Cerebral and muscle tissue oxygenation during exercise in healthy adults: A systematic review

Highlights

• •The findings are consistent in showing greater deoxygenation in the muscles during exercise, reflecting the oxygen (O₂) utilization.
• •Muscle O₂ availability becomes compromised when an individual reaches the exhaustion point by reducing blood flow and decreasing muscle O₂ extraction.
• •Cerebral tissue experiences an increase in O₂ delivery with increased exercise intensity, suggesting a greater engagement of the brain areas to sustain the exercise.
• •At the exhaustion point, cerebral oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise.

Abstract

Background

Near-infrared spectroscopy (NIRS) technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise. Since this technology has been growing and is now successfully used in laboratory and sports settings, this systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and oxygen (O₂) changes (i.e., the balance between O₂ delivery and O₂ consumption) within the cerebral and muscle systems during exercise.

Methods

A systematic review was conducted using PubMed, Embase, Scopus, and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise. This review considered manuscripts written in English and available before February 9, 2023. Each step of screening involved evaluation by 2 independent authors, with disagreements resolved by a third author. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies.

Results

Twenty studies were included, of which 80% had good methodological quality, and involved 290 young or middle-aged adults. Different types of exercises were used to assess cerebral and muscle hemodynamic changes, such as cycling (n = 11), treadmill (n = 1), knee extension (n = 5), isometric contraction of biceps brachii (n = 3), and duet swim routines (n = 1). The cerebral hemodynamics analysis was focused on the frontal cortex (n = 20), while in the muscle, the analysis involved vastus lateralis (n = 18), gastrocnemius (n = 3), biceps brachii (n = 5), deltoid (n = 1), and intercostal muscle (n = 1). Overall, muscle deoxygenation increases during exercise, reaching a plateau in voluntary exhaustion, while in the brain, oxyhemoglobin concentration increases with exercise intensity, reaching a plateau or declining at the exhaustion point.

Conclusion

Muscle and cerebral oxygenation respond differently to exercise, with muscle increasing O₂ utilization and cerebral tissue increasing O₂ delivery during exercise. However, at the exhaustion point, both muscle and cerebral oxygenation become compromised. This is characterized by a reduction in blood flow and a decrease in O₂ extraction in the muscle, while in the brain, oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise.

Graphical Abstract

1. Introduction

Near-infrared spectroscopy (NIRS) is a non-invasive tool for monitoring changes in both cerebral and skeletal muscle oxygenation during exercise.1, 2, 3, 4 NIRS operates on the distinct absorption properties of chromophores within the near-infrared range of 700–1000 nm.^5,6 The near-infrared light is able to penetrate several centimeters into biological tissues (reaching approximately 2–3 cm in adult heads and 4–5 cm in muscle), where hemoglobin and myoglobin (only in muscles) absorb the light photons.^7,8 The NIRS signal offers information about oxygenation changes in the small blood vessels (i.e., arterioles, capillaries, venules) because large blood vessels may completely absorb light photons.^5,8 The absorption rate of the light photons is different for oxygenated (absorption peak around 850 nm) and deoxygenated chromophores (absorption peak around 760 nm), which allows photodetectors to differentiate them.^5,6 The difference in the tissue absorbency allows us to understand the balance between oxygen (O₂) delivery and O₂ consumption in the cerebral cortex and skeletal muscles.⁵

Different NIRS-based measurement techniques have been developed to measure tissue oxygenation. These include continuous-wave-based systems that emit light with a constant intensity, frequency-domain systems that modulate light intensity using a sinusoidal function, and time-domain systems that measure light's time of flight in addition to intensity.^3,8,9 Among these, continuous-wave NIRS systems are the most commonly used in research.^8,9 However, these systems determine changes in chromophore concentrations from a baseline value (relative changes) rather than absolute concentrations.^5,7 Despite this limitation, NIRS technology enables real-time quantitative monitoring of crucial physiological measures. Using the modified Beer–Lambert law, it is possible to calculate changes in concentration of oxyhemoglobin ([HbO₂]) and deoxyhemoglobin ([HHb]) over time, indicating the balance between O₂ delivery and extraction in the local tissue, respectively.^2,4, 5, 6, 7, 8^,10, 11, 12 In addition, the sum of [HbO₂] and [HHb] (total hemoglobin [tHb]) is considered an index of localized blood flow in tissue, and the difference between [HbO₂] and [HHb] (characterized as [Hb_diff]) is used as an index of tissue O₂ extraction. The ratio between [HbO₂] and [tHb], which represents the tissue saturation (TSI, expressed in percentage), reflects an index of changes in tissue O₂ saturation, indicating the balance between O₂ delivery and tissue O₂ consumption.^4,7,12 Overall, the NIRS-derived parameter can be an indicator of the physiological status (i.e., blood flow and local O₂ consumption) of both cerebral and muscular systems during exercise.¹²

NIRS systems have been validated against gold-standard techniques in humans. For example, cerebral NIRS data have been validated against functional magnetic resonance imaging, which is considered the gold standard for neuroimaging. Previous studies have demonstrated a strong correlation between functional magnetic resonance imaging blood O₂ level-dependent signal and NIRS measures ([HbO₂] and [HHb]) during motor^13,14 and cognitive^15,16 tasks. Moreover, existing evidence has reported the validity of muscle NIRS measurements (e.g., [HbO₂] and [HHb]) in humans by comparing these measures with venous blood because NIRS signals are related to changes in venous saturation under varying oxygenation statuses of human muscles.17, 18, 19 Therefore, NIRS is a valid and reliable technique to measure both cerebral and muscle hemodynamics.

