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The earliest neuropathological changes of Alzheimer’s disease, the beta-amyloid plaques, usually appear first in olfactory parts of the brain including the olfactory bulb, anterior olfactory nucleus, and entorhinal cortex. I totally lost my ability to smell several years before I developed any measurable cognitive impairment. Almost all people with Alzheimer’s have at least some impairment of olfaction, but most are not aware of it unless tested, probably because it comes on so gradually.
Understanding the neural mechanism underlying the transition from suicidal ideation to action is crucial but remains unclear. To explore this mechanism, we combined resting-state functional connectivity (rsFC) and computational modeling to investigate differences between those who attempted suicide(SA) and those who hold only high levels of suicidal ideation(HSI).
Methods
A total of 120 MDD patients were categorized into SA group (n=47) and HSI group (n=73). All participants completed a resting-state functional MRI scan, with three subregions of the insula and the dorsal anterior cingulate cortex (dACC) being chosen as the region of interest (ROI) in seed-to-voxel analyses. Additionally, 86 participants completed the balloon analogue risk task (BART), and a five-parameter Bayesian modeling of BART was estimated.
Results
In the SA group, the FC between the ventral anterior insula (vAI) and the superior/middle frontal gyrus (vAI-SFG, vAI-MFG), as well as the FC between posterior insula (pI) and MFG (pI-MFG), were lower than those in HSI group. The correlation analysis showed a negative correlation between the FC of vAI-SFG and psychological pain avoidance in SA group, whereas a positive correlation in HSI group. Furthermore, the FC of vAI-MFG displayed a negative correlation with loss aversion in SA group, while a positive correlation was found with psychological pain avoidance in HSI group.
Conclusion
In current study, two distinct neural mechanisms were identified in the insula which involving in the progression from suicidal ideation to action. Dysfunction in vAI FCs may gradually stabilize as individuals experience heightened psychological pain, and a shift from positive to negative correlation patterns of vAI-MFC may indicate a transition from state to trait impairment. Additionally, the dysfunction in PI FC may lead to a lowered threshold for suicide by blunting the perception of physical harm.
Motivational impairment associated with deficits in processing the anticipation of future reward is hypothesized to be a cardinal feature of schizophrenia spectrum disorders (SZ). Evidence from short-term follow-up (6-week post-treatment) studies suggests that these deficits may improve or be reversed with treatment, although longer-term outcomes are unknown. Here we examined the one-year trajectory of functional activation in brain circuitry associated with reward anticipation in people with recent onset SZ who participated in coordinated specialty care (CSC) treatment, hypothesizing normalization of brain response mirroring previous short-term findings in first-episode individuals.
Method
Blood oxygen level-dependent (BOLD) response in the dorsal anterior cingulate cortex, anterior insula, and ventral striatum (VS) associated with reward anticipation during the Incentivized Control Engagement Task (ICE-T) was analyzed in a baseline sample of 49 healthy controls (HCs) and 52 demographically matched people with SZ, with follow-up data available for 35 HCs and 17 people with SZ.
Results
In agreement with our hypothesis, significant time × diagnosis interactions were observed across all regions, in which reward anticipation-associated BOLD response increased in SZ to above baseline HC levels at follow-up. Increased VS activation was associated with decreased reality distortion symptoms over the follow-up period. Baseline reward anticipation-associated BOLD response in the right anterior insula was associated with improvement in reality distortion symptoms.
Conclusions
These findings suggest that functional deficits in reward anticipation may be reversed after one year of CSC in recent onset participants with SZ, and that this improvement is associated with reduced positive symptoms in the illness.
Eating disorders fundamentally involve disturbances in the experience of the physical sensations in one’s body based on internal signals, referred to as interoception. Interoceptive prediction errors (mismatch between anticipation and experience of physical sensation) may relate to anticipatory anxiety, avoidant behavior, and difficulty learning from experience. Deficits in making sense of brain signals related to internal body experience suggest a reliance on external signals is needed as a means to achieve recovery.
