Cingulate Research Articles

Associations Between Intertemporal Food Choice and BMI in Adult Women: An fMRI Study Using a Quasi-realistic Design.

Impulsivity resulting in unrestrained eating has been implicated as a contributing factor for obesity. Delay discounting (DD) tasks where individuals choose between a smaller immediate reward and a larger delayed reward provide useful data to describe impulsive decision-making and to determine the extent to which delayed rewards are discounted. To study the association between body mass index(BMI) and delay discounting for food and money in adult women. We used a DD task with real food rewards to investigate impulsive decision-making as related to BMI in participants who self-identified as women. Participants in group A had a mean BMI of 21.4 (n = 14), and participants in group B had a mean BMI of 32.2 (n = 14). Each group was tested in a hungry state during a single session. We performed fMRI during a DD task requiring participants to choose between a food item (one sandwich) constituting a smaller immediate reward and multiple food items (two, three, or four sandwiches) constituting a series of larger delayed rewards available at different intervals. The steepness of the discounting curve for food was determined from these decisions. Participants then completed a monetary discounting task to facilitate a comparison of the discounting of food and monetary rewards. Participants in group B discounted food rewards more steeply than monetary rewards. Decisions for delayed rewards led to increased activations of brain areas related to executive control on fMRI, such as the head of the caudate nucleus and the anterior cingulate cortex (ACC) in group A, but not group B participants. Our findings suggest that group B had difficulty deciding against the immediate food rewards due to insufficient recruitment of cortical control areas. Therefore, impulsivity is an important target for behavioral interventions in individuals with obesity.

Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia.

Neonatal hypoxic-ischemic encephalopathy disproportionately affects low- and middle-income countries, where ≈96% of affected infants reside. The current standard of care, therapeutic hypothermia, is frequently ineffective in this setting, likely because injury may be occurring earlier during labor. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal caffeine administration in near-term lambs following global ischemic injury to support the development of earlier treatment strategies targeting the fetus in utero as well as the infant postnatally. Ewes were randomly assigned to receive either 1 g IV caffeine citrate or placebo before delivery and placental transport assessed. Near-term lambs (141-143 days) of both sexes were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Lambs that received caffeine in utero also received 20 mg/kg IV caffeine citrate following resuscitation and 10 mg/(kg·d) IV for 2 days. An additional cohort received 60 mg/kg followed by 30 mg/(kg·d) (low dose versus high dose) postnatally. Biochemical, histological, and neurological outcome measures in lambs were assessed over a 6-day period. Perinatal caffeine administration demonstrated excellent placental transport kinetics and was well tolerated with lamb plasma levels comparable to those targeted in neonates with apnea of prematurity. Caffeine administration resulted in a systemic immunomodulatory effect, evidenced by significant reductions in proinflammatory IP-10 levels. Treated lambs demonstrated improved neurodevelopmental outcomes, while histological analysis revealed that caffeine reduced gray matter injury and attenuated inflammation in the cingulate and parasagittal cortex. This neuroprotective effect was greater and via a different mode of action than we previously reported for azithromycin. A higher caffeine dosing regimen demonstrated significant toxicity. Perinatal caffeine administration is well tolerated, attenuates systemic and brain inflammation, and contributes to improvements in histological and neurological outcomes in an ovine model of neonatal hypoxic-ischemic encephalopathy.

Methylphenidate differentially alters corticostriatal connectivity after traumatic brain injury.

