MFG rsFC. Conversely, in the context of optimal family flexibility, food insecurity was associated with low levels of AI and MFG rsFC. Conditional indirect analysis suggests that the links among food insecurity, rsFC, and impulsive behavior depend on family flexibility. Research Highlights: Adolescent food insecurity was associated with anterior insula and middle frontal gyrus connectivity only at certain levels of family flexibility.High family flexibility attenuated the link between food insecurity and neural connectivity, while low levels of family flexibility increased this risk.High left anterior insula and left middle frontal gyrus connectivity was associated with increased impulsivity 1 year later. [ABSTRACT FROM AUTHOR]

• In our study, cerebral fissure measurements of healthy fetuses between 20–24 weeks of gestation were obtained. • Normal reference values were determined for these anatomical structures, which are closely related to fetal cortical development. • All four main fissures examined in our study were found to enlarge with advancing gestational age. • The reference intervals we obtained will be helpful for clinicians interested in neurosonography. • Cerebral fissure measurements may provide additional information about actual gestational age and cortical maturation. We aimed to establish normal reference ranges for insula, sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF) measured by prenatal ultrasonography (USG) between 20–24 weeks of gestation in healthy fetuses. A total of 186 fetuses in the second trimester were evaluated by transabdominal USG. All measurements were obtained by a single clinician. The study was divided into four subgroups (Group A: 20–20 weeks six days, Group B: 21–21 weeks six days, Group C: 22–22 weeks six days, Group D: 23–23 weeks six days). Eight fetuses (4.23 %) between 20 and 21 weeks of gestation could not be included in the study because the sulcus borders could not be clearly evaluated. Measurements were obtained in all fetuses over 21 weeks of gestation. Reference ranges were obtained for insula, SF, POF, and CF in all fetuses and subgroups. At 20 and 23 weeks and six days gestation, mean insula depth was 14.96 ± 1.62 mm (min 11.0 mm − max 18.9 mm), mean SF depth was 6.96 ± 1.35 mm (min 3.6 mm − max 10.0 mm), mean POF depth was 2.05 ± 0.66 mm (min 1.1 mm − max 5.6 mm) and mean CF depth was 2.42 ± 0.68 mm (min 1.5 mm − 6.1 mm). There was a correlation between the cerebellum and cisterna magna and all fissure depths. Our nomograms of healthy fetuses may be helpful in the early detection of cortical maturation abnormalities. [ABSTRACT FROM AUTHOR]

Trait self-report mindfulness scales measure one's disposition to pay nonjudgmental attention to the present moment. Concerns have been raised about the validity of trait mindfulness scales. Despite this, there is extensive literature correlating mindfulness scales with objective brain measures, with the goal of providing insight into mechanisms of mindfulness, and insight into associated positive mental health outcomes. Here, we systematically examined the neural correlates of trait mindfulness. We assessed 68 correlational studies across structural magnetic resonance imaging, task-based fMRI, resting-state fMRI, and EEG. Several consistent findings were identified, associating greater trait mindfulness with decreased amygdala reactivity to emotional stimuli, increased cortical thickness in frontal regions and insular cortex regions, and decreased connectivity within the default-mode network. These findings converged with results from intervention studies and those that included mindfulness experts. On the other hand, the connections between trait mindfulness and EEG metrics remain inconclusive, as do the associations between trait mindfulness and between-network resting-state fMRI metrics. ERP measures from EEG used to measure attentional or emotional processing may not show reliable individual variation. Research on body awareness and self-relevant processing is scarce. For a more robust correlational neuroscience of trait mindfulness, we recommend larger sample sizes, data-driven, multivariate approaches to self-report and brain measures, and careful consideration of test–retest reliability. In addition, we should leave behind simplistic explanations of mindfulness, as there are many ways to be mindful, and leave behind simplistic explanations of the brain, as distributed networks of brain areas support mindfulness. [ABSTRACT FROM AUTHOR]

• The degree of fluid satiety differentially affects taste-aversive memory formation. • H3 receptor activation in the insular cortex disrupted CTA only under fluid deprivation regimen. • RAMH in the insular cortex decreases novel appetitive response only in the ad libitum regime. • H3 receptor activation during ad libitum conditioning accelerates aversive memory extinction. Conditioned taste aversion (CTA) is a robust associative learning; liquid deprivation during this conditioning allows researchers to obtain readable measures of associative learning. Recent research suggests that thirst could be a crucial motivator that modulates conditioning and memory extinction processes, highlighting the importance of the body's internal state during learning. Furthermore, the histaminergic system is one of the major modulatory systems controlling several behavioral and neurobiological functions, such as feeding, water intake, and nociception. Therefore, this research aimed to assess the effect of H3 histaminergic receptor activation in the insular cortex (IC) during CTA. For this, we conditioned adult male Wistar rats under two regimens: water deprivation and water ad libitum. A classical CTA protocol was used for water deprivation. Before CTA acquisition, 10 μM R-α-methylhistamine (RAMH), an H3 receptor agonist, was injected into the IC. Results showed that RAMH injections decreased CTA in water-deprived rats without affecting the significant aversion conditioning in rats that were given water ad libitum. Moreover, RAMH accelerated the process of aversive memory extinction under ad libitum water conditions. According to our findings, the degree of liquid satiety differentially affected taste-aversive memory formation, and H3 histamine receptors were more involved under water deprivation conditions during acquisition. However, these receptors modulated the strength of aversive conditioning by altering the rate of aversive memory extinction in the absence of deprivation. In conclusion, histaminergic activity in the IC may influence taste memory dynamics through different mechanisms depending on the degree of liquid satiety or deprivation during conditioning. [ABSTRACT FROM AUTHOR]

The insula is a complex brain region central to the orchestration of taste perception, interoception, emotion, and decision-making. Recent research has shed light on the intricate connections between the insula and other brain regions, revealing the crucial role of this area in integrating sensory, emotional, and cognitive information. The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain. We summarize its role in interoceptive and exteroceptive sensory processing, illustrating insular function as a bridge connecting internal and external experiences. Drawing on recent research, we delineate the insular involvement in emotional processes, highlighting its implications in psychiatric conditions, such as anxiety, depression, and addiction. We further discuss the insular contributions to cognition, focusing on its significant roles in time perception and decision-making. Collectively, the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes. Through this review, we hope to highlight the importance of the insula as an interface between sensation, emotion, and cognition, and to inspire further research into this fascinating brain region. [ABSTRACT FROM AUTHOR]