Real-time cerebral oxygenation analysis has important applications in the fields of clinical and sports sciences, contributing to understanding brain function during exercise. Neural activation in response to a stimulus causes increased energy demands in the activated brain area. This demand leads to rapid vasodilatation, increasing cerebral blood flow in such areas, to meet the increased metabolic needs and O₂ uptake with an increased O₂ supply.^20,21 Since the vasodilatation precedes and overshoots the need, the increased cortical activity is associated with increased [HbO₂] and decreased [HHb].²⁰ In fact, several studies have analyzed the cerebral hemodynamics, especially of the prefrontal cortex (PFC), during physical exercises.^4,6,20 The results showed alterations in brain oxygenation according to the exercise intensity, indicating an increase in cerebral oxygenation (which has been linked to increased cortical activity^1,20,22,23) during moderate aerobic exercise, possibly due to the requirement to control movement.^20,24,25 However, it decreases when the individual reaches voluntary exhaustion (maximal intensity exercise), reflecting impaired central involvement during neuromuscular control.26, 27, 28

In the skeletal muscle system, NIRS has been applied to assess oxidative metabolism in different muscles (e.g., arm, leg, and respiratory muscles) and exercise intensity (e.g., moderate, heavy, and severe exercise).^2,4,6 The increase in [HbO₂] and decrease in [HHb] are indications of O₂ availability, while the reduction in [HbO₂] and increase in [HHb] indicate the O₂ consumption in the local muscle. The use of NIRS can aid in understanding the efficiency of the muscular system in providing and using O₂ during exercise. For example, lower O₂ availability has been considered indicative of compromised cardiac output and muscle blood flow.29, 30, 31 Taken together, the application of NIRS in both cerebral and muscle systems during an exercise session may contribute to the understanding of central and peripheral hemodynamic and metabolic processes.

Recent advancements in NIRS technology have allowed for the simultaneous measurement of both cerebral and skeletal muscle oxygenation. The synchronized analysis of these systems facilitates a comprehensive understanding of the blood flow during exercise sessions, enhancing our knowledge about possible mechanisms for how muscles and the brain cope with O₂ demand and the wider balance between O₂ delivery and utilization. Since this technology has been growing and is now successfully used in laboratory and sports settings, this systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and O₂ changes (i.e., the balance between O₂ delivery and O₂ consumption) within the cerebral and muscle systems during exercise. The review focused on healthy adults and “pure” exercise (e.g., without any condition that could affect the individual oxygenation response, such as local hypoxia, altitude conditions, or any manipulation of the environment/individual)^28,32, 33, 34 in order to exclude any confounding effect.

2. Methods

This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022295233) and written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines updated in 2020³⁵ and the Cochrane recommendation for systematic review.³⁶

2.1. Search strategy

Searches were conducted up to February 9, 2023, on PubMed, Embase, Scopus, and Web of Science. The search strategy included terms related to exercise, NIRS measurements, and cerebral and muscular systems. The full search strategy is presented in Table 1. Manuscripts identified through database searches were downloaded to a reference manager software where duplicates were excluded. Two of 3 authors (DOS, VSB, and PCRS) independently performed the initial screen by reviewing the titles and abstracts. Full texts were reviewed when the information in the title and abstract was unclear. The third author made the final decision in case of inconsistencies between the 2 authors.

Table 1.

Search strategy.

Search	Query
#1	Exercise OR physical activity OR physical exercise OR fitness OR training OR sport* OR rehabilitation OR endurance OR aerobic OR strength OR resistance OR cycling OR swim* OR walk* OR treadmill (Title/Abstract/Keywords)
AND
#2	Functional neuroimaging OR “near infrared spectroscopy” OR “functional near infrared spectroscopy” OR “fNIRS” OR “NIRS” OR Hemodynamic* OR oxim* OR spectroscopy OR haemoglobin OR hemoglobin OR oxyhemoglobin OR deoxyhemoglobin OR oxygenation OR tissue saturation (Title/Abstract/Keywords)
AND
#3	Cortex OR cortical OR brain OR cerebral OR central (Title/Abstract/Keywords)
AND
#4	Muscle OR muscular OR skeletal muscle OR peripheric (Title/Abstract/Keywords)

Abbreviations: fNIRS = functional near-infrared spectroscopy; NIRS = near-infrared spectroscopy.

2.2. Eligibility criteria

Manuscripts were included if they simultaneously investigated cerebral and muscle hemodynamic changes using the NIRS system (regardless of system brands) during exercise and included only healthy adults. For this review, we considered manuscripts written in English; cross-sectional, randomized, and non-randomized controlled trials; and observational studies. We excluded pre-print and open-label studies, review articles, commentaries, conference abstracts, study protocols, and manuscripts composed of populations of adolescents or children. In addition, we excluded manuscripts that have manipulated the basal condition of individuals (e.g., by using local hypoxia protocol, interfering with blood flow or the respiratory system, simulating altitude conditions, manipulating climatic conditions, or administering any type of supplementation, medication, or tobacco).

2.3. Data extraction

Data from each study were independently extracted by 2 of the 6 authors (DOS, VSB, PCRS, FMR, ABM, and RV) and then synthesized into a table format. Any uncertainty or incomplete information arising from the extracted data was resolved through discussion with a third author. The extracted variables included: (a) study design; (b) participants’ characteristics; (c) exercise protocol; (d) comparisons performed in the study; methods used to collect and analyze the NIRS data of (e) cerebral and (f) muscular systems; (g) additional measurements assessed in the study; (h) main results; and (i) conclusions.

