Rewiring the Brain: How the Nervous System Heals Itself
Lucas Angles
Illustrations by: Yuchen Wang
You wake up one morning and immediately feel that something is off. As you grab a shirt and a pair of pants off the floor, you realize you can somehow put your shirt on with your right hand and your pants on with your left. You decide to further test your newfound ability; after making a pot of coffee, you discover that you’re fully capable of pouring the coffee with one hand while simultaneously reading a book with the other. This skill may sound like a superpower to most of us, but for those with “split-brain,” or callosal syndrome, these experiences are common.
In neurotypical individuals, the brain is separated into the left and right hemispheres. The two halves communicate through the corpus callosum, which can be thought of as a drawbridge, allowing each hemisphere of the brain to coordinate neural activity. This neural bridge consists of a network of connections spanning the midsection of the brain. Neural “checkpoints” carefully guard against unlawful travelers by monitoring for abnormal signals. However, in epileptic brains, these checkpoints are absent, allowing any neural signal to cross this bridge. Those with epilepsy experience seizures as a result of random signals traveling through the corpus callosum uninhibited.
Logically, in one form of epilepsy treatment, surgeons sever the corpus callosum, effectively “raising the drawbridge” to stop any signals from getting across. This disconnection results in the “split-brain” phenomenon that gives the syndrome its name. As the two hemispheres can no longer communicate, the movement of a body part is not registered by the rest of the brain, causing half of the body to operate unconsciously. However, seizures may still persist after the corpus callosum has been severed. In this case, surgeons remove the regions where uncontrolled signaling originates. These procedures involve full or partial removal of the damaged brain region, the size of which can range from a fraction of a centimeter to an entire hemisphere [1].
Surgery: The Last Resort for Epilepsy Treatment
However, the removal of an entire hemisphere of the human brain is a significant clinical decision and typically only reserved for epileptic patients who have already tried every other possible treatment. In fact, only about 3% of eligible Americans elect to undergo any sort of epileptic surgery each year due to its invasive nature. More than 2.2 million Americans are currently diagnosed with epilepsy, making it the fourth most common neurological disease in the United States [1]. “Epilepsy,” however, is often used as an umbrella term. Because there are hundreds of similar neurodegenerative conditions that may result in epileptic seizures, neurologists typically group them all together for ease of treatment. As these conditions all manifest in the same symptoms, they can generally be treated in the same manner. Doctors commonly prescribe a combination of strict diet and medication, which works to stop indiscriminate neural signaling, regardless of the underlying condition. [2].
Hospitals in the U.S. perform around 100 hemispherectomies per year, primarily to treat severe childhood brain damage [3]. The culprit in most surgical cases is Perinatal Arterial Ischemic Stroke (PAIS), a severe form of fetal stroke [4]. Much like how barges move cargo up and down a river, red blood cells act as couriers and deliver oxygen to other cells they pass by. A stroke is actually much like the recent blockage of the Suez Canal. Blood flow to the brain is obstructed, depriving neurons of oxygen and thereby killing them. Neurological damage from PAIS manifests as rapid convulsions of a specific body part. These seizures result from the haphazard firing of neurons controlling voluntary movement. Anti-seizure medicine is often used as a primary form of treatment for PAIS damage. These drugs act as a bouncer, blocking signals before they begin in order to stop neurons from firing repeatedly [2]. However, if neurologists observe no noticeable improvement with medication, surgery may be performed as a last resort [4].
How to Detach a Hemisphere, In Part Or In Whole
A hemispherectomy can take anywhere from five to twelve hours to complete, and it consists of three phases: incision, removal, and reattachment. [5]. After the brain is exposed, surgeons begin by severing the corpus callosum [6]. This procedure ensures that the damage stays localized to the extracted hemisphere and cannot cause seizures after the operation. The impaired hemisphere is then disconnected from the brainstem and inner lining of the skull before being removed. The extracted skull fragment is then replaced, and the scalp is sutured shut [5, 6].
