Brain development provides insights into adolescent depression

Lead research Professor Nick Allen from the Melbourne School of Psychological Sciences said, “It is well known that the brain continues to change and remodel itself during adolescence as part of healthy development.”

“In this study, we found that the pattern of development (such as changes in brain structure between ages twelve to sixteen) in several key brain regions differed between depressed and non-depressed adolescents,” Professor Allen said.

The brain regions involved include areas associated with the experience and regulation of emotion, as well as areas associated with learning and memory. 



“The findings are an important breakthrough for exploring possible causes of depression in adolescence. They also suggest that both prevention and treatment for depression (even for early signs and symptoms of depression) in adolescence is essential, especially targeting those in the early years of adolescence aged twelve to sixteen,” he said.

“We also observed some differences between males and females. For males, less growth in an area of the brain involved in processing threat and other unexpected events that is a critical part of the brain’s fear circuitry, was associated with depression. On the other hand, for females, greater growth of this area was found to be associated with depression.” 



“This is important information because depression becomes much more common amongst girls during adolescence, and these findings tell us about some of the neurobiological factors that might play a role in this gender difference,” he said.

Professor Allen says adolescence is a period during the lifespan where risk for developing depression dramatically increases.

The study examined eighty-six adolescents (41 female) with no history of depressive disorders before age 12 by using a Magnetic Resonance Imaging (MRI) scanner, which allowed researchers to measure the volume of particular brain regions of interest. 

Participants underwent an MRI scan first at age twelve and again at age sixteen, when rates of depression were beginning to increase. 

Researchers also conducted detailed interviews with each of the participants at four different time points between age twelve and age eighteen. Thirty participants experienced a first episode of a depressive disorder during the follow-up period.

These findings have recently been published in the American Journal of Psychiatry.

Study first to offer detailed map of mouse’s cerebral cortex

The mammalian cerebral cortex, long thought to be a dense single interrelated tangle of neural networks, actually has a “logical” underlying organizational principle, according to a study appearing in the journal Cell.

Researchers have identified eight distinct neural subnetworks that together form the connectivity infrastructure of the mammalian cortex — the part of the brain involved in higher-order functions such as cognition, emotion and consciousness.

“This study is the first comprehensive mapping of the most developed region of the mammalian brain: the cerebral cortex. The cortex is highly complex and made up of many densely interconnected structures, but when you strip it down, is organized into a small number of subnetworks,” said senior author Hongwei Dong of the USC Institute for Neuroimaging and Informatics (INI).

The cerebral cortex is the outermost layer of neural tissue in the brain and is one of the most extensively studied brain structures in the field of neuroscience. However, before this study, its underlying organizational principle was still largely unclear.

“Think about it: The brain is built for logic, so it’s organization must be logical. The brain’s architectural organization is arranged such that all of its substructures most efficiently work in conjunction to produce appropriate behaviors,” said Dong, associate professor of neurology at the Keck School of Medicine of USC. “We want to find the code to how the brain is structurally organized.”

The study is also a reminder that while there is more data than ever, the quality and reliability of information still matters. In contrast to past patchwork attempts, Dong and his team undertook an effort to directly develop a whole-brain mouse atlas of brain pathways. Across the cortex, they injected fluorescent molecules. These molecules were then transported along the brain’s “cellular highways” — the neuronal pathways — and meticulously tracked using a high-resolution microscope.

The uniformity and completeness of the scientists’ effort across the entire cortex provided for a searchable image database of cortical connections, which the researchers are making open-access and publicly available.

It also allowed them to reliably see patterns: the seemingly inscrutable mass of connections in the cerebral cortex is highly organized, consisting of eight distinct subnetworks that are relatively segregated.

“The systematic and comprehensive manner in which the data were collected lent itself to a detailed analysis through which these subnetworks emerged,” explained co-lead author Houri Hintiryan of the USC Laboratory of Neuro Imaging.