2.4. Methodological quality assessment

Two authors (2 of the 6 authors; DOS, VSB, PCRS, ABM, FMR, and RV) independently assessed the methodological quality (risk of bias) of the included studies using the Joanna Briggs Institute Critical Appraisal Checklist.³⁷ Disagreements in the assessments between the reviewers were resolved by a third author (DOS or VSB). This appraisal assesses the methodological quality of a study and determines the extent to which a study has addressed the possibility of bias in its design, conduct, and analysis.³⁷ Since all studies included were cross-sectional, we used a Joanna Briggs Institute Critical Appraisal Checklist specific to cross-sectional studies. The assessment is based on 8 critical aspects of the study: (a) the criteria for inclusion in the sample were clearly defined; (b) the study subjects and setting were described in detail; (c) the exposure was measured in a valid and reliable way; (d) objective, standard criteria were used for measurement of the condition; (e) confounding factors were identified; (f) strategies to deal with confounding factors were stated; (g) the outcomes were measured in a valid and reliable way; and (h) appropriate statistical analysis was used.³⁷ Each item was scored as 1 (the study does fulfill the specified criteria), 0 (the study does not fulfill the stated criteria), unclear (the criteria are not clearly identified in the report), or not applicable (the criteria were not relevant to the study), thus yielding a maximum of 8 points. Studies were judged to be low (>70%), moderate (50%–70%), and high risk of bias (<50%).

3. Results

3.1. Study selection

A total of 4773 records were identified through the initial search. After removing 2474 duplicates and 2272 records based on titles and abstracts, 27 studies were identified for full-text screening. Of these, 7 studies were excluded due to the following reasons: adolescent population (n = 1); without NIRS muscle or cerebral measurements (n = 3); cerebral and muscle oxygenation were not evaluated simultaneously (n = 3). Finally, 20 articles were included in the systematic reviews. The summary of the study selection is presented within the PRISMA flow diagram (Fig. 1).

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart showing the screening process. NIRS = near-infrared spectroscopy.

3.2. Study characteristics

Supplementary Table 1 shows the characteristics of the 20 studies included in the systematic review. The studies were published from 2008 to 2022 and involved a total of 290 young or middle-aged adults. The sample size varied between 1 and 28 participants (median = 12). Ten studies recruited only male participants,38, 39, 40, 41, 42, 43, 44, 45, 46, 47 4 studies only female,48, 49, 50, 51 and 5 studies recruited both sexes.52, 53, 54, 55, 56 One study did not report the sex.⁵⁷ Six studies mentioned that participants were physically active,^{39,40,42,44,47,52} 7 studies did not specify the level of physical activity,^41,43,45,53, 54, 55, 56 3 studies included both short-term and long-term aerobically trained participants,^38,48,49 1 study included cyclists,⁵⁷ 1 study well-trained cyclists or triathletes,⁴⁶ 1 study elite synchronized swimmers,⁵⁰ and 1 sub-elite futsal players.⁵¹ Different types of exercises were used to assess cerebral and muscle hemodynamic changes, such as cycling,^38,39,42,44,46, 47, 48, 49^,53,55,57 treadmill,⁴⁵ knee extension,^{40,41,51,54,56} isometric contraction of the biceps brachii (BB),^41,43,52 and duet swim routines.⁵⁰

3.3. NIRS data acquisition and analysis

In all studies, the NIRS data were assessed during exercise. In addition, the analyses were performed considering the difference between data collected during exercise and at pre-test while resting (baseline). Thus, the delta (∆ = NIRS data during exercise – NIRS data during baseline) was considered in all analyses. In the cerebral measurements, 11 studies evaluated only the left PFC,^{38,40,41,44,46,}48, 49, 50^,52,54,57 3 studies assessed the right PFC,^39,43,55 1 study evaluated the right frontal cortex,⁴⁵ 1 study assessed both left and right PFC,⁵¹ 1 study assessed the PFC (without specifying the hemisphere) and motor cortex,⁴⁷ 1 study evaluated the contra-lateral frontal lobe,⁵⁶ 1 study assessed the frontal cortex,⁴² and 1 study evaluated the midline forehead.⁵³ In the muscular measurements, 11 studies different sets were used in the optodes placement: (a) 6 studies placed them in the right vastus lateralis (VL);^{39,46,47,50,51,57} (b) 2 studies in the VL without specifying the body side;^40,42 (c) 2 studies in the dominant VL;^54,56 (d) 2 studies in both left and right VL;⁴⁴ (e) 2 studies in the left VL and left gastrocnemius;^38,48 (f) 2 studies in both right VL and right BB;^45,55 (g) 1 study in the BB and dominant VL;⁴¹ (h) 1 study in the left BB;⁴³ (i) 1 study in both left and right VL and left gastrocnemius;⁴⁹ (j) 1 study in the right BB;⁵² and (k) 1 study in the left VL, left deltoid, and intercostal muscle.⁵³

An important parameter involved in estimating the hemoglobin concentration is the differential pathlength factor (DPF), which may be incorporated into the modified Beer–Lambert law. DPF is a multiplicative correction factor that accounts for the mean optical pathlength the light travels within the tissue to the light source-detector separation distance.^7,58 In the cerebral analysis, 5 studies reported the DPF: 4 studies used age-dependent factor^45,48,49,55 and 1 study used 5.93.⁵⁷ In the muscle analysis, 3 studies reported the DPF: 2 studies used 5.51 (for the leg) and 4.16 (for the arm),^45,55 and 1 used 3.83⁵⁷ as the factor.

In cerebral and muscle analysis, the sampling frequency varied between 0.5 Hz and 50 Hz. Three studies did not inform the sampling frequency.^41,42,53 Regarding the filter, only 4 studies presented the methods used to filter the NIRS signals.^41,47,51,53

Sixteen studies analyzed [HHb],38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49^,51,52,55,57 13 studies analyzed [HbO₂],39, 40, 41, 42, 43, 44, 45, 46, 47^,51,52,55,57 12 studies analyzed [tHb],39, 40, 41, 42, 43, 44, 45, 46, 47^,51,52,55 8 studies analyzed TSI,39, 40, 41^{,44,45,50,51,55} 2 studies analyzed [Hb_diff],^46,52 2 studies analyzed cerebral and muscle blood volume and oxygenation,^54,56 and 1 study analyzed O₂ extraction⁵³ as outcome for both cerebral and muscular measurements.

