Phineas Gage in a bottle: Alcohol decreases prefrontal activity

There are many ways to become famous. Phineas Gage, an American railway construction foreman in the mid-19th century, experienced one of the most improbable (and least recommended) paths to eternal fame. Few first-year psychology students around the world will have escaped the story of Phineas, and his mishap with an iron rod used to tamp blasting powder into a hole in the rock in preparation for a controlled explosion. Things didn’t go to plan, and the explosion was rather lacking in control. Wikipedia relates the story:

“Rocketed from the hole, the tamping iron‍—‌1 1⁄4 inches (3.2 cm) in diameter, three feet seven inches (1.1 m) long, and weighing 13 1⁄4 pounds (6.0 kg)‍—‌entered the left side of Gage’s face in an upward direction, just forward of the angle of the lower jaw. Continuing upward outside the upper jaw and possibly fracturing the cheekbone, it passed behind the left eye, through the left side of the brain, and out the top of the skull through the frontal bone.”

Improbably, Phineas Gage survived, and it is his survival that secured his place in the hall of fame of neuroscience. After the accident, his behavior seems to have been altered dramatically. According to his physician, “the balance between his intellectual faculties and animal propensities seems to have been destroyed”. Phineas apparently became grossly profane, irreverent, and showed “but little deference for his fellows.”

We now know that those changes in personality likely resulted from damage to Phineas Gage’s frontal lobes, the part of the brain now commonly implicated in numerous aspects of executive control, including in particular the tempering of a person’s level of aggression. No wonder, then, that Phineas experienced a lasting change in personality, although the exact details of this personality change are actually remarkably fuzzy.

Our knowledge of how the brain operates, and what parts are involved in particular aspects of our behavior and cognition, has expanded considerably since the mid-19th century. Modern technology has played a major role in this development as we have moved from tamping irons to non-invasive techniques, such as functional magnetic resonance imaging (fMRI), which we have discussed here previously on several occasions. fMRI exploits the fact that when neurons in a particular brain region are active, more fresh oxygen-rich blood flows into these regions, replacing oxygen-depleted blood. fMRI detects these changes in blood flow, via magnetic resonance (hence the name), allowing us to measure how active a brain region is at any given time.

A recent article in the Psychonomic Society’s journal Cognitive, Affective, & Behavioral Neuroscience reported a study using fMRI that focused on why people often become aggressive and even violent after drinking alcohol. Most existing theories have linked this aggression to alcohol-related changes in the functioning of the prefrontal cortex: Alcohol may have consequences that are less permanent than those suffered by Phineas, but perhaps it acts on the same regions as that mid-19th century tamping iron?

Researchers Thomas Denson, Kate Blundell, Timothy Schofield, Mark Schira, and Ulrike Krämer addressed this question by inviting participants to the laboratory to consume an alcoholic beverage containing vodka or a placebo (in the control condition), before participating in an aggression-eliciting task. The amount of alcohol consumed was calibrated to each participant’s weight to achieve a level of intoxication of .05; that is, the point at which it is illegal to drive in most jurisdictions.

Participants in both conditions were told that they would be consuming alcohol. The drinks were mixed in front of participants, using a vodka bottle to add the alcohol (in the experimental condition) or tonic-water placebo (in the control condition). In the control condition, a small amount of vodka was smeared on the rim of the participant’s cup to provide an odor of alcohol.

The task was the Taylor Aggression Paradigm (TAP), which is illustrated in the figure below and which was administered while participants were lying in the fMRI scanner. The basic idea behind the TAP is that participants believe they are competing against an opponent on a reaction-time task. Depending on whether they win or lose on a given trial, they administer or receive a noise blast to/from their opponent. In reality, no opponent exists and the sequence of wins and losses, as well as the intensity of the noise blasts delivered by the “opponent” are controlled by a computer.

As shown in the figure, participants first decide on a level of aggression that they wish to deliver to the opponent (on an intensity scale from 1 to 4) should they win the next trial. They then wait for a colored square to appear, whereupon they press a button as quickly as possible. On a “winning” trial, when participants were “faster” than the imaginary opponent, the burst of noise of the pre-determined level of intensity was (ostensibly) delivered to the opponent. On a “losing” trial, the participant would be exposed to the noise blast selected by the opponent. Denson and colleagues created two “opponents” that differed in the level of provocation: Opponent 1 only delivered noise blasts of intensity 1 or 2, whereas Opponent 2 delivered blasts of intensity 3 or 4 only.

The main behavioral results are shown in the figure below, which plots the participant-selected noise level across trials for each opponent in the two conditions.

Aggression was greater overall when the game was played against a high-provocation opponent.

No surprises there.

But what does this have to do with Phineas Gage?

The figure below shows the effects of alcohol on brain activation in certain regions in the brain that were selected to be of interest on the basis of prior theory. The figure shows that brain activation was lowered by alcohol in the prefrontal cortex (PFC; top panel), caudate (second panel), and ventral striatum (third panel). The opposite result, heightened activity due to alcohol, was observed in the hippocampus.

These results are compatible with the idea that the PFC is instrumental in controlling aggression, and that alcohol lowers the functioning of the PFC to control that aggression.

Further confirmation of the role of the PFC in managing aggression was obtained by correlating activity in the dorsomedial and dorsolateral PFC with aggressive behavior. These results are shown in the figure below: it is clear that activity was related to aggression, but only for intoxicated participants.

Denson and colleagues opine that when considered together, these findings

“suggest that when intoxicated, the PFC becomes dysregulated relative to sobriety, but that the activity that is present may facilitate intoxicated aggression.”

The results reported by Denson and colleagues are largely consistent with a growing body of research about the neural basis of aggression, and how it is triggered by altering the function of the prefrontal cortex, the limbic system and reward-related regions of the brain.

Alcohol seems to trigger those changes much like a tamping iron does, although with (usually) considerably less permanence.

Psychonomics article featured in this post:

Denson, T. F., Blundell, K. A., Schira, M. M., & Krämer, U. M. (2018). The Neural Correlates of Alcohol-related Aggression. Cognitive, Affective, & Behavioral Neuroscience. DOI: 10.3758/s13415-017-0558-0.

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