Brain Injury

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ibij20

Unclear outcomes of heart rate variability

following a concussion: a systematic review

J. Charron, C. Soto-Catalan, V. Marcotte L’Heureux & AS. Comtois

To cite this article: J. Charron, C. Soto-Catalan, V. Marcotte L’Heureux & AS. Comtois (2021):
Unclear outcomes of heart rate variability following a concussion: a systematic review, Brain Injury,
DOI: 10.1080/02699052.2021.1891459

To link to this article: https://doi.org/10.1080/02699052.2021.1891459

Published online: 13 Jul 2021.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=ibij20
BRAIN INJURY
https://doi.org/10.1080/02699052.2021.1891459

RESEARCH ARTICLE

Unclear outcomes of heart rate variability following a concussion: a systematic review

J. Charron , C. Soto-Catalan, V. Marcotte L’Heureux, and AS. Comtois
Department of Exercise Science, University of Quebec in Montreal, Montreal, Canada

ABSTRACT ARTICLE HISTORY

Purpose: : To systematically regroup articles that were published since the latest systematic search, but Received 8 September 2020
with specific inclusion criteria to help comparison that will offer a focused presentation of methods and Revised 12 January 2021
results. This will offer a full overview of HRV’s behavior at rest and during exercise in adults post- Accepted 10 February 2021
concussion. KEYWORDS
Methods: : The systematic review was conducted using the Preferred Reporting Items for Systematic Heart rate variability;
Reviews and Meta-Analysis (PRISMA) method. A computer-based systematic search was conducted in concussion; mTBI; cardiac
December 2019 through the Pubmed, Scopus and SPORTDiscus databases. A manual search was per­ autonomic function; ANS
formed through the reference list of all articles retained. The reliability of the systematic search was
assured by having the article selection process entirely repeated by a second author.
Results: : The systematic search yielded a total of 15 articles to be further analyzed. Results show
impairment of HRV during exercise for individuals with concussion, heterogenous studies with lack of
control over confounding factors and only less than half of the results showing a significant difference
between individuals with concussion and controls.
Conclusion: : Further research should try standardizing HRV measurement protocols that control con­
founding factors to allow easier comparison between studies and allows the possibility for an eventual
meta-analysis.

Introduction
A concussion is a physiological injury caused by biomechanical
forces that are transmitted to cerebral tissues from a direct blow
to the head or an indirect one that transmits forces to the head.
Such injury causes a series of neurometabolic events and func­
tional alterations that temporally brings physical, neurological,
emotional, and circadian symptoms that cannot be explained by
alcohol, drugs, or preexisting pathologies (1–3).The numbers of
concussions yearly in the United States only is estimated to
1.6–3.8 million. However, those numbers are believed to be
much greater, as concussion is an underreported injury from
which many will never be diagnosed or treated (4,5). Concussion
brings symptoms such as; headache, dizziness, nausea, photo/
phonophobia, fatigue, postural lightheadness, difficulty with
memory, word finding and concentration, irritability, anxiety,
depression, and insomnia all of which affect both physiological
and psychological processes (6).
Because cardiac autonomic function can reflect both these
processes (7), Blake et al. considered it to be the ideal construct
to assess the impact of concussion, an opinion we also share
(8). Cardiac autonomic function can be observed using heart
rate variability (HRV) which is the time variation between two
consecutive RR intervals (9). Shaffer et al consider it as an
emerging property of interdependent regulatory systems that
operate on different time scales adapting to challenges to
achieve optimal performance (10). HRV reflects the ability of
the cardiovascular system to adapt from internal and external
stressors, such as changes to environmental, social, or
physiological factors (10,11). Because HRV offers the possibi­
lity to observe the dynamic actions of both autonomic branches
(sympathetic and parasympathetic), it is believed to be
a reliable tool to reflect autonomic function (11–14).
HRV is currently used in several clinical situations to pre­
dict increased risks associated with neuropathic diabetes, myo­
cardial infarction, heart attack, sudden death, to investigate the
autonomic nervous system’s (ANS) behavior, to study links
between physiological and psychological factors, to assess cog­
nitive development, and to be used as a diagnostic and ther­
apeutic tool (9,11,12,14,15). More recently, it has been used to
observe ANS behavior following a concussion (8). As promis­
ing as this tool sounds, several factors must be taken into
consideration when building study methodology and analysis.
HRV is a very sensitive measure that is affected by age, gender,
breathing rate, level of physical fitness, body position, drugs
(antipsychotics, antidepressants, antihypertensive, benzodiaze­
pine, and beta-blockers), menstrual cycle, time of the day,
alcohol consumption, face cooling, and emotional stress
(9,11,16–21).
The relationship between concussion and autonomic
dysfunction has been of growing interest in the past years
because of promising results showing HRV could be
a marker of recovery (22,23). Previous studies have already
shown that measures of cardiac autonomic function, such
as heart rate (HR) and heart rate variability (HRV) at rest
were modified following more severe traumatic brain inju­
ries in children; HR is elevated and HRV is reduced and

CONTACT J. Charron charron.jeremie@courrier.uqam.ca Département Des Sciences De L’activité Physique, Université Du Québec À Montréal, C.P. 8888, Succ.
Centre-ville, Montréal H3C 3P8, Canada.
© 2021 Taylor & Francis Group, LLC
2 J. CHARRON ET AL.
also during steady walking on treadmill (24–26). As for
adults, the first study on the subject dates from 2004 by
Gall et al. who observed HRV at rest and during steady
effort in junior male hockey players (18 years old). Their
results presented a lower RR interval, LF, and HF powers 5-
and 10-days post-injury in the group with concussion (27).
Later, Tan et al., showed a decreased SDNN in war veterans
with previous concussion when compared to sex and age-
corrected normative data (28). However, La Fountaine et al.
did not find any significant differences for LF, HF, and LF/
HF between three adults with concussion and three con­
trols (29). Blake et al.’s systematic review presented addi­
tional studies that obtained similar conflicting results in
both children and adults (27,28,30–32). However, they con­
cluded that the evidence was still too limited to demon­
strate an alteration of HR and HRV parameters at rest
following a concussion (8).
Blake et al., did a thorough review by regrouping studies on
a very new topic. However, the inclusion criteria were very
broad: original data presented in either an abstract or full-text
article available in English that included HRV or HR as an
outcome in individuals with concussion 6 years and older with
a comparison group (8). Out of their 13 included articles, 4
were abstracts, one was an animal model (rats), one did not
give any indication on the timeline since the concussion, two
were on children and some had data exclusively on HR and
nothing on HRV. The inclusion of abstracts limits the ability to
properly interpret the data as there is no access to the complete
methods. However, those criteria were understandable as the
number of studies were much more limited at the moment of
publication.
The previous systematic search was conducted in June 2014
(8), therefore no articles more recent than 2014 were presented.
Thus, this presents the opportunity to include a wider array of
studies that may have been published since then. The purpose of
this systematic review is to systematically regroup articles that
were published since the latest systematic search, but with spe­
cific inclusion criteria to help comparison that will offer
a focused presentation of the methods and results. This will
perhaps provide a complete to date overview of HRV’s behavior
at rest and during exercise in adults with concussion. The
included articles from Blake et al. that correspond to the inclu­
sion criteria defined herein will be added to the pool of studies to
present the most thorough overview allowable of HRV behavior
at rest and during exercise in adults with concussion.
Increasing current knowledge on the link between HRV and
concussion could give practitioners a noninvasive biomarker
(23) to assess concussion. This would be beneficial because the
current determination of concussion diagnosis is based on
clinical judgment that lacks objective measures (33). HRV
analysis could also help guide practitioners in athlete/patient’s
rehabilitation progress.
Methods
Data source and search strategy
This theoretical research was conducted by following the
PRISMA method (34). Three of the four electronic databases
suggested by the University of Quebec in Montreal (UQAM)
library services were systematically searched on
December 4th, 2019. The three following retained databases
were: PubMed, Scopus, and SPORTDiscus. ERIC (ProQuest)
was discarded due to its educational focus. The following
research strategy was used in all three databases: «Heart
Rate Variability» OR HRV OR «Autonomic Nervous
System» OR ANS AND mTBI OR Concuss* OR «Traumatic
Brain Injury». All three database searches were directed
toward articles in the field of title, abstract, and keywords
published since January 1st, 2014.
Manual search
A manual search was also performed from the reference lists of
all retained articles from the systematic search. Selected articles
by Blake et al. (8) that met our inclusion criteria were added to
present the best possible picture of HRV behavior following
a concussion.
Inclusion and exclusion criteria
Type
Only original full-texts from peer-reviewed journals were
selected; serial, books, book sections, abstracts, reviews, com­
ments, and conference papers were discarded before starting
the PRISMA method.
Duplicates
All duplicate articles were manually discarded by placing all
titles in alphabetical order in EndNote X9.
Titles
If authors could clearly identify by reading the title that the
article did not present HRV measures on adults with concus­
sion (18 years old and above), the article was discarded.
Abstracts
If by reading the abstract authors could clearly identify that the
article did not present HRV measures on adults with concus­
sion (18 years old and above) with a comparison (control)
group, the article was discarded.
Language
If the article was in any other language than English or French,
the article was discarded.
Text
If an article did not present standard HRV measures (as pre­
sented in the Task Force Guidelines) (9) with standard units (ms,
ms2, %, n.u.) on adults with concussion (18 years old and above)
and control groups (a pre-concussion and post-concussion mea­
sure on the same participant could also be considered a control
group), the article was discarded. If some participants were
younger than 18 years old and were mixed with older adults,
the article was discarded. Logarithmically transformed (Ln)
units were also accepted. HRV values had to be presented in
a numerical way either in text or in a table. If only graphical
results were presented, the article was discarded. The device used
to assess HRV parameters had to be ECG based. Previously

