NASA Slide Deck 2

A Synergistic Approach to Assess Risk to the Central
Nervous System During Long-Duration Space Exploration

Meaghan Roy-O’Reilly1, Ajitkumar Mulavara2, Thomas Williams3
1
Department of Neurology, University of Texas Health Science Center, Houston, TX
2
KBRwyle, Houston, TX
3
National Aeronautics and Space Administration Johnson Space Center, Houston, TX
Introduction
• Operational performance, behavioral

competency and crewmember health
depend on the integrity of the central
nervous system (CNS).
• Spaceflight-associated alterations in
sensorimotor function, cognition, behavior
and CNS structure and connectivity have
been reported.
• Future long-duration space exploration
will expose the CNS to environmental
stressors of unprecedented duration
and/or intensity.
Research Goal & Aims
CBS Integrated Research Plan Goal:
“Evaluate synergistic effects of simultaneous exposures to
spaceflight hazards on crewmember CNS and their operationally
relevant performance during future exploration missions, including
missions to the Moon and Mars.”
Research Emphasis 2: Operational performance measures that will

best indicate CBS performance decrements on ground and in flight
1. Identify potential decrements (and impairments) in operational performance

2. Identify “integrated” brain/behavior domains/pathways linked to performance
3. Identify biomarkers linked to performance standards
Synergistic Approach: Clinical Research & Med Operations
How can our patients better inform our short and Interfacing with Operational Medicine and JSC
long-term research questions? Clinical Teams:
1. Optimization of Operational CNS Assessments
in Crewmembers
2. Targeted Monitoring of Long-Term Mental
Health in Crew Members
Aerospace Medicine Clerkship: Space
Physiology, Sensorimotor Systems, SANS,
Countermeasures, CO2 Exposure, HERA Egress,
ISS and Gateway Hab, Neurosciences, Behavioral
Health and Performance, Exploration Medical
Capabilities, Exercise Physiology, Radiation How can research initiatives rapidly advance clinical
care?
Review Article: Alterations in Brain Structure and Evidence Report: Assessment of Candidate CBS
Function Following Long-Duration Spaceflight Operational Performance Measures
Review Article:
Alterations in Brain Structure and Function Following Long-Duration Spaceflight
Product: Summary of current knowledge on spaceflight-associated changes in the brain as

measured by magnetic resonance imaging (MRI).
Hypothesis: Structural and connectivity changes within the brain and their correlation with
CNS deficits may inform identification of CNS pathways at risk during spaceflight
Method:
• Analysis of 10 neuroimaging studies utilizing MRI scans (anatomical MRI, diffusion MRI,
FLAIR MRI or functional MRI) in short and long-duration astronauts and cosmonauts.
• Several studies included ~6 month follow up scans and functional assessment correlation
• Results were compared against neuroimaging studies in spaceflight analogs
Macrostructural
Review Article:Alterations
Results
Macrostructural changes in included altered brain position, tissue crowding, CSF distribution, increased
ventricular size, periventricular white matter hyperintensities (WMH), reduced gray matter volumes
Duration Effect: Association between longer mission duration, periventricular WMH and greater increases in
ventricular volume
Post-Flight: Follow-up scans showed resolution of gray matter volume changes, with persistent ventricular
volume increases and WMH. Global loss of white matter was noted from post-flight scan to follow-up scan.
Enlarged Ventricular System in US Crew Enlarged Ventricular System in Russian Cosmonauts

(Adapted from Roberts et al. 2017 and 2019) (From Ombergen et al. 2019)
% Change in Ventricular Volume vs.
Mission Length
Days
Microstructural
Review Article:Alterations
Results
Microstructural changes included altered white matter tract organization in the somatosensory, vestibular,
visual, motor and cerebellar pathways.
Reduced connectivity seen between the vestibular nuclei and other major brain regions, as well as the
cerebellum and other major brain regions.
Visual System Somatosensory System Motor System