Traumatic brain injury commonly impairs attention and executive function, and disrupts the large-scale brain networks that support these cognitive functions. Abnormalities of functional connectivity are seen in corticostriatal networks, which are associated with executive dysfunction and damage to neuromodulatory catecholaminergic systems caused by head injury. Methylphenidate, a stimulant medication that increases extracellular dopamine and noradrenaline, can improve cognitive function following TBI. In this experimental medicine add-on study to a randomised, double-blind, placebo-controlled clinical trial, we test whether administration of methylphenidate alters corticostriatal network function and influences drug response. 43 moderate-severe traumatic brain injury patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. 28 patients were included in the neuropsychological and functional imaging analysis (4 females, mean age 40.9±12.7, range 20-65) and underwent functional MRI and neuropsychological assessment after each block. 123I-Ioflupane SPECT Dopamine Transporter (DAT) scans were performed, and specific binding ratios were extracted from caudate subdivisions. Functional connectivity and the relationship to cognition was compared between drug and placebo conditions. Methylphenidate increased caudate to anterior cingulate cortex functional connectivity compared to placebo and decreased connectivity from the caudate to default mode network. Connectivity within the default mode network was also decreased by methylphenidate administration and there was a significant relationship between caudate functional connectivity and DAT binding during methylphenidate administration. Methylphenidate significantly improved executive function in TBI patients, and this was associated with alterations in the relationship between executive function and right anterior caudate functional connectivity. Functional connectivity is strengthened to brain regions including the anterior cingulate that are activated when attention is focused externally. These results show that methylphenidate alters caudate interactions with cortical brain networks involved in executive control. In contrast, caudate functional connectivity reduces to default mode network regions involved in internally focused attention and that deactivate during tasks that require externally focused attention. These results suggest that the beneficial cognitive effects of methylphenidate may be mediated through its impact on the caudate. Methylphenidate differentially influences how the caudate interacts with large-scale functional brain networks that exhibit co-ordinated but distinct patterns of activity required for attentionally demanding tasks.

Elucidating the neuropathological and molecular heterogeneity of amyloid-beta and tau in Alzheimer's disease through machine learning and transcriptomic integration.

Discerning functional brain network variations related to neuropathological aggregates in Alzheimer's disease (AD), including amyloid-beta (Abeta) and phosphorylated tau (p-tau), is crucial for understanding their link to cognitive decline and underlying molecular mechanisms. However, these variations are often confounded by normal aging-related changes, complicating interpretation. To address this challenge, we first defined Alzheimer's continuum cases (Abeta positive (A+), n = 129) and normal elderly (Abeta negative (A-), n = 160) using cerebral spinal fluid amyloid levels, and then applied a novel deep learning approach to resting-state connectivity using functional magnetic resonance imaging (fMRI) of the 289 subjects to disentangle A+-specific dimensions in brain network alterations from those shared with A- individuals. The identified A+-specific dimensions were further refined to predict individual Abeta and p-tau levels separately. We observed that resulting brain signatures, defined from A+-specific dimensions for predicting these two CSF biomarkers, were both attributed to the right superior temporal and anterior cingulate cortices and associated with attention and memory domains. When linking the brain signatures to gene expression data from a public transcriptomic atlas, we found that the brain signatures were associated with molecular pathways involving synaptic dysfunction and disruptions in pathways containing activity of excitatory neurons, astrocytes, and microglia. For A--shared dimensions, the Aβ-linked brain signature involved the left fusiform and right middle cingulate cortices, correlating with the language cognitive measurement and language-related molecular pathways. The p-tau-linked signature predominantly involved the right insula and inferior temporal cortices, correlating with the aging-related molecular pathways. Collectively, our findings provided new insights in understanding of Alzheimer's continuum pathological biomarkers.

Brain encoding during perceived control as a prospective predictor of improvement in quality of life.

Perceived control is strongly related to mental health and well-being. Specifically, lack of perceived control has been associated with learned helplessness and stress-related disorders, such as depression and anxiety. However, it is unknown whether brain activation to control and its protective effect against stress can predict changes in quality of life. To address this gap, we examined the neural underpinning of controllability in healthy females (N=40) performing the Value of Control task in an fMRI scanner. Quality of life and perceived stress were assessed at baseline and 6-month follow-up. Increased brain activation for control was found within the putamen, insula, thalamus, mid-cingulate, dorsolateral prefrontal cortex, motor cortex, and cerebellum. In contrast, increased brain activation for lack of control was found within the posterior cingulate and prefrontal cortices. In an exploratory analysis, an elastic-net algorithm was used to identify brain predictors of quality of life 6 months later. The right putamen's activation to control was selected as the best prospective predictor of improvement in life enjoyment and satisfaction and this association was mediated by changes in perceived stress. Our findings suggest that neural responsiveness to control may have utility as a potential marker of quality of life and resilience to adversity.

EEG Oscillatory Activity and Resting-State Networks Associated with Neurocognitive Function in Mild Traumatic Brain Injury.

