**4. Measuring the brain activities related to the motor stimulation using NIRS**

#### **4.1 Physiological processes associated with brain activity**

Physiological events associated with brain activity can be subdivided into intracellular events, events occurring at the cell membranes and those that are mediated by neurovascular coupling and occur within the vascular space. Increased brain activity is correlated not only with oxygen consumption but also with glucose consumption. The brain has only negligible stores of glucose and therefore relies both on the circulating glucose and on the active transport system which moves glucose across the blood-brain barrier. Increased activity in brain cells is associated with an increase in glucose consumption and

What Does Cerebral Oxygenation Tell Us About Central Motor Output? 309

technique can only assess the responses of the most superficial portions of the cerebral

Neuroimaging studies have reported a proportional relationship between cortical signals and exerted joint force in humans, indicating that brain signals are positively correlated to voluntary efforts, as a high level of effort is required for exerting greater muscle force (Liu et al., 2007; Liu et al., 2003). Recently several authors have proposed combining neuroimaging techniques with the classical twitch interpolation to investigate the central aspects of fatigue after and during ongoing exercise. Most studies on central fatigue have investigated isometric contractions of isolated muscle groups. Post et al. (2009) showed, during a sustained high force contraction, that the hemodynamic response (BOLD signal) in the most important motor (output) areas increased (primary sensorimotor cortex, supplementary motor area, premotor area), whereas the voluntary activation (accessed via the twitchinterpolation technique) of the index finger muscle during a unilateral task decreased with time. This finding suggests that although the central nervous system (CNS) increased its input to the motor areas, these increases did not overcome fatigue-related changes in the voluntary drive to the motor units. During a progressive maximal cycling exercise, Rupp and Perrey (2008) showed a decrease in prefrontal cortical oxygenation before motor performance failure, which may be compatible with the notion of a role for the prefrontal cortex in the reduction of motor output by the cessation of exercise. However, this finding was not associated with a decrease in voluntary activation, but measured 6 min postexercise. Support for the role of a failure of the CNS to excite the motor neurons adequately (i.e., central fatigue) in fatigue during challenging exercises has been provided by the finding that voluntary activation of skeletal muscles is reduced after fatiguing exercise. This suboptimal muscle activation has also been functionally observed via lowered surface electromyographic (EMG) activity on several occasions during fatiguing exercises (Mendez-Villanueva et al., 2007). However, what triggers these acute changes in the CNS behaviour remains to be determined. Central fatigue may be elicited by low brain oxygenation, i.e., by insufficient O2 delivery and/or low pressure gradient to drive the diffusion of O2 from the capillaries to the mitochondria. Direct and indirect evidences support the contention that inadequate cerebral oxygenation depresses cortical neuron excitability, although the mechanisms remain debated (for review see Nybo and Rasmussen, 2007). The non-invasive technique of NIRS offers real-time measurement of oxygenation and hemodynamic responses in tissues, and thus, constitutes a relevant tool to enhance our current knowledge of central (CNS) and peripheral (muscle) determinants of whole-body exercise performance. Some studies have reported that muscle deoxygenation occurs during repeated cycling tests (Racinais et al., 2007). However, exercises of this nature appear to induce a fairly constant level of deoxygenation in prime mover muscles across repetitions, and therefore authors have suggested that muscle O2 uptake was well preserved and was not likely to represent a limiting factor. Data on cerebral oxygenation changes during fatiguing tests are currently presented in the literature. Based on studies conducted during constant workload exercise, incremental test to maximal effort (Rupp and Perrey, 2008), and supramaximal exercise (Shibuya et al., 2004b), the deoxygenation of the cerebral cortex has, in general, been incriminated in the cessation of exercise, or at least in the reduction of exercise intensity. This finding, however, is confounded by the availability of O2 (Subudhi et al., 2007). Although an association exists between cerebral oxygenation and performance in various

cortex.

thus the intracellular glucose concentration might fall in the early activation period (Villringer and Dirnagl, 1995). This transient drop in glucose is accompanied by a transient rise in local lactate concentration (Villringer and Dirnagl, 1995). Magistretti and Pellerin (Magistretti and Pellerin, 1999a, b) have provided new insights on the role of astrocytes in coupling neuronal activity with energy metabolism. They propose an initial glycolytic processing which occurs in astrocytes during activation, resulting in a transient lactate overproduction; followed by a recoupling phase during which lactate is oxidised by neurons. In addition to the events taking place intracellularly, local brain activity induces a local arteriolar vasodilation (Villringer and Dirnagl, 1995). Although small arteries and arterioles probably contain less than 5% of the blood volume in the brain parenchyma, they control most of the resistance and therefore blood flow at a local level. As a consequence of local vasodilation the local cerebral blood volume as well as the blood flow increase. This relationship between neuronal activity and vascular response is termed "neurovascular coupling". In other words, the changes in Hbtot most probably reflect the match between oxygen supply and oxygen demand, whereas changes in O2Hb reflect the alterations in cerebral blood flow, an overshoot in cerebral oxygenation during brain activation. Several NIRS studies conducted in the past fifteen years have demonstrated that activation- induced changes in brain activity can be assessed non-invasively during the performance of various whole-body motor activities (Maki et al., 1995; Obrig et al., 1996).

