In a study of nearly 1,000 mother-child pairs, researchers from the Bloomberg School of Public health found that prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), a frequently prescribed treatment for depression, anxiety and other disorders, was associated with autism spectrum disorder (ASD) and developmental delays (DD) in boys. The study, published in the online edition of Pediatrics, analyzed data from large samples of ASD and DD cases, and population-based controls, where a uniform protocol was implemented to confirm ASD and DD diagnoses by trained clinicians using validated standardized instruments.
The study included 966 mother-child pairs from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study based at the University of California at Davis’ MIND Institute. The researchers broke the data into three groups: Those diagnosed with autism spectrum disorder (ASD), those with developmental delays (DD) and those with typical development (TD). The children ranged in ages two to five. A majority of the children were boys – 82.5% in the ASD group were boys, 65.6% in the DD group were boys and 85.6% in the TD were boys. While the study included girls, the substantially stronger effect in boys alone suggests possible gender difference in the effect of prenatal SSRI exposure.
“We found prenatal SSRI exposure was nearly 3 times as likely in boys with ASD relative to typical development, with the greatest risk when exposure took place during the first trimester,” said Li-Ching Lee, Ph.D., Sc.M., psychiatric epidemiologist in the Bloomberg School’s Department of Epidemiology. “SSRI was also elevated among boys with DD, with the strongest exposure effect in the third trimester.”
The data analysis was completed by Rebecca Harrington, Ph.D., M.P.H, in conjunction with her doctoral dissertation at the Bloomberg School. Dr. Lee was one of her advisors.
Serotonin is critical to early brain development; exposure during pregnancy to anything that influences serotonin levels can have potential effect on birth and developmental outcomes. The prevalence of ADS continues to rise. According to the Centers for Disease Control and Prevention, an estimated 1 in 68 children in the U.S. is identified with ADS, and it is almost five times more common among boys than girls. One may question whether the increased use of SSRI in recent years is a contributor to the dramatic rise of ASD prevalence.
"This study provides further evidence that in some children, prenatal exposure to SSRIs may influence their risk for developing an autism spectrum disorder,” said Irva Hertz-Picciotto, Ph.D., M.P.H., chief of the Division of Environmental and Occupational Health in the UC Davis Department of Public Health Sciences and a researcher at the UC Davis MIND Institute. “This research also highlights the challenge for women and their physicians to balance the risks versus the benefits of taking these medications, given that a mother’s underlying mental-health conditions also may pose a risk, both to herself and her child.”
Regarding treatment, the authors note that maternal depression itself carries risks for the fetus, and the benefits of using SSRI during pregnancy should be considered carefully against the potential harm. The researchers also note that large sample studies are needed to investigate the effects in girls with ASD. Limitations of the study acknowledged include the difficulty in isolating SSRI effects from those of their indications for use, lack of information on SSRI dosage precluded dose-response analyses, and the relatively small sample of DD children resulted in imprecise estimates of association, which should be viewed with caution.
Differences in brain connectivity may help explain the social impairments common in those who have autism spectrum disorders, new research suggests.
The small study compared the brains of 25 teens with an autism spectrum disorder to those of 25 typically developing teens, all aged 11 to 18. The researchers found key differences between the two groups in brain “networks” that help people to figure out what others are thinking, and to understand others’ actions and emotions.
"It is generally agreed that the way the networks are organized is not typical [in those with autism]," explained study lead researcher Inna Fishman, assistant research professor of psychology at San Diego State University.
The prevailing idea until now, she said, has been that these neurological networks are under-connected in people with autism. However, “we found they were over-connected — they talk to each other way more than expected at that age.”
The study is published in the April 16 online edition of JAMA Psychiatry.
Study provides new insight into how toddlers learn verbs
Parents can help toddlers’ language skills by showing them a variety of examples of different actions, according to new research from the University of Liverpool.
Previous research has shown that verbs pose particular difficulties to toddlers as they refer to actions rather than objects, and actions are often different each time a child sees them.