3.4. Cerebral and muscle hemodynamic changes during exercise

Fig. 2 summarizes the main results and Supplementary Table 2 presents a synthesis of the results and conclusions of each study. Overall, during an incremental cycling test, muscle (e.g., VL) [HHb]^{38,39,44,46,48,49,55,57} and [tHb]^39,46,55 increased, while muscle [HbO₂]^39,44,46,57 and [Hb_diff]⁴⁶ decreased. Studies revealed an increase in cerebral (i.e., PFC) [HHb],^46,55,57 [HbO₂],^39,46,55,57 [tHb],^39,46 and [Hb_diff].⁴⁶ Similarly, in the high-intensity interval cycling exercise, VL [HbO₂] decreased and PFC [HbO₂] increased, whereas both VL and PFC [HHb] progressively increased until the end.⁴⁴ In response to the submaximal cycling exercise, there was an increase in VL [HHb]⁴⁷ and a decrease in VL [HbO₂],⁴⁷ as well as an increase in both PFC [HbO₂]⁴⁷ and [HHb].⁴⁷ In contrast, prolonged cycling resulted in a decrease in VL [HHb] and an increase in VL [HbO₂] and [tHb]. Cortical [HbO₂] and [tHb] increased, while cortical [HHb] decreased during prolonged cycling.⁴² In a custom supine pedaling protocol, there was an increase in VL O₂ extraction, whereas cerebral O₂ extraction had a linear decrease.⁵³

Fig. 2.

Summary of main results. Most studies used cycling exercises (n = 11), with different protocols. Other types of exercises used were treadmill exercise (n = 1), duet swim routines (n = 1), knee isokinetic exercise (n = 5), and contraction of biceps brachii (n = 3). The arrows indicate an increase or decrease in NIRS variables in the leg muscle (solid black), arm muscle (dashed black), and cerebral tissue (gray). The thickness of the arrows indicates the number of studies that found such results. Detailed results of each study can be found in Supplementary Table 1, including the effects of fatigue state on the cerebral and muscle oxygenation responses. * Contradictory results. ^# Fatigue state may alter the results (Supplementary Table 1). Hb_diff = difference between HbO₂ and HHb; HbO₂ = oxyhemoglobin; HHb = deoxyhemoglobin; NIRS = near-infrared spectroscopy; tHb = total hemoglobin; TSI = tissue saturation.

In a treadmill exercise, 1 study⁴⁵ reported the muscle hemodynamic in active muscle (i.e., VL), less active muscle (i.e., BB), and cerebral tissue (i.e., frontal cortex), which showed that both leg and arm muscles decreased [HbO₂] and TSI, while [HHb] and [tHb] increased. BB muscle presented higher deoxygenation at peak exercise vs. VL muscle. In the cerebral cortex, TSI decreased, while [HbO₂], [HHb], and [tHb] increased. In elite-level synchronized swimmers, the VL TSI dropped during dynamic leg-kicking exercises and the PFC hemodynamic was unchanged throughout the exercise.⁵⁰

During isometric knee flexion/extension, individuals presented a decrease in VL [HbO₂]^{40,44,51,54,56} and [tHb],^40,54,56 and an increase in VL [HHb].^40,44,51 In the PFC, individuals presented an increase in [HbO₂],^40,51,54,56 [HHb],⁴⁰ and [tHb].^40,54,56 In contrast, 1 study found a decrease in PFC [HHb] during knee extension.⁵¹ During isometric contractions of BB, studies found a decrease in muscle [HbO₂]^41,43,52 and an increase in muscle [HHb].^41,43,52 In addition, cerebral [HbO₂]^43,52 and [tHb]⁵² increased during isometric contractions, while [HHb] decreased.^43,52

3.5. Methodological quality assessment (risk of bias)

The methodological quality ranged from 2 (25%; indicating high risk of bias) to 8 (100%; indicating low risk of bias). Nearly all the studies demonstrated good overall quality, as shown in Table 2; 16 studies were classified as having low risk,38, 39, 40^,42,44, 45, 46^,48, 49, 50, 51, 52^,54, 55, 56, 57 2 studies as moderate risk,^47,53 and 2 studies as high risk of bias.^41,43

Table 2.

Methodological quality assessment based on Joanna Briggs Institute (JBI) Critical Appraisal Checklist.

	Criteria and score								Total score/%	Risk of bias
	#1	#2	#3	#4	#5	#6	#7	#8
Bhambhani et al. (2014)52	1	0	1	1	1	1	1	1	7/87.5	Low
Buzza et al. (2016)49	1	1	1	1	1	1	1	1	8/100	Low
Buzza et al. (2019)48	1	1	1	1	1	1	1	1	8/100	Low
Buzza et al. (2020)38	1	1	1	1	1	1	1	1	8/100	Low
Caen et al. (2019)39	1	1	1	1	1	1	1	1	8/100	Low
Cherouveim et al. (2022)40	1	1	1	1	1	1	1	1	8/100	Low
Ellwien et al. (2017)53	U	0	1	1	U	U	1	1	4/50.0	Moderate
Formenti et al. (2018)51	1	1	1	1	1	1	1	1	8/100	Low
Ganesan et al. (2013)41	0	0	1	0	0	0	1	U	2/25.0	High
Jones and Cooper (2018)50	0	1	1	1	1	1	1	1	7/87.5	Low
Kounalakis and Geladas (2012)42	0	1	1	1	1	1	1	1	7/87.5	Low
Matsuura et al. (2011)54	U	1	1	1	1	1	1	1	7/87.5	Low
Oka and Asgher (2021)43	1	0	1	0	0	0	1	0	3/37.5	High
Peltonen et al. (2013)55	U	1	1	1	1	1	1	1	7/87.5	Low
Pereira et al. (2009)56	1	1	1	1	1	1	1	0	7/87.5	Low
Perentis et al. (2021)44	1	1	1	1	1	1	1	1	8/100	Low
Racinais et al. (2014)57	U	1	1	1	1	1	1	1	6/75.0	Low
Rissanen et al. (2012)45	1	1	1	1	1	1	1	1	8/100	Low
Rupp and Perry (2008)46	1	1	1	1	1	1	1	1	8/100	Low
Rupp et al. (2013)47	0	1	1	1	0	0	1	1	5/62.5	Moderate