validated device that was concluded as equivalent to an ECG
reading was also accepted.
Contacting authors
If any specifications were required to determine whether an
article was discarded or not (e.g. if the method section was
lacking some elements necessary for inclusion or was
uncleared and therefore left some doubt in the reviewer’s
mind), the corresponding author was contacted twice by
e-mail (one-week interval). If there was no answer, a final
attempt was made by contacting a coauthor on ResearchGate.
com if any of the other authors had a profile. If no answer was
received, the article was discarded. The authors were contacted
only for clarifications and not to give their opinion on whether
the article should be included or not.
Classification, extraction, analysis
All data from selected articles were extracted to an Excel
spreadsheet, classified by authors.
Verification methods
The PRISMA method was reconducted by a second reviewer
(VML) independently to validate the selected articles. Any
disagreement between the two reviewers (JC & VML) over
Figure 1. Flow diagram of the search strategy and article selection process.
BRAIN INJURY 3
the eligibility of particular studies were resolved by a third
reviewer (ASC).
Statistical analysis
Some study designs focused on comparing resting measures of
HRV with an experimental protocol (ex: Valsalva maneuver).
Therefore, some studies did not conduct statistical analysis on
resting measures between the control and concussion group. By
using the mean, standard deviation and n of each study that had
not performed comparison between the concussion group and
control group at rest, we were able to conduct unpaired t-tests on
GraphPad to determine statistical significance between every
means presented. Statistical significance was set at p˂0.05.
Results
Search results
The systematic search and the manual search yielded a total of
15 peer-reviewed publications containing relevant data
(23,27,29,32,35–44). Out of the 15 articles, only three from
Blake et al.’s review met our inclusion criteria (27,29,32). The
flow diagram of the article selection process can be found
below (Figure 1).
4 J. CHARRON ET AL.
Results summary
Results were organized by condition (rest vs exercise) and by
position at rest, since HRV response is position (supine, sitting,
standing) dependent, especially for RR-intervals, Low
Frequency power (LF) (0.04–0.15 Hz), and High Frequency
power (HF) (0.15–0.4 Hz) measures (46).
Table 1 presents all participant characteristics from each
included study. Results show that most studies used mixed
groups (men and female regrouped) except three that con­
ducted their study exclusively on males (27,35,42).
Participant’s age ranged, based on reported means, from
18 years old up to 40 (when standard deviation is taken into
consideration, age can go up to nearly 60 years old). A few
studies presented participants that previously had a concussion
(23,27,35,40,43). Finally, the delay since the concussion
occurred was variable. Some studies were conducted in an
acute state of concussion (less than 2 weeks) (23,27,29,39–44)
and some studies were conducted several months post-
concussion (32,35–38).
Table 2 presents results from three studies that included an
exercise protocol (27,29,35). La Fountaine et al. and Abaji et al.
used the same protocol, which is a 3-min isometric hand grip
test (IHGT) (29,35). Gall et al. used a cycling protocol on
a stationary bike at a constant load for 10 minutes (27).
Results show that during the cycling protocol, individuals with
concussion have lower HRV in all measurements except LFnu
and LF/HF ratio that are higher when compared to the control
group. The difference between LF/HF ratio at 10 ± 1.4 days is no
longer significant. As for the IHGT, La Fountaine et al. did not
find a significant difference in LF/HF ratio (29) as opposed to
Abaji et al. that found individuals with concussion had a ratio
over three times higher than controls (35).
Table 3 presents HRV measurements taken at rest in
a supine position. Only one study took supine measurements
during the early phase of concussion and did not find any
statistically different HRV measures (41). Hilz et al. conducted
four studies with participants that had sustained a concussion
within months prior to data collection (32,36–38). Two studies
found significantly lower RR intervals in individuals with con­
cussion compared to the control group (32,38). Standard
deviation of the RR interval (SDRR) was also lower in two
studies (32,37). The coefficient of variation of the RR interval
(CVRR) was lower in only one (32) but there may have been
a mistake in the 2017 study because it seems very unlikely that
both means and standard deviation (SD) in both groups were
exactly the same (5.7 ± 3.3) (38). Root mean square of the
successive differences (RMSDD) was significantly higher in the
group with concussion in one study (32) and significantly
lower in another (37). As for the spectral analysis, absolute
LF is significantly lower in one study (37), but significantly
higher in two studies when expressed in normalized units (n.
u.) (32,38), while absolute HF was significantly lower in two
studies (32,37), and the same can be said when expressed in n.u
(32,38). Absolute total power (TP) was significantly lower in
the only study that presented this measure (37). As for the LF/
HF ratio, two studies found it to be significantly higher (32,38)
and the other two found no statistical differences (36,37).
Tables 4 and 5 present HRV measurements taken in
a standing position. RR interval was found to be significantly
lower in the group with concussion at 4.7 ± 2.1 days and
18.1 ± 7.9 days, but no longer significant at 25.5 ± 8.2 days
(23). SDRR was found to be significantly lower in two studies
(23,32). CVRR was found to be significantly lower in only one
study (32). There was no significant difference in RMSSD in
any study (32,38). Absolute LF power is significantly lower in
two measures (23,38), but higher in two others (23). When
expressed in n.u., only one study found it to be significantly
higher (23). Absolute HF power and HFnu was found to be
significantly lower in only one study (23). Statistical signifi­
cance of total power cannot be presented with certainty
because it appears clearly that there was a mistake in the results
presented by Senthinathan et al. for this measure (23). It seems
very unlikely that the standard deviation is the same in both
groups at three different times (SD = 1848.5 the first, 1051.4
the second and 900.3 the third time). As for the LF/HF ratio,
only one study obtained a significantly higher measure (23).
Two studies measured the 30:15 ratio, the first one found it to
be significantly lower (32), but the second did not observe any
statistical difference (38). Finally, Sample Entropy (SampEn)
was found to be significantly lower in two of the three measures
from Senthinathan et al. (23).
Tables 6 and 7 present HRV measurements taken in a seated
position. Articles by Liao et al. (39) and Sung et al. 2016a (44)
were included in this table because their protocols were identical
to Sung et al. 2016b (45). The latter specified the seated position
unlike the other two. RR interval was found to be significantly
lower twice in Senthinathan et al.s’ study (23) and higher in Gall
et al.’s study at 1.8 ± 0.2 days post-concussion (27). SDRR was
found to be significantly lower in two studies (23,27). Standard
deviation of the NN interval (SDNN) was found to be signifi­
cantly lower in individuals with concussion in every study pre­
senting that measure (43,44). RMSSD was found to be
significantly lower in Purkayastha et al. and Huang et al. studies
(40,43), but only for the first measure at 4 ± 1 days in
Purkayastha et al.’s study (43). As for the spectral analysis, LF
and HF were expressed as absolute values (ms2), percent (%), n.
u. and logarithmically transformed (Ln) units. In absolute
values, LF was found to be significantly lower once (23) and
HF twice (23,40). When expressed in percent, LF (40) and HF
(45) were found to be significantly higher once each. When
expressed in n.u. every study found statistically significant
results; LFnu being lower in four measures (23,27) and higher
in one (23) and the opposite pattern for HFnu (4 higher (23,27),
1 lower (23)). When expressed logarithmically, LnLF was found
to be lower thrice (44) and LnHF to be lower twice (43).
Furthermore, logarithmically expressed Very Low Frequency
power (LnVLF) and Total Power (LnTP) were found to be
significantly lower in every study that included those measures
(43,44). Absolute Total Power was found to be significantly
higher at first in Senthinathan et al.’s study but lower twice
afterward (23). LF/HF ratio was expressed in absolute value
and logarithmically transformed. In absolute value, it was
found to be significantly higher four times (23,27,40). When
logarithmically transformed, no significant difference between
the group with concussion and controls was found. Finally,
Table 1. Participants characteristics.
n Concussion n Concussion n Concussion Age Time Since previous GCS Age
Authors (total)/mix Male Female Concussion mTBI n of mTBI Score n Controls Controls Device used for HRV recordings
Abaji et al. (35) 12 12 - 21.4 (1.1) 95 (63) days 2.8 (1.7) - 12 22.1 (1.6) HR monitor (RS800CX from Polar Electro, Kempele,
Finland)
Gall et al., (27) 14 14 - 18.1 (0.4) Rest: 1.8 (0.2) days Exercise: 5.0 1.9 (0.3) - 14 18.8 (0.4) Burdick EK-10
(1.4) days*** Electrocardiograph
Hilz et al., (32) 20 17 3 37 (13.3) 20 (11) months - 14.5 20 25.6 (8.8) 3-lead ECG
(0.6)
Hilz et al., (36) 24 17 7 34 (12) 32 (24) months - 14.5 27 30 (11) 3-lead ECG
(0.6)
Hilz et al., (37) 25 18 7 35.0 (13.2) 34 (29) months - - 29 31.2 (12.2) 3-lead ECG
Hilz et al., (38) 20 14 6 33.1 (13.5) 25.2 (20.5) months - - 20 29 (10) 3-lead ECG
Huang et al., (40) 23 15 8 20 (1.2) 4 (1) days 1 (1) - 23** 20 (1.5) 3-lead ECG (Solar 8000i patient monitor; GE
Healthcare, Chicago, Illinois)
Johnson et al., (41) 11 6 5 20 (2) 5 (3) days - - 10 22 (2) 3-lead ECG (DA100C, Biopac Systems, Goleta, CA)
La Fountaine et al., (29) 3 2 1 19 (2) 48 h - - 3 19 (2) 3-lead ECG
La Fountaine et al., (42) 10 10 - 19 (1.06) 48 h - - 10 19.8 (1.0) 3-lead ECG
Liao et al., (39) 165 65 100 40.08 (11.08) less than 2 weeks - 14.75 82 30.71 (12.09) ECG HRV monitor (LR8Z11) (Yangyin Corp., Taiwan)
Purkayastha et al., (43) 21–31* 22 9 20 (1.5) Visit 1: 4 (1) 1 (1) - 31 20 (1.2) 3-lead ECG (Solar 8000i patient monitor, GE
Visit 2: 22 (4) Visit 3: 95 (11) days Healthcare, IL, USA)
Senthinathan et al., (23) 11 4 7 19.9 (0.8) less than 1 week 2.2 (0.3) - 11 20.3 (0.6) Polar HR Monitors
Sung et al., (44) 331 131 200 40 (24) less than 2 weeks - 14.85 152 27.5 (14) ECG HRV monitor (LR8Z11) (Yangyin Corp., Taiwan)
(0.18)
Sung et al., (45) 181 72 109 38.47 (9.27) less than 2 weeks - - 83 30.52 (10.44) ECG HRV monitor (LR8Z11) (Yangyin Corp., Taiwan)
Mean (SD) * Study loss participants to follow up **some controls had have previous concussions ***Exercise protocol was started 5 days post-concussion while rest measures were taken in the first 48 h
BRAIN INJURY
5
 6

