Institute News: Ask the Brain

Why is the brain shaped like it is?

by Sabbi Lall |

The human brain has a very striking shape, and one feature stands out large and clear: the cerebral cortex with its stereotyped pattern of gyri (folds and convolutions) and sulci (fissures and depressions). This characteristic folded shape of the cortex is a major innovation in evolution that allowed an increase in the size and complexity of the human brain.

How the brain adopts these complex folds is surprisingly unclear, but probably involves both shape changes and movement of cells. Mechanical constraints within the overall tissue, and imposed by surrounding tissues also contribute to the ultimate shape: the brain has to fit into the skull after all. McGovern postdoc Jonathan Wilde has a long-term interest in studying how the brain develops, and explained to us how the shape of the brain initially arises.

In the case of humans, our historical reliance upon intelligence has driven a massive expansion of the cerebral cortex.

“Believe it or not, all vertebrate brains begin as a flat sheet of epithelial cells that folds upon itself to form a tube,” explains Wilde. “This neural tube is made up of a single layer of neural stem cells that go through a rapid and highly orchestrated process of expansion and differentiation, giving rise to all of the neurons in the brain. Throughout the first steps of development, the brains of most vertebrates are indistinguishable from one another, but the final shape of the brain is highly dependent upon the organism and primarily reflects that organism’s lifestyle, environment, and cognitive demands.”

So essentially, the brain starts off as a similar shape for creatures with spinal cords. But why is the human brain such a distinct shape?

“In the case of humans,” explains Wilde, “our historical reliance upon intelligence has driven a massive expansion of the cerebral cortex, which is the primary brain structure responsible for critical thinking and higher cognitive abilities. Accordingly, the human cortex is strikingly large and covered in a labyrinth of folds that serve to increase its surface area and computational power.”

The anatomical shape of the human brain is striking, but it also helps researchers to map a hidden functional atlas: specific brain regions that selectively activate in fMRI when you see a face, scene, hear music and a variety of other tasks. I asked former McGovern graduate student, and current postdoc at Boston Children’s Hospital, Hilary Richardson, for her perspective on this more hidden structure in the brain and how it relates to brain shape.

Illustration of person rappelling into the brain's sylvian fissure.
The Sylvian fissure is a prominent groove on each side of the brain that separates the frontal and parietal lobes from the temporaal lobe. McGovern researchers are studying a region near the right Sylvian fissure, called the rTPJ, which is involved in thinking about what another person is thinking. Image: Joe Laney

“One of the most fascinating aspects of brain shape is how similar it is across individuals, even very young infants and children,” explains Richardson. “Despite the dramatic cognitive changes that happen across childhood, the shape of the brain is remarkably consistent. Given this, one open question is what kinds of neural changes support cognitive development. For example, while the anatomical shape and size of the rTPJ seems to stay the same across childhood, its response becomes more specialized to information about mental states – beliefs, desires, and emotions – as children get older. One intriguing hypothesis is that this specialization helps support social development in childhood.”

We’ll end with an ode to a prominent feature of brain shape: the “Sylvian fissure,” a prominent groove on each side of the brain that separates the frontal and parietal lobes from the temporal lobe. Such landmarks in brain shape help orient researchers, and the Sylvian fissure was recently immortalized in this image, from a postcard by illustrator Joe Laney.

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How does the brain focus?

by Sabbi Lall |

This is a very interesting question, and one that researchers at the McGovern Institute for Brain Research are actively pursuing. It’s also important for understanding what happens in conditions such as ADHD. There are constant distractions in the world, a cacophony of noise and visual stimulation. How and where we focus our attention, and what the brain attends to vs. treating as background information, is a big question in neuroscience. Thanks to work from researchers, including Robert Desimone, we understand quite a bit about how this works in the visual system in particular. What his lab has found is that when we pay attention to something specific, neurons in the visual cortex responding to the object we’re focusing upon fire in synchrony, whereas those responding to irrelevant information become suppressed. It’s almost as if this synchrony “increases the volume” so that the responding neurons rise above general noise.

Synchronized activity of neurons occurs as they oscillate together at a particular frequency, but the frequency of oscillation really matters when it comes to attention and focus vs. inattention and distraction. To find out more about this, I asked a postdoc in the Desimone lab, Yasaman Bagherzadeh about the role of different “brainwaves,” or oscillations at different frequencies, in attention.

