Social Deficits Research Articles

OCCUPATIONAL THERAPY PRE-ASSESSMENT OF LOW GRADE GLIOMA PATIENT WITH COMPLEX NEEDS ALMOST HALVES POST-OPERATIVE LENGTH OF STAY

Abstract AIMS Due to tumour eloquence, patients with low grade gliomas (LGGs) often have complex Occupational Therapy (OT) needs post-operatively. This need can impact length of stay and OT resource. Limited studies have focused on pre-assessment for this patient group. To address these challenges, we aimed to identify the impact of a newly-introduced Occupational Therapy (OT) pre-surgical assessment service for low grade glioma patients. METHOD Patients (n=16, prospective, consecutive, Jan-Jul 2023) planned for LGG surgery at Leeds Teaching Hospitals NHS Trust were offered an OT pre-assessment. Mixed methods analysis. Assessments and data collected included existing needs and deficits, length of stay, and OT sessions (number/contacts, time spent). Comparison was made to patients (n=16, retrospective, consecutive, Jun-Dec 2022) planned for LGG surgery who had not received this service. Complexity was defined using standardised, clinically-accepted factors (social, cognitive and/or physical deficits). RESULTS Patients with complex needs (4 in each group) benefitted significantly from OT pre-assessment with reductions in: length of stay (11.9 v 6.5 days, 45.4% decrease), median time spent (134 v 95 mins, 29.1% decrease), median number of contacts (5.4 v 3.4, 37.0% decrease). Patient, surgeon, CNS and other AHP feedback was overwhelm-ingly positive. CONCLUSION Patients with complex needs undergoing surgery for low grade gliomas significantly benefit from pre- assessment; reducing length of stay and liberating occupational therapy resource. This also reduces costs and increases productivity/efficiency. Further work in more LGG patients, other brain tumour patients, and the identification of key pre-assessment variables and interventions will guide the development of the service.

From antidepressants and psychotherapy to oxytocin, vagus nerve stimulation, ketamine and psychedelics: how established and novel treatments can improve social functioning in major depression.

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions.

Unraveling the socio-cognitive consequences of KCC2 disruption in zebrafish: implications for neurodevelopmental disorders and therapeutic interventions.

During postnatal brain development, maintaining a delicate balance between excitation and inhibition (E/I) is essential for the precise formation of neuronal circuits. The K+/cl- cotransporter 2 (KCC2) is instrumental in this process, and its dysregulation is implicated in various neurological disorders. This study utilized zebrafish (Danio rerio) to investigate the socio-cognitive consequences of KCC2 disruption. Through CRISPR-Cas9 technology, biallelic kcc2a knockout zebrafish larvae were generated, revealing behavioral abnormalities, including impaired social interactions and memory deficits. Molecular analyses unveiled alterations in key genes associated with the GABAergic and glutamatergic systems, potentially contributing to E/I imbalance. Additionally, KCC2 disruption influenced the expression of oxytocin and BDNF, crucial regulators of social behaviors, synaptic plasticity, and memory formation. The study also explored the therapeutic potential of KCC2 modulation using pharmaceuticals, showing the rescuing effects of CLP-290 and LIT-001 on social abnormalities. However, the selective impact of LIT-001 on social behaviors, not memory, highlights the complexity of neurobehavioral modulation. In summary, this study sheds light on the pivotal role of KCC2 in shaping socio-cognitive functions and suggests potential therapeutic avenues for KCC2-related neurological disorders.

A systematic review of the effect of sandplay therapy on social communication deficits in children with autism spectrum disorder.

