Expectations shape our perception, profoundly influencing how we interpret the world. Positive expectations about sensory stimuli can alleviate distress and reduce pain through what’s known as the placebo effect, while negative expectations may heighten anxiety and exacerbate pain. In the new study, Luo, Kishida, and colleagues investigated the impact of the hedonic aspect of expectations on subjective experiences.

Specifically, the researchers measured neurobehavioral responses to the taste of hot sauce among individuals with a wide range of taste preferences. In total, 47 participants completed the tasks while undergoing functional magnetic resonance imaging scanning. The researchers identified participants who liked versus those who strongly disliked spicy flavors and provided contextual cues about the spiciness of the sauce to be tasted. That way, they were able to dissociate the effects of positive and negative expectations from sensory stimuli (i.e., visual and taste stimuli), which were the same across all participants.

The results showed that positive expectations lead to modulations in the intensity of subjective experience. These modulations were accompanied by increased activity in brain regions previously linked to pleasure, information integration, and the placebo effect, including the anterior insula, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex. By contrast, negative expectations decreased hedonic experience and increased neural activity in the Neurological Pain Signature network.

Taken together, these findings demonstrate that hedonic aspects of one’s expectations asymmetrically shape how the brain processes sensory input and associated behavioral reports of one’s subjective experiences of intensity, pleasure, and pain. The results suggest a dissociable impact of hedonic information. While positive expectations facilitate higher-level information integration and reward processing, negative expectations prime lower-level processes related to pain and emotions. According to the authors, this study demonstrates the powerful role of hedonic expectations in shaping subjective reality and suggests potential avenues for consumer and therapeutic interventions targeting expectation-driven neural processes.

The authors add, “Our study highlights how hedonic expectations shape subjective experiences and neural responses, offering new insights into the mechanisms behind pain perception.”

‘We wanted to go beyond isolated events,’ says research leader Ana Triana. ‘Our behaviour and mental states are constantly shaped by our environment and experiences. Yet, we know little about the response of brain functional connectivity to environmental, physiological, and behavioral changes on different timescales, from days to months.’

The study found that our brains do not respond to daily life in immediate, isolated bursts. Instead, brain activity evolves in response to sleep patterns, physical activity, mood, and respiration rate over many days. This suggests that even a workout or a restless night from last week could still affect your brain — and therefore your attention, cognition and memory — well into next week.

The research also revealed a strong link between heart rate variability — a measure of the heart’s adaptability — and brain connectivity, particularly during rest. This suggests that impacts on our body’s relaxation response, like stress management techniques, could shape our brain’s wiring even when we are not actively concentrating on a task. Physical activity was also found to positively influence the way brain regions interact, potentially impacting memory and cognitive flexibility. Even subtle shifts in mood and heart rate left lasting imprints for up to fifteen days.

Study goes beyond a snapshot

The research is unusual in that few brain studies involve detailed monitoring over days and weeks. ‘The use of wearable technology was crucial’, says Triana. ‘Brain scans are useful tools, but a snapshot of someone lying still for half an hour can only show so much. Our brains do not work in isolation.’

Triana was herself the subject of the research, monitored as she went about her daily life. Her unique role as both lead author and study participant added complexity, but also brought firsthand insights into how best to maintain research integrity over several months of personalized data collection.

‘At the beginning, it was exciting and a bit stressful. Then, routine settles in and you forget,’ says Triana. Data from the devices and twice-weekly brain scans were complemented by qualitative data from mood surveys.

The researchers identified two distinct response patterns: a short-term wave lasting under seven days and a long-term wave up to fifteen days. The former reflects rapid adaptations, like how focus is impacted by poor sleep, but it recovers quickly. The long wave suggests more gradual, lasting effects, particularly in areas tied to attention and memory.

Single-subject studies offer opportunities for improving mental health care

The researchers hope their innovative approach will inspire future studies that combine brain data with everyday life to help personalise mental health treatment.

‘We must bring data from daily life into the lab to see the full picture of how our habits shape the brain, but surveys can be tiring and inaccurate,’ says study co-author, neuroscientist and physician Dr Nick Hayward. ‘Combining concurrent physiology with repeated brain scans in one person is crucial. Our approach gives context to neuroscience and delivers very fine detail to our understanding of the brain.’

The study is also a proof-of-concept for patient research. Tracking brain changes in real time could help detect neurological disorders early, especially mental health conditions where subtle signs might be missed.

“Linking brain activity with physiological and environmental data could revolutionize personalized healthcare, opening doors for earlier interventions and better outcomes,” says Triana.

Ribosomes turn upside-down in hungry cells

Scientists have observed that yeast cells have a remarkable adaptation to starvation: their mitochondria get coated by a swarm of massive molecular complexes called ribosomes. Intrigued by this odd phenomenon, the Mattei Team at EMBL Heidelberg and the Jomaa Lab at the University of Virginia School of Medicine explored it in greater detail using single-particle cryo-electron microscopy and cryo-electron tomography.

Ribosomes are the cell’s heavyweight molecular machinery that produces proteins. It turned out, however, that in hungry yeast cells, the ribosomes that crowd on the surface of the mitochondria don’t produce anything. They are hibernating.

“One way for a cell to survive stressful conditions until better days is to reduce its use of energy to a minimum,” explained Olivier Gemin, EIPOD Postdoctoral Fellow in the Mattei Team who led this new study. “Producing proteins demands a lot of energy, which can be saved by blocking ribosomes.”

Why the hibernating ribosomes attach to the surface of mitochondria is a mystery.

“There could be different explanations,” said Team Leader Simone Mattei. “A starved cell will eventually start digesting itself, so the ribosomes might be coating the mitochondria to protect them. They might also attach to trigger a signalling cascade inside the mitochondria.”

Another possibility that Mattei is investigating relates to the fact that starving cells need a way to quickly start producing energy once food (in the form of glucose) is available again. Since mitochondria are the energy producers of the cell, having ribosomes nearby to produce necessary proteins might help this process along.

What made the scientists’ jaws drop was noticing that the ribosomes attach to the mitochondrial outer membrane in a way that contradicts what’s been known about them before.

“So far, ribosomes were known to interact with membranes only via their large subunit. But in starved cells, we saw that they do this upside-down, via the small subunit!” said Mattei.

In their future studies, the team will investigate how and why the ribosomes attach in such an unusual way.

Cancer cells go through the hell they create

The struggles of the starved yeast cells have some similarities to those of cancer cells.

Believe it or not, being a cancer cell is really tough. When a tumour becomes aggressive, its cells grow so rapidly that their demand for nutrients and oxygen outpaces the supply. This means most cancer cells are constantly starving in a kind of hell they create for themselves.

Yet, they survive and even multiply.

“That’s why we need to understand the basics of adaptation to starvation and how these cells become dormant to stay alive and avoid death,” said Ahmad Jomaa, Assistant Professor and Group Leader at the University of Virginia’s School of Medicine and a senior co-author of the study. “For that, we use yeast first, because we can manipulate it much more easily. Beyond this, we try to starve cultured cancer cells too, which is not easy, to figure out how they overcome starvation and can sometimes lead to cancer relapse.”

Understanding the principles of this adaptation could help us find ways to override it, making cancer cells vulnerable to starvation and thus more susceptible to treatment.