Insular Cortex Research Articles

Exploring the link between inflammation and brain function after metabolic-bariatric surgery: A year-long fMRI study.

Metabolic-bariatric surgery (MBS) transcends weight loss and offers wide-ranging health benefits, including positive effects on brain function. However, the mechanisms behind these effects remain unclear, particularly in the context of significant postoperative changes in the inflammatory profile characteristic of MBS. Understanding how inflammation influences postoperative brain function can enhance our decision-making on patient eligibility for MBS and create new opportunities to improve the outcomes of this popular treatment. To identify brain regions where spontaneous neural activity and functional connectivity are linked with the evolving inflammatory profile following MBS. We investigated the relationship between the perioperative ratio of interleukin (IL)-6 to IL-10 and both the amplitude of low-frequency fluctuation (ALFF) and functional connectivity across 375 brain regions. We examined 36 patients at three time points: 1 week before, and 3 and 12 months after laparoscopic sleeve gastrectomy. Initially, the IL-6/IL-10 ratio increased during the early postoperative period but then decreased to levels lower than the preoperative values 1 year after surgery. We observed that ALFF in four subcortical structures decreased with a rising IL-6/IL-10 ratio and increased with a declining ratio. Conversely, 16 cortical regions displayed the opposite trend. Additionally, functional connectivity between the left insula and bilateral medial prefrontal cortex increased with a rising IL-6/IL-10 ratio and decreased with a declining ratio. Our study is the first to identify brain regions significantly linked to inflammation after MBS. Importantly, many of the discovered areas were previously shown to be involved in the pathogenesis of obesity or are targets of contemporary medical treatments. Consequently, our findings offer valuable insights for future obesity research, especially in the context of potential therapeutic opportunities.

A distributed subcortical circuit linked to instrumental information-seeking about threat

Daily life for humans and other animals requires switching between periods of threat- and reward-oriented behavior. We investigated neural activity associated with spontaneous switching, in a naturalistic task, between foraging for rewards and seeking information about potential threats with 7T fMRI in healthy humans. Switching was driven by estimates of likelihood of threat and reward. Both tracking of threat and switching to a vigilant mode in which people sought more information about potential threats were associated with specific but distributed patterns of activity spanning habenula, dorsal raphe nucleus (DRN), anterior cingulate cortex, and anterior insula cortex. Different aspects of the distributed activity patterns were linked to monitoring the threat level, seeking information about the threat, and actual threat detection. A distinct pattern of activity in the same circuit and elsewhere occurred during returns to reward-oriented behavior. Individual variation in DRN activity reflected individual variation in the seeking of information about threats.

Specification of claustro-amygdalar and palaeocortical neurons and circuits.

The ventrolateral pallial (VLp) excitatory neurons in the claustro-amygdalar complex and piriform cortex (PIR; which forms part of the palaeocortex) form reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that results in adaptive behaviours1-5. Early-life disruptions in these circuits are linked to neuropsychiatric disorders4-8, highlighting the importance of understanding their development. Here we reveal that the transcription factors SOX4, SOX11 and TFAP2D have a pivotal role in the development, identity and PFC connectivity of these excitatory neurons. The absence of SOX4 and SOX11 in post-mitotic excitatory neurons results in a marked reduction in the size of the basolateral amygdala complex (BLC), claustrum (CLA) and PIR. These transcription factors control BLC formation through direct regulation of Tfap2d expression. Cross-species analyses, including in humans, identified conserved Tfap2d expression in developing excitatory neurons of BLC, CLA, PIR and the associated transitional areas of the frontal, insular and temporal cortex. Although the loss and haploinsufficiency of Tfap2d yield similar alterations in learned threat-response behaviours, differences emerge in the phenotypes at different Tfap2d dosages, particularly in terms of changes observed in BLC size and BLC-PFC connectivity. This underscores the importance of Tfap2d dosage in orchestrating developmental shifts in BLC-PFC connectivity and behavioural modifications that resemble symptoms of neuropsychiatric disorders. Together, these findings reveal key elements of a conserved gene regulatory network that shapes the development and function of crucial VLp excitatory neurons and their PFC connectivity and offer insights into their evolution and alterations in neuropsychiatric disorders.

Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum

Although 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized. To investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB. Longitudinal case-control study with mean (SD) follow-up of 3.8 (2.3) years. Cases were recruited consecutively between 2007 and 2022 at a referral center and among the population. Patients with probable DLB or mild cognitive impairment with Lewy bodies (MCI-LB) were included. Individuals without cognitive impairment were included from a population-based cohort balanced on age and sex for comparison. All participants completed at least 1 follow-up assessment by design. Patients with MCI-LB and DLB. Rate of change in FDG-PET was assessed as standardized uptake value ratios (SUVr). Clinical progression was assessed with the Clinical Dementia Rating Sum of Boxes (CDR-SB) score. Thirty-five patients with probable DLB, 37 patients with MCI-LB, and 100 individuals without cognitive impairment were included. The mean (SD) age of the DLB and MCI-LB groups combined (n = 72) was 69.6 (8.2) years; 66 patients (92%) were men and 6 (8%) were women. At follow-up, 18 participants (49%) with MCI-LB had progressed to probable DLB. Patients with MCI-LB had a faster decline in FDG-SUVr, compared with that of participants without cognitive impairment, in the posterior cingulate, occipital, parietal, temporal, and lateral frontal cortices. The same regions showed greater metabolic decline in patients with DLB than in participants without cognitive impairment, with the addition of anterior-middle cingulate, insula, and medial frontal orbital cortices. Rates of change in FDG-PET in these brain regions were combined into a region of interest (ROI) labeled longitudinal FDG-PET LB meta-ROI. The rate of change in FDG-SUVr in the meta-ROI correlated with the rate of change in CDR-SB, and sample size estimates were reported for potential clinical trials in DLB. Findings were confirmed in the subsample with neuropathologic confirmation (n = 20). This study found that brain hypometabolism begins to evolve during the prodromal stages of DLB with changes paralleling symptomatic progression. These data may inform clinical practice and trials planning to use FDG-PET for biologic staging, monitoring disease progression, and potentially assessing treatment response.

Beyond what was said: Neural computations underlying pragmatic reasoning in referential communication.

The ability to infer a speaker's utterance within a particular context for the intended meaning is central to communication. Yet, little is known about the underlying neurocomputational mechanisms of pragmatic inference, let alone relevant differences among individuals. Here, using a reference game combined with model-based functional magnetic resonance imaging (fMRI), we showed that an individual-level pragmatic inference model was a better predictor of listeners' performance than a population-level model. Our fMRI results showed that Bayesian posterior probability was positively correlated with activity in the ventromedial prefrontal cortex (vmPFC) and ventral striatum and negatively correlated with activity in dorsomedial PFC, anterior insula (AI), and inferior frontal gyrus (IFG). Importantly, individual differences in higher-order reasoning were correlated with stronger activation in IFG and AI and positively modulated the vmPFC functional connectivity with AI. Our findings provide a preliminary neurocomputational account of how the brain represents Bayesian belief inferences and the neural basis of heterogeneity in such reasoning.

Retrieval of an ethanol-conditioned taste aversion promotes GABAergic plasticity in the anterior insular cortex.

