One of the most-viewed PNAS articles in the last week is “Locus coeruleus–amygdala circuit disrupts prefrontal control to impair fear extinction.” Explore the article here: https://ow.ly/yFH250Ywubb.
Stress undermines extinction learning and hinders exposure-based clinical therapies for a variety of neuropsychiatric disorders. In both animals and humans, dysfunction in the ventromedial prefrontal cortex (vmPFC) contributes to stress-impaired extinction, but the neural circuit by which stress modulates vmPFC function is not known. We hypothesize that locus coeruleus (LC) norepinephrine undermines extinction learning by recruiting projections from the basolateral amygdala (BLA) to vmPFC. Using a combination of circuit-specific chemogenetics and calcium imaging, we find that activation of LC noradrenergic neurons mimics a behavioral stressor (footshock), induces freezing behavior, reduces spontaneous neuronal activity in the vmPFC, impairs extinction learning, and alters the population dynamics of vmPFC ensembles.
Amyloid beta deposition between neurons and tau aggregation within neurons are both hallmarks of Alzheimer’s disease, and evidence suggests that the latter is potentially more significant than the former [1]. While some potential therapies have been discovered that may disaggregate these tau tangles after they have formed [2], no therapy has yet been approved by the FDA to do this.
Maternal immune activation (MIA) during pregnancy perturbs fetal neurodevelopment, with natural killer (NK) cells emerging as key contributors to neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD).
Clinical studies consistently report NK cell dysfunction in ASD patients and their mothers, characterized by altered cytotoxicity, hyperactivation at rest, functional exhaustion on stimulation, and skewed receptor/genetic profiles.
Uterine NK (uNK) cells, indispensable for placental and fetal development, can paradoxically promote NDDs when hyperactivated, releasing granzyme B (GZMB) that disrupts fetal brain structure and function.
Maternal immune activation (MIA), triggered by infection or inflammation during pregnancy, is a well-recognized risk factor for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Clinical cohort studies and rodent models suggest that natural killer (NK) cells play a significant role in NDD pathogenesis, but the underlying mechanisms remain poorly defined. Here, we summarize the key immune mediators involved in MIA-induced NDDs, emphasizing microglia as a central hub. We then examine emerging evidence implicating aberrant NK cell activation in ASD, underscoring their overlooked contribution to impaired neurodevelopment. Finally, we discuss potential mechanisms of NK cell–microglia crosstalk in NDDs. Elucidating these interactions in the context of MIA will be crucial for developing preventive and therapeutic strategies against inflammation-driven NDDs.
Among adults with DownSyndrome, clinical and biological staging of AlzheimerDisease showed greater concordance compared to sporadic cases, supporting the use of cognition-based staging for clinical trial enrollment. Most discordant cases exhibited more advanced pathology than clinical stage, highlighting resilience mechanisms in this population.
This cross-sectional study examines data for participants in the Alzheimer Biomarker Consortium–Down Syndrome study to gauge the concordance of clinical and biological Alzheimer disease staging.
New in JNeurosci from Kosteletou-Kassotaki et al: A white matter tract connecting the inferior colliculus to the basolateral amygdala via the MGB of the thalamus is linked to better hearing ability and higher self-reported fearfulness in people.
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Rapid and efficient fear processing is essential for survival. In vision, this function is supported by a well-characterized subcortical pathway consisting of direct projections from the pulvinar of the thalamus to the amygdala in the human brain. In contrast, the existence of an analogous shortcut for fear in audition has been demonstrated in non-human animals, but remains unconfirmed in humans. To address this question, we used probabilistic streamline tractography and fixel-based analysis on diffusion-weighted images from Human Connectome Project participants of either sex, to reconstruct candidate auditory subcortical pathways and examine their associations with affective and auditory behavioral measures. Our findings revealed a robust white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body (MGB) of the thalamus. Remarkably, higher fiber density in this tract was associated with better hearing ability in noise and increased self-reported fearfulness, supporting its role in auditory and affective function. Conversely, a control analysis of the core thalamocortical pathway from ventral MGB to primary auditory cortex (PAC), representing the main route for auditory processing, was associated with auditory ability but not with affective measures. These findings provide previously unreported evidence for an auditory colliculo-geniculo-amygdala “low road” in humans, aligning with evolutionarily conserved pathways for fear described in non-human species.
Significance Statement Rapid fear processing is crucial for survival. While a visual subcortical “low road” for fear is well characterized in humans, the existence of an analogous human auditory shortcut remains undetermined. Using diffusion magnetic resonance imaging tractography, we provide evidence for a white matter tract connecting the inferior colliculus to basolateral amygdala via the medial geniculate body of the thalamus, which is associated with hearing ability and self-reported fearfulness. Our findings provide novel evidence for an auditory colliculo-geniculo-amygdala direct route in humans, revealing an evolutionarily conserved pathway for fear previously described in non-human species.
GLP-1 medications used to treat diabetes and obesity were associated with a reduced need for hospital care and sickness absence due to psychiatric reasons, a new study shows. The large register-based study was carried out in collaboration between the University of Eastern Finland, Karolinska Institutet in Stockholm and Griffith University in Australia.