So that scientists around the world may continue to look for fundamental structural insights, the full, interactive imaging dataset is viewable at Mouse Connectome Project, providing a resource for researchers interested in studying the anatomy and function of cortical networks throughout the brain.

“It really is quite tedious,” Dong said of collecting the data, “and labor-intensive, and it requires highly specialized skills and technology. But think of the Human Genome Project and how much it accelerated the process of discovery and the whole field when infrastructures existed for people to share and compare. That was our motivation.”

How these subnetworks interact will provide a crucial baseline from which to better understand diseases of “disconnection” such as autism and Alzheimer’s disease, in which the manifestations of symptoms are potentially a result of disordered or damaged connections.

The researchers’ map of the mouse cerebral cortex can be compared to data on disease-affected brains, brains in development and genetic information. It will also offer necessary context for humans, who behaved just like other mammals only a few thousand years ago and who still share most underlying basic behavioral characteristics such as hunger and pain.

“The fundamental logic of mammalian brains is the same, particularly when it comes to basic behaviors such as eating, sleeping and social behaviors” said Dong, who noted that similar studies in humans have thus far not gotten to the cellular level. “There are lots of organizing principles to brain structures that we are just beginning to understand.”

The researchers identified the brain subnetworks based on their high degree of interconnectivity — though relatively independent, several structures provide communication routes through which the subnetworks interact. Combined with behavioral data from past research and information about subcortical targets, these interconnections imply remarkable functional significance for the subnetworks.

Four of the eight identified subnetworks in the mouse cortex relate to sensation and movement of the body — what the researchers dub somatic sensorimotor. In particular, the researchers identified separate subnetworks for movements in the face, upper limbs, lower limbs and trunk, and whiskers. Together, these networks facilitate motor behaviors such as eating and drinking, reaching and grabbing, locomotion and exploration of the environment.

Two other subnetworks are comprised of structures located along the midline of the cerebral cortex. These medial subnetworks seem devoted to the integration of visual, auditory and somatic sensory information, according to the study. Several other structures located along the side of the brain form two lateral subnetworks, one of which potentially serves to regulate the internal status of the body (i.e., taste, hunger, visceral information) and the other as a “mega-integration” subnetwork that allows the interaction of information from nearly the entire cortex.

Why does the brain remember dreams?

Some people recall a dream every morning, whereas others rarely recall one. A team led by Perrine Ruby, an Inserm Research Fellow at the Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1), has studied the brain activity of these two types of dreamers in order to understand the differences between them. In a study published in the journal Neuropsychopharmacology, the researchers show that the temporo-parietal junction, an information-processing hub in the brain, is more active in high dream recallers. Increased activity in this brain region might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, thereby facilitating the encoding of dreams in memory.

The reason for dreaming is still a mystery for the researchers who study the difference between “high dream recallers,” who recall dreams regularly, and “low dream recallers,” who recall dreams rarely. In January 2013 (work published in the journal Cerebral Cortex), the team led by Perrine Ruby, Inserm researcher at the Lyon Neuroscience Research Center, made the following two observations: “high dream recallers” have twice as many time of wakefulness during sleep as “low dream recallers” and their brains are more reactive to auditory stimuli during sleep and wakefulness. This increased brain reactivity may promote awakenings during the night, and may thus facilitate memorisation of dreams during brief periods of wakefulness.

In this new study, the research team sought to identify which areas of the brain differentiate high and low dream recallers. They used Positron Emission Tomography (PET) to measure the spontaneous brain activity of 41 volunteers during wakefulness and sleep. The volunteers were classified into 2 groups: 21 “high dream recallers” who recalled dreams 5.2 mornings  per week in average, and 20 “low dream recallers,” who reported 2 dreams per month in average. High dream recallers, both while awake and while asleep, showed stronger spontaneous brain activity in the medial prefrontal cortex (mPFC) and in the temporo-parietal junction (TPJ), an area of the brain involved in attention orienting toward external stimuli.

