Insular Cortex Research Articles

Travelling beyond time: shared brain system for self-projection in the temporal, political and moral domains.

Mental time travel (MTT), a cornerstone of human cognition, enables individuals to mentally project themselves into their past or future. It was shown that this self-projection may extend beyond the temporal domain to the spatial and social domains. What about higher cognitive domains? Twenty-eight participants underwent functional magnetic resonance imaging (fMRI) while self-projecting to different political, moral and temporal perspectives. For each domain, participants were asked to judge their relationship to various people (politicians, moral figures, personal acquaintances) from their actual or projected self-location. Findings showed slower, less accurate responses during self-projection across all domains. fMRI analysis revealed self-projection elicited brain activity at the precuneus, medial and dorsolateral prefrontal cortex, temporoparietal junction and anterior insula, bilaterally and right lateral temporal cortex. Notably, 23.5% of active voxels responded to all three domains and 27% to two domains, suggesting a shared brain system for self-projection. For ordinality judgement (self-reference), 52.5% of active voxels corresponded to the temporal domain specifically. Self-projection activity overlapped mostly with the frontoparietal control network, followed by the default mode network, while self-reference showed a reversed pattern, demonstrating MTT's implication in spontaneous brain activity. MTT may thus be regarded as a 'mental-experiential travel', with self-projection as a domain-general construct and self-reference related mostly to time. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Changed resting-state connectivity of anterior insular cortex affects subjective pain reduction after knee arthroplasty: A longitudinal study

The mechanism of chronic knee osteoarthritis (OA) pain and postoperative pain due to knee arthroplasty has not been elucidated. This could be involved neuroplasticity in brain connectivity. To clarify the mechanism of chronic knee OA pain and postoperative pain, we examined the relationship between resting-state functional connectivity (rs-FC) and clinical measurements in knee OA before and after knee arthroplasty, focusing on rs-FCs with the anterior insular cortex (aIC) as the key region. Fifteen patients with knee OA underwent resting-state functional magnetic resonance imaging and clinical measurements shortly before and 6 months after knee arthroplasty, and 15 age- and sex-matched control patients underwent an identical protocol. Seed-to-voxel analysis was performed to compare the clinical measurements and changed rs-FCs, using the aIC as a seed region, between the preoperative and postoperative patients, as well as between the operative and control patients. In preoperative patients, rs-FCs of the aIC to the OFC, frontal pole, subcallosal area, and medial frontal cortex increased compared with those of the control patients. The strength of rs-FC between the left aIC and right OFC decreased before and after knee arthroplasty. The decrease in rs-FC between the left aIC and right OFC was associated with decreased subjective pain score. Our study showed a correlation between longitudinally changed rs-FC and clinical measurement before and after knee arthroplasty. Rs-FC between the aIC and OFC have the potential to elucidate the mechanisms of knee OA pain and postoperative pain due to knee arthroplasty.

A sex-stratified analysis of the genetic architecture of human brain anatomy

Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared male and female participants. Here we screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes in the UK Biobank and establish a general concordance between male and female participants in heritability estimates, genetic correlations, and variant-level effects. Notable exceptions include higher mean heritability in the female group for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and a common variant with stronger effect in male participants mapping to RBFOX1 - a gene linked to multiple neuropsychiatric disorders more common in men. This work suggests that common variant influences on human brain anatomy are largely consistent between males and females, with a few exceptions that will guide future research in growing datasets.

Not All Stroop-Type Tasks Are Alike: Assessing the Impact of Stimulus Material, Task Design, and Cognitive Demand via Meta-analyses Across Neuroimaging Studies.

The Stroop effect is one of the most often studied examples of cognitive conflict processing. Over time, many variants of the classic Stroop task were used, including versions with different stimulus material, control conditions, presentation design, and combinations with additional cognitive demands. The neural and behavioral impact of this experimental variety, however, has never been systematically assessed. We used activation likelihood meta-analysis to summarize neuroimaging findings with Stroop-type tasks and to investigate whether involvement of the multiple-demand network (anterior insula, lateral frontal cortex, intraparietal sulcus, superior/inferior parietal lobules, midcingulate cortex, and pre-supplementary motor area) can be attributed to resolving some higher-order conflict that all of the tasks have in common, or if aspects that vary between task versions lead to specialization within this network. Across 133 neuroimaging experiments, incongruence processing in the color-word Stroop variant consistently recruited regions of the multiple-demand network, with modulation of spatial convergence by task variants. In addition, the neural patterns related to solving Stroop-like interference differed between versions of the task that use different stimulus material, with the only overlap between color-word, emotional picture-word, and other types of stimulus material in the posterior medial frontal cortex and right anterior insula. Follow-up analyses on behavior reported in these studies (in total 164 effect sizes) revealed only little impact of task variations on the mean effect size of reaction time. These results suggest qualitative processing differences among the family of Stroop variants, despite similar task difficulty levels, and should carefully be considered when planning or interpreting Stroop-type neuroimaging experiments.