This study aimed to investigate the characteristics of resting-state electroencephalography (EEG) activity and brain networks in patients with mild traumatic brain injury (mTBI) and their association with neurocognitive function (NCF). We analyzed 26 patients with subacute mTBI and 21 healthy controls. The subacute mTBI group (9 females, 17 males) had a mean age of 29.9 ± 9.9 years, and the healthy controls (11 females, 10 males) had a mean age of 29.7 ± 11.5 years. Current source density, lagged phase synchronization, and resting-state network activity were analyzed using exact low-resolution electromagnetic tomography (eLORETA) with 60 s resting-state EEG data. In addition, a correlation analysis was performed between these EEG parameters and NCF in patients with mTBI. We used the statistical nonparametric mapping method in eLORETA to correct for multiple comparisons. There were no significant differences in EEG parameters between the patients with mTBI and healthy controls. However, in patients with mTBI, correlation analysis revealed negative correlations between theta activity in the anterior cingulate cortex and verbal short-term memory and between activity in the memory perception network and verbal memory. Our findings suggest that resting-state EEG may be clinically useful in investigating the mechanism of NCF decline in patients with mTBI.

Sex Differences in Human Brain Structure at Birth

BackgroundSex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.MethodsHere, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0–28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.ResultsOn average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).ConclusionsOur findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.

Valenced tactile information is evoked by neutral visual cues following emotional learning

Abstract Learning which stimuli in our environment co-occur with painful or pleasurable events is critical for survival. Previous research has established the basic neural and behavioral mechanisms of aversive and appetitive conditioning; however, it is unclear precisely what information content is learned. Here we examined the degree to which aspects of the unconditioned stimulus (US)—sensory information versus affective salience—are transferred to the conditioned stimulus (CS). To decode what stimuli features (e.g., valence vs. discriminative somatosensation) are represented in patterns of brain activation elicited during appetitive (soft touch) and aversive (painful touch) conditioning to faces, a novel approach to using modeling with representational similarity analysis (RSA) based on theoretically driven representational patterns of interest (POIs) was applied to fMRI data. Once associations were learned through conditioning, globally, the CS reactivated US representational patterns showing conditioning-dependent reactivation in specific high-order brain regions: In the dorsal anterior cingulate cortex, the CS reactivated patterns associated with the affective salience of the US—suggesting that, with affective conditioning, these regions carry forward the affective associations of the experience.

The Role of the Insular Cortex and Serotonergic System in the Modulation of Long-Lasting Nociception.

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

Regional variations in cingulate cortex glutamate levels: A magnetic resonance spectroscopy study at 3T.

Regional variations in glutamate levels across the cingulate cortex, decreasing rostral-to-caudal, have been observed previously in healthy volunteers using proton magnetic resonance spectroscopy (1H-MRS) at 7T. This study sought to explore cingulate cortex glutamate trends further by investigating whether a similar gradient could be detected at 3T, the effect of sex, as well as whether individual variations gave rise to more than one regional glutamate pattern. 1H-MRS at 3T (Phillips Elition, semi-Localization by Adiabatic Selective Refocusing, TE/TR = 32/5000) was acquired in four cingulate regions: the anterior, mid-anterior, mid-posterior, and posterior cortices, in 50 healthy participants (26F) scanned at a fixed time of day and with controlled food intake. K-means clustering was used to characterize the presence of distinct regional patterns, which were then compared between sex and clusters. In addition, cortical thickness was compared between clusters, and in relation to glutamate. Aligned with 7T findings, we demonstrated that average glutamate levels decreased rostral-to-caudal in the healthy cingulate cortex. No effect of sex was found, suggesting similar resting glutamate levels in both sexes. Interestingly, the majority of participants were characterized by glutamate levels that did not significantly change across the cingulate (65%). Different regional patterns in cortical thickness between clusters offer further evidence into these distinct glutamate variations and suggest both a neuroanatomical and functional role may lead to these findings. This study provides a much needed foundation for further research to determine the implications of neurotransmission patterns in health and disease.