Table 2. Short-Term HRV during exercise in individuals with concussion.

Authors RR (ms) SDRR (ms) LF (ms2) LFnu HF (ms2) HFnu Total Power (ms2) LF/HF
Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI
J. CHARRON ET AL.

Time since mTBI

La Fountaine et al., (29) * - - - - - - - - - - - - - - 2.2 2.7
48 h (1.0) (1.7)
Gall et al., (27)** 504.1 466.3 12.8 10.8 35.1 17.4 88.3 91.0 3.9 1.9 11.7 9.0 86.8 60.4 8.6 10.6
5 ± 1.4 days (7.8) (7.4) (1.1) (1.1) (7.1) (2.9) (2.2) (0.7) (0.8) (0.3) (2.2) (0.7) (22.8) (10.7) (1.6) (0.8)
Gall et al., (27)** 512.1 466.1 13.3 10.6 24.5 14.4 86.7 89.3 3.2 1.9 13.3 10.7 90.2 58.6 8.5 8.7
10 ± 1.4 days (13.7) (13.6) (1.3) (1.0) (4.4) (5) (2.1) (0.8) (0.3) (0.6) (2.1) (0.8) (18.8) (12.6) (1.8) (1.4)
Abaji et al., (35)* - - - - - - - - 1293.8 399.4 - - - - 1.68 5.48
95 ± 63 days (1029.2) (197) (1.33) (4.78)
Mean (SD)
Bold: significant at p˂0.05
*Data taken during a 3 min isometric hand grip test (IHGT) **Data taken during 10 min of cycling at constant load on an ergometer

Table 3. Short-term heart rate variability at rest in supine position.

Authors RR (ms) SDRR (ms) CVRR (%) RMSSD (ms) LF (ms2) LFnu HF (ms2) HFnu Total Power (ms2) LF/HF

Time since mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI Controls mTBI

Johnson et al., (41) 1022 1009 - - - - 108 101 - - - - 2294 2459 - - - - - -

5 ± 3 days (197) (168) (99) (83) (2314) (2058)
Hilz et al., (32) 1024.3 874.2 53.3 36.7 5.1 4.1 30.1 56.3 1141.9 804.9 50.3 69.1 1507.2 298.1 49.7 30.9 - - 1.2 3.0
20 ± 11 months (165.4) (157.8) (26.4) (23.7) (2.4) (2.5) (23.6) (31.4) (1070) (928.1) (16.2) (14.8) (1591.4) (309.8) (16.2) (14.8) (0.7) (1.9)
Hilz et al., (38) 1041 943.1 59.4 50.9 5.7 5.7 63.9 47.1 2650.3 1881.2 49.6 61.2 1837.4 1117.7 50.4 38.8 - - 1.4 2.7
25.2 ± 20.5 months (166.7) (123.5) (36.5) (27) (3.3) (3.3) (40.3) (27.7) (4336) (1983) (14.3) (15.9) (1935.3) (1232.6) (14.3) (15.9) (0.7) (2.6)
Hilz et al., (36) 888.3 857.7 - - - - - - 1001.5 782.8 51 48.7 1609.3 1171.5 48.1 51.3 - - 1.5 1.4
32 ± 24 months (149.8) (127.5) (1213.6) (950.1) (24.4) (24.4) (2287) (1559.7) (24.4) (24.4) (1.3) (1.7)
Hilz et al., (32) 908.4 868.7 59 38.6 6.6 4.5 48.4 31.2 2417.7 953.5 - - 1188.7 567.4 - - 3606.4 1520.9 3.0 3.6
34 ± 29 months (132.9) (138) (29.3) (18.6) (3.3) (2.1) (27.8) (18.3) (2441.6) (867.8) (1374.6) (581.9) (3544.7) (1300.25) (2.1) (3.1)
Mean (SD)
Bold: significant at p˂0.05
 Table 4. Short-term HRV at rest in standing position in controls.
Authors
RR SDRR CVRR RMSSD LF HF Total Power
Time since mTBI (ms) (ms) (%) (ms) (ms2) LFnu (ms2) HFnu (ms2) LF/HF 30:15 Ratio SampEn
Senthinathan et al., (23) 814.6 82.1 - - 2526 79 686.1 20.9 6415 5.2 - 1.1
4.7 ± 2.1 days (46) (6.9) (404.3) (3.6) (163) (3.6) (1848.5) (0.9) (0.1)
Senthinathan et al., (23) 816 81.6 - - 2519.9 77.9 603.7 21.8 6724.5 5.8 - 1.2
18.1 ± 7.9 days (24) (5.3) (601.8) (4.3) (127.3) (4.3) (1051.4) (1.3) (0.1)
Senthinathan et al., (23) 775.3 73.2 - - 1430.3 73.4 559 26.6 4161.9 7.1 - 1.1
25.5 ± 8.2 days (29.7) (6.3) (251.1) (5.7) (159.7) (5.6) (900.3) (2.5) (0.1)
Hilz et al., (32) 786.1 83.6 10.9 33.2 4805.9 91.5 392.2 8.5 - 23.4 1.6 -
20 ± 11 months (121.4) (32.8) (3.4) (15) (3453.5) (7.2) (371.8) (7.2) (18.3) (0.3)
Hilz et al., (38) 801 49.1 6.1 24.8 1319.8 80.8 292.8 19.2 - 8.2 1.5 -
25.2 ± 20.5 months (131.5) (25.4) (2.8) (13.5) (1292.7) (12.5) (314.1) (12.5) (9.5) (0.3)
Mean (SD)
Bold: significant at p˂0.05

Table 5. Short-term HRV at rest in standing position in individuals with concussion.

