Analog Science Fiction and Fact - Jan-Feb 2014

by Penny Publications

  I think the best bet is to develop a protein such as a specif ic kind of opsin and use a virus to introduce the gene into the brain. But there are lots of difficulties. The engineered form of these viruses might not behave like the reproducible, communicable viruses that some nefarious person could simply release into the air. Instead they may have to be brought into direct contact with the subjects.

  Now is a good time to remind you that I'm not advocating any of this. Exactly the opposite, in fact—and I think it's helpful to try to figure out the worst case scenario that we might actually have to deal with in the future.

  If you're going to be slipping something into the brain, why not make it permanently active rather than dependent on an external stimulus such as radiation? You could do this but without the on/off switch you'd lose control over the stimulation, and I suspect the result would be a lot less effective. The brain adapts to a continuous stimulus.

  What kind of influence could some unscrupulous manipulator wield with this stimulation? I can imagine a lot of things, some of which are far more malicious than just subtle manipulation. It can be lethal if, for example, the targets are brainstem neurons that regulate fundamental physiological processes. Destroy enough of them and the victim dies on the spot. But let's not venture into the realm of assassination—if committing violence is the goal, there are plenty of ways that are much simpler than brain stimulation.

  Let's assume the goal is to influence a person's judgment. I'm convinced that this is possible with the system I've outlined in this article. Experiments in primates proved it years ago.

  In one fascinating experiment reported in 1990 by the laboratory of William Newsome at Stanford, researchers influenced a monkey's perceptual judgment of a moving stimulus. 9 The monkey viewed a screen that displayed a bunch of moving dots and received a reward when it correctly identified the direction of motion. To make the task more difficult, all the dots weren't necessarily moving in the same direction—there was a lot of random motion interposed on the overall movement, so the direction of motion was merely a drift and could be difficult to discern. The monkey made its response by shifting its gaze to a certain location, and researchers tracked these eye movements.

  Once the monkey had learned the task, the researchers inserted tiny wires into a specific region of the monkey's cortex called the middle temporal (MT) area. 10 MT is known to process visual information related to motion. If you record the electrical activity of a neuron in MT while the animal is watching a visual stimulus, the neuron tends to become active only when the stimulus moves in a certain direction. These neurons act like little motion detectors, and they are specific for the direction of motion. For instance, a neuron may be tuned for motion that is downward and to the left, and when an object moves in this general direction the neuron fires a lot of action potentials (also known as spikes—these are abrupt changes in electrical potential that neurons use to encode and transmit information).

  Newsome and his colleagues used electrical stimulation to influence the monkey's response during the motion task. Neurons in MT that are tuned for the same direction of motion tend to cluster together. By stimulating with a low current limited to a small region—a procedure known as micro stimulation—Newsome could activate neurons that are mostly tuned for some specific direction. Even with microstimulation you can't control what you stimulate, as I mentioned earlier, so the experiment wasn't perfect—the researchers probably stimulated a number of neurons they wanted to avoid. Even so, Newsome and his colleagues discovered they could bias the monkey's decision. For instance, if they stimulated neurons that were tuned to a direction of motion that was different than the motion of the stimulus, the monkey would miss more often than otherwise. And its incorrect responses tended to be in the direction preferred by the stimulated neurons. In other words, the monkey often incorrectly decided that the stimulus was moving in the direction dictated by the stimulated neurons instead of the actual motion of the stimulus.

  Notice how this perceptual nudging had to be specific. You can't just stimulate the whole brain or even a somewhat small section of it and expect to get this effect. The brain processes information in a highly complex manner. This is clearly evident in the way it processes visual information: not only is there a specific cortical region for detecting motion, there are also regions devoted to color, shape, location, object recognition, and so forth. These are distinct and separate regions that focus on only one aspect of the visual stimulus. Somehow all these different networks pool their calculations so that you see, for example, a yellow car moving down the road, but the neurons that "see" yellow, detect motion, and determine that the object is a car are in quite distant locations. Influencing what people perceive or how they respond to it will not be a simple task, but instead requires highly precise selection and targeting.

  You can achieve this precision roughly with microstimulation, providing you can record from neurons, as well as stimulate so that you can find your target. But you can also attain such precision by targeting neurons that have specific biochemical characteristics such as the use of certain signaling molecules, or receptors for these molecules, or some other kind of protein that identifies the neurons as participants in a particular network. Perhaps you could also target neurons that are active at specific times. There are lots of ways to do it with brain stimulation if you can insert some sort of substance into the brain that is used by only certain kinds of neurons.

