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Opportunities in Neuroscience for Future Army Applications
inherited genome and epigenetic1 modifications of it regulate the expression of proteins critical for neural cell functions. This regulated gene expression produces signaling elements (transmitters), signal receivers (receptors), guidance of communication processes (axons and dendrites), and cell–cell recognition materials.
Known genetic markers may, for example, allow identification of individuals at greater risk of damage from exposure to chemical agents or more likely to succumb to post-traumatic stress disorder. The cost of genetic tests is likely to decrease substantially in the next decade, while their effectiveness will increase markedly. Of the 20,000-25,000 genes in the human genome, more than 100 are involved in axonal guidance alone (Sepp et al., 2008). At least 89 genes have been shown to be involved in the faulty formation of the axon’s myelin sheath (dysmyelination), associated with the development of schizophrenia (Hakak et al., 2001). Understanding the human genes associated with development of the brain and peripheral nervous system can shed light on differential human susceptibilities to brain injury and may aid in predicting which pharmacological agents will be useful for sustaining performance. The Army should position itself to take advantage of the continuing scientific progress in this area.
A proteomic marker (a type of biomarker) is a protein (generally an enzyme) whose concentration, either systemically or in specific tissues, can serve as a reliable and readily measurable indicator of a condition or state that is difficult or even impossible to assay directly. Small variations in gene structure (polymorphisms) are often associated with differences in concentration of a particular protein in a particular tissue of a particular individual, so there are important linkages between genetic factors and proteomic markers. However, specific enzyme concentrations (including tissue-specific concentration) can also be influenced (upregulated or downregulated) in response to environmental factors that vary on timescales of hours, or roughly the timescale of preparation for and conduct of an Army operation. Thus, proteomic markers can vary with recent or current conditions (environmental stressors, for example) and can also reflect the genetic traits of an individual soldier.
Proteomic markers known to signal a change in vigilance or cognitive behavior include salivary amylase, blood homovanillic acid (which correlates with dopamine metabolism), and lactic acid (a metabolic product of glucose metabolism that increases as a result of intense muscle exercise). Proteomic factors associated with fatigue resistance include microtubule-associated protein 2 and the muscarinic acetylcholine receptor. Comparison of an individual’s current concentration (titer) of one of these proteomic markers with his or her baseline titer could quantify one or more neural (cognitive/behavioral) states relevant to the status of the individual’s current abilities.
Neurohormones and neuropeptides—biologically active molecules much smaller than proteins or the nucleic acids of the genome—are another emerging class of markers of neurological and cognitive state and of psychophysiological response to stress. A study of candidates for the U.S. Navy Sea, Air, and Land Forces (SEALs) found that candidates with strong stress-hormone reactions to behavioral challenges like abrupt changes or interruptions are less likely to complete training successfully than those with weak reactions (Taylor et al., 2006, 2007). Another example is the work discussed in Chapter 3 on oxytocin, a neuropeptide signal, which is released when an individual experiences a sense of trust (Kosfeld et al., 2005; Zak et al., 2005). Hormonal markers are easily gathered with simple blood draws. The level in the bloodstream of a neural signaling molecule such as oxytocin has at best a very indirect relationship to its level in the brain; it may be necessary to figure out how to monitor its release in the hypothalamus. The monitoring of neurohormones and neuropeptides is likely to be a powerful means of identifying individuals who are well suited to particular tasks and may lend itself to assessing candidates for Special Operations training in particular.
Neuroimaging technologies available in the 2008-2010 time frame allow visualization of brain regions that are activated during action-guiding cognitive processes such as decision making. These activation patterns enable brain activity to be correlated with behavior. These imaging technologies and techniques include structural magnetic resonance imaging for volumetric analysis of brain regions, functional magnetic resonance imaging (fMRI) for cognitive control networks, diffusion tensor imaging for transcranial fibers, and hyperspectral electroencephalography (EEG).
Applications to Soldier Training
As an example relevant to evaluation of training, fMRI scans before and after training sessions can be compared to examine changes in the brain’s response to novel training-related stimuli. Novel visual and auditory inputs activate the brain in specific regions. An analysis of event-related potentials combined with fMRI before and after novel auditory cues revealed that a particular event-related potential (a P300-like potential, which is to say a positive potential occurring approximately 300 msec after a triggering stimulus) is associated with fMRI patterns of activity in the bilateral foci of the middle part of the superior temporal gyrus (Opitz et al., 1999). Only novel sounds evoke a contrasting event-related potential (an N400-like negative potential). Individuals with a strong response of the second type also have fMRI scans showing activation in the right prefrontal cortex. These
An epigenetic modification refers to changes in gene expression from mechanisms other than alteration of the underlying DNA sequence.