To explore the efficacy of sandplay therapy in intervening social communication deficits in children with autism spectrum disorders (ASD), and whether this efficacy is influenced by the age of the children and the dosage of sandplay therapy intervention. Following the PICOS principle, randomized controlled trials (RCTs) related to sandplay therapy for social communication deficits in ASD children were retrieved from seven databases: PubMed, WOS, The Cochrane Library, Embase, CNKI, Wanfang, and VIP, from the inception of each database to November 10, 2023. Two experimenters independently conducted study screening and excluded studies with concomitant diseases, incomplete data, unextractable data, and non-randomized controlled trials. The PEDro scale was used for methodological quality assessment, and the GRADEprofiler method was employed to evaluate the quality of evidence. Stata17 software was used for meta-analysis, subgroup analysis, sensitivity analysis, and publication bias testing. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as the effect statistics. A total of 12 RCTs (791 cases) were included. Sandplay therapy had a positive impact on the social communication deficits of ASD children [SMD = -1.42, 95%CI (-1.79, -1.04), P < 0.001]. Subgroup analysis revealed that sandplay therapy administered during the early school age (449 cases, SMD = -1.44, P < 0.05), for a duration of 22-28 weeks (208 cases, SMD = 1.69, P < 0.05), and with a frequency of once per week (218 cases, SMD = -1.67, P < 0.05) was most effective in improving on social communication deficits of ASD children. The quality of evidence in this study was rated as high, with good methodological quality, including 12 studies with better quality and no detection of bias risk. The study had high heterogeneity, which was attributed to the measurement tools and intervention duration through subgroup analysis, with no inconsistency found. Additionally, no downgrade factors related to imprecision, publication bias, or indirectness were identified. In conclusion, sandplay therapy is an effective measure to improve social communication deficits in children with ASD, and current evidence recommends early intervention using an individual sandplay therapy or integrated sandplay therapy intervention program once a week for 22-28 weeks, which can serve as evidence-based clinical guidance. www.crd.york.ac.uk, identifier (CRD420234821750).

Autism spectrum disorder-like behaviors induced by hyper-glutamatergic NMDA receptor signaling through hypo-serotonergic 5-HT1A receptor signaling in the prefrontal cortex in mice exposed to prenatal valproic acid.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, social deficits, and cognitive impairments. Maternal use of valproic acid (VPA) during pregnancy is associated with an increased risk of ASD in offspring. The prevailing pathophysiological hypothesis for ASD involves excitation/inhibition (E/I) imbalances and serotonergic dysfunction. Here, we investigated the association between glutamatergic-serotonergic neuronal interactions and ASD-like behaviors in mice exposed to prenatal VPA. Prenatal VPA exposure induced excessive repetitive self-grooming behavior and impaired social behavior and object recognition memory in young adult period. Prenatal VPA mice showed hyper-glutamatergic function (increase in basal extracellular glutamate levels and CaMKII phosphorylation) and hypo-serotonergic function (decrease in 5-hydroxyindoleacetic acid and stimulation-induced serotonin [5-HT] release, but an increase in 5-HT transporter expression) in the prefrontal cortex. Treatment with a low-affinity NMDA receptor antagonist (memantine), a selective 5-HT reuptake inhibitor (fluoxetine), and a 5-HT1A receptor agonist (tandospirone) attenuated both the increase in CaMKII phosphorylation and ASD-like behavior of prenatal VPA mice. Opto-genetic activation of the serotonergic neuronal system attenuated impairments in social behavior and object recognition memory in prenatal VPA mice. WAY-100635-a 5-HT1A receptor antagonist-antagonized the effect of fluoxetine on impaired social behavior and object recognition memory. These results suggest that E/I imbalance and ASD-like behavior are associated with hypo-serotonergic receptor signaling through 5-HT1A receptors in prenatal VPA mice.

Social contexts are associated with higher emotional awareness than nonsocial contexts: Evidence in a sample of people with and without major depressive disorder.

Growing evidence suggests that social contexts may prompt qualitatively distinct experiences of emotions than nonsocial contexts. In this study of people's naturalistic daily emotional experiences, we examined in adults with and without major depressive disorder (MDD) whether experiencing emotions in a social context (with others) versus nonsocial context (without others) was associated with greater emotional clarity and attention to one's emotional experience (i.e., emotional awareness). Based on evidence that social stimuli are highly salient to social species, we predicted that interactions with social others-and especially close social others-would be associated with greater emotional awareness. We furthermore expected that individuals with MDD, who tend to have diminished emotional clarity and social deficits, might experience less emotional awareness in social settings than healthy controls. Across a 2-week experience sampling study that concluded in 2019, we assessed emotional awareness when people were interacting with others (vs. not) and interacting with close (vs. nonclose) others among adults with current MDD (n = 53), remitted MDD (n = 80), and healthy controls (n = 87). As expected, attention to emotion and emotional clarity were higher in social versus nonsocial contexts and when interacting with close versus nonclose others. Contrary to expectations that these effects would be weaker among those with current MDD, the current MDD group showed enhanced emotional clarity in social versus nonsocial settings compared to the other two groups. Insofar as emotional clarity is beneficial to well-being, these findings suggest those with MDD may especially benefit from social contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Restoring social deficits in IRSp53-deleted mice: chemogenetic inhibition of ventral dentate gyrus Emx1-expressing cells

