Functional Movement Disorder Is Associated with Abnormal Interoceptive Brain Activity: A Task-based Functional MRI Study.

Background: Aberrant interoceptive processing has been hypothesized to contribute to the pathophysiology of functional neurological disorder, although findings have been inconsistent. Here, we utilized functional magnetic resonance imaging (fMRI) to examine neural correlates of interoceptive attention - the conscious focus and awareness of bodily sensations - in functional movement disorder (FMD). Methods: We used voxelwise analyses to compare blood oxygenation level-dependent responses between 13 adults with hyperkinetic FMD and 13 healthy controls (HCs) during a task requiring attention to different bodily sensations and to an exteroceptive stimulus. Additionally, we examined between-group differences in self-reported measures of interoception and evaluated their relationship with neural activity. Results: Interoceptive conditions (heartbeat, stomach and 'body', indicating sensations from the body part or limb affected in FMD participants) activated a network involving the precuneus, the posterior cingulate cortex (PCC) and caudate nucleus (CN) bilaterally, and the right anterior insula (aINS) (p <0.05, corrected). Group differences in brain activity were mainly driven by processing of disease-related interoceptive signals, which in the FMD group was associated with a broader neural activation than monitoring gastric interoception, while no group differences were detected during cardiac interoception. Differences based on interoceptive focus (body vs heartbeat and stomach) between FMD subjects and HCs were found in PCC, CN, angular gyrus, thalamus, and in the mid-insula (p <0.05, corrected). Conclusions: This is, to our knowledge, the first study showing that FMD is associated with abnormal interoceptive processing in regions involved in monitoring body state, attentional focus, and homeostatic inference.

Right anterior insula ASL hypoperfusion as a diagnostic biomarker of prodromal and mild dementia with Lewy bodies: preliminary evidence using a Bayesian approach.

Identifying and validating a biomarker with high specificity in early-stage dementia with Lewy bodies (DLB) using a feasible method is crucial to enhance the current suboptimal diagnostic procedure. Previous research revealed abnormalities, including hypoperfusion in the right anterior insular cortex at group level, in prodromal DLB. Exploring hypoperfusion of the right anterior insula, at an individual-level and assessing its relevance as a potential imaging biomarker in early DLB, has, to our knowledge, not been investigated. Our preliminary study aims to assess the feasibility of the technique and to provide a methodological framework for further investigation. We assessed the feasibility and accuracy of the hypoperfusion of the right anterior insula per arterial spin labelling magnetic resonance imaging (ASL-MRI) as a diagnostic biomarker in early DLB and provided rough estimates of its sensitivity and specificity. Defining the region of interest based on previous research, we established the biomarker as the hypoperfusion of the right anterior insula. Discriminative and analytical performances were assessed in comparison to a control group of treatment-resistant depression patients. Bayesian diagnostic reasoning was employed to assess the biomarker diagnostic usability in early DLB in two scenarios: healthy elderly controls and mild cognitive impairment. Additionally, we updated probabilities by integrating data from the Mayo-clinic cognitive fluctuations scale and real-time quaking-induced conversion (RT-QuIC) α-synuclein data. Lastly, a whole-brain perfusion analysis of DLB patients was conducted to identify further brain regions with discriminative abilities. We successfully replicated the right anterior insular hypoperfusion (RAI-Hypo) in all DLB patients at the individual level. The overall sensitivity of the biomarker was 96%, and the specificity was 92%. Bayesian testing revealed the biomarker's highest performance in early-stage DLB with cognitive fluctuations, showcasing a diagnostic potential associated with a high precision and moderate accuracy. In a cognitively non-impaired population, the RAI-Hypo showed a limited usability and lacked in selectivity to qualify as a screening tool. The exploratory whole-brain analysis revealed perfect discriminative capacities in the bilateral anterior insulae and the left inferior parietal lobule. Further studies are needed to confirm our preliminary results. If performance is maintained in subsequent studies and is compared to a more suitable control population, the proposed biomarker may be eventually sufficient to discriminate early-stage DLB from non-DLB.

Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain.

BACKGROUND: The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. OBJECTIVE/HYPOTHESIS: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). METHODS: N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. RESULTS: Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. CONCLUSIONS: LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.