The first procedure of this kind, performed in the 1920s, was termed an “anatomical hemispherectomy” and has since been used to treat a variety of seizure disorders [3]. In an anatomical hemispherectomy, surgeons remove the patient’s entire hemisphere. The frontal, parietal, temporal, and occipital lobes are all separated from the healthy brain, leaving only essential deep-brain systems like the thalamus and basal ganglia behind. These structures can remain intact, as they may actually work to prevent seizures [7]. Since the outer structures control vision and movement, patients often experience partial peripheral vision loss and weakness in half of their body after surgery. Prolonged operation times and extensive blood loss are relatively common risks of the procedure because so much of the brain tissue is removed. A buildup of excess fluid in the space of the removed hemisphere, called hydrocephalus, also occurs in about 20% of patients. Because of these risks, surgeons today tend to remove an entire hemisphere only when the whole region is damaged [5].
Similarly, the inherent risks associated with anatomical hemispherectomies have led surgeons to seek a more targeted approach when treating neurological damage. Over the last two decades, functional hemispherectomies have risen in popularity as a safer, less invasive alternative to anatomical resection [8]. In this procedure, rather than removing one full hemisphere, only the regions responsible for communication between hemispheric connections to deep-brain structures are severed to prevent seizures. However, both halves of the brain still remain inside the skull. This technique drastically lowers the risk of complications compared to an anatomical hemispherectomy. Leaving both halves of the brain intact is like plugging a leak with a cork. This approach makes fluid buildup in the brain rare, and surgeons can perform the surgery with minimal blood loss. After all of its connections are severed, the targeted hemisphere cannot respond to messages from its complement and acts as a static placeholder. With a success rate comparable to that of an anatomic hemispherectomy at over 85% and 90% reduction in hydrocephalus, functional resections have become a much more standard procedure in the United States [8, 9].
The sheer scale of this eight-hour surgery can seem frightening. However, recent research has shown rapid neural restructuring in the brains of children who underwent hemispherectomies can compensate for this loss of tissue. Many young patients exhibit striking improvements in motor and cognitive functioning in the years following surgery [10]. This adaptive response demonstrates the brain’s versatility and allows scientists to study neural changes following a hemispherectomy to potentially rewire neural pathways and bypass areas of neural damage.
Structural Changes in the Brain
For much of the 20th century, the world regarded the brain as one of the most structurally static organs in the human body. During development, cognitive and intellectual advances were thought to be purely psychological, with no relation to the brain’s anatomical structure. Scientists did not observe neurons multiplying after birth, nor were patients observed regrowing lost portions of grey matter [11]. However, studies in the mid-1900s conducted on people who suffered strokes suggested that the brain could adapt its structure to accommodate substantial alterations. Researchers noticed that subjects with large regions of cell death repurposed their remaining neurons to make up for functional loss, coining the term “neuroplasticity” to describe the phenomenon [11]. While scientists 100 years ago were primarily concerned with the brain’s general structure, today we can begin to understand neuroplasticity mechanisms at a cellular level.
A process called long-term potentiation (LTP) helps explain neuroplasticity at the neuronal level. When a neuron in the brain regularly fires due to a repeated thought or action, the cell is modified to enhance that connection, creating branched structures that attach to the receiving cell body. This growth, combined with the increased production of chemical signals, leads to a significant increase in signaling strength [12]. The neuron then fires more readily and requires a less powerful stimulus to activate, resulting in a domino effect that can stimulate thousands of connected neurons. Put simply, neurons that fire together wire together. Researchers have observed this transformation in children, adults, and the elderly. They have concluded that LTP is the mechanism behind processes such as learning and memory since it results in the rapid creation of novel connections that encode new thoughts and experiences. Although LTP occurs on a molecular level at any age, the drastic structural reorganization of brain cells after a hemispherectomy is primarily seen in very young children. These impressive changes have been attributed to three significant neural shifts: developmental, adaptive, and reactive plasticity.
Developmental Plasticity
Developmental plasticity refers primarily to the flexibility of neuronal connections in an infant’s brain after birth. Synapses, or the cellular bridges between individual neurons, are primarily formed through LTP, which means connections are only developed and strengthened through continued use and experience. In the first two years of a newborn’s life, the rate of synapse formation skyrockets as they experience the world around them [13]. For example, when a baby learns a new sound or color, neurons responsible for hearing or vision begin making connections with other neurons that code for memories. This phenomenon is why certain childhood memories come to mind after listening to a song or taking in a smell! After the period of synaptic development, neurons undergo ‘synaptic pruning,’ a process similar to housekeeping, in which the connections to infrequently used neurons are destroyed to free up space for synapse formation later in life. This process explains why young children can pick up foreign languages much more readily than adults – the synaptic connections used for the language are used early and therefore safe from destruction [14, 15]. Researchers have observed brain volume to decrease over time, suggesting that this synaptic cleanup actually changes the brain’s physical structure [16].