Notes: Criteria #1: Were the criteria for inclusion in the sample clearly defined? #2: Were the study subjects and the setting described in detail? #3: Was the exposure measured in a valid and reliable way? #4: Were objective, standard criteria used for measurement of the condition? #5: Were confounding factors identified? #6: Were strategies to deal with confounding factors stated? #7: Were the outcomes measured in a valid and reliable way? #8: Was appropriate statistical analysis used? (1) indicates the article does fulfill the specified criteria, (0) indicates the article does not fulfill the stated criteria, or (U) indicates that it is unclear whether the article fulfills the criteria.

4. Discussion

This systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and O₂ changes (i.e., the balance between O₂ delivery and O₂ consumption) within the cerebral and muscle systems during exercise. We examined 20 studies, of which most (80%) had good methodological quality. In summary, the studies focused on the PFC area for cortical analysis; however, there were discrepancies in the muscles assessed (e.g., 11 different sets were used in the muscle optodes placement). Most of the studies analyzed the change of [HHb], [HbO₂], and [tHb]. The studies involved small sample sizes and varied in terms of individuals' physical activity level, exercise protocol, NIRS data processing, and NIRS outcomes, which makes the results difficult to generalize. Despite this, the studies showed relevant information about changes in cerebral and muscle oxygenation during different types of exercise and intensity efforts.

4.1. Hemodynamic changes during cycling

Eleven studies examined cycling exercise. However, the protocols varied between studies (e.g., prolonged cycling, constant-power test until exhaustion, incremental cycling test until voluntary exhaustion, or high-intensity interval exercise). Overall, the studies reported that muscle [HHb] increased and [HbO₂] decreased during cycling exercises, changes that suggest an increased muscle tissue O₂ extraction. However, exercising until voluntary exhaustion may limit the O₂ extraction, reducing blood flow or decreasing muscle tissue oxygenation. Although interesting results have been found relative to muscle oxygenation, there is a gap in the evidence regarding different muscles. The focus of most of these studies was the VL muscle (the primary muscle involved in cycling exercise), but the analyses of different muscles (e.g., less involved muscles during cycling exercise) may help to advance knowledge of the redistribution of blood flow during exercise.⁵⁹ In cerebral (e.g., PFC) measurements, the response to cycling exercise is different between studies. While some studies found both cerebral [HbO₂] and [HHb] increased during submaximal and exhaustive exercise,^39,46,57 other studies reported contradictory findings, such as no significant changes in [HbO₂] with an increase in [HHb] and [tHb] throughout the exercise,⁴⁴ or an increase in cerebral [HbO₂] and decrease in the [HHb] during exercise.⁴² The discrepancies observed among studies findings (i.e., the lack of consistency) might be attributed to variations in cycling protocols. Moreover, population characteristics such as physical fitness levels, age, and sex could act as additional factors contributing to contradictory results. These variations in exercise protocols and participant demographics across studies could potentially account for the observed discrepancies.

Although all studies focused on analyzing the frontal cortex, Rupp and colleagues⁴⁷ verified both PFC and motor cortex hemodynamics during 3 successive 80-min cycling bouts. Interestingly, they found different oxygenation responses, in particular, during the first 80 min, where motor cortex [HbO₂] decreased, and PFC [HbO₂] increased in response to exercise. These results demonstrate the specificity of O₂ delivery and activation patterns in motor-related cortical areas during submaximal exercise. However, more studies are necessary to confirm the motor cortex oxygenation response during exercise.

Cerebral and muscle oxygenation responses are related to exercise intensity. Healthy young men cycling at 40 revolutions per minute (r/min) or 80 r/min for 90 min presented lower values of muscle [tHb] and [HbO₂] at 80 r/min than 40 r/min after 30 min of exercise, while both [HHb] and TSI remained the same between cadences. In addition, cerebral TSI was lower at 80 r/min than at 40 r/min during the exercise and both [tHb] and [HbO₂] were lower at 80 r/min than 40 r/min at the end of exercise.⁴² During submaximal cycling exercise, healthy young adults had an increase in leg O₂ extraction from rest to 130% of resting heart rate (HR) and then stabilized. In the brain, the O₂ extraction has a linear decrease with exercise level (130%, 150%, and 170% of resting HR).⁵³ These findings suggest that higher cycling intensity is related to compromised muscle and cerebral blood volume and cerebral oxygenation.⁴² A possible explanation may be attributed to the reduction in cardiac output in the higher intensity. A compromised cardiac output may affect regional muscle oxygenation and cause local vasoconstriction or inhibit vasodilatation,⁴² limiting O₂ delivery to skeletal muscles, which may lead to an anaerobiosis process and, as a consequence, inhibit muscle contraction and induce muscle fatigue.^60,61 Similarly, in the brain, impaired cardiac output may affect cerebral blood volume and cerebral blood flow,⁴² inducing central fatigue.⁶² As a result, a reduction in cardiac output may precede task failure.⁶⁰