Exploring arterial anatomy of the internal capsule: an analysis of the deep vascular structures and related white matter pathways.

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. 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. 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 ± 2.32mm, and to the first MLA on A1 is 5.35 ± 1.84mm. MLA branching from A1 and proximal A2 ranged from 5 to 9, while LLA originating from the MCA ranged from 7 to 12. 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.

AGR – 2 The Multi-Dimensional Role of Neuropsychology in Diagnostically Complex Epilepsy Patients: Refining the Surgical Plan and Post-Operative Expectations

Abstract Objective We present a case highlighting the importance of neuropsychological involvement at all phases of a pre-surgical epilepsy work-up, including clinical interview, neuropsychological evaluation, Wada testing, extra-operative electrical stimulation mapping (ESM), and psychoeducation. Method A 24-year-old, right-handed, Caucasian female presented with non-lesional, intractable left-hemisphere localization-related epilepsy characterized by frequent experiences of déjà vu and autonomic sensations. Results Neuropsychological evaluation revealed weaknesses in processing speed and verbal memory implicating left hippocampal involvement. Wada testing suggested minimal contralateral memory support, indicating poor candidacy for resective surgery. The patient underwent prolonged sEEG monitoring to refine a plan for device implantation (i.e., responsive neurostimulation; RNS). No typical events were captured during extended study. Episodic somatosensory changes were captured, which had no electrographic correlate and were presumed to be non-epileptic. ESM evoked the patient’s classic semiology, elucidating nuanced information about her seizure onset zone and network. Barriers to extended monitoring and consistent, reliable engagement during ESM included depression, anxiety, and trauma; considerable neuropsychologist-led emotional support was required. Typical seizure semiology was elicited during stimulation of entorhinal cortices, posterior and anterior hippocampi, amygdala, cingulate and insula. RNS placement included a depth electrode targeting the medial structures (via a posterior approach) with a sub-temporal strip. Conclusions Involvement of neocortical and mesial temporal structures, coupled with a clear neuropsychiatric component, were believed to be poly-etiological factors to the patient’s presentation. Neuropsychological input at all phases of pre-surgical assessment was instrumental in systematically identifying and addressing her complex needs. Psychotherapeutic intervention was suggested to be equally as important to clinical, long-term patient outcome.

Periaqueductal gray connectivity in spinal cord injury-induced neuropathic pain.

Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting-state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. Ten SCI patients (SCI+NP, n=7, and SCI-NP, n=3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed-to-voxel analysis using PAG as the seed region and then group-based analysis comprising three groups (SCI+NP, SCI-NP, and HC). Age and gender were considered as confounding variables. Compared to HCs, SCI+NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI-NP, SCI+NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V.

Characterization of neural networks involved in transdiagnostic emotion dysregulation from a pilot randomized controlled trial of a neurostimulation-enhanced behavioral intervention

