As a human with a brain, we often think we understand how the brain works. However, sometimes hearing crazy facts about the brain makes us realize that the human brain is more complex and impressive than we realized. Case studies involving sick patients allow for interesting insights into how the brain functions. In the article, we will discuss cases that will likely make you think twice about what you thought you knew about how brains work.
1. A Fluid-Filled Brain Still Worked
In pop culture, we are told that birds have brains the size of an almond and elephants have brains too heavy to carry. From early biology classes, we might know that the human brain is about three pounds and about the size of two fists. From colloquial language, we understand that there are two hemispheres to the brain (a consequence of being asked if we are a left-brain thinker or right-brain thinker). It is, however, possible to find clinical cases that defy our common understanding of the brain. Therefore, it was a shock to doctors to find that a 44-year-old man in France had an unusually small brain volume and a large amount of cervical spinal fluid (CSF). Although the size of the man’s brain was more than 50-75% reduced in comparison to the neurotypical brain size, he maintained the ability to control motor commands, communicate, and other cognitive functions such as making decisions and creating new memories.
The man first came to the hospital with a complaint about muscle weakness in his left leg. After attributing the motor issue to a neurological condition, the doctor, Lionel Feuillet, performed a computed tomography (CT) scan of the patient’s brain to assess for a possible stroke or other brain damage. On the CT scan, it was evident that the ventricles of the brain, or hollow chambers to aid the production, transport, and removal of CSF, were enlarged significantly. The doctors later attributed the reason for this fluid buildup to a ventriculoarterial shunt, or a procedure where clinicians remove the trapped fluid with a tube (or shunt) to siphon the extra CSF into the bloodstream and arteries in the brain.
Clinicians perform a ventriculoarterial shunt in extreme cases of postnatal hydrocephalus. Postnatal hydrocephalus is a condition of increased fluid in the ventricles of the brain sometimes present in young children. As a teenager, the man underwent this procedure due to ataxia and paresis in the man’s left leg created by the extra fluid and ventricle enlargement. Since the shunt procedure, he had sustained a normal life. This case provides an interesting perspective into the plasticity of the brain, or how the brain adapts to abnormal changes to nervous tissue caused by trauma such as a stroke, tumor, or brain injury. Here’s a link to the story of the man with a fluid-filled brain.
2. Sea Squirt “Eats its own Brain” During Metamorphosis
Marine sea squirts called tunicates (part of the Chordata phylum) require more energy during the metamorphosis stages. When young and in larvae form, these organisms look a lot like tadpoles. Unlike tadpoles, however, the larvae are unable to feed. During the development stages beyond larvae, the tunicates require energy. Since they are unable to feed, the organism results to reducing its central nervous system, and specifically its cerebral ganglion cells. These cerebral ganglion cells enable larvae to move and escape rapidly from danger. Therefore, the organism has garnered the name the sea squirt that can “eat its own brain.” Despite the reduction of these cells, the organism does not reduce all central nervous system tissue.
After developing past the larvae stage, they localize onto stable regions on the ocean floor, such as rocks. From there, the tunicates become suspension feeders and filter the water for nutrients. Removal of the cerebral ganglion cells for movement makes the stagnant adult life cycle possible. The tunicates can reproduce in colonies on this same surface. During this transition, the larvae lose their notochords (or vertebrate-like structure). Since tunicates begin their life cycle with a vertebrate and then no longer require it during adult life, tunicates provide an interesting perspective into the development and evolution of fish. Certainly, this model animal links both invertebrate and vertebrate animals and acts as an interesting model organism for understanding the early development of the notochord (or what eventually becomes the spine in most animals).
3. Restoring sight and subsequent depression in the previously blind
Depression in blind individuals with restored vision, has been recorded since the early 1700’s. This phenomenon first garnered attention by a couple of philosophers. A thought experiment originally posed by John Locke and William Molyneux, asks if a blind person first gained the ability to see, they would not immediately form the association between the abstract object and the tangible one, such as the idea of a shape and the sight of a shape. How would one distinguish between a sphere and cube? Multiple studies have been designed as a result of this thought experiment. One of which, involves the case of a young girl in India who received surgery to treat her congenital cataracts, which clouded the lens of her eye. Six months after the surgery, the young girl began to recognize her family member solely by sight. The delay of learning the ability to recognize objects, people, and places by sight requires time for the visual cortical regions to adapt and adjust to the new sensory information. During this time of adaption, it is common for patients to develop feelings of depression, confusion, and frustration.