A Map of Transcriptomic Signatures of Different Brain Areas in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the disease are still under-investigated. In this study, a whole-transcriptome analysis was carried out on brain samples from the hippocampus (HI), temporal and parietal cortices (TC and PC, respectively), cingulate cortex (CG), and substantia nigra (SN) of six subjects with a definite AD diagnosis and three healthy age-matched controls in duplicate. The transcriptomic results showed a greater number of differentially expressed genes (DEGs) in the TC (1571) and CG (1210) and a smaller number of DEGs in the HI (206), PC (109), and SN (60). Furthermore, the GSEA showed a difference between the group of brain areas affected early (HI and TC) and the group of areas that were subsequently involved (PC, CG, and SN). Notably, in the HI and TC, there was a significant downregulation of shared DEGs primarily involved in synaptic transmission, while in the PC, CG, and SN, there was a significant downregulation of genes primarily involved in protein folding and trafficking. The course of AD could follow a definite time- and severity-related pattern that arises from protein misfolding, as observed in the PC, CG, and SN, and leads to synaptic impairment, as observed in the HI and TC. Therefore, a map of the molecular and biological processes involved in AD pathogenesis may be traced. This could aid in the discovery of novel biological targets in order to develop effective and well-timed therapeutic approaches.

Early childhood family threat and longitudinal amygdala-mPFC circuit development: Examining cortical thickness and gray matter-white matter contrast

Early threat-associated cortical thinning may be interpreted as accelerated cortical development. However, non-adaptive processes may show similar macrostructural changes. Examining cortical thickness (CT) together with grey/white-matter contrast (GWC), a proxy for intracortical myelination, may enhance the interpretation of CT findings. In this prospective study, we examined associations between early life family-related threat (harsh parenting, family conflict, and neighborhood safety) and CT and GWC development from late childhood to middle adolescence. MRI was acquired from 4200 children (2069 boys) from the Generation R study at ages 8, 10 and 14 years (in total 6114 scans), of whom 1697 children had >1 scans. Linear mixed effect models were used to examine family factor-by-age interactions on amygdala volume, caudal and rostral anterior cingulate (ACC) and medial orbitofrontal cortex (mOFC) CT and GWC. A neighborhood safety-by-age-interaction was found for rostral ACC GWC, suggesting less developmental change in children from unsafe neighborhoods. Moreover, after more stringent correction for motion, family conflict was associated with greater developmental change in CT but less developmental change in GWC. Results suggest that early threat may blunt ACC GWC development. Our results, therefore, do not provide evidence for accelerated threat-associated structural development of the amygdala-mPFC circuit between ages 8–14 years.

Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.

Prior work from our lab and others demonstrates that the endocannabinoid system is a promising avenue for improving fear memory deficits in posttraumatic stress disorder (PTSD). Specifically, 7.5mg of delta-9-tetrahydrocannabinol (THC) decreases fear responding in healthy adults and increases prefrontal cortex activation during extinction learning and fear renewal in adults with PTSD. The present study will determine whether there is a dose-dependent effect of THC on short-term (24h) and long-term (one week) fear learning and memory in adults with PTSD. Using a randomized, double-blind, placebo-controlled design, N = 36 adults with PTSD completed the study and were randomized to receive placebo (PBO, n = 11), 5mg of THC (n = 11), or 10mg of THC (n = 14) prior to fear extinction learning. Participants completed a Pavlovian conditioning paradigm with extinction recall and fear renewal occurring 24h and one week later, where we measured concurrent functional imaging and behavioral responses. Twenty-four hours after drug administration, individuals with PTSD given 5mg of THC exhibited greater anterior cingulate cortex and prefrontal cortex activation during early fear renewal. One week later, individuals given 10mg of THC exhibited greater hippocampus activation during extinction recall and prefrontal cortex activation during fear renewal. These data suggest that dosing and timing are critical for facilitating fear memory processes in PTSD, and that low-dose oral THC prior to extinction learning can affect brain indices of fear learning and memory both acutely and one week after administration.

A chronometric relationship between circuits underlying learning and error monitoring in the basal ganglia and salience network

Abstract Healthy individuals readily adjust their behaviour in response to errors using learning mechanisms. This raises the question of how error-related neural mechanisms underlie the learning process and its progress. In this study, 21 healthy participants performed a challenging functional magnetic resonance imaging (fMRI) task to answer this question. We assessed the evolution of error-related neural response as a function of learning progress. We tested the hypothesis that the dorsal anterior cingulate cortex (dACC) and anterior insula, key regions of the error monitoring neural circuitry, reflect both the performance of an action and its improvement. Given the nature of trial-and-error learning, we also expected an involvement of the striatum, particularly the putamen. We found that error-related neural activity (in the dACC and anterior insula) was similar following correct responses and errors in an initial learning period. However, as learning progressed, the activity continuously decreased in response to correct events and increased after errors. In opposition, during the initial learning phase, the putamen activity was modulated by errors, but, as it progressed, this region became unaffected by response outcomes. In sum, our study provides neural evidence for an interaction between the mechanisms underlying error monitoring and learning, contributing to clarifying how error-related neural responses evolve with learning.