Authors
RR SDRR CVRR RMSSD LF HF Total Power 30:15
Time since mTBI (ms) (ms) (%) (ms) (ms2) LFnu (ms2) HFnu (ms2) LF/HF Ratio SampEn
Senthinathan et al., (23) 748.7 81.6 - - 3509 85.2 760.8 14.8 7350.9 7.2 - 0.9
4.7 ± 2.1 days (41.5) (13.1) (1260.1) (2.4) (318.1) (2.4) (1848.5) (1.0) (0.1)
Senthinathan et al., (23) 734.2 64.7 - - 1411.6 80.1 237.8 19.8 3793.7 5.9 - 0.9
18.1 ± 7.9 days (29.7) (7.4) (397.1) (3.5) (152.1) (3.5) (1051.4) (1.2) (1.1)
Senthinathan et a.,(23) 751.8 75.7 - - 1882.9 77.7 505.9 22.2 4725.7 5.5 - 1.0
25.5 ± 8.2 days (34.6) (10.4) (501.9) (4.4) (180.5) (4.4) (900.3) (1.3) (0.1)
Hilz et al., (32) 726 56.5 7.7 24 2450 90.4 228.1 9.6 - 31 1.3 -
20 ± 11 months (114) (33) (4) (19.3) (2110.3) (10.1) (291.8) (10.1) (37.5) (0.3)
Hilz et al., (38) 775.6 39.4 4.9 23.2 1123.6 79.2 313.3 20.8 - 7.1 1.4 -
25.2 ± 20.5 months (132.8) (23) (2.5) (16.8) (1247.6) (15.2) (466.8) (15.2) (6.3) (0.3)
Mean (SD)
Bold: significant at p˂0.05
BRAIN INJURY
7
 8

Table 6. Short-term HRV at rest in sitting position in controls.

Authors
J. CHARRON ET AL.