Blunted sensitivity to ethanol's aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the anterior insular cortex (aIC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuit's potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic currents onto aIC-BLA projections would be facilitated as a consequence of retrieval of an ethanol-conditioned taste aversion (CTA). Consistent with this hypothesis, frequency of mIPSCs was increased 1 hr following retrieval of an ethanol-CTA across cell layers in aIC-BLA projection neurons. This increase in GABAergic plasticity occurred in a circuit-specific, time-limited, and ethanol-CTA retrieval-dependent manner. Additionally, local inhibitory inputs onto layer 2/3 aIC-BLA projection neurons were greater in number and strength following ethanol-CTA. Finally, DREADD-mediated inhibition of aIC parvalbumin-expressing cells blunted the retrieval of ethanol-CTA in male, but not female, mice. Collectively, this work implicates a circuit-specific and memory retrieval-dependent increase in GABAergic tone following retrieval of an ethanol-CTA, thereby advancing our understanding of how the aversive effects of ethanol are encoded in the brain.Significance statement Sensitivity to the aversive properties of ethanol contributes to motivation to consume alcohol. However, the plasticity-associated mechanisms through which ethanol's aversive effects are represented within neural circuits are largely unidentified. In the present study, we used whole-cell patch clamp electrophysiology combined with synaptic input mapping to identify alterations in GABAergic plasticity within the anterior insula, and within cells projecting from the anterior insula to the basolateral amygdala. We demonstrate learning and circuit-specific alterations in GABAergic tone following retrieval of an ethanol-conditioned taste aversion, as well as a male-specific role for parvalbumin-expressing interneurons in modulating the strength of an ethanol-conditioned taste aversion. Combined, these findings provide novel insights into how the aversive properties of ethanol are encoded within brain circuitry.

Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.

Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life. Here, 160 young and cognitively healthy participants from the Chinese PREVENT cohort underwent 3 T arterial spin labelling and T1 MRI and genetic testing for APOE and MAPT rs242557 status. Using FSL, we performed a whole brain voxel-wise analysis and a global mean grey matter analysis comparing for the effects of both risk genes on cerebral perfusion. No significant alterations were seen for APOE genotype, but in MAPT rs242557 A carriers, we observed a significantly hyperperfusion in the left anterior cingulate cortex and left insular cortex. There were no effects of APOE or MAPT status on the global perfusion. These results are novel and may suggest that MAPT genotypes demonstrated a distinct hemodynamic profile in a very young age.

Directed connectivity in theta networks supports action-effect integration

The ability to plan and carry out goal-directed behavior presupposes knowledge about the contingencies between movements and their effects. Ideomotor accounts of action control assume that agents integrate action-effect contingencies by creating action-effect bindings, which associate movement patterns with their sensory consequences. However, the neurophysiological underpinnings of action-effect binding are not yet well understood. Given that theta band activity has been linked to information integration, we thus studied action-effect integration in an electrophysiological study with N=31 healthy individuals with a strong focus on theta band activity. We examined how information between functional neuroanatomical structures is exchanged to enable action planning. We show that theta band activity in a network encompassing the insular cortex (IC), the anterior temporal lobe (ATL), and the inferior frontal cortex (IFC) supports the establishment of action-effect bindings. All regions revealed bi-directional effective connectivities, indicating information transfer between these regions. The IC and ATL create a loop for information integration and the conceptual abstraction of it. The involvement of anterior regions of the IFC, particularly during the acquisition phase of the action-effect, likely reflects episodic control mechanisms in which a past event defines a “template” of what action-effect is to be expected. Taken together, the current findings connect well with major cognitive concepts. Our study suggests a functional relevance of theta band activity in an IC-ATL-IFC network, which in turn implies that basic ideomotor action-effect integration is implemented through theta band activity and effective connectivities between temporo-frontal structures.

Altered Neural Responses to Punishment Learning in Conduct Disorder.

Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision-making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared to typically-developing controls (TDCs). 75 youths with CD and 99 TDCs (9-18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies. Using fMRI data in conjunction with computational modeling indices (learning rate α), we investigated group differences for the three learning conditions in whole-brain and regions-of-interest (ROI) analyses, including the ventral striatum and insula. Whole-brain analysis revealed typical neural responses for RL in both groups. However, linear regression models for the ROI analyses revealed that only the response pattern of the (anterior) insula during punishment learning was different in CD compared to TDCs. Youths with CD have atypical neural responses to learning from punishment (but not from reward), specifically in the insula. This suggests a selective dysfunction of RL mechanisms in CD thereby contributing to 'punishment insensitivity/hyposensitivity' as a hallmark of the disorder. As the (anterior) insula is involved in avoidance behaviors related to negative affect or arousal, insula dysfunction in CD may contribute to inappropriate behavioral decision-making, which increases the risk for reckless, antisocial, and aggressive behaviors in affected youth.