Basal parasympathetic deficits in C9orf72 hexanucleotide repeat expansion carriers relate to smaller frontoinsula and thalamus volume and lower empathy.

Diminished basal parasympathetic nervous system activity is a feature of frontotemporal dementia that relates to left frontoinsula dysfunction and empathy impairment. Individuals with a pathogenic expansion of the hexanucleotide repeat in chromosome 9 open reading frame 72 (C9orf72), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, provide a unique opportunity to examine whether parasympathetic activity is disrupted in genetic forms of frontotemporal dementia and to investigate when parasympathetic deficits manifest in the pathophysiological cascade. We measured baseline respiratory sinus arrhythmia, a parasympathetic measure of heart rate variability, over two minutes in a sample of 102 participants that included 19 asymptomatic expansion carriers (C9+ asymp), 14 expansion carriers with mild cognitive impairment (C9+ MCI), 16 symptomatic expansion carriers with frontotemporal dementia (C9+ FTD), and 53 expansion-negative healthy controls (C9- HC) who also underwent structural magnetic resonance imaging. In follow-up analyses, we compared baseline respiratory sinus arrhythmia in the C9+ FTD group with an independent age-, sex-, and clinical severity-matched group of 26 people with sporadic behavioral variant frontotemporal dementia. The Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating-Sum of Boxes score was used to quantify behavioral symptom severity, and informant ratings on the Interpersonal Reactivity Index provided measures of participants' current emotional (empathic concern) and cognitive (perspective-taking) empathy. Results indicated that the C9+ FTD group had lower baseline respiratory sinus arrhythmia than the C9+ MCI, C9+ asymp, and C9- HC groups, a deficit that was comparable to that of sporadic behavioral variant frontotemporal dementia. Linear regression analyses indicated that lower baseline respiratory sinus arrhythmia was associated with worse behavioral symptom severity and lower empathic concern and perspective-taking across the C9orf72 expansion carrier clinical spectrum. Whole-brain voxel-based morphometry analyses in participants with C9orf72 pathogenic expansions found that lower baseline respiratory sinus arrhythmia correlated with smaller gray matter volume in the left frontoinsula and bilateral thalamus, key structures that support parasympathetic function, and in the bilateral parietal lobes, occipital lobes, and cerebellum, regions that are also vulnerable in individuals with C9orf72 expansions. This study provides novel evidence that basal parasympathetic functioning is diminished in FTD due to C9orf72 expansions and suggests that baseline respiratory sinus arrhythmia may be a potential non-invasive biomarker that is sensitive to behavioral symptoms in the early stages of disease.

Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption.

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing. Although the high comorbidity of cigarette smoking with drinking behaviors may collectively affect brain activity, there could be independent effects of smoking in alcohol use disorder that impact brain function and behavior. We hypothesized that smoking status, independent of alcohol use, would be associated with aberrations of nucleus accumbens functional connectivity to brain regions that facilitate reward processing, salience attribution, and inhibitory control. Resting state functional magnetic resonance imaging data from thirty-one nonsmokers and nineteen smoking individuals were analyzed using seed-based correlations of the bilateral accumbens with all other brain voxels. Statistical models accounted for drinks consumed per week. The smoking group demonstrated significantly higher functional connectivity between the left accumbens and the bilateral insula and anterior cingulate cortex, as well as hyperconnectivity between the right accumbens and the insula. Confirmatory analyses using the insula and cingulate clusters generated from the original analysis as seed regions reproduced the hyperconnectivity in smokers between the bilateral insular regions and the accumbens. In conclusion, smoking status had distinct effects on neural activity; hyperconnectivity between the accumbens and insula in smokers may reflect enhanced encoding of the reinforcing effects of smoking and greater orientation toward smoking-associated stimuli.

An MRI-based study of the insula in a South African population.

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.

Progressive remodeling of structural networks following surgery for operculo-insular epilepsy.

