Anti-seizure drugs don’t work in about a third of people with epilepsy. But for people with focal epilepsy, whose seizures originate in a discrete area of the brain, surgery is sometimes an option. The diseased brain tissue that’s removed also offers a rare opportunity to discover epilepsy-related genes.
Many mutations causing epilepsy have been discovered by testing DNA taken from the blood. But it’s becoming clear that not all epilepsy mutations show up on blood tests. So-called somatic mutations can arise directly in tissues like the brain during early prenatal development. Even within the brain, these mutations may affect only a fraction of the cells — those descended from the original mutated cell. This can create a “mosaic” pattern, with affected and unaffected cells sometimes intermingling.
One of the first such mutations to be described, by Ann Poduri, MD, MPH, and colleagues at Boston Children’s Hospital in 2012, was in Dante, a young boy who was having relentless daily seizures. The entire right side of Dante’s brain was malformed and enlarged, and he underwent a drastic operation, hemispherectomy, to remove it. Only later, studying brain samples from Dante and similar children, did Poduri find the genetic cause: a mutation in the gene AKT3. It affected only about a third of Dante’s brain cells. …
The earlier autism can be diagnosed, the more effective interventions typically are. But the signs are often subtle or can be misinterpreted at young ages. As a result, many children aren’t diagnosed until age 2 or even older. Now, a study shows that electroencephalograms (EEGs), which measure the brain’s electrical activity, can accurately predict or rule out autism spectrum disorder (ASD) in babies as young as 3 months old. It appears today in Scientific Reports.
The beauty of EEG is that it’s already used in many pediatric neurology or developmental pediatric settings. “EEGs are low-cost, non-invasive and relatively easy to incorporate into well-baby checkups,” says study co-author Charles Nelson, PhD, director of the Laboratories of Cognitive Neuroscience at Boston Children’s Hospital. “Their reliability in predicting whether a child will develop autism raises the possibility of intervening very early, well before clear behavioral symptoms emerge.” …
Mouse brains are tiny and smooth. Ferret brains are larger and convoluted. And ferrets, members of the weasel family, could provide the missing link in understanding how we humans acquired our big brains.
Children with microcephaly, whose brains are abnormally small, have a part in the story too. Microcephaly is notorious for its link to the Zika virus, but it can also be caused by mutations in various genes. Some of these genes have been shown to be essential for growth of the cerebral cortex, the part of our brain that handles higher-order thinking.
“I’m trained as a neurologist, and study kids with developmental brain diseases,” said Walsh in a press release from the Howard Hughes Medical Institute, which gave him a boost to his usual budget to support this work. “I never thought I’d be peering into the evolutionary history of humankind.” …
What drives me as a scientist has changed over the course of my career. It was my fascination with experimentation that first got me interested in biology. In high school, I took vials of fruit flies to a radiation oncology department and tested the effects of radiation on the mutation rate. When I came to the U.S. to study biochemistry in college, I was drawn to the mysteries of the brain. While my PhD and postdoctoral work continued on very fundamental questions about how neurons connect to each other, advances in genetics and neuroscience allowed me to bring rigorous basic science approaches to clinical questions. So more and more, my science is driven by a need to bring treatments to the patients I see in the clinic. Fortunately, this is no longer a long-term, aspirational goal, but something within reach in my career. …
Babies can hear and respond to sounds, including language, before birth. In fact, research shows that babies learn to recognize words in the womb. Now, an advanced MRI technique called diffusion tensor imaging is providing a fine-tuned view of when different brain areas mature, including the areas that process sound. And the findings suggest that babies born prematurely may have disruptions in auditory brain development and in speech.
Investigators at Boston Children’s Hospital, Brigham and Women’s Hospital, Washington University School of Medicine in St. Louis and University College London analyzed advanced MRI brain images from 90 preterm infants and 15 infants born at full term (40 weeks). Fifty-six of the preterm infants were imaged at multiple time points. As shown above, the team focused on a particular fold in the brain called Heschl’s gyrus (HG). This area contains the primary auditory cortex, the first part of the auditory cortex to receive sound signals, and the non-primary auditory cortex, which plays a higher-level role in processing those stimuli.
