First of all, we are already doing some forms of brain control in the clinic. There are several options to achieve brain control, such as deep brain stimulation, electroconvulsive therapy and transcranial magnetic stimulation. Deep brain stimulation delivers small electric shocks to certain areas of the brain to stop them from working, while electroconvulsive therapy uses electric currents to trigger seizures. Transcranial magnetic stimulation actually uses a magnetic field to stimulate areas of the brain.
These technologies are currently being used to treat neurological and mental health diseases ranging from depression to epilepsy. If we define brain control as the ability to alter an individual’s thinking or emotions, then alleviating somebody’s depression, and therefore changing that person’s mood, through manipulating neurons can be considered a form of brain control.
Although current brain modulation strategies have some clinical efficacy in altering brain function, they can be severely ineffective in a significant population of patients. In addition to this inconsistency in effectiveness across large patient populations, current strategies also suffer from a wide variety of drawbacks including the inability to target areas deep inside the brain and the need to surgically implant electrodes. Most importantly, these strategies are not precise enough to manipulate micro-neural circuits located within larger regions of the brain. The ideal solution is to have a technique that is noninvasive, capable of targeting microcircuits deep inside the brain and capable of activating or inactivating neurons at the timescale of microseconds, since neurons talk to each other within microseconds.
One such ideal tool could be optogenetics, which is a newly developed technique that utilizes light in order to control neural activity. Optogenetics exploits proteins known as opsins, which are found in bacteria and other microbes. Attached to a light-sensitive cofactor called a retinal, opsins can translate light sensory input into the movement of ions across the cell membrane.
Given that ion transport also occurs when neurons communicate with each other, researchers began to realize that opsins may be exploited to control neural activity through modulation of ion movements. In 2005, neuroscientists engineered neurons grown on cell cultures to express microbial opsins, rendering these neurons light-sensitive. They then showed that shining a light on these neurons allowed them to precisely control the neurons’ activities. Conveniently, opsins also have a high temporal resolution, which means that they can be measured precisely with respect to time, allowing researchers to manipulate the neurons on a timescale of microseconds.
These initial findings inspired subsequent studies utilizing optogenetics to manipulate specific neural circuits not only in cell cultures but also in living animal systems. Different studies have applied optogenetics to study various aspects of brain function, including mood and cognitive abilities. In an Inception-like feat, neuroscientists at MIT utilized optogenetics to create “false” memories in mice by manipulating the hippocampus, the brain’s center of learning and memory.
Over this past summer I used optogenetics in rats to influence their decision-making in a behavioral choice task in order to identify the neural correlates underlying how organisms learn about rules in the environment. In terms of clinically-relevant research, optogenetics has also been used to prevent cocaine addiction, abort seizures and enhance memory functions.
The power and utility of optogenetics in these mouse studies point to potential applications in humans, especially given several recent improvements to the technologies. First, modern advances in molecular engineering have now allowed clinicians to deliver genes to specific neurons in a human patient. Such a delivery is accomplished by packaging the gene inside a benign virus, which is then injected into the patient.
This virus-mediated approach can be used to deliver opsins to human patients, rendering neurons of interest light-sensitive. Moreover, this approach also allows clinicians to target neurons based on their genetic profile, which is more precise than current simulation strategies. More studies to optimize virus-mediated gene delivery in humans will extremely benefit optogenetic applications in the clinic.
Following the delivery of opsin genes, it is then necessary to deliver light to specific areas. Traditionally, light delivery is accomplished by the implantation of optic fibers, which are essentially strips of glass that can collect light from one end and illuminate the other. However, the need to implant optic fibers has been overcome by the development of opsins that are sensitive to red-shifted light, which is light that has been shifted to the red end of the spectrum. This light has been shown to penetrate the skull and deep tissues within the brain.
If we develop more potent red-shifted opsins, it may be possible to achieve brain control in humans by simply shining a light on an individual’s head, obviating the need to drill into the skull.