Introduction: Operculo-insular epilepsy (OIE) is a rare condition amenable to surgery in well-selected cases. Despite the high rate of neurological complications associated with OIE surgery, most postoperative deficits recover fully and rapidly. We provide insights into this peculiar pattern of functional recovery by investigating the longitudinal reorganization of structural networks after surgery for OIE in 10 patients. Methods: Structural T1 and diffusion-weighted MRIs were performed before surgery (t0) and at 6 months (t1) and 12 months (t2) postoperatively. These images were processed with an original, comprehensive structural connectivity pipeline. Using our method, we performed comparisons between the t0 and t1 timepoints and between the t1 and t2 timepoints to characterize the progressive structural remodeling. Results: We found a widespread pattern of postoperative changes primarily in the surgical hemisphere, most of which consisted of reductions in connectivity strength (CS) and regional graph theoretic measures (rGTM) that reflect local connectivity. We also observed increases in CS and rGTMs predominantly in regions located near the resection cavity and in the contralateral healthy hemisphere. Finally, most structural changes arose in the first six months following surgery (i.e., between t0 and t1). Discussion: To our knowledge, this study provides the first description of postoperative structural connectivity changes following surgery for OIE. The ipsilateral reductions in connectivity unveiled by our analysis may result from the reversal of seizure-related structural alterations following postoperative seizure control. Moreover, the strengthening of connections in peri-resection areas and in the contralateral hemisphere may be compatible with compensatory structural plasticity, a process that could contribute to the recovery of functions seen following operculo-insular resections for focal epilepsy.

Striatal GABA levels correlate with risk sensitivity in monetary loss.

Background: Decision-making under risk is a common challenge. It is known that risk-taking behavior varies between contexts of reward and punishment, yet the mechanisms underlying this asymmetry in risk sensitivity remain unclear. Methods: This study used a monetary task to investigate neurochemical mechanisms and brain dynamics underpinning risk sensitivity. Twenty-eight participants engaged in a task requiring selection of visual stimuli to maximize monetary gains and minimize monetary losses. We modeled participant trial-and-error processes using reinforcement learning. Results: Participants with higher subjective utility parameters showed risk preference in the gain domain (r = -0.59) and risk avoidance in the loss domain (r = -0.77). Magnetic resonance spectroscopy (MRS) revealed that risk avoidance in the loss domain was associated with γ-aminobutyric acid (GABA) levels in the ventral striatum (r = -0.42), but not in the insula (r = -0.15). Using functional magnetic resonance imaging (fMRI), we tested whether risk-sensitive brain dynamics contribute to participant risky choices. Energy landscape analyses demonstrated that higher switching rates between brain states, including the striatum and insula, were correlated with risk avoidance in the loss domain (r = -0.59), a relationship not observed in the gain domain (r = -0.02). Conclusions: These findings from MRS and fMRI suggest that distinct mechanisms are involved in gain/loss decision making, mediated by subcortical neurometabolite levels and brain dynamic transitions.

Uncovering Interoceptive Human Insular Lobe Function through Intraoperative Cortical Stimulation-A Review.

The insular cortex, a critical hub in the brain's sensory, cognitive, and emotional networks, remains an intriguing subject of study. In this article, we discuss its intricate functional neuroanatomy, emphasizing its pivotal role in processing olfactory information. Through concise exploration, we delve into the insula's diverse connectivity and its involvement in sensory integration, particularly in olfaction. Stimulation studies in humans reveal compelling insights into the insula's contribution to the perception of smell, hinting at its broader implications for cognitive processing. Additionally, we explore an avenue of research in which studying olfactory processing via insular stimulation could unravel higher-level cognitive processes. This innovative approach could help give a fresh perspective on the interplay between sensory and cognitive domains, offering valuable insights into the neural mechanisms underlying cognition and emotion. In conclusion, future research efforts should emphasize a multidisciplinary approach, combining advanced imaging and surgical techniques to explore the intricate functions of the human insula. Moreover, awake craniotomies could offer a unique opportunity for real-time observation, shedding light on its neural circuitry and contributions to higher-order brain functions. Furthermore, olfaction's direct cortical projection enables precise exploration of insular function, promising insights into cognitive and emotional processes. This multifaceted approach will deepen our understanding of the insular cortex and its significance in human cognition and emotion.