Cerebral and muscle hemodynamics are altered in voluntary exhaustion. Cyclists performing an incremental cycling test until exhaustion presented a non-linear increase in both cerebral [HHb] and [HbO₂] concomitantly to the first ventilatory threshold. Cerebral [HHb] further increased, while [HbO₂] reached a plateau after the second ventilatory threshold. VL [HbO₂] displayed a non-linear decrease, while VL [HHb] increased between the first and second ventilatory thresholds, following an attenuation after the second ventilatory threshold.⁵⁷ Similarly, during progressive maximal cycling, well-trained cyclists who exercised to exhaustion showed a continuous increase in the VL and PFC [tHb] until the second ventilatory threshold and then stabilized. Also, the individuals increased VL [HHb] during exercise, whereas both VL [HbO₂] and [Hb_diff] decreased continuously from the beginning of the test until exhaustion. Cerebral [HHb] increased during exercise until the end. In contrast, cerebral [HbO₂] and [Hb_diff] increased during exercise to second ventilatory thresholds, then dropped until the end-point of the test (exhaustion).⁴⁶ Taken together, these results suggest that the metabolic and ventilatory events may affect both cerebral and muscle oxygenation levels during an incremental test.^46,57 Muscle fatigue has been related to a reduction in microcirculation and disturbances in oxidative metabolism, which may impair muscle function.⁶³ Furthermore, a decrease in the PFC oxygenation before exhaustion (motor performance failure) implies the role of the PFC in the reduction of motor output at the cessation of exercise.⁴⁶

Different muscles respond differently to exercise. For example, during incremental cycling exercise, deoxygenation in the BB was more severe than in the leg muscle.⁵⁵ A possible explanation for such difference may be the exercise pressor reflex function.^64,65 Basically, the exercise pressor reflex is a function related to the autonomic nervous system's response to increased metabolic demand during physical activity. This function is a chain of events that is not directly related to an increase in O₂ delivery, but it implies the O₂ supply to active muscles while decreasing the O₂ for non-active muscles.^64,65 Thus, exercise pressor reflex functions may contribute to circulatory adjustment, resulting in a redistribution of blood flow between more and less active muscles. Also, previous studies reported a higher [HHb] in the VL compared to gastrocnemius muscles during ramp incremental cycling or square-wave constant load (SWCL) cycling.^38,48,49 The variations in muscle fiber characteristics^38,48,49 and the recruitment pattern of such muscles during different exercise intensities (e.g., intercostal muscle and arm muscle deoxygenation increased the contribution during maximal cycling exercise) may influence the oxygenation response during exercise.

Leg muscles (but not arm muscle or cerebral) deoxygenation differs between sexes. Peltonen and colleagues⁵⁵ compared men vs. women during incremental cycling protocol and revealed that VL [HHb] increased in both sexes but significantly more in men than women at peak exercise. Additionally, cerebral and arm muscle oxygenation showed similarities in both sexes. The discrepancy in leg muscle deoxygenation may be attributed to a sex-specific response in matching O₂ delivery and utilization with systemic circulation, vascular resistance, and blood pressure.^55,66 Previous studies have indicated that men tend to have higher cardiac output and blood volume compared to women.⁶⁷ These factors appear to contribute to reduced peripheral resistance in active leg muscles, thus creating conditions conducive to efficient deoxygenation.⁵⁵ Furthermore, variations in factors such as vascular responsiveness, regulation of blood flow to muscles, and blood perfusion may exist between men and women,⁶⁷ leading to differences in muscle deoxygenation. Additionally, hormonal differences (i.e., testosterone and estrogen) between men and women may impact muscle oxygenation.^68,69 Sex hormones influence various vasoactive substances and pathways involved in vascular smooth muscle contraction, potentially affecting deoxygenation levels during exercise.⁷⁰ In contrast, similar oxygenation levels observed in inactive muscles and the cerebral tissue suggest that both men and women tend to exhibit similar regulation of regional blood flow.⁵⁵ Therefore, the disparity in leg muscle deoxygenation demonstrates that O₂ delivery and utilization are sex-specific, whereas this distinction is not observed in the arm or cerebral regions.

Beyond sex, the current training load and age affect the central and peripheral hemodynamics. Three studies^38,48,49 used the same cycling exercise protocol (ramp incremental cycling and SWCL cycling) and compared the current training load in different age groups and sexes (women: 18–30 years; women and men: 40–60 years). Buzza et al.⁴⁸ found that, in the ramp incremental test, long-term trained young women presented higher [HHb] in the VL and gastrocnemius compared to those who were short-term trained, but not in the SWCL test. In contrast, Buzza et al.⁴⁹ reported that short-term trained and long-term trained older women (40–60 years) presented no difference in [HHb] in the gastrocnemius during ramp incremental and SWCL test exercises. They found that only VL [HHb] increased during exercise. These findings indicate that O₂ extraction is reduced in older women compared to young women. Both studies did not find a difference in PFC [HHb] between groups during the ramp incremental and SWCL tests, which suggest that age and training status do not seem to affect O₂ extraction in the PFC in adult women during exercise.⁴⁸ The third study analyzed both short- and long-term trained men and identified that [HHb] was greater in gastrocnemius but not the VL in long- compared to short-term trained during the SWCL test. There was no difference during the ramp incremental test. In addition, in 90% of gas exchange threshold during SWCL test, long-term trained presented greater [HHb] in the PFC compared to short-term trained, suggesting that long-term vs. short-term trained older men utilize more O₂ in the PFC. Taken together, these results provided evidence that O₂ extraction is age, sex, and training load dependent.