IRSp53 is a synaptic scaffold protein reported to be involved in schizophrenia, autism spectrum disorders, and social deficits in knockout mice. Identifying critical brain regions and cells related to IRSp53 deletion is expected to be of great help in the treatment of psychiatric problems. In this study, we performed chemogenetic inhibition within the ventral dentate gyrus (vDG) of mice with IRSp53 deletion in Emx1-expressing cells (Emx1-Cre;IRSp53 flox/flox). We observed the recovery of social deficits after chemogenetic inhibition within vDG of Emx1-Cre;IRSp53 flox/flox mice. Additionally, chemogenetic activation induced social deficits in Emx1-Cre mice. CRHR1 expression increased in the hippocampus of Emx1-Cre;IRSp53 flox/flox mice, and CRHR1 was reduced by chemogenetic inhibition. Htd2, Ccn1, and Atp61l were decreased in bulk RNA sequencing, and Eya1 and Ecrg4 were decreased in single-cell RNA sequencing of the hippocampus in Emx1-Cre;IRSp53 flox/flox mice compared to control mice. This study determined that the vDG is a critical brain region for social deficits caused by IRSp53 deletion. Social deficits in Emx1-Cre;IRSp53 flox/flox mice were recovered through chemogenetic inhibition, providing clues for new treatment methods for psychiatric disorders accompanied by social deficits.

Selective vulnerability of parvocellular oxytocin neurons in social dysfunction

Selective vulnerability offers a conceptual framework for understanding neurodegenerative disorders such as Parkinson’s disease, where specific neuronal types are selectively affected and adjacent ones are spared. However, the applicability of this framework to neurodevelopmental disorders, particularly those characterized by atypical social behaviors, such as autism spectrum disorder, remains uncertain. Here we show that an embryonic disturbance, known to induce social dysfunction in male mice, preferentially impaired the gene expression crucial for neural functions in parvocellular oxytocin (OT) neurons—a subtype linked to social rewards—while neighboring cell types experienced a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits in early adulthood, concurrent with cell-type-specific sustained recovery of pivotal gene expression within parvocellular OT neurons. Collectively, our data shed light on the transcriptomic selective vulnerability within the hypothalamic social behavioral center and provide a potential therapeutic target through specific neonatal neurostimulation.

Age-related unstable transient states and imbalanced activation proportion of brain networks in people with autism spectrum disorder: A resting-state fMRI study using coactivation pattern analyses

Abstract The atypical static brain functions related to the executive control network (ECN), default mode network (DMN), and salience network (SN) in people with autism spectrum disorder (ASD) has been widely reported. However, their transient functions in ASD are not clear. We aim to identify transient network states (TNSs) using coactivation pattern (CAP) analysis to characterize the age-related atypical transient functions in ASD. CAP analysis was performed on a resting-state fMRI dataset (78 ASD and 78 healthy control (CON) juveniles, 54 ASD and 54 CON adults). Six TNSs were divided into the DMN-TNSs, ECN-TNSs, and SN-TNSs. The DMN-TNSs were major states with the highest stability and proportion, and the ECN-TNSs and SN-TNSs were minor states. Age-related abnormalities on spatial stability and TNS proportion were found in ASD. The spatial stability of DMN-TNSs was found increasing with age in CON, but was not found in ASD. A lower proportion of DMN-TNSs was found in ASD compared with CON of the same age, and ASD juveniles had a higher proportion of SN-TNSs while ASD adults had a higher proportion of ECN-TNSs. The abnormalities on spatial stability and TNS proportion were related to social deficits. Our results provided new evidence for atypical transient brain functions in people with ASD.

Sexuality and Gender Issues in Autistic Youth: A Series of 6 Cases and a Literature Review

Autism Spectrum Disorder (ASD) involves challenges in social communication and repetitive behaviors, impacting daily functioning. Individuals with ASD face unique difficulties regarding sexuality, often experiencing mismatches between sexual development and social maturity, leading to potential inappropriate behaviors. Social competence deficits may limit their understanding of sexuality, increasing risks of offending or victimization. Gender differences in sexual behavior are evident, with males showing earlier and more frequent sexual activity, while females demonstrate greater flexibility in sexual orientation. This paper presents six clinical cases highlighting the diverse experiences of sexuality and gender identity in autistic individuals, offering insights into the complex interactions between ASD, gender, and sexual behavior.

