tral nervous system (CNS) and peripheral (muscle) factors contribute to the onset of fatigue during prolonged physical exertion. However, the neurophysiological basis of CNS fatigue is not understood. There has been little systematic neuroscience research into the causes of CNS fatigue and potential countermeasures to it. Given the ever-increasing mental demands on today’s warfighter, along with emerging evidence showing the potential for nutrition to reduce CNS fatigue during sustained periods of physical and mental exertion, there is much to be gained by applying neuroscience research to improve warfighter performance. At a minimum, the tools should include functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation, more sophisticated behavioral studies in humans, and basic neurochemical and physiological assessments in rodents.2

Good evidence is emerging to suggest that CNS fatigue may be caused, in part, by reduced availability of glucose, the main energy source for the brain, and/or an imbalance of neurotransmitters/neuromodulators, including serotonin, dopamine, adenosine, and ammonia. Under some circumstances, an increase of inflammatory cytokines and elevated brain temperature could also play a role (Bautmans et al., 2008; Miller, 2009).

Carbohydrate and/or caffeine feedings during exercise are the most well-established nutritional strategies used to delay both physical and mental fatigue. Less information is available on promising new nutritional strategies such as tyrosine supplementation, which has been shown to benefit mental performance in military-specific situations, and novel food and spice extracts and phytochemicals derived from traditional medicines like quercetin and curcumin. Phytochemicals may work by virtue of their antioxidant and anti-inflammatory activity as well as their ability to provide sustained energy within the brain and muscle. Although claims of enhanced mental performance during long periods of physical or mental stress are made for a range of nutritional supplements, including branched-chain amino acids (BCAAs), ginseng, ginkgo biloba, and choline, there is little scientific support for these claims.

The development of fatigue during sustained periods of physical and mental stress is a complex and poorly understood phenomenon. During prolonged exercise, many factors contribute to the production and onset of fatigue. These factors can operate peripherally—that is, in the muscles—most importantly through depletion of the intramuscular carbohydrate stores and/or through inhibition of adenosine triphosphate (ATP) hydrolysis due to the accumulation of metabolic waste products such as phosphates and hydrogen ions (Davis and Fitts, 1998). They also act centrally in the brain, but the physiological mechanisms of CNS fatigue are just now beginning to be unraveled. Good evidence is emerging that demonstrates how important a role the CNS plays in the processes of fatigue.

Unfortunately, advances in understanding fatigue and its consequences for performance have been held back because physiologists almost exclusively study peripheral factors in fatigue (e.g., those that involve muscle, heart, or blood) in isolation from CNS involvement, whereas psychologists study mental factors (e.g., cognition, mood, vigilance, sleepiness) in isolation from peripheral interactions. Although mind and body are inextricably linked in the onset and consequences of fatigue, there has been very little focus on the neurophysiological basis of the complex interactions between the brain and peripheral factors.

Nowhere is an understanding of the biological mechanisms by which the CNS and peripheral factors in fatigue interact more important than in sustaining today’s soldiers. The increased speed, complexity, and lethality of modern warfare make it even more important than in the past to understand how to sustain or enhance physical and cognitive performance. It is also important to maintain mood and motivation as the foundation of both physical and mental performance. Without such an understanding, it will be difficult to move past outdated strategies such as nutrition and exercise training to offset muscle-specific fatigue or caffeine to maintain wakefulness. This section presents a working model of the factors associated with fatigue during sustained periods of physical and mental exertion. It then briefly reviews emerging evidence of the neurobiological basis of fatigue. This new understanding, along with the likelihood that nutrition can play an important role in mitigating CNS fatigue, can provide the foundation for what should become an area of emphasis in neuroscience research and applications relevant to soldier performance.

A working model of the factors involved in fatigue is shown in Figure 5-1. Fatigue results from mental and physical factors that ultimately increase the conscious perception of fatigue and the impairment of mental and physical performance. Physical performance requires not only the capacity of muscle to maintain its force production but also adequate motivation or effort, mental alertness, clarity of thought, decision-making ability, and mood (Davis and Bailey, 1997; Davis, 2000). Neural processes, including higher-level cognitive processing, are important components of the fatigue state, whose symptoms at onset include decreased energy, motivation, arousal, and vigor, as well as increased tiredness, perception of effort, and force sensation. These feelings of fatigue almost always occur before the muscle actually loses the ability to maintain the required force or power output (Hampson et al., 2001). Although highly trained individuals (e.g., superathletes) can persevere for longer in a fatigued state through motivation and willpower, more generally an individual’s perception that he or she can persevere and perform as well in a fatigued state as when well rested is not borne out by objective measures of cognitive performance.


Animal studies are necessary to gain understanding of neurobiological mechanisms of fatigue to a degree that is not possible using human trials.

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