Family problems experienced in childhood and adolescence affect brain development

New research has revealed that exposure to common family problems during childhood and early adolescence affects brain development, which could lead to mental health issues in later life.

The study led by Dr Nicholas Walsh, lecturer in developmental psychology at the University of East Anglia, used brain imaging technology to scan teenagers aged 17-19. It found that those who experienced mild to moderate family difficulties between birth and 11 years of age had developed a smaller cerebellum, an area of the brain associated with skill learning, stress regulation and sensory-motor control. The researchers also suggest that a smaller cerebellum may be a risk indicator of psychiatric disease later in life, as it is consistently found to be smaller in virtually all psychiatric illnesses.

Previous studies have focused on the effects of severe neglect, abuse and maltreatment in childhood on brain development. However the aim of this research was to determine the impact, in currently healthy teenagers, of exposure to more common but relatively chronic forms of ‘family-focused’ problems. These could include significant arguments or tension between parents, lack of affection or communication between family members, physical or emotional abuse, and events which had a practical impact on daily family life and might have resulted in health, housing or school problems.

Dr Walsh, from UEA’s School of Psychology, said: “These findings are important because exposure to adversities in childhood and adolescence is the biggest risk factor for later psychiatric disease. Also, psychiatric illnesses are a huge public health problem and the biggest cause of disability in the world.

“We show that exposure in childhood and early adolescence to even mild to moderate family difficulties, not just severe forms of abuse, neglect and maltreatment, may affect the developing adolescent brain. We also argue that a smaller cerebellum may be an indicator of mental health issues later on. Reducing exposure to adverse social environments during early life may enhance typical brain development and reduce subsequent mental health risks in adult life.”

The study, which was conducted with the University of Cambridge and the Medical Research Council Cognition and Brain Sciences Unit, Cambridge, is published in the journal NeuroImage: Clinical.

The 58 teenagers who took part in the brain scanning were drawn from a larger study of 1200 young people, whose parents were asked to recall any negative life events their children had experienced between birth and 11 years of age. The interviews took place when the children were aged 14 and of the 58, 27 were classified as having been exposed to childhood adversities. At ages 14 and 17 the teenagers themselves also reported any negative events and difficulties they, their family or closest friends had experienced during the previous 12 months.

A “significant and unexpected” finding was that the participants who reported stressful experiences when aged 14 were subsequently found to have increased volume in more regions of the brain when they were scanned aged 17-19. Dr Walsh said this could mean that mild stress occurring later in development may ‘inoculate’ teenagers, enabling them to cope better with exposure to difficulties in later life, and that it is the severity and timing of the experiences that may be important.

“This study helps us understand the mechanisms in the brain by which exposure to problems in early-life leads to later psychiatric issues,” said Dr Walsh. “It not only advances our understanding of how the general psychosocial environment affects brain development, but also suggests links between specific regions of the brain and individual psychosocial factors. We know that psychiatric risk factors do not occur in isolation but rather cluster together, and using a new technique we show how the general clustering of adversities affects brain development.”

The researchers also found at that those who had experienced family problems were more likely to have had a diagnosed psychiatric illness, have a parent with a mental health disorder and have negative perceptions of their how their family functioned.

Figure 1: Typical slow gamma (left), fast gamma (center) and theta (right) brain-wave patterns measured during voluntary actions in rats.

Banding together to control movement

Synchrony is critical for the proper functioning of the brain. Synchronous firing of neurons within regions of the brain and synchrony between brain waves in different regions facilitate information processing, yet researchers know very little about these neural codes. Now, new research led by Tomoki Fukai of the RIKEN Brain Science Institute reveals how one region of the brain uses multiple brain-wave frequency bands to control movement.

Control of movement requires activation of numerous muscle groups in correct sequence, a function achieved by the motor cortex. To investigate the contribution of brain waves to this process, Fukai and his colleagues inserted multi-channel electrodes into the motor cortex of rats to record brain-wave patterns as the animals learned to push, hold and then pull a lever to obtain a food reward. They also developed a machine-learning technique to extract spike sequences of individual neurons from the recorded waves. 

