Illustration of the thought processes in the brain 1254 x 836
Illustration of the thought processes in the brain

Scientists have toyed for many years with the idea that we could modify or even abrogate abnormal brain activity by applying electric current to the brain. Initially, these were crude attempts, such as electric shock therapy (ECT), that were meant to treat deep depression. The blowback from physicians, nurses, and the public at large eventually put the practice as initially done, dialing back on the current and doing the procedure in much more controlled settings.

Now, thanks to advances in our understanding of how this tangle of biological electric wires that make up our brain actually works, we are able to much more precisely target electric currents that control certain functions and essentially reboot the ones that have gone awry.

Initially, the obvious targets were the obvious ones: Parkinson’s disease, intractable pain, depression refractive to drugs. Then, a recent paper was published with a surprising target and astonishing results. To understand the paper and its mind-blowing implications, we first need to understand something about electrical brain stimulation. What follows is a short, accessible, albeit, somewhat simplified explanation. So, stick with me.


Deep brain stimulation

When the FDA approved Deep Brain Stimulation (DBS) in the late 90’s, I remember my reaction of apprehension and disbelief. Did they think that they could implant electrodes in this incredibly complex and delicate mass of interconnected neurons with such great precision as to get a very specific, predictable, and consistent response? The answer was yes they did, and, in fact, they could.

The neurosurgical procedure is not trivial, but it is now used to treat drug-resistant Parkinson’s disease, essential tremor (meaning we don’t know what causes it; nothing essential about it), as well as psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Quite an advance from the days of high current whole brain electroshock therapy. Except that, in both cases, we still don’t really know why it works. But, fortunately, it does.

The advantage of implanting the electrodes in predetermined, well-defined regions of the brain is the assurance that these areas will get the electrical pulse. The obvious disadvantage is that it requires brain surgery, something never to be taken lightly. Efforts to make the procedure less risky eventually led to the development of Transcranial Magnetic Stimulation (or TMS). This procedure involves placing electrodes on the skull so as to affect specific areas of the brain where a motor (such as Parkinson’s disease) or psychiatric (such as intractable depression) problem occurs.

Sounds good in theory, right? Except that it is difficult to target the electricity to the right brain areas, and only to the right brain areas. There is another problem: In order to penetrate the skull to deliver an electric current deep into the brain, you need to employ high-frequency electric pulses. But neurons don’t “hear” high-frequency currents. They respond only to low frequency. Looks like an unsolvable problem? But don’t sell human ingenuity short.


The breakthrough

Dr. Edward Boyden and his colleagues at MIT found an ingenious way to penetrate the skull with high-frequency electric current, yet deliver to the neurons the low frequency that they require for eliciting a response. How do they do it?

Here is an example from simple math. How much is 1,001 minus 1,000? One, of course. You can look at it as if the 1,000 in the second number “cancels out” the 1,000 in the first, and what you have left is 1. As Boyden, quoted in an article in the New York Times, explains “if you deliver (from one electrode) 1000 hertz and 1001 hertz (from another electrode) to the brain, the neurons will react as if you delivered 1 hertz.” Why? “Because where currents intersected inside the brain, the frequencies interfered with each other, essentially canceling out all but the difference between them and leaving a low-frequency current that neurons in that location responded to.” Simple, but brilliant.

What is remarkable about this technique is its extreme precision: When they targeted the hippocampus of mice, only neurons of that region were activated, and none in the adjacent areas. The significance of this technical breakthrough cannot be overstated. It opens the way to precisely targeted manipulation of malfunctioning neurons. Here is an example of what can be achieved with this new technique.


Manipulating honesty

In their hilarious movie, Duck Soup the Marx brothers captured the essence of what we call today “alternative facts,” common currency in today’s political life. But it also raises deep philosophical questions about truth. Why is there a moral imperative in all societies and religions to tell the truth? And why did human societies devise rules to avoid cheating?

Think of it. There is a serious conflict between honesty and material self-interest. Yet, most people behave by and large, honestly. Monkeys and apes, when they cheat or steal, they do it furtively. Even my unsophisticated dog casts a sidelong glance when he knows that he did something that he shouldn’t be doing, like taking a bite out of my sandwich. We have evolved respect for honesty because it is the connective tissue that keeps our society together, as well as the gorilla’s troop, the feral dog’s band, and more. And just to make sure we stay on the straight and narrow path of truth, cheating invites punishment in all functioning societies. This implies that social animals, us included, underwent natural selection in favor of honesty. It makes you wonder, does it not, whether and where in the brain is the center that controls honesty? And, whether it can be manipulated to increase or decrease honest behavior?

I recently came across an article published in the April 25, 2017 issue of the Proceeding of the National Academy of Sciences titled “Increased honesty in humans with noninvasive brain stimulation.” Tantalizing! Here are the details.

A hundred and forty-five (145) participants in the study completed a die-rolling task where they could misreport their outcomes to increase their earnings, thereby pitting honest behavior against personal gain. While performing this task, they were stimulated with a transcranial direct current (tDSC) over their right dorsolateral prefrontal cortex (DL- PFC). The prefrontal cortex is the executive center of the brain, involved in decision-making.

Cheating was substantial in the control conditions, either sham (no current) or decreased neural excitability (reversing the polarity of the current). Thirty-seven percent of all responses were dishonest. When neural excitability was enhanced with tDSC, however, the cheating rate fell to 15%, a dramatic 60% decrease. Additional experiments demonstrated that the stimulation-induced increase in honesty was functionally specific: It did not affect other types of behavioral control related to self-interest, risk-taking, and impulsivity. Moreover, cheating was only reduced when it benefited the participants themselves rather than another person.

Now, before you jump to the conclusion that honesty resides exclusively behind your forehead (that’s where the DL-PFC is), we should note that this area has extensive connections to many other cortical and sub-cortical areas, which most likely participate in the decision-making function of the prefrontal cortex.

So, not only is there a neural manifestation of the natural selection pressure, to be honest, an honesty center so to speak, but also it appears to be modifiable with electrical stimulation. As the authors conclude,

“[T]he human brain implements specialized processes that enable us to remain honest when faced with opportunities to cheat for personal material gain.”


Dov Michaeli, MD, PhD

Dov Michaeli, M.D., Ph.D. loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us.

He was a professor and basic science researcher at the University of California San Francisco where he also taught biochemistry to medical students. During this time he was also the Editor of Lange Medical Publications, a company that developed and produced medical texts that were widely used by health professionals around the world.

He eventually left academia to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early-stage biotech company that developed products to improve post-surgical pain control.

He is now retired and enjoys working out, following the stock market, traveling the world, and, of course, writing for TDWI.


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