Movies have the ability to trigger our emotions and affect us in powerful ways. But the impact is not the same among all the audience and, according to our results, also not between women and men. In this study, we used an electroencephalogram (EEG) to register the brain activity of a group of 30 students while they watched a violent scene. The results showed that both male and female groups activated the left temporal lobe. However, the female group also activated the left insula and orbitofrontal areas of both hemispheres. The results of Hotelling's T-squared distribution also showed significant differences in occipital areas of the brain in favour of women. Thus, our findings evidence that the violent scene activated emotional areas in both male and female groups, but in women there was also an activation of brain areas related to shape and colour recognition and to cognitive processes. [ABSTRACT FROM AUTHOR]

Background: The objective of frontal lobe disconnection (FD) is to isolate the frontal lobe without removing brain parenchyma, to achieve epilepsy outcomes comparable to those for frontal lobectomy but with fewer complications, since a large post-operative cavity is not created. Method: Main surgical steps include "Identification of the central sulcus" to ensure the preservation of motor function, and "Frontal lobe disconnection" comprising: 1) fronto-parietal disconnection; 2) fronto-basal disconnection; 3) anterior corpus callosotomy; and 4) insula and basal ganglia disconnection. Conclusion: In performing FD, consideration of the disconnection boundary based on an anatomical understanding of white matter tracts is essential. [ABSTRACT FROM AUTHOR]

The frequency of behavioral and psychological symptoms of dementia (BPSD) is high, and it is a challenge to elucidate its neural substrates underlying their development. In recent years, many findings have been reported on the relationship between BPSD and brain volume in dementia patients. However, the results are not fully conclusive. Furthermore, there have been few population-based studies. Therefore, the relationship between BPSD and brain volume was investigated as an exploratory study. Of the 927 older persons who participated in the fifth Nakayama study, 90 were included in this analysis, consisting of 52 patients with mild cognitive impairment and 38 patients with dementia, with head MRI and the Neuropsychiatric Inventory (NPI) data. Multiple regression analysis was used to examine the association between the total score of each BPSD score on the NPI and brain volume estimated by FreeSurfer. On multivariate adjustment, even after false discovery rate correction, insular cortical volumes decreased significantly as total scores for apathy/indifference increased (p value = 0.002, q-value = 0.01). Similarly, total brain volume decreased significantly as total scores for appetite and eating disturbance increased (p value = 0.03), and parietal, temporal, and hippocampal cortical volumes also decreased significantly as total scores for appetite and eating disturbance increased (all p and q values < 0.05). This study's results suggest that apathy is negatively correlated with insular cortical volume, and that appetite and eating disturbance are also correlated with brain regions, including parietal, temporal, and hippocampal volume in a community-dwelling older population. [ABSTRACT FROM AUTHOR]

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods: We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. Results: Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness (σ = -0.165, SE = 0.047, Z = -3.515, P < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning (σ = -0.226, SE = 0.093, Z = -2.443, P = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression (σ = -0.141, SE = 0.060, Z = -2.336, P = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning (σ = -0.239, SE = 0.139, Z = -1.710, P = 0.044), particularly in frontal, occipital, and insular cortical regions. Conclusions: Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015). [ABSTRACT FROM AUTHOR]

Thalamocortical pathways fromthe rodent ventral posterior (VP) thalamic complex to the somatosensory cerebral cortex areas are a key model in modern neuroscience. However, beyond the intensively studied projection from medial VP (VPM) to the primary somatosensory area (S1), the wiring of these pathways remains poorly characterized. We combined micropopulation tract-tracing and single-cell transfection experiments to map the pathways arising from different portions of the VP complex inmalemice. We found that pathways originating fromdifferent VP regions show differences in area/lamina arborization pattern and axonal varicosity size. Neurons fromthe rostral VPM subnucleus innervate trigeminal S1 in point-to-point fashion. In contrast, a caudal VPMsubnucleus innervates heavily and topographically second somatosensory area (S2), but not S1. Neurons in a third, intermediate VPM subnucleus innervate through branched axons both S1 and S2, with markedly different laminar patterns in each area. A small anterodorsal subnucleus selectively innervates dysgranular S1. The parvicellularVPMsubnucleus selectively targets the insular cortex and adjacent portions of S1 and S2. Neurons in the rostral part of the lateral VP nucleus (VPL) innervate spinal S1, while caudal VPL neurons simultaneously target S1 and S2. Rostral and caudal VP nuclei show complementary patterns of calcium-binding protein expression. In addition to the cortex, neurons in caudal VP subnuclei target the sensorimotor striatum. Our finding of a massive projection fromVP to S2 separate fromthe VP projections to S1 adds critical anatomical evidence to the notion that different somatosensory submodalities are processed in parallel in S1 and S2. [ABSTRACT FROM AUTHOR]

Dance is associated with beneficial outcomes in motor and non-motor domains in Parkinson's disease (PD) and regular participation may help delay symptom progression in mild PD. However, little is known about the neurobiological mechanisms of dance interventions for PD. The present case study explored potential neuroplastic changes in a 69-year-old male with mild PD participating in regular dance classes over 29 weeks. Functional MRI was performed at four timepoints (pre-training, 11 weeks, 18 weeks, 29 weeks), where the individual imagined a dance choreography while listening to the corresponding music. Neural activity was compared between dance-imagery and fixation blocks at each timepoint. Analysis of functionally defined regions revealed significant blood-oxygen-level-dependent (BOLD) signal activation in the supplementary motor area, right and left superior temporal gyri and left and right insula, with modulation of these regions observed over the training period except for the left insula. The results suggest the potential for dance to induce neuroplastic changes in people with PD in regions associated with motor planning and learning, auditory processing, rhythm, emotion, and multisensory integration. The findings are consistent with dance being a multimodal therapeutic activity that could provide long-term benefits for people with PD. [ABSTRACT FROM AUTHOR]

The insular cortex (IC) is a brain region that both receives relevant sensory information and is responsible for emotional and cognitive processes, allowing the perception of sensory information. The IC has connections with multiple sites of the pain matrix, including cortico-cortical interactions with the anterior cingulate cortex (ACC) and top-down connections with sites of descending pain inhibition. We explored the changes in the extracellular release of serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA), after inflammation was induced by carrageenan injection. Additionally, we explored the role of 5HT receptors (the 5HT1A, 5HT2A, and 5HT3 receptors) in the IC after inflammatory insult. The results showed an increase in the extracellular levels of 5HT and 5-HIAA during the inflammatory process compared to physiological levels. Additionally, the 5HT1A receptor was overexpressed. Finally, the 5HT1A, 5HT2A, and 5HT3 receptor blockade in the IC had antinociceptive effects. Our results highlight the role of serotonergic neurotransmission in long-lasting inflammatory nociception within the IC. [ABSTRACT FROM AUTHOR]