Interoceptive Processing in Functional Gastrointestinal Disorders.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic gastrointestinal symptoms in the absence of overt pathology and affect a significant percentage of the worldwide population. They are commonly accompanied by co-morbid psychiatric symptomatology and are associated with significant suffering and great healthcare services utilization. There is growing evidence that dysregulation of the gut-brain axis and disturbances in the processing of afferent interoceptive signals lie at the heart of these disorders. In this context, the aim of the current review was to detect and critically review original articles focusing on the role of interoception in the pathophysiology of FGIDs. Our search yielded 38 relevant studies. FGID patients displayed increased visceral sensitivity, enhanced attention to gastrointestinal interoceptive cues, and greater emotional arousal when coping with gut-derived sensations. Neuroimaging studies have shown significant structural and functional changes in regions of the interoceptive network, while molecular and genetic studies have revealed significant associations between interoceptive signaling and deficits in excitatory neurotransmission, altered endocrine and immune physiological pathways, and aberrant expression of transient receptor potential channel genes. Finally, there were emerging data suggesting that interoception-based interventions may reduce physical symptoms and improve quality of life and should be integrated into FGID clinical management practices.

Brain circuits in autonomous sensory meridian response and related phenomena.

Autonomous sensory meridian response (ASMR) is characterized by a tingling sensation with a feeling of relaxation and a state of flow. We explore the neural underpinnings and comorbidities of ASMR and related phenomena with altered sensory processing. These phenomena include sensory processing sensitivity (SPS), synaesthesia, Alice in Wonderland syndrome and misophonia. The objective of this article is to uncover the shared neural substrates and distinctive features of ASMR and its counterparts. ASMR, SPS and misophonia exhibit common activations in the brain regions associated with social cognition, emotion regulation and empathy. Nevertheless, ASMR responders display reduced connectivity in the salience network (SN), while individuals with SPS exhibit increased connectivity in the SN. Furthermore, ASMR induces relaxation and temporarily reduces symptoms of depression, in contrast to SPS and misophonia, which are linked to depression. These observations lead us to propose that ASMR is a distinct phenomenon owing to its attention dispatch mechanism and its connection with emotion regulation. We suggest that increased activations in the insula, along with reduction in connectivity within the salience and default mode networks in ASMR responders, may account for their experiences of relaxation and flow states. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Erratum: Resting state functional connectivity of the rat claustrum.

[This corrects the article DOI: 10.3389/fnana.2019.00022.].

Decision-making shapes dynamic inter-areal communication within macaque ventral frontal cortex.

Macaque ventral frontal cortex is comprised of a set of anatomically heterogeneous and highly interconnected areas. Collectively these areas have been implicated in many higher-level affective and cognitive processes, most notably the adaptive control of decision-making. Despite this appreciation, little is known about how subdivisions of ventral frontal cortex dynamically interact with each other during decision-making. Here we assessed functional interactions between areas by analyzing the activity of thousands of single neurons recorded from eight anatomically defined subdivisions of ventral frontal cortex in macaques performing a visually guided two-choice probabilistic task for different fruit juices. We found that the onset of stimuli and reward delivery globally increased communication between all parts of ventral frontal cortex. Inter-areal communication was, however, temporally specific, occurred through unique activity subspaces between areas, and depended on the encoding of decision variables. In particular, areas 12l and 12o showed the highest connectivity with other areas while being more likely to receive information from other parts of ventral frontal cortex than to send it. This pattern of functional connectivity suggests a role for these two areas in integrating diverse sources of information during decision processes. Taken together, our work reveals the specific patterns of interareal communication between anatomically connected subdivisions of ventral frontal cortex that are dynamically engaged during decision-making.

Association between irritable temperament and glucose metabolism in the left insula and the right cerebellum.

INTRODUCTION: Affective temperaments are assumed to have biological and neural bases. In the present study, we analyzed 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images of healthy participants to explore the neural basis of affective temperaments. METHOD: We utilized data of affective temperament measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire and 18F-FDG PET images of healthy participants from two of our previous studies. A multiple regression analysis was performed to assess the association between 18F-FDG uptake and temperament scores using Statistical Parametric Mapping 12. RESULTS: The final sample included 62 healthy participants. Whole-brain analysis revealed a cluster of 18F-FDG uptake that was significantly and positively associated with irritable temperament scores in the right cerebellum (Crus II, VIII, and IX). After further adjustment for the other four temperament scores, whole-brain analysis revealed a cluster of 18F-FDG uptake significantly and positively associated with irritable temperament scores in the left insula and right cerebellum (Crus II, VIII, and IX). However, no significant association was found between 18F-FDG uptake and the other four temperaments (depressive, cyclothymic, hyperthymic, and anxious). CONCLUSIONS: The left insula and right cerebellum of the cerebrocerebellar circuit may be one of the neural bases of irritable temperament.