“Studies in humans have shown that enhanced synchrony between neurons in the alpha range –8–12 Hz— is actually associated with inattention and distracting information,” explains Bagherzadeh, “whereas enhanced gamma synchrony (about 30-150 Hz) is associated with attention and focus on a target. For example, when a stimulus (through the ears or eyes) or its location (left vs. right) is intentionally ignored, this is preceded by a relative increase in alpha power, while a stimulus you’re attending to is linked to an increase in gamma power.”

Attention in the Desimone lab (no pun intended) has also recently been focused on covert attention. This type of spatial attention was traditionally thought to occur through a mental shift without a glance, but the Desimone lab recently found that even during these mental shifts, animal sneakily glance at objects that attention becomes focused on. Think now of something you know is nearby (a cup of coffee for example), but not in the center of your field of vision. Chances are that you just sneakily glanced at that object.

Previously these sneaky glances/small eye movements, called microsaccades (MS for short), were considered to be involuntary movements without any functional role. However, in the recent Desimone lab study, it was found that a MS significantly modulates neural activity during the attention period. This means that when you glance at something, even sneakily, it is intimately linked to attention. In other words, when it comes to spatial attention, eye movements seem to play a significant role.

Various questions arise about the mechanisms of spatial attention as a result this study, as outlined by Karthik Srinivasan, a postdoctoral associate in the Desimone lab.

“How are eye movement signals and attentional processing coordinated? What’s the role of the different frequencies of oscillation for such coordination? Is there a role for them or are they just the frequency domain representation (i.e., an epiphenomenon) of a temporal/dynamical process? Is attention a sustained process or rhythmic or something more dynamic?” Srinivasan lists some of the questions that come out of his study and goes on to explain the implications of the study further. “It is hard to believe that covert attention is a sustained process (the so-called ‘spotlight theory of attention’), given that neural activity during the attention period can be modulated by covert glances. A few recent studies have supported the idea that attention is a rhythmic process that can be uncoupled from eye movements. While this is an idea made attractive by its simplicity, it’s clear that small glances can affect neural activity related to attention, and MS are not rhythmic. More work is thus needed to get to a more unified theory that accounts for all of the data out there related to eye movements and their close link to attention.”

Answering some of the questions that Bagherzadeh, Srinivasan, and others are pursuing in the Desimone lab, both experimentally and theoretically, will clear up some of the issues above, and improve our understanding of how the brain focuses attention.

Do you have a question for The Brain? Ask it here.

 

How do neurons communicate (so quickly)?

by Sabbi Lall |

Neurons are the most fundamental unit of the nervous system, and yet, researchers are just beginning to understand how they perform the complex computations that underlie our behavior. We asked Boaz Barak, previously a postdoc in Guoping Feng’s lab at the McGovern Institute and now Senior Lecturer at the School of Psychological Sciences and Sagol School of Neuroscience at Tel Aviv University, to unpack the basics of neuron communication for us.

“Neurons communicate with each other through electrical and chemical signals,” explains Barak. “The electrical signal, or action potential, runs from the cell body area to the axon terminals, through a thin fiber called axon. Some of these axons can be very long and most of them are very short. The electrical signal that runs along the axon is based on ion movement. The speed of the signal transmission is influenced by an insulating layer called myelin,” he explains.

Myelin is a fatty layer formed, in the vertebrate central nervous system, by concentric wrapping of oligodendrocyte cell processes around axons. The term “myelin” was coined in 1854 by Virchow (whose penchant for Greek and for naming new structures also led to the terms amyloid, leukemia, and chromatin). In more modern images, the myelin sheath is beautifully visible as concentric spirals surrounding the “tube” of the axon itself. Neurons in the peripheral nervous system are also myelinated, but the cells responsible for myelination are Schwann cells, rather than oligodendrocytes.

“Neurons communicate with each other through electrical and chemical signals,” explains Boaz Barak.

“Myelin’s main purpose is to insulate the neuron’s axon,” Barak says. “It speeds up conductivity and the transmission of electrical impulses. Myelin promotes fast transmission of electrical signals mainly by affecting two factors: 1) increasing electrical resistance, or reducing leakage of the electrical signal and ions along the axon, “trapping” them inside the axon and 2) decreasing membrane capacitance by increasing the distance between conducting materials inside the axon (intracellular fluids) and outside of it (extracellular fluids).”

Adjacent sections of axon in a given neuron are each surrounded by a distinct myelin sheath. Unmyelinated gaps between adjacent ensheathed regions of the axon are called Nodes of Ranvier, and are critical to fast transmission of action potentials, in what is termed “saltatory conduction.” A useful analogy is that if the axon itself is like an electrical wire, myelin is like insulation that surrounds it, speeding up impulse propagation, and overcoming the decrease in action potential size that would occur during transmission along a naked axon due to electrical signal leakage, how the myelin sheath promotes fast transmission that allows neurons to transmit information long distances in a timely fashion in the vertebrate nervous system.