COLLABORATION-INCLUSION MODEL: STAKEHOLDERS PERCEPTION OF ITS IMPEDIMENTS AS A SOCIO-COMMUNICATION SKILL DEFICIT INTERVENTION STRATEGY IN LEARNERS WITH AUTISM IN NAIROBI COUNTY, KENYA

Autism Spectrum Disorder is a lifelong neurological disorder that affects individuals’ ability to communicate and socialize. It is commonly evident by age three but some cases can take long to be noticed. Parents' lack of awareness and cultural barriers are commonly associated with the delay. Research-based evidence indicates that the best approach to address social communication skill deficits in learners with ASD is by the use of a collaborative multidisciplinary team approach. This is more optimally done in an inclusive setting, both at school and in society. In this approach, speech therapists and other stakeholders collaboratively and consultatively work together as a team. While this has worked perfectly on many occasions, it has not always produced positive results, especially in developing countries like Kenya. It is important to review the key impediments to this model so that families, practitioners and policymakers can work together to ameliorate the situation created by the impediments. The main objective of this research was to consolidate what stakeholders perceive to be barriers to the effective use of the collaborative-inclusion model and what should be done to improve the current situation. Participants were selected purposefully, with an interview schedule and open-ended questionnaires as the main tools of data collection. Main impediments were found to be cultural barriers, poor training, shortage of physical and human resources, attitude and lack of support from administrators. Solutions include in-service training, the creation of awareness, training of more teachers, the inclusion of inclusion strategies in teacher training curriculum, and more funding by both county and national governments.&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt; Article visualizations:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;img src="/-counters-/soc/0725/a.php" alt="Hit counter" /&gt;&lt;/p&gt;

Early life seizures and olfactory communication in rats.

Early life seizures (ELS) are commonly associated with autism spectrum disorder (ASD); however, the exact role of ELS in the pathology is unknown. Prior studies have demonstrated social deficits, a core feature of ASD, following ELS; consequently, alterations in sensory modalities may contribute to the overall social deficits. Considering the speculated contribution of sensory deficit to social communication, we examined the developmental consequences of early postnatal kainic acid (KA)-induced seizures on olfactory preference and neural markers in the olfactory bulb in both male and female Sprague Dawley rats. KA-induced seizures or saline was administered. Rats were then exposed to a series of biologically relevant scents including male scent, female scent, nest scent, and phenylethylamine during the juvenile period and again during adulthood. Alterations in sensory modalities were expected to be expressed via abnormal preference for certain scents and/or production of abnormal ultrasonic vocalizations in response to scents. The olfactory bulbs were also assessed for the biologically relevant markers glial fibrillary acidic protein (GFAP) and calcium/calmodulin-dependent protein kinase II (CAMKII). Our findings resulted in no significant differences in olfactory preference following ELS for juveniles or adults compared to controls. Similarly, there were no differences in GFAP expression or the ratio of phosphorylated CAMKII to CAMKII in either olfactory bulb. Interestingly, despite a lack of treatment differences, different scents were shown to elicit different responses in juvenile rats, yet these differences subsided in adulthood. Overall, the results of this study suggest that olfaction does not contribute to socialization deficit following ELS within the KA model.

Sleepless nights and social plights: medial septum GABAergic hyperactivity in a neuroligin 3-deficient autism model.

Social deficits represent a core symptom domain of autism spectrum disorder (ASD), which is often comorbid with sleep disturbances. In this issue of the JCI, Sun et al. explored a medial septum (MS) circuit linking these behaviors in a neuroligin 3 conditional knockout model of autism. They identified GABAergic neuron hyperactivity following neuroligin 3 deletion in the MS. This hyperactivity resulted in the inhibition of the downstream preoptic area (POA) and hippocampal CA2 region, resulting in sleep loss and social memory deficits, respectively. Inactivating the hyperactive MS GABA neurons or activating the POA or CA2 rescued the behavioral deficits. Together, these findings deepen our understanding of neural circuits underlying social and sleep deficits in ASD.

α-Synuclein aggregation decreases cortico-amygdala connectivity and impairs social behavior in mice

