As humans, we tend to consider our emotional states as a direct response to the experiences of our lives. Traffic may make us frustrated, betrayal may make us angry, or the ever-grinding wear of modern life might make us depressed.

Dig into the science of the brain, though, and one must realize that our emotional states are really just electrical signals zinging around our neurons. And as such, they can even be influenced by direct electrical stimulation.

One group of researchers found this out when they inadvertently discovered a “switch” that induced massive depression in a patient in mere seconds. For all the complexities of the human psyche, a little electricity proved more than capable of swaying it in an instant.

Electric Feel

Deep brain stimulation has, in recent decades, become a well-established treatment for multiple conditions, including Parkinson’s disease. The treatment regime involves using precisely placed electrodes to deliver high-frequency pulses of electricity that help quell undesirable symptoms, such as tremors and muscle rigidity. When implanting electrodes deep in the brain tissue, surgeons aim for an area called the subthalamic nucleus. It’s a small region deep in the brain where electrical stimulation can dramatically improve motor control in Parkinson’s patients. In turn, this can reduce a patient’s reliance on medications, allowing them to treat their condition with fewer undesirable side effects.

Images captured from the patient during stimulation testing show the effect in action. The first panel shows the patient’s usual expression, while the second shows a drop in facial expression within 17 seconds after stimulation of contact zero. the third photograph shows the patient crying and expressing despair 4 minutes after engaging electrical stimulation. Finally, the last photograph shows the patient laughing just over a minute after the stimulation was disengaged. Credit: research paper

In 1999, a team of surgeons carrying out this routine work discovered something unexpected. Move the point of electrical stimulation just two millimeters lower, and you don’t treat Parkinson’s at all. Instead, you can accidentally trigger profound, immediate depression.

The patient was a sixty-five-year-old woman who had suffered from Parkinson’s disease for three decades. Despite treatment with high doses of contemporary Parkinson’s medications, she suffered tremors and other serious motor control symptoms. With the pharmaceutical treatment having limited effect, the decision was made to pursue therapy via brain stimulation. During the implantation of four electrodes in the patient’s subthalamic region, surgeons followed the then-standard protocol. Stimulation was tested through four different contact points on each of the four electrodes, intending to find the sweet spot that best alleviated the patient’s symptoms without causing side effects to speech, movement, or posture. Typically, electrical stimulation through some of the contacts would lead to therapeutic benefits, while others would have no effect or negative effects.

After the surgical implantation, contact zero of the leftmost electrode sat in the substantia nigra. When researchers applied a stimulation of 2.4 volts at 130 Hz through this contact, a reaction was noticed within mere seconds. As seen in images captured during the test, the patient’s face rapidly transformed into an expression of profound sadness.

The patient leaned over, cried, and verbalized strong negative feelings of hopelessness and worthlessness. “I’m falling down in my head, I no longer wish to live, to see anything, hear anything, feel anything…” the patient was recorded as saying in the research paper. “Everything is useless, always feeling worthless, I’m scared in this world.” No feelings of physical pain were reported; the symptoms seemed strictly limited to intense emotional distress.

The patient’s distress is readily visible in images taken during the stimulation procedure. The research paper notes that on a clinical basis, the patient’s self-described feelings fulfilled most of the diagnostic criteria for major depressive disorder. As quickly as the negative feelings arrived, though, they would soon disappear. The depressive state vanished for the patient within ninety seconds of switching off the stimulation to the contact in question. Soon enough, for several minutes after, the patient was reported as being in a “hypomanic” state, more positive and making jokes with the test examiners. Notably, the patient was aware of the adverse event and able to recall it clearly.

In later tests, PET scans were used to map blood flow in the brain during stimulation of contact zero, as researchers tried to map out the causative effect at play. Credit: research paper

The researchers would later verify the phenomenon was reproducible by repeating the stimulation in tests on a later date. During these tests, the patient was unaware whether stimulation was real or simulated. The same response was noted—stimulation through the contact in question zero produced immediate, severe depression that resolved within a minute of cessation.

Crucially, simulating the stimulation had no effect whatsoever, and the same depression-causing effect was noted whether the patient was or wasn’t taking the typical levodopa medication. Meanwhile, outside of this strange effect, the stimulation implant was otherwise doing its job. Stimulation through contacts one and two of the left electrode, positioned just two millimeters higher in the subthalamic nucleus proper, dramatically improved the patient’s motor symptoms without affecting mood. Medical imaging would later confirm that contact zero sat in the central substantia nigra, while the therapeutically-beneficial contacts were clearly within the subthalamic nucleus above.

Similar results were published in 2008 with a 62-year old male patient. The patient noted a “fantastic” sense of joy when the negative stimulation was ceased. Credit: research paper

The startling results led to a research paper. Beyond that, further work was limited, likely for multiple reasons. For one, there’s not a whole lot of utility in making patients feel deep despair, and furthermore, there are grand ethical reasons why that generally isn’t allowed.

Nevertheless, a similar effect was later apparent in another patient. A paper published in 2008 reported the case of a 62-year-old man with Parkinson’s disease. Similarly to the original patient, stimulation to the substantia nigra caused an “acute depressive state” in which “the patient was crying and expressing that he did not want to live.” In much the same way, cessation of stimulation led to the feelings ceasing in mere seconds. Ultimately, n=2 is a small number, but it served as more evidence to suggest that this was a reliable and repeatable effect that could be generated with electrical brain stimulation.

This accidental discovery provides a somewhat stark example of how emotions work in the brain. The fact that major depression can be switched on and off within seconds by stimulating a few cubic millimeters of brain tissue suggests that for all our thoughts and experiences, what we feel can potentially be manipulated with mere electricity. Ultimately, the sheer complexity of the brain makes it hard for us to glean greater insight, but regardless, it reminds us that we are perhaps little more than very complicated machines.