Personalized mRNA Vaccine Shows Promise Against Melanoma: Moderna and Merck say their personalized mRNA cancer vaccine improved outcomes in a Phase 3 trial involving 1,137 patients with surgically removed stage IIB–IV melanoma. Patients received either the individualized vaccine, intismeran, plus Merck’s immunotherapy Keytruda, or Keytruda alone. According to an interim analysis, the combination significantly extended both recurrence-free survival and distant metastasis-free survival, although the companies have not yet released detailed results. Intismeran is customized to encode as many as 34 mutations unique to each patient’s tumor, training the immune system to recognize cancer-specific proteins. Earlier Phase 2 data showed a 49 percent reduction in recurrence or death and a 59 percent reduction in distant metastasis or death. Experts called the Phase 3 result significant but cautioned that survival and subgroup data remain pending. (Ars Technica)

China Tests Chemogenetic Brain Therapies in Humans: At least seven clinical trials in China are testing chemogenetic therapies that allow doctors to selectively suppress targeted brain circuits, marking the first known clinical use of a technology long confined to neuroscience research. The approach uses engineered receptors called DREADDs, introduced into selected neurons with viral vectors. A drug such as clozapine can then activate the receptors and reduce signaling specifically in those cells. Trials are targeting conditions including drug-resistant epilepsy, Parkinson’s disease, and neuropathic pain, potentially offering an alternative to destructive brain surgery. Researchers caution that viral gene delivery can provoke serious immune reactions and that human safety remains uncertain. Still, if successful, the technique could establish a new class of highly targeted, circuit-based treatments for neurological and psychiatric disorders. (C&EN)

Scientists Model How One Thought Becomes Another: Researchers studying the seemingly continuous “stream of thought” have identified a possible computational mechanism governing when one thought gives way to another. Participants either generated words freely or let their minds wander during brief sessions, pressing a key whenever they noticed a transition between coherent thought episodes. The distribution of those transition times was best explained by an accumulation-to-threshold model: information appears to build until some internal boundary is reached, triggering a shift in thought. Intriguingly, people with a greater self-reported tendency toward disorganized thinking tended to have lower inferred transition thresholds. The researchers caution that the nature of the accumulating signal remains unknown, but the work offers a rare quantitative framework for studying how spontaneous conscious experience unfolds through time. (OUP Academic)

Severe Amnesia May Fragment Conscious Experience: Three patients with profound anterograde amnesia repeatedly reported feeling as though they had only just awakened, suggesting that memory loss can disrupt more than recollection—it may alter the perceived continuity of consciousness itself. All three had suffered autoimmune encephalitis producing extensive bilateral inflammation of the hippocampus. Their experiences recalled the famous case of musician Clive Wearing, who repeatedly recorded statements equivalent to “I am now awake” after catastrophic memory damage. Researchers propose calling the phenomenon “Stream of Consciousness Impairment.” Normally, new experiences are continuously integrated with immediately preceding ones, creating a sense of mental continuity. When hippocampal memory mechanisms are devastated, that stitching process may fail, leaving successive conscious moments feeling disconnected from one another. The cases highlight memory’s potentially fundamental role in constructing a continuous subjective present. (OUP Academic)

Flexible Brain Circuits Reuse Cognitive Building Blocks: The brain may achieve its extraordinary flexibility partly by reusing the same neural circuitry for very different mental operations. MIT and Princeton researchers studying mice identified populations of prefrontal cortex neurons that could store either sensory information or plans for future actions in working memory. Rather than maintaining completely separate neural populations for each type of content, the brain appears able to redeploy common computational modules depending on what a task requires. That supports the longstanding idea of cognitive “compositionality,” in which reusable neural building blocks are combined in different ways to generate complex behavior. Such an architecture could explain how a limited number of brain circuits supports the enormous variety of activities humans and other animals perform, from recalling information to planning actions and adapting rapidly to new circumstances. (MIT News)

Brain Maintains Goals Using Two Neural Codes: How does the brain remember what it is doing for minutes at a time without constant reminders? Researchers recording individual neurons in epilepsy patients found that the hippocampus and medial frontal cortex maintain task context in strikingly different ways. When instructions were explicitly provided, hippocampal representations changed rapidly over time, while medial frontal cortex activity remained comparatively stable. But when participants had to infer an underlying context themselves, the hippocampus switched to a more stable coding strategy. The findings suggest that the brain does not rely on a single mechanism for sustaining goal-directed behavior. Instead, neural representations can be either dynamic or persistent depending on task demands. Such flexibility may allow people to maintain intentions while simultaneously incorporating new information—a fundamental requirement for planning, working memory and extended purposeful behavior. (Nature)