We report, in a cohort of 16 patients presenting with epilepsy arising from the insulo-opercular cortex solely, the outcome following SEEG-guided radiofrequency thermocoagulation (RFTC). Good outcomes (Engel class 1) are reported in 88% at 2 months and 67% at 18 months among the 9 of the 16 cases who had electrodes implanted following parasagittal trajectories. No one had an Engel class 1 outcome at 1 year in the group of 7 patients who had electrodes inserted solely orthogonally. No complications occurred. The benefit-risk ratio of the SEEG-guided RFTC procedure proved to be particularly favorable for patients presenting an epileptogenic focus located in the insula or in the medial aspect of the operculum, especially when using parasagittally, rather than orthogonally, implanted electrodes to coagulate. Therefore, this technique could be used, in selected cases, as the first-line therapeutic option procedure related to insular epilepsy, providing, in many cases, complete control over epileptic disease.
This chapter is about the use of direct electrical stimulation with short current pulses to estimate from recorded SEEG responses the functional connectivity of the insula. First, we review some studies of the literature which reported both intra-insular and extra-insular connectivity, using the anterior-posterior gyral decomposition of the insula. Second, we present the mapping of the responses to insula stimulation from 301 patients explored in SEEG from the database of the F-TRACT project. We show that the SEEG responses are highly spatially resolved on the whole brain, as demonstrated when comparing the stimulations between the anterior and posterior parts of the insula at different spatial resolution of the Lausanne parcellation scheme. In general, the responses to electrical stimulation of the insula are particularly numerous, in comparison to the stimulation of other areas, which suggests that insula is a structure densely connected to the rest of the cortex.
Invasive EEG investigation of the insular cortex has been performed with increasing frequency since the mid-nineties, in various forms of focal drug-resistant epilepsies. These include patients with a clear-cut intra-insular epileptogenic lesion, such as a focal cortical dysplasia, as well as patients whose non-invasive pre-surgical evaluation suggests perisylvian epilepsy, temporal plus epilepsy, sleep hypermotor epilepsy, MRI-negative frontal, and parietal lobe epilepsies. SEEG is currently the preferred method to investigate the insula, using orthogonal, oblique, or a combination of both trajectories, with no evidence of higher risk of intracranial bleeding than in other brain regions. Intra-insular ictal EEG patterns are often characterized by a prolonged focal discharge restricted to one of the five insular gyri, militating for a dense enough sampling of the insular cortex in suspected insular epilepsies. SEEG also offers the potential to perform thermolesion of insular epileptogenic zones which, together with MRI-guided laser ablation, represent a possibly safer alternative treatment to open-skull surgical resection of the insula.
The insular cortex is an extensively connected brain region that has recently gained considerable interest due to its elusive role in several pathological conditions and its involvement in a variety of functions. Structural connectivity studies have identified connections to the frontal, temporal, and parietal cortices, with both a rostro-caudal and a dorso-ventral organizational pattern. The insula is also widely connected to subcortical structures. The use of diffusion-weighted imaging in insular epilepsy has not yet reached its full potential; however, it may still provide some insights into its pathophysiology, assess long-term consequences, and help prevent operative complications. This chapter explores the insula’s structural connectivity and promising applications in the field of insular epilepsy.