BackgroundEmotional dysregulation is a serious and impairing mental health problem. We examined functional activity and connectivity of neural networks involved in emotional dysregulation at baseline and following a pilot neurostimulation-enhanced cognitive restructuring intervention in a transdiagnostic clinical adult sample. MethodsNeuroimaging data were analyzed from adults who scored 89 or higher on the Difficulties with Emotion Regulation (DERS) scale and had at least one DSM-5 diagnosis. These participants were part of a pilot randomized, double-blind, placebo-controlled trial combining a single therapeutic session of cognitive restructuring with active or sham transcranial magnetic stimulation over the dorsolateral prefrontal cortex. During the study, participants engaged in an emotional regulation task using personalized autobiographical stressors while undergoing functional magnetic resonance imaging (fMRI) before and after the pilot intervention. The fMRI task required participants to either experience the emotions associated with the memories or apply cognitive restructuring strategies to reduce their distress. ResultsWhole-brain fMRI results during regulation at baseline revealed increased activation in the dorsal frontoparietal network but decreased activation in the supplementary motor area, cingulate cortex, insula, and ventrolateral prefrontal cortex (vlPFC). Emotion dysregulation was associated with greater vmPFC and amygdala activation and functional connectivity between these regions. The strength of functional connectivity between the dlPFC and other frontal regions was also a marker of emotional dysregulation. Preliminary findings from a subset of participants who completed the follow-up fMRI scan showed that active neurostimulation improved behavioral indices of emotion regulation more than sham stimulation. A whole-brain generalized psychophysiological interaction analysis indicated that active neurostimulation selectively increased occipital cortex connectivity with both the insula and the dlPFC. Region-of-interest functional connectivity analyses showed that active neurostimulation selectively increased dlPFC connectivity with the insula and orbitofrontal cortex (OFC). ConclusionInsufficient neural specificity during the emotion regulation process and over-involvement of frontal regions may be a marker of emotional dysregulation across disorders. OFC, vlPFC, insula activity, and connectivity are associated with improved emotion regulation in transdiagnostic adults. In this pilot study, active neurostimulation led to neural changes in the emotion regulation network after a single session; however, the intervention findings are preliminary, given the small sample size. These functional network properties can inform future neuroscience-driven interventions and larger-scale studies.

The oxytocinergic system and racial ingroup bias in empathic neural activity

Studies have indicated that the human brain exhibits a more robust neural empathic response towards individuals of the same racial ingroup than those of the outgroup. However, the impact of the oxytocinergic system on the dynamic connectivity between brain regions involved in racial ingroup bias in empathy (RIBE) and its implications for real-life social interaction intention remains unclear. To address this gap, we employed functional magnetic resonance imaging (fMRI) to investigate RIBE-modulated neural activities and the influence of the oxytocinergic system at both neural and behavioral levels. Participants homozygous for the A/A and G/G genotypes of the oxytocin receptor gene (OXTR) rs53576 polymorphism underwent scanning while making judgments about painful versus non-painful stimuli in same-race versus other-race scenarios following either oxytocin (OT) or placebo treatment. The results revealed greater activity in the anterior cingulate cortex (ACC) and anterior insula (AI) in response to same-race compared to other-race models in the G/G group but not in the A/A group. RIBE also modulated the connections between bilateral AI and the ACC, and the effect of OT on this modulatory effect was moderated by genotype rs53576 and interpersonal trust. Moreover, more extensive changes in AI-ACC connections were associated with higher levels of revenge intention in the low interpersonal trust group. Overall, our findings suggest a pivotal role of the oxytocinergic system in the RIBE-modulated neural activities and revenge intention in human interactions with the modulatory effect of interpersonal trust.This article is part of the Special Issue on “Empathic Pain”.

Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank

Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI. For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses. We constructed fully adjusted models that included age, time, sex, Lancet Commission dementia risk factors, stroke, and hospital admissions with a participant random effect. Primary outcomes were hippocampal volume and white matter hyperintensities, both of which are established markers of neurodegeneration, and exploratory analyses investigated the cortical thickness of Desikan-Killiany-Tourville atlas regions. The main cognitive outcomes were reaction time, fluid intelligence, and prospective and numeric memory. Surgeries were calculated cumulatively starting from 8years before the baseline evaluation. Of 502 412participants in the UK Biobank study, 492 802participants were eligible for inclusion in this study, of whom 46 706underwent MRI. Small adverse associations with cognition were found per surgery: reaction time increased by 0·273ms, fluid intelligence score decreased by 0·057correct responses, prospective memory (scored as correct at first attempt) decreased (odds ratio 0·96 [95% CI 0·95to 0·97]), and numeric memory maximum correct matches decreased by 0·025in fully adjusted models. Surgeries were associated with smaller hippocampal volume (β=-5·76mm³ [-7·89to-3·64]) and greater white matter hyperintensities volume (β=100·02 mm³ [66·17to 133·87]) in fully adjusted models. Surgeries were also associated with neurodegeneration of the insula and superior temporal cortex. This population-based study corroborates that surgeries are generally safe but cumulatively are associated with cognitive decline and neurodegeneration. Perioperative brain health should be prioritised for older and vulnerable patients, particularly those who have multiple surgical procedures. The Australian and New Zealand College of Anaesthetists (ANZCA) Foundation and the University of Sydney.

