This approach has produced major breakthroughs. However, it has not fully explained a central feature of human thinking: how all these separate systems come together to form a single, unified mind.

Researchers at the University of Notre Dame set out to address that question. Using advanced neuroimaging, they examined how the brain is organized overall and how that organization gives rise to intelligence.

“Neuroscience has been very successful at explaining what particular networks do, but much less successful at explaining how a single, coherent mind emerges from their interaction,” said Aron Barbey, the Andrew J. McKenna Family Professor of Psychology in Notre Dame’s Department of Psychology.

General Intelligence and Connected Cognitive Abilities

Psychologists have long observed that skills like attention, memory, perception, and language tend to be linked. People who perform well in one area often perform well in others. This pattern is known as “general intelligence.” It influences how effectively individuals learn, solve problems, and adapt across academic, professional, social, and health settings.

For more than a century, this pattern has suggested that human cognition is unified at a deep level. What scientists have lacked is a clear explanation for why that unity exists.

“The problem of intelligence is not one of functional localization,” said Barbey, who also directs the Notre Dame Human Neuroimaging Center and the Decision Neuroscience Laboratory. “Contemporary research often asks where general intelligence originates in the brain — focusing primarily on a specific network of regions within the frontal and parietal cortex. But the more fundamental question is how intelligence emerges from the principles that govern global brain function — how distributed networks communicate and collectively process information.”

To explore this broader perspective, Barbey and his team, including lead author and Notre Dame graduate student Ramsey Wilcox, tested a framework known as the Network Neuroscience Theory. Their findings were published in Nature Communications.

The Network Neuroscience Theory Explained

According to the researchers, general intelligence is not a specific ability or mental strategy. Instead, it reflects a pattern in which many cognitive skills are positively related. They propose that this pattern stems from how efficiently the brain’s networks are structured and how well they work together.

To evaluate this idea, the team analyzed brain imaging and cognitive performance data from 831 adults in the Human Connectome Project. They also examined an independent group of 145 adults in the INSIGHT Study, funded by the Intelligence Advanced Research Projects Activity’s SHARP program. By combining measures of brain structure and brain function, the researchers created a detailed picture of large-scale brain organization.

Rather than tying intelligence to a single brain region or function, the Network Neuroscience Theory views it as a property of the brain as a whole. Intelligence, in this framework, depends on how effectively networks coordinate and reorganize themselves to handle different challenges.

Barbey and Wilcox describe this as a major shift in perspective.

“We found evidence for system-wide coordination in the brain that is both robust and adaptable,” Wilcox said. “This coordination does not carry out cognition itself, but determines the range of cognitive operations the system can support.”

“Within this framework, the brain is modeled as a network whose behavior is constrained by global properties such as efficiency, flexibility and integration,” Wilcox said. “These properties are not tied to individual tasks or brain networks, but are characteristics of the system as a whole, shaping every cognitive operation without being reducible to any one of them.”

“Once the question shifts from where intelligence is to how the system is organized,” Wilcox noted, “the empirical targets change.”

Intelligence as Whole Brain Coordination

The findings supported four main predictions of the Network Neuroscience Theory.

First, intelligence does not reside in a single network. It arises from processing distributed across many networks. The brain must divide tasks among specialized systems and combine their outputs when necessary.

Second, successful coordination requires strong integration and long-distance communication. Barbey described “a large and complex system of connections that serve as ‘shortcuts’ linking distant brain regions and integrating information across the networks.” These connections allow far apart areas of the brain to exchange information efficiently, supporting unified processing.

Third, integration depends on regulatory regions that guide how information flows. These hubs help orchestrate activity across networks, selecting the right systems for the job. Whether someone is interpreting subtle clues, learning a new skill, or deciding between careful analysis and quick intuition, these regulatory areas help manage the process.

Finally, general intelligence depends on balancing local specialization with global integration. The brain performs best when tightly connected local clusters operate efficiently while still maintaining short communication paths to distant regions. This balance supports flexible and effective problem solving.

Across both groups studied, differences in general intelligence consistently matched these large-scale organizational features. No single brain area or traditional “intelligence network” explained the results.

“General intelligence becomes visible when cognition is coordinated,” Barbey noted, “when many processes must work together under system-level constraints.”

Implications for Artificial Intelligence and Brain Development

The implications extend beyond understanding human intelligence. By focusing on large-scale brain organization, the findings offer insight into why the mind functions as a unified system in the first place.

This perspective may also explain why intelligence tends to increase during childhood, decline with aging, and be especially vulnerable to widespread brain injury. In each situation, what changes most is large-scale coordination rather than isolated functions.

The results also contribute to debates about artificial intelligence. If human intelligence depends on system-level organization rather than a single general-purpose mechanism, then building artificial general intelligence may require more than simply scaling up specialized tools.

“This research can push us into thinking about how to use design characteristics of the human brain to motivate advances in human-centered, biologically inspired artificial intelligence,” Barbey said.

“Many AI systems can perform specific tasks very well, but they still struggle to apply what they know across different situations.” Barbey said. “Human intelligence is defined by this flexibility — and it reflects the unique organization of the human brain.”