Approximately 70% of patients with insular epilepsy require invasive investigation prior to resective or ablative surgery. Two broad techniques can be employed to invasively sample the insula and insular epileptogenic network. The first and most commonly used technique, stereo-electroencephalography (SEEG), involves the placement of intracerebral electrodes through drill-holes under stereotactic conditions (with or without robotic assistance) in the insula and relevant peri-insular network targets. The open technique involves the placement of depth electrodes within the insular cortex following the opening of the Sylvian fissure, in addition to peri-Sylvian grids over the cortical convexities or strips over the fronto-temporal-basal lobes/interhemispheric space. While there are no guidelines to decide which method to resort to, there are relative advantages, disadvantages, and scenarios where each may be beneficial. The vast majority of centers favor the SEEG technique, as it is minimally invasive, is associated with the lowest morbidity, and is particular adapted for investigating insular epileptic networks that usually involve widespread multi-lobar anatomical sites and deep structures (e.g., cingulate, mesial temporal structures, etc.). SEEG is also well-suited for bilateral cases and cases that involve reoperations, both of which are not infrequent in insular epilepsy. Finally, SEEG is an appealing option in patients in whom minimally invasive ablation (laser ablation or radiofrequency ablation) is being considered. In SEEG, insular electrodes can be placed through a trans-opercular orthogonal approach and/or through an oblique parasagittal approach (trans-frontally and/or trans-parietally). The open technique, on the other hand, is particularly suited for patients with superficial lesional epilepsy in whom the epileptogenic zone is clearly unilateral but requires invasive functional mapping, such as dominant hemisphere temporal lobe epilepsy with suspected insular involvement.
Firefighters are frequently exposed to stressful situations and are at high risk of developing post-traumatic stress disorder (PTSD). Hyperresponsiveness to threatening and emotional stimuli and diminishment of executive control have been suggested as manifestations of PTSD.
Aims
To examine brain activation in firefighters with PTSD by conducting an executive control-related behavioural task with trauma-related interferences.
Method
Twelve firefighters with PTSD and 14 healthy firefighters underwent functional magnetic resonance imaging (fMRI) while performing a Stroop match-to-sample task using trauma-related photographic stimuli. Seed-based functional connectivity analysis was conducted using regions identified in fMRI contrast analysis.
Results
Compared with the controls, the participants with PTSD had longer reaction times when the trauma-related interferences were presented. They showed significantly stronger brain activation to interfering trauma-related stimuli in the left insula, and had weaker insular functional connectivity in the supplementary motor area and the anterior cingulate cortex than the controls. They also showed a significant correlation between left insula–supplementary motor area connectivity strength and the hyperarousal subscale of the Clinician-Administered PTSD Scale.
Conclusions
Our findings indicate that trauma-related stimuli elicit excessive brain activation in the left insula among firefighters with PTSD. Firefighters with PTSD also appear to have weak left insular functional connectivity with executive control-related brain regions. This aberrant insular activation and functional connectivity could be related to the development and maintenance of PTSD symptoms in firefighters.
While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations.
Methods
The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure. We probed both sustained attention and working memory processes using a Continuous Performance Task in the scanner.
Results
We found significant negative associations between resilience and activation in the bilateral anterior insula engaged during sustained attention. Multivariate twin modelling showed that the association between resilience and the left and right insula activation was mostly driven by common genetic factors, accounting for 71% and 87% of the total phenotypic correlation between these variables, respectively. There were no significant associations between wellbeing/resilience and neural activity engaged during working memory updating.
Conclusions
The findings suggest that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention but not working memory updating. This possibly suggests a pattern of ‘neural efficiency’ (i.e. more efficient and/or attenuated activity) in people who may be more resilient to trauma.
Understanding when to trust and establishing judgments of trustworthiness are complex processes that are critical and essential for human life. Appropriate judgments in trustworthiness lead to the formation of cooperative, mutually beneficial relationships that facilitate personal success, a sense of achievement, increased well-being, and quality of life. The trust game is an economic decision-making game that was specifically designed to measure trust. It is an important and unique instrument, as it measures the entirety of the trust process. Research investigating brain activation during participation of the trust game has shown many brain regions and networks involved in the processes of trust. Whether some of these regions are necessary for various trust processes has been determined by studying trust game performances in individuals with lesions in specific trust-related brain areas. This chapter reviews lesion studies in patients with damage to the insula, amygdala, and prefrontal cortex, with a focus on how such patients perform on various aspects of the trust game and how the findings have informed our understanding of the neuroanatomical correlates of trust. Additionally, we review briefly some functional neuroimaging research on the involvement of the temporal parietal junction and ventral striatum in the trust process.
