5 Unsolved Mysteries Of The Brain

Pyramidal neuron in medial prefrontal cortex of macaque.

Image courtesy of brainmaps.org

1. How is information coded in neural activity?

Neurons, the specialized cells of the brain, can produce brief spikes of voltage in their outer membranes. These electrical pulses travel along specialized extensions called axons to cause the release of chemical signals elsewhere in the brain. The binary, all-or-nothing spikes appear to carry information about the world: What do I see? Am I hungry? Which way should I turn? But what is the code of these millisecond bits of voltage? Spikes may mean different things at different places and times in the brain. In parts of the central nervous system (the brain and spinal cord), the rate of spiking often correlates with clearly definable external features, like the presence of a color or a face. In the peripheral nervous system, more spikes indicates more heat, a louder sound, or a stronger muscle contraction.
As we delve deeper into the brain, however, we find populations of neurons involved in more complex phenomena, like reminiscence, value judgments, simulation of possible futures, the desire for a mate, and so on—and here the signals become difficult to decrypt. The challenge is something like popping the cover off a computer, measuring a few transistors chattering between high and low voltage, and trying to guess the content of the Web page being surfed.
It is likely that mental information is stored not in single cells but in populations of cells and patterns of their activity. However, it is currently not clear how to know which neurons belong to a particular group; worse still, current technologies (like sticking fine electrodes directly into the brain) are not well suited to measuring several thousand neurons at once. Nor is it simple to monitor the connections of even one neuron: A typical neuron in the cortex receives input from some 10,000 other neurons.
Although traveling bursts of voltage can carry signals across the brain quickly, those electrical spikes may not be the only—or even the main—way that information is carried in nervous systems. ­Forward-looking studies are examining other possible information couriers: glial cells (poorly understood brain cells that are 10 times as common as neurons), other kinds of signaling mechanisms between cells (such as newly discovered gases and peptides), and the biochemical cascades that take place inside cells.


2. How are memories stored and retrieved?

When you learn a new fact, like someone’s name, there are physical changes in the structure of your brain. But we don’t yet comprehend exactly what those changes are, how they are orchestrated across vast seas of synapses and neurons, how they embody knowledge, or how they are read out decades later for retrieval.
One complication is that there are many kinds of memories. The brain seems to distinguish short-term memory (remembering a phone number just long enough to dial it) from long-term memory (what you did on your last birthday). Within long-term memory, declarative memories (like names and facts) are distinct from non­declarative memories (riding a bicycle, being affected by a subliminal message), and within these general categories are numerous subtypes. Different brain structures seem to support different kinds of learning and memory; brain damage can lead to the loss of one type without disturbing the others.
Nonetheless, similar molecular mechanisms may be at work in these memory types. Almost all theories of memory propose that memory storage depends on synapses, the tiny connections between brain cells. When two cells are active at the same time, the connection between them strengthens; when they are not active at the same time, the connection weakens. Out of such synaptic changes emerges an association. Experience can, for example, fortify the connections between the smell of coffee, its taste, its color, and the feel of its warmth. Since the populations of neurons connected with each of these sensations are typically activated at the same time, the connections between them can cause all the sensory associations of coffee to be triggered by the smell alone.
But looking only at associations—and strengthened connections between neurons—may not be enough to explain memory. The great secret of memory is that it mostly encodes the relationships between things more than the details of the things themselves. When you memorize a melody, you encode the relationships between the notes, not the notes per se, which is why you can easily sing the song in a different key.
Memory retrieval is even more mysterious than storage. When I ask if you know Alex Ritchie, the answer is immediately obvious to you, and there is no good theory to explain how memory retrieval can happen so quickly. Moreover, the act of retrieval can destabilize the memory. When you recall a past event, the memory becomes temporarily susceptible to erasure. Some intriguing recent experiments show it is possible to chemically block memories from reforming during that window, suggesting new ethical questions that require careful consideration.
3. What does the baseline activity in the brain represent?