The research was conducted with co-authors Babak Hemmatian and Lav Varshney of Stony Brook University.

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Jellyfish galaxies get their name from the long, flowing streams of gas that stretch out behind them, resembling tentacles. These galaxies race through crowded galaxy clusters filled with extremely hot gas. As they move, that surrounding gas pushes against them like a powerful headwind, sweeping their own gas backward into trailing strands. Astronomers call this process ram-pressure stripping.

This newly identified galaxy sits at z = 1.156, which means its light has traveled for 8.5 billion years to reach us. In other words, we are seeing it as it appeared when the universe was much younger.

The observation offers an unusual glimpse into how galaxies were reshaped long ago and raises new questions about what conditions were really like 8.5 billion years in the past.

A Clear View Into the Distant Universe

The team uncovered the galaxy while studying the COSMOS field — Cosmic Evolution Survey Deep field — a region of the sky that has been examined extensively by multiple telescopes. Astronomers selected this area because it lies far from the crowded plane of the Milky Way, reducing interference from nearby stars and dust. It is also positioned so that telescopes in both hemispheres can observe it, and it lacks bright foreground objects that might block the view. This makes it an ideal window into the distant universe.

“We were looking through a large amount of data from this well-studied region in the sky with the hopes of spotting jellyfish galaxies that haven’t been studied before,” said Dr. Ian Roberts, Banting Postdoctoral Fellow at the Waterloo Centre for Astrophysics in the Faculty of Science. “Early on in our search of the JWST data, we spotted a distant, undocumented jellyfish galaxy that sparked immediate interest.”

Bright Blue Star Formation in Stripped Gas

The galaxy itself has a fairly typical disk shape. What makes it stand out are the bright blue clumps scattered along its trailing streams. These glowing knots are extremely young stars. Their ages indicate they likely formed outside the main body of the galaxy, within the gas that was pushed away. That type of star formation is consistent with what astronomers expect in jellyfish galaxies experiencing ram-pressure stripping.

Rethinking Galaxy Clusters in the Early Universe

Studying this object has challenged previous assumptions about the early universe. Many scientists believed that galaxy clusters at that time were still assembling and that ram-pressure stripping was relatively rare. The new findings suggest otherwise.

“The first is that cluster environments were already harsh enough to strip galaxies, and the second is that galaxy clusters may strongly alter galaxy properties earlier than expected,” Roberts said. “Another is that all the challenges listed might have played a part in building the large population of dead galaxies we see in galaxy clusters today. This data provides us with rare insight into how galaxies were transformed in the early universe.”

If confirmed by further research, these results could reshape understanding of how dense cosmic environments influenced galaxy evolution billions of years ago.

To investigate further, Roberts and his colleagues have applied for additional observing time with JWST to explore this galaxy in greater detail.

The study, “JWST Reveals a Candidate Jellyfish Galaxy at z=1.156,” was published in The Astrophysical Journal.

The findings were published in Nature Communications. The research was led by AnnaLynn Williams, PhD, of the University of Rochester Wilmot Cancer Institute, along with co-corresponding author Kevin Krull, PhD, of St. Jude Children’s Research Hospital.

Lifestyle Changes May Help Reverse Biological Aging

There may be encouraging news ahead. Ongoing work at Wilmot suggests that some of the accelerated aging seen in young survivors could potentially be slowed or even reversed through healthy habits such as quitting smoking, exercising regularly, and improving diet, Williams said.

“Young cancer survivors have many more decades of life to live,” she said. “So, if these accelerated aging changes are occurring early on and setting them on a different trajectory, the goal is to intervene to not only increase their lifespan but improve their quality of life.”

Many survivors treated in childhood or young adulthood are working toward finishing school, launching careers, gaining independence, or starting families. Cognitive challenges can make those milestones harder to reach.

“It’s kind of like a perfect storm,” Williams said. “This is why we see many survivors having worse educational and employment outcomes than their siblings.”

Williams, who is also a cancer survivor, serves as an assistant professor in the Department of Surgery and is part of Wilmot’s Cancer Prevention and Control research program, which focuses on reducing long-term symptoms in survivors.

Study Tracks Long Term Survivors

The study included about 1,400 participants treated at St. Jude. All were at least five years beyond their cancer therapy, and some had survived for decades. Most had been treated for acute lymphoblastic leukemia (ALL) or Hodgkin lymphoma.

Researchers found evidence of faster biological aging regardless of the type of treatment received during childhood. However, chemotherapy was linked to the greatest acceleration. Because chemotherapy can alter DNA structure and cause widespread cellular damage, it appears to have the strongest effect on the aging process.

Biological Age Linked to Brain Function

The investigators also identified a close connection between cellular aging and cognitive performance. Survivors whose biological age was higher than their actual chronological age had more difficulty with memory and attention.

For individuals who received radiation directly to the brain, Williams said the priority is preventing further decline.

Scientists are now trying to pinpoint when accelerated aging begins. That research is ongoing at Wilmot.

