by Matt Gaidica
Neuroscience Graduate Program
University of Michigan, Ann Arbor (USA)
Human achievement at high altitude requires the performance of skilled behaviors with cognitive clarity. To better understand how the brain changes at high altitude during a motor task we used the actiCAP Xpress Bundle to characterize motor circuit changes up to 4,130 meters in the Himalayan mountains of Nepal.
The high altitude brain has been of great interest since Angelo Mosso performed detailed studies of respiration and cerebral blood flow in the late nineteenth century1. Since then it has been known that the reduction in atmospheric pressure at increasing altitudes requires the body to work harder to maintain oxygen levels necessary for life2. If the body becomes deficient in oxygen it is considered in a state of hypoxia. How humans adapt, compensate, or ultimately succumb to hypoxic exposure is critical information in regards to high altitude exploration3,4. Our current understanding of the hypoxic cascade largely fails to describe the neuronal underpinnings of altered cognition and task performance. We stand here at an exciting intersection in history where we both appreciate skilled behaviors as an expression of the brain and have the technology to answer critical questions in neuroscience related to high altitude.
Successfully executing motor skills may mean the difference between life and death in high altitude environments (i.e. greater than 2,500 meters). The ability to tie ropes, operate clips, or manipulate small tools are just some of the skills we take for granted at the oxygen-rich sea level. There is a long history of anecdotes supporting the notion that either the will or capacity to perform such skills is compromised even at moderate altitudes, and further exacerbated at greater heights5. While it is clear that the brain’s motor circuitry undergoes changes at high altitude6, little is known about the implications of those changes on motor task performance and skilled behaviors. Foundational studies on motor circuit adaptations in response to brain insults have led to enormous advances in brain machine interfaces (BMIs)7 and treatments for movement disorders8. Surely developing countermeasures for high altitude motor dysfunction would benefit from that vast literature, if we had a clearer picture of the brain in this unique environment.
We aimed to characterize such task-related neuronal activity by using the Brain Products actiCAP Xpress Bundle to measure cortical encephalography (EEG) during a seven-day trek to Annapurna Base Camp situated at 4,130 meters in the Nepalese Himalayas. To achieve this we developed a self-paced, reach-to-grasp task based on a homologous rodent task that we are using to study motor behavior in the laboratory9. Our reaching platform integrates sensors directly with the Brain Products V-Amp EEG amplifier, along with a wrist-based accelerometer. In total, we captured 16-channels of cortical EEG over motor brain regions in two subjects with time-locked markers for each stage of the movement: initiation, object lift-off, and object retrieval.
In general, the information garnered from EEG reflects macro-level brain dynamics emergent of the neuronal activity from underlying cortical substructures. This activity may be intrinsic to the area of recording, or represent distant inputs and/or coupling from connected brain regions10. We focused our attention on the central motor axis involved in reaching, grasping, and fine motor movements11, consisting of electrodes C3, Cz, and C4 based on standard 10-20 EEG locations. Our technical analysis began with filtering the wideband EEG data into five frequency bands classically associated with mammalian physiology12: Delta 0.5-3.5 Hz; Theta 4-8 Hz; Alpha 7.5-12.5 Hz; Beta 13-30 Hz; Gamma 30-100 Hz. Our primary hypothesis was that that beta band oscillations would be enhanced during skilled reaching at high altitude. To test this hypothesis, we calculated a trial-by-trial z-score of the power envelope and estimated a phase locking value13 to determine if any frequency bands showed a distinct pattern of activity when time-locked to our sensor markers. Data were then plotted as a function of altitude.
Contrary to our primary hypothesis that beta band oscillations would be enhanced during skilled reaching at high altitude, we found the greatest and most significant effect present in the delta band. Our data demonstrated increasing phase and amplitude synchrony mid-reach that significantly correlated with our altitude profile. Although we experienced mild levels of hypoxia (i.e. less than 90% blood oxygen saturation), no deficits in task performance were encountered, suggesting that our findings may represent early brain compensations not yet exposed by behavior. We presented this in graphical form as a poster at the 2017 International Hypoxia Symposia.
