Music brings memories back to the brain injured

In the first study of its kind, two researchers have used popular music to help severely brain-injured patients recall personal memories. Amee Baird and Séverine Samson outline the results and conclusions of their pioneering research in the recent issue of the journal Neuropsychological Rehabilitation.

Although their study covered a small number of cases, it’s the very first to examine ‘music-evoked autobiographical memories’ (MEAMs) in patients with acquired brain injuries (ABIs), rather than those who are healthy or suffer from Alzheimer’s Disease.

In their study, Baird and Samson played extracts from ‘Billboard Hot 100’ number-one songs in random order to five patients. The songs, taken from the whole of the patient’s lifespan from age five, were also played to five control subjects with no brain injury. All were asked to record how familiar they were with a given song, whether they liked it, and what memories it invoked.

Doctors Baird and Samson found that the frequency of recorded MEAMs was similar for patients (38%–71%) and controls (48%–71%). Only one of the four ABI patients recorded no MEAMs. In fact, the highest number of MEAMs in the whole group was recorded by one of the ABI patients. In all those studied, the majority of MEAMs were of a person, people or a life period and were typically positive. Songs that evoked a memory were noted as more familiar and more liked than those that did not.

As a potential tool for helping patients regain their memories, Baird and Samson conclude that: “Music was more efficient at evoking autobiographical memories than verbal prompts of the Autobiographical Memory Interview (AMI) across each life period, with a higher percentage of MEAMs for each life period compared with AMI scores.”

“The findings suggest that music is an effective stimulus for eliciting autobiographical memories and may be beneficial in the rehabilitation of autobiographical amnesia, but only in patients without a fundamental deficit in autobiographical recall memory and intact pitch perception.”

The authors hope that their ground-breaking work will encourage others to carry out further studies on MEAMs in larger ABI populations. They also call for further studies of both healthy people and those with other neurological conditions to learn more about the clear relationship between memory, music and emotion; they hope that one day we might truly “understand the mechanisms underlying the unique memory enhancing effect of music”.

Balancing old and new skills

To learn new motor skills, the brain must be plastic: able to rapidly change the strengths of connections between neurons, forming new patterns that accomplish a particular task. However, if the brain were too plastic, previously learned skills would be lost too easily.

A new computational model developed by MIT neuroscientists explains how the brain maintains the balance between plasticity and stability, and how it can learn very similar tasks without interference between them.

The key, the researchers say, is that neurons are constantly changing their connections with other neurons. However, not all of the changes are functionally relevant — they simply allow the brain to explore many possible ways to execute a certain skill, such as a new tennis stroke.

“Your brain is always trying to find the configurations that balance everything so you can do two tasks, or three tasks, or however many you’re learning,” says Robert Ajemian, a research scientist in MIT’s McGovern Institute for Brain Research and lead author of a paper describing the findings in the Proceeding of the National Academy of Sciences the week of Dec. 9. “There are many ways to solve a task, and you’re exploring all the different ways.”

As the brain explores different solutions, neurons can become specialized for specific tasks, according to this theory.

Noisy circuits

As the brain learns a new motor skill, neurons form circuits that can produce the desired output — a command that will activate the body’s muscles to perform a task such as swinging a tennis racket. Perfection is usually not achieved on the first try, so feedback from each effort helps the brain to find better solutions.

This works well for learning one skill, but complications arise when the brain is trying to learn many different skills at once.  Because the same distributed network controls related motor tasks, new modifications to existing patterns can interfere with previously learned skills.

“This is particularly tricky when you’re learning very similar things,” such as two different tennis strokes, says Institute Professor Emilio Bizzi, the paper’s senior author and a member of the McGovern Institute.

In a serial network such as a computer chip, this would be no problem — instructions for each task would be stored in a different location on the chip. However, the brain is not organized like a computer chip. Instead, it is massively parallel and highly connected — each neuron connects to, on average, about 10,000 other neurons.

That connectivity offers an advantage, however, because it allows the brain to test out so many possible solutions to achieve combinations of tasks. The constant changes in these connections, which the researchers call hyperplasticity, is balanced by another inherent trait of neurons — they have a very low signal to noise ratio, meaning that they receive about as much useless information as useful input from their neighbors.