Interoception, the processing of internal bodily signals, is proposed as the fundamental mechanism underlying emotional experiences. Interoceptive and emotional processing appear distorted in psychiatric disorders. However, our understanding of the neural structures involved in both processes remains limited. To explore the feasibility of enhancing interoception and emotion, we conducted two studies using high‐definition transcranial direct current stimulation (HD‐tDCS) applied to the right anterior insula. In study one, we compared the effects of anodal HD‐tDCS and sham tDCS on interoceptive abilities (sensibility, confidence, accuracy, emotional evaluation) in 52 healthy subjects. Study two additionally included physical activation through ergometer cycling at the beginning of HD‐tDCS and examined changes in interoceptive and emotional processing in 39 healthy adults. In both studies, HD‐tDCS was applied in a single‐blind cross‐over online design with two separate sessions. Study one yielded no significant effects of HD‐tDCS on interoceptive dimensions. In study two, significant improvements in interoceptive sensibility and confidence were observed over time with physical preactivation, while no differential effects were found between sham and insula stimulation. The expected enhancement of interoceptive and emotional processing following insula stimulation was not observed. We conclude that HD‐tDCS targeting the insula does not consistently increase interoceptive or emotional variables. The observed increase in interoceptive sensibility may be attributed to the activation of the interoceptive network through physical activity or training effects. Future research on HD‐tDCS involving interoceptive network structures could benefit from protocols targeting larger regions within the network, rather than focusing solely on insula stimulation. This is the first report on the feasibility of enhancing interoceptive and emotion processing through insula stimulation using HD‐tDCS. In contrast to research suggesting an attenuation of interoceptive and emotional processes through the inhibition of this interoceptive network structure, our findings highlight the complexity of enhancing these processes by neurostimulation of the anterior insula. We derive recommendations to increase the effectiveness of HD‐tDCS in the context of interoceptive abilities stimulation. [ABSTRACT FROM AUTHOR]

Objective: Parkinson's disease dementia (PDD) and Dementia with Lewy bodies (DLB) are two syndromes categorized under synucleinopathy, sharing comparable symptoms. The identification of biomarkers would offer an accurate approach for improved diagnosis, treatment, and monitoring of treatment efficacy for these distinct forms of dementia. Method: This study utilized spectral analysis and nonlinear dynamic analysis to compare electroencephalogram (EEG) characteristics between PDD and DLB patients. EEG data was collected from 30 PDD patients, 36 DLB patients, and 36 healthy subjects at rest. Following a conditioning phase to minimize noise and eliminate artifacts, we derived spectral and complexity features using Welch's method and sample entropy. Analysis of variance with repeated measures was performed to compare spectral features and nonlinear dynamics of brain activity between the groups. Results: Post hoc comparison showed that in the control group, the power of delta and theta bands was lower and the power of alpha and beta bands was higher than in patients with PDD and DLB. (P < 0.05). In the theta and alpha bands, the PDD group showed greater power than the DLB group (P < 0.05). Furthermore, there was a significant main effect of diagnosis (F = 4.67, P = 0.007), and also the diagnosis by region interaction for complexity values (F = 4.58, P = 0.009). Post hoc analysis showed that the EEG complexity of the control group was significantly higher than that of the PDD and DLB groups in the frontal, central, temporal and parietal regions (P < 0.05). Moreover, the EEG complexity of the PDD group was significantly higher than that of the DLB group in the central, temporal and parietal regions (P < 0.05). Conclusion: Although both PDD and DLB had almost similar patterns compared to the control group, they showed differences in the EEG power spectrum and its nonlinear dynamics. Our findings indicated marked diffuse slowing and lower cortical complexity or activity in DLB patients compared to PDD in all regions, especially in the central, temporal and parietal areas. [ABSTRACT FROM AUTHOR]

Purpose: The insula, a cortical structure buried deep within the sylvian fissure, has long posed a surgical challenge. Comprehensive knowledge of the insular anatomy is therefore integral to preoperative planning and safe interventional procedures. Since magnetic resonance imaging (MRI) is a favoured modality for the identification of cerebral structures, this study aimed to investigate the morphology and morphometry of the insula in a South African population, using MRI scans. Methods: One-hundred MRI studies of insulae (n = 200 hemispheres) were retrospectively analysed for morphological features and morphometric parameters. Results: The insulae were predominantly trapezoidal in shape (Laterality: Left: 82%; Right: 78%; Sex: Male: 84%, Female: 76%). The central insular sulcus was almost always "well seen" (Laterality: Left: 97%; Right: 99%; Sex: Male: 99%, Female: 97%). The middle short insular gyrus (MSG) was most variable in visibility, especially when compared across the sexes (p = 0.004). Insular gyri widths were comparable in both cerebral hemispheres; the posterior long gyrus (PLG) presented with the smallest mean widths. Anterior lobule (AL) widths were larger than those of the posterior lobule (PL). Widths of the insular gyri and lobules were generally larger in males than in females. The MSG and PLG widths in the left hemisphere, AL width in the right hemisphere, and the PL width in both hemispheres were significantly larger in males than in females (p = 0.001; p = 0.005; p = 0.041; p = 0.001, p = 0.015, respectively). Conclusion: MRI scans may be used to accurately interpret insular anatomy. The data obtained may aid neurosurgeons to perform safe insula-related surgical procedures. [ABSTRACT FROM AUTHOR]

Trauma type moderates the impact of trauma exposure on clinical symptomatology; however, the impact of trauma type on the neural correlates of emotion regulation is not as well understood. This study examines how violent and nonviolent trauma differentially influence the neural correlates of conditioned fear and extinction. We aggregated psychophysiological and fMRI data from three studies; we categorized reported trauma as violent or nonviolent, and subdivided violent trauma as sexual or nonsexual. We examined skin conductance responses (SCR) during a fear conditioning and extinction paradigm. For fMRI data analyses, we conducted region-specific and whole-brain analyses. We examined associations between beta weights from specific brain regions and CAPS scores. The group exposed to violent trauma showed significantly higher SCR during extinction recall. Those exposed to nonviolent trauma showed significantly higher functional activation during late extinction learning. The group exposed to violent trauma showed higher functional connectivity within the default mode network (DMN) and between the DMN and frontoparietal control network. For secondary analyses of sexual vs nonsexual trauma, we did not observe any between-group differences in SCR. During late extinction learning, the group exposed to sexual trauma showed significantly higher activation in the prefrontal cortex and precuneus. During extinction recall, the group exposed to nonsexual trauma showed significantly higher activation in the insular cortex. Violent trauma significantly impacts functional brain activations and connectivity in brain areas important for perception and attention with no significant impact on brain areas that modulate emotion regulation. Sexual trauma impacts brain areas important for internal perception. [ABSTRACT FROM AUTHOR]

