Neuroimaging Perspective Research Articles

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.

OSBA: An Open Neonatal Neuroimaging Atlas and Template for Spina Bifida Aperta

We present the Open Spina Bifida Aperta (OSBA) atlas, an open atlas and set of neuroimaging templates for spina bifida aperta (SBA). Traditional brain atlases may not adequately capture anatomical variations present in pediatric or disease-specific cohorts. The OSBA atlas fills this gap by representing the computationally averaged anatomy of the neonatal brain with SBA after fetal surgical repair. The OSBA atlas was constructed using structural T2-weighted and diffusion tensor MRIs of 28 newborns with SBA who underwent prenatal surgical correction. The corrected gestational age at MRI was 38.1 ± 1.1 weeks (mean ± SD). The OSBA atlas consists of T2-weighted and fractional anisotropy templates, along with nine tissue prior maps and region of interest (ROI) delineations. The OSBA atlas offers a standardized reference space for spatial normalization and anatomical ROI definition. Our image segmentation and cortical ribbon definition are based on a human-in-the-loop approach, which includes manual segmentation. The precise alignment of the ROIs was achieved by a combination of manual image alignment and automated, non-linear image registration. From the clinical and neuroimaging perspective, the OSBA atlas enables more accurate spatial standardization and ROI-based analyses and supports advanced analyses such as diffusion tractography and connectomic studies in newborns affected by this condition.

Revealing the mechanism of central pain hypersensitivity in primary dysmenorrhea: evidence from neuroimaging.

Primary dysmenorrhea (PDM) is the most common problem in menstruating women. A number of functional magnetic resonance imaging (fMRI) study have revealed that the brain plays a crucial role in the pathophysiology of PDM. However, these results have been inconsistent, and there is a lack of a comprehensive fMRI study to clarify the onset and long-term effects of PDM. The aim of this study was thus to investigate the onset and long-term effects of PDM in a cohort of patients with PDM. This study employed a cross-sectional design with prospective data collection, in which 25 patients with PDM and 20 healthy controls (HCs) were recruited. The patients with PDM underwent fMRI scans both during the PDM during the pain phase (PDM-P) and nonpain phase (PDM-NP). The long-term effects of PDM on the brain was assessed by comparing PDM-NP findings with those of HCs, and the central mechanism of PDM was assessed by comparing the PDM-P findings with those of PDM-NP. To identify changes in brain function, the amplitude of low-frequency fluctuations and the regional homogeneity (ReHo) were measured. To assess changes in brain structure, voxel-based morphometry (VBM) was applied. The periaqueductal gray (PAG) was set as a region of for conducting seed-based whole-brain functional connectivity (FC) analysis. Subsequently, Pearson correlation analyses were employed to evaluate the associations between the abnormal brain region and the clinical information of the patients. There were neither functional nor structural differences between patients in the PDM-NP and HCs. Compared with those in PDM-NP, those in PDM-P showed increased ReHo in the left dorsolateral prefrontal cortex (DLPFC) but decreased FC between PAG and right superior parietal gyrus, bilateral inferior parietal gyrus, right calcarine gyrus, left superior occipital gyrus, left precentral gyrus, right DLPFC, and left crus I of the cerebellar hemisphere. The results from this study suggest that the mechanism of central pain hypersensitivity of PDM may be related to the disorder of the FC between the PAG and descending pain modulation system, default mode network (DMN), and occipital lobe. These findings could help us better understand the pathophysiology of PDM from a neuroimaging perspective.

Understanding the role of mental pain in suicidal individuals: from clinical to neuroimaging perspective.