BrainVision Analyzer 2 gave us the tools necessary to visualize and interpret our data leading to a larger discussion about the potential roles for delta oscillations at high altitude. Existing literature on delta oscillations can be viewed from two angles. On one hand, there exists a strong positive correlation between enhanced delta oscillations and homeostatic processes involved in states of fatigue, disease, sleep, hypoxia14 and general anesthesia15. On the other hand, delta oscillations appear to establish an oscillatory framework for sensorimotor processing. This forms the basis of more complex phase-amplitude coupling of motor signals16,17. Furthermore, low frequency oscillations in the delta band optimally decode hand velocity18, movement direction19, and predict task accuracy20. While the direct source of delta oscillations is unclear21,22, we hypothesize that the task-related enhancement we observed is a sensorimotor response necessary to maintain task coordination. That said, from a network perspective, one neural system is telling the body to slow down (homeostatic), while the other neural system is telling the body to perform (sensorimotor). In the context of our data, the “performance system” was more salient and thus influenced behavior over the “slow-down” system. For future research, one prediction is an asymptote for task-related delta oscillations. The brain and body may enter absolute survival mode, prioritizing vital functions over sensorimotor processing.
To understand neuronal adaptations of task performance at high altitude in the context of two competing regimes is an exciting future direction in need of further study. While many high-altitude countermeasures that are currently in place likely work to reduce homeostatic drive, it may be possible to positively augment the sensorimotor system using technologies such as transcranial electric or magnetic stimulation.
Trek Tip #1: Power
Historically, power limitations and equipment size have been logistically limiting to conducting mobile, highly agile studies in extreme environments. We mitigated these barriers using the Brain Products suite of tools including the BrainVision Recorder software on a Microsoft Surface tablet, enabling us to record more than six hours per day and store all equipment among two 35-liter packs. Using a Goal Zero solar charger with a battery pack, and leveraging AC power when it was available along the trek, we were fortunate to never run low on power.
Trek Tip #2: Noise
The advantage of having Brain Product’s Analyzer 2 software on-hand was clear our very first day. Upon arriving at the first guesthouse in Tikhedhungga we setup the task and began recording. It quickly became an electrophysiologist’s worst nightmare, seeing all channels down the screen breaking past the five-hundred-millivolt thresholds with large sinusoids. Did we break the amplifier? Snap the head cap wires? The noise appeared regular, which lead us to believe there was common source, immediately suggesting power lines were the culprits. However, turning on the 50- and 60-Hz notch filters in Recorder did not take care of it. We recorded thirty seconds of data, opened it in Analyzer, and within a few clicks ran a Fast Fourier Transform analysis. There it was an enormous peak at 52.5 Hz, right outside the roll-off of the 50 Hz notch filter, and strong confirmation that we were not among regulated power plants. We had to get out of the hut, and in fact, from thereon we made all our recordings outside of the villages.
Trek Tip #3: Elements
Leaving the confines of the villages eliminated electrical noise from our recordings, but we in turn became vulnerable to the weather as a variable in our task. At locations above than 3,000 meters we became engulfed in a rising fog from the valley below around three o’clock every day. While this never turned into rain, it drowned the sun and caused a large temperature drop. Oscillations in motor regions of the brain are not only modulated by intention to move, and actions themselves, but also sensory input and feedback16. Therefore, if our fingertips or bodies were significantly colder at high altitudes, our results become more difficult to interpret. We attempted to control for this by layering clothing and assessing any discomfort using daily questionnaires (including the Lake Louise Score).
The Harvard Travellers Club financially supported this study. Brain Vision LLC, sponsored all equipment. This study received “non-regulated” status by the University of Michigan Medical School Institutional Review Board (ID: HUM00119637).
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 Milledge, J. S., West, J. B. & Schoene, R. B. High Altitude Medicine and Physiology Fourth Edition. (CRC Press, 2007).
 Miscio, G., Milano, E., Aguilar, J., et al. Functional involvement of central nervous system at high altitude. Exp. Brain Res. 194, 157–162 (2009).
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