Preparatory activity of anterior insula predicts conflict errors: integrating convolutional neural networks and neural mass models.

Preparatory brain activity is a cornerstone of proactive cognitive control, a top-down process optimizing attention, perception, and inhibition, fostering cognitive flexibility and adaptive attention control in the human brain. In this study, we proposed a neuroimaging-informed convolutional neural network model to predict cognitive control performance from the baseline pre-stimulus preparatory electrophysiological activity of core cognitive control regions. Particularly, combined with perturbation-based occlusion sensitivity analysis, we pinpointed regions with the most predictive preparatory activity for proactive cognitive control. We found that preparatory arrhythmic broadband neural dynamics in the right anterior insula, right precentral gyrus, and the right opercular part of inferior frontal gyrus (posterior ventrolateral prefrontal cortex), are highly predictive of prospective cognitive control performance.  The pre-stimulus preparatory activity in these regions corresponds to readiness for conflict detection, inhibitory control, and overall elaborate attentional processing. We integrated the convolutional neural network with biologically inspired Jansen-Rit neural mass model to investigate neurostimulation effects on cognitive control. High-frequency stimulation (130 Hz) of the left anterior insula provides significant cognitive enhancement, especially in reducing conflict errors, despite the right anterior insula's higher predictive value for prospective cognitive control performance. Thus, effective neurostimulation targets may differ from regions showing biomarker activity. Finally, we validated our theoretical finding by evaluating intrinsic neuromodulation through neurofeedback-guided volitional control in an independent dataset. We found that left anterior insula was intrinsically modulated in real-time by volitional control of emotional valence, but not arousal. Our findings further highlight central role of anterior insula in orchestrating proactive cognitive control processes, positioning it at the top of hierarchy for cognitive control.

Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease - pain type matters: A double-blinded randomized sham-controlled trial.

OBJECTIVES: Altered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. METHODS: This was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. RESULTS: Twenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). CONCLUSION: Our preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

Expectation of pain and relief: A dynamical model of the neural basis for pain-trauma co-morbidity.

Posttraumatic Stress Disorder (PTSD) is highly co-morbid with chronic pain conditions. When present, PTSD significantly worsens chronic pain outcomes. Likewise, pain contributes to a more severe PTSD as evidenced by greater disability, more frequent use of harmful opioid analgesics and increased pain severity. The biomechanism behind this comorbidity is incompletely understood, however recent work strongly supports the widely-accepted role of expectation, in the entanglement of chronic pain and trauma symptoms. This work has shown that those with trauma have a maladaptive brain response while expecting stress and pain, whereas those with chronic pain may have a notable impairment in brain response while expecting pain relief. This dynamical expectation model of the interaction between neural systems underlying expectation of pain onset (traumatic stress) and pain offset (chronic pain) is biologically viable and may provide a biomechanistic insight into pain-trauma comorbidity. These predictive mechanisms work through interoceptive pathways in the brain critically the insula cortex. Here we highlight how the neural expectation-related mechanisms augment the existing models of pain and trauma to better understand the dynamics of pain and trauma comorbidity. These ideas will point to targeted complementary clinical approaches, based on mechanistically separable neural biophenotypes for the entanglement of chronic pain and trauma symptoms.

Involvement of the cingulate cortex and insula in patients with trigeminal neuralgia: A clinical and volumetric study.

AIM: Advanced neuroimaging strategies may provide new insights into the underlying mechanisms of trigeminal neuralgia (TN). The objective of this study is to measure central pain centers in patients with long-standing trigeminal neuralgia and compare them to those of normal individuals. The findings of this study could improve the understanding of central region changes related to pain and improve the diagnosis and management of chronic trigeminal pain. MATERIAL AND METHODS: We examined radiologic data from 20 patients with trigeminal neuralgia and 28 healthy controls who underwent 3D iso T1-weighted brain MRI at our university hospital between 2018 and 2023. Patients with a minimum pain duration of 5 years were included and compared with healthy controls. Additionally, patients were categorized into groups based on the presence of vascular compression. The pain-related subcortical structures, such as the cingulate cortex and insula, were analyzed volumetrically using volBrain software. The results were evaluated statistically. RESULTS: Significant differences were observed in the measurement of the posterior insula (p = 0.014) when comparing patients with trigeminal neuralgia and healthy subjects. Additionally, group comparisons based on the presence of vascular compression revealed significant differences in the Middle Cingulate Cortex (0.036) and Posterior Cingulate Cortex (0.031) between groups, which may be related to the etiological factor. CONCLUSION: Understanding changes in central regions related to pain can aid in the diagnosis and management of chronic trigeminal pain.