Neuroscientists have mostly studied changes in brain activity that correlate with stimuli we can present in the laboratory, such as a picture, a touch, or a sound. But the activity of the brain at rest—its “baseline” activity—may prove to be the most important aspect of our mental lives. The awake, resting brain uses 20 percent of the body’s total oxygen, even though it makes up only 2 percent of the body’s mass. Some of the baseline activity may represent the brain restructuring knowledge in the background, simulating future states and events, or manipulating memories. Most things we care about—reminiscences, emotions, drives, plans, and so on—can occur with no external stimulus and no overt output that can be measured.
One clue about baseline activity comes from neuroimaging experiments, which show that activity decreases in some brain areas just before a person performs a goal-directed task. The areas that decrease are the same regardless of the details of the task, hinting that these areas may run baseline programs during downtime, much as your computer might run a disk-defragmenting program only while the resources are not needed elsewhere.
In the traditional view of perception, information from the outside world pours into the senses, works its way through the brain, and makes itself consciously seen, heard, and felt. But many scientists are coming to think that sensory input may merely revise ongoing internal activity in the brain. Note, for example, that sensory input is superfluous for perception: When your eyes are closed during dreaming, you still enjoy rich visual experience. The awake state may be essentially the same as the dreaming state, only partially anchored by external stimuli. In this view, your conscious life is an awake dream.
4. How do brains simulate the future?

When a fire chief encounters a new blaze, he quickly makes predictions about how to best position his men. Running such simulations of the future—without the risk and expense of actually attempting them—allows “our hypotheses to die in our stead,” as philosopher Karl Popper put it. For this reason, the emulation of possible futures is one of the key businesses that intelligent brains invest in.
Yet we know little about how the brain’s future simulator works because traditional neuroscience technologies are best suited for correlating brain activity with explicit behaviors, not mental emulations. One idea suggests that the brain’s resources are devoted not only to processing stimuli and reacting to them (watching a ball come at you) but also to constructing an internal model of that outside world and extracting rules for how things tend to behave (knowing how balls move through the air). Internal models may play a role not only in motor acts, like catching, but also in perception. For example, vision draws on significant amounts of information in the brain, not just on input from the retina. Many neuroscientists have suggested over the past few decades that perception arises not simply by building up bits of data through a hierarchy but rather by matching incoming sensory data against internally generated expectations.
But how does a system learn to make good predictions about the world? It may be that memory exists only for this purpose. This is not a new idea: Two millennia ago, Aristotle and Galen emphasized memory as a tool in making successful predictions for the future. Even your memories about your life may come to be understood as a special subtype of emulation, one that is pinned down and thus likely to flow in a certain direction.
5. What are emotions?

We often talk about brains as information-processing systems, but any account of the brain that lacks an account of emotions, motivations, fears, and hopes is incomplete. Emotions are measurable physical responses to salient stimuli: the increased heartbeat and perspiration that accompany fear, the freezing response of a rat in the presence of a cat, or the extra muscle tension that accompanies anger. Feelings, on the other hand, are the subjective experiences that sometimes accompany these processes: the sensations of happiness, envy, sadness, and so on. Emotions seem to employ largely unconscious machinery—for example, brain areas involved in emotion will respond to angry faces that are briefly presented and then rapidly masked, even when subjects are unaware of having seen the face. Across cultures the expression of basic emotions is remarkably similar, and as Darwin observed, it is also similar across all mammals. There are even strong similarities in physiological responses among humans, reptiles, and birds when showing fear, anger, or parental love.
Modern views propose that emotions are brain states that quickly assign value to outcomes and provide a simple plan of action. Thus, emotion can be viewed as a type of computation, a rapid, automatic summary that initiates appropriate actions. When a bear is galloping toward you, the rising fear directs your brain to do the right things (determining an escape route) instead of all the other things it could be doing (rounding out your grocery list). When it comes to perception, you can spot an object more quickly if it is, say, a spider rather than a roll of tape. In the realm of memory, emotional events are laid down differently by a parallel memory system involving a brain area called the amygdala.
One goal of emotional neuroscience is to understand the nature of the many disorders of emotion, depression being the most common and costly. Impulsive aggression and violence are also thought to be consequences of faulty emotion regulation.