December 26

Open Borders: Remapping the Brain

While reading articles online, you may occasionally stumble across headlines like “Scientists find fear center of the brain,” or “Could this really be where the mind resides?” You might have also heard a TED talk where the speaker discusses how they discovered a part of the brain that makes decisions. Such expressions can take more poetic forms too: in the book The Feeling of Life Itself, the author and researcher Christof Koch continuously refers to the claustrum, a small, and enigmatic ring of neurons encircling the deepest parts of the brain, as the “seat of consciousness.” In the Kavanaugh hearings, Christine Blasey Ford meditated on how her memories of trauma were “indelible in the hippocampus,” a distinctive brain structure shaped like a seahorse. Even textbooks structure their lessons on movement around the “homunculus,” a map of the body in a region called the motor strip, with each part controlled by a different subsection of the strip assigned to it.

Though these sources don’t make the statement outright, all of these claims require a fundamental assumption that goes unacknowledged and unexamined. For such headlines to be true, each part of the brain must have a specific set of functions, unchanging and unique to it alone. In other words, the claustrum could not be the seat of consciousness if consciousness were located elsewhere half of the time, or if it was performed everywhere simultaneously.

On its face, the concept appears obvious. Our body mostly consists of highly specialized organs that carry out a few specific tasks, subdivided into specialized regions. Our heart will only ever maintain blood flow, using the atrium to take blood in and the ventricles to pump it out. We use our intestines to digest (itself divided into multiple function sections), and nearly every organ behaves similarly. If anything, it would be odd for the brain not to follow suit.

On an even simpler level, a generally static brain map just seems intuitive. When someone takes sudden damage to specific brain regions, they usually lose very specific mental functions. This relationship is so fundamental, it even formed the basis for our earliest understanding of the nervous system. In ancient Egypt, battlefield surgeons noticed that blows to the head often caused soldiers to lose certain functions, such as speech or motion, depending on where in the head they were struck. These observations led them to realize the brain controlled the body, with certain locations controlling certain functions. Other cultures also came to similar conclusions (the ancient Greeks and Romans even reached this same conclusion by examining similar battlefield injuries), and it eventually became an obvious consensus, standing for thousands of years with little reason for doubt.

As you almost certainly guessed, however, that is far from the end of the story. Sudden traumatic destruction of certain brain regions in adults does cause irreversible damage in most cases. On the other hand, not all trauma is sudden, not all trauma happens to adults, and loss of specific mental functions are not always due to brain damage or even any kind of trauma. In these cases, the results tend to be markedly different.

What happens if brain trauma occurs slowly, over decades, instead of immediately, over seconds? At the age of 14, a French teenager developed a blockage in his skull, preventing fluid from leaving [1]. After going to the hospital, the problem seemed to be solved. He went on to live a normal life, becoming a civil servant, getting married, and having two children. When he was 44, he went for a routine checkup after feeling mild leg weakness. His doctor ran a routine brain scan to see if the weakness was caused by the nervous system, and they were surprised by what they found.

The Frenchman appeared to possess little, if any brain at all. Instead, the vast majority of his skull was filled with fluid, with only a thin sheet of tissue pressed up against the skull remaining. Nearly every doctor consulted said his condition “should not be compatible with life.” While no one can definitively say why he survived, most believe the slow pace allowed the damaged parts of the brain to slowly transfer their functions to surviving regions over time. In such a case, mental function clearly defies regionalization.

emptyheadHowever, that is a single, isolated, special case. What about something a bit more common, where many people do not suffer trauma, but instead are born with regions of the brain they can’t use? For example, tens of thousands of children are born blind each year. All of them are born with a visual cortex, a large region of the back surface of the brain devoted to sight, which would remain unused for vision, consuming space and energy without contributing anything to cognition, if the brain were truly static.

Instead, the function of the “visual cortex” changes greatly for the blind. When a blind person is shown images, their visual cortex shows little activity (for hopefully obvious reasons). Unlike those with sight, however, the visual cortex does respond to a wide range of other inputs.  These include those somewhat similar to vision, such as other fundamental senses like touch and hearing, to those entirely distinct from its former function, most notably speech, language, and even math [2-4].