Frontal trans opercular approaches to the insula: building the mental picture from procedure-guided anatomical dissection.

BACKGROUND: Performing transopercular frontal approaches to the insula, widely used in glioma surgeries, necessitates a meticulous understanding of both cortical and subcortical neuroanatomy. This precision is vital for preserving essential structures and accurately interpreting the results of direct electrical stimulation. Nevertheless, acquiring a compelling mental image of the anatomy of this region can be challenging due to several factors, among which stand out its complexity and the fact that white matter fasciculi are imperceptible to the naked eye in the living brain. AIM: In an effort to optimize the study of the anatomy relevant to this topic, we performed a procedure-guided laboratory study using subpial dissection, fiber dissection, vascular coloration, and stereoscopic photography in a "real-life" surgical perspective. METHODS: Nine cerebral specimens obtained from body donation were extracted and fixed in formalin. Colored silicone injection and a variant of Klinglers's technique were used to demonstrate vascular and white matter structures, respectively. We dissected and photographed the specimens in a supero-antero-lateral view to reproduce the surgeon's viewpoint. The anatomy related to the development of the surgical corridor and resection cavity was documented using both standard photography and the red-cyan anaglyph technique. RESULTS: The anatomy of frontal transopercular approaches to the insula involved elements of different natures-leptomeningeal, cortical, vascular, and fascicular-combining in the surgical field in a complex disposition. The disposition of these structures was successfully demonstrated through the aforementioned anatomical techniques. Among the main structures in or around the surgical corridor, the orbital, triangular, and opercular portions of the inferior frontal gyrus are critical landmarks in the cortical stage, as well as the leptomeninges of the Sylvian fissure and the M2-M4 branches of the middle cerebral artery in the subpial dissection stage, and the inferior fronto-occipital, uncinate and arcuate fasciculi, and the corona radiata in establishing the deep limits of resection. CONCLUSIONS: Procedure-guided study of cerebral hemispheres associating subpial, vascular, and fiber dissection from a surgical standpoint is a powerful tool for the realistic study of the surgical anatomy relevant to frontal transopercular approaches to the insula.

The association between early regulatory problems and adult peer relationship quality is mediated by the brain's allostatic-interoceptive system.

BACKGROUND: Early regulatory problems (RPs), i.e., problems with crying, sleeping, and/or feeding during the first years, increase the risk for avoidant personality traits in adulthood, associated with social withdrawal and anxiety. Even more, RPs are linked with functional alterations in the adult default mode and salience networks, comprising the brain's allostatic-interoceptive system (AIS) and playing a role in social interactions. We investigated whether RPs assessed in infancy are associated with difficulties in adult peer relationships mediated by functional alterations of the AIS. METHODS: As part of a large case-controlled prospective study, 42 adults with previous RPs and 70 matched controls (mean age = 28.48, SD = 2.65, 51% male) underwent fMRI during rest. The analysis focused on the intrinsic functional connectivity (iFC) of key nodes of the AIS. Peer relationship quality was assessed via a semi-structured Life Course Interview and the YASR scale. In these same individuals, RPs were assessed at ages 5, 20 and 56 months. RESULTS: RPs in infancy were associated with lower-quality peer relationships and enhanced functional connectivity of the AIS nodes in adulthood, with a stronger effect for multiple and persistent RPs compared with transient-multiple or single-persistent RPs. Importantly, iFC changes of the dorsal mid insula, a primary interoceptive cortex with frontal and temporal regions, mediated the relationship between early RPs and adult peer relationship quality. CONCLUSIONS: Results indicate long-lasting social and neural changes associated with early RPs. Our findings further implicate the AIS in both interoceptive and social processes, while indicating the need for early screening of early RPs.