Music Creates Shared Stories Inside Human Brains: Music may generate surprisingly similar imagined worlds in different listeners. Researchers asked 20 people undergoing fMRI scans to listen to unfamiliar instrumental excerpts and imagine each piece as a story. Participants later described what they imagined, and the accounts showed substantial agreement: about 71 percent matched previously established consensus narratives for the musical excerpts. When participants heard spoken versions of those narratives, agreement rose to 94 percent. Brain imaging revealed stimulus-specific activity in auditory regions but, crucially, shared patterns across music, speech and recalled stories in the default mode network and association cortex. The findings suggest that musical meaning extends beyond sound processing. Music appears capable of generating higher-order, modality-independent representations resembling the semantic “gist” produced by language, providing a window into shared imagination and subjective meaning-making. (Nature)

New Microscope Captures Brain Electricity in Milliseconds: A new high-speed imaging system could let neuroscientists watch electrical activity unfold across nearly an entire vertebrate brain at once. MIT researchers modified a microscopy approach to record voltage changes throughout the brains of zebrafish, capturing neural events at millisecond timescales. Traditional calcium imaging can reveal which neurons are active but responds relatively slowly compared with the electrical impulses neurons actually use to communicate. The new approach more directly tracks those rapid signals across widely distributed neural populations. In experiments, researchers observed brain-wide activity patterns triggered when zebrafish were exposed to ultraviolet light. Mapping such activity could eventually help reveal how networks distributed across different brain regions cooperate to produce perception, memory, decisions and emotion. The technology offers a new route toward studying cognition as an emergent whole-brain process. (MIT News)

Human Neurons May Be Tiny Biological Computers: Individual human neurons may possess substantially greater computational power than comparable cells in rats, suggesting human intelligence depends not only on brain size and connectivity but also on unusually sophisticated cellular machinery. Researchers developed a deep-learning-based “Functional Complexity Index” that measures how difficult it is for an artificial neural network to reproduce a biological neuron’s input-output behavior. Human cortical pyramidal neurons scored significantly higher than rat neurons. Their advantage appeared to stem largely from larger and more elaborate dendritic trees and stronger nonlinear signaling involving NMDA receptors. The results imply that single neurons are not merely simple switches embedded within an intelligent network; each may perform complex computations locally. Researchers say such biological architecture could also inspire future artificial-intelligence systems built from computationally richer artificial neurons rather than today’s comparatively simple units. (PubMed Central (PMC))

Estrogen Therapy Linked With Less Alzheimer’s Pathology: A large retrospective analysis has found an association between estrogen-only hormone therapy and lower levels of dementia and Alzheimer’s-related brain pathology, though researchers stress the results do not prove hormone therapy prevents the disease. Investigators examined data from 21,462 women, including thousands who later underwent autopsy and hundreds who received brain scans or biomarker testing. Estrogen users had 39 percent lower odds of a dementia diagnosis and 35 percent lower odds of showing Alzheimer’s pathology at autopsy after researchers adjusted for several factors. Biomarkers also suggested less amyloid accumulation. However, participants generally began treatment much later in life than women typically do today, making direct clinical recommendations inappropriate. The study nevertheless adds important evidence to the complicated relationship between estrogen, aging, memory and neurodegeneration. (ScienceDaily)

Brain Separates Pleasant and Unpleasant Value Signals: Human decisions may depend on partly separate neural systems for evaluating desirable and undesirable possibilities. Researchers recorded intracranial brain activity from participants with implanted electrodes while they rated pleasant and unpleasant scenarios and made choices between options. Activity in the ventromedial prefrontal cortex tracked positive value, particularly the attractiveness of pleasant choices. By contrast, activity in the anterior insula tracked unpleasant value and the degree to which undesirable possibilities should be avoided. The two systems became especially distinct when the emotional nature of an option conflicted with the way a choice was framed. The findings challenge a purely unified model in which one brain circuit simply assigns everything a single value score. Instead, decision-making may combine complementary systems specialized for pursuing desirable outcomes and avoiding bad ones. (Nature)

Falling Confidence May Foreshadow OCD Symptoms: Drops in confidence may precede episodes of obsessive-compulsive symptoms rather than simply resulting from them. Researchers followed 137 people with obsessive-compulsive disorder for two weeks using smartphone-based assessments. Participants logged symptom episodes, completed daily questionnaires and periodically performed a perceptual decision-making task designed to measure metacognition—the ability to judge the accuracy of one’s own decisions. Both self-reported confidence and experimentally measured metacognitive confidence tended to decline before participants subsequently reported OCD symptoms. The reverse pattern was not observed: symptom episodes did not reliably predict later reductions in confidence. The researchers also found that laboratory measures of decision confidence corresponded with participants’ subjective confidence in everyday life. While the study does not establish a single cause of OCD, it suggests fluctuating metacognitive uncertainty could potentially provide an early warning signal for symptom escalation. (Nature)