Myelin seems to be critical to healthy functioning of the nervous system; in fact, disruptions in the myelin sheath have been linked to a variety of disorders.

Former McGovern postdoc, Boaz Barak. Photo: Justin Knight

“Abnormal myelination can arise from abnormal development caused by genetic alterations,” Barak explains further. “Demyelination can even occur, due to an autoimmune response, trauma, and other causes. In neurological conditions in which myelin properties are abnormal, as in the case of lesions or plaques, signal transmission can be affected. For example, defects in myelin can lead to lack of neuronal communication, as there may be a delay or reduction in transmission of electrical and chemical signals. Also, in cases of abnormal myelination, it is possible that the synchronicity of brain region activity might be affected, for example, leading to improper actions and behaviors.”

Researchers are still working to fully understand the role of myelin in disorders. Myelin has a long history of being evasive though, with its origins in the central nervous system being unclear for many years. For a period of time, the origin of myelin was thought to be the axon itself, and it was only after initial discovery (by Robertson, 1899), re-discovery (Del Rio-Hortega, 1919), and skepticism followed by eventual confirmation, that the role of oligodendrocytes in forming myelin became clear. With modern imaging and genetic tools, we should be able to increasingly understand its role in the healthy, as well as a compromised, nervous system.

Do you have a question for The Brain? Ask it here.

What is CRISPR?

by The Brain |

CRISPR (which stands for Clustered Regularly Interspaced Short Palindromic Repeats) is not actually a single entity, but shorthand for a set of bacterial systems that are found with a hallmarked arrangement in the bacterial genome.

When CRISPR is mentioned, most people are likely thinking of CRISPR-Cas9, now widely known for its capacity to be re-deployed to target sequences of interest in eukaryotic cells, including human cells. Cas9 can be programmed to target specific stretches of DNA, but other enzymes have since been discovered that are able to edit DNA, including Cpf1 and Cas12b. Other CRISPR enzymes, Cas13 family members, can be programmed to target RNA and even edit and change its sequence.

The common theme that makes CRISPR enzymes so powerful, is that scientists can supply them with a guide RNA for a chosen sequence. Since the guide RNA can pair very specifically with DNA, or for Cas13 family members, RNA, researchers can basically provide a given CRISPR enzyme with a way of homing in on any sequence of interest. Once a CRISPR protein finds its target, it can be used to edit that sequence, perhaps removing a disease-associated mutation.

In addition, CRISPR proteins have been engineered to modulate gene expression and even signal the presence of particular sequences, as in the case of the Cas13-based diagnostic, SHERLOCK.

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Can the brain recover after paralysis?

by The Brain |

Why is it that motor skills can be gained after paralysis but vision cannot recover in similar ways? – Ajay, Puppala

Thank you so much for this very important question, Ajay. To answer, I asked two local experts in the field, Pawan Sinha who runs the vision research lab at MIT, and Xavier Guell, a postdoc in John Gabrieli’s lab at the McGovern Institute who also works in the ataxia unit at Massachusetts General Hospital.

“Simply stated, the prospects of improvement, whether in movement or in vision, depend on the cause of the impairment,” explains Sinha. “Often, the cause of paralysis is stroke, a reduction in blood supply to a localized part of the brain, resulting in tissue damage. Fortunately, the brain has some ability to rewire itself, allowing regions near the damaged one to take on some of the lost functionality. This rewiring manifests itself as improvements in movement abilities after an initial period of paralysis. However, if the paralysis is due to spinal-cord transection (as was the case following Christopher Reeve’s tragic injury in 1995), then prospects for improvement are diminished.”

“Turning to the domain of sight,” continues Sinha, “stroke can indeed cause vision loss. As with movement control, these losses can dissipate over time as the cortex reorganizes via rewiring. However, if the blindness is due to optic nerve transection, then the condition is likely to be permanent. It is also worth noting that many cases of blindness are due to problems in the eye itself. These include corneal opacities, cataracts and retinal damage. Some of these conditions (corneal opacities and cataracts) are eminently treatable while others (typically those associated with the retina and optic nerve) still pose challenges to medical science.”

