It’s 3 PM and you’re hitting a midday lull. You had two cups of coffee in the morning, but you figure that you need another, desperately. You grab your third cup, take a few sips, and immediately the caffeine hits you; you’re ready to take on the world.
Ever wonder what happens in your brain to make the switch between down-and-out tired, and borderline over-caffeinated? As it turns out, the baseline levels of activity in your brain drastically change depending on your mental mindset. These changes in neural activity across different arousal levels are referred to as “brain states.”
Brain state researcher Russell Milton, a member of Valentin Dragoi’s lab at the University of Texas at Houston, explained that “changes in brain state occur when the body transitions through the sleep/wake cycle, as well as throughout the day when we modulate our activity levels.” As these levels vary over the course of a day, so do our brain states, making this topic an integral aspect of our daily lives.
Milton’s new study uses novel technologies to shed light on neural environments across varied brain states. His results suggest that “natural fluctuations in brain state throughout the day play a key role in shaping prefrontal activity in the brains of higher animals.”
What’s new and why wireless?
In today’s world, we hear so much about “wireless capabilities,” and Milton’s work is no exception. Rather than using traditional methods, where animals assume a fixed position with tethered wires recording neural activity, Milton’s experiments allowed animals to freely roam around their enclosed arena. This is particularly significant, as Milton points out that “the brain evolved to control body movements,” and restraining motor behaviors likely has widespread effects on neural activity. Previous work informed his hypotheses, but Milton pointed out that the established literature lacks the methods to “allow animals to engage in more natural behavioral patterns,” and therefore likely cannot accurately capture the changes in their totality.
Previous studies have used electroencephalography (EEG) techniques, which involve noninvasively placing electrodes along the scalp to study brain states. Milton points out that these seminal findings are extremely valuable, but that “EEG cannot detect the activity of individual neurons,” so the extent to which these changes are found in the spiking activity of large population of neurons remains unclear. Rather than using a coarse measure of neural activity, like those measured using EEG, Milton and his team implanted a wireless array, which can record 96 neurons at any given time. This increase in resolution was critical to their findings, says Milton, “Neurons are the fundamental computational unit of the brain, so it is desirable to record at the single-cell resolution whenever possible.”
For Milton’s experiments, the 96-channel array was inserted into the dorsolateral prefrontal cortex of two rhesus macaques. The prefrontal cortex is what neuroscientists say makes the human brain “human,” This area is conserved in macaques, making them an appropriate model system to study this area and how it controls decision making. Responsible for high-level cognitive reasoning, the prefrontal cortex doesn’t fully develop until your 20’s – sound familiar? Previous studies on brain states have looked at sensory areas, like visual or auditory cortex. Milton, however, hypothesized that executive functions, like those carried out in the prefrontal cortex, may be even more affected across brain states. By recording from the prefrontal cortex, Milton was able to draw conclusions about brain states in decision-making brain areas.
Brain states measured via neuronal synchrony
The hallmark measure for evaluating brain states has long been synchrony. Synchrony measures how coordinated groups of neurons are in their firing patterns. When you’re drowsy or in deep sleep, large groups of cells fire together, or are silent together, forming oscillations in the spiking activity. This kind of activity is highly synchronous, as neurons are acting in similar ways at the same time. Opposing this, when you’re wide awake and actively engaged, your brain enters a desynchronized state – meaning neurons are firing independently of one another. Neurons that are active at different times have low levels of synchrony. Neuroscientists think that desynchronized brain states allow our brains to take in more information, leading to an “enhanced processing mode, reserved for behavioral contexts in which more cognitive resources are required,” as Milton explains.
Milton first started by replicating the coarse synchrony results found in EEG studies. He also found that when animals were drowsy or napping, their brains entered a synchronized state of activity. On an EEG recording, these aligned changes in firing patterns are visible with the naked eye. However, when the animals were awake and engaged with their environment, their brains entered a desynchronized state.
The novel technological methods Milton used, with their fine temporal and spatial precision, highlighted that animals’ brain states tend to change before their behavioral state. How many times have you woken up in bed in the morning and resolved to not move and get your day started? This change in neural activity going from sleep to wake can be detected in the animals’ brains before they move from their sleeping position.
Different cell types should do different things?
Milton’s work further expands on the synchronous nature of neurons by examining how different cell types changed their activity across brain states.
Signals produced by neurons are either excitatory or inhibitory – they make electrical activity in the brain more or less likely to happen. Milton explained that both neuronal types exist in a delicate balance. “Neuronal networks would either go silent or explode with activity, if not for a mix of both excitatory and inhibitory neurons to balance the system,” he says. The excitatory neurons send information to the cells they are connected to, and the inhibitory cells dampen overzealous activity.
The field has posited multiple theories on how these two groups interact during synchronized, restful brain states, where overall activity is reduced. Milton suggests that “one possible explanation for this [decreased activity during synchronized states] is that a small subset of inhibitory neurons is more active during restful states in order to more strongly suppress the overall population.” Milton found that both excitatory and inhibitory cells fire more often when animals were awake and actively engaged with their environment, and fire less when animals were resting, or even awake but not engaged with their surroundings.
Milton’s data didn’t back up the idea that a small subset of inhibitory neurons run the show. His array results showed that excitatory and inhibitory neuronal populations change their activity in similar ways, with more activity and less coordinated firing when the animal was awake and engaged. Milton says this shows that “the impact of brain states on neurons in the prefontal cortex is highly uniform, influencing different neuronal populations in similar ways.”
What does this mean for me?
Milton’s experiments lay the groundwork for brain states during naturalistic behaviors, informing the field on previously speculative hypotheses.
Although the field was aware that our brain assumes different signatures when we’re about to nap compared to when we’re wired from caffeine, Milton’s work supports the idea that these brain states occur on a spectrum, rather than being isolated points of neural computation. Furthermore, the similarity between populations of different cell types emphasizes the dynamic interactions between groups of cells in our brains.
Long story short, when you’re debating that afternoon pick-me-up, take comfort in the fact that science says that cup of coffee makes your brain more capable of getting that pile of work done. It’s not all in your head – or is it?