IntroductionIn the attempt to shed light on the phenomenology of suicide, this contribution focuses on the role of mental pain as a main ingredient of suicide.ObjectivesPrevious studies have shown that mental pain, childhood negative experiences, and maltreatment are associated with suicide risk. Neuroimaging studies demonstrated that such emotional pain shares the same neuroanatomical circuit of somatic pain. Furthermore, concepts related to death, failure, or other unfortunate circumstances activate specific cerebral areas in a suicidal individual compared to a non-suicidal subject.MethodsThe author, through a multicenter investigation, conducted a sizeable clinical study on mental pain related to psychiatric disorders and suicide risk. With this aim, a dataset of more than 2200 psychiatric patients is explored to investigate suicide risk, mental pain, childhood trauma, and the role of depressive symptomatology. Implications emerging from neuroimaging studies are investigated.ResultsA framework emerges about the role of childhood traumatization in mediating between suicide risk and mental pain; furthermore, when individuals experience high mental pain and high depressive symptomatology, regardless of the diagnoses, they are exposed to higher suicide risk.ConclusionsSuch results are presented in light of neuroimaging studies’ role in identifying how mental pain and brain activation are detected in suicidal individuals. Therefore, this contribution aims to understand better mental pain’s role in clinical practice and research activities.Disclosure of InterestNone Declared

Tumor-like Lesions in Primary Angiitis of the Central Nervous System: The Role of Magnetic Resonance Imaging in Differential Diagnosis.

Primary Angiitis of the Central Nervous System (PACNS) is a rare disease and its diagnosis is a challenge for several reasons, including the lack of specificity of the main findings highlighted in the current diagnostic criteria. Among the neuroimaging pattern of PACNS, a tumefactive form (t-PACNS) is a rare subtype and its differential diagnosis mainly relies on neuroimaging. Tumor-like mass lesions in the brain are a heterogeneous category including tumors (in particular, primary brain tumors such as glial tumors and lymphoma), inflammatory (e.g., t-PACNS, tumefactive demyelinating lesions, and neurosarcoidosis), and infectious diseases (e.g., neurotoxoplasmosis). In this review, the main features of t-PACNS are addressed and the main differential diagnoses from a neuroimaging perspective (mainly Magnetic Resonance Imaging-MRI-techniques) are described, including conventional and advanced MRI.

The neural effects of acupuncture for stroke: a protocol for systematic review and meta-analysis based on fMRI.

Stroke is one of the most common causes of death and is the main cause of persistent and acquired disability in adults worldwide. Acupuncture is recommended by the World Health Organization as an alternative and complementary strategy for stroke treatment. However, the mechanism of the neural effects of acupuncture on stroke is still lacking a uniform conclusion. The purpose of this study is to clarify the neural effects of acupuncture for stroke from the perspective of neuroimaging. Seven databases, including PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, VIP Database, Wan-Fang Data, and Chinese Biomedical Database, will be searched comprehensively according to the search strategy. All of them will be retrieved from the date of database establishment to December 31, 2023. All randomized controlled trials and observational studies will be considered for inclusion. The risk of bias will be assessed by the Cochrane Risk of Bias tool. Functional imaging of the whole brain in the resting functional state will be the primary outcome. A meta-analysis of primary outcome will be performed using Seed-based D Mapping with Permutation of Subject Images software. The data will be synthesized using a random effects model. Meta-analysis of other clinical data will be performed using RevMan 5.3 software. Publication bias will be assessed through funnel plots. Reports will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis. This study will aggregate the results of independent studies to provide overall evidence for the neural effects of acupuncture for stroke. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=500306, Identifier CRD42024500306.

Sex‐specific neuropsychiatric burden distinguished by APOE4 status and cortical thickness

AbstractBackgroundThe APOE ε4 (APOE4) allele is a genetic risk factor for Alzheimer’s disease (AD). Prior work by our group found a significant association between the APOE4 allele and presence of psychosis as well as overall increased neuropsychiatric symptom (NPS) burden in female APOE4 homozygote AD patients, with no effect present in males. In this study, we sought to examine the relationship between APOE4 carrier status and sex on NPS burden from a neuroimaging perspective, with the aim to determine what brain regions may be driving this effect.MethodA cohort of 752 AD patients were selected from the National Alzheimer’s Coordinating Center (NACC) database: 104 APOE4 homozygotes (40F|64M), 304 APOE4 heterozygotes (160F|144M) and 310 APOE4 non‐carriers (131F|179M). Presence of NPS was identified using the Neuropsychiatric Inventory (NPI). Structural T1‐weighted images were downloaded from the NACC imaging dataset and cortical thickness measures corresponding to frontal, cingulate, temporal and parietal regions were assessed. Statistical analysis included a Bayesian multilevel regression where cortical thickness was modeled as an outcome variable against an interaction between sex and APOE4 homozygote status (0|1), while controlling for heterozygote status, APOE4 non‐carrier status, age, sex and MMSE as predictor variables. Within‐ and between‐groups mean differences in thickness were measured as a probability density estimate (Highest Density interval), and partial correlation was used to examine NPI correlates to thickness.ResultFemale APOE4 homozygotes displayed a high probability (>90%HDI) of greater cortical thickness in the posterior cingulate and isthmus cingulate regions bilaterally and reduced cortical thickness in temporal regions (Figure 1). Cortical thickness in the fusiform cortex was positively correlated to greater NPI burden (p<0.05) among female homozygotes, and negatively correlated to NPI burden among female heterozygotes. Cortical thickness in males, regardless of carrier status, did not correlate to NPI burden in any region.ConclusionThis study highlights an important relationship between the fusiform cortex and NPI burden in female APOE4 carriers, marking a female‐specific effect. Future work should further disentangle sex differences in APOE4 status and psychosis with a focus on the fusiform cortex as a potential region of interest.