Abstract The frequency of behavioral and psychological symptoms of dementia (BPSD) is high, and it is a challenge to elucidate its neural substrates underlying their development. In recent years, many findings have been reported on the relationship between BPSD and brain volume in dementia patients. However, the results are not fully conclusive. Furthermore, there have been few population-based studies. Therefore, the relationship between BPSD and brain volume was investigated as an exploratory study. Of the 927 older persons who participated in the fifth Nakayama study, 90 were included in this analysis, consisting of 52 patients with mild cognitive impairment and 38 patients with dementia, with head MRI and the Neuropsychiatric Inventory (NPI) data. Multiple regression analysis was used to examine the association between the total score of each BPSD score on the NPI and brain volume estimated by FreeSurfer. On multivariate adjustment, even after false discovery rate correction, insular cortical volumes decreased significantly as total scores for apathy/indifference increased (p value = 0.002, q-value = 0.01). Similarly, total brain volume decreased significantly as total scores for appetite and eating disturbance increased (p value = 0.03), and parietal, temporal, and hippocampal cortical volumes also decreased significantly as total scores for appetite and eating disturbance increased (all p and q values

Background: This study aimed to investigate the neural mechanisms that differentiate mind--body practices from aerobic physical activities and elucidate their effects on cognition and healthy aging. We examined functional brain connectivity in older adults (age > 60) without pre-existing uncontrolled chronic diseases, comparing Tai Chi with Water Aerobics practitioners. Methods: We conducted a cross-sectional, case--control fMRI study involving two strictly matched groups (n = 32) based on gender, age, education, and years of practice. Seed-to-voxel analysis was performed using the Salience, and Frontoparietal Networks as seed regions in Stroop Word-Color and N-Back tasks and Resting State. Results: During Resting State condition and using Salience network as a seed, Tai Chi group exhibited a stronger correlation between Anterior Cingulate Cortex and Insular Cortex areas (regions related to interoceptive awareness, cognitive control and motor organization of subjective aspects of experience). In N-Back task and using Salience network as seed, Tai Chi group showed increased correlation between Left Supramarginal Gyrus and various cerebellar regions (related to memory, attention, cognitive processing, sensorimotor control and cognitive flexibility). In Stroop task, using Salience network as seed, Tai Chi group showed enhanced correlation between Left Rostral Prefrontal Cortex and Right Occipital Pole, and Right Lateral Occipital Cortex (areas associated with sustained attention, prospective memory, mediate attention between external stimuli and internal intention). Additionally, in Stroop task, using Frontoparietal network as seed, Water Aerobics group exhibited a stronger correlation between Left Posterior Parietal Lobe (specialized in word meaning, representing motor actions, motor planning directed to objects, and general perception) and different cerebellar regions (linked to object mirroring). Conclusion: Our study provides evidence of differences in functional connectivity between older adults who have received training in a mind--body practice (Tai Chi) or in an aerobic physical activity (Water Aerobics) when performing attentional and working memory tasks, as well as during resting state. [ABSTRACT FROM AUTHOR]

Cinema, a modern titan of entertainment, holds power to move people with the artful manipulation of auditory and visual stimuli. Despite this, the mechanisms behind how sensory stimuli elicit emotional responses are unknown. Thus, this study evaluated which brain regions were involved when sensory stimuli evoke auditory- or visual-driven emotions during film viewing. Using functional magnetic resonance imaging (fMRI) decoding techniques, we found that brain activities in the auditory area and insula represent the stimuli that evoke emotional response. The observation of brain activities in these regions could provide further insights to these mechanisms for the improvement of film-making, as well as the development of novel neural techniques in neuroscience. In near feature, such a "neuro-designed" products/ applications might gain in popularity. [ABSTRACT FROM AUTHOR]

Background and objectives: The internal capsule is supplied by perforators originating from the internal carotid artery, middle cerebral artery, anterior choroidal artery and anterior cerebral artery. The aim of this study is to examine the vascular anatomy of the internal capsule, along with its related white matter anatomy, in order to prevent potential risks and complications during surgical interventions. Methods: Twenty injected hemispheres prepared according to the Klingler method were dissected. Dissections were photographed at each stage. The findings obtained from the dissections were illustrated to make them more understandable. Additionally, the origins of the arteries involved in the vascularization of the internal capsule, their distances to bifurcations, and variations in supplying territories have been thoroughly examined. Results: The insular cortex and the branches of the middle cerebral artery on the insula and operculum were observed. Following decortication of the insular cortex, the extreme capsule, claustrum, external capsule, putamen and globus pallidus structures were exposed. The internal capsule is shown together with the lenticulostriate arteries running on the anterior, genu and posterior limbs. Perforators supplying the internal capsule originated from the middle cerebral artery, anterior cerebral artery, internal carotid artery and anterior choroidal artery. The internal capsule's vascular supply varied, with the medial lenticulostriate arteries (MLA) and lateral lenticulostriate arteries (LLA) being the primary arteries. The anterior limb was most often supplied by the MLA, while the LLA and anterior choroidal artery dominated the genu and posterior limb. The recurrent artery of Heubner originated mostly from the A2 segment. The distance from the ICA bifurcation to the origin of the first LLA on M1 is 9.55 ± 2.32 mm, and to the first MLA on A1 is 5.35 ± 1.84 mm. MLA branching from A1 and proximal A2 ranged from 5 to 9, while LLA originating from the MCA ranged from 7 to 12. Conclusion: This study provides comprehensive understanding of the arterial supply to the internal capsule by combining white matter dissection. The insights gained from this study can help surgeons plan and execute procedures including oncological, psychosurgical, and vascular more accurately and safely. The illustrations derived from the dissections serve as valuable educational material for young neurosurgeons and other medical professionals. [ABSTRACT FROM AUTHOR]

