Our physiological responses provide a window into our emotions. In a phenomenon known as introspection, the brain is constantly communicating with the rest of the body to not only relay information about what is going on around but also inside our bodies. When you feel fear, for example, your heart rate increases and breathing becomes heavier. The emotions that begin in the brain are transmitted throughout the body.

Emerging studies now suggest that changes in the body can also manipulate our emotions. A sudden heart rate increase, for instance, may generate feelings of anxiety even if no external threat is present. Several anxiety-related disorders have been associated with greater sensitivity to changes in the body. Until now, the extent to which psychological responses influence our emotions have not been well studied. Thanks to a recent report published in Nature, we may be one step closer to understanding how cardiac activity directly influences emotions and behavior.

The first challenge investigators had to overcome was how to manipulate the heart without harming their mice subjects. Other studies that have applied electric nerve stimulation or pharmacological interventions often generate major side effects for the animal and muddle the experiment's results. Instead, Hsueh et. al designed a wearable vest fashioned with a red LED light at the chest, that when turned on, selectively stimulated the muscles of the heart. Through a biological technique known as optogenetics, the team introduced the animals to a gene that enabled the expression of light sensitive channelrhodopsin (ChRime) ion channels exclusively in the heart. When exposed to the red LED light, these ChRime proteins activate to stimulate the heart’s muscles. This allowed researchers to control the heart rates of the animals by simply flashing the light on and off. Mice that were not exposed to the ChRime gene, and therefore did not experience any change in heart rate from the light, were kept as controls.

By electronically controlling the light, the animals’ heart rates could be brought up to 900 beats per minute, a 36% increase from their resting heart rate. The next challenge for researchers was to determine whether, or rather if, this increase was enough to influence the animals' emotions. Since mice cannot tell you when they feel anxious, Hsueh et. al had to be creative in how they measured anxiety.

Fitted with an optogenetic vest, each mouse was first placed into an open box where they could freely explore. Once they had an opportunity to acclimate to the new environment, investigators began flashing the red LED-light to increase the mouse's heart rate. Immediately, researchers observed that the light-stimulated mice began avoiding the center, opting instead to cling to perimeters of the box. A video camera above the box tracking their movements confirmed that during the stimulation, these mice were spending significantly less time in the center, compared to the control mice. Although nothing about the box itself had changed, the mice were exhibiting signs of anxiety. This was the clue that increasing heart rate alone could induce fear-driven behaviors.

Next, investigators upped the stakes by placing the mice on an elevated plus maze. Much like the name implies, this maze consists of four perpendicular arms that stand above the floor. Two of the arms, however, are insulated by walls that do not allow the animal to see over the edge. In this experiment, the mouse must overcome the very real fear of falling whenever they walk across the open arms of the maze. As expected, the light-stimulated mice spent more of their time in the closed arms, not only during the stimulation but also after the blinking light was turned off. The increase in heart rate may have made the animals more sensitive to the fear of falling.

Did increasing heart rate also influence how quickly the mice acquired new fears? To answer this question, investigators trained the mice to press a lever for a water reward, but at random, 10% of those lever pushes would gently shock the animal. Optogentically stimulating the heart did not change how well the animals learned the task, but it did reduce their willingness to press the lever once they experienced the initial shock. The light-stimulated mice not only began pressing the lever less but also were more hesitant to press the lever again after each shock. In comparison, the control mice only exhibited this level of fear when shock frequency was increased to 30%.

The most interesting findings, however, were what researchers saw in the brain. Fifteen minutes after optogenetic stimulation, the experimental mice underwent whole-brain mapping. Intermediate early gene Fos, a biomarker for neural activation, was fluorescently tagged to identify which regions were most active during the stimulation. Compared to the controls, the mice that experienced the induced cardiac stimulation displayed increased activity in the insular cortex and brainstem. Both these regions have long been implicated for their role in consciousness. The insular cortex, in particular, is distinct in its ability to regulate complex emotions such as self-awareness, empathy and compassion, in addition to the biological feelings of pain, fatigue and hunger.

Hsueh et. al observed that when heart rate increases, there is a corresponding surge of activity in the insular cortex, suggesting a clear line of communication between the brain and the heart. To determine to the extent to which this part of the brain mediates behavior, the team applied the same optogenetic technique to the brain and introduced ion channels sensitive to blue light into the insular cortex. Turning this light on, however, blocked neural activity. This allowed researchers to optically stimulate cardiac activity, while simultaneously suppressing activity in the insular cortex.

To their surprise, investigators found that when they suppressed activity in this brain region, the mice no longer exhibited anxiety in response to the cardiac stimulation. Either the animals were not aware of the changes in cardiac activity, or they were no longer responding to it with fear. Regardless, these findings suggest that the insular cortex plays a key role in regulating introspection.

One question, however, remains unanswered: how do chronic elevations in heart rate influence emotion and brain activity? Anxiety disorders often develop over the course of weeks to years due to chronic activation of the body’s fight or flight response. As complex as these disorders are, we are only beginning to understand how changes in the body influence our emotions.

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