Most models of neural activity don’t include noise, but the MIT team says noise is a critical element of the brain’s learning ability. “Most people don’t want to deal with noise because it’s a nuisance,” Ajemian says. “We set out to try to determine if noise can be used in a beneficial way, and we found that it allows the brain to explore many solutions, but it can only be utilized if the network is hyperplastic.”

This model helps to explain how the brain can learn new things without unlearning previously acquired skills, says Ferdinando Mussa-Ivaldi, a professor of physiology at Northwestern University.

“What the paper shows is that, counterintuitively, if you have neural networks and they have a high level of random noise, that actually helps instead of hindering the stability problem,” says Mussa-Ivaldi, who was not part of the research team.

Without noise, the brain’s hyperplasticity would overwrite existing memories too easily. Conversely, low plasticity would not allow any new skills to be learned, because the tiny changes in connectivity would be drowned out by all of the inherent noise.

The model is supported by anatomical evidence showing that neurons exhibit a great deal of plasticity even when learning is not taking place, as measured by the growth and formation of connections of dendrites — the tiny extensions that neurons use to communicate with each other.

Like riding a bike

The constantly changing connections explain why skills can be forgotten unless they are practiced often, especially if they overlap with other routinely performed tasks.

“That’s why an expert tennis player has to warm up for an hour before a match,” Ajemian says. The warm-up is not for their muscles, instead, the players need to recalibrate the neural networks that control different tennis strokes that are stored in the brain’s motor cortex.

However, skills such as riding a bicycle, which is not very similar to other common skills, are retained more easily. “Once you’ve learned something, if it doesn’t overlap or intersect with other skills, you will forget it but so slowly that it’s essentially permanent,” Ajemian says.

The researchers are now investigating whether this type of model could also explain how the brain forms memories of events, as well as motor skills.

The Smoking Gun: Fish Brains and Nicotine

In researching neural pathways, it helps to establish an analogous relationship between a region of the human brain and the brains of more-easily studied animal species. New work from a team led by Carnegie’s Marnie Halpern hones in on one particular region of the zebrafish brain that could help us understand the circuitry underlying nicotine addiction. It is published the week of December 9 by Proceedings of the National Academy of Sciences.

The mammalian habenular nuclei, in a little-understood and difficult-to-access part of the brain, are involved in regulating both dopamine and serotonin, two neurotransmitters involved in motor control, mood, learning, and addiction. But unlike the mammalian habenulae, the habenular nuclei of fish are located dorsally, making them easy for scientists to access and study. However, some outstanding questions remained about the properties of the zebrafish habenulae, creating a roadblock for truly linking these structures as analogous in fish and humans. In particular, it was unresolved whether zebrafish habenular neurons produce the neurotransmitter acetylcholine, which is enriched in this region of the mammalian brain and activates the same receptors to which nicotine is known to bind.

The new work by lead author Elim Hong and colleagues confirms that the pathway between the habenula and another part of the brain called the midbrain interpenduncular nucleus utilizes acetylcholine in zebrafish, as it does in humans. The work also shows that there is a left-right difference in this part of the fish brain.

The purpose of this asymmetry is unknown, but, as demonstrated by electrophysiological recordings with collaborator Jean-Marie Mangin of the University of Pierre and Marie Curie, it results in differences in neural activity between the brain hemispheres. Other research in Halpern’s lab indicates that such left-right differences could influence behavior. Hong performed these experiments through a European Molecular Biology Organization Short-Term Fellowship while hosted in the laboratory of Claire Wyart in Paris, France.

The team further showed that this acetylcholine pathway in zebrafish responds in a similar way to nicotine as does the analagous pathway in the mammalian brain. This makes the zebrafish a good model for studying the brain chemistry of nicotine addiction.

“Our work demonstrates broader uses for zebrafish in studying the function of the habenula and addresses a major weakness in the field, which was the poor characterization of neurotransmitter identity in this area,” said Hong. “Going forward, these results will help us study how brain circuitry influences nicotine addiction.”

Concussion secrets unveiled in mice and people

There is more than meets the eye following even a mild traumatic brain injury. While the brain may appear to be intact, new findings reported in Nature suggest that the brain’s protective coverings may feel the brunt of the impact.