The surgical treatment of insular gliomas requires specialized knowledge. Over the last three decades, increased momentum in surgical resection of insular gliomas shifted the focus from one of expectant management to maximal safe resection to establish a diagnosis, characterize tumor genetics, treat preoperative symptoms (i.e., seizures), and delay malignant transformation through tumor cytoreduction. A comprehensive review of the literature was performed regarding insular glioma classification/genetics, insular anatomy, surgical approaches, and patient outcomes. Modern large, published series of insular resections have reported a median 80% resection, 80% improvement in preoperative seizures, and postsurgical permanent neurologic deficits of less than 10%. Major complication avoidance includes recognition and preservation of eloquent cortex for language and respecting the lateral lenticulostriate arteries.
The prediction of alcohol consumption in youths and particularly biomarkers of resilience, is critical for early intervention to reduce the risk of subsequent harmful alcohol use.
Methods
At baseline, the longitudinal relaxation rate (R1), indexing grey matter myelination (i.e. myeloarchitecture), was assessed in 86 adolescents/young adults (mean age = 21.76, range: 15.75–26.67 years). The Alcohol Use Disorder Identification Test (AUDIT) was assessed at baseline, 1- and 2-year follow-ups (12- and 24-months post-baseline). We used a whole brain data-driven approach controlled for age, gender, impulsivity and other substance and behavioural addiction measures, such as problematic cannabis use, drug use-related problems, internet gaming, pornography use, binge eating, and levels of externalization, to predict the change in AUDIT scores from R1.
Results
Greater baseline bilateral anterior insular and subcallosal cingulate R1 (cluster-corrected family-wise error p < 0.05) predict a lower risk for harmful alcohol use (measured as a reduction in AUDIT scores) at 2-year follow-up. Control analyses show that other grey matter measures (local volume or fractional anisotropy) did not reveal such an association. An atlas-based machine learning approach further confirms the findings.
Conclusions
The insula is critically involved in predictive coding of autonomic function relevant to subjective alcohol cue/craving states and risky decision-making processes. The subcallosal cingulate is an essential node underlying emotion regulation and involved in negative emotionality addiction theories. Our findings highlight insular and cingulate myeloarchitecture as a potential protective biomarker that predicts resilience to alcohol misuse in youths, providing novel identifiers for early intervention.
Smoking is socially accepted or tolerated and produces neither intoxication nor immediate adverse consequences. Nicotine binds to acetylcholine receptors, indirectly resulting in dopamine release and positive reinforcement. Nicotine effects become conditioned to smoking-related stimuli, including taste and tactile sensations, adding to the reward value of smoking. Two-thirds of daily smokers are addicted to nicotine. Situations associated with smoking trigger tobacco craving, especially during nicotine withdrawal. The nicotine withdrawal syndrome includes irritability, anxiety, anger, and depression. Relief of these symptoms promotes continued smoking. Emotional states similar to withdrawal symptoms also elicit craving. Stopping tobacco use is very difficult for addicted smokers with psychiatric conditions, as well as for those who began tobacco use during adolescence. Tobacco use shortens lifespan by an average of 13--14 years. Half of all heavy smokers die from a tobacco-related disease. Nicotine vapor is less toxic than tobacco smoke, but electronic cigarette users often become smokers. Some addicted individuals maintain that nicotine dependence is the hardest SUD to overcome.