Selective Brain Activations and Connectivities Related to the Storage and Recall of Human Object-Location, Reward-Location, and Word-Pair Episodic Memories.

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial parahippocampal system were higher in the right hemisphere. The activations in the face and object processing ventrolateral visual cortical stream regions FFC, PIT, V8 and TE2p were higher in the object-location in scene task than the reward-location task, and were higher in the right hemisphere. For reward-location in scene episodic memory, activations were also high in the ventromedial visual cortical spatial stream to the hippocampus, but were also selectively high in storage in key reward cortical regions (ventromedial prefrontal 10r, 10v, 10d; pregenual anterior cingulate d32, p24, p32, s32; and medial orbitofrontal cortex reward-related pOFC, 11l, OFC). For word-pair episodic memory, activations were lower in the ventromedial visual and medial parahippocampal spatial cortical stream, and were higher in language-related regions in Broca's area (44, 45, 47l), and were higher in the left hemisphere for these regions and for the many highly connected inferior frontal gyrus regions in the left hemisphere. Further, effective connectivity analyses during the episodic memory tasks showed that the direction of connectivity for these systems was from early visual cortical regions V2-V4 to the ventromedial visual cortical regions VMV1-3 and VVC for spatial scene processing; was from the pregenual anterior cingulate and orbitofrontal cortex reward systems to the hippocampal system; and was from the FFC/V8/PIT system to TE2p in the visual inferior temporal visual cortex, which has connectivity to lateral parahippocampal TF, which in turn has forward effective connectivity to the hippocampus.

Distinct Roles of Medial Prefrontal Cortex Subregions in the Consolidation and Recall of Remote Spatial Memories.

It is a common belief that memories, over time, become progressively independent of the hippocampus and are gradually stored in cortical areas. This view is mainly based on evidence showing that prefrontal cortex (PFC) manipulations impair the retrieval of remote memories, while hippocampal inhibition does not. More controversial is whether activity in the medial PFC is required immediately after learning to initiate consolidation. Another question concerns functional differences among PFC subregions in forming and storing remote memories. To address these issues, we directly contrasted the effects of loss-of-function manipulations of the anterior cingulate cortex (aCC) and the ventromedial PFC, which includes the infralimbic (IL) and prelimbic (PL) cortices, before testing and immediately after training on the ability of CD1 mice to recall the hidden platform location in the Morris water maze. We injected an AAV carrying the hM4Di receptor into the PL-IL or aCC. Interestingly, pretest administrations of clozapine-N-oxide (CNO; 3 mg/kg) revealed that the aCC, but not the PL-IL, was necessary to recall remote spatial information. Furthermore, systemic post-training administration of CNO impaired memory recall at remote, but not recent, time points in both groups. These findings revealed a functional dissociation between the two prefrontal areas, demonstrating that both the PL-IL and the aCC are involved in early consolidation of remote spatial memories, but only the aCC is engaged in their recall.

The impact of cannabidiol placebo on amygdala-based neural responses to an acute stressor.

Cannabidiol (CBD) impacts brain regions implicated in anxiety reactivity and stress reactivity (e.g., amygdala, anterior cingulate cortex (ACC), anterior insula (AI)); however, placebo-controlled studies are mixed regarding CBD's anxiolytic effects. We previously reported that CBD expectancy alone can alter subjective, physiological, and endocrine markers of stress/anxiety; however, it is unclear whether these findings reflect altered brain reactivity. This study evaluated whether CBD expectancy independently alters amygdala resting-state functional connectivity (rsFC) with the ACC and AI following acute stress. Thirty-eight (20 females) healthy adults were randomly assigned to receive accurate or inaccurate information regarding the CBD content of a CBD-free oil administered during a single experimental session. Following a baseline resting state MRI scan, participants administered their assigned oil sublingually, engaged in a stress task (serial subtraction with negative feedback) inside the scanner, and underwent another resting state MRI scan. Amygdala rsFC with the ACC and AI was measured during each scan, and the subjective state was assessed at six time points. Outcomes were analyzed using ANCOVA. CBD expectancy (vs CBD-free expectancy) was associated with significantly weaker rsFC between the left amygdala and right ACC (p = 0.042), but did not systematically alter amygdala-AI rsFC (p-values > 0.05). We also replicated our previously reported CBD expectancy effects on subjective stress/anxiety in the scanner context. CBD placebo effects may be sufficient to alter neural responses relevant to its purported anxiolytic and stress-relieving properties. Future work is needed to replicate these results and determine whether CBD expectancy and pharmacology interact to alter neural anxiety reactivity and stress reactivity.

