Erratum: Resting state functional connectivity of the rat claustrum.

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

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'.

Epilepsy alters brain networks in patients with insular glioma.

AIMS: We intend to elucidate the alterations of cerebral networks in patients with insular glioma-related epilepsy (GRE) based on resting-state functional magnetic resonance images. METHODS: We collected 62 insular glioma patients, who were subsequently categorized into glioma-related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups. RESULTS: No significant alterations in functional connectivity were found in either hemisphere insular glioma. Using graph theoretical analysis, differences were found in visual, sensorimotor, and default mode networks (p < 0.05). When the glioma located in the left hemisphere, the degree centrality was reduced in the GE group compared to the GnE group. When the glioma located in the right insula, the degree centrality, nodal efficiency, nodal local efficiency, and nodal clustering coefficient of the GE group were lower than those of the GnE group. CONCLUSION: The impact of insular glioma itself and GRE on the brain network is widespread. The networks altered by insular GRE differ depending on the hemisphere location. GRE reduces the nodal properties of brain networks than that in insular glioma.

Effects of long-term antipsychotic medication on brain instability in first-episode schizophrenia patients: a resting-state fMRI study.

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms.

BOLD signal variability as potential new biomarker of functional neurological disorders.

BACKGROUND: Functional neurological disorder (FND) is a common neuropsychiatric condition with established diagnostic criteria and effective treatments but for which the underlying neuropathophysiological mechanisms remain incompletely understood. Recent neuroimaging studies have revealed FND as a multi-network brain disorder, unveiling alterations across limbic, self-agency, attentional/salience, and sensorimotor networks. However, the relationship between identified brain alterations and disease progression or improvement is less explored. METHODS: This study included resting-state functional magnetic resonance imaging (fMRI) data from 79 patients with FND and 74 age and sex-matched healthy controls (HC). First, voxel-wise BOLD signal variability was computed for each participant and the group-wise difference was calculated. Second, we investigated the potential of BOLD signal variability to serve as a prognostic biomarker for clinical outcome in 47 patients who attended a follow-up measurement after eight months. RESULTS: The results demonstrated higher BOLD signal variability in key networks, including the somatomotor, salience, limbic, and dorsal attention networks, in patients compared to controls. Longitudinal analysis revealed an increase in BOLD signal variability in the supplementary motor area (SMA) in FND patients who had an improved clinical outcome, suggesting SMA variability as a potential state biomarker. Additionally, higher BOLD signal variability in the left insula at baseline predicted a worse clinical outcome. CONCLUSION: This study contributes to the understanding of FND pathophysiology, emphasizing the dynamic nature of neural activity and highlighting the potential of BOLD signal variability as a valuable research tool. The insula and SMA emerge as promising regions for further investigation as prognostic and state markers.

Abnormal brain spontaneous neural activity in neuromyelitis optica spectrum disorder with neuropathic pain.

Background: Neuropathic pain is one of the most common symptoms in neuromyelitis optica spectrum disorder (NMOSD). Notwithstanding, its underlying mechanism remains obscure. Methods: The amplitude of low-frequency fluctuations (ALFF) metric was employed to investigate spontaneous neural activity alterations via resting-state functional magnetic resonance imaging (rs-MRI) data from a 3.0 T MRI scanner, in a sample of 26 patients diagnosed with NMOSD with neuropathic pain (NMOSD-WNP), 20 patients with NMOSD but without neuropathic pain (NMOSD-WoNP), and 38 healthy control (HC) subjects matched for age and sex without the comorbidity of depressive or anxious symptoms. Results: It was observed that patients with NMOSD-WNP displayed a significant ALFF decrease in the left amygdala and right anterior insula, relative to both patients with NMOSD-WoNP and HC subjects. Furthermore, ALFF values in the left amygdala were negatively correlated with the scores of the Douleur Neuropathique en 4 Questions and McGill Pain Questionnaire (both sensory and affective descriptors) in patients with NMOSD-WNP. Additionally, there were negative correlations between the ALFF values in the right anterior insula and the duration of pain and the number of relapses in patients with NMOSD-WNP. Conclusion: The present study characterizes spontaneous neural activity changes in brain regions associated with sensory and affective processing of pain and its modulation, which underscore the central aspects in patients with NMOSD-WNP. These findings might contribute to a better understanding of the pathophysiologic basis of neuropathic pain in NMOSD.