Diabetes and obesity are associated with an increased risk of mental health symptoms, and similarly, individuals with mental disorders have an elevated risk of metabolic diseases such as obesity and diabetes. Researchers have long been interested in the connections between these conditions and in how pharmacological treatments may affect both metabolic and mental health disorders.
The present study included nearly 100,000 participants, more than 20,000 of whom had used GLP-1 medications. Participants were followed through Swedish national registers between 2009 and 2022. The study’s findings were published in The Lancet Psychiatry.
Slavoj Žižek, Carlo Rovelli, Alenka Zupančič debate subjectivity, and how it relates to the world around it.
What does the hard problem get wrong?
With a free trial, you can watch the full debate NOW at https://iai.tv/video/the-self-and-the… tend to think of ourselves as observers of the world and experience as something different from the material stuff that makes up reality. Yet at the same time as human beings, we are at once part of the universe and part of that reality. And this profoundly puzzling relationship, that we are both part of something and yet separate from it, has been at the centre of Western thought. Materialists claim there is only physical material. But if so, thought, experience, and consciousness become illusory. Idealists argue there is only consciousness, but then it is reality that becomes an illusion. While dualists hold that both the self and the world exist, but that the connection between the two is mysterious. Is the self part of the world or necessarily outside of it? Was Kant right that the distinction between subject and object is necessary for experience to be possible? Or are these deep metaphysical questions beyond us, and our theories and language incapable of uncovering the ultimate state of things? #zizek #philosophy #physics #consciousness #quantum #quantumphysics Slavoj Žižek is one of the most famous philosophers in the world and is the author of more than 50 books, including most recently at the time of the debate Zero Point. Alenka Zupančič is a leading Lacanian philosopher and social theorist. She is a professor at The European Graduate School and at the University of Nova Gorica. Joining from America, Carlo Rovelli is a leading theoretical physicist, the author of several best-selling books, and a founding figure in the field of quantum gravity. His recent book, Reality Is Not What It Seems, has ethical implications for the nature of the self and personal identity. Jack Symes hosts. 00:00 Introduction 00:37 Carlo Rovelli on reality 05:22 Alenka Zupančič: is our knowledge incomplete, or reality itself? 07:55 Slavoj Žižek: how can a stone have freedom? 09:28 Carlo Rovelli on freedom 11:17 Can we ever resolve the relationship between the self and the world around us? 11:35 The problem with David Chalmers The Institute of Art and Ideas features videos and articles from cutting edge thinkers discussing the ideas that are shaping the world, from metaphysics to string theory, technology to democracy, aesthetics to genetics. Subscribe today! https://iai.tv/subscribe?utm_source=Y… For debates and talks: https://iai.tv For articles: https://iai.tv/articles For courses: https://iai.tv/iai-academy/courses.
We tend to think of ourselves as observers of the world and experience as something different from the material stuff that makes up reality. Yet at the same time as human beings, we are at once part of the universe and part of that reality. And this profoundly puzzling relationship, that we are both part of something and yet separate from it, has been at the centre of Western thought. Materialists claim there is only physical material. But if so, thought, experience, and consciousness become illusory. Idealists argue there is only consciousness, but then it is reality that becomes an illusion. While dualists hold that both the self and the world exist, but that the connection between the two is mysterious.
Is the self part of the world or necessarily outside of it? Was Kant right that the distinction between subject and object is necessary for experience to be possible? Or are these deep metaphysical questions beyond us, and our theories and language incapable of uncovering the ultimate state of things?
Despite denying any conscious awareness of the bar, the participant could answer correctly at a level well above chance. The participant even showed evidence of being able to pay attention to the bar – they were faster to respond when an arrow (placed in a healthy area of their visual field) correctly indicated the location of the bar.
The most popular interpretation (though not the only one) is that people with blindsight can see these objects, but not see them consciously. They see what is there, but it all goes on unconsciously, below their awareness.
The phenomenon of inattentional blindness seems to show you can see without the information crossing into your consciousness. Anyone can experience inattentional blindness. The phenomenon has been known about for a long time, but we can most easily get a handle on it by looking at a well-known experiment reported in 1999.
Patients with leptomeningeal metastasis (LM) have historically had few treatment options. Now, researchers from The University of Texas MD Anderson Cancer Center have found a combination of targeted therapies, tucatinib and trastuzumab, plus the chemotherapy drug, capecitabine, may improve symptoms and extend survival in some breast cancer patients with LM.
The Phase II study, published today in Nature Cancer, included 17 female patients with newly diagnosed LM and HER2+ breast cancer. Median overall survival (OS) in those treated with the combination therapy increased from a historical average of 4.4 months to 10 months. At the 18-month mark, 41% of patients were still alive. Under the combination treatment, disease progression also stalled, with a median of seven months before central nervous system progression, and 7 of 12 evaluable patients also had improved neurologic deficits.
“The combination achieved a clinically meaningful improvement in overall survival compared to historical controls,” said lead author Rashmi Murthy, M.D., associate professor of Breast Medical Oncology. “For these patients, who often face limited treatment options, our results represent a step forward, offering new hope in how we treat and manage leptomeningeal metastasis.”