As seen in these sample images, the primary cortex has largely matured at 28 weeks’ postmenstrual age (PMA), whereas the non-primary auditory cortex has had a surge in development between 28 and 40 weeks’ PMA. Both regions appeared underdeveloped in the premature infants as compared with the infants born at term.
The study further found that disturbed maturation of the non-primary cortex was associated with poorer expressive language ability at age 2. The team suggests that this area may be especially vulnerable to disruption in a premature birth because it is undergoing such rapid change.
The study was published in eNeuro, an open-access journal from the Society for Neuroscience. Jeffrey Neil, MD, PhD, of Boston Children’s Department of Neurology, was senior author on the paper. First author Brian Monson, PhD, is now at the University of Illinois at Urbana-Champaign. Read more in the university’s press release.
Like all cells, the neurons of our nervous system depend on mitochondria to generate energy. Mitochondria need constant rejuvenation and turnover, and that’s especially true in neurons because of their high energy needs for signaling and “firing.” Mitochondria are especially abundant at presynaptic sites — the tips of axons that form synapses or junctions with other neurons and release neurotransmitters.
But the process of maintaining mitochondrial number and quality, known as mitostasis, also poses particular challenges in neurons. Increasingly, mitostasis is providing a helpful lens for understanding neurodegenerative disorders. Problems with mitostasis are implicated in Parkinson’s disease, Alzheimer’s disease, ALS, autism, stroke, multiple sclerosis, hypoxia and more. …
Autism spectrum disorder (ASD) is increasingly linked with dysfunction of the cerebellum, but the details, to date, have been murky. Now, a rare genetic syndrome known as tuberous sclerosis complex (TSC) is providing a glimpse.
TSC includes features of ASD in about half of all cases. Previous brain autopsies have shown that patients with TSC, as well as patients with ASD in general, have reduced numbers of Purkinje cells, the main type of neuron that communicates out of the cerebellum.
In a 2012 mouse study, team led by Mustafa Sahin, MD, at Boston Children’s Hospital, knocked out a TSC gene (Tsc1) in Purkinje cells. They found social deficits and repetitive behaviors in the mice, together with abnormalities in the cells.
Neuropathic pain is chronic pain originating through some malfunction of the nervous system, often triggered by an injury. It causes hypersensitivity to innocuous stimuli and is often extremely debilitating. It doesn’t respond to existing painkillers — even opioids can’t reach it well.
New research in a mouse model, described last week in Cell Reports, deconstructed neuropathic pain and could offer new leads for treating it. The carefully done study showed that two major neuropathic pain symptoms in patients — extreme touch sensitivity and extreme cold sensitivity — operate through separate pathways.
“We think this separation will allow targeted drug-based therapies in the future,” says Michael Costigan, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, who was the study’s senior investigator. “If our results stand experimental scrutiny by others, this will be profoundly important in our overall understanding of neuropathic pain.” …
Babies’ brains are like sponges — highly tuned to incoming sensory information and readily rewiring their circuits. But when so-called critical periods close, our brains lose much of this plasticity. Classic experiments reveal this in the visual system: when kittens and mice had one eye covered shortly after birth, that eye was blind for life, even after the covering was removed. The brain never learned to interpret the visual inputs.
In 2010, a study led by Takao Hensch, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, showed that levels of a protein called Lynx1 rise just as the critical period for visual acuity closes. When the researchers deleted the Lynx1 gene in mice, the critical period reopened and mice recovered vision in the blind eye.
Light affects us even without impinging on our awareness. In 1995, Charles Czeisler and colleagues at Harvard Medical School described people who lacked visual perception due to retinal degeneration, but nevertheless responded to light subconsciously — despite being blind, their melatonin level was suppressed, and they appeared to synchronize their circadian clock with the solar day. Across the pond at Oxford, Russell Foster and colleagues were finding the same in mice, and learned that these responses began in the eye.
These discoveries spurred an intense research effort that continues to this day. What system confers subconscious sight, and how does it differ from the system that generates visual experience? …