Two distinct networks for encoding goals and forms of action: An effective connectivity study.

Goal-directed actions are characterized by two main features: the content (i.e., the action goal) and the form, called vitality forms (VF) (i.e., how actions are executed). It is well established that both the action content and the capacity to understand the content of another's action are mediated by a network formed by a set of parietal and frontal brain areas. In contrast, the neural bases of action forms (e.g., gentle or rude actions) have not been characterized. However, there are now studies showing that the observation and execution of actions endowed with VF activate, in addition to the parieto-frontal network, the dorso-central insula (DCI). In the present study, we established-using dynamic causal modeling (DCM)-the direction of information flow during observation and execution of actions endowed with gentle and rude VF in the human brain. Based on previous fMRI studies, the selected nodes for the DCM comprised the posterior superior temporal sulcus (pSTS), the inferior parietal lobule (IPL), the premotor cortex (PM), and the DCI. Bayesian model comparison showed that, during action observation, two streams arose from pSTS: one toward IPL, concerning the action goal, and one toward DCI, concerning the action vitality forms. During action execution, two streams arose from PM: one toward IPL, concerning the action goal and one toward DCI concerning action vitality forms. This last finding opens an interesting question concerning the possibility to elicit VF in two distinct ways: cognitively (from PM to DCI) and affectively (from DCI to PM).

Insula uses overlapping codes for emotion in self and others.

In daily life, we must recognize others' emotions so we can respond appropriately. This ability may rely, at least in part, on neural responses similar to those associated with our own emotions. We hypothesized that the insula, a cortical region near the junction of the temporal, parietal, and frontal lobes, may play a key role in this process. We recorded local field potential (LFP) activity in human neurosurgical patients performing two tasks, one focused on identifying their own emotional response and one on identifying facial emotional responses in others. We found matching patterns of gamma- and high-gamma band activity for the two tasks in the insula. Three other regions (MTL, ACC, and OFC) clearly encoded both self- and other-emotions, but used orthogonal activity patterns to do so. These results support the hypothesis that the insula plays a particularly important role in mediating between experienced vs. observed emotions.

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.

Altered dynamic functional connectivity of insular subdivisions among male cigarette smokers.

Background: Insular subdivisions show distinct patterns of resting state functional connectivity with specific brain regions, each with different functional significance in chronic cigarette smokers. This study aimed to explore the altered dynamic functional connectivity (dFC) of distinct insular subdivisions in smokers. Methods: Resting-state BOLD data of 31 smokers with nicotine dependence and 27 age-matched non-smokers were collected. Three bilateral insular regions of interest (dorsal, ventral, and posterior) were set as seeds for analyses. Sliding windows method was used to acquire the dFC metrics of different insular seeds. Support vector machine based on abnormal insular dFC was applied to classify smokers from non-smokers. Results: We found that smokers showed lower dFC variance between the left ventral anterior insula and both the right superior parietal cortex and the left inferior parietal cortex, as well as greater dFC variance the right ventral anterior insula with the right middle cingulum cortex relative to non-smokers. Moreover, compared to non-smokers, it is found that smokers demonstrated altered dFC variance of the right dorsal insula and the right middle temporal gyrus. Correlation analysis showed the higher dFC between the right dorsal insula and the right middle temporal gyrus was associated with longer years of smoking. The altered insular subdivision dFC can classify smokers from non-smokers with an accuracy of 89.66%, a sensitivity of 96.30% and a specify of 83.87%. Conclusions: Our findings highlighted the abnormal patterns of fluctuating connectivity of insular subdivision circuits in smokers and suggested that these abnormalities may play a significant role in the mechanisms underlying nicotine addiction and could potentially serve as a neural biomarker for addiction treatment.

Behavioral dishonesty in multiscenes: Associations with trait honesty and neural patterns during (dis)honesty video-watching.