Gestational CBD Shapes Insular Cortex in Adulthood.

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.

Interoceptive signals shape the earliest markers and neural pathway to awareness at the visual threshold

Variations in interoceptive signals from the baroreceptors (BRs) across the cardiac and respiratory cycle can modulate cortical excitability and so affect awareness. It remains debated at what stages of processing they affect awareness-related event-related potentials (ERPs) in different sensory modalities. We investigated the influence of the cardiac (systole/diastole) and the respiratory (inhalation/exhalation) phase on awareness-related ERPs. Subjects discriminated visual threshold stimuli while their electroencephalogram, electrocardiogram, and respiration were simultaneously recorded. We compared ERPs and their intracranial generators for stimuli classified correctly with and without awareness as a function of the cardiac and respiratory phase. Cyclic variations of interoceptive signals from the BRs modulated both the earliest electrophysiological markers and the trajectory of brain activity when subjects became aware of the stimuli: an early sensory component (P1) was the earliest marker of awareness for low (diastole/inhalation) and a perceptual component (visual awareness negativity) for high (systole/exhalation) BR activity, indicating that BR signals interfere with the sensory processing of the visual input. Likewise, activity spread from the primary visceral cortex (posterior insula) to posterior parietal cortices during high and from associative interoceptive centers (anterior insula) to the prefrontal cortex during low BR activity. Consciousness is thereby resolved in cognitive/associative regions when BR is low and in perceptual centers when it is high. Our results suggest that cyclic fluctuations of BR signaling affect both the earliest markers of awareness and the brain processes underlying conscious awareness.

Neural response to monetary incentives in acquired adolescent depression after mild traumatic brain injury: Stage 2 Registered Report.

Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are post hoc: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate 'task-negative' brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of 'task-positive' regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.

Comparative study on structural and functional brain differences in mild cognitive impairment patients with tinnitus.

Tinnitus may be associated with various brain changes. However, the degenerative changes in patients with tinnitus have not been extensively investigated. We aimed to evaluate degenerative, structural, and functional brain changes in patients with mild cognitive impairment (MCI) who also suffer from tinnitus. This study included participants aged 60 to 80 years with MCI and a hearing level better than 40 dB. The participants were classified into two groups: MCI with tinnitus (MCI-T) and MCI without tinnitus (MCI-NT). All patients underwent Tinnitus Handicap Inventory (THI), 3 T brain MRI, F18-florapronol PET, and F18-FDG PET. The MCI-T group exhibited higher β-amyloid deposition in the superior temporal gyrus, temporal pole, and middle temporal gyrus compared to the MCI-NT group (p < 0.05 for all). Additionally, the MCI-T group showed increased metabolism in the inferior frontal gyrus, insula, and anterior cingulate cortex (ACC) (p < 0.005 for all). The THI score was strongly correlated with increased volume in the insula, ACC, superior frontal gyrus, supplementary motor area, white matter near the hippocampus, and precentral gyrus (p < 0.05 for all). Moreover, the MCI-T group demonstrated higher metabolic activity in the default mode network (DMN) and lower activity in the executive control network (ECN) (p < 0.05 for all). In the MCI-T group, the posterior DMN was positively correlated with the visual network and negatively with the ECN, whereas in the MCI-NT group, it correlated positively with the ECN. The MCI-T group exhibited greater β-amyloid accumulation in the auditory cortex and more extensive changes across various brain networks compared with the MCI-NT group, potentially leading to diverse clinical symptoms such as dementia with semantic deficits or depression. Tinnitus in MCI patients may serve as a biomarker for degenerative changes in the temporal lobe and alterations in brain network dynamics.