Abnormal accumulation of insoluble α-synuclein (α-Syn) inclusions in neurons, neurites, and glial cells is the defining neuropathology of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Accumulation of α-Syn inclusions in the amygdala has been well-documented in post-mortem studies of PD and DLB brains, as well as preclinical animal models of these conditions. Though α-Syn pathology is closely associated with neurodegeneration, there is a poor correlation between neuronal loss in the amygdala and the clinical features of PD and DLB. Moreover, functional interaction between the cerebral cortex and the amygdala is critical to regulating emotion, motivation, and social behaviors. The cortico-amygdala functional interaction is likely to be disrupted by the development of α-Syn pathology in the brain. Thus, we hypothesize that neuronal α-Syn inclusions disrupt cortical modulation of the amygdala circuits and are sufficient to drive social behavioral deficits. In the present work, we designed a series of longitudinal studies to rigorously measure the time courses of neurodegeneration, functional impairment of cortico-amygdala connectivity, and development of amygdala-dependent social behavioral deficits to test this hypothesis. We injected α-Syn preformed fibrils (PFFs) into the dorsal striatum to induce α-Syn aggregation in the amygdala and the medial prefrontal cortex (mPFC) of C57BL6 mice of both sexes, followed by a detailed analysis of temporal development of α-Syn pathology, synaptic deficits, and neuronal loss in the amygdala, as well as behavioral deficits at 3–12 months post injections. Development of α-Syn inclusions caused losses of cortical axon terminals and cell death in the basolateral amygdala (BLA) at 6- and 12-months post injections, respectively. At a relatively early stage of 3 months post injections, the connection strength of the mPFC-BLA synapse was decreased in PFFs-injection mice compared to controls. Meanwhile, the PFFs-injected mice showed impaired social interaction behavior, which was rescued by chemogenetic stimulation of mPFC-BLA connections. Altogether, we presented a series of evidence to delineate circuit events in the amygdala associated with the accumulation of α-Syn inclusions in the mouse brain, highlighting that functional impairment of the amygdala is sufficient to cause social behavior deficits. The present work further suggests that early circuit modulation could be an effective approach to alleviate symptoms associated with α-Syn pathology, necessitating studies of functional consequences of α-Syn aggregation.

Investigating brain–gut microbiota dynamics and inflammatory processes in an autistic-like rat model using MRI biomarkers during childhood and adolescence

Autism spectrum disorder (ASD) is characterized by social interaction deficits and repetitive behaviors. Recent research has linked that gut dysbiosis may contribute to ASD-like behaviors. However, the exact developmental time point at which gut microbiota alterations affect brain function and behavior in patients with ASD remains unclear. We hypothesized that ASD-related brain microstructural changes and gut dysbiosis induce metabolic dysregulation and proinflammatory responses, which collectively contribute to the social behavioral deficits observed in early childhood. We used an autistic-like rat model that was generated via prenatal valproic acid exposure. We analyzed brain microstructural changes using diffusion tensor imaging (DTI) and examined microbiota, blood, and fecal samples for inflammation biomarkers. The ASD model rats exhibited significant brain microstructural changes in the anterior cingulate cortex, hippocampus, striatum, and thalamus; reduced microbiota diversity (Prevotellaceae and Peptostreptococcaceae); and altered metabolic signatures. The shift in microbiota diversity and density observed at postnatal day (PND) 35, which is a critical developmental period, underscored the importance of early ASD interventions. We identified a unique metabolic signature in the ASD model, with elevated formate and reduced acetate and butyrate levels, indicating a dysregulation in short-chain fatty acid (SCFA) metabolism. Furthermore, increased astrocytic and microglial activation and elevated proinflammatory cytokines—interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)—were observed, indicating immune dysregulation. This study provided insights into the complex interplay between the brain and the gut, and indicated DTI metrics as potential imaging-based biomarkers in ASD, thus emphasizing the need for early childhood interventions.

A protective role for EFTUD2 in the brain

In this issue of Neuron, Yang etal.1 report MFDM-like phenotypes in mice with deletion of Eftud2 in their Purkinje cells (PCs), namely cerebellar atrophy alongside motor and social deficits, similar to phenotypes observed in MFDM patients. The absence of Eftud2 caused mis-splicing of Atf4, reduced Scd1 and Gch1, and promoted ferroptosis-regulated PC death.

Efficacy of a Culturally Adapted Emotion Recognition Training Program in Improving Facial Emotion Recognition in Persons with Schizophrenia