To find out more about this area of child language, University psychologists asked a group of toddlers to watch one of two short videos.
They then examined whether watching a cartoon star repeat the same action, compared to a character performing three different actions, affected the children’s understanding of verbs.
Developmental psychologist, Dr Katherine Twomey, said: “Knowledge of how children start to learn language is important to our understanding of how they progress throughout preschool and school years.
“This is the first study to indicate that showing toddlers similar but, importantly, not identical actions actually helped them understand what a verb refers to, instead of confusing them as you might expect.”
Dr Jessica Horst from the University of Sussex who collaborated on the research added: “It is a crucial first step in understanding how what children see affects how they learn verbs and action categories, and provides the groundwork for future studies to examine in more detail exactly what kinds of variability affect how children learn words.”
How brain structures grow as memory develops
Our ability to store memories improves during childhood, associated with structural changes in the hippocampus and its connections with prefrontal and parietal cortices. New research from UC Davis is exploring how these brain regions develop at this crucial time. Eventually, that could give insights into disorders that typically emerge in the transition into and during adolescence and affect memory, such as schizophrenia and depression.
Located deep in the middle of the brain, the hippocampus plays a key role in forming memories. It looks something like two curving fingers branching forward from a common root. Each branch is a folded-over structure, with distinct areas in the upper and lower fold.
“For a long time it was assumed that the hippocampus didn’t develop at all after the first couple of years of life,” said Joshua Lee, a graduate student at the UC Davis Department of Psychology and Center for Mind and Brain. Improvements in memory were thought to be due entirely to changes in the brain’s outer layers, or cortex, that manage attention and strategies. But that picture has begun to change in the past five years.
Recently, Lee, Professor Simona Ghetti at the Center for Mind and Brain and Arne Ekstrom, assistant professor in the UC Davis Center for Neuroscience, used magnetic resonance imaging to map the hippocampus in 39 children aged eight to 14 years.
While subfields of the hippocampus have been mapped in adult humans and animal studies, it’s the first time that they have been measured in children, Ghetti said.
“This is really important to us, because it allows us to understand the heterogeneity along the hippocampus, which has been examined in human adults and other species” Ghetti said.
Looking at three subregions — the cornu ammonis (CA) 1, CA3/dentate gyrus and subiculum — they found that the first two expanded with age, with the most pronounced growth in the right hippocampus. Only in the oldest 25 percent of the children, within a few months either side of 14, did the sizes of all three regions decrease.
When they tested the children for memory performance, children with a larger CA3/dentate gyrus tended to perform better, they found. The work was published online March 15 by the journal Neuroimage.
In a related study in collaboration with the laboratory of Professor Silvia Bunge at UC Berkeley, published March 27 in Cerebral Cortex, the researchers also demonstrated how white matter connections projecting from the hippocampus to the brain cortex are related to memory function in children.
“White matter” tracts connect the prefrontal and parietal regions of the brain cortex, which control how we pay attention to things and engage in memory strategies, with the media-temporal lobe, the area that includes the hippocampus.
In the study, children performed a memory test that prompted them either to actively memorize an item — and therefore engage the prefrontal and parietal cortices — or to view an image passively. The ability to successfully modulate attention was linked to development of white matter tracts linking the prefrontal and parietal cortex tothe mediatemporal lobe, Ghetti said, but not to fronto-parietal connections.
Existence of new neuron repair pathway discovered
Most of your neurons can’t be replaced.
Other parts of your body – such as skin and bone – can be replaced by the body growing new cells, but when you injure your neurons, you can’t just grow new ones; instead, the existing cells have to repair themselves.
In the case of axon injury, the neuron is able to repair or sometimes even fully regenerate its axon. But neurons have two sides – the axon (which sends signals to other cells) and the dendrite (which receives signals from other cells).
Melissa Rolls, an associate professor of biochemistry and molecular biology at Penn State and director of the Huck Institutes’ Center for Cellular Dynamics, has done extensive comparisons of axons and dendrites – culminating recently in a paper published in Cell Reports.