RR SDRR SDNN RMSSD LF LF LnLF HF HF LnHF LnVLF LnTP Total Power

Time since mTBI (ms) (ms) (ms) (ms) (ms2) (%) LFnu (ms2) (ms2) (%) HFnu (ms2) (ms2) (ms2) (ms2) LF/HF LnLF/HF SampEn
Gall et al., (27) 925.5 85.3 - - 1227.9 - 62.3 - 839.7 - 37.7 - - - 3531.6 2.1 - -
1.8 ± 0.2 days (28.6) (4.7) (222.6) (4.1) (167.3) (4.1) (459.2) (0.4)
La Fountaine, (41) - - - - - - - 3.63 - - - 3.36 - - - - - -
48 h (0.48) (0.5)
La Fountaine, (29) - - - - - - - - - - - - - - - 2.3 - -
48 h (1.8)
Purkayastha et al., (42) - - - 73 2051 - - - 2356 - - - - - 6757 - - -
4 ± 1 days (31) (1555) (2700) (5766)
Huang et al., (40) 963 - - 70.5 1807 30 - - 2274 - - - - - 5681 0.89 - -
4 ± 1 days (112) (30.5) (1726) (14) (2038) (3600) (0.45)
Senthinathan et al., (23) 910.5 78 - - 1604.9 - 56.7 - 1242.6 - 47.5 - - - 4938.5 1.8 - 1.5
4.7 ± 2.1 days (52.8) (7.8) (428.9) (5.3) (314.9) (5.7) (995.8) (0.4) (0.1)
Gall et al., (27) 951.6 79.9 - - 1100.8 - 65.7 - 809.4 - 34.3 - - - 3322.6 2.7 - -
6.8 ± 0.2 days (42.2) (8.1) (150.2) (4.2) (192.8) (4.2) (630.7) (0.6)
La Fountaine, (42) - - - - - - - 3.61 - - - 3.5 - - - - - -
9 days (0.28) (0.42)
Sung et al., (44)* - - 47.5 - - 63.24 - 6.46 - 25.43 - 5.66 7.01 7.76 - - 0.9 -
less than 2 weeks (27) (24.55) (1.23) (15.67) (1.37) (1.13) (1.09) (0.96)
Sung et al., (45) - - 48.5 - - 63.84 - 6.57 - 21.43 - 5.48 7.37 7.9 - - 1.09 -
less than 2 weeks (26) (20.59) (1.85) (11.67) (1.22) (1.92) (1.13) (0.95)
Liao et al., (39)* - - 52.5 - - 60.24 - 6.86 - 28.43 - 5.78 7.71 7.95 - - 0.93 -
less than 2 weeks (27.5) (21.57) (1.94) (11.67) (1.02) (1.23) (1.29) (0.99)
La Fountaine, (29) - - - - - - - - - - - - - - - 1.6 - -
2 weeks (1.1)
Senthinathan et al., (23) 889 88.3 - - 2321.5 - 55.6 - 1480.6 - 44.2 - - - 8039 1.7 - 1.6
18.1 ± 7.9 days (20) (6.6) (624) (5.3) (446.4) (5.2) (1383.2) (0.4) (0.1)
Purkayastha et al., (42) - - - 73 2051 - - - 2356 - - - - - 6757 - - -
22 ± 4 days (31) (1555) (2700) (5766)
Senthinathan et al., (23) 872 81.4 - 1925.8 - 57.8 - 1514.9 - 42.1 - - - 6868.1 2.3 - 1.3
25.5 ± 8.2 days (28.3) (8.1) (486.8) (5) (539.8) (5) (1685.2) (0.7) (0.1)
Sung et al., (44) - - 47.5 - - 63.24 - 6.46 - 25.43 - 5.66 7.01 7.76 - - 0.9 -
6 weeks (27) (24.55) (1.23) (15.67) (1.37) (1.13) (1.09) (0.96)
Purkayastha et al., (43) - - - 73 2051 - - - 2356 - - - - - 6757 - - -
95 ± 11 days (31) (1555) (2700) (5766)
Abaji et al., (35) - - - - - - - - 1293 - - - - - - 1.68 - -
95 ± 63 days (1029.2) (1.33)
Mean (SD)
Bold: significant at p˂0.05
*Both articles were written by same authors and were presumed as seated measures because their third article did mention data collection position and the described methodology was almost identical
Table 7. Short-term HRV at rest in sitting position in individuals with concussion.
Authors
RR SDRR SDNN RMSSD LF LF LnLF HF HF LnHF LnVLF LnTP Total Power
Time since mTBI (ms) (ms) (ms) (ms) (ms2) (%) LFnu (ms2) (ms2) (%) HFnu (ms2) (ms2) (ms2) (ms2) LF/HF LnLF/HF SampEn
Gall et al.,(27) 954 79.8 - - 1334,2 - 67.1 - 829.3 - 29.3 - - - 3238.2 2.6 - -
1.8 ± 0.2 days (30.4) (6.2) (267) (4.8) (198.8) (3.4) (444.3) (0.4)
La Fountaine,(42) - - - - - - - 3.59 - - - 3.26 - - - - - -
48 h (0.4) (0.58)
La Fountaine,(29) - - - - - - - - - - - - - - - 3.3 - -
48 h (2.9)
Purkayastha et al.,(42) - - - 53 2330 - - - 1367 - - - - - 5289 - - -
4 ± 1 days (29) (2663) (1556) (4457)
Huang et al.,(40) 897 - - 52.5 1775 42 - - 1086 - - - - - 4377 2.4 - -
4 ± 1 days (125) (30.3) (1121) (13) (1085) (2975) (1.8)
Senthinathan et al., (23) 829.5 73.8 - - 1965 - 67.1 - 1096.5 - 32.9 - - - 8146.8 2.5 - 1.3
4.7 ± 2.1 days (37.7) (14.1) (790) (3.6) (461.31) (3.6) (4772.2) (0.4) (0.1)
Gall et al.,(27) 949.3 83.7 - - 1191.4 - 70.4 - 901.8 - 28.7 - - - 3501.7 2.5 - -
6.8 ± 0.2 days (23.2) (9.1) (227.6) (2.8) (303.8) (2.9) (798.2) (0.3)
La Fountaine,(42) - - - - - - - 3.43 - - - 3.10 - - - - - -
9 days (0.35) (0.59)
Sung et al.,(44)* - - 38 - - 63.01 - 5.97 - 27.88 - 5.37 6.59 7.32 - - 0.81 -
less than 2 weeks (25.5) (23.84) (1.41) (17.79) (1.84) (1.17) (1.2) (1.04)
Sung et al.,(45) - - 38.5 - - 63.03 - 6.17 - 27.09 - 5.33 6.54 7.28 - - 0.84 -
less than 2 weeks (22.5) (21.68) (1.48) (10.21) (1.26) (1.14) (1.45) (1.15)
Liao et al.,(39)* - - 38 - - 61.07 - 6.01 - 27.54 - 5.41 6.52 7.31 - - 0.74 -
less than 2 weeks (21.5) (21.5) (1.84) (17.61) (1.04) (1.75) (1.18) (1.02)
La Fountaine,(29) - - - - - - - - - - - - - - - 2.3 - -
2 weeks (0.8)
Senthinathan et al.,(23) 842.5 66 - - 1443.7 - 62.6 - 844.3 - 37.6 - - - 4195.8 2.4 - 1.4
18.1 ± 7.9 days (31.2) (7.8) (379.4) (5.1) (216.9) (5.1) (1193.6) (0.4) (0.1)
Purkayastha et al.,(42) - - - 63 2007 - - - 1915 - - - - - 5515 - - -
22 ± 4 days (42) (2320) (2383) (4350)
Senthinathan et al.,(23) 876.4 78.4 - - 1971.7 - 53.2 - 1493.5 - 46.7 - - - 5563.9 1.8 - 1.4
25.5 ± 8.2 days (36.6) (7.7) (578.1) (5) (362.8) (5) (1132.4) (0.4) (0.1)
Sung et al.,(44) - - 37 - - 62.67 - 5.93 - 26.92 - 5.2 6.61 7.27 - - 0.83 -
6 weeks (29) (24.64) (1.46) (19.79) (2.05) (1.27) (1.3) (1.05)
Purkayastha et al.,(43) - - - 80 2023 - - - 2912 - - - - - 7580 - - -
95 ± 11 days (45) (1614) (3606) (7079)
Abaji et al.,(35) - - - - - - - - 1225.6 - - - - - - 1.93 - -
95 ± 63 days (777.5) (1.66)
Mean (SD)
Bold: significant at p˂0.05
*Both articles were written by same authors and were presumed as seated measures because their third article did mention data collection position and the described methodology was almost identical
BRAIN INJURY
9
10 J. CHARRON ET AL.
SampEn was significantly lower for Senthinathan et al. for the
first two measurements, but higher for the last one (23).
Overall, unpaired t-tests were performed on 203 measure­
ments, yielding a total of 100 significant differences between
those with concussion and controls (49.26%) and 103 non-
significant differences (50.74%).
Discussion
Participant characteristics
Results from Table 1 present several problems because of the
wide variation in timeline and age, but also the fact that most
studies used mixed groups. Men and women grouping is