Using a newly developed mouse trauma model, senior author Dorian McGavern, Ph.D., scientist at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, watched specific cells mount an immune response to the injury and try to prevent more widespread damage. Notably, additional findings suggest a similar immune response may occur in patients with mild head injury.

In this study, researchers also discovered that certain molecules, when applied directly to the mouse skull, can bypass the brain’s protective barriers and enter the brain. The findings suggested that, in the mouse trauma model, one of those molecules may reduce effects of brain injury.

Although concussions are common, not much is known about the effects of this type of damage. As part of this study, Lawrence Latour, Ph.D., a scientist from NINDS and the Center for Neuroscience and Regenerative Medicine, examined individuals who had recently suffered a concussion but whose initial scans did not reveal any physical damage to brain tissue. After administering a commonly used dye during MRI scans, Latour and his colleagues saw it leaking into the meninges, the outer covers of the brain, in 49 percent of 142 patients with concussion.

To determine what happens following this mild type of injury, researchers in Dr. McGavern’s lab developed a new model of brain trauma in mice.

"In our mice, there was leakage from blood vessels right underneath the skull bone at the site of injury, similar to the type of effect we saw in almost half of our patients who had mild traumatic brain injury. We are using this mouse model to look at meningeal trauma and how that spreads more deeply into the brain over time," said Dr. McGavern.

Dr. McGavern and his colleagues also discovered that the intact skull bone was porous enough to allow small molecules to get through to the brain. They showed that smaller molecules reached the brain faster and to a greater extent than larger ones. “It was surprising to discover that all these protective barriers the brain has may not be concrete. You can get something to pass through them,” said Dr. McGavern.

The researchers found that applying glutathione (an antioxidant that is normally found in our cells) directly on the skull surface after brain injury reduced the amount of cell death by 67 percent. When the researchers applied glutathione three hours after injury, cell death was reduced by 51 percent. “This idea that we have a time window within which to work, potentially up to three hours, is exciting and may be clinically important,” said Dr. McGavern.

Glutathione works by decreasing levels of reactive oxygen species (ROS) molecules that damage cells. In this study, high levels of ROS were observed at the trauma site right after the physical brain injury occurred. The massive flood of ROS set up a sequence of events that led to cell death in the brain, but glutathione was able to prevent many of those effects.

In addition, using a powerful microscopic technique, the researchers filmed what was happening just beneath the skull surface within five minutes of injury. They captured never-before-seen details of how the brain responds to traumatic injury and how it mobilizes to defend itself.

Initially, they saw cell death in the meninges and at the glial limitans (a very thin barrier at the surface of the brain that is the last line of defense against dangerous molecules). Cell death in the underlying brain tissue did not occur until 9-12 hours after injury. “You have death in the lining first and then this penetrates into the brain tissue later. The goal of therapies for brain injury is to protect the brain tissue,” said Dr. McGavern.

Almost immediately after head injury, the glial limitans can break down and develop holes, providing a way for potentially harmful molecules to get into the brain. The researchers observed microglia (immune cells that act as first responders in the brain against dangerous substances) quickly moving up to the brain surface, plugging up the holes.

Findings from Dr. McGavern’s lab indicate that microglia do this in two ways. According to Dr. McGavern, “If the astrocytes, the cells that make up the glial limitans, are still there, microglia will come up to ‘caulk’ the barrier and plug up gaps between individual astrocytes. If an astrocyte dies, that results in a larger space in the glial limitans, so the microglia will change shape, expand into a fat jellyfish-like structure and try to plug up that hole. These reactions, which have never been seen before in living brains, help secure the barrier and prevent toxic substances from getting into the brain.”

Studies have suggested that immune responses in the brain can often lead to severe damage. Remarkably, the findings in this study show that the inflammatory response in a mild traumatic brain injury model is actually beneficial during the first 9-12 hours after injury.

Mild traumatic brain injuries are a growing public health concern. According to a report from the Centers of Disease Control and Prevention, in 2009 at least 2.4 million people suffered a traumatic brain injury and 75 percent of those injuries were mild. This study provides insight into the damage that occurs following head trauma and identifies potential therapeutic targets, such as antioxidants, for reducing the damaging effects.