4.2. Hemodynamic changes during treadmill exercise and synchronized swimming routines

There is a discrepancy between the number of studies that have simultaneously analyzed cerebral and muscle hemodynamic changes during cycling (n = 11), walking/running (n = 1), or swimming (n = 1). A possible explanation may be the NIRS technology used in the studies. The use of a stationary cycle ergometer instead of a treadmill or swimming may facilitate data collection; however, there are wireless NIRS systems available that allow individuals greater freedom of movement. Further studies are required to explore the hemodynamic changes in different exercises to better understand the balance of cerebral and muscle O₂ supply and demand according to exercise contexts.

Despite the small number of studies using treadmill and swimming exercises, the results are in line with the findings in cycling studies. Rissanen and colleagues⁴⁵ analyzed the oxygenation responses in active (i.e., VL) and less active muscles (i.e., BB) and cerebral tissue (i.e., frontal cortex) of young men during incremental treadmill exercise. The study showed that [HbO₂] and TSI decreased from baseline walking to peak exercise while [HHb] and [tHb] increased in both leg and arm muscles. Cerebral measurements showed that TSI decreased while [HbO₂], [HHb], and [tHb] increased. Deoxygenation at peak exercise was greater in the arm muscle compared to the leg muscle and cerebral tissue, which could also be explained by the exercise pressor reflex function,^64,65 as mentioned above. The authors concluded that O₂ delivery to BB (less active muscle) may be limited by an accelerated increase in ventilation at high running intensities. In addition, a greater capacity for blood O₂ carrying is associated with a greater level of VL deoxygenation at peak treadmill exercise.

Jones and Cooper⁵⁰ examined changes in peripheral muscle and brain oxygenation in elite-level synchronized swimmers. They observed a rapid decrease in VL TSI (%) during dynamic leg-kicking exercise, indicating an initial constriction accompanied by heightened O₂ consumption. Interestingly, cerebral oxygenation, analyzed in the PFC, remained constant throughout the exercise, leading the authors to propose a protective mechanism of the cerebral system. Similar results were found during maximal dry breath-holds, where cerebral oxygenation was maintained compared to reduced muscle oxygenation.⁷¹ Taken together, these findings are in line with cerebral autoregulation mechanisms. This mechanism contributes to cerebral blood flow regulation, which is key to maintaining a constant nutrient and O₂ supply, thus enabling adequate neural function.⁷² Therefore, the human diving response is O₂-conserving in supplying O₂ to the brain, while the muscle O₂ stores are depleted.⁷¹

4.3. Hemodynamic changes during knee isokinetic exercise

Knee extension induces muscle deoxygenation. Previous studies reported an increase in VL [HHb] and a reduction in VL [HbO₂] during unilateral knee extension.^40,44,51 In addition, a slow speed of movement during exercises promotes higher VL [HHb] than exercises performed with a normal speed.⁵¹ Taken together, these results demonstrated the O₂ utilization in local tissue during exercise and slow movement may elicit larger muscle deoxygenation, maximizing the levels of metabolic stress.⁵¹

The PFC oxygenation response during knee extension is contradictory. Cherouveim et al.⁴⁰ revealed a rapid increase in both PFC [HbO₂] and [tHb], while PFC [HHb] slowly increased during knee flexion. Formenti et al.⁵¹ found a decrease in PFC [HHb] and an increase in PFC [HbO₂] during the exercise. In contrast, Perentis and colleagues⁴⁴ did not find significant changes in PFC [HHb] and [HbO₂]. Such differences may be related to the different protocols used in these studies, such as knee isokinetic exercise performed at 60°/s and an intensity corresponding to 60% of the maximal voluntary contraction,⁴⁰ unilateral knee extensions at ∼50% of 1 repetition maximum in 3 different paces (1 s, 3 s, and 5 s for both concentric and eccentric phases),⁵¹ and high-intensity interval isokinetic exercise (7 sets of 5 repetitions with 15-s intervals between sets).⁴⁴ Furthermore, voluntary exhaustion was achieved by participants in only 1 out of 3 studies,⁵¹ of which might have contributed to conflicting results in cerebral oxygenation.

Corroborating the influence of voluntary exhaustion in both muscle and cerebral oxygenation, 2 studies^54,56 reported an increase in cerebral oxygenation and cerebral blood volume along with a decline in muscle oxygenation and muscle blood volume during the static and dynamic knee extensions until voluntary exhaustion. The results were independent of sex and intensity.⁵⁴ These findings suggest that muscle fatigue was not due to a lack of cerebral oxygenation throughout the contractions but due to intramuscular factors, such as reduced blood volume and O₂ availability in the muscle tissue during resistance exercise.^54,56

4.4. Hemodynamic changes during arm contraction

BB contraction increases local deoxygenation. Similar to knee isokinetic exercise, the BB muscle, during isometric or isokinetic contraction, presented an increase in [HHb] and a decrease in [HbO₂],^41,43,52 such that [HHb] increases progressively with increasing intensity (20%, 40%, and 60% of maximal voluntary contraction)⁵² and increases even more with muscle fatigue.⁴³ These findings imply a greater O₂ utilization by the muscle fiber during BB contraction, mainly in high-intensity exercises.^41,43,52

In the brain, [HbO₂] and [tHb] increased steadily with the increasing intensity during isometric contractions, while [HHb] decreased from 20% to 40% and remained reduced at the same level from 40% to 60% maximal voluntary contraction.⁵² Also, PFC [HbO₂] increased and [HHb] decreased at the beginning of exercise, but [HHb] increased when exercise intensity reached the exhaustion point.⁴³ The increased [HbO₂] indicates enhanced cerebral oxygenation (that may be interpreted as increased cortical activation) which, combined with motor recruitment (evidenced by increased root mean square electromyography in the muscle), demonstrates the role of the PFC in the motor unit recruitment to maintain the target force.⁵² The increased PFC [HHb] may be a physiological indicator for analysis of the limit of exercise and fatigue caused by exhaustive exercise.⁴³ In addition, muscle fatigue during BB contraction is mediated by peripheral O₂ availability instead of impaired cerebral oxygenation,⁵² corroborating previous studies that found similar results during knee isokinetic exercise.^54,56