a problem because there are some differences in HRV readings:
men have higher LF power (17,47,48), higher HF power
(17,48), higher LF/HF ratio (17,47,48), higher NN intervals
(48) than women. On the other hand, women present time-
domain HRV that is lower by 8–11% when compared to men
(17), their SDNN is also lower when in supine position (49)
and their menstrual cycle might affect results (20). Before the
age of 30, women also exhibit lower RMSSD, SDNN, and
pNN50, a difference that persists up to 50 years old (50).
These differences potentially affect results by causing larger
standard deviations.
Furthermore, the age of participants will also affect results. In
fact, there is a decrease in SDNN (48,50,51), CVNN (48),
RMSSD (47,48,50), LF (47,48,52), LnLF (51), HF (47,48,52),
LnHF (51), Total Power (47,52), LnTP (51), VLF (47), HFnu
(52,53), and pNN50 (50) with aging and an increase in LFnu (53)
and LF/HF (47,48,52,53). There is a demonstrated negative
correlation between age and HRV (17). Some studies had wide
age range of participants (18–50 years old), which makes it hard
to compare because biological aging can affect HRV regardless of
concussion (there are so many measures that might have been
affected by the aging process and not necessarily by the concus­
sion). Finally, a recent meta-analysis from 2016 by Koenig and
Thayer, which included over 63 000 participants, showed
a significant effect of age on HRV results (54).
In addition, included studies herein have measured HRV at
variable times, some took measurements in an early concussion
phase and some went as far as 34 ± 29 months post-concussion,
which is either in a post-concussion syndrome phase or con­
sidered as being healed. The fact that certain participants were
healed was a concern at first because we thought healed patient
would perhaps not present any HRV differences. However,
studies by Senthinathan et al. (23) and Abaji et al. (35) showed
that despite participants being asymptomatic, the autonomic
nervous system (ANS) disturbances persisted weeks-months
post-injury during change of physical state (sitting to standing
or IHGT). These results suggest that symptom identification
alone may not be the best determinant for recovery. On the
other hand, it should be mentioned that these HRV distur­
bances persisted in a physical effort state, but were not seen at
rest (35). This could explain why there were little statistically
different measures in Hilz et al.’s studies, which were all done
in a rested state (32,36–38). It could also mean that
a concussion has a long-lasting effect that limits the ability to
properly respond to physiological stressors. At first, we
expected that the number of previous concussions might affect
the results because repeated concussions cause increased risk of
long-term persistence of symptoms (55), but included studies
showed there was no need for symptoms to be present to
observe ANS disturbances (23,32,35). It also showed there are
heightened and prolonged ANS disturbances with increased
number of previous concussions (23).
At last, several other external factors can affect results, such
as: nicotine intake, caffeine, cardioactive medication, time
of day, level of alcohol use, fitness level (active people show
higher HRV than sedentary ones and athletes show even
greater HRV than active people in all time-domain measures,
LF power and LF/HF), age, and digestion (18,53,56,57). Table 1
shows how the current literature is difficult to interpret and
compare because of several confounding factors affecting HRV
measures, which are very sensitive to internal and external
stressors. This table also highlights how important it is to
standardize data collection methods to present accurate
analysis.
HRV during exercise
Table 2 shows unequivocally that HRV is impaired during
constant cycling on a stationary bike as every variable was
significantly different from the control group except the LF/
HF ratio at 10 ± 1.4 days, suggesting that the autonomic
balance might be restored during exercise at that time post-
injury (27). During the IHGT, LaFountaine et al. did not obtain
statistical significance, but this might be explained by the
limited number of participants (n = 3) (29) that makes finding
statistical significance difficult. On the other hand, Abaji et al.
found statistical differences in HF power and LF/HF ratio in
post-concussive male hockey players (35). Both these studies
used the IGHT as a form of passive physical activity, since it
recreates a similar hemodynamic stress as seen during active
exercise (58) without causing changes in ventilation rate,
a factor that affects HRV (59,60).
Moreover, Abaji et al. measured several other HRV markers
but did not present them in numeric form and made it impos­
sible to include them in the results of this review. Their results
section also presented several comparisons between rest and
exercise on the same group (35). Results gathered for this
review are as expected in an exercise situation, which is
a decreased HRV probably due to a withdrawal in parasympa­
thetic activity (61,62). This can be concluded by the elevated
LF/HF ratio that is usually interpreted as an indication of
sympathovagal balance (35,63) an increase that has been pre­
viously reported following a concussion (39). In this balance,
LF represents the sympathetic branch of ANS (SNS) and HF
the parasympathetic branch (PSNS), more specifically, HF is
directly linked to the respiratory sinus arrhythmia (RSA) (13).
The LF relationship to the sympathetic tone is controversial; it
was suggested that it would more appropriately reflect barore­
flex modulation instead of cardiac sympathetic tone (13).
There was also an article by Billman that suggested PSNS
affected 50% of LF signal resulting in SNS taking only 25% of
LF (64). This means that perhaps we should not consider LF/
HF as a valid indicator of sympathovagal balance as the para­
sympathetic branch affects the LF measures at a larger degree