Cross-situational inconsistency is common in the expression of honesty traits; yet, there is insufficient emphasis on behavioral dishonesty across multiple contexts. The current study aimed to investigate behavioral dishonesty in various contexts and reveal the associations between trait honesty, behavioral dishonesty, and neural patterns of observing others behave honestly or dishonestly in videos (abbr.: (dis)honesty video-watching). First, the results revealed limitations in using trait honesty to reflect variations in dishonest behaviors and predict behavioral dishonesty. The finding highlights the importance of considering neural patterns in understanding and predicting dishonest behaviors. Second, by comparing the predictive performance of seven types of data across three neural networks, the results showed that functional connectivity in the hypothesis-driven network during (dis)honesty video-watching provided the highest predictive power in predicting multitask behavioral dishonesty. Last, by applying the feature elimination method, the midline self-referential regions (medial prefrontal cortex, posterior cingulate cortex, and anterior cingulate cortex), anterior insula, and striatum were identified as the most informative brain regions in predicting behavioral dishonesty. In summary, the study offered insights into individual differences in deception and the intricate connections among trait honesty, behavioral dishonesty, and neural patterns during (dis)honesty video-watching.

Altered functional connectivity of insular subregions in subjective cognitive decline.

Objective: Recent research has highlighted the insula as a critical hub in human brain networks and the most susceptible region to subjective cognitive decline (SCD). However, the changes in functional connectivity of insular subregions in SCD patients remain poorly understood. The present study aims to clarify the altered functional connectivity patterns within insular subregions in individuals with SCD using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: In this study, we collected rs-fMRI data from 30 patients with SCD and 28 healthy controls (HCs). By defining three subregions of the insula, we mapped whole-brain resting-state functional connectivity (RSFC). We identified several distinct RSFC patterns of the insular subregions. Specifically, for positive connectivity, three cognitive-related RSFC patterns were identified within the insula, suggesting anterior-to-posterior functional subdivisions: (1) a dorsal anterior zone of the insula that shows RSFC with the executive control network (ECN); (2) a ventral anterior zone of the insula that shows functional connectivity with the salience network (SN); and (3) a posterior zone along the insula that shows functional connectivity with the sensorimotor network (SMN). Results: Compared to the controls, patients with SCD exhibited increased positive RSFC to the sub-region of the insula, demonstrating compensatory plasticity. Furthermore, these abnormal insular subregion RSFCs are closely correlated with cognitive performance in the SCD patients. Conclusion: Our findings suggest that different insular subregions exhibit distinct patterns of RSFC with various functional networks, which are affected differently in patients with SCD.

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.

Interoception in Autism: A Narrative Review of Behavioral and Neurobiological Data.

While exteroceptive sensory processing is a hallmark of autism spectrum disorder, how interoceptive processing may impact and contribute to symptomatology remains unclear. In this comprehensive narrative review on interoception in autism, we discuss: 1) difficulties with assessing interoception; 2) potential interoceptive differences; 3) interactions between neural systems for interoception, attention, sensorimotor processing, and cognition; and 4) potential differences in neural circuits involved in interoception. In general, there are mixed findings on potential interoception differences in autism. Nevertheless, some data indicate differences in integration of interoceptive and exteroceptive information may contribute to autism symptomatology. Neurologically, interoceptive processing in autism may be impacted by potential differences in the development, morphometry, and connectivity of key interoceptive hubs (vagal processing, brainstem, thalamus, insula), though much work is needed on this topic.

Laser interstitial thermal therapy for first-line treatment of insular glioma.