Listening to the inner voice

Perhaps the most controversial book ever written in the field of psychology, was Julian Janes’ mid-seventies classic, “The Origin of Consciousness in the Breakdown of the Bicameral Mind.” In it, Jaynes reaches the stunning conclusion that the seemingly all-pervasive and demanding gods of the ancients, were not just whimsical personifications of inanimate objects like the sun or moon, nor anthropomorphizations of the various beasts, real and mythical, but rather the culturally-barren inner voices of bilaterally-symmetric brains not yet fully connected, nor conscious, in the way we are today.

In his view, all people of the day would have “heard voices”, similar to the schizophrenic. They would have been experienced as a hallucinations of sorts, coming from outside themselves as the unignorable voices of gods, rather than as commands originating from the other side of the brain. After a long hiatus, the study the inner voice, and the larger mental baggage that comes along with having one, has returned to the fore. Vaughan Bell, a researcher from King’s College in London, recently published an insightful call to arms in PlOS Biology for psychologists and neurobiologists to create a new understanding of these phenomena.

A coherent inner narrative in synch with our actions, is something most of us take for granted. Yet not everyone can take such possession. The congenitally deaf, for example, may later acquire auditory and communicative function through the use of cochlear implants. However, their inner experiences of sound-powered word, which they acquire through the reattribution of percepts of a previous gestural or visual nature, is something not typically shared or appreciated at the level of the larger public. A similar lack of comprehension at the research community level exists regarding those with physically intact senses, but with some other mental process gone awry. We may note with familiarity the shuffling and muttering of a homeless schizophrenic, yet have no systematic way to comprehend their intuitions, no matter how deluded they may appear.

Bell notes that current neurocognitive theories tend to ignore how those who hear voices first acquire what he describes as “internalized social actors.” In addition to live social interactions, “offline” social interaction with an internal model of those individuals holding significant power in our lives would seem like a handy feature to have. We can readily imagine entirely non-pathological situations where such a model would be of benefit. A young child cut from a school basketball team which they worked hard to make, may be temporality devastated, but hardly traumatized. If they renew their efforts to make the team the next year and practice each day in their backyard, they might imagine the coach who cut them watching their every shot with a critical eye. While this hallucinated guidance would be entirely benign, if the person they imagine is instead an abusive parent or classmate, the internal model might eventually take on a more sinister nature.

It would seem that at least in some individuals, the internal model seems able to get the upper hand, particularly when that hand is forced. We might imagine a school child tasked with the tedium of a seemingly endless recitation—saying the rosary beads, for example, in the catholic school days of yore. The familiar “Hail Mary, full of Grace……” might, after so many repetitions, transform in the mind into something else, despite the earnestness of the professor of faith. “Hail Mary, full of …..” might instead be completed with a different choice word that intrudes from another collective in the brain despite the alarmed child’s efforts to suppress it. In the situation where this is vocalized externally, completely out of control as in full blown Tourette’s syndrome, the child now has a problem.

The idea that separate voices represent separate hemispheres may be a good starting point, but it can readily be dispatched as far as being the whole story. Auditory hallucinations can take the form of multiple social actors, clearly outnumbering our hemispheres, and all with different tones, personalities, and persistence of identity. Attempts have been made to localize brain activity to a particular narrative using EEG recording, or to elicit a hallucination using magnetic stimulation. While the occasional inciteful anecdote may be gleaned from these kinds of investigations, we should not expect much fine detail to ever be had from them. The cortical area known as the temporoparietal junction routinely emerges as a favorite among brain imagers because of its geometric location at the pinnacle of the major fold in the brain. Unfortunately, until there exists a large scale minimally damaging recording technology we are probably going to have to content ourselves with looking closer at what subjects have to say about their own auditory hallucinations, than what their brains might have to say.

As children we learn to talk by talking to ourselves. Unless marooned on an island, we tend to abandon this behavior in polite company for fear of stigmatization, among other things. If the line between normalcy and pathology for hearing voices, or even talking to them, (so long as they do not command undesirable physical actions), is drawn with a greater acceptance for normalcy, a clearer understanding of the inner voice might be sooner in hand.