(Image caption: These figures show lagged maturation of connections in ADHD between the default mode network, involved in internally-directed thought (i.e., daydreaming) and shown on the left of each figure, and two brain networks involved in externally-focused attention, shown on the right of each figure. The width of each arc represents the number of lagged connections between two regions within each network. Connections that normally increase with age and that are hypoconnected in ADHD are shown in blue; connections that normally decrease with age and that are hyperconnected in ADHD are shown in red.)

Slow to mature, quick to distract: ADHD brain study finds slower development of key connections

A peek inside the brains of more than 750 children and teens reveals a key difference in brain architecture between those with attention deficit hyperactivity disorder and those without.

Kids and teens with ADHD, a new study finds, lag behind others of the same age in how quickly their brains form connections within, and between, key brain networks.

The result: less-mature connections between a brain network that controls internally-directed thought (such as daydreaming) and networks that allow a person to focus on externally-directed tasks. That lag in connection development may help explain why people with ADHD get easily distracted or struggle to stay focused.

What’s more, the new findings, and the methods used to make them, may one day allow doctors to use brain scans to diagnose ADHD — and track how well someone responds to treatment. This kind of neuroimaging “biomarker” doesn’t yet exist for ADHD, or any psychiatric condition for that matter.

The new findings come from a team in the University of Michigan Medical School’s Department of Psychiatry. They used highly advanced computing techniques to analyze a large pool of detailed brain scans that were publicly shared for scientists to study. Their results are published in the Proceedings of the National Academy of Sciences.

Lead author Chandra Sripada, M.D., Ph.D., and colleagues looked at the brain scans of 275 kids and teens with ADHD, and 481 others without it, using “connectomic” methods that can map interconnectivity between networks in the brain.

The scans, made using function magnetic resonance imaging (fMRI) scanners, show brain activity during a resting state. This allows researchers to see how a number of different brain networks, each specialized for certain types of functions, were “talking” within and amongst themselves.

The researchers found lags in development of connection within the internally-focused network, called the default mode network or DMN, and in development of connections between DMN and two networks that process externally-focused tasks, often called task-positive networks, or TPNs. They could even see that the lags in connection development with the two task-related networks — the frontoparietal and ventral attention networks — were located primarily in two specific areas of the brain.

The new findings mesh well with what other researchers have found by examining the physical structure of the brains of people with and without ADHD in other ways.

Such research has already shown alterations in regions within DMN and TPNs. So, the new findings build on that understanding and add to it. 

The findings are also relevant to thinking about the longitudinal course of ADHD from childhood to adulthood. For instance, some children and teens “grow out” of the disorder, while for others the disorder persists throughout adulthood. Future studies of brain network maturation in ADHD could shed light into the neural basis for this difference.

“We and others are interested in understanding the neural mechanisms of ADHD in hopes that we can contribute to better diagnosis and treatment,” says Sripada, an assistant professor and psychiatrist who holds a joint appointment in the U-M Philosophy department and is a member of the U-M Center for Computational Medicine and Bioinformatics. “But without the database of fMRI images, and the spirit of collaboration that allowed them to be compiled and shared, we would never have reached this point.”  

Sripada explains that in the last decade, functional medical imaging has revealed that the human brain is functionally organized into large-scale connectivity networks. These networks, and the connections between them, mature throughout early childhood all the way to young adulthood. “It is particularly noteworthy that the networks we found to have lagging maturation in ADHD are linked to the very behaviors that are the symptoms of ADHD,” he says. 

Studying the vast array of connections in the brain, a field called connectomics, requires scientists to be able to parse through not just the one-to-one communications between two specific brain regions, but the patterns of communication among thousands of nodes within the brain. This requires major computing power and access to massive amounts of data – which makes the open sharing of fMRI images so important.

“The results of this study set the stage for the next phase of this research, which is to examine individual components of the networks that have the maturational lag,” he says. “This study provides a coarse-grained understanding, and now we want to examine this phenomenon in a more fine-grained way that might lead us to a true biological marker, or neuromarker, for ADHD.”

Sripada also notes that connectomics could be used to examine other disorders with roots in brain connectivity – including autism, which some evidence has suggested stems from over-maturation of some brain networks, and schizophrenia, which may arise from abnormal connections. Pooling more fMRI data from people with these conditions, and depression, anxiety, bipolar disorder and more could boost connectomics studies in those fields.

How our brain networks: Research reveals white matter ‘scaffold’ of human brain

For the first time, neuroscientists have systematically identified the white matter “scaffold” of the human brain, the critical communications network that supports brain function.

Their work, published Feb. 11 in the open-source journal Frontiers in Human Neuroscience, has major implications for understanding brain injury and disease. By detailing the connections that have the greatest influence over all other connections, the researchers offer not only a landmark first map of core white matter pathways, but also show which connections may be most vulnerable to damage.

"We coined the term white matter ‘scaffold’ because this network defines the information architecture which supports brain function," said senior author John Darrell Van Horn of the USC Institute for Neuroimaging and Informatics and the Laboratory of Neuro Imaging at USC.

"While all connections in the brain have their importance, there are particular links which are the major players," Van Horn said.

Using MRI data from a large sample of 110 individuals, lead author Andrei Irimia, also of the USC Institute for Neuroimaging and Informatics, and Van Horn systematically simulated the effects of damaging each white matter pathway.