Fukai and his colleagues found that brain waves of different frequencies appeared during distinct stages of the movements. Fast gamma waves, with frequencies of around 100 hertz, were most prominent when the rats pushed or pulled the lever, whereas slow gamma waves, with frequencies of 25–40 hertz, peaked when the rats held the lever to prepare for the next pull. Theta waves (4–10 hertz) peaked while the rats held the lever, and the initiation of the pulling movement coincided with a specific phase of these oscillations (Fig. 1).

Both frequencies of gamma waves were coupled to the theta waves such that the peaks of all three brain-wave frequencies occurred at the same time. The activity of different types of nerve cells in different layers of the motor cortex was also synchronized with specific brain-wave frequencies. Importantly, cells encoding different stages of the sequential movements fired in distinct phases of the theta waves. 

The results suggest that theta waves play an important role in coordinating the neuronal activity underlying the planning and execution of voluntary movement. Theta waves are known to be important for the processing of spatial information in the hippocampus, but this is the first time that a similar code has been observed in the motor cortex.

“We are currently using machine-learning techniques to study how phase-locked spikes in different layers of the motor cortex encode motor information,” says Fukai. “We are also studying whether a similar oscillatory coordination takes place in the prefrontal cortex during decision-making.”

Mechanism behind the activation of dormant memory cells discovered

The electrical stimulation of the hippocampus in in-vivo experiments activates precisely the same receptor complexes as learning or memory recall. This has been discovered for the first time and the finding has now been published in the highly respected journal “Brain Structure Function”. “This may form the basis for the use of medications aimed at powering up dormant or less active memory cells,” says Gert Lubec, Head of Fundamental Research / Neuroproteomics at the University Department of Paediatrics and Adolescent Medicine at the MedUni Vienna. 

“This discovery has far-reaching consequences both for the molecular understanding of memory formation and the understanding of the clinical electrical stimulation, which is already possible, of areas of the brain for therapeutic purposes,” says the MedUni Vienna researcher.  Similar principles are currently already being used in the field of deep brain stimulation. With this technology, an implanted device delivers electronic impulses to the patient’s brain. This physical stimulation allows neuronal circuits to be influenced that control both behaviour and memory.

The latest findings very much form part of the highly controversial subject of “cognitive enhancement”. Scientists are currently discussing the possibility of improving mental capacity through the use of drugs - including in healthy subjects of all age groups, but especially in patients with age-related impairments of cognitive processes.

With regard to the study design, two electrodes were implanted into the brain in an animal model. One transferred electrical impulses to stimulate the hippocampus, while the other transferred the electrical signals away. “These electrical potentials are the electrical equivalent of memory and are known as LTP (Long Term Potentiation),” explains Lubec. The generation of LTP in an in-vivo experiment was accompanied by specific changes in the receptor complexes - the same receptor complexes that are also activated during learning and memory formation.

Seizing Control of Brain Seizures

A few years after serving in the Israeli army during the first Gulf War, Daniela Kaufer made a startling discovery about the effect of psychological stress on the brain. As a graduate student at the Hebrew University she showed that the kind of extreme stress experienced in combat can break down the physiological barriers that normally protect the brain.

She could not have known it then, but the finding would eventually lead her to uncover a key change in brain chemistry that triggers epileptic seizures. The Bakar Fellows Program is now helping her refine a strategy to block the threat and protect the brain from damage caused by physical trauma and other insults.

A physiological line of defense normally prevents circulating blood from entering the brain. Known as the blood-brain barrier, the tightly controlled system buffers the brain from exposure to bacteria and other blood-borne invaders. Kaufer’s research has revealed how brain trauma can disrupt brain function once the barrier is breached.

In lab research as a postdoc at Stanford in 2002, Kaufer and her Israeli colleague Alon Friedman examined what happens in the brain when the barrier is compromised. They found that seizures were likely if – and only if – the brain came in contact with blood that had been circulating in the body.