Promise of a bonus counter-productive in brains with high dopamine levels

Some people perform better and others worse when promised a high bonus. Brain researcher Esther Aarts of the Donders Institute in Nijmegen has demonstrated for the first time that the amount of dopamine in the brain plays a role in this regard. The journal Psychological Science will publish the results on February 13.

It has been known for some time that not everyone performs better after being promised a bonus. Scientists have published contradictory results regarding the cause. The study by Esther Aarts now shows that the differences can be explained by differences in the level of dopamine in the brain. People with a high level of dopamine in a specific brain region – the striatum – perform worse after a being promised a bonus, and people with a low level of dopamine in the same area perform better. Aarts used a PET (Positron Emission Tomography) scanner to examine the amount of dopamine in the brains of subjects. She conducted this research in Berkeley, California (USA), where she worked as a post-doctoral researcher for two years.

Overdose of dopamine
The promise of a bonus provides an additional spurt of the ‘motivation substance’ dopamine in the brain. ‘For people who usually have high levels of dopamine, the promise of a bonus causes a type of dopamine overdose in the striatum’, explains Aarts. ‘Our test subjects were asked to perform a task that required considerable concentration. An overdose of dopamine makes this difficult. People who usually have less dopamine are less likely to have an overdose of dopamine, and they therefore perform better after being promised a bonus.’

Concentration desired
Test subjects performed a computer task that elicited conflicting reactions, therefore requiring considerable concentration: an arrow appears on the screen, pointing either left or right. The word ‘left’ or ‘right’ is written in the middle of the arrow. Subjects were asked to ignore the direction indicated by the arrow and mention only the direction described by the word. For half of the attempts, a bonus of 15 cents was promised for a correct answer. In the other half, the subjects received only 1 cent for each correct answer. People who usually have a high level of dopamine performed better in the low-pay condition than they did in the high-pay condition. The reverse was observed for people with low levels of dopamine: they performed better with high rewards than they did with low rewards.

Flexibility or focus
‘This knowledge could make it possible to apply bonuses more effectively, but it would require observing the standard dopamine levels of people, as well as the nature of the task that they must perform’, reports Aarts. ‘It makes quite a difference whether the task is flexible and creative or whether it requires a great deal of focus. Our research shows how people perform on tasks that require considerable focus’. Given the high cost of PET scans, Aarts is now looking for easier ways of measuring dopamine levels. ‘I hope to be able to relate dopamine levels to scores on questionnaires. In the future, this might eliminate the need for PET scans for determining the quantity of dopamine in the brain’.

Understanding the basic biology of bipolar disorder

Scientists know there is a strong genetic component to bipolar disorder, but they have had an extremely difficult time identifying the genes that cause it. So, in an effort to better understand the illness’s genetic causes, researchers at UCLA tried a new approach.

Instead of only using a standard clinical interview to determine whether individuals met the criteria for a clinical diagnosis of bipolar disorder, the researchers combined the results from brain imaging, cognitive testing, and an array of temperament and behavior measures. Using the new method, UCLA investigators — working with collaborators from UC San Francisco, Colombia’s University of Antioquia and the University of Costa Rica — identified about 50 brain and behavioral measures that are both under strong genetic control and associated with bipolar disorder. Their discoveries could be a major step toward identifying the specific genes that contribute to the illness.

The results are published in the Feb. 12 edition of the journal JAMA Psychiatry.

A severe mental illness that affects about 1 to 2 percent of the population, bipolar disorder causes unusual shifts in mood and energy, and it interferes with the ability to carry out everyday tasks. Those with the disorder can experience tremendous highs and extreme lows — to the point of not wanting to get out of bed when they’re feeling down. The genetic causes of bipolar disorder are highly complex and likely involve many different genes, said Carrie Bearden, a senior author of the study and an associate professor of psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior.