The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular efferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix. These striatal compartments have distinct embryologic origins, afferent and efferent connectivity, dopamine pharmacology, and susceptibility to injury. Striosome and matrix appear to occupy separate sets of cortico-striato-thalamo-cortical loops, so a bias in insulo-striate projections toward one compartment may also embed an insular subregion in distinct regulatory and functional networks. Compartment-specific mapping of insulo-striate structural connectivity is sparse; the insular subregions are largely unmapped for compartment-specific projections. In 100 healthy adults, diffusion tractography was utilized to map and quantify structural connectivity between 19 structurally-defined insular subregions and each striatal compartment. Insulo-striate streamlines that reached striosome-like and matrix-like voxels were concentrated in distinct insular zones (striosome: rostro- and caudoventral; matrix: caudodorsal) and followed different paths to reach the striatum. Though tractography was generated independently in each hemisphere, the spatial distribution and relative bias of striosome-like and matrix-like streamlines were highly similar in the left and right insula. 16 insular subregions were significantly biased toward 1 compartment: 7 toward striosome-like voxels and 9 toward matrix-like voxels. Striosome-favoring bundles had significantly higher streamline density, especially from rostroventral insular subregions. The biases in insulo-striate structural connectivity that were identified mirrored the compartment-specific biases identified in prior studies that utilized injected tract tracers, cytoarchitecture, or functional MRI. Segregating insulo-striate structural connectivity through either striosome or matrix may be an anatomic substrate for functional specialization among the insular subregions. [ABSTRACT FROM AUTHOR]

The reported rate of the occurrence of unilateral spatial neglect (USN) is highly variable likely due to the lack of validity and low sensitivity of classical tools used to assess it. Virtual reality (VR) assessments try to overcome these limitations by proposing immersive and complex environments. Nevertheless, existing VR‐based tasks are mostly focused only on near space and lack analysis of psychometric properties and/or clinical validation. The present study evaluates the clinical validity and sensitivity of a new immersive VR‐based task to assess USN in the extra‐personal space and examines the neuronal correlates of deficits of far space exploration. The task was administrated to two groups of patients with right (N = 28) or left (N = 11) hemispheric brain lesions, also undergoing classical paper‐and‐pencil assessment, as well as a group of healthy participants. Our VR‐based task detected 44% of neglect cases compared to 31% by paper‐and‐pencil tests in the total sample. Importantly, 30% of the patients (with right or left brain lesions) with no clear sign of USN on the paper‐and‐pencil tests performed outside the normal range in the VR‐based task. Voxel lesion‐symptom mapping revealed that deficits detected in VR were associated with lesions in insular and temporal cortex, part of the neural network involved in spatial processing. These results show that our immersive VR‐based task is efficient and sensitive in detecting mild to strong manifestations of USN affecting the extra‐personal space, which may be undetected using standard tools. [ABSTRACT FROM AUTHOR]

In this study, we ran a meta-analysis of neuroimaging studies to pinpoint the neural regions that are commonly activated across space, time, and numerosity, and we tested the existence of gradient transitions among these magnitude representations in the brain. Following PRISMA guidelines, we included in the meta-analysis 112 experiments (for space domain), 114 experiments (time domain), and 115 experiments (numerosity domain), and we used the activation likelihood estimation method. We found a system of brain regions that was commonly recruited in all the three magnitudes, which included bilateral insula, the supplementary motor area (SMA), the right inferior frontal gyrus, and bilateral intraparietal sulci. Gradiental transitions between different magnitudes were found along all these regions but insulae, with space and numbers leading to gradients mainly over parietal regions (and SMA) whereas time and numbers mainly over frontal regions. These findings provide evidence for the GradiATOM theory (Gradient Theory of Magnitude), suggesting that spatial proximity given by overlapping activations and gradients is a key aspect for efficient interactions and integrations among magnitudes. [ABSTRACT FROM AUTHOR]

Sex differences in pain sensitivity have contributed to the fact that medications for curing chronic pain are unsatisfactory. However, the underlying mechanism remains to be elucidated. Brain‐derived estrogen participates in modulation of sex differences in pain and related emotion. G protein‐coupled receptor 30 (GPR30), identified as a novel estrogen receptor with a different distribution than traditional receptors, has been proved to play a vital role in regulating pain affected by estrogen. However, the contribution of its distribution to sexually dimorphic pain‐related behaviors has not been fully explored. In the current study, immunofluorescence assays were applied to mark the neurons expressing GPR30 in male and female mice (in metestrus and proestrus phase) in pain‐related brain regions. The neurons that express CaMKIIα or VGAT were also labeled to observe overlap with GPR30. We found that females had more GPR30‐positive (GPR30+) neurons in the primary somatosensory (S1) and insular cortex (IC) than males. In the lateral habenula (LHb) and the nucleus tractus solitarius (NTS), males had more GPR30+ neurons than females. Moreover, within the LHb, the expression of GPR30 varied with estrous cycle phase; females in metestrus had fewer GPR30+ neurons than those in proestrus. In addition, females had more GPR30+ neurons, which co‐expressed CaMKIIα in the medial preoptic nucleus (mPOA) than males, while males had more than females in the basolateral complex of the amygdala (BLA). These findings may partly explain the different modulatory effects of GPR30 in pain and related emotional phenotypes between sexes and provide a basis for comprehension of sexual dimorphism in pain related to estrogen and GPR30, and finally provide new targets for exploiting new treatments of sex‐specific pain. [ABSTRACT FROM AUTHOR]

Alcohol exposure affects brain structure, but the extent to which its effects differ across development remains unclear. Several countries are considering changes to recommended guidelines for alcohol consumption, so high‐quality evidence is needed. Many studies have been conducted among small samples, but recent efforts have been made to acquire large samples to characterize alcohol's effects on the brain on a population level. Several large‐scale consortia have acquired such samples, but this evidence has not been synthesized across the lifespan. We conducted a systematic review of large‐scale neuroimaging studies examining effects of alcohol exposure on brain structure at multiple developmental stages. We included studies with an alcohol‐exposed sample of at least N = 100 from the following consortia: ABCD, ENIGMA, NCANDA, IMAGEN, Framingham Offspring Study, HCP and UK BioBank. Twenty‐seven studies were included, examining prenatal (N = 1), adolescent (N = 9), low‐to‐moderate‐level adult (N = 11) and heavy adult (N = 7) exposure. Prenatal exposure was associated with greater brain volume at ages 9–10, but contemporaneous alcohol consumption during adolescence and adulthood was associated with smaller volume/thickness. Both low‐to‐moderate consumption and heavy consumption were characterized by smaller volume and thickness in frontal, temporal and parietal regions, and reductions in insula, cingulate and subcortical structures. Adolescent consumption had similar effects, with less consistent evidence for smaller cingulate, insula and subcortical volume. In sum, prenatal exposure was associated with larger volume, while adolescent and adult alcohol exposure was associated with smaller volume and thickness, suggesting that regional patterns of effects of alcohol are similar in adolescence and adulthood. This systematic review of large‐scale neuroimaging studies examining the effects of alcohol exposure on brain structure across multiple developmental stages showed that adult alcohol consumption was characterized by smaller volume and thickness in frontal, temporal, and parietal regions, and reductions in insula, cingulate, and subcortical structures. Adolescent alcohol consumption had similar effects, but with less consistent evidence for smaller cingulate, insula, and subcortical volume. This suggests that regional patterns of effects of alcohol are similar in adolescence and adulthood. [ABSTRACT FROM AUTHOR]