Central mechanisms of acupuncture in relieving visceral hypersensitivity in functional gastrointestinal disorders: A narrative review

Abstract Visceral hypersensitivity (VH), one of the major symptoms of functional gastrointestinal disorders (FGIDs), impacts the social life and quality of life of the patients. Because of the complex pathological mechanism, the drug therapy for VH has unsatisfactory clinical efficacy and induces side effects. Alternative strategies acting on the central nervous system with few side effects are urgently needed. We summarize the central mechanisms of acupuncture in relieving VH to provide theoretical support for the clinical application of acupuncture in the treatment of VH in FGIDs. In this study, we retrieved the related articles from PubMed and Web of Science with the key words of “acupuncture,”“electroacupuncture,” and “visceral hypersensitivity.” According to the sensory conduction, perception, and emotion-related pathways involved in VH, we summarize the central mechanism of acupuncture in relieving VH from the perspectives of molecular biology and neuroimaging. The pathogenesis of VH in FGIDs involves the peripheral and central nervous systems, which are responsible for the transmission and perception of visceral sensations as well as the regulation of emotion. The widespread nature of VH indicates the involvement of the central nervous system. Acupuncture mediates the signaling pathways between the gastrointestinal tract and the brain to regulate gastrointestinal function and relieve VH. Acupuncture relieves VH by integrating multiple pathways and targets. The available studies in this field mainly focus on the regulation of a specific target or chemical transmitter by acupuncture, while the exact connection among these targets remains to be clarified by multilevel and multitarget studies.

Hyperconnectivity of the lateral amygdala in long-term methamphetamine abstainers negatively correlated with withdrawal duration.

Introduction: Several studies have reported structural and functional abnormalities of the amygdala caused by methamphetamine addiction. However, it is unknown whether abnormalities in amygdala function persist in long-term methamphetamine abstainers. Methods: In this study, 38 long-term male methamphetamine abstainers (>12months) and 40 demographically matched male healthy controls (HCs) were recruited. Considering the heterogeneous nature of the amygdala structure and function, we chose 4 amygdala subregions (i.e., left lateral, left medial, right lateral, and right medial) as regions of interest (ROI) and compared the ROI-based resting-state functional connectivity (FC) at the whole-brain voxel-wise between the two groups. We explored the relationship between the detected abnormal connectivity, methamphetamine use factors, and the duration of withdrawal using correlation analyses. We also examined the effect of methamphetamine use factors, months of withdrawal, and sociodemographic data on detected abnormal connectivity through multiple linear regressions. Results: Compared with HCs, long-term methamphetamine abstainers showed significant hyperconnectivity between the left lateral amygdala and a continuous area extending to the left inferior/middle occipital gyrus and left middle/superior temporal gyrus. Abnormal connections negatively correlated with methamphetamine withdrawal time (r = -0.85, p < 0.001). The linear regression model further demonstrated that the months of withdrawal could identify the abnormal connectivity (βadj = -0.86, 95%CI: -1.06 to -0.65, p < 0.001). Discussion: The use of methamphetamine can impair the neural sensory system, including the visual and auditory systems, but this abnormal connectivity can gradually recover after prolonged withdrawal of methamphetamine. From a neuroimaging perspective, our results suggest that withdrawal is an effective treatment for methamphetamine.