Earlier neurobiological models of substance addictions proposed that addiction is the product of an imbalance between two separate, but interacting, neural systems: (1) an impulsive and amygdala-striatum dependent system that promotes automatic and habitual behaviors, and (2) a “reflective” prefrontal cortex dependent system for decision-making, forecasting the future consequences of a behavior, and inhibitory control. These impulsive and reflective systems are analogous to Daniel Kahneman’s model of System I and System II thinking, or the Behavioral Activation System (BAS) and the Behavioral Inhibition System (BIS). Here, the reflective system controls the impulsive system through several distinct mechanisms that regulate impulses. However, this control is not absolute – hyperactivity within the impulsive system can override the reflective system. Most prior research has focused either on the impulsive system (especially the ventral striatum and its mesolimbic dopamine projections) as a mechanism promoting the motivation and drive to seek drugs, or on the reflective system (prefrontal cortex) as a mechanism for decision-making and impulse control. More recent evidence suggests that a largely overlooked structure, the insula, also plays a key role in maintaining addiction (craving). Hence, a triadic model of addiction incorporates these three systems that are associated with archetypal behaviors in addiction: craving, motivation to procure the drug, poor decision-making, lack of impulse control, and deficits in self-regulation.
“Temporal plus” epilepsy (TPE) is a term that is used when the epileptogenic zone (EZ) extends beyond the boundaries of the temporal lobe. Stereotactic electroencephalography (SEEG) has been essential to identify additional EZs in adjacent structures that might be part of the temporal lobe/limbic network.
Objective:
We present a small case series of temporal plus cases successfully identified by SEEG who were seizure-free after resective surgery.
Methods:
We conducted a retrospective analysis of 156 patients who underwent SEEG in 5 years. Six cases had TPE and underwent anterior temporal lobectomy (ATL) with additional extra-temporal resections.
Results:
Five cases had a focus on the right hemisphere and one on the left. Three cases were non-lesional and three were lesional. Mean follow-up time since surgery was 2.9 years (SD ± 1.8). Three patients had subdural electrodes investigation prior or in addition to SEEG. All patients underwent standard ATL and additional extra-temporal resections during the same procedure or at a later date. All patients were seizure-free at their last follow-up appointment (Engel Ia = 3; Engel Ib = 2; Engel Ic = 1). Pathology was nonspecific/gliosis for all six cases.
Conclusion:
TPE might explain some of the failures in temporal lobe epilepsy surgery. We present a small case series of six patients in whom SEEG successfully identified this phenomenon and surgery proved effective.
Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions.
Methods
Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions.
Results
A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular–dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients.
Conclusions
The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.
Cognitive changes that accompany the gradual degradation of neural systems are countervailed by a set of attention-related processes that serve to reorganize and maintain function with advancing age. This chapter focuses on the potential role of the right hemisphere fronto-parietal network in maintenance of adequate sustained attention to the environment by older adults, as well as self-monitoring of changes in their cognition and behavior over time. Modulation of norepinephrine activity in the locus coeruleus, via its impact on this right lateralized network, may be of particular importance in increasing the capacity of older people to preserve cognitive functioning as a multitude of biological changes take place in their brains. We review studies demonstrating that noninvasive electrical brain stimulation to the right prefrontal cortex improves both sustained attention and error awareness, suggesting that this key interconnected hub region in the right hemisphere holds the potential to be exploited and upregulated in older adults to ameliorate deficits.
Adolescence is a period of heightened susceptibility to peer influences, and deviant peer affiliation has well-established implications for the development of psychopathology. However, little is known about the role of brain functions in pathways connecting peer contexts and health risk behaviors. We tested developmental cascade models to evaluate contributions of adolescent risk taking, peer influences, and neurobehavioral variables of risk processing and cognitive control to substance use among 167 adolescents who were assessed annually for four years. Risk taking at Time 1 was related to substance use at Time 4 indirectly through peer substance use at Time 2 and insular activation during risk processing at Time 3. Furthermore, neural cognitive control moderated these effects. Greater insular activation during risk processing was related to higher substance use for those with greater medial prefrontal cortex activation during cognitive control, but it was related to lower substance use among those with lower medial prefrontal cortex activation during cognitive control. Neural processes related to risk processing and cognitive control play a crucial role in the processes linking risk taking, peer substance use, and adolescents’ own substance use.