than the sympathetic one, which is supposed to be the main
one. Despite this controversy, LF/HF is still widely used in
HRV literature. However, it was suggested that SD1/SD2
could also reflect sympathovagal balance as Poincaré width
(SD2) and Poincaré length (SD1) reflects parasympathetic acti­
vation and sympathetic antagonism to vagal tone, respec­
tively (65).
Thus, results from Table 2 are easier to compare as two of
them used the same protocol and all three of them conducted
their study on athletes. This factor is important because the
level of physical activity also affects HRV. As a matter of fact,
SDNN, RMSSD, and NN are higher in male athletes when
compared to active males (57) and as for women athletes:
SDNN, NN, RMSSD, TP, VLF, LF, HF are all higher and LF/
HF lower (57). Findings also showed that RMSSD is higher in
active people when compared to sedentary ones (53). Further
research on exercise, HRV, and concussion should observe
HRV while training at several intensities as this also affects
HRV- with greater exercise intensity, a lower HRV is
observed- (66).
HRV in supine position
Table 3 presents results taken in a supine position. Most studies
in this table can be easily compared to one another because 4
out of 5 studies were conducted by Hilz et al. and used the
protocol each time (32,36–38). These studies were all con­
ducted several months post-injury, which makes
a comparison with the fifth study (Johnson et al.) (41) difficult
because it was conducted in an early phase of concussion
(5 ± 3 days) and with a different methodology. Hilz et al.
conducted their tests between 9:00 AM and 2:00 PM on
a reclining armchair, in a quiet room at 24°C and stable
humidity (32,36–38) while Johnson et al. measured during
10 minutes of supine rest in a quiet rested state with partici­
pants abstaining from alcohol, caffeine, and exercise for 12 h,
and food for 2 h (41). Both protocols controlled several con­
founding factors which is good, but unfortunately, they did not
control the same ones, making a comparison between them
difficult. Also, the article by Hilz et al. conducted in 2015 added
one element, which is controlled breathing (36). This has an
effect on HRV outcomes, because all HRV measures increase
(except LF) under paced breathing (17). It was previously
shown that not only breathing frequency, but also respiratory
depth (tidal volume) can influence HRV (18).
It was also criticized that insufficient attention was brought
to the environment during HRV measuring by Heather in 2014
(63). The studies presented in Table 3, however, do give suffi­
cient attention to this element. Furthermore, this table allows
to see that HRV in supine position does not appear to be
affected in the early phase of concussion, but this statement
cannot be generalized because there is only one study with
a limited sample of participants (n = 11) (41).
HRV in standing position
Tables 4 and 5 present results taken in a standing position.
Results from both of Hilz et al.’s studies’ can easily be com­
pared between each other as previously mentioned because of
BRAIN INJURY 11
the identical protocol (32,38).The other results can be com­
pared between each other because they were all taken by the
same authors in the same study as repeated measures (23) but
studies by Hilz et al. and Senthinathan et al. cannot be com­
pared together because the latter gave very little details about
aspects they did or did not control during data acquisition (23).
RR intervals appear to be affected for the first 3 weeks post-
injury, but these differences disappear when going further. LF
power expressed in absolute unit is clearly affected in
a standing position, but results are somehow peculiar because
at 18.1 ± 7.9 days and 20 ± 11 months, a higher LF power for
the control group rather than in the group with concussion can
be seen and the opposite is seen at 4.7 ± 2.1 days and
25.5 ± 8.2 days (23,32).
Hilz et al. also presented a peculiar results for LF/HF ratio
with a ratio over 20, which is the only study we encountered
presenting such a high LF/HF ratio (32). When roughly calculat­
ing the ratio (LF:2450 ms2, HF: 228.1 ms2) we reached a ratio of
10.74 not 31 like Hilz et al. presented. Perhaps the authors made
a methodological mistake in their calculations. We hypothesized
that the results might have been 2.34 ± 1.83 instead of 23.4 ± 18.3
and 3.1 ± 3.75 instead of 31 ± 3.75. These results would make
more sense and are close to what is seen in other studies. The
study by Hilz et al. in 2011 shows a lower 30:15 ratio for the
group with concussion, which indicates that baroreflexes are
compromised because of inadequate sympathetic and parasym­
pathetic responses to orthostatic stress (change of stature by
passing from sitting to standing) (32).
HRV in seated position
Tables 6 and 7 present results taken in a seated position.
Results from this section are difficult to compare because the
angle at which the back is placed during the HRV acquisition
will affect the results. As a matter of fact, there will be
a regulatory challenge caused by the radiational shift in the
body’s blood mass (46). Therefore, if the angle is different, the
gravitational challenge might be as well. No study mentioned at
what angle the back was placed and whether this factor was
well controlled for repeated measures. Some studies acquired
resting HRV on a stationary bike (27) and some other in an
upright chair (35,40,43). Results from Sung et al. and Liao et al.
can be easily compared because they used the same protocols,
which was 5 min of resting HRV measured twice in the morn­
ing with 100 min interval between both measures. Although,
there were few details given on confounding factors (43,44).
Thus, it can be concluded that SDNN, LnVLF and LnTP are
diminished in the fist 2 weeks post-injury. SampEn is usually
lower in individuals with concussion, meaning that the time-
domain signals are more regular in those than in controls (67),
as reported in Senthinathan et al.’s study (23).
Also, spectral domain results expressed in n.u. seem like
a promising way of obtaining a clearer view of HRV because
every study that presented such measures found significant
differences but did not when expressed in absolute units
(except one measurement by Senthinathan et al.) (23,27).
Thus, the tables herein include a lot of studies making compar­
ison difficult as there are so many different protocols and
testing conditions (controlled temperature (35,40,43), control
12 J. CHARRON ET AL.
of time of day (35,41,44,45) and periods allowed for blood
volume shift stabilization (40,42,43).
Conclusion
Several interesting papers have shed more light on the subject
roughly six years after the first systematic search on cardiac
autonomic impairment following a concussion. However, even
though our inclusion criteria slightly differ from those of the
previous review by Blake et al. (8), we reach somehow the same
conclusion. This conclusion being that the evidence that proves
impairment of HRV following a concussion is limited at rest
and in exercise setting.
Also, further research must take some time to address con­
founding factors affecting HRV in their methods and analysis,
as there are several that will highly impact the conclusions that
can be drawn from the data.
Therefore, it appears difficult to reach a robust consensus
based on the current literature’s situation since there are so
many confounding factors that can affect HRV (age, level of
physical activity, data acquisition conditions, and gender) and
they were, for the most part, not considered in study designs.
Furthermore, only roughly 50% of the results were significantly
different, suggesting that autonomic dysfunction in individuals
with concussion cannot be affirmed with certainty.
Further research should try to standardize HRV acquisition
protocols for rigorous control of confounding factors that will
permit a better comparison between studies and allow the
possibility for eventual robust meta-analysis. Future studies
should also observe HRV behavior at different exercise inten­
sities in individuals with concussion and perhaps use linear
regression to understand how ventilation rate affects HRV
results during a physical effort.
List of abbreviations
MTBI: Mild Traumatic Brain Injury
HRV: Heart Rate Variability
LF: Low Frequency Power
HF: High Frequency Power
RMSSD: Root Mean Square of Successive Differences
CVRR: Coefficient of Variation of the RR Intervals
SDRR: Standard Deviation of the RR Intervals
SampEn: Sample Entropy
IHGT: Isometric Hand Grip Test
Aknowledgement
Authors would like to thank all researchers referenced in this study, as well
as all scientific investigations that were read, but unfortunately not
included.
Declaration of interest
This research did not receive any specific grant from funding agencies in
the public, commercial, or not-for-profit sectors. The authors certify that
there is no conflict of interest with any financial organization regarding
the material discussed in the manuscript.
ORCID
J. Charron http://orcid.org/0000-0002-7280-5823
References
1. Giza CC, Hovda DA.The new neurometabolic cascade of
concussion. Neurosurgery. 2014;75(Suppl 4):S24–33. doi:10.1227/
NEU.0000000000000505.
2. Leddy J, Haider M, Ellis M, Willer B. Exercise is medicine for
concussion. Curr Sports Med Rep. 2018;17:262–70. doi:10.1249/
JSR.0000000000000505.
3. McCrory P, Feddermann-Demont N, Dvorak J, Cassidy JD,
McIntosh A, Vos PE, Echemendia RJ, Meeuwisse W,
Tarnutzer AA. What is the definition of sports-related concussion:
a systematic review. Br J Sports Med. 2017;51:877–87. doi:10.1136/
bjsports-2016-097393.
4. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and
impact of traumatic brain injury: a brief overview. J Head Trauma
Rehabil. 2006;21:375–78. doi:10.1097/00001199-200609000-00001.
5. McCrea M, Kelly JP, Randolph C, Cisler R, Berger L. Immediate
neurocognitive effects of concussion. Neurosurgery. discussion
1040-1032. 2002;50:1032–40. doi:10.1097/00006123-200205000-
00017.
6. Mullally WJ. Concussion. Am J Med. 2017;130:885–92.
doi:10.1016/j.amjmed.2017.04.016.
7. Kim H-G, Cheon E-J, Bai D-S, Lee YH, Koo B-H. Stress and heart
rate variability: a meta-analysis and review of the literature.
Psychiatry Investig. 2018;15:235–45. doi:10.30773/pi.2017.08.17.
8. Blake TA, McKay CD, Meeuwisse WH, Emery CA. The impact of
concussion on cardiac autonomic function: a systematic review.
Brain Inj. 2016;30:132–45. doi:10.3109/02699052.2015.1093659.
9. TFESCNASPE. Heart rate variability: standards of measurement,
physiological interpretation and clinical use. Task force of the
European society of cardiology and the North American society
of pacing and electrophysiology. Circulation. 1996;93:1043–65.
doi:10.1161/01.CIR.93.5.1043.
10. Shaffer F, McCraty R, Zerr CL. A healthy heart is not a metronome:
an integrative review of the heart’s anatomy and heart rate varia­
bility. Front Psychol. 2014;5:1040. doi:10.3389/fpsyg.2014.01040.
11. Prinsloo GE, Rauch HG, Derman WE. A brief review and clinical
application of heart rate variability biofeedback in sports, exercise,
and rehabilitation medicine. Phys Sportsmed. 2014;42:88–99.
doi:10.3810/psm.2014.05.2061.
12. Berntson GG, Bigger JT Jr., Eckberg DL, Grossman P,
Kaufmann PG, Malik M, Nagaraja HN, Porges SW, Saul JP,
Stone PH, et al. Heart rate variability: origins, methods, and
interpretive caveats. Psychophysiology. 1997;34:623–48.
13. Rahman F, Pechnik S, Gross D, Sewell L, Goldstein DS. Low
frequency power of heart rate variability reflects baroreflex func­
tion, not cardiac sympathetic innervation. Clin Auton Res.
2011;21:133–41. doi:10.1007/s10286-010-0098-y.
14. Sztajzel J. Heart rate variability: a noninvasive electrocardiographic
method to measure the autonomic nervous system. Swiss Med
Wkly. 2004;134:514–22. 2004/35/smw-10321.
15. La Rovere MT, Bigger JT Jr., Marcus FI, Mortara A, Schwartz PJ.
Baroreflex sensitivity and heart-rate variability in prediction of total
cardiac mortality after myocardial infarction. ATRAMI (Autonomic
Tone and Reflexes After Myocardial Infarction) Investigators. Lancet.
1998;351:478–84. doi:10.1016/S0140-6736(97)11144-8.
16. Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M,
Malliani A. Power spectrum analysis of heart rate variability to
assess the changes in sympathovagal balance during graded ortho­
static tilt. Circulation. 1994;90:1826–31. doi:10.1161/01.
CIR.90.4.1826.
17. Nunan D, Sandercock GR, Brodie DA. A quantitative systematic
review of normal values for short-term heart rate variability in
healthy adults. Pacing Clin Electrophysiol. 2010;33:1407–17.
doi:10.1111/j.1540-8159.2010.02841.x.