Adaptive Plasticity
While developmental plasticity is principally concerned with the nervous system’s maturation over time, adaptive plasticity involves practice and repetition. This process is prevalent in athletes, musicians, and others who go through repeated motions or tasks. As you rehearse a given action, the required neurons develop their connections, leading to easier recall and repetition, allowing you to perform the activity faster and more accurately [17]. Researchers examining musicians’ brains have revealed a significant increase in grey matter in the regions associated with music production and speech, indicating actual structural changes in the brain in response to practice [17]. Similar to findings related to developmental plasticity, studies have shown that children and adolescents are most prone to developing structural modification, though these alterations can continue well into adulthood [18]. The time dependency of adaptive plasticity is reflected in the top athletes and musicians today. Most have started honing their craft exceptionally early in their lives, quickly developing the neural connections they need with each practice.
Reactive Plasticity
The final type of neural change –– reactive plasticity –– is concerned with the deprivation of neural signals from a part of the brain. This process follows the loss of sensory input over long periods of time and is most commonly associated with people who are blind or deaf [19]. Pop culture often portrays blind and deaf individuals as having heightened senses. Characters like Matt Murdock in Marvel’s Daredevil are portrayed to gain superhuman levels of perception, allowing them to experience the world in a novel way. Although this phenomenon has been exaggerated for dramatic effect, researchers have observed alteration in brain structure and added sensory strength in blind and deaf people as a compensatory mechanism. A study of infants born deaf found that neurons typically utilized in hearing can instead participate in the visual pathway to enhance optical acuity [19]. As is the case with other types of plasticity, reactive plasticity is most active during early childhood and decreases in intensity with age. The same study found that adults who were born deaf had difficulty recognizing speech even after receiving a cochlear implant, a device that partially restores hearing. Neurons responsible for processes of hearing had already shifted to the visual system in early childhood and were now fixed in that position [10]. As all types of plasticity have a high dependence on age, many surgeons will only perform hemispherectomies on children younger than five years old to avoid debilitating loss of brain function. The change in brain structure following surgery is truly astounding.
Implications of Neuroplasticity on Hemispherectomy Outcome
We can witness many of these changes occurring in real-time in the sensorimotor system, a neuronal pathway that encompasses both the sensory system (responsible for touch) and the motor system (responsible for muscle contraction). Many think that each hemisphere of the brain gives and receives signals from the same side of the body, such as your right hemisphere controlling your right hand. Instead, your nerve cords “twist” and change sides at the junction where the brain meets the spine. Fibers originating in the right hemisphere cross over, connecting to muscles on your left side and vice versa [19]. This crossover explains why numbness and weakness in the side of the body opposite of the removed brain tissue are common after a hemispherectomy. Patients who have had their left hemisphere detached may have trouble raising their right arm or may walk with a limp in their right leg, as neurons that were once present to control such actions have been completely removed during surgery.
But how do patients move their arms and legs at all after a hemispherectomy if these pathways are severed? The answer lies in the remarkable plasticity of the brain. Scientists have recently observed that hemispherectomy patients show activation of the brain after a brief sensory stimulus on their skin [20]. Activation of the motor cortex through magnetic stimulation also resulted in movement on the same side of the body [21]. This phenomenon is most likely due to the combined effort of developmental, adaptive, and reactive plasticity, which work in tandem to strengthen signals through nerve pathways that do not “cross over.” The very act of trying to move a finger begins the process of LTP in these motor neurons, making the action progressively easier through the creation of more efficient synapses. By shifting the pathways typically used for movement and touch, half of the brain can take on the entire body’s sensorimotor processing.