Afferent Projections to the Calca/CGRP-Expressing Parabrachial Neurons in Mice.

The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons that regulate responses to a variety of interoceptive and cutaneous sensory signals. One lateral PB subpopulation expresses the Calca gene, which codes for the neuropeptide calcitonin gene-related peptide (CGRP). These PBCalca /CGRP neurons relay signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet their inputs and their neurochemical identity are only partially understood. We mapped the afferent projections to the lateral part of the PB in mice using conventional cholera toxin B subunit (CTb) retrograde tracing and then used conditional rabies virus retrograde tracing to map monosynaptic inputs specifically targeting the PBCalca /CGRP neurons. Using vesicular GABA (vGAT) and glutamate (vGLUT2) transporter reporter mice, we found that lateral PB neurons receive GABAergic afferents from regions such as the lateral part of the central nucleus of the amygdala, lateral dorsal subnucleus of the bed nucleus of the stria terminalis, substantia innominata, and ventrolateral periaqueductal gray. Additionally, they receive glutamatergic afferents from the infralimbic and insular cortex, paraventricular nucleus, parasubthalamic nucleus, trigeminal complex, medullary reticular nucleus, and nucleus of the solitary tract. Using anterograde tracing and confocal microscopy, we then identified close axonal appositions between these afferents and PBCalca /CGRP neurons. Finally, we used channelrhodopsin-assisted circuit mapping and found that GABAergic neurons of the central nucleus of the amygdala directly inhibit the PBCalca /CGRP neurons. These findings provide a comprehensive neuroanatomical framework for understanding the afferent projections regulating the PBCalca /CGRP neurons.

Sex differences in resting-state fMRI functional connectivity related to humor styles.

Research on how functional connectivity (FC) during resting-state relates to humor styles and sex is limited. This study aimed to address this knowledge gap by analyzing resting-state fMRI data from 56 healthy participants and measuring FC. In addition, participants completed the Humor Styles Questionnaire. We found distinct FC patterns linked to humor styles that differed by sex. Men demonstrated stronger FC between the anterior cingulate cortex (ACC) and the right anterior insula (rAI), right inferior frontal gyrus (rIFG) and right frontal pole (rFP), and between the right rostral prefrontal cortex (rRPFC) and rIFG. These patterns were associated with aggressive and self-enhancing humor. Conversely, women exhibited stronger FC between rRPFC and the posterior cingulate gyrus (PCC), left rostral prefrontal cortex (lRPFC) and right thalamus, correlating with self-defeating and less aggressive humor. These findings suggest a neurobiological basis for sex differences in humor, indicating that men's FC between the salience network (SN), particularly in cognitive monitoring regions, may be linked to aggressive humor. Their FC between the executive control network (ECN) and between the SN and ECN are related to self-enhancing humor and reflect an emphasis on executive function. Conversely, women's FC between the SN and default mode network is correlated with self-defeating humor, suggesting a stronger focus on self-reflection and social relationships.

Resting state EEG source derived salience network theta connectivity mediates anxiety in community dwelling individuals reporting childhood trauma.