  Could you nudge someone's mind in this way without their realizing it? I'm pretty sure the answer is yes. In the 1950s and '60s, a few physicians began stimulating the brain of human patients as part of the diagnosis or treatment of various neurological and psychiatric disorders. José Manuel Rodriguez Delgado, a physician and scientist (then at Yale University) well known for his electrical stimulation experiments, performed operations in which he implanted electrodes along with a stimulator and receiver that could be operated remotely with a transmitter (he called the device a "stimoceiver"). He would often stimulate patients without warning, and since he used small currents, the patient was generally unaware of when the stimulator was turned on. 11

  In one of the Delgado's patients, the stimulation caused the patient's head to turn. Yet the patient apparently believed he had initiated the movement voluntarily. When asked why he moved his head, he provided reasonable responses: he was looking for something, he heard a noise, or he just felt restless. 12 He seemed completely unaware that the real reason he turned his head was because his brain had been stimulated, so he invented an explanation for his action.

  Although stealthy stimulation is feasible, there are probably many more things you can do if the subject is willing and nothing has to be concealed.

  Brain Activation by Manifest Stimulation

  The number of options increases when you don't have to be sneaky. You can get the patient to swallow a pill, accept an injection, apply an ointment, and stick his head against a radiator—provided you can assure him it's all safe and effective. Any portion of the brain could be targeted if you could use strong fields instead of, say, weak infrared beams.

  When most people think of brain stimulation, they probably think about medical treatments. That's probably because they're heard something about deep brain stimulation, or DBS for short. The modern version of DBS began in the 1980s when physicians discovered that stimulation of some deep structures in the brain could alleviate symptoms of movement disorders such as essential tremor and Parkinson's disease. (Actually, DBS began in the 1950s with researchers such as Delgado at Yale and Robert Heath at Tulane University, but these days most people have forgotten these pioneers or don't want to think about them, because Delgado and Heath sometimes got into trouble for going a little too far with their experiments.)

  In DBS, neurosurgeons implant thin electrodes into the patient's brain and connect the electrodes to stimulators. The electrodes need to be placed in precise locations (which varies depending on the disorder), but these days surgeons have imagi
ng tools and computer guidance systems to help them hit small targets. DBS doesn't cure diseases but it generally relieves the symptoms and permits patients to reduce their medications, which is a big help because the medications often have severe side effects, particularly at high doses.

  DBS has also occasionally improved mood and helped to alleviate symptoms of psychiatric disorders, such as obsessive-compulsive disorder, in which patients feel completely taken over by certain ideas or feel compelled to repeat certain rituals or chores. Psychiatrists and neurologists have recently started trying to expand the number of applications of DBS, testing its effectiveness on patients with Alzheimer's disease, depression, coma, and even morbid obesity.

  But since DBS involves a craniotomy, there are risks. And they're serious: brain damage, hemorrhaging, infection, and seizures have occurred during the electrode implantation procedure or subsequent stimulation. (Serious complications are rare but they do happen.) Yet people are willing to take these risks, sometimes just to lose weight. Think of how many people would be willing to undergo a procedure that was just as effective, and probably more so, but didn't require any surgery.

  Brain activation by manifest stimulation wouldn't be limited to alleviating symptoms—it could be applied to anyone who wanted to enhance their brain power or influence emotions. Depending on how precisely you could target the networks and systems, I think it would be possible to enhance memory, elevate mood, decrease fear or anxiety, and much else. I also wonder if you might be able to adjust personality to suit the occasion. Perhaps your job requires you to be a bear but you have an unfortunate tendency to take your work home with you, much to the displeasure of your family. Maybe brain stimulation could provide a switch to go back and forth, from the hard-nosed boss during the day to the nice family guy at night.

  Or it might be able to spark a talent such as creativity. In 2003 Allan Snyder at the University of Sydney and his colleagues reported that they increased creativity in a few experimental subjects by stimulating the left hemisphere with transcranial magnetic stimulation, 13 which depending on the stimulus parameters can inhibit the target. Snyder seems to believe in that old and, in my opinion, highly oversimplified adage which says the left half of the brain is for logic and the right is for creativity. By inhibiting the left, you would presumably increase creativity. Snyder claims that the art work of a few of his subjects showed greater creativity when they were stimulated. I'm skeptical—as I mentioned earlier, the brain isn't that simple—but I think you could genuinely boost creativity with the stimulation system I've outlined in this article.

  But there are a lot of things I think are quite unlikely, no matter how advanced brain stimulation techniques become or how they are used. Because of its complexity, the human brain is extremely difficult to control or fool. You've probably read stories about stimulating the brain of a person to produce an artificial or virtual reality, so the subject thinks he's living in the real world even while he's strapped to a chair. To fool the brain like that you'd need to stimulate every sensory channel perfectly, and the brain has a lot of them, many of which we're only vaguely aware. Proprioception, for example—your brain has to maintain an updated representation of your body's position so that you can move without falling over or bumping into anything. And since all brains are unique and process information differently—the variability in imaging experiments illustrates this, but there is a lot of additional evidence for it—you'd have to program the stimulation perfectly for each individual. If the stimulation isn't perfect the brain will detect contradictions, and the person is likely to experience something akin to seasickness.

  I have the same deep skepticism for the notion that humans can become hopelessly addicted to electrical stimulation in the so-called pleasure centers. These "centers" are actually complicated circuits, not just buttons you can push. 14 And the brain adapts, so chronic stimulation would have varying effects.