You might be wondering what makes lesions in the eye and spinal cord hard to overcome. Some systems (the blood, skin, and intestine are good examples) contain a continuously active stem cell population in adults. These cells can divide and replenish lost cells in damaged regions. While “adult-born” neurons can arise, elements of a degenerating or damaged retina, optic nerve, or spinal cord cannot be replaced as easily lost skin cells can. There is currently a very active effort in the stem cell community to understand how we might be able to replace neurons in all cases of neuronal degeneration and injury using stem cell technologies. To further explore lesions that specifically affect the brain, and how these might lead to a different outcome in the two systems, I turned to Xavier Guell.

“It might be true that visual deficits in the population are less likely to recover when compared to motor deficits in the population. However, the scientific literature seems to indicate that our body has a similar capacity to recover from both motor and visual injuries,” explains Guell. “The reason for this apparent contradiction is that visual lesions are usually not in the cerebral cortex (but instead in other places such as the retina or the lens), while motor lesions in the cerebral cortex are more common. In fact, a large proportion of people who suffer a stroke will have damage in the motor aspects of the cerebral cortex, but no damage in the visual aspects of the cerebral cortex. Crucially, recovery of neurological functions is usually seen when lesions are in the cerebral cortex or in other parts of the cerebrum or cerebellum. In this way, while our body has a similar capacity to recover from both motor and visual injuries, motor injuries are more frequently located in the parts of our body that have a better capacity to regain function (specifically, the cerebral cortex).”

In short, some cells cannot be replaced in either system, but stem cell research provides hope there. That said, there is remarkable plasticity in the brain, so when the lesion is located there, we can see recovery with training.

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Why do I talk with my hands?

by The Brain |

This is a very interesting question sent to us by Gabriel Castellanos (thank you!) Many of us gesture with our hands when we speak (and even when we do not) as a form of non-verbal communication. How hand gestures are coordinated with speech remains unclear. In part, it is difficult to monitor natural hand gestures in fMRI-based brain imaging studies as you have to stay still.

“Performing hand movements when stuck in the bore of a scanner is really tough beyond simple signing and keypresses,” explains McGovern Principal Research Scientist Satrajit Ghosh. “Thus ecological experiments of co-speech with motor gestures have not been carried out in the context of a magnetic resonance scanner, and therefore little is known about language and motor integration within this context.”

There have been studies that use proxies such as co-verbal pushing of buttons, and also studies using other imaging techniques, such as electroencephalography (EEG) and magnetoencephalography (MEG), to monitor brain activity during gesturing, but it would be difficult to precisely spatially localize the regions involved in natural co-speech hand gesticulation using such approaches. Another possible avenue for addressing this question would be to look at patients with conditions that might implicate particular brain regions in coordinating hand gestures, but such approaches have not really pinpointed a pathway for coordinating speech and hand movements.

That said, co-speech hand gesturing plays an important role in communication. “More generally co-speech hand gestures are seen as a mechanism for emphasis and disambiguation of the semantics of a sentence, in addition to prosody and facial queues,” says Ghosh. “In fact, one may consider the act of speaking as one large orchestral score involving vocal tract movement, respiration, voicing, facial expression, hand gestures, and even whole body postures acting as different instruments coordinated dynamically by the brain. Based on our current understanding of language production, co-speech or gestural events would likely be planned at a higher level than articulation and therefore would likely activate inferior frontal gyrus, SMA, and others.”

How this orchestra is coordinated and conducted thus remains to be unraveled, but certainly the question is one that gets to the heart of human social interactions.

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Does our ability to learn new things stop at a certain age?

by The Brain |

This is actually a neuromyth, but it has some basis in scientific research. People’s endorsement of this statement is likely due to research indicating that there is a high level of synaptogenesis (formation of connections between neurons) between ages 0-3, that some skills (learning a new language, for example) do diminish with age, and some events in brain development, such as connections in the visual system, are tied to exposure to a stimulus, such as light. That said, it is clear that a new language can be learned later in life, and at the level of synaptogenesis, we now know that synaptic connections are plastic.

If you thought this statement was true, you’re not alone. Indeed, a 2017 study by McGrath and colleagues found that 18% of the public (N = 3,045) and 19% of educators (N = 598) believed this statement was correct.

Learn more about how teachers and McGovern researchers are working to target learning interventions well past so-called “critical periods” for learning.

Yanny or Laurel?

Anne Trafton |

“Yanny” or “Laurel?” Discussion around this auditory version of “The Dress” has divided the internet this week.

In this video, brain and cognitive science PhD students Dana Boebinger and Kevin Sitek, both members of the McGovern Institute, unpack the science — and settle the debate. The upshot? Our brain is faced with a myriad of sensory cues that it must process and make sense of simultaneously. Hearing is no exception, and two brains can sometimes “translate” soundwaves in very different ways.