Functional to structural plasticity in unilateral sudden sensorineural hearing loss: neuroimaging evidence

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.

Neural plasticity in Parkinson's disease: a neuroimaging perspective.

Neural plasticity in Parkinson's disease: a neuroimaging perspective.

Insular dysfunction of interoception in major depressive disorder: from the perspective of neuroimaging.

Interoception plays a crucial role in maintaining bodily homeostasis and promoting survival, and is considered the basis of human emotion, cognition, and self-formation. A malfunction of interoception is increasingly suggested to be a fundamental component of different mental health conditions, and depressive disorders have been especially closely associated. Interoceptive signaling and processing depends on a system called the "interoceptive pathway," with the insula, located in the deep part of the lateral fissure, being the most important brain structure in this pathway. Neuroimaging studies have revealed alterations in the structure and function of the insula in a large number of individuals with depression, yet the precise relationship between these alterations and interoceptive dysfunction remains unclear. The goal of this review is to examine the evidence that exists for dysfunction of interoception in people with Major Depressive Disorder (MDD), and to determine the associated specific alterations in the structure and function of the insula revealed by neuroimaging. Overall, three aspects of the potential relationship between interoceptive dysfunction and alterations in insular function in people with depression have been assessed, namely clinical symptoms, quantitative measures of interoceptive function and ability, and interoceptive modulation. To conclude, several specific limitations of the published studies and important lines of enquiry for future research are offered.

The Objective Dementia Severity Scale Based on MRI with Contrastive Learning: A Whole Brain Neuroimaging Perspective.

In the clinical treatment of Alzheimer's disease, one of the most important tasks is evaluating its severity for diagnosis and therapy. However, traditional testing methods are deficient, such as their susceptibility to subjective factors, incomplete evaluation, low accuracy, or insufficient granularity, resulting in unreliable evaluation scores. To address these issues, we propose an objective dementia severity scale based on MRI (ODSS-MRI) using contrastive learning to automatically evaluate the neurological function of patients. The approach utilizes a deep learning framework and a contrastive learning strategy to mine relevant information from structural magnetic resonance images to obtain the patient's neurological function level score. Given that the model is driven by the patient's whole brain imaging data, but without any possible biased manual intervention or instruction from the physician or patient, it provides a comprehensive and objective evaluation of the patient's neurological function. We conducted experiments on the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset, and the results showed that the proposed ODSS-MRI was correlated with the stages of AD 88.55% better than all existing methods. This demonstrates its efficacy to describe the neurological function changes of patients during AD progression. It also outperformed traditional psychiatric rating scales in discriminating different stages of AD, which is indicative of its superiority for neurological function evaluation.

Data-driven multimodal fusion: approaches and applications in psychiatric research.

In the era of big data, where vast amounts of information are being generated and collected at an unprecedented rate, there is a pressing demand for innovative data-driven multi-modal fusion methods. These methods aim to integrate diverse neuroimaging perspectives to extract meaningful insights and attain a more comprehensive understanding of complex psychiatric disorders. However, analyzing each modality separately may only reveal partial insights or miss out on important correlations between different types of data. This is where data-driven multi-modal fusion techniques come into play. By combining information from multiple modalities in a synergistic manner, these methods enable us to uncover hidden patterns and relationships that would otherwise remain unnoticed. In this paper, we present an extensive overview of data-driven multimodal fusion approaches with or without prior information, with specific emphasis on canonical correlation analysis and independent component analysis. The applications of such fusion methods are wide-ranging and allow us to incorporate multiple factors such as genetics, environment, cognition, and treatment outcomes across various brain disorders. After summarizing the diverse neuropsychiatric magnetic resonance imaging fusion applications, we further discuss the emerging neuroimaging analyzing trends in big data, such as N-way multimodal fusion, deep learning approaches, and clinical translation. Overall, multimodal fusion emerges as an imperative approach providing valuable insights into the underlying neural basis of mental disorders, which can uncover subtle abnormalities or potential biomarkers that may benefit targeted treatments and personalized medical interventions.

Changes in brain structure and related functional connectivity during menstruation in women with primary dysmenorrhea.