Disturbances of Interoception in Schizophrenia – Focus on Neuroimaging

Abstract: The current paper presents the most recent theoretical understanding of interoception (INTC) in light of the predictive processing framework and the Embodied Predictive Interoceptive Coding model and reviews recent experimental data on different interoceptive disturbances in schizophrenia (SCZ) such as lower interoceptive accuracy, nociceptive dysfunction reflected by reduced pain sensitivity, disturbed thermoregulation, impaired gastrointestinal regulation, cardiovascular and respiratory dysfunction, and immune disturbances. The immense clinical implications of these disturbances are discussed in the context of the high rates of morbidity and mortality in SCZ related to suicide and cardiac death. Next, the potential of INTC-related treatments is reviewed, and conclusions are made on the evidence for the use of vagus nerve stimulation, mindfulness-based interventions, and exercise therapy. The neuroimaging perspective is given in a brief account of the INTC-related findings in healthy individuals suggesting the right anterior insula and anterior cingulate cortex as key brain areas for interoceptive awareness, accuracy, and sensibility, by supporting higher-order representation and integration of visceral, and somatosensory interoception with exteroceptive information. In SCZ, on the other hand, neuroimaging research on specific interoceptive abilities is lacking but indirect evidence points to disrupted activation of major INTC network hubs. There is converging evidence of changes in these hubs in terms of both structure and function (volume reductions, aberrant activation, and connectivity). This narrative review identifies several gaps in contemporary INTC-related research in SCZ that need to be addressed in future experimental and clinical studies to elucidate the exact nature of the disturbances of interoceptive abilities in modalities other than cardioception; the interactions between different interoceptive modalities; the association between interoceptive abilities and other mental functions (such as emotion recognition and regulation, decision making, learning, memory, etc.); the efficacy of nonpharmacological and pharmacological INTC-based interventions; and the relation of disturbed interoceptive abilities with brain structure and function.

Patterns of abnormal activations in severe mental disorders a transdiagnostic data-driven meta-analysis of task-based fMRI studies.

Studies suggest severe mental disorders (SMDs), such as schizophrenia, major depressive disorder and bipolar disorder, are associated with common alterations in brain activity, albeit with a graded level of impairment. However, discrepancies between study findings likely to results from both small sample sizes and the use of different functional magnetic resonance imaging (fMRI) tasks. To address these issues, data-driven meta-analytic approach designed to identify homogeneous brain co-activity patterns across tasks was conducted to better characterize the common and distinct alterations between these disorders. A hierarchical clustering analysis was conducted to identify groups of studies reporting similar neuroimaging results, independent of task type and psychiatric diagnosis. A traditional meta-analysis (activation likelihood estimation) was then performed within each of these groups of studies to extract their aberrant activation maps. A total of 762 fMRI study contrasts were targeted, comprising 13 991 patients with SMDs. Hierarchical clustering analysis identified 5 groups of studies (meta-analytic groupings; MAGs) being characterized by distinct aberrant activation patterns across SMDs: (1) emotion processing; (2) cognitive processing; (3) motor processes, (4) reward processing, and (5) visual processing. While MAG1 was mostly commonly impaired, MAG2 was more impaired in schizophrenia, while MAG3 and MAG5 revealed no differences between disorder. MAG4 showed the strongest between-diagnoses differences, particularly in the striatum, posterior cingulate cortex, and ventromedial prefrontal cortex. SMDs are characterized mostly by common deficits in brain networks, although differences between disorders are also present. This study highlights the importance of studying SMDs simultaneously rather than independently.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.