OBJECTIVE: Insular gliomas pose a significant surgical challenge due to the complex surrounding functional and vascular anatomy. The authors report their experience using a novel framework for the treatment of insular gliomas with laser interstitial thermal therapy (LITT) and provide representative case examples emphasizing indications, rationale, and technical pearls. METHODS: A prospectively gathered institutional database was used to identify patients with newly diagnosed insular gliomas who underwent LITT between 2015 and 2023. The proposed framework of insular glioma management is guided by tumor size and extent of extra-insular tumor involvement. Patients with tumors localized to the insula (insula-only) were treated with single-session or staged LITT. Patients with insular tumors with frontotemporal involvement (insular+) were treated with insular LITT and standard frontotemporal resection of extra-insular tumor. Clinical and volumetric lesional characteristics were analyzed, with particular emphasis on extent of cytoreductive treatment and safety. RESULTS: Of the 261 patients treated at the authors' institution with LITT between 2015 and 2023, 33 LITT procedures were identified involving 22 unique patients with treatment-naive insular gliomas. Of the 22 patients, 12 had insular-only tumors and were treated with LITT alone, while 10 patients had insular+ lesions and were treated with LITT and resection. The median tumor volume for insular-only tumors was 13.4 cm3 (IQR 10.6, 26.3 cm3), with a median extent of treatment of 100% (IQR 92.1%, 100%). Insular+ lesions were significantly larger, with a median volume of 81.2 cm3 (IQR 51.9, 97 cm3) and median extent of treatment of 96.6% (IQR 93.7%, 100%). All patients with insular-only tumors were discharged the day after ablation, while insular+ patients had significantly longer hospital stays, with 50% staying more than 3 days. Overall, 8% of insular-only patients had permanent neurological deficits compared with 33% of insular+ patients. Two patients' tumors progressed during follow-up: one patient with WHO grade 4 astrocytoma and the other with diffuse glioma not otherwise specified. Patients with grade 4 tumors had the highest rate of permanent neurological deficit (43%) and a larger decline in postoperative Karnofsky Performance Status score (p = 0.046). CONCLUSIONS: The authors present their experience using a novel insular glioma treatment paradigm that incorporates LITT into the broader framework of insular glioma surgery. Their findings suggest that insular LITT is feasible and may allow for high rates of cytoreduction while potentially ameliorating the risks of conventional insular glioma surgery.

Atypical neural encoding of faces in individuals with autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) experience pervasive difficulties in processing social information from faces. However, the behavioral and neural mechanisms underlying social trait judgments of faces in ASD remain largely unclear. Here, we comprehensively addressed this question by employing functional neuroimaging and parametrically generated faces that vary in facial trustworthiness and dominance. Behaviorally, participants with ASD exhibited reduced specificity but increased inter-rater variability in social trait judgments. Neurally, participants with ASD showed hypo-activation across broad face-processing areas. Multivariate analysis based on trial-by-trial face responses could discriminate participant groups in the majority of the face-processing areas. Encoding social traits in ASD engaged vastly different face-processing areas compared to controls, and encoding different social traits engaged different brain areas. Interestingly, the idiosyncratic brain areas encoding social traits in ASD were still flexible and context-dependent, similar to neurotypicals. Additionally, participants with ASD also showed an altered encoding of facial saliency features in the eyes and mouth. Together, our results provide a comprehensive understanding of the neural mechanisms underlying social trait judgments in ASD.

Increased anterior insula connectivity associated with cognitive maintenance in amnestic mild cognitive impairment: a longitudinal study.

The insula, a crucial hub of the human brain network, can be divided into anterior and posterior regions. Previous studies have reported that different insula subregions play various roles in amnestic mild cognitive impairment (aMCI). However, the longitudinal changes in the functional connectivity (FC) of each insula subregion in aMCI patients over time remain unclear. Twenty aMCI patients and 20 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (fMRI) scans and neuropsychological assessments at baseline and at the 15-month follow-up. FMRI data were preprocessed using SPM 12 and the CONN toolbox. Two-way analysis of covariance was used to compare longitudinal changes in the FC of each insula subregion with covariates including sex, age, education, follow-up interval, volume of gray matter, and global correlation (GCOR). Pearson's correlation was used to evaluate the relationship between insula subregional FC and neuropsychological performance in aMCI patients. In aMCI patients, the right anterior insula exhibited significantly increased FC with the left anterior cingulate cortex, whereas the left posterior insula exhibited decreased FC with the right precuneus compared with HCs. Furthermore, FC between the right anterior insula and left anterior cingulate cortex was significantly correlated with global cognition at follow-up. The current findings revealed different functional alterations in the insula subregions and provided new insights into the neurodegenerative process in aMCI patients.

The neurostructural consequences of glaucoma and their overlap with disorders exhibiting emotional dysregulations: A voxel-based meta-analysis and tripartite system model.

BACKGROUND: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores overlaps with morphological alterations observed in anxiety and depression. METHODS: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with alterations in generalized anxiety disorder (GAD) and major depressive disorder (MDD). RESULTS: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. LIMITATIONS: While the study identified significant morphological alterations, the number of studies from both the glaucoma and GAD cohorts remains limited due to the lack of independent studies meeting our inclusion criteria. CONCLUSION: The study proposes a tripartite brain model for glaucoma, with visual processing changes related to the lingual gyrus and additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of glaucoma.