Neuroimaging studies have identified altered brain structures and functions in women with primary dysmenorrhea (PDM). However, previous studies focused on either structural or functional changes in specific brain regions rather than combining structural and functional analysis. Therefore, this prospective cross-sectional study aimed to investigate the changes in whole brain structure, and functional variation along with structural abnormalities in women with PDM during menstruation. In all, 31 patients with PDM (PTs) and 31 healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were applied to investigate structural changes based on high-resolution T1-weighted magnetic resonance images. Functional connectivity (FC) analysis was performed to evaluate functional variations related to the brain regions that showed structural group differences. Pearson correlation analysis was performed to assess the relationship between neuroimaging changes and clinical measures. Compared to HCs, PTs had reduced gray matter volume (GMV) in the right superior temporal gyrus (STG) and reduced thickness in the bilateral orbitofrontal cortex (OFC), left postcentral gyrus (PoCG), and left superior occipital gyrus (SOG). Among these areas, the STG and PoCG are responsible for altered resting-state FC patterns in PTs. Results showed decreased FC between the STG and the left cerebellar posterior lobe (poCb), the right dorsolateral prefrontal cortex (DLPFC), and the left precentral gyrus (PrCG). Results also showed decreased FC between the PoCG and the right precuneus and the right DLPFC. We also found greater FCs between the PoCG and the bilateral poCb, the left middle temporal gyrus (MTG), and the left angular gyrus. In addition, the FCs between the STG and poCb, and DLPFC in PTs were positively correlated with history and Cox menstrual symptom scale (CMSS) scores, respectively, while the FCs between STG and PrCG were negatively correlated with the onset age of PDM. Our research found structural abnormalities and related FC changes in several brain regions that were mainly involved in the emotional and sensory aspects of menstrual pain in PDM. These findings could help us understand the occurrence of PDM from a neuroimaging perspective.

Uncovering How Musicians Develop Perfect Pitch: A Literature Review

Introduction: Absolute pitch (AP), or more commonly known as “perfect pitch”, is the rare ability to label pitches without needing a reference note. While its mechanisms are still unknown, there are many different theories regarding how and why some individuals develop AP, while others do not. Some argue that the ability is genetically inherited, while others argue that AP is a skill preferentially learned at a young age, with links to musical training and tonal language learning. This review investigates the possible factors that lead to AP development, as well as possible neurobiological underpinnings of the ability. Methods: A literature search was conducted using scientific databases to reveal studies examining the impact of genetic, learning, musical training, language, and neuroimaging on AP development. Empirical studies written in English were examined for this review, with emphasis on how AP is differentially reflected in developmental and neuroimaging perspectives. Results: Genetics, learning, musical training, and language all play a role in AP development, with some having a greater impact than others. Young children are easily taught absolute pitch using training programs, while it is much more difficult in adults. Furthermore, the apparent critical period for AP development closely resembles the time frame of the critical period of language acquisition. The phenomenon of AP is apparent through localized brain function, which differs from non-AP individuals. Discussion: Genetic, musical training, and language all play an interconnected role in the development of AP. However, neuroimaging research is vastly separate, not integrating findings from other areas. Overall, looking at the various factors combined allows for a more complete understanding of AP. Conclusion: Currently, there is a lack of research linking genetic and environmental influences on AP development with specific brain structure and function, which future neuroimaging research should seek to do. Understanding AP development benefits musicians and furthers an understanding of human perception of the auditory environment.

Psychotic Symptom, Mood, and Cognition-associated Multimodal MRI Reveal Shared Links to the Salience Network Within the Psychosis Spectrum Disorders.

Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP. Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability in discriminating among SZ, SAD, and BP. We observed shared links to functional and structural covariation in prefrontal, medial temporal, anterior cingulate, and insular cortices among SZ, SAD, and BP, although they were linked with different clinical domains. The salience (SAN), default mode (DMN), and fronto-limbic (FLN) networks were the three identified multimodal MRI features within the psychosis spectrum disorders from psychotic symptom, mood, and cognition associations. In addition, using these networks, we can classify patients and controls and distinguish among SZ, SAD, and BP, including their first-degree relatives. The identified multimodal SAN may be informative regarding neural mechanisms of comorbidity for psychosis spectrum disorders, along with DMN and FLN may serve as potential biomarkers in discriminating among SZ, SAD, and BP, which may help investigators better understand the underlying mechanisms of psychotic comorbidity from three different disorders via a multimodal neuroimaging perspective.