The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular's connections to the limbic system might play a role in the aversive and emotional component of pain, its connections to the descending pain system might be involved in pain intensity coding. Here, we used anterograde tracing with viral expression of mCherry fluorescent protein, to examine the connectivity of insular axons to different brainstem nuclei involved in the descending modulation of pain in detail. We found extensive connections to the main areas of descending pain control, namely, the periaqueductal gray (PAG) and the raphe magnus (RMg). In addition, we also identified an extensive insular connection to the parabrachial nucleus (PBN). Although not as extensive, we found a consistent axonal input from the insula to different noradrenergic nuclei, the locus coeruleus (LC), the subcoereuleus (SubCD) and the A5 nucleus. These connections emphasize a prominent relation of the insula with the descending pain modulatory system, which reveals an important role of the insula in pain processing through descending pathways. [ABSTRACT FROM AUTHOR]

Many expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular cortex (IC), a brain region involved in emotional processing and linked to psychiatric disorders. The IC is divided into two territories: the anterior IC (aIC), processing socioemotional signals, and the posterior IC (pIC), specializing in interoception and pain perception. Pyramidal neurons in the aIC and pIC exhibit sex-specific electrophysiological properties, including variations in excitability and the excitatory/inhibitory balance. We investigated IC's cellular properties and synaptic strength in the offspring of both sexes from mice exposed to low-dose CBD during gestation (E5–E18; 3 mg/kg, s.c.). Prenatal CBD exposure induced sex-specific and territory-specific changes in the active and passive membrane properties, as well as intrinsic excitability and the excitatory/inhibitory balance, in the IC of adult offspring. The data indicate that in utero CBD exposure disrupts IC neuronal development, leading to a loss of functional distinction between IC territories. These findings may have significant implications for understanding the effects of CBD on emotional behaviors in offspring. [ABSTRACT FROM AUTHOR]

Interoception, the sense of the physiological condition of our body, is impaired in individuals with autism spectrum disorders. Evidence suggests that subclinical autistic traits are mild manifestations of autistic symptoms, present in the general population. We examined the resting-state functional connectivity (rsFC) associating with interoception and autistic traits in 62 healthy young adults. Autistic traits correlated negatively with the rsFC between the lateral ventral anterior insula and anterior cingulate cortex. Interoceptive accuracy and sensibility correlated positively with the rsFC between interoceptive brain networks and the cerebellum, supplementary motor area, and visual regions. The results suggest that a negative relationship between interoception and autistic traits is largely accounted for by both self-report measures and decreased rsFC amongst the interoceptive brain network. [ABSTRACT FROM AUTHOR]

Altered functional connectivity has been demonstrated in key brain regions involved in pain processing in painful diabetic peripheral neuropathy. However, the impact of neuropathic pain treatment on functional connectivity does not appear to have been investigated. Sixteen participants underwent resting state functional MRI when optimally treated for neuropathic pain during their involvement in the Optimal Pathway for Treating Neuropathic Pain in Diabetes Mellitus trial and 1 week following withdrawal of treatment. On discontinuation of pain treatment, there was an increase in functional connectivity between the left thalamus and primary somatosensory cortex (S1) and the left thalamus and insular cortex, key brain regions that are involved in cerebral processing of pain. The changes in functional connectivity between scans also correlated with measures of pain (baseline pain severity and Neuropathic Pain Symptom Inventory). Moreover, when participants were stratified into higher- and lower-than-average baseline pain subgroups, the change in thalamic-S1 cortical functional connectivity between scans was significantly greater in those with high baseline pain compared with the lower-baseline-pain group. This study shows that thalamo-cortical functional connectivity has the potential to act as an objective biomarker for neuropathic pain in diabetes for use in clinical pain trials. Article Highlights: Functional connectivity alterations have been found in the brain in painful diabetic peripheral neuropathy (DPN), but the impact of treatment on these measures is unknown. The study was aimed to address the question of whether functional connectivity between key pain processing brain regions will increase on withdrawal of treatment. Study findings show discontinuation of neuropathic pain treatment leads to increases in functional connectivity between the thalamus and primary somatosensory and insular cortices. Cerebral functional connectivity demonstrates the potential to act as an objective biomarker for painful DPN in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Frontotemporal lobar degeneration (FTLD) is associated with FTLD due to tau (FTLD-tau) or TDP (FTLD-TDP) inclusions found at autopsy. Arterial Spin Labeling (ASL) MRI is often acquired in the same session as a structural T1- weighted image (T1w), enabling detection of regional changes in cerebral blood flow (CBF). We hypothesize that ASL-T1w registration with more degrees of freedom using boundary-based registration (BBR) will better align ASL and T1w images and show increased sensitivity to regional hypoperfusion differences compared to manual registration in patient participants. We hypothesize that hypoperfusion will be associated with a clinical measure of disease severity, the FTLD-modified clinical dementia rating scale sum-of-boxes (FTLD-CDR). Materials and methods: Patients with sporadic likely FTLD-tau (sFTLD-tau; N = 21), with sporadic likely FTLD-TDP (sFTLD-TDP; N = 14), and controls (N = 50) were recruited from the Connectomic Imaging in Familial and Sporadic Frontotemporal Degeneration project (FTDHCP). Pearson's Correlation Coefficients (CC) were calculated on cortical vertex-wise CBF between each participant for each of 3 registration methods: (1) manual registration, (2) BBR initialized with manual registration (manual+BBR), (3) and BBR initialized using FLIRT (FLIRT+BBR). Mean CBF was calculated in the same regions of interest (ROIs) for each registration method after image alignment. Paired t-tests of CC values for each registration method were performed to compare alignment. Mean CBF in each ROI was compared between groups using t-tests. Differences were considered significant at p < 0.05 (Bonferroni-corrected). We performed linear regression to relate FTLD-CDR to mean CBF in patients with sFTLD-tau and sFTLD-TDP, separately (p < 0.05, uncorrected). Results: All registration methods demonstrated significant hypoperfusion in frontal and temporal regions in each patient group relative to controls. All registration methods detected hypoperfusion in the left insular cortex, middle temporal gyrus, and temporal pole in sFTLD-TDP relative to sFTLD-tau. FTLD- CDR had an inverse association with CBF in right temporal and orbitofrontal ROIs in sFTLD-TDP. Manual+BBR performed similarly to FLIRT+BBR. Discussion: ASL is sensitive to distinct regions of hypoperfusion in patient participants relative to controls, and in patients with sFTLD-TDP relative to sFTLD-tau, and decreasing perfusion is associated with increasing disease severity, at least in sFTLD-TDP. BBR can register ASL-T1w images adequately for controls and patients. [ABSTRACT FROM AUTHOR]