Vision: Optic nerve, thalamus, optic Primary Motor: Voluntary movement,
Primary Sensory: Perception of all sensory
radiations, occipital cortex postural control
modalities, including vestibular and
proprioceptive
Cognitive: Visuospatial processing, visual Cognitive: Translation of internal/external
attention, visuomotor control, visual states into motor commands, planning of
Cognitive: Body spatial representation,
recognition (object, facial, emotional), goal-directed behavior, sensorimotor
sensorimotor integration
visually-guided decision making integration
Spaceflight-associated alterations in the brain extend to cortical structures

known to be involved in cognition and behavior
Comparison
Review to Spaceflight
Article: Analogs
Results
Shared features between spaceflight-associated CNS changes and those seen in spaceflight analogs and
terrestrial disease may facilitate identification of the major underlying stressors
Alteration Long-Duration Head Down Bedrest Isolation/ Normal Pressure
Spaceflight Confinement Hydrocephalus
Brain position Present Present Unknown Present
Tissue crowding Present Present Unknown Present
Ventricular volume changes/WMH Present Absent/equivocal Unknown Present
White matter microstructure Present Absent/equivocal Temporo-parietal Present

changes
Gray matter alterations Present Present/similar Decreased frontal Present/similar
volume
Altered connectivity Present Present Unknown Present
Sensorimotor Deficits Present Present Unknown Present
Cognitive Deficits Present Present Present Present

ReviewConclusions
Article: Results
• Spaceflight is associated with alterations in major CNS pathways, including the vestibular system,
visual system, somatosensory system, motor system and cerebellar system.
• Altered sensorimotor input during spaceflight may result in extensive central adaptation extending
to the cognitive level, affecting cognitive functions. Further study is required to determine whether
these adaptations have the potential to become maladaptive, particularly in regards to mission
phase.
• While controversial, adaptive ventricular expansion in response to microgravity may have the
potential to result in CNS pathology and therefore represents a high priority, akin to the strong
clinical and research initiatives investigating the management and mechanisms of SANS
Sources Results
Review Article:
1. Koppelmans V, Bloomberg JJ, Mulavara AP, Seidler RD. Brain structural plasticity with spaceflight. NPJ Microgravity 2016; 2: 2.
2. Alperin N, Bagci AM, Lee SH. Spaceflight-induced changes in white matter hyperintensity burden in astronauts. Neurology 2017; 89(21): 2187-2191.
3. Demertzi A, Van Ombergen A, Tomilovskaya E, Jeurissen B, Pechenkova E, Di Perri C et al. Cortical reorganization in an astronaut's brain after long-
duration spaceflight. Brain Struct Funct 2016; 221(5): 2873-6.
4. Lee JK, Koppelmans V, Riascos RF, Hasan KM, Pasternak O, Mulavara AP et al. Spaceflight-Associated Brain White Matter Microstructural Changes and
Intracranial Fluid Redistribution. JAMA Neurol 2019; 76(4): 412-419
5. Riascos RF, Kamali A, Hakimelahi R, Mwangi B, Rabiei P, Seidler RD et al. Longitudinal Analysis of Quantitative Brain MRI in Astronauts Following
Microgravity Exposure. J Neuroimaging 2019; 29(3): 323-330
6. Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV et al. Effects of Spaceflight on Astronaut Brain Structure as Indicated
on MRI. N Engl J Med 2017; 377(18): 1746-1753
7. Roberts DR, Brown TR, Nietert PJ, Eckert MA, Inglesby DC, Bloomberg JJ et al. Prolonged Microgravity Affects Human Brain Structure and Function.
AJNR Am J Neuroradiol 2019.
8. Van Ombergen A, Jillings S, Jeurissen B, Tomilovskaya E, Ruhl RM, Rumshiskaya A et al. Brain Tissue-Volume Changes in Cosmonauts. N Engl J Med
2018; 379(17): 1678-16
9. Van Ombergen A, Jillings S, Jeurissen B, Tomilovskaya E, Rumshiskaya A, Litvinova L et al. Brain ventricular volume changes induced by long-duration
spaceflight. Proc Natl Acad Sci U S A 2019; 116(21): 10531-10536
10. Pechenkova E, Nosikova I, Rumshiskaya A, Litvinova L, Rukavishnikov I, Mershina E et al. Alterations of Functional Brain Connectivity After Long-
Duration Spaceflight as Revealed by fMRI. Front Physiol 2019; 10: 761.

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A Synergistic Approach to Assess Risk to the Central

Nervous System During Long-Duration Space Exploration

• Operational performance, behavioral

Research Emphasis 2: Operational performance measures that will

1. Identify potential decrements (and impairments) in operational performance

Product: Summary of current knowledge on spaceflight-associated changes in the brain as

Enlarged Ventricular System in US Crew Enlarged Ventricular System in Russian Cosmonauts

Visual System Somatosensory System Motor System

Spaceflight-associated alterations in the brain extend to cortical structures

Tissue crowding Present Present Unknown Present

Ventricular volume changes/WMH Present Absent/equivocal Unknown Present

White matter microstructure Present Absent/equivocal Temporo-parietal Present

Sensorimotor Deficits Present Present Unknown Present

Cognitive Deficits Present Present Present Present

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