Oliver Sacks, shared the story of one patient who struggled with depression after recovering from blindness. Virgil, the man Sacks writes about, had cataracts and acute retinitis pigmentosea (a disorder that damages the retina of the eye over time). As a result, he decided to go to Dr. Hamlin for a formal diagnosis. The doctor suggested that despite Virgil’s retina, Virgil could regain vision after a simple cataract extraction procedure. After lifelong blindness, Virgil decided to undergo the procedure. As Virgil regained the ability to see, he was disoriented by light, color, and movement. He had no visual experience, and thus faced a challenge; he needed to learn to perceive the world and create visual memory and associations. At home, Virgil struggled to identify the whole object. His cat was just a paw, nose, tail, and ear. Virgil was unable to see his cat and identify the animal in front of him.
For sighted individuals, it is easy to imagine places and things from different perspectives and angles. However, for Virgil, each new perspective in a room remained uncorrelated with the other perspective of the same room. As a result, Virgil felt as though he constantly existed in unfamiliar spaces. Learning these associations and visual experiences requires the remapping and restructuring of the neurons in the visual cortex. Due to the plastic nature of the brain, in blind individuals who learn braille, other cortical regions can encode or respond to information such as touch. After regaining sight, the neurons in these cortical regions must rewire and communicate with new neurons to begin to respond to visual stimuli and associate different visual shapes with each other. During this process, Virgil felt hopeless and between two worlds, one he could see and one that he previously knew.
There are more recent cases where restoration of sight is a mixed blessing. There are even some cases of suicide after the restoration of sight. However in this case it was likely because the person felt abandoned more so than difficulty adapting to the use of sight. Recovery from blindness can be very positive but it is important to understand that it is not always a quick and easy process.
4. Mirror Neurons and Learning from Mimicry
In the late 1980s, studies in the ventral premotor cortex of the macaque monkey brain revealed that certain neurons respond to both the movement of an experimenter reaching for or picking up food and the monkey performing the same action. Much like the phrase “monkey see, monkey do,” these neurons react to seeing and action and doing the same action. Researchers first suggested that these neurons helped the animal to ‘mirror’ the actions of other animals within its environment; hence the name “mirror neurons.” The mirror-neuron system also responds to reaching movements, mouth actions, facial gestures, and hand movements. Within the system, these neurons either modulate their activity to seeing and performing multiple action types (like gripping, grasping, and holding), seeing and performing one action type (just holding), or solely observing multiple action types. The differences across these types of mirror neurons helps to computationally compress similar information across multiple actions, allocate resources to different and intricate action type movements, and encode parts of action sequences (such as reaching, grabbing and then holding a coffee cup).
A famous experiment from Rizzolatti in 1996, tests mirror neuron activity (recorded from the ventrolateral subdivision of the premotor cortex) in motor tasks. In the task, first the experimenter picks up grains from a flat surface. During this time, the mirror neuron fires more or is more active in response to this visual information. Then the macaque performs the same action. This time the activity of the neuron also increases. Then the experimental picks up the grains with a tool rather than with their hand. The neurons do not fire to this visual information. Even in the dark, when the macaque performs this action of picking up grains, there is increased activity of the mirror neuron (although lesser in amplitude and frequency of action potentials). Together, the field postulates that these neurons integrate visual information with motor information to mitigate the learning of certain tasks and movements.
5. Patient HM had his hippocampus removed and how this shaped our thinking on memory
The patient H.M., later identified as Henry Molaison after his death in 2008, began having minor seizures after a bike accident at the age of 7. As he grew to be a teenage, he began experiencing major seizures. Since these seizures prevented Henry from leading a stable work life and home life, he sought the advice of William Scoville, a practicing neurosurgeon in Connecticut. Scoville suggested resective surgery, a procedure that required Scoville to remove brain tissue from the “seizure focus” or origin of Henry’s seizures.
Around the same time, Brenda Milner researched two severely amnesic patients, P.B. and F.C. as part of her doctorate thesis work at McGill University with Donald Hebb. After Henry’s procedure, Scoville called the neurosurgeon involved in P.B. and F.C.’s treatment of epilepsy. Henry began experiencing severe memory impairment after the resective surgery. Soon, Milner began to visit Henry and record H.M.’s memory difficulties to share with the scientific community. Although H.M. no longer experienced seizures, he failed to remember daily events and newly introduced names. H.M., however, remembered events from his childhood 11 years before his surgery. Together, H.M. suffered from anterograde amnesia (where he could not form new memories) and retrograde amnesia (where he lost his previous memories from when Henry was 16 to 27).