Sensorimotor systems have existed in our evolutionary history for millions of years. From the first fish to humans, the direct pathway that such signals take through the brain has remained extremely simple and unchanged. However, the neurons that govern speech utilize a much more complex network of connections to help manage the intricacies of language. As a result, it is exponentially more challenging to recover functionality in a language than simply moving your arm. Although each hemisphere of the brain may appear identical, one half is dominant over the other in conducting specific tasks. In fact, in 90% of people, the left hemisphere plays a primary role in speech and language comprehension [22]. Therefore, if the left hemisphere is the half that requires surgery, it may not be easy for the individual to retain language and speech. This fact is reflected in the lower language test scores of those who have had their speech-dominant left hemisphere removed. Conversely, researchers have found minimal decreases in the language capacity in those who have had their non-dominant hemisphere removed [23].
However, those who undergo surgery — even in their dominant hemisphere — show significant improvement in speech over time [23]. Because of reactive neuroplasticity, patients who are minimally vocal in the weeks following surgery can reroute their speech pathways to the opposite hemisphere. Areas that once served as secondary functional regions to their dominant counterparts are “switched on” and used similarly to the original pathway. As the brain is structurally symmetrical, similar areas on the non-dominant hemisphere send and receive the same signals as the original, essentially acting as a replacement. In the same way that you can wear the same sock on different feet as they are physically similar, your brain can utilize these rarely used regions to regain function. The remaining hemisphere can gain further support by recruiting surrounding neurons to help deal with this new processing burden. These nearby cells aid in the signaling involved with language interpretation, association, and production, allowing the patient to speak more easily [24].
Researchers often examine patients with hemispherectomies to analyze the universal patterns of human neuroplasticity. As you read this sentence, your brain’s neurons are constantly modifying themselves so that you can remember, interpret, and communicate information more effectively. Scientists hope to model these processes to aid with neural rehabilitation from strokes, traumatic brain injury, or neurodegeneration. This damage can result in debilitating loss of function in multiple aspects of cognition, preventing the individual from participating in many day-to-day activities. Much of the current research on treating such disorders focuses on regrowing missing neurons [25]. However, by researching how and when plastic responses occur, scientists may one day be able to induce malleability in the brain long past the so-called “critical period” of adolescence. With this reconstruction, adults with lost function in areas like the motor cortex or the language pathway could rewire their neuronal circuitry to bypass damaged areas. Much like a detour around a blocked road, plastic neurons would form new connections that avoid these injured regions, instead utilizing alternative pathways to transmit messages. By studying the response of those who have lost vital brain tissue, we can turn our attention from regrowth to reuse.
REFERENCES
Schiltz, N. K., & Fernandez-Baca Vaca, G. (2018). Epidemiologist’s view: Addressing the epilepsy surgery treatment gap with minimally-invasive techniques. Epilepsy Research, 142, 179–181. doi: 10.1016/j.eplepsyres.2018.01.013
Rogawski, M. A., Löscher, W., & Rho, J. M. (2016). Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harbor Perspectives in Medicine, 6(5). doi:10.1101/cshperspect.a022780
Lin, Y., Harris, D. A., Curry, D. J., & Lam, S. (2015). Trends in outcomes, complications, and hospitalization costs for hemispherectomy in the United States for the years 2000-2009. Epilepsia, 56(1), 139–146. doi: 10.1111/epi.12869
Armstrong-Wells, J., & Ferriero, D. M. (2014). Diagnosis and acute management of perinatal arterial ischemic stroke. Neurol Clin Pract, 4(5), 378–385. doi: 10.1212/CPJ.0000000000000077
Fountas, K. N., Smith, J. R., Robinson, J. S., Tamburrini, G., Pietrini, D., & Di Rocco, C. (2006). Anatomical hemispherectomy. Child’s Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery, 22(8), 982–991. doi:10.1007/s00381-006-0135-2
Miller, J. W., & Hakimian, S. (2013). Surgical treatment of epilepsy. Continuum (Minneapolis, Minn.), 19(3 Epilepsy), 730–742. doi:10.1212/01.CON.0000431398.69594.97
Deransart, C., Vercueil, L., Marescaux, C., & Depaulis, A. (1998). The role of basal ganglia in the control of generalized absence seizures. Epilepsy Research, 32(1–2), 213–223. doi:10.1016/s0920-1211(98)00053-9
Villemure, J.-G., & Daniel, R. T. (2006). Peri-insular hemispherotomy in paediatric epilepsy. Child’s Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery, 22(8), 967–981. doi:10.1007/s00381-006-0135-2
Kim, J.-S., Park, E.-K., Shim, K.-W., & Kim, D. S. (2018). Hemispherotomy and functional hemispherectomy: Indications and outcomes. Journal of Epilepsy Research, 8(1), 1–5.