Both of these examples are rather striking incarnations of cortical remapping, where the brain can reshape its circuits to best take advantage of its inputs, or to accommodate other changes elsewhere, rewriting the brain’s functional ‘map’ to better fit the body. Though dramatic, cortical remapping is not actually a self-contained or specialized phenomenon: it is a large-scale version of neuroplasticity, where our neurons can change their features and connections to better respond to ever-changing incoming information. If you’re healthy, micro-scale neuroplasticity allows you to learn. However, if you have larger issues (e.g. if you are blind, or if you are a French civil servant), macro-scale neuroplasticity allows your brain to recover and to maintain somewhat normal function.

In other words, these boundaries become fluid under profound stress. Such changes are enabled by a process that’s always active, regardless of health status. Could these boundaries mistakenly remap in the absence of stress, or even further, could all functions actually be far less strictly bounded than originally thought? These fundamental questions and contradictions have begun a nascent re-evaluation of how we think about region and function relate to one another that threatens to upend our entire understanding of the nervous system as a whole.

The first such investigation was published by a group from Stanford in early 2019, examining how thirst affects the brain, a seemingly simple question on its face [5]. Traditionally, thirst has been considered relatively well-understood: the hypothalamus, a primitive region mostly controlling survival-necessary operations, contains hydration sensors that can detect low water content and signal to the rest of the brain and body that more water is needed, which we interpret as ‘thirst.’

Relatively straightforward, right? Not exactly. The Stanford group found that when animals are thirsty, they do not show activity changes in only their hypothalamus. They also show profound differences in nearly every region of the brain (including those from earlier, the motor strip and the hippocampus), none of which have been previously linked to thirst. Further, these changes were not universal, but particular to each brain region examined.

Such findings imply a specific role for each region in thirst, instead of a single change made to the brain overall, which would reduce the likelihood that each region’s change was actually meaningful. Instead, these findings point to a scenario where all regions are affected to some degree by the inputs, and each plays a corresponding role in its processing. Such a view lies in stark contrast to the consensus: far less parcellated, far more integrated.

This only covers the inputs into the brain, though. What about the outputs of the brain, our behavior? You hopefully won’t find this too surprising at this point, but the production of behavior is about as integrated as its response to inputs. A second study this year from another group in London recorded activity from 42 brain regions before mice chose actions in a behavioral task, specifically whether to walk or not [6].

A strictly-parcellated understanding would suggest that the motor strip would contain nearly all of the observed changes before movement in these mice, with little activity elsewhere. Instead, they found the opposite. Nearly every region played a part, feeding into a greater pattern of brain activity that together produces motion, instead of a single region exerting complete control on its own. These findings extend this new integrated view of the brain from the inputs to the outputs, while implying the same about everything in between, though more study is certainly needed.

Since time immemorial, a single view of the brain has predominated: function is well-defined, static, and uniquely localized. Recently, these maps have begun to come apart, due to cases both typical and atypical, for processes both mundane and profound, in sickness and in health. While far more research remains to be done, it is quickly becoming clear that our past models are quickly becoming less and less tenable, and a new, more fluid consensus is slowly emerging, though we do not yet know its final form, if it even has one at all. All we can truly know is that our understanding will never quite be the same.

  1. Feuillet, L., Dufour, H., Pelletier, J. (2007). The brain of a white-collar worker. The Lancet. 370:262.
  2. Burton, H. (2003). Visual Cortex Activity in Early and Late Blind People. J Neurosci. 23:4005-4011.
  3. Bedny, M., et al. (2011). Language processing in the occipital cortex of congenitally blind adults. Proc. Natl. Acad. Sci. USA. 108:4429-4434.
  4. Kanjlia, S., et al. (2016). Absence of visual experience modifies the neural basis of numerical thinking. Proc. Natl. Acad. Sci. USA. 113:11172-11171.
  5. Allen, W., et al. (2019). Thirst regulates motivated behavior through modulation of brainwide neural population dynamics. Science. 364:eaav3932.
  6. Steinmetz, N., et al. (2019). Distributed coding of choice, action and engagement across the mouse brain. Nature. 576:266-273.