Cortical surface-based morphometry in cognitive impairment in sporadic cerebral small vessel disease

Background: Analysis of structural MR images plays a key role in assessing the underlying substrate of cognitive impairment (CI) in sporadic age-related cerebral small vessel disease (SVD), leading to up to 45% of all cases of dementia. The variety of MR-morphometry results in SVD requires extensive research and comparisons with clinical data. Aims: to assess the characteristics of brain atrophy in cognitive impairment in patients with SVD using surface-based morphometry (SBM). Materials and methods: A prospective study was conducted assessing patients with SVD and CI of varying severity (subjective - subCI, moderate - MCI and dementia) and a group of volunteers matched by gender and age. MRI was performed with subsequent analysis of MRI signs of SVD and calculation of the general SVD index and processing of T1mpr images using the SBM method with general and regional quantitative assessment of the brain, including the thickness of the cerebral cortex. Results: the main group with SVD consisted of 173 patients, the control group included 47 healthy volunteers. As the severity of structural changes in the brain and the severity of CI increased, there was a significant (p0.05) decrease in the thickness of the cortex of certain regions according to a similar pattern: the cingulate gyri, mainly their posterior sections; medial and middle sections of the frontal lobes, various parts of the insular cortex, temporo-parietal areas (especially the supramarginal gyri). The volume of the brain itself (total volume, gray and white matter) in SVD had significant differences only with controls, but not between groups of patients with different severity of CI. The volume of white matter hyperintensities was significantly different between the groups with dementia and MCI, dementia and sub-CI (p 0.0001). Conclusions: The data obtained during the study confirm the secondary/mixed nature of atrophy in SVD. The wide variety of regions with significant thinning of the cortex limits the specification of the progression of CI in SVD based on their atrophy. This allows the quantitative measurement of the cortex to be used only as an auxiliary method in assessing the prediction of SVD progression.

Low-intensity focused ultrasound to the insula differentially modulates the heartbeat-evoked potential: A proof-of-concept study

ObjectiveThe 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. MethodsHealthy 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. ResultsRelative 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. ConclusionsThese results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. SignificanceOur 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.

Map activation of various brain regions using different frequencies of electroacupuncture ST36, utilizing the FosCreER strategy

Objective: Electroacupuncture (EA) is an alternative treatment option for pain. Different frequencies of EA have different pain-relieving effects; however, the central mechanism is still not well understood. Methods: The Fos2A-iCreER (TRAP):Ai9 mice were divided into three groups (sham, 2 Hz, and 100 Hz). The mice were intraperitoneally injected with 4-hydroxytamoxifen (4-OHT) immediately after EA at Zusanli (ST36) for 30 min to record the activated neurons. One week later, the mice were sacrificed, and the number of TRAP-treated neurons activated by EA in the thalamus, amygdala, cortex, and hypothalamus was determined. Results: In the cortex, 2 Hz EA activated more TRAP-treated neurons than 100 Hz EA did in the cingulate cortex area 1 (Cg1) and primary somatosensory cortex (S1), and 2 and 100 Hz EAs did not differ from sham EA. TRAP-treated neurons activated by 2 Hz EA were upregulated in the insular cortex (IC) and secondary somatosensory cortex (S2) compared with those activated by 100 Hz and sham EA. In the thalamus, the number of TRAP-treated neurons activated by 2 Hz EA was elevated in the paraventricular thalamic nucleus (PV) compared with those activated by sham EA. In the ventrolateral thalamic nucleus (VL), the number of TRAP-treated neurons activated by 2 Hz EA was significantly upregulated compared with those activated by 100 Hz EA, and sham EA showed no difference compared with 2 or 100 Hz EA. TRAP-treated neurons were more frequently activated in the ventral posterolateral thalamic nucleus (VPL) by 2 Hz EA than by 100 Hz or sham EA. Conclusions: Low-frequency EA ST36 effectively activates neurons in the Cg1, S1, S2, IC, VPL, PV, and VL. The enhanced excitability of the aforementioned nuclei induced by low-frequency EA may be related to its superior efficacy in the treatment of neuropathological pain.

The Seeking Proxies for Internal States (SPIS) Model of OCD - A Comprehensive Review of Current Findings and Implications for Future Directions.

The Seeking Proxies for Internal States (SPIS) model of obsessive-compulsive disorder (OCD) explains symptoms of OCD as stemming from attenuated access to internal states, which is compensated for by using proxies, which are indices of these states that are more discernible or less ambiguous. Internal states in the SPIS model are subjective states that are not accessible to others, encompassing physiological states, motivations, preferences, memories, and emotions. Compensatory proxies in OCD include fixed rules and rituals as well as seeking and relying on external information. In the present review, we outline the SPIS model and describe its basic tenets. We then use the SPIS conceptualization to explain two pivotal OCD-related phenomena - obsessive doubt and compulsive rituals. Next, we provide a detailed overview of current empirical evidence supporting the SPIS in several domains, including physiological states, emotions, sense of understanding, decision-making, and sense of agency. We conclude by discussing possible neural correlates of the difficulty in accessing internal states, focusing on the anterior insular cortex (AIC) and highlighting potential clinical implications of the model to the treatment of OCD.