18. Quintana DS, Heathers JA. Considerations in the assessment of
heart rate variability in biobehavioral research. Front Psychol.
2014;5:805.
19. Sandrone G, Mortara A, Torzillo D, La Rovere MT,
Malliani A, Lombardi F. Effects of beta blockers (atenolol or
metoprolol) on heart rate variability after acute myocardial
infarction. Am J Cardiol. 1994;74:340–45. doi:10.1016/0002-
9149(94)90400-6.
20. Sato N, Miyake S. Cardiovascular reactivity to mental stress: rela­
tionship with menstrual cycle and gender. J Physiol Anthropol
Appl Human Sci. 2004;23:215–23. doi:10.2114/jpa.23.215.
21. Seong HM, Lee JS, Shin TM, Kim WS, Yoon YR, Yoon YR. The
analysis of mental stress using time-frequency distribution of heart
rate variability signal. Conf Proc IEEE Eng Med Biol Soc.
2004;2006:283–85. doi:10.1109/IEMBS.2004.1403147.
22. Paniccia M, Verweel L, Thomas S, Taha T, Keightley M, Wilson KE,
Reed N. Heart rate variability in healthy non-concussed youth
athletes: exploring the effect of age, sex, and concussion-like
symptoms. Front Neurol. 2017;8:753. doi:10.3389/fneur.2017.00753.
23. Senthinathan A, Mainwaring LM, Hutchison M. Heart rate varia­
bility of athletes across concussion recovery milestones:
a preliminary study. Clin J Sport Med. 2017;27:288–95.
doi:10.1097/JSM.0000000000000337.
24. Biswas AK, Scott WA, Sommerauer JF, Luckett PM. Heart rate
variability after acute traumatic brain injury in children. Crit Care
Med. 2000;28:3907–12. doi:10.1097/00003246-200012000-00030.
25. Goldstein B, Toweill D, Lai S, Sonnenthal K, Kimberly B.
Uncoupling of the autonomic and cardiovascular systems in
acute brain injury. Am J Physiol. 1998;275:R1287–1292.
doi:10.1152/ajpregu.1998.275.4.R1287.
26. Katz-Leurer M, Rotem H, Keren O, Meyer S. Heart rate and heart
rate variability at rest and during exercise in boys who suffered
a severe traumatic brain injury and typically-developed controls.
Brain Inj. 2010;24:110–14. doi:10.3109/02699050903508234.
27. Gall B, Parkhouse W, Goodman D.Heart rate variability of recently
concussed athletes at rest and exercise. Med Sci Sports Exerc.
2004;36(8):1269–74.doi:10.1249/01.MSS.0000135787.73757.4D.
28. Tan G, Fink B, Dao TK, Hebert R, Farmer LS, Sanders A, Pastorek N,
Gevirtz R. Associations among pain, PTSD, mTBI, and heart rate
variability in veterans of Operation Enduring and Iraqi Freedom:
a pilot study. Pain Med. 2009;10:1237–45. doi:10.1111/j.1526-
4637.2009.00712.x.
29. La Fountaine MF, Heffernan KS, Gossett JD, Bauman WA, De
Meersman RE. Transient suppression of heart rate complexity in
concussed athletes. Auton Neurosci. 2009;148:101–03. doi:10.1016/j.
autneu.2009.03.001.
30. Gall B, Parkhouse WS, Goodman D. Exercise following a sport
induced concussion. Br J Sports Med. 2004;38:773–77. doi:10.1136/
bjsm.2003.009530.
31. Hanna-Pladdy B, Berry ZM, Bennett T, Phillips HL, Gouvier WD.
Stress as a diagnostic challenge for postconcussive symptoms: sequelae
of mild traumatic brain injury or physiological stress response. Clin
Neuropsychol. 2001;15:289–304. doi:10.1076/clin.15.3.289.10272.
32. Hilz MJ, DeFina PA, Anders S, Koehn J, Lang CJ, Pauli E,
Flanagan SR, Schwab S, Marthol H. Frequency analysis unveils
cardiac autonomic dysfunction after mild traumatic brain injury.
J Neurotrauma. 2011;28:1727–38. doi:10.1089/neu.2010.1497.
33. McCrory P, Meeuwisse W, Dvorak J, Aubry M, Bailes J, Broglio S,
Cantu RC, Cassidy D, Echemendia RJ, Castellani RJ, et al. Consensus
statement on concussion in sport-the 5(th) international conference
on concussion in sport held in Berlin, October 2016. Br J Sports Med.
2017;51:838–47. doi:10.1136/bjsports-2017-097699.
34. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC,
Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The
PRISMA statement for reporting systematic reviews and
meta-analyses of studies that evaluate health care interventions:
explanation and elaboration. Ann Intern Med. 2009;151:W65–94.
doi:10.7326/0003-4819-151-4-200908180-00136.
35. Abaji JP, Curnier D, Moore RD, Ellemberg D.Persisting effects of
concussion on heart rate variability during physical exertion.
J Neurotrauma. 2016;33(9):811–17.doi:10.1089/neu.2015.3989.
BRAIN INJURY 13
36. Hilz MJ, Aurnhammer F, Flanagan SR, Intravooth T, Wang R,
Hösl KM, Pauli E, Koehn J. Eyeball pressure stimulation unveils
subtle autonomic cardiovascular dysfunction in persons with
a history of mild traumatic brain injury. J Neurotrauma.
2015;32:1796–804. doi:10.1089/neu.2014.3842.
37. Hilz MJ, Liu M, Koehn J, Wang R, Ammon F, Flanagan SR,
Hösl KM. Valsalva maneuver unveils central baroreflex dysfunc­
tion with altered blood pressure control in persons with a history of
mild traumatic brain injury. BMC Neurol. 2016;16. doi:10.1186/
s12883-016-0584-5.
38. Hilz MJ, Wang R, Markus J, Ammon F, Hösl KM, Flanagan SR,
Winder K, Koehn J. Severity of traumatic brain injury correlates
with long-term cardiovascular autonomic dysfunction. J Neurol.
2017;264:1956–67. doi:10.1007/s00415-017-8581-1.
39. Liao KH, Sung CW, Chu SF, Chiu WT, Chiang YH, Hoffer B, Ou
JC, Chen KY, Tsai SH, Lin CM, et al. Reduced power spectra of
heart rate variability are correlated with anxiety in patients with
mild traumatic brain injury. Psychiatry Res. 2016;243:349–56.
doi:10.1016/j.psychres.2016.07.001.
40. Huang M, Frantz J, Moralez G, Sabo T, Davis PF, Davis SL,
Bell KR, Purkayastha S. Reduced resting and increased elevation
of heart rate variability with cognitive task performance in con­
cussed athletes. J Head Trauma Rehabil. 2019;34:45–51.
doi:10.1097/HTR.0000000000000409.
41. Johnson BD, O’Leary MC, McBryde M, Sackett JR, Schlader ZJ,
Leddy JJ. Face cooling exposes cardiac parasympathetic and sym­
pathetic dysfunction in recently concussed college athletes. Physiol
Rep. 2018;6:e13694. doi:10.14814/phy2.13694.
42. La Fountaine MF, Hohn AN, Testa AJ, Weir JP. Attenuation of
spontaneous baroreceptor sensitivity after concussion. Med Sci
Sports Exerc. 2019;51:792–97. doi:10.1249/MSS.0000000000001833.
43. Purkayastha S, Williams B, Murphy M, Lyng S, Sabo T, Bell KR.
Reduced heart rate variability and lower cerebral blood flow associated
with poor cognition during recovery following concussion. Auton
Neurosci. 2019;220:102548. doi:10.1016/j.autneu.2019.04.004.
44. Sung CW, Chen KY, Chiang YH, Chiu WT, Ou JC, Lee HC,
Tsai SH, Lin JW, Yang CM, Tsai YR, et al. Heart rate variability
and serum level of insulin-like growth factor-1 are correlated with
symptoms of emotional disorders in patients suffering a mild trau­
matic brain injury. Clin Neurophysiol. 2016;127:1629–38.
doi:10.1016/j.clinph.2015.08.006.
45. Sung CW, Lee HC, Chiang YH, Chiu WT, Chu SF, Ou JC, Tsai SH,
Liao KH, Lin CM, Lin JW, et al. Early dysautonomia detected by
heart rate variability predicts late depression in female patients
following mild traumatic brain injury. Psychophysiology.
2016;53:455–64. doi:10.1111/psyp.12575.
46. Walawalkar S. A study of variation in heart rate variability with
changes in posture in young adult indian males. J Med Sci Clin Res.
2014;2:503–14.
47. Agelink MW, Malessa R, Baumann B, Majewski T, Akila F, Zeit T,
Ziegler D. Standardized tests of heart rate variability: normal
ranges obtained from 309 healthy humans, and effects of age,
gender, and heart rate. Clin Auton Res. 2001;11:99–108.
doi:10.1007/BF02322053.
48. Voss A, Schroeder R, Heitmann A, Peters A, Perz S,
Hernandez AV. Short-term heart rate variability–influence of gen­
der and age in healthy subjects. PLoS One. 2015;10:e0118308.
doi:10.1371/journal.pone.0118308.
49. Pikkujamsa SM, Makikallio TH, Airaksinen KE, Huikuri HV.
Determinants and interindividual variation of R-R interval dynamics
in healthy middle-aged subjects. Am J Physiol Heart Circ Physiol.
2001;280:H1400–1406. doi:10.1152/ajpheart.2001.280.3.H1400.
50. Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four
hour time domain heart rate variability and heart rate: relations
to age and gender over nine decades. J Am Coll Cardiol.
1998;31:593–601. doi:10.1016/S0735-1097(97)00554-8.
51. Yukishita T, Lee K, Kim S, Yumoto Y, Kobayashi A, Shirasawa T,
Kobayashi H. Age and sex-dependent alterations in heart rate varia­
bility: profiling the characteristics of men and women in their 30s.
Anti-Aging Medicine. 2010;7:94–99. doi:10.3793/jaam.7.94.
14 J. CHARRON ET AL.
52. Moodithaya SS, Avadhany ST. Comparison of cardiac autonomic
activity between pre and post menopausal women using heart rate
variability. Indian J Physiol Pharmacol. 2009;53:227–34.
53. Melo RC, Santos MD, Silva E, Quiterio RJ, Moreno MA, Reis MS,
Verzola IA, Oliveira L, Martins LE, Gallo-Junior L, et al. Effects of age
and physical activity on the autonomic control of heart rate in healthy
men. Braz J Med Biol Res. 2005;38:1331–38. doi:10.1590/S0100-
879X2005000900007.
54. Koenig J, Thayer JF. Sex differences in healthy human heart rate
variability: a meta-analysis. Neurosci Biobehav Rev.
2016;64:288–310. doi:10.1016/j.neubiorev.2016.03.007.
55. Guskiewicz KM, McCrea M, Marshall SW, Cantu RC, Randolph C,
Barr W, Onate JA, Kelly JP. Cumulative effects associated with recur­
rent concussion in collegiate football playersThe NCAA concussion
stud y. JAMA. 2003;290:2549–55. doi:10.1001/jama.290.19.2549.
56. Galetta F, Franzoni F, Femia FR, Roccella N, Pentimone F,
Santoro G.Lifelong physical training prevents the age-related
impairment of heart rate variability and exercise capacity in
elderly people. J Sports Med Phys Fitness. 2005;45(2):217–21.
57. Medina Corrales M, Torres B, Esquivel A, Antonio M, Salazar G,
Naranjo Orellan AJ. Normal values of heart rate variability at rest
in a young, healthy and active Mexican population. Health. 2012;4
58. Araujo CG, Duarte CV, Goncalves Fde A, Medeiros HB,
Lemos FA, Gouvea AL. Hemodynamic responses to an isometric
handgrip training protocol. Arq Bras Cardiol. 2011;97:413–19.
doi:10.1590/s0066-782x2011005000102.
59. Draghici AE, Taylor JA.The physiological basis and measurement
of heart rate variability in humans. J Physiol Anthropol. 2016;35
(1):22.doi:10.1186/s40101-016-0113-7.
60. Petrofsky J, Prowse M, Remigio W, Raju C, Salcedo S,
Sirichotiratana M, Madani P, Chamala RR, Puckett E, Wong M,
et al. The use of an isometric handgrip test to show autonomic
damage in people with diabetes. Diabetes Technol Ther.
2009;11:361–68. doi:10.1089/dia.2008.0094.
61. Breuer HW, Skyschally A, Schulz R, Martin C, Wehr M, Heusch G.
Heart rate variability and circulating catecholamine concentrations
during steady state exercise in healthy volunteers. Br Heart J.
1993;70:144–49. doi:10.1136/hrt.70.2.144.
62. Carter JB, Banister EW, Blaber AP.Effect of endurance exercise on
autonomic control of heart rate. Sports Med. 2003;33(1):33–46.
doi:10.2165/00007256-200333010-00003.
63. Heathers JA. Everything Hertz: methodological issues in
short-term frequency-domain HRV. Front Physiol. 2014;5:177.
doi:10.3389/fphys.2014.00177.
64. Billman GE. The LF/HF ratio does not accurately measure cardiac
sympatho-vagal balance. Front Physiol. 2013;4:26. doi:10.3389/
fphys.2013.00026.
65. Ardissino M, Nicolaou N, Vizcaychipi M. Non-invasive real-
time autonomic function characterization during surgery via
continuous Poincaré quantification of heart rate variability.
J Clin Monit Comput. 2019;33:627–35. doi:10.1007/s10877-
018-0206-4.
66. Michael S, Graham KS, Davis GMO. Cardiac autonomic responses
during exercise and post-exercise recovery using heart rate varia­
bility and systolic time intervals-a review. Front Physiol.
2017;8:301. doi:10.3389/fphys.2017.00301.
67. Richman JS, Moorman JR. Physiological time-series analysis using
approximate entropy and sample entropy. Am J Physiol Heart Circ
Physiol. 2000;278:H2039–2049. doi:10.1152/ajpheart.2000.278.6.
H2039.