Campbell, J., & Sharma, A. (2016). Visual cross-modal re-organization in children with cochlear implants. PLOS ONE, 11(1), e0147793. doi:10.14581/jer.18001
Shaffer, J. (2016). Neuroplasticity and clinical practice: Building brain power for health. Frontiers in Psychology, 7, 1118. doi:10.1371/journal.pone.0147793
Morris, R. G. M. (2003). Long-term potentiation and memory. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 358(1432), 643–647. doi:10.3389/fpsyg.2016.01118
Huttenlocher, P. R., & Dabholkar, A. S. (1997). Regional differences in synaptogenesis in human cerebral cortex. The Journal of Comparative Neurology, 387(2), 167–178. doi:10.1098/rstb.2002.1230
Klein, D., Mok, K., Chen, J.-K., & Watkins, K. E. (2014). Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals. Brain and Language, 131, 20–24. DOI:10.1002/(sici)1096-9861(19971020)387:2<167::aid-cne1>3.0.co;2-z
Ismail, F. Y., Fatemi, A., & Johnston, M. V. (2017). Cerebral plasticity: Windows of opportunity in the developing brain. European Journal of Paediatric Neurology: EJPN: Official Journal of the European Paediatric Neurology Society, 21(1), 23–48. doi:10.1016/j.bandl.2013.05.014
Sussman, D., Leung, R. C., Chakravarty, M. M., Lerch, J. P., & Taylor, M. J. (2016). The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy. Brain and Behavior, 6(4), e00457. doi:10.1016/j.ejpn.2016.07.007
Abdul-Kareem, I. A., Stancak, A., Parkes, L. M., & Sluming, V. (2011). Increased gray matter volume of left pars opercularis in male orchestral musicians correlate positively with years of musical performance. Journal of Magnetic Resonance Imaging, 33(1), 24–32. doi:10.1002/brb3.457 doi:10.1002/jmri.22391
Schnack, H. G., van Haren, N. E. M., Brouwer, R. M., Evans, A., Durston, S., Boomsma D. I., , Khan, R. S., & Hulshoff Pol, H. E. (2015). Changes in thickness and surface area of the human cortex and their relationship with intelligence. Cerebral Cortex (New York, N.Y.: 1991), 25(6), 1608–1617. doi: 10.1093/cercor/bht357
Kinsbourne, M. (2013). Somatic twist: a model for the evolution of decussation. Neuropsychology, 27(5), 511–515. doi:10.1093/cercor/bht357
Graveline, C. J., Mikulis, D. J., Crawley, A. P., & Hwang, P. A. (1998). Regionalized sensorimotor plasticity after hemispherectomy fMRI evaluation. Pediatric Neurology, 19(5), 337–342. doi:10.1037/a0033662
Benecke, R., Meyer, B. U., & Freund, H. J. (1991). Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation. Experimental Brain Research, 83(2), 419–426. doi:10.1016/S0887-8994(98)00082-4
Corballis, M. C. (2014). Left brain, right brain: facts and fantasies. PLOS Biology, 12(1), e1001767. doi:10.1007/BF00231167
Liégeois, F., Connelly, A., Baldeweg, T., & Vargha-Khadem, F. (2008). Speaking with a single cerebral hemisphere: fMRI language organization after hemispherectomy in childhood. Brain and Language, 106(3), 195–203. doi:10.1371/journal.pbio.1001767
Ivanova, A., Zaidel, E., Salamon, N., Bookheimer, S., Uddin, L. Q., & de Bode, S. (2017). Intrinsic functional organization of putative language networks in the brain following left cerebral hemispherectomy. Brain Structure & Function, 222(8), 3795–3805. doi:10.1016/j.bandl.2008.01.010
Björklund, A., & Lindvall, O. (2000). Self-repair in the brain: Neurobiology. Nature, 405(6789), 892–893, 895. doi:10.1007/s00429-017-1434-y