Background: Facial emotion recognition (FER) deficits are being considered as core features of social cognitive deficits in schizophrenia, associated with socio-occupational dysfunction. Social cognition intervention programs have been shown to improve these deficits; however, there are no such intervention strategies in India. In this study, we aim to examine the efficacy of Training of Affect Recognition – Indian Version (TAR-IV) to enhance the FER abilities of people with schizophrenia. Methods: In an open-label experimental design, 36 participants with schizophrenia underwent 12 sessions of TAR-IV as an add-on to treatment as usual (TAU), while 29 participants with schizophrenia continued TAU (pharmacological treatment with or without occupational therapy and vocational rehabilitation services). Clinical and functional assessments were done using the positive and negative syndrome scale (PANSS) and socio-occupational functioning scale. Emotion recognition abilities were assessed on the tool for recognition of emotions in neuropsychiatric disorders at baseline, post-intervention, and follow-up (two to three months post-intervention). Results: The intervention group showed significant improvements in FER ( P = .001) and socio-occupational functioning ( P = .008) after receiving the TAR-IV, which remained significant at two months follow-up. A lower age of onset and poorer neurocognitive function at baseline predicted greater changes in emotion recognition ability following the intervention. Conclusions: This study demonstrated the efficacy of TAR-IV, the Indian adaptation of social cognition intervention, in improving emotion recognition abilities and socio-occupational functioning in patients with schizophrenia. These findings need to be replicated in randomized controlled trials.

The Role of Parvalbumin Interneurons in Autism Spectrum Disorder.

As an important subtype of GABAergic interneurons, parvalbumin (PV) interneurons play a critical role in regulating cortical circuits and neural networks. Abnormalities in the development or function of PV interneurons have been linked to autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by social and language deficits. In this review, we focus on the abnormalities of PV interneurons in ASD, including quantity and function and discuss the underlying mechanisms of impairments in PV interneurons in the pathology of ASD. Finally, we propose potential therapeutic approaches targeting PV interneurons, such as transplanting MGE progenitor cells and utilizing optogenetic stimulation in the treatment of ASD.

Neuroimaging meta-analyses reveal convergence of interoception, emotion, and social cognition across neurodegenerative diseases.

Simultaneous interoceptive, emotional, and social cognition deficits are observed across neurodegenerative diseases. Indirect evidence suggests shared neurobiological bases underlying these impairments, termed the allostatic-interoceptive network (AIN). However, no study has yet explored the convergence of these deficits in neurodegenerative diseases or examined how structural and functional changes contribute to cross-domain impairments. A PRISMA Activated Likelihood Estimate (ALE) metanalyses encompassed studies meeting inclusion criteria: interoception, emotion, or social cognition tasks; neurodegenerative diseases (behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasias (PPAs) Alzheimer's disease (AD), Parkinson's Disease (PD), multiple sclerosis (MS)); and neuroimaging (structural: MRI voxel-based morphometry; functional: fMRI and FDG-PET). From 20,593 studies, 170 met inclusion criteria (58 interoception, 65 emotion, and 47 social cognition) involving 7032 participants (4963 patients and 2069 healthy controls). In all participants combined, conjunction analyses revealed AIN involvement of the insula, amygdala, orbitofrontal cortex, anterior cingulate, striatum, thalamus, and hippocampus across domains. In bvFTD this conjunction was replicated across domains, with further involvement of the temporal pole, temporal fusiform cortex, and angular gyrus. A convergence of interoception and emotion in the striatum, thalamus, and hippocampus in PD and the posterior insula in PPAs was also observed. In AD and MS, disruptions in the AIN were observed during interoception, but no convergence with emotion was identified. Neurodegeneration induces dysfunctional AIN across atrophy, connectivity, and metabolism, more accentuated in bvFTD. Findings bolster the predictive coding theories of large-scale AIN, calling for more synergistic approaches to understanding interoception, emotion, and social cognition impairments in neurodegeneration.

Chronic administration of low dose aspirin alleviates ASD-like behaviors and activates AMPK in valproic acid-exposed rats

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder distinguished by deficits in social communication and the presence of restricted/repetitive behaviors. There has been a global increase in the prevalence of ASD, yet the underlying causes of ASD remain inadequately understood, and there is currently no pharmacological intervention for the core symptoms of ASD. However, recent studies have suggested that aspirin may have the potential for use in the treatment of ASD. MethodPregnant rats were administered either VPA or normal saline on gestational day 12.5. The male pups were administered a low dose of aspirin (1 mg/kg) or a vehicle control daily from postnatal day 23 to day 52. ASD-like behaviors were assessed by social interaction, spontaneous grooming test, open field test and light-dark transitions. The activity of AMP-activated protein kinase (AMPK) was quantified by measuring the level of p-AMPK using an immunoblotting assay. ResultsChronic administration of low dose aspirin resulted in significant improvements in social approach deficits, a reduction in repetitive grooming, and the alleviation of anxiety-like behavior in ASD rats. Furthermore, aspirin administration also led to the activation of AMPK in the hippocampus of rats exposed to VPA. ConclusionsThese results raise the question of the need for further investigation of agents with mechanisms related to aspirin in ASD.