“We know that the axon side can repair itself,” says Rolls, “and we know a bunch of the molecular players. But we really didn’t know whether neurons have the same capacity to regenerate their dendrites, and so that’s what we set out to find in this study.”
“Our lab uses a Drosophila model system, where the dendrites are very accessible to manipulation,” she says, “so we decided that we would start by removing all the dendrites from the neurons to see if they could regenerate. We didn’t start with anything subtle, like taking off just a few dendrites. We said ‘Let’s just push the system to its maximum and see if this is even possible.’ And we were surprised because we found that not only is it possible, it’s actually much faster than axon regeneration: at least in the cells that we’re using, axon regeneration takes a day or two to initiate, while dendrite regeneration typically initiates within four to six hours and it works really well. All the cells where we removed the dendrites grew new dendrites – none of them died; so it’s clear that these cells have a way to both detect dendrite injury and initiate regrowth of the injured part.”
(Image caption: During the learning processes, extensions grow on neurons. Synapses are located at the end of these extensions (left: as seen in nature; right: reconstruction). When the synapse growth is based on the correlated development of all synaptic components, it can remain stable for long periods of time. Credit: © MPI of Neurobiology/ Meyer)
Synapses – stability in transformation
Nothing lasts forever. This principle also applies to the proteins that make up the points of contact between our neurons. It is due to these proteins that the information arriving at a synapse can be transmitted and then received by the next neuron. When we learn something, new synapses are created or existing ones are strengthened. To enable us to retain long-term memories, synapses must remain stable for long periods of time, up to an entire lifetime. Researchers at the Max Planck Institute of Neurobiology in Martinsried near Munich have found an explanation as to how a synapse achieves remaining stable for a long time despite the fact that its proteins must be renewed regularly.
Learning in the laboratory
“We were interested first of all in what happens to the different components of a synapse when it grows during a learning process,” explains study leader Volker Scheuss. An understanding of how the components grow could also provide information about the long-term stability of synapses. Hence, the researchers studied the growth of synapses in tissue culture dishes following exposure to a (learning) stimulus. To do this, they deliberately activated individual synapses using the neurotransmitter glutamate: scientists have long known that glutamate plays an important role in learning processes and stimulates the growth of synapses. Over the following hours, the researchers observed the stimulated synapses and control synapses under a 2-photon microscope. To confirm the observed effects, they then examined individual synapses with the help of an electron microscope. “When you consider that individual synapses are only around one thousandth of a millimetre in size, this was quite a Sisyphean task,” says Tobias Bonhoeffer, the Director of the department where the research was carried out.
Synaptic stability – a concerted effort
The scientists discovered that during synapse growth the different protein structures always grew coordinated with each other. If one structural component was enlarged alone, or in a way that was not correctly correlated with the other components, its structural change would collapse soon after. Synapses with such incomplete changes cannot store any long-term memories.
The study findings show that the order and interaction between synaptic components is finely tuned and correlated. “In a system of this kind, it should be entirely possible to replace individual proteins while the rest of the structure maintains its integrity,” says Scheuss. However, if an entire group of components breaks away, the synapse is destabilised. This is also an important process given that the brain could not function correctly without the capacity to forget things. Hence, the study’s results provide not only important insight into the functioning and structure of synapses, they also establish a basis for a better understanding of memory loss, for example in the case of degenerative brain diseases.
Why your nose can be a pathfinder
When I was a child I used to sit in my grandfather’s workshop, playing with wood shavings. Freshly shaven wood has a distinct smell of childhood happiness, and whenever I get a whiff of that scent my brain immediately conjures up images of my grandfather at his working bench, the heat from the fireplace and the dog next to it.
Researchers at the Kavli Institute for Systems Neuroscience have recently discovered the process behind this phenomenon. The brain, it turns out, connects smells to memories through an associative process where neural networks are linked through synchronised brain waves of 20-40 Hz.