Decision-makers may follow either the direct-response method or strategy method. While the two elicitation methods are theoretically equivalent, it is uncertain whether they lead to the same outcomes in practice. To explore this issue, we conduct an experiment based on a reward-punishment game under both methods, in which functional magnetic resonance imaging (fMRI) is used to provide neural evidence for uncovering the underlying behavioural mechanisms. The results show that both the reward and punishment rates are significantly higher under the strategy method compared to the direct-response method. We develop behavioural models to explain these differences and identify the ownership effect, strategic thinking, and counterfactual thinking as potential drivers. Comparison of neural activity between the two treatments demonstrates that during reward/no-reward decisions, the direct-response treatment accrues stronger activation in the bilateral anterior insula, indicating that decision-makers overweigh reward cost due to ownership effect, which consequently leads to reduced willingness to impose rewards. Conversely, during punishment/no-punishment decisions, the strategy treatment causes stronger activations in the bilateral anterior insula and inferior parietal lobule, implying that decision-makers perceive strong unfairness due to counterfactual thinking, which further results in more punishment decisions. Moreover, our findings reveal that strategic thinking influences decision-making during long-term interactions. [ABSTRACT FROM AUTHOR]

How does alcohol consumption alter synaptic transmission across time, and do these alcohol-induced neuroadaptations occur similarly in both male and female mice? Previously we identified that anterior insular cortex (AIC) projections to the dorsolateral striatum (DLS) are uniquely sensitive to alcohol-induced neuroadaptations in male, but not female mice, and play a role in governing binge alcohol consumption in male mice (Haggerty et al., 2022). Here, by using high-resolution behavior data paired with in-vivo fiber photometry, we show how similar levels of alcohol intake are achieved via different behavioral strategies across sexes, and how inter-drinking session thirst states predict future alcohol intakes in females, but not males. Furthermore, we show how presynaptic calcium activity recorded from AIC synaptic inputs in the DLS across 3 weeks of water consumption followed by 3 weeks of binge alcohol consumption changes across, fluid, time, sex, and brain circuit lateralization. By time-locking presynaptic calcium activity from AIC inputs to the DLS to peri-initiation of drinking events we also show that AIC inputs into the left DLS robustly encode binge alcohol intake behaviors relative to water consumption. These findings suggest a fluid-, sex-, and lateralization-dependent role for the engagement of AIC inputs into the DLS that encode binge alcohol consumption behaviors and further contextualize alcohol-induced neuroadaptations at AIC inputs to the DLS. [ABSTRACT FROM AUTHOR]

The ventral frontal cortex (VFC) in macaques is involved in many affective and cognitive processes and has a key role in flexibly guiding reward-based decision-making. VFC is composed of a set of anatomically distinct subdivisions that are within the orbitofrontal cortex, ventrolateral prefrontal cortex, and anterior insula. In part, because prior studies have lacked the resolution to test for differences, it is unclear if neural representations related to decision-making are dissociable across these subdivisions. Here we recorded the activity of thousands of neurons within eight anatomically defined subdivisions of VFC in male macaque monkeys performing a two-choice probabilistic task for different fruit juice outcomes. We found substantial variation in the encoding of decision variables across these eight subdivisions. Notably, ventrolateral Area 12l was unique relative to the other areas that we recorded from as the activity of single neurons integrated multiple attributes when monkeys evaluated the different choice options. Activity within Area 12o, in contrast, more closely represented reward probability and whether reward was received on a given trial. Orbitofrontal Area 11m/l contained more specific representations of the quality of the outcome that could be earned later on. We also found that reward delivery encoding was highly distributed across all VFC subdivisions, while the properties of the reward, such as its flavor, were more strongly represented in Areas 11m/l and 13m. Taken together, our work reveals the diversity of encoding within the various anatomically distinct subdivisions of VFC in primates. [ABSTRACT FROM AUTHOR]

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely utilized to investigate plasticity mechanisms and functional reorganization in multiple sclerosis (MS). Among many resting state (RS) networks, a significant role is played by the salience network (SN, ventral attention network). Previous reports have demonstrated the involvement of osteopontin (OPN) in the pathogenesis of MS, which acts as a proinflammatory cytokine ultimately leading to neurodegeneration. Concentration of serum OPN was related to MRI findings 10.22±2.84 years later in 44 patients with MS. Local and interhemispheric correlations (LCOR, IHC), ROI-to-ROI and seed-based connectivity analyses were performed using serum OPN levels as independent variable along with age and gender as nuisance variables. We found significant associations between OPN levels and local correlation in right and left clusters encompassing the central opercular- and insular cortices (p-FDR = 0.0018 and p-FDR = 0.0205, respectively). Moreover, a significant association was identified between OPN concentration and interhemispheric correlation between central opercular- and insular cortices (p-FDR = 0.00015). Significant positive associations were found between OPN concentration and functional connectivity (FC) within the SN (FC strength between the anterior insula ventral division and 3 other insular regions, F(2,13) = 7.84, p-FDR = 0.0117). Seed-based connectivity analysis using the seven nodes of the SN resulted in several positive and inverse associations with OPN level. Serum OPN level may predict FC alterations within the SN in 10 years. [ABSTRACT FROM AUTHOR]

Interoception plays an important role in emotion processing. However, the neurobiological substrates of the relationship between visceral responses and emotional experiences remain unclear. In the present study, we measured interoceptive sensitivity using the heartbeat discrimination task and investigated the effects of individual differences in interoceptive sensitivity on changes in pulse rate and insula activity in response to subjective emotional intensity. We found a positive correlation between heart rate and valence level when listening to music only in the high interoceptive sensitivity group. The valence level was also positively correlated with music-elicited anterior insula activity. Furthermore, a region of interest analysis of insula subregions revealed significant activity in the left dorsal dysgranular insula for individuals with high interoceptive sensitivity relative to individuals with low interoceptive sensitivity while listening to the high-valence music pieces. Our results suggest that individuals with high interoceptive sensitivity use their physiological responses to assess their emotional level when listening to music. In addition, insula activity may reflect the use of interoceptive signals to estimate emotions. [ABSTRACT FROM AUTHOR]