Abstract P212: Microinjection of the novel angiotensin, alamandine-(1-5) into insular cortex, increase blood pressure

It is well known that the renin-angiotensin system plays a critical role in cardiovascular control and hydro-electrolyte homeostasis. At least in some circumstances Alamandine (Ala) and Angiotensin-(1-7) can have selective actions such as reported in the insular córtex (IC). Hydrolysis of Angiotensin-(1-7) by angiotensin converting enzyme (ACE) can form the heptapeptide Angiotensin-(1-5) and recently our group demonstrated that hydrolysis of Ala by ACE can form Ala-(1-5). In this study we aimed to evaluate the cardiovascular effects produced by microinjection of Ala-(1-5) and Angiotensin-(1-5) into the rostral region of the posterior IC. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Unilateral microinjection of vehicle (0,9% NaCl, 100nL, n=4), Ala (40pmol/100nl, n=7), Ala-(1-5) (400pmol/100nl, n=7) or Angiotensin-(1-5) (400pmol/100nl, n=5) were made into IC (+1.5mm rostral to the bregma). At the baseline, there was no difference between the groups (Vehicle: 85±2 mmHg and 388±5bpm, Ala: 83±9mmHg and 389±10bpm, Ala-(1–5): 91±6mmHg and 386±7bpm or Ang-(1-5): 96±9mmHg and 375±6bpm). Vehicle microinjection was performed as a control for nonspecific effects (ΔMAP:2±1mmHg, ΔHR:4±2bpm, ΔRSNA:3±1%). Ala microinjection into IC, confirmed our previous data showing a long-lasting (18±3min) increase in MAP (Δ=14±2mmHg), and this effect was associated with a significant increase in HR (Δ=32±4bpm) and in RSNA (Δ=36±6%). These responses were elicited immediately after Ala microinjection. When compared with vehicle and, very different from what was observed with Ala, microinjection of Ala-(1–5) evoked a significant increase in blood pressure without altering RSNA or HR (ΔMAP:22±2mmHg, ΔHR:-1±3bpm, ΔRSNA:1±3%). Differently from Ala evoked responses, the effects of Ala-(1–5) had a shorter duration (5.88±1.9min) without delay to beginning the effects. On other hand, microinjection of Angiotensin-(1-5) did not elicited autonomic and cardiovascular effects (ΔMAP:-1±3mmHg, ΔHR:-2±2bpm, ΔRSNA:2±3%). In conclusion, these data showed that the IC is a brain site that has unique effects of Ala (increase in MAP, HR and RSNA) and Ala-(1-5) (increase in MAP only) contrasting with the essentially absent effects of Angiotensin-(1-7) and Angiotensin-(1-5). These findings will contribute to extend our understanding of the brain renin-angiotensin system.

Age-related changes of interoceptive brain networks: Implications for interoception and alexithymia.

Aging is known to be associated with a decline in interoceptive abilities and changes in emotional processing, including alexithymia. As the brain areas supporting interoceptive awareness participate in the perception of emotion, we suggested that interoceptive decline and alexithymia in older adults may share common neural ground. To test this hypothesis, we administered functional magnetic resonance imaging-based heartbeat detection task to 62 adults of diverse ages (range 18-73) and evaluated a larger sample of older and younger adults using questionnaires characterizing interoceptive sensibility, alexithymia, and depressive attitudes. We found that increasing age was linked to decreased activation during the interoceptive task, including the right insular-opercular and supplementary motor areas (SMAs). Age also affected task-based functional connectivity, with two major effects being a decrease in the connectivity of the SMA-insular network and an increase in the connectivity of the prefrontal-lateral occipital network. Path analysis performed for interoceptive accuracy as the endogenous variable revealed that the impact of age was mediated by the functional activation of the insular cortex and SMA and by the connectivity between these areas. Another path analysis using alexithymia as the endogenous variable while controlling for depressive attitudes showed that the effect of age was mediated by interoceptive decline. The study supports the role of central mechanisms in age-related interoceptive decline and shows its implications for alexithymia. Since alexithymia represents a risk factor for mental and cardiovascular diseases, the study findings may open an important direction toward maintaining older adults' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).