Despite H.M. severe memory loss, H.M. could remember temporary information, such as the number for the local pizza joint, due to intact working memory. Further, he performed well on tasks that required integrating cognitive and motor information due to procedural memory use across trials. An example of this task is to draw a star shape using the reflection of the page in a mirror as the sole guide (this task is quite hard to do on your first try). He could also draw detailed topographical depictions of his current residence and form habits.
Later research showed that H.M.’s memory failed at certain tasks due to the bilateral removal of anterior portion of the parahippoampal gyrus and the hippocampi. These brain regions have been implicated in the role of declarative memory, or memory involved in both episodic and semantic knowledge of the experienced events during the day and learned concepts and facts. Although H.M. could not lead a normal life after the surgery, his legacy shaped our understanding of the functions of memory systems, how memory mechanisms allow for communication across brain regions, and translational research of memory across animal models and humans.
6. The critical period for learning languages, seeing the world, and more
The critical period is a period during early development in the baby brain in which experiential and environmental features greatly shape future cognitive functions. Without experiences in early life, exposure of the same features later in life cannot be learned at the same capacity. For example, ‘feral children’ or children completely isolated from human contact during early life have great difficulty learning how to speak and form social connections as adults.
Two examples of the critical period include the development of binocular vision and language acquisition. In the 1960s, an animal study from Hubel and Wiesel first proved the existence of a critical period during visual development during monocular deprivation at an early age. During the experiment, the model animal had one sutured eye that did not receive any visual information in early stages of development. After the critical period of development, the sutures were removed, and the animal’s two eyes could receive visual information. Despite both eyes functioning normally, the animal experienced functional blindness in the previously sutured eye due to the visual cortex’s inability to process the visual information from the previously sutured eye. On another level, young children can learn multiple languages by exposure to these languages much faster than older children and adults. Together, the critical period provides and interesting perspective on the plasticity of learning across time and development.
Some of the factors important for starting and ending a critical period include certain cellular changes such as the rewiring or change in synaptic architecture between inhibitory neurons (or neurons that inhibit other neurons). The inhibitory network of cells develops later than the excitatory network of cells. Thus, the wiring of inhibitory network of neurons later in development play a role in creating the critical period window. This theory has been tested by recent research looking at increasing the maturation of inhibitory neurons such as basket cells which release a chemical signal called GABA. The early maturation of these neurons resulted in an earlier end to the critical window. Other molecular mechanisms, such as change in composition of chemical signals in the extracellular matrix of the cell, are also involved in forming this window. Recent research focuses on understanding how we can reopen these critical periods later in life and how reopening the critical period can be applied to clinical settings. An example of recent research on how critical periods can be reopened.
7. Brains often work by reducing neural connections not making new ones: Synaptic pruning
This is a great video where Dr. Jeff Lichtman talks about the synaptic pruning of neuromuscular junctions.
During normal development, the brain must prune, or decrease, the number of connections between neurons to regulate, learn, and conserve energy. Two neurons can communicate at a synapse, or a structural element on the neuronal process (like the axon), that forms a small junction between the presynaptic neurons and the postsynaptic neuron. Sometimes, it is more beneficial to remove this connection between the two neurons all together. This elimination of the synapse, or pruning, begins at infancy and continues into early adulthood. Pruning initiates learning by removing unused synaptic connections. Such pruning helps connections appear together more frequently and robustly, such as two neurons raising in activity together. This process initiates learning while conserving important and limited neuronal resources. Learning can be achieved in a set of neurons (input information) that correlate with the activity of another neuron (output information). After learning, only one or a smaller set of neurons will correlate with the activity of the downstream neurons. Pruning helps to remove the synapses and connections between the other set of neurons that no longer correlate with the activity of the downstream neuron. This affect results in more specific kinds of association, such as the association between liking or disliking broccoli after trying it for a couple of times.