  So if I'm right about the development of this futuristic kind of brain stimulation, we can look forward to a lot of things in the near future, but there are limits. Comfortably so, in my view.

  But what about the stealthy version? Should we be worried in the coming decades about what I've called mind nudging? I'm not sure, but I'm going to keep an eye on neuroscience research.

  I hope I'm wrong, and it seems far-fetched to even consider the possibility of such a blatant disregard for basic civil rights. In the still of the night when it's quiet and I can ponder stuff without any sort of distraction, I can almost convince myself that stealthy stimulation could never happen. But then I remember all the unpleasant things that have occurred in history. Most of those things were probably regarded as far-fetched and highly unlikely—until they happened.

  Yes, I'm familiar with residents of psych wards who claim that their brains are receiving instructions beamed by Martians. Yes, those people are funny, in a sad sort of way, I suppose. So do I remind you of one of them? Well, I'm not quite that bad yet, but I want to end this article by asking you a question: Are you sure you know where your thoughts and decisions come from?

  Footnotes:

  1 I sometimes use "light" as a generic term for electromagnetic radiation. When there is a possibility of confusion, I use the term when I'm specifically referring to the sliver of the spectrum that we can see.

  2 Actually it images metabolism, which is an indirect measure of neural activity. There are other methods of imaging brain activity, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), but these machines cost millions of dollars.

  3 Transgenic techniques are sometimes called "knock outs" because usually a certain gene is deleted or knocked out of the animal's genome. In this way researchers can study the function of the gene by observing the deficits caused by its absence. Insertion of a gene, as is the case when an opsin gene is incorporated into a transgenic animal, is known as a "knock in."

  4 Polina Anikeeva et al. 2012. "Optetrode: a multichannel readout for optogenetic control in freely moving mice." Nature Neuroscience.

  5 Jan Tønnesen et al. 2011. "Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model." PLoS ONE.

  5 Jan Tønnesen et al. 2011. "Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model." PLoS ONE.

  6 Toshinori Kato, Atsushi Kamei, Sachio Takashima, and Takeo Ozaki. 1993. "Human Visual Cortical Function During Photic Stimulation Monitoring by Means of Near-Infrared Spectroscopy." Journal of Cerebral Blood Flow and Metabolism.

  7 Actually, if the stimulation were mild the person probably wouldn't even notice. An increase in intensity, however, would scramble the timing and synchronization of neural communication, resulting in confusion—the person might stop what they're doing, lose their train of thought, or begin making awkward or repetitive movements. Greater intensities would probably elicit a seizure.

  8 Jonathon Wells et al. 2008. "Frontiers in Optical Stimulation of Neural Tissues: past, present, and future." Proceedings of SPIE.

  9 C. Daniel Salzman, Kenneth H. Britten, and William T. Newsome. 1990. "Cortical microstimulation influences perceptual judgements of motion direction." Nature.

  10 Located, appropriately enough, around the middle of the temporal cortex, which is at the side of the head. MT is also called V5, the fifth in a series of cortical areas that process visual information.

  11 Patients can't detect low-current stimulation unless the stimulation occurs in a region that is especially sensitive. For example, stimulation of the cortex in the occipital lobe (at the back of the head) often produces noticeable flashes of light in the patients because this region is devoted to visual information. But if the electrode is placed outside of such sensory regions, nothing much generally happens. Wilder Penfield of the Montreal Neurological Institute became famous for mapping the human cortex by stimulating the exposed brain surface durin
g neurosurgery. Every once in a while Penfield could elicit flashbacks or memories when he stimulated the cortex at the temporal lobe in epileptic patients, but most of the time stimulation beyond the sensory areas produced no conscious experience.

  12 José M.R. Delgado. 1969. Physical Control of the Mind: Toward a Psychocivilized Society.

  13 Transcranial magnetic stimulation uses powerful, time-varying magnetic fields to induce electric fields in the brain, which causes currents to flow, thereby stimulating the brain without having to do a craniotomy. The experiment of Snyder and his colleagues is found in: Allan W. Snyder, Elaine Mulcahy, Janet L. Taylor, D. John Mitchell, Perminder Sachdev, and Simon C. Gandevia. 2003. "Savant-like skills exposed in normal people by suppressing the left fronto-temporal lobe." Journal of Integrative Neuroscience.

  14 The concept of pleasure centers became popular after the work of James Olds beginning in the mid-1950s. Olds and his colleagues discovered that rats will exhaustively press a bar to deliver a spurt of electric current to certain portions of their brain. But humans aren't rats. And besides, I'm not sure the rats were really loving it either. If the same stimulation is delivered continuously, the rats will work just as hard to turn it off.

  About the Author:

  Kyle Kirkland earned a doctorate in neuroscience and spent a lot of time building models of neural networks and probing the brains of mice with little tungsten electrodes. Later he left the lab and became a writer. He is the author of Neuroelectricity: The Past, Present, and Future of Brain Stimulation.