2009 : WHAT WILL CHANGE EVERYTHING?

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Associate Professor of Psychology and Neuroscience; Stanford University
NEUROPHENOMICS + TARGETED STIMULATION = PSYCHOLOGICAL OPTIMIZATION?

The fashionable phrase "game-changing" can imply not only winning a game (usually with a dramatic turnaround), but also changing the rules of the game. If we could change the rules of the mind, we would alter our perception of the world, which would change everything (at least for humans). Assuming that the brain is the organ of the mind, what are the brain's rules, and how might we transcend them? Technological developments that combine neurophenomics with targeted stimulation will offer answers within the next century.

In contrast to genomics, less talk (and funding) has been directed towards phenomics. Yet, phenomics is the logical endpoint of genomics (and a potential bottleneck for clinical applications). Phenomics has traditionally focused on a broad range of individual characteristics including morphology, biochemistry, physiology, and behavior. "Neurophenomics," however, might more specifically focus on patterns of brain activity that generate behavior. Advances in brain imaging techniques over the past two decades now allow scientists to visualize changes in the activity of deep-seated brain regions at a spatial resolution of less than a millimeter and a temporal resolution of less than a second. These technological breakthroughs have sparked an interdisciplinary revolution that will culminate in the mapping of a "neurophenome." The neural patterns of activity that make up the neurophenome may have genetic and epigenetic underpinnings, but can also respond dynamically to environmental contingencies. The neurophenome should link more closely than behavior to the genome, could have one-to-many or many-to-one mappings to behavior, and might ideally explain why groups of genes and behaviors tend to travel together. Although mapping the neurophenome might sound like a hopelessly complex scientific challenge, emerging research has begun to reveal a number of neural signatures that reliably index not only the obvious starting targets of sensory input and motor output, but also more abstract mental constructs like anticipation of gain, anticipation of loss, self-reflection, conflict between choices, impulse inhibition, and memory storage / retrieval (to name but a few...). By triangulating across different brain imaging modalities, the neurophenome will eventually point us towards spatially, temporally, and chemically specific targets for stimulation.

Targeted neural stimulation has been possible for decades, starting with electrical methods, and followed by chemical methods. Unfortunately, delivery of any signal to deep brain regions is usually invasive (e.g., requiring drilling holes in the skull and implanting wires or worse), unspecific (e.g., requiring infusion of neutoransmitter over minutes to distributed regions), and often transient (e.g., target structures die or protective structures coat foreign probes). Fortunately, better methods are on the horizon. In addition to developing ever smaller and more temporally precise electrical and chemical delivery devices, scientists can now nearly instantaneously increase or decrease the firing of specific neurons with light probes that activate photosensitive ion channels. As with the electrical and chemical probes, these light probes can be inserted into the brains of living animals and change ongoing behavior. But at present, scientists still have to insert invasive probes into the brain. What if one could deliver the same spatially and temporally targeted bolus of electricity, chemistry, or even light to a specific brain location without opening the skull? Such technology does not yet exist — but given the creativity, brilliance, and pace of recent scientific advances, I expect that relevant tools will emerge in the next decade (e.g., imagine the market for "triangulation helmets"...). Targeted and hopefully noninvasive stimulation, combined with the map that comprises the neurophenome, will revolutionize our ability to control our minds.

Clinical implications of this type of control are straightforward, yet startling. Both psychotherapy and pharmacotherapy look like blunt instruments by comparison. Imagine giving doctors or even patients the ability to precisely and dynamically control the firing of acetylcholine neurons in the case of dementia, dopamine neurons in the case of Parkinson's disease, or serotonin neurons in the case of unipolar depression (and so on...). These technological developments will not only improve clinical treatment, but will also advance scientific theory. Along with applications designed to cure will come demands for applications that aim to enhance. What if we could precisely but noninvasively modulate mood, alertness, memory, control, willpower, and more? Of course, everyone wants to win the brain game. But are we ready for the rules to change?