One way the synapse between two neurons prunes is with the help of microglia. Microglia are another cell type in the brain that are not classified as neuronal cells. Microglia have many functions including removing toxic levels of potassium, damaged and unnecessary cells, and siphoning off certain toxins from the bloodstream at the blood-brain barrier. As microglia manage and maintain synapses, they prevent the excess of dendritic spines and other pathological markers for certain diseases. Schizophrenia has been linked to the inability to prune the excess of synaptic connections during development. Current research is looking at the link between microglia and the onset of schizophrenia. More on schizophrenia and the role of synaptic pruning in disease presentation:
8. People can survive without a Cerebellum
There are around 86 billion neurons in the entire brain. The cerebellum has around 69 billion neurons making up over 80 percent of the neurons in the brain. It might be quite surprising to hear that people can live without a cerebellum. Looking at past cases of primary cerebellar agenesis motor control is typically impaired but not always. Language and speech comprehension can be impaired as well as mental development.
There was a case of complete primary cerebellar agenesis in a 24-year-old female patient which was published in 2014. Cerebellar agenesis is when a person does not have a cerebellum. This individual was not able to stand unassisted until age 4 and could not walk unassisted until age 7. It was not until age 6 that she could talk clearly. However, she was able to overcome these struggles and got married and had a child. Issues with dizziness, nausea, and vomity at age 24 led to CT and MRI scans showing there were no remnants of cerebellum tissue.
Jonathan Keleher is a 33-year-old male that has Cerebellar agenesis. This was discovered at age 5 as he was late hitting developmental milestones for sitting, walking, and talking. Over time it is believed that other brain areas were trained to do tasks typically performed by the cerebellum. This has allowed him to make progress to the point where he has a job and can live a relatively normal life.
9. Medical Cases Where Nearly Half the Brain is Removed
Rasmussen’s Syndrome can damage one side of the brain to the point where a hemispherectomy is needed. A hemispherectomy is a surgery where up to 1/2 of the brain is removed. In children, this can be successful because pediatric brain plasticity allows the other side of the brain to take over the function of the diseased half. After surgery, one-half of the body is paralyzed and therapy is needed to help recover the function on the side that has become paralyzed. In the case above, the patient was able to walk out of the rehabilitation center 4 weeks after surgery.
10. Seven-Second Memory
Clive Wearing has a severe case of amnesia to the point where he is said to have a 7-second memory. He has had this condition for over 20 years. What is surprising is that he can still play music. Before a virus caused damage to his brain, he was a conductor and musician. It is his short-term memory that has been severely affected. The only person he recognizes is his wife.
Anterograde amnesia is when an individual can not create new memories. Long-term memories can still be intact. This is the case for Clive who he does not remember anything that happened in the past 20 years. Even when he sees his son he expects him to be 20 years younger. He is aware of his surroundings and can ask reasonable questions such as how long have I been here. When the answer of 20 years is given he can deliver a thoughtful response showing his high level of intellect is still there. However, he quickly forgets the conversation and acknowledges that he can not remember recent events.
His mood changes from euphoric to depressed in a matter of seconds. It is clear that he struggles with his condition and he continuously thinks he is awake for the first time. Then a few seconds later he thinks this is the first time he has ever been awake and even documents this daily in his journal. He always thinks he is doing things for the first time, such as this is the first time I have ever seen my writing. His wife left him and then remarried him years later and continues to look after him.
11. Mike the headless chicken and the brainstem
On September 10th, 1945, the Olsen family prepared for dinner on their farm. Lloyd Olsen decided to head over to ready one of his roosters. Soon after beheading the chicken, Lloyd realized that the rooster, Mike, had not died. Instead, Mike continued to peck and preened his feathers. The farmer had missed the rooster’s neck and brainstem. Thus, Mike could perform basic functions, sustain his vital functions, as well as continue certain motor behaviors. For 18 months after the event, Mike became famous and known as the “headless wonder chicken” and a yearly festival has been created in his name.
How did the chicken survive despite the event? Lloyd’s axe missed the rooster’s jugular vein, which transports blood from the head to the heart; this prevented major blood loss. The brain stem is responsible for controlling heart rate and breathing. Further evidence suggests that the brain stem is important for the sleep cycle and for transporting information from the peripheral nervous system to the central nervous system, such as motor commands and touch. Since Mike’s brain stem was intact, his homeostatic functions, or self-regulating vital processes, could carry on. Some bird species also possess a balance organ called the lumbosacral organ in the pelvic region. This balance system allowed Mike to control motor movements despite losing the inner ear’s vestibular system also responsible for the balance. Unfortunately, the Olsen family had to feed Mike using eyedrops and isolate him from other chickens due to his injury. Together, it is amazing to see how vital the brainstem can be for survival. Read more about the famous chicken.
Pel is a Neuroscience Ph.D. Candidate at the Johns Hopkins University School of Medicine.