– We all know that smell is connected to memories, Kei Igarashi, lead author, explains.– We know that neurons in different brain regions need to oscillate in synchrony for these regions to speak effectively to each other. Still, the relationship between interregional coupling and formation of memory traces has remained poorly understood. So we designed a task to investigate how odour-place representation evolved in the entorhinal and hippocampal region, to figure out whether learning depends on coupling of oscillatory networks.
Smell guides the way in maze
The researchers designed a maze for rats, where a rat would see a hole to poke its nose into. When poking into the hole, the rat was presented with one of two alternative smells. One smell told the rat that food would be found in the left food cup behind the rat. The other smell told it that there was food in the right cup. The rat would soon learn which smell would lead to a reward where. After three weeks of training, the rats chose correctly on more than 85% of the trials. In order to see what happened inside the brain during acquisition, 16–20 electrode pairs were inserted in the hippocampus and in different areas of the entorhinal cortex.
After the associations between smell and place were well established, the researchers could see a pattern of brain wave activity (the electrical signal from a large number of neurons) during retrieval.
Coherent brain activity evolves with learning
– Immediately after the rat is exposed to the smell there is a burst in activity of 20–40 Hz waves in a specific connection between an area in the entorhinal cortex, lateral entorhinal cortex (LEC), and an area in the hippocampus, distal CA1 (dCA1), while a similar strong response was not observed in other connections, Igarashi explains.
This coherence of 20–40 Hz activity in the LEC and dCA1 evolved in parallel with learning, with little coherence between these areas before training started. By the time the learning period was over, cells were phase locked to the oscillation and a large portion of the cells responded specifically to one or the other of the smell-odour pairs.
Long distance communication in brain mediated by waves
– This is not the first time we observe that the brain uses synchronised wave activity to establish network connections, Edvard Moser, director of the Kavli Institute for Systems Neuroscience says. – Both during encoding and retrieval of declarative memories there is an interaction between these areas mediated through gamma and theta oscillations. However, this is the first study to relate the development of a specific band of oscillations to memory performance in the hippocampus. Together, the evidence is now piling up and pointing in the direction of cortical oscillations as a general mechanism for mediating interactions among functionally specialised neurons in distributed brain circuits.
So, there you have it – the signals from your nose translate and connect to memories in an orchestrated symphony of signals in your head. Each of these memories connects to a location, pinpointed on your inner map. So when you feel a wave of reminiscence triggered by a fragrance, think about how waves created this connection in the first place.
University of Missouri researchers have previously shown that a genetic pre-disposition to be more or less motivated to exercise exists. In a new study, Frank Booth, a professor in the MU College of Veterinary Medicine, has found a potential link between the genetic pre-disposition for high levels of exercise motivation and the speed at which mental maturation occurs.
For his study, Booth selectively bred rats that exhibited traits of either extreme activity or extreme laziness. Booth then put the rats in cages with running wheels and measured how much each rat willingly ran on their wheels during a six-day period. He then bred the top 26 runners with each other and bred the 26 rats that ran the least with each other. They repeated this process through 10 generations and found that the line of running rats chose to run 10 times more than the line of “lazy” rats.
Booth studied the brains of the rats and found much higher levels of neural maturation in the brains of the active rats than in the brains of the lazy rats.
“We looked at the part of the brain known as the ‘grand central station,’ or the hub where the brain is constantly sending and receiving signals,” Booth said. “We found a big difference between the amount of molecules present in the brains of active rats compared to the brains of lazy rats. This suggests that the active rats were experiencing faster development of neural pathways than the lazy rats.”
Booth says these findings may suggest a link between the genes responsible for exercise motivation and the genes responsible for mental development. He also says this research hints that exercising at a young age could help develop more neural pathways for motivation to be physically active.
“This study illustrates a potentially important link between exercise and the development of these neural pathways,” Booth said. “Ultimately, this could show the benefits of exercise for mental development in humans, especially young children with constantly growing brains.”