4.5. Studies limitations and future directions

The major limitations of this study are in regard to NIRS processing. Not all studies reported detailed information about sampling frequency, signal correction by DPF, or the applied filter methods. Studies that reported these aspects of NIRS processing showed great variability. For example, 5 out of 20 studies reported that the DPF was used in cerebral analysis, and in 2 of them it represented different values (age-dependent factor or 5.93). In the muscle analysis, 3 studies reported the DPF, which again varied between studies. The utilization of a fixed DPF value among subjects, typically ranging between 3 and 6,^2,58,73 is common in NIRS analyses. However, accurate assessment of hemodynamic changes depends on the use of precise DPF values in NIRS signal calculations.⁷⁴ DPF values should ideally vary between subjects due to differences in the anatomical structure and tissue composition of the brain (e.g., skull thickness and cerebrospinal fluid)⁷⁴ and muscle (e.g., subcutaneous adipose tissue thickness and muscle condition).⁷⁵ The use of constant DPF does not account for possible variation between subjects; as a result, the hemodynamics estimation may not be accurately calculated, causing serious crosstalk errors.^74,75 Hence, employing a constant DPF for all subjects is not recommended.⁷ Several studies have proposed equations or algorithms to precisely calculate the DPF.73, 74, 75, 76 However, to the best of our knowledge, there is no consensus on better DPF estimates. Further investigation is necessary to determine the ideal DPF algorithm or equation for both muscular and cerebral NIRS. Additionally, we recommend clearly documenting all processing steps to enhance study comparison and reproducibility.

It is notable that all studies have evaluated the frontal cortex. The focus on the frontal cortex instead of other cortex areas (e.g., motor cortex) during exercise is not exclusive, but it is prevalent for several reasons: (a) the frontal cortex is more accessible for analysis compared to other parts of the head or cortex, which may be covered by hair, potentially obstructing or absorbing NIRS light;⁷⁷ (b) it is known that the PFC has projection to pre-motor areas and plays a crucial role in movement planning, goal-directed behavior, and decision-making;⁷⁸ additionally, the PFC is associated with various features induced by exercise, such as affective processing,⁷⁹ cognitive functions,⁸⁰ and mood status;⁸¹ (c) previous study suggests that the patterns of hemodynamic responses to exercise are similar in the PFC and motor areas;⁸² and (d) as previously mentioned in the discussion, there is consistent evidence showing that inadequate PFC oxygenation is related to central fatigue and, consequently, impairs motor performance.^6,20 These factors demonstrate the important contribution of PFC analysis during exercise. Nonetheless, future studies should explore other cortical areas, like motor areas, to gain a deeper understanding of the involvement of different brain regions during both maximal and submaximal exercise and their roles in performance.

Regarding muscle oxygenation, since previous studies showed different hemodynamic responses between muscles, further studies are necessary to provide information about the dynamic between O₂ delivery and utilization in different sites of the body. In addition, cardiac output should be measured simultaneously with hemodynamic changes in different sites of the body for a better understanding of blood flow redistribution during exercise. Finally, although hemodynamic changes during cycling and knee extension exercises have been extensively researched, investigations into other exercises (e.g., treadmill, swimming) are scarce.

While we excluded studies that manipulated the basal condition of individuals (e.g., blood flow restriction and exercise in hypoxia) to eliminate any confounding effects, NIRS data analysis may offer crucial insights into O₂ supply responses in various exercise contexts. Existing evidence demonstrates the significance of the NIRS system for comprehending cerebral and muscle hemodynamic responses during exercise, especially with additional manipulations affecting oxygenation status.⁶ For instance, previous studies have compared changes in muscle and cerebral tissue oxygenation between normoxia and hypoxia during exercise.^28,83, 84, 85, 86, 87, 88 Therefore, a systematic understanding of both central and peripheral oxygenation changes in situations where O₂ availability is limited could pave the way for further comprehensive reviews.

5. Conclusion

The present systematic review provides an overview of simultaneous O₂ delivery and utilization in both muscle and cerebral tissue during exercise. Overall, muscle and cerebral oxygenation respond differently to exercise. While muscle shows an increase in O₂ utilization (indicated by increased [HHb]) during exercise, cerebral tissue experiences an increase in O₂ delivery (indicated by increased [HbO₂]) with increased exercise intensity. These adjustments suggest an increase in O₂ consumption to maintain muscle activity and a greater engagement of the PFC to sustain the exercise. However, when an individual reaches the exhaustion point, both muscle and cerebral oxygenation become compromised. This is characterized by a reduction in blood flow and a decrease in O₂ extraction in the muscle; and, in the brain, the oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise. Additionally, our systematic review revealed that different muscles respond differently to exercise in terms of oxygenation (e.g., less active muscles exhibit greater deoxygenation than more active muscles); muscle but not cerebral deoxygenation differs between sexes; and O₂ extraction is age- and training level-dependent.

Despite the relevant evidence compiled in this systematic review, there are some limitations that should be considered with caution when interpreting the data, such as variations in exercise protocols, analysis of only a few brain areas (i.e., predominantly frontal areas) and muscles (i.e., predominantly in one active muscle), small sample sizes, and insufficient information about data processing. Therefore, future studies are necessary to confirm the results identified in our review. Finally, based on this review, we believe that advances in knowledge in the area of exercise physiology and physical training will continue in an integrative way, further improving the interpretation of different types of exercise and intensities of effort, and their impacts on hemodynamic adjustments in the brain and muscles.