They showed that a very common protein in blood called albumin accelerates signaling between neurons to abnormal levels. Neurons become overexcited and can cause seizures.

“We were surprised, even a little disappointed, that it was such a common component of the blood  – nothing exotic at all  – that led to epilepsy,” recalls Kaufer, associate professor of integrative biology.

She and Friedman went to on to show that albumin interacts with a ubiquitous cell protein called TGF-Beta receptor to cause the damage.

In the healthy brain, TGF-Beta signaling affects activity of star-shaped sister cells of neurons called astrocytes, which normally limit neuron-to-neuron firing signals across the synapse. But when albumin stimulates TGF-Beta receptors, astrocytes lose some of their control. Neuron signaling spikes dangerously, and promotes the development of epileptic seizures.

“Researchers knew that following traumatic brain injury the risk of epilepsy was great, but they didn’t know why,” Kaufer says.

As luck would have it, a prescription drug for hypertension blocks TGF-Beta signaling.  With support from the Bakar Fellows program, Kaufer is now carrying out research to confirm that blocking abnormal TGF-Beta activity can prevent epilepsy from a range of insults.

She expects that her and Friedman’s lab research, coupled with clinical studies, will demonstrate the drug’s ability to protect the brain and move it into use in emergency medicine to prevent victims of brain trauma from becoming epileptic.

Kaufer and Friedman’s research is suggesting too that a number of assaults besides physical trauma – from brain infections to stroke – can also weaken the blood-brain barrier, and lead to the development of epilepsy through TGF-beta signaling. Emergency medicine physicians need only determine if the barrier has been breached to know if a patient is at risk for seizures.

Fortunately, the condition of the blood-brain barrier can be assessed using a safe and  straightforward FDA-approved MRI protocol, so screening for epilepsy risk is within reach, says Kaufer.

“Right now, if someone comes to the emergency room with traumatic brain injury, they have a 10 to 50 percent chance of developing epilepsy. But you don’t know which ones, nor do you have a way of preventing it. And epilepsy from brain injuries is the type most unresponsive to drugs.

“I’m very hopeful and that our research can spare these patients the added trauma of epilepsy.”

Researchers provide standardized nomenclature for the architecture of insect brains

When you’re talking about something as complex as the brain, the task isn’t any easier if the vocabulary being used is just as complex. An international collaboration of neuroscientists has not only tripled the number of identified brain structures, but created a simple lexicon to talk about them, which will be enormously helpful for future research on brain function and disease.

Nick Strausfeld and Linda Restifo, both professors in the Department of Neuroscience at the University of Arizona, worked with colleagues in Japan who led the project, and colleagues in Germany and in the UK to produce a comprehensive atlas of neuroanatomical centers and computational centers of the insect brain. In the process, the team identified many previously unknown structures. By providing the research community with a unified system of terminology, they set the stage for a systematic effort to elucidate brain structures and functions that carry over to functions of the human brain.

An article about the work appears in the scientific journal Neuron, regarded by many as one of the flagship publications of neuroscience; the online version includes an 80-page data supplement. The data will be publicly available within 6 months and include hundreds of images and 3-D video animations – amounting to an invaluable resource that will enable neuroscientists to work more efficiently, compare their results and obtain more meaningful interpretations.

"This effort provides a three-dimensional road map for describing structures for all insect brains, and enables comparisons with other arthropods," said Strausfeld, director of the UA Center for Insect Science. "It has huge value in describing network relationships between computational centers in the brain."

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Study reveals workings of working memory

Keep this in mind: Scientists say they’ve learned how your brain plucks information out of working memory when you decide to act.

Say you’re a busy mom trying to wrap up a work call now that you’ve arrived home. While you converse on your Bluetooth headset, one kid begs for an unspecified snack, another asks where his homework project has gone, and just then an urgent e-mail from your boss buzzes the phone in your purse. During the call’s last few minutes these urgent requests — snack, homework, boss — wait in your working memory. When you hang up, you’ll pick one and act.