Childhood trauma (CT) has been consistently linked with etiology of anxiety and depression. Finding biomarkers that mediate the relationship between CT and psychopathology is important and electroencephalography (EEG) can be a useful and cost-effective tool serving this purpose. Hence, in the current research we investigated resting state EEG biomarkers associated with CT and how these may link to psychopathology of anxiety and depression in adults. A total of 324 community recruited participants (age range 15-93 years) completed standard self-report scales of CT, anxiety and depression, and also underwent an eyes-closed resting state EEG recording session. Based on several functional neuroimaging studies, which have shown that connectivity in the salience network with major nodes in the anterior cingulate cortex (ACC) and insula is modulated by CT, we derived salience network connectivity measures from resting state EEG source imaging. Also given that theta band (3-7 Hz) neural oscillations have been shown to have an ACC source, we specifically focused on theta band salience network connectivity. The results showed significant positive correlation between CT and both anxiety and depression. We also found that theta band salience network connectivity, but not network activity, had a significant inverse relationship with CT and specifically mediated the relationship between CT and anxiety, but not depression. Interrogating the subcomponents of CT, theta connectivity in the salience network mediated the relationship between anxiety and both emotional abuse and physical neglect. These results showcase the utility of a resting state EEG source imaging-based biomarker in understanding the mechanistic associations between CT and psychopathology in community dwelling individuals.

Association of altered cortical gyrification and working memory in male early abstinent alcohol-dependent individuals.

Alcohol dependence (AD) is an addictive disorder with multifaceted neurobiological features. Recent research on the pathophysiological mechanisms of AD has emphasized the important role of dysconnectivity. Cortical gyrification is known to be a reliable marker of neural connectivity. This study aimed to explore cortical gyrification using the local gyrification index (LGI) between alcohol-dependent patients and controls. Magnetic resonance images were collected from 60 early abstinent patients with AD (5-12 days after stopping alcohol consumption) and 59 controls and preprocessed using FreeSurfer, followed by surface-based morphometry (SBM) analysis to compare the LGI between the two groups. Cognitive performance was assessed using the Spatial Working Memory (SWM) test in the Cambridge Neuropsychological Test Automated Battery (CANTAB). The relationship between LGI, cognitive performance, and clinical variables was also explored in the patient group. Compared with controls, patients with AD exhibited significantly decreased LGI in several regions, including the postcentral gyrus, precentral gyrus, middle frontal, superior temporal, middle temporal, insula, superior parietal, and inferior parietal cortex. AD patients did worse than controls in several SWM measures. Furthermore, decreased LGI in the left postcentral was negatively correlated with working memory performance after multiple comparison corrections in the patient group. Alcohol-dependent individuals exhibit abnormal patterns of cortical gyrification, which may be underlying neurobiological markers of AD. Our findings further indicate that working memory deficits may be related to abnormalities in cortical gyrification in alcohol addiction.

MR study on white matter injury in patients with acute diquat poisoning

To explore the microstructural damage of white matter in acute diquat (DQ) poisoning patients using diffusion kurtosis imaging (DKI) and Tract-based Spatial Statistics (TBSS). This study included 19 DQ poisoning patients and 19 age-matched controls. MRI was performed using a 3.0 T Philips Achieva scanner with sequences including 3D T1WI, T2WI, DWI, 3D T2WI-FLAIR, and DKI (3 b-values, 15 directions). DICOM to NIFTI image form conversion was done using MRIcron's Dcm2niigui, followed by motion and eddy current correction with FSL to create a brain mask. Scalar indicators (MK, AK, RK, FAK) were calculated with DKE software. TBSS was used for spatial normalization, skeletonization, and projection of DKI indices for group analysis with TFCE for multiple comparison correction (P < 0.025). After the screening and enrollment process, 19 DQ-poisoned patients and 19 healthy volunteers were analyzed. No significant age or sex differences were found between groups. For Mean Kurtosis (MK), the right corticospinal tract showed a significant difference with a mean difference of 0.21 (95 % CI: 0.15-0.27) and P = 0.000503. Axial Kurtosis (AK) in the left superior longitudinal fasciculus had a mean difference of 0.18 (95 % CI: 0.12-0.24) and P = 0.0024. Fractional Anisotropy of Kurtosis (FAK) in the right corticospinal tract showed a mean difference of 0.19 (95 % CI: 0.13-0.25) and P = 0.0000318. Axial Kurtosis (AK) positively correlated with blood drug levels (r = 0.52, P < 0.05). Seven patients developed subcortical leukodystrophy, mainly in the frontal parietal lobe, with possible insular lobe involvement. DQ poisoning primarily damages the right corticospinal tract, right cingulate gyrus, and left superior longitudinal fasciculus, potentially causing movement and visual impairments. The injury involves demyelination and axonal degeneration, with asymmetrical damage between hemispheres. The left superior longitudinal fasciculus injury is dose-dependent, and unlike prior studies, dopaminergic nuclei were unaffected. The frontal parietal lobe is predominantly affected, with some insular lobe involvement in DQ poisoning patients.