In a recent pilot study, Williams examined tissue and cell samples taken before and after treatment from 50 people with Hodgkin lymphoma and compared them with samples from 50 healthy individuals. Working with John Ashton, PhD, MBA, director of the Genomics Shared Resource at Wilmot, she analyzed the data to determine whether the aging process starts during treatment or develops years later.

Other Wilmot researchers are carrying out related studies in women with breast cancer and in older adults with leukemia, aiming to find ways to reverse treatment-related aging. One recent study has already demonstrated that exercise can help counteract aging linked to cancer.

The National Cancer Institute funded Williams’ study.

At the same time, researchers have repeatedly observed high levels of polyamines in many types of cancer, where they are linked to aggressive tumor growth. This contrast has created a scientific puzzle. How can the same molecules that appear to promote longevity also be associated with cancer?

A Molecular Puzzle in Cancer Metabolism

Although the connection between polyamines and cancer has been recognized for years, the detailed mechanisms behind their role in tumor progression have remained unclear. Cancer cells are known to alter their metabolism, relying heavily on aerobic glycolysis to rapidly generate energy. However, exactly how polyamines influence this metabolic shift has not been fully understood.

Adding to the complexity, eIF5A1 has well established functions in normal, healthy cells. A closely related protein, eIF5A2, shares 84% of its amino acid sequence but has been linked to cancer development. Why two nearly identical proteins behave so differently has been a major unanswered question.

Large Scale Proteomic Analysis Reveals Distinct Pathways

To investigate, a team led by Associate Professor Kyohei Higashi from the Faculty of Pharmaceutical Sciences at Tokyo University of Science in Japan carried out an in-depth study using advanced molecular and proteomic methods. Their results were published in Volume 301, Issue 8 of the Journal of Biological Chemistry. The findings clarify how polyamines stimulate cancer cell growth through biological routes that differ from those involved in healthy aging.

The researchers worked with human cancer cell lines to examine how polyamines affect protein production and metabolism. They first reduced polyamine levels using a drug, then restored them by adding spermidine. This approach allowed them to directly measure the impact of polyamines on cancer cells. Using high-resolution proteomic techniques, they analyzed changes across more than 6,700 proteins.

Their results showed that polyamines primarily boost glycolysis, the process that quickly converts glucose into energy, rather than enhancing mitochondrial respiration, which is more closely tied to healthy aging. The team also found that polyamines increase levels of eIF5A2 and five ribosomal proteins, including RPS 27A, RPL36AL, and RPL22L1, all of which are associated with cancer severity.

eIF5A1 vs eIF5A2 in Normal and Cancer Cells

A side by side comparison of eIF5A1 and eIF5A2 provided critical insight. “The biological activity of polyamines via eIF5A differs between normal and cancer tissues,” explains Dr. Higashi. “In normal tissues, eIF5A1, activated by polyamines, activates mitochondria via autophagy, whereas in cancer tissues, eIF5A2, whose synthesis is promoted by polyamines, controls gene expression at the translational level to facilitate the proliferation of cancer cells.”

In other words, polyamines trigger very different effects depending on which protein they influence. In healthy cells, they support cellular maintenance and energy production. In cancer cells, they help drive rapid growth.

How Polyamines Increase eIF5A2

Further experiments uncovered how polyamines raise eIF5A2 levels. Under typical conditions, production of the eIF5A2 protein is restrained by a small regulatory RNA molecule called miR-6514-5p. The researchers found that polyamines disrupt this natural brake, allowing eIF5A2 to be produced in greater amounts. They also showed that eIF5A2 controls a distinct group of proteins compared to eIF5A1, reinforcing the idea that these two similar proteins carry out separate functions.

Implications for Cancer Therapy and Supplement Safety

These findings carry important implications for both cancer treatment and the use of polyamine supplements. The results highlight how strongly biological context matters. In healthy tissues, polyamines may provide anti-aging benefits through eIF5A1. In tissues that are cancerous or at risk of becoming malignant, the same molecules can stimulate tumor growth through eIF5A2. This dual behavior helps explain why polyamines have been so challenging to interpret in medical research.

The study also identifies a promising new therapeutic target. “Our findings reveal an important role for eIF5A2, regulated by polyamines and miR-6514-5p, in cancer cell proliferation, suggesting that the interaction between eIF5A2 and ribosomes, which regulates cancer progression, is a selective target for cancer treatment,” remarks Dr. Higashi. Targeting eIF5A2 specifically could, in theory, slow cancer growth without interfering with the beneficial effects linked to eIF5A1.

Overall, this research marks a significant advance in understanding the complex and sometimes contradictory roles of polyamines. In the future, scientists may be able to design strategies that preserve their positive effects on healthy aging while reducing their potential to support cancer development.

This study was supported in part by a Grant-in-Aid for Scientific Research (C) (No. 18K06652) from the Japan Society for the Promotion of Science, the Hamaguchi Foundation for the Advancement of Biochemistry, and an Extramural Collaborative Research Grant of the Cancer Research Institute, Kanazawa University, Japan.