When you do that, according to Brown University psychology researchers whose findings appear in the journal Neuron, you’ll employ brain circuitry that links a specific chunk of the striatum called the caudate and a chunk of the prefrontal cortex centered on the dorsal anterior premotor cortex. Selecting from working memory, it turns out, uses similar circuits to those involved in planning motion.

In lab experiments with 22 adult volunteers, the researchers used magnetic resonance imaging to track brain activity during a carefully designed working memory task. They also measured how quickly the subjects could choose from working memory — a phenomenon the scientists called “output gating.”

“In the immediacy of what we’re doing we have this small working memory capacity where we can hang on to a few things that are going to be useful in a few moments, and that’s where output gating is crucial,” said study senior author David Badre, professor of cognitive, linguistic, and psychological sciences at Brown.

From the perspective of cognition, said lead author and postdoctoral scholar Christopher Chatham, input gating — choosing what goes into working memory — and output gating allow people to maintain a course of action (e.g., finish that Bluetooth call) while being flexible enough to account for context in planning what’s next.

Of cognition and wingdings

In their experiments Badre, Chatham, and co-author Michael Frank, associate professor of cognitive, linguistic, and psychological sciences, provided their volunteers with four different versions of a similar working memory task. The versions distinguished output gating from input gating so that the anatomical action observed in the MRI could reliably associate with output gating behavior.

In each round, volunteers saw a sequence of characters — either letters of the alphabet or wingdings (typographical symbols like stars and snowflakes). Before or after the sequence, the volunteers were also given a context cue in the form of a numeral that told them which kind of character would be relevant at end of the task (e.g., “1” might mean a wingding while “2” might mean a letter). The last step for volunteers was to select between groups of characters on the screen that included whichever contextually relevant character they had seen in the sequence (e.g., if the subject had seen a “1” and later a snowflake during the sequence, they should select the group that included a snowflake).

When the context numeral came first, say a “2,” volunteers would “input gate” only letters into their working memory. When it came time to make a selection, they’d simply “output gate” the correct letter from the letters in working memory. If the context came last, people would have to input gate everything they saw into working memory, making all the real thinking a matter of output gating. If the context cue came last, they would carry a higher load of characters in working memory. To address this disparity, the experimenters created two more conditions in which a global context indicator, “3,” required people to keep everything they saw in working memory whether it came before the sequence or after.

With this experimental design the researchers could measure performance and monitor brain activity with subjects who had distinct moments of input and output gating, regardless of the character load in working memory.

People accomplished the tasks with a range of speeds, which the researchers regarded as a proxy for the amount of cognitive work volunteers had to do. People were slowest in making a selection when they got the context cue last and then had to gate just one specific symbol out of memory (e.g., they saw the sequence, then saw a 1, and then had to choose the option with a wingding they had seen). People were fastest at making a selection when they were given the context first and then had to pick the one character of that kind that they saw (e.g., they saw a “2,” then the sequence in which only letters mattered, and then had to choose the option with a letter they had seen).

In analyzing the results, Chatham and his co-authors found that the caudate and the dorsal anterior premotor cortex, contributed distinctly to the reaction times they saw. These separate roles in the partnership agree with computational models of how the brain works.

“The division of labor that’s specifically posited by these computational models is one in which there is a basically a context being represented in the prefrontal cortex that determines the overall efficiency of going from stimulus to response – like a route,” Chatham said. “The striatum is involved in the actual gating of that flow of information,” he said, “like traffic lights along the route.”

So the cortex interprets the context, while the striatum implements the gating. When the context is unhelpfully general and the gating is very specific, for example, the task takes a lot of time.

The findings help advance studies of how cognition works in the brain and could help psychiatrists analyze behavior in people where those areas of the brain have been injured, the researchers said. It also highlights how similar brain circuits can execute different functions – motion and working memory gating.