Microglia: Friend and foe in tauopathy.

Aggregation of misfolded microtubule associated protein tau into abnormal intracellular inclusions defines a class of neurodegenerative diseases known as tauopathies. The consistent spatiotemporal progression of tau pathology in Alzheimer's disease (AD) led to the hypothesis that tau aggregates spread in the brain via bioactive tau "seeds" underlying advancing disease course. Recent studies implicate microglia, the resident immune cells of the central nervous system, in both negative and positive regulation of tau pathology. Polymorphisms in genes that alter microglial function are associated with the development of AD and other tauopathies. Experimental manipulation of microglia function can alter tau pathology and microglia-mediated neuroinflammatory cascades can exacerbate tau pathology. Microglia also exert protective functions by mitigating tau spread: microglia internalize tau seeds and have the capacity to degrade them. However, when microglia fail to degrade these tau seeds there are deleterious consequences, including secretion of exosomes containing tau that can spread to neurons. This review explores the intersection of microglia and tau from the perspective of neuropathology, neuroimaging, genetics, transcriptomics, and molecular biology. As tau-targeted therapies such as anti-tau antibodies advance through clinical trials, it is critical to understand the interaction between tau and microglia.

The Basal Forebrain Cholinergic Nuclei and Their Relevance to Schizophrenia and Other Psychotic Disorders.

The basal forebrain cholinergic nuclei (BFCN) provide the main cholinergic input to prefrontal cortices, the hippocampi, and amygdala. These structures are highly relevant for the regulation and maintenance of many cognitive functions, such as attention and memory. In vivo neuroimaging studies reported alterations of the cholinergic system in psychotic disorders. Particularly, a downregulation of nicotinic and muscarinic acetylcholine receptors has been found. Crucially, such alterations in neurotransmission have been associated with cognitive impairments and positive and negative symptoms. Recent pharmacological studies support these findings, as they demonstrated an association between the manipulation of cholinergic transmission and an attenuation in symptom severity. Targeting acetylcholine receptors has therefore become a focus for the development of novel psychopharmacological drugs. However, many open questions remain. For instance, it remains elusive what causes such alterations in neurotransmission. While evidence supports the idea that BFCN structural integrity is altered in schizophrenia, it remains to be determined whether this is also present in other psychotic disorders. Furthermore, it is unclear when throughout the course of the disorder these alterations make their appearance and whether they reflect changes in the BFCN alone or rather aberrant interactions between the BFCN and other brain areas. In this review, the specific role of the BFCN and their projections are discussed from a neuroimaging perspective and with a focus on psychotic disorders alongside future directions. These directions set the stage for the development of new treatment targets for psychotic disorders.

Hybrid 18F-florbetapir PET/MRI for assessing myelin recovery in GFAP-A patients.

Glial fibrillary acidic protein astrocytopathy (GFAP-A) is a rare autoimmune disease of the central nervous system that was newly reported in 2016. Previous studies have speculated that the pathological mechanism and clinical outcome of GFAP-A lie in the demyelination of the central nervous system, but due to the limitations of MR, this conclusion has not been further confirmed from the perspective of neuroimaging. A non-invasive, quantitative measurement of demyelination would be clinically valuable, given its critical role in mediating GFAP-A. Here, we report a case in which we use 18F-florbetapir positron emission tomography-magnetic resonance imaging (PET/MRI) to evaluate myelin recovery with follow-up in the patient with GFAP-A. Our patient displayed a decreased uptake of PET tracer 18F-florbetapir in the brain lesions and lower distribution volume ratio in the damaged white matter lesions compared to the normal-appearing white matter, indicating significant intracranial demyelination. After treatment, the 18F-florbetapir PET/MRI examination showed a significant increase in the uptake of 18F-florbetapir in the brain lesions, along with a reduced Expanded Disability Status Scale score. Although only a small number of patients have been validated, this case first reported 18F-florbetapir PET/MRI could quantitatively and non-invasively assess the myelin recovery in GFAP-A patients, which may lead to improvements in the early diagnosis and long-term prognosis.