They found that the most important areas of white and gray matter don’t always overlap. Gray matter is the outermost portion of the brain containing the neurons where information is processed and stored. Past research has identified the areas of gray matter that are disproportionately affected by injury.

But the current study shows that the most vulnerable white matter pathways – the core “scaffolding” – are not necessarily just the connections among the most vulnerable areas of gray matter, helping explain why seemingly small brain injuries may have such devastating effects.

"Sometimes people experience a head injury which seems severe but from which they are able to recover. On the other hand, some people have a seemingly small injury which has very serious clinical effects," says Van Horn, associate professor of neurology at the Keck School of Medicine of USC. "This research helps us to better address clinical challenges such as traumatic brain injury and to determine what makes certain white matter pathways particularly vulnerable and important."

The researchers compare their brain imaging analysis to models used for understanding social networks. To get a sense of how the brain works, Irimia and Van Horn did not focus only on the most prominent gray matter nodes – which are akin to the individuals within a social network. Nor did they merely look at how connected those nodes are.

Rather, they also examined the strength of these white matter connections, i.e. which connections seemed to be particularly sensitive or to cause the greatest repercussions across the network when removed. Those connections which created the greatest changes form the network “scaffold.”

"Just as when you remove the internet connection to your computer you won’t get your email anymore, there are white matter pathways which result in large scale communication failures in the brain when damaged," Van Horn said.

When white matter pathways are damaged, brain areas served by those connections may wither or have their functions taken over by other brain regions, the researchers explain. Irimia and Van Horn’s research on core white matter connections is part of a worldwide scientific effort to map the 100 billion neurons and 1,000 trillion connections in the living human brain, led by the Human Connectome Project and the Laboratory of Neuro Imaging at USC.

Irimia notes that, “these new findings on the brain’s network scaffold help inform clinicians about the neurological impacts of brain diseases such as multiple sclerosis, Alzheimer’s disease, as well as major brain injury. Sports organizations, the military and the US government have considerable interest in understanding brain disorders, and our work contributes to that of other scientists in this exciting era for brain research.”

The Strange Neuroscience of Immortality

In the basement of the Northwest Science Building here at Harvard University, a locked door is marked with a pink and yellow sign: “Caution: Radioactive Material.” Inside researchers buzz around wearing dour expressions and plastic gloves. Among them is Kenneth Hayworth. He’s tall and gaunt, dressed in dark-blue jeans, a blue polo shirt, and gray running shoes. He looks like someone who sleeps little and eats less.

Hayworth has spent much of the past few years in a windowless room carving brains into very thin slices. He is by all accounts a curious man, known for casually saying things like, “The human race is on a beeline to mind uploading: We will preserve a brain, slice it up, simulate it on a computer, and hook it up to a robot body.” He wants that brain to be his brain. He wants his 100 billion neurons and more than 100 trillion synapses to be encased in a block of transparent, amber-colored resin—before he dies of natural causes.

Why? Ken Hayworth believes that he can live forever.

But first he has to die.

"If your body stops functioning, it starts to eat itself," he explains to me one drab morning this spring, "so you have to shut down the enzymes that destroy the tissue." If all goes according to plan, he says cheerfully, "I’ll be a perfect fossil." Then one day, not too long from now, his consciousness will be revived on a computer. By 2110, Hayworth predicts, mind uploading—the transfer of a biological brain to a silicon-based operating system—will be as common as laser eye surgery is today.

Connectomics: Mapping the Neural Network Governing Male Roundworm Mating

In a study published today online in Science, researchers at Albert Einstein College of Medicine of Yeshiva University have determined the complete wiring diagram for the part of the nervous system controlling mating in the male roundworm Caenorhabditis elegans, an animal model intensively studied by scientists worldwide.

The study represents a major contribution to the new field of connectomics – the effort to map the myriad neural connections in a brain, brain region or nervous system to find the specific nerve connections responsible for particular behaviors. A long-term goal of connectomics is to map the human “connectome” – all the nerve connections within the human brain.

Because C. elegans is such a tiny animal – adults are one millimeter long and consist of just 959 cells – its simple nervous system totaling 302 neurons make it one of the best animal models for understanding the millions-of-times-more-complex human brain.

The Einstein scientists solved the structure of the male worm’s neural mating circuits by developing software that they used to analyze serial electron micrographs that other scientists had taken of the region. They found that male mating requires 144 neurons – nearly half the worm’s total number – and their paper describes the connections between those 144 neurons and 64 muscles involving some 8,000 synapses. A synapse is the junction at which one neuron (nerve cell) passes an electrical or chemical signal to another neuron.

"Establishing the complete structure of the synaptic network governing mating behavior in the male roundworm has been highly revealing," said Scott Emmons, Ph.D., senior author of the paper and professor in the department of genetics and in the Dominick P. Purpura Department of Neuroscience at Einstein. "We can see that the structure of this network has spatial characteristics that help explain how it exerts neural control over the multi-step decision-making process involved in mating."

In addition to determining how the neurons and muscles are connected, Dr. Emmons and his colleagues for the first time accurately measured the weights of those connections, i.e., an estimate of the strength with which one neuron or muscle communicates with another.