Objective: The cingulate sulcus sign (CSS) has been observed in patients with idiopathic normal pressure hydrocephalus (iNPH), suggesting potential disruptions in cerebrospinal fluid circulation and compromised glymphatic system. Although there are similarities in the underlying mechanisms between cerebral small vessel disease (CSVD) and iNPH, the relationship between CSS and CSVD remains unclear. This study aimed to investigate the prevalence and potential mechanisms of CSS in patients with CSVD. Methods: Data from patients diagnosed with CSVD at Shengjing Hospital of China Medical University between January 2020 and October 2022 were retrospectively collected, including general information, global cognitive function [assessed by measuring Mini-Mental State Examination (MMSE)], and four CSVD magnetic resonance imaging (MRI) markers [(white matter hyperintensity (WMH), cerebral microbleeds (CMBs), lacunes, and enlarged perivascular spaces (EPVS)], CSS and the Evan's index (EI). Results: A total of 308 patients were included, and CSS was detected in 80 patients (26%). Univariate analysis revealed that MMSE scores in the CSS group were significantly lower compared to the non-CSS group (p < 0.001). Multivariable analysis showed an independent correlation between CSS and the presence of lacunes (odds ratio [OR] 0.358, 95% confidence interval [CI] 0.193-0.663, p = 0.001), presence of lobar dominant CMBs (OR 2.683, 95%CI 1.385-5.195, p = 0.003), periventricular WMH Fazekas score (OR 1.693, 95% CI 1.133-2.529, p = 0.01), and EI (OR 1.276, 95% CI 1.146-1.420, p < 0.001). Conclusion: This preliminary study showed that CSS can be observed in some patients with CSVD. The presence of CSS may represent different mechanisms of CSVD pathogenesis and reflect differences in the degree of cerebrospinal fluid (CSF)/interstitial fluid (ISF) stasis. [ABSTRACT FROM AUTHOR]

• Feeding induced increases in the amplitudes of jejunal myoelectrical signals. • The feeding-induced increase was abolished by vagotomy. • The feeding-induced increase was abolished by posterior insular cortical inhibition. • Feeding changed the autonomic activity. • These changes were abolished by posterior insular cortical inhibition. The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic control. The insular cortex is one of the brain regions that may regulate the muscle motility. In this study, we examined whether, and how, the insular cortex, especially the posterior part, regulates gastrointestinal motility by recording jejunal myoelectrical signals in response to feeding in freely moving male rats. Feeding was found to induce increases in jejunal myoelectrical signal amplitudes. This increase in the jejunal myoelectrical signals was abolished by vagotomy and pharmacological inhibition of the posterior insular cortex. Additionally, feeding induced a decrease and increase in sympathetic and parasympathetic nervous activities, respectively, both of which were eliminated by posterior insular cortical inhibition. These results suggest that the posterior insular cortex regulates jejunal motility in response to feeding by modulating autonomic tone. [ABSTRACT FROM AUTHOR]

Predictive processing (PP) stands as a predominant theoretical framework in neuroscience. While some efforts have been made to frame PP within a cognitive domain‐general network perspective, suggesting the existence of a "prediction network," these studies have primarily focused on specific cognitive domains or functions. The question of whether a domain‐general predictive network that encompasses all well‐established cognitive domains exists remains unanswered. The present meta‐analysis aims to address this gap by testing the hypothesis that PP relies on a large‐scale network spanning across cognitive domains, supporting PP as a unified account toward a more integrated approach to neuroscience. The Activation Likelihood Estimation meta‐analytic approach was employed, along with Meta‐Analytic Connectivity Mapping, conjunction analysis, and behavioral decoding techniques. The analyses focused on prediction incongruency and prediction congruency, two conditions likely reflective of core phenomena of PP. Additionally, the analysis focused on a prediction phenomena‐independent dimension, regardless of prediction incongruency and congruency. These analyses were first applied to each cognitive domain considered (cognitive control, attention, motor, language, social cognition). Then, all cognitive domains were collapsed into a single, cross‐domain dimension, encompassing a total of 252 experiments. Results pertaining to prediction incongruency rely on a defined network across cognitive domains, while prediction congruency results exhibited less overall activation and slightly more variability across cognitive domains. The converging patterns of activation across prediction phenomena and cognitive domains highlight the role of several brain hubs unfolding within an organized large‐scale network (Dynamic Prediction Network), mainly encompassing bilateral insula, frontal gyri, claustrum, parietal lobules, and temporal gyri. Additionally, the crucial role played at a cross‐domain, multimodal level by the anterior insula, as evidenced by the conjunction and Meta‐Analytic Connectivity Mapping analyses, places it as the major hub of the Dynamic Prediction Network. Results support the hypothesis that PP relies on a domain‐general, large‐scale network within whose regions PP units are likely to operate, depending on the context and environmental demands. The wide array of regions within the Dynamic Prediction Network seamlessly integrate context‐ and stimulus‐dependent predictive computations, thereby contributing to the adaptive updating of the brain's models of the inner and external world. [ABSTRACT FROM AUTHOR]

Enactive cognition emphasizes co‐constructive roles of humans and their environment in shaping cognitive processes. It is specifically engaged in the mental simulation of behaviors, enhancing the connection between perception and action. Here we investigated the core network of brain regions involved in enactive cognition as applied to mental simulations of physical exercise. We used a neuroimaging paradigm in which participants (N = 103) were required to project themselves running or plogging (running while picking‐up litter) along an image‐guided naturalistic trail. Using both univariate and multivariate brain imaging analyses, we find that a broad spectrum of brain activation discriminates between the mental simulation of plogging versus running. Critically, we show that self‐reported ratings of daily life running engagement and the quality of mental simulation (how well participants were able to imagine themselves running) modulate the brain reactivity to plogging versus running. Finally, we undertook functional connectivity analyses centered on the insular cortex, which is a key region in the dynamic interplay between neurocognitive processes. This analysis revealed increased positive and negative patterns of insular‐centered functional connectivity in the plogging condition (as compared to the running condition), thereby confirming the key role of the insular cortex in action simulation involving complex sets of mental mechanisms. Taken together, the present findings provide new insights into the brain networks involved in the enactive mental simulation of physical exercise. [ABSTRACT FROM AUTHOR]