Enhanced behavioural and neural sensitivity to punishments in chronic pain and fatigue.

Chronic pain and fatigue in musculoskeletal disease contribute significantly to disability, and recent studies suggest an association with reduced motivation and excessive fear avoidance. In this behavioural neuroimaging study, we aimed to identify the specific behavioral and neural changes associated with musculoskeletal pain and fatigue during reward and loss decision-making. Twenty-nine participants with chronic inflammatory arthritis and 28 healthy controls performed an instrumental learning task (4-armed bandit) during 3T brain fMRI. Computational analyses with reinforcement learning models were used to quantify the hidden variables involved in reward and loss decision-making, compare them across groups and finally relate them to brain activity. We found that participants with chronic pain had higher sensitivity to punishments and increased activity associated with the punishment prediction error in the right posterior insular cortex, putamen, pallidum, and dorsolateral prefrontal cortex. Functional network connectivity analysis showed that insula centrality correlated with subjective reports of fatigue and pain during the task. The findings of this exploratory study suggest that pain and fatigue in chronic pain relate to objective behavioural changes in loss-decision making, which can be mapped to a specific pattern of activity in brain circuits of motivation and decision-making. The proposed parametric signature, characterized most notably by increased punishment sensitivity, is distinct from patterns previously reported in psychiatric conditions and it aligns with predictions of the fear avoidance model of pain.

Agonists of the opioid δ-receptor improve irritable bowel syndrome-like symptoms via the central nervous system.

Irritable bowel syndrome (IBS) is a common condition that is challenging to treat, and novel drugs are needed for this condition. Previously, a chronic vicarious social defeat stress (cVSDS) mouse model exhibits IBS-like symptoms. Also agonists of the opioid δ-receptor exert anti-stress effects in rodents with minimal adverse effects. Here, we evaluated the effects of δ-receptor agonists on the IBS-like symptoms in cVSDS mice. cVSDS mice (male C57BL/6J mice) were prepared following a 10-day exposure to witness of social defeat stress. Subsequently, intestinal peristaltic motility and abdominal hyperalgesia were evaluated using the charcoal meal test (CMT) and capsaicin-induced hyperalgesia test (CHT), respectively. Extracellular glutamate levels were measured using in vivo brain microdialysis. The drug was singly administrated 30 min before testing. In cVSDS mice, systemic (10 mg kg-1) and intracerebroventricular (30 nmol) administration of a δ-receptor agonist regulated intestinal peristalsis in the CMT and relieved abdominal pain in the CHT. Effects of systemic administration were blocked by intracerebroventricular injection of a δ-receptor inhibitor. Local infusion of the δ-receptor agonist (0.6 nmol) into the insular cortex improved cVSDS-induced intestinal hypermotility. The in vivo brain microdialysis study showed that re-exposure to VSDS elevated the extracellular glutamate levels in the IC, which was restored by the δ-receptor agonist. We propose that agonists of opioid δ-receptors are potential drugs for the radical treatment of IBS because they can ameliorate IBS-like symptoms via the CNS, specifically the insular cortex.