"The field of psychiatric genetics has long struggled to find an effective approach to begin dissecting the genetic basis of bipolar disorder," Bearden said. "This is an innovative approach to identifying genetically influenced brain and behavioral measures that are more closely tied to the underlying biology of bipolar disorder than the clinical symptoms alone are."

The researchers assessed 738 adults, 181 of whom have severe bipolar disorder. They used high-resolution 3-D images of the brain, questionnaires evaluating temperament and personality traits of individuals diagnosed with bipolar disorder and their non-bipolar relatives, and an extensive battery of cognitive tests assessing long-term memory, attention, inhibitory control and other neurocognitive abilities.

Approximately 50 of these measures showed strong evidence of being influenced by genetics. Particularly interesting was the discovery that the thickness of the gray matter in the brain’s temporal and prefrontal regions — the structures that are critical for language and for higher-order cognitive functions like self-control and problem-solving — were the most promising candidate traits for genetic mapping, based on both their strong genetic basis and association with the disease.

"These findings are really just the first step in getting us a little closer to the roots of bipolar disorder," Bearden said. "What was really exciting about this project was that we were able to collect the most extensive set of traits associated with bipolar disorder ever assessed within any study sample. These data will be a really valuable resource for the field."

The individuals assessed in this study are members of large families living in Costa Rica’s central valley and Antioquia, Colombia. The families were founded by European and native Amerindian populations about 400 years ago and have a very high incidence of bipolar disorder. The groups were chosen because they have remained fairly isolated since their founding and their genetics are therefore simpler for scientists to study than those of general populations.

The fact that the findings aligned so closely with those of previous, smaller studies in other populations was surprising even to the scientists, given the subjects’ unique genetic background and living environments.

"This suggests that even if the specific genetic variants we identify may be unique to this population, the biological pathways they disrupt are likely to also influence disease risk in other populations," Bearden said.

The researchers’ next step is to use the genomic data they collected from the families — including full genome sequences and gene expression data— to begin identifying the specific genes that contribute to risk for bipolar disorder. The researchers also plan to extend their investigation into the children and teens in these families. They hypothesize that many of the bipolar-related brain and behavioral differences found in adults with bipolar disorder had their origins in adolescent neurodevelopment.

Meditation helps pinpoint neurological differences between two types of love

These findings won’t appear on any Hallmark card, but romantic love tends to activate the same reward areas of the brain as cocaine, research has shown.

Now Yale School of Medicine researchers studying meditators have found that a more selfless variety of love — a deep and genuine wish for the happiness of others without expectation of reward — actually turns off the same reward areas that light up when lovers see each other.

“When we truly, selflessly wish for the well-being of others, we’re not getting that same rush of excitement that comes with, say, a tweet from our romantic love interest, because it’s not about us at all,” said Judson Brewer, adjunct professor of psychiatry at Yale now at the University of Massachusetts.

Brewer and Kathleen Garrison, postdoctoral researcher in Yale’s Department of Psychiatry, report their findings in a paper scheduled to be published online Feb. 12 in the journal Brain and Behavior.

The neurological boundaries between these two types of love become clear in fMRI scans of experienced meditators. The reward centers of the brain that are strongly activated by a lover’s face (or a picture of cocaine) are almost completely turned off when a meditator is instructed to silently repeat sayings such as “May all beings be happy.”

Such mindfulness meditations are a staple of Buddhism and are now commonly practiced in Western stress reduction programs, Brewer notes. The tranquility of this selfless love for others — exemplified in such religious figures such as Mother Theresa or the Dalai Llama — is diametrically opposed to the anxiety caused by a lovers’ quarrel or extended separation. And it carries its own rewards.

“The intent of this practice is to specifically foster selfless love — just putting it out there and not looking for or wanting anything in return,” Brewer said. “If you’re wondering where the reward is in being selfless, just reflect on how it feels when you see people out there helping others, or even when you hold the door for somebody the next time you are at Starbucks.”

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.”