Many of our efforts in social interactions are dedicated to learning about others. Adolescents with autism have core deficits in social learning, but a mechanistic understanding of these deficits and how they relate to neural development is lacking. The present study aimed to specify how adolescents with and without autism represent and acquire social knowledge and how these processes are implemented in neural activity. Typically developing adolescents (n = 26) and adolescents with autism spectrum disorder (ASD) (n = 20) rated in the magnetic resonance scanner how much 3 peers liked a variety of items and received trial-by-trial feedback about the peers' actual preference ratings. In a separate study, we established the preferences of a new sample of adolescents (N = 99), used to examine population preference structures. Using computational models, we tested whether participants in the magnetic resonance study relied on preference structures during learning and how model predictions were implemented in brain activity. Typically developing adolescents relied on average population preferences and prediction error updating. Importantly, prediction error updating was scaled by the similarity between items. In contrast, preferences of adolescents with ASD were best described by a No-Learning model that relied only on the participant's own preferences for each item. Model predictions were encoded in neural activity. Typically developing adolescents encoded prediction errors in the putamen, and adolescents with ASD showed greater encoding of own preferences in the angular gyrus. We specified how adolescents represent and update social knowledge during learning. Our findings indicate that adolescents with ASD rely only on their own preferences when making social inferences.

The ability of herpes simplex virus (HSV) to establish lifelong latency in sensory neurons makes it one of the most pervasive viruses worldwide. Although most HSV infections are asymptomatic or cause limited cutaneous symptoms, some give rise to serious central nervous system (CNS) manifestations. Both primary HSV infection and subsequent reactivation events can cause viral replication and spread within the brain, ultimately leading to pathologic inflammation and direct CNS damage. In addition to fulminant presentations of HSV encephalitis, subclinical HSV CNS infections have been implicated in neurodevelopmental, cognitive, and neurodegenerative impairment. Here, we review the pathogenesis of HSV infection and resulting CNS manifestations across the human lifespan. Identifying the mechanisms of HSV-induced CNS damage, and therefore the populations at highest risk for neurological morbidity, may provide a better understanding of the role viruses play in neurological diseases and inform novel approaches to treatment.

Inflammation and mitochondrial-dependent oxidative stress are interrelated processes implicated in multiple neuroinflammatory disorders, including Alzheimer’s disease (AD) and depression. Exposure to elevated temperature (hyperthermia) is proposed as a non-pharmacological, anti-inflammatory treatment for these disorders; however, the underlying mechanisms are not fully understood. Here we asked if the inflammasome, a protein complex essential for orchestrating the inflammatory response and linked to mitochondrial stress, might be modulated by elevated temperatures. To test this, in preliminary studies, immortalized bone-marrow-derived murine macrophages (iBMM) were primed with inflammatory stimuli, exposed to a range of temperatures (37–41.5 °C), and examined for markers of inflammasome and mitochondrial activity. We found that exposure to mild heat stress (39 °C for 15 min) rapidly inhibited iBMM inflammasome activity. Furthermore, heat exposure led to decreased ASC speck formation and increased numbers of polarized mitochondria. These results suggest that mild hyperthermia inhibits inflammasome activity in the iBMM, limiting potentially harmful inflammation and mitigating mitochondrial stress. Our findings suggest an additional potential mechanism by which hyperthermia may exert its beneficial effects on inflammatory diseases.

Neonatal herpes simplex virus (nHSV) is a devastating infection impacting approximately 14,000 newborns globally each year. Infection is associated with high neurologic morbidity and mortality, making early intervention and treatment critical. Clinical outcomes of symptomatic nHSV infections are well-studied, but little is known about the frequency of, or outcomes following, sub-clinical or asymptomatic nHSV. Given the ubiquitous nature of HSV infection and frequency of asymptomatic shedding in adults, subclinical infections are underreported, yet could contribute to long-term neurological damage. To assess potential neurological morbidity associated with subclinical nHSV infection, we developed a low-dose (100 PFU) HSV infection protocol in neonatal C57BL/6 mice. At this dose, HSV DNA was detected in the brain by PCR but was not associated with acute clinical symptoms. However, months after initial inoculation with 100 PFU of HSV, we observed impaired mouse performance on a range of cognitive and memory performance tasks. Memory impairment was induced by infection with either HSV-1 or HSV-2 wild-type viruses, but not by a viral mutant lacking the autophagy-modulating Beclin-binding domain of the neurovirulence gene γ34.5. Retroviral expression of wild type γ34.5 gene led to behavioral pathology in mice, suggesting that γ34.5 expression may be sufficient to cause cognitive impairment. Maternal immunization and HSV-specific antibody treatment prevented offspring from developing neurological sequelae following nHSV-1 infection. Altogether, these results support the idea that subclinical neonatal infections may lead to cognitive decline in adulthood, with possible profound implications for research on human neurodegenerative disorders such as Alzheimer’s Disease.

Background: Many of our efforts in social interactions are dedicated to learning about others. Adolescents with autism have core deficits in social learning, but a mechanistic understanding of these deficits and how they relate to neural development is lacking. The current study aimed to specify how adolescents with and with autism represent and acquire social knowledge and how these processes are implemented in neural activity.Methods: Typically developing (TD) adolescents (N=26) and adolescents with autism (N=20) rated in the MR scanner how much three peers liked a variety of items and received trial-by-trial feedback about the peer’s actual preference ratings. In a separate study, we established the preferences of a new sample of adolescents (N=99), used to examine population preference structures. Using computational models, we tested whether participants in the MR study relied on preference structures during learning and how model predictions were implemented in brain activity.Results: TD adolescents relied on average population preferences and prediction error (PE) updating. Importantly, PE updating was scaled by the similarity between items. In contrast, preferences of adolescents with autism were best described by a No-learning model that relied only on participants own preferences for each item. Model predictions were encoded in neural activity. TD adolescents encoded PEs in the putamen and adolescents with autism showed greater encoding of own preferences in the angular gyrus.Conclusions: We specified how adolescents represent and update social knowledge during learning. Our findings indicate that adolescents with ASD rely only on their own preferences when making social inferences.