The limbic and extra-limbic encephalitis associated with glutamic acid decarboxylase (GAD)-65 antibodies: an observational study.

We aimed to define the clinical features and outcomes of encephalitis associated with anti-GAD65 Abs. In addition, we reviewed cases published in the literature with GAD65 encephalitis. We retrospectively studied 482 consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder. Nineteen patients were enrolled (3.94% of the cohort). Twelve (63.16%) patients were females, and the mean age at onset of the cohort was 31.68 ± 13.88 years. The following clinical-neuroimaging syndromes were identified: limbic encephalitis (n = 10), limbic plus extra-limbic encephalitis (n = 6), meningoencephalitis (n = 1), extralimbic encephalitis (n = 1), and unclassified (n = 1). The mesial temporal lobes were the most frequently affected (n = 13, 68.42%) in the brain magnetic resonance imaging (MRI), followed by frontal lobes (21%), and insular lobes (21%). Epileptiform discharges (94.4%), mostly from temporal lobes, were the most common electroencephalogram (EEG) finding. Most patients received immunotherapy and were followed for a mean duration of 21 months. A total of 73 patients, including 54 from the literature and 19 presented from the current series, were analyzed. Limbic encephalitis was the predominant presentation, and most patients received immunotherapy. Outcomes varied considerably. Considering patients from the literature and this series (n = 70), mortality was 5.7%. Also, 82.8% of patients had persistent neurologic manifestations, including seizures and cognitive impairment following immunotherapy. Limbic encephalitis is the most common form of GAD65 encephalitis, while a smaller proportion of patients may have signs of extra-limbic involvement. Most patients have persistent manifestations following combined immunotherapy with a relatively low mortality rate.

Moral conviction interacts with metacognitive ability in modulating neural activity during sociopolitical decision-making.

The extent to which a belief is rooted in one's sense of morality has significant societal implications. While moral conviction can inspire positive collective action, it can also prompt dogmatism, intolerance, and societal divisions. Research in social psychology has documented the functional characteristics of moral conviction and shows that poor metacognition exacerbates its negative outcomes. However, the cognitive and neural mechanisms underlying moral conviction, their relationship with metacognition, and how moral conviction is integrated into the valuation and decision-making process remain unclear. This study investigated these neurocognitive processes during decision-making on sociopolitical issues varying in moral conviction. Participants (N = 44) underwent fMRI scanning while deciding, on each trial, which of two groups of political protesters they supported more. As predicted, stronger moral conviction was associated with faster decision times. Hemodynamic responses in the anterior insula (aINS), anterior cingulate cortex (ACC), and lateral prefrontal cortex (lPFC) were elevated during decisions with higher moral conviction, supporting the emotional and cognitive dimensions of moral conviction. Functional connectivity between lPFC and vmPFC was greater on trials higher in moral conviction, elucidating mechanisms through which moral conviction is incorporated into valuation. Average support for the two displayed groups of protesters was positively associated with brain activity in regions involved in valuation, particularly vmPFC and amygdala. Metacognitive sensitivity, the ability to discriminate one's correct from incorrect judgments, measured in a perceptual task, negatively correlated with parametric effects of moral conviction in the brain, providing new evidence that metacognition modulates responses to morally convicted issues.

Effects of childhood trauma on sustained attention in major depressive disorder: the mediating role of brain activity and functional connectivity

BackgroundSustained attention deficits were reported more significant in patients with major depressive disorder (MDD) than in healthy controls (HCs), and are pivotal in both the development and aggravation of depression. Childhood trauma is also common in MDD and the exposure to childhood trauma may impede sustained attention and increase the treatment resistance in MDD. However, the underlying neuro-mechanisms link the childhood trauma to sustained attention deficits in MDD remain unclear.MethodsWe collected resting-state functional magnetic resonance imaging data, and measured childhood trauma severity using the Childhood Trauma Questionnaire and sustained attention using the Continuous Performance Test, Identical Pairs version. After excluding subjects with significant head movement, 45 MDDs and 54 HCs were included in the analysis. We compared fractional amplitude of low-frequency fluctuation (fALFF) between the groups, conducted whole-brain correlation analysis between the fALFF and sustained attention in the MDD group, and defined significant regions as the regions of interest for the seed-to-whole brain functional connectivity (FC) analysis. We further performed mediation analyses to investigate the relationships among the childhood trauma, fALFF and FC values, and the level of sustained attention in the MDD group.ResultsCompared with HCs, MDDs exhibited higher fALFF in the right middle frontal gyrus and left inferior frontal gyrus, and lower fALFF in the bilateral insular cortex, left medial orbital superior frontal gyrus and left angular gyrus (ANG.L). Whole-brain correlation analysis showed that impaired sustained attention was associated with increased fALFF in the left postcentral gyrus (PoCG.L), and FC of PoCG.L-left precentral gyrus (PreCG.L) and ANG.L-right superior temporal gyrus (STG.R) in the MDD group. Furthermore, mediation analyses showed that the fALFF in PoCG.L, and FC of PoCG.L-PreCG.L and ANG.L-STG.R mediated the relationship between the childhood trauma and sustained attention in the MDD group.ConclusionThe fALFF in PoCG.L, and FC of PoCG.L-PreCG.L and ANG.L-STG.R might be potential neural substrate in the association between the childhood trauma and poor sustained attention in the MDDs, and might serve as potential intervention targets for the treatment of sustained attention deficits in MDDs with childhood trauma history.

The striatal compartments, striosome and matrix, are embedded in largely distinct resting state functional networks.

The striatum is divided into two interdigitated tissue compartments, the striosome and matrix. These compartments exhibit distinct anatomical, neurochemical, and pharmacological characteristics and have separable roles in motor and mood functions. Little is known about the functions of these compartments in humans. While compartment-specific roles in neuropsychiatric diseases have been hypothesized, they have yet to be directly tested. Investigating compartment-specific functions is crucial for understanding the symptoms produced by striatal injury, and to elucidating the roles of each compartment in healthy human skills and behaviors. We mapped the functional networks of striosome and matrix in humans in vivo . We utilized a diverse cohort of 674 healthy adults, derived from the Human Connectome Project, including all subjects with complete diffusion and functional MRI data and excluding subjects with substance use disorders. We identified striatal voxels with striosome-like and matrix-like structural connectivity using probabilistic diffusion tractography. We then investigated resting state functional connectivity (rsFC) using these compartment-like voxels as seeds. We found widespread differences in rsFC between striosome-like and matrix-like seeds ( p < 0.05, FWE corrected for multiple comparisons), suggesting that striosome and matrix occupy distinct functional networks. Slightly shifting seed voxel locations (<4 mm) eliminated these rsFC differences, underscoring the anatomic precision of these networks. Striosome-seeded networks exhibited ipsilateral dominance; matrix-seeded networks had contralateral dominance. Next, we assessed compartment-specific engagement with the triple-network model (default mode, salience, and frontoparietal networks). Striosome-like voxels dominated rsFC with the default mode network bilaterally. The anterior insula (a primary node in the salience network) had higher rsFC with striosome-like voxels. The inferior and middle frontal cortices (primary nodes, frontoparietal network) had stronger rsFC with matrix-like voxels on the left, and striosome-like voxels on the right. Since striosome-like and matrix-like voxels occupy highly segregated rsFC networks, striosome-selective injury may produce different motor, cognitive, and behavioral symptoms than matrix-selective injury. Moreover, compartment-specific rsFC abnormalities may be identifiable before disease-related structural injuries are evident. Localizing rsFC differences provides an anatomic substrate for understanding how the tissue-level organization of the striatum underpins complex brain networks, and how compartment-specific injury may contribute to the symptoms of specific neuropsychiatric disorders.