#### **4.2 Brain activity and motor performance**

The NIRS is applicable under a variety of conditions ranging from bedside monitoring in intensive care to documenting the effects of maximal whole body exercise in the physiology laboratory. To date, several studies have used NIRS to examine alterations in cerebral oxygenation during dynamic exercise, and have found an increase in cerebral oxygenation with medium and high-intensity exercise (Bhambhani et al., 2007; Shibuya et al., 2004a; Subudhi et al., 2007; Suzuki et al., 2004).

While a rather detailed understanding of brain activity during hand movement has been developed (Dettmers et al., 1995), less is known about the functional anatomy of motor control for leg or foot movements. Due to its advantages compared to other neuroimaging techniques, NIRS technique allows recording of cerebral activity during ordinary gait (Fig. 6). For instance, Miyai et al. (2001) were able to compare cerebral activities evoked during gait, alternating foot movements, arm swing and motor imagery of gait. Gait-related responses along the central sulcus were medial and caudal to activity associated with arm swing, in agreement with the known somatotopic organisation of the motor cortex (Perec, 1974). Crucially, these authors showed that walking increased cerebral activity bilaterally in the medial primary sensori-motor cortices and the supplementary motor area, and to a greater extent than the alternation of foot movements. Unfortunately, the spatial distribution and intensity of these responses were not statistically compared. In a different NIRS study, Suzuki et al. (2004) examined the effect of various walking speeds on cerebral activity. They demonstrated that cerebral activity in the prefrontal cortex and premotor cortex tended to increase as the locomotion speed increased, whereas cerebral activity in the medial sensorimotor cortex was not influenced by the locomotion speed. In summary, NIRS is particularly useful for studying the cortical bases of locomotion control. Unfortunately, given the limited depth penetration of the infrared light (a few centimetres from the skull surface), the NIRS

thus the intracellular glucose concentration might fall in the early activation period (Villringer and Dirnagl, 1995). This transient drop in glucose is accompanied by a transient rise in local lactate concentration (Villringer and Dirnagl, 1995). Magistretti and Pellerin (Magistretti and Pellerin, 1999a, b) have provided new insights on the role of astrocytes in coupling neuronal activity with energy metabolism. They propose an initial glycolytic processing which occurs in astrocytes during activation, resulting in a transient lactate overproduction; followed by a recoupling phase during which lactate is oxidised by neurons. In addition to the events taking place intracellularly, local brain activity induces a local arteriolar vasodilation (Villringer and Dirnagl, 1995). Although small arteries and arterioles probably contain less than 5% of the blood volume in the brain parenchyma, they control most of the resistance and therefore blood flow at a local level. As a consequence of local vasodilation the local cerebral blood volume as well as the blood flow increase. This relationship between neuronal activity and vascular response is termed "neurovascular coupling". In other words, the changes in Hbtot most probably reflect the match between oxygen supply and oxygen demand, whereas changes in O2Hb reflect the alterations in cerebral blood flow, an overshoot in cerebral oxygenation during brain activation. Several NIRS studies conducted in the past fifteen years have demonstrated that activation- induced changes in brain activity can be assessed non-invasively during the performance of various

The NIRS is applicable under a variety of conditions ranging from bedside monitoring in intensive care to documenting the effects of maximal whole body exercise in the physiology laboratory. To date, several studies have used NIRS to examine alterations in cerebral oxygenation during dynamic exercise, and have found an increase in cerebral oxygenation with medium and high-intensity exercise (Bhambhani et al., 2007; Shibuya et al., 2004a;

While a rather detailed understanding of brain activity during hand movement has been developed (Dettmers et al., 1995), less is known about the functional anatomy of motor control for leg or foot movements. Due to its advantages compared to other neuroimaging techniques, NIRS technique allows recording of cerebral activity during ordinary gait (Fig. 6). For instance, Miyai et al. (2001) were able to compare cerebral activities evoked during gait, alternating foot movements, arm swing and motor imagery of gait. Gait-related responses along the central sulcus were medial and caudal to activity associated with arm swing, in agreement with the known somatotopic organisation of the motor cortex (Perec, 1974). Crucially, these authors showed that walking increased cerebral activity bilaterally in the medial primary sensori-motor cortices and the supplementary motor area, and to a greater extent than the alternation of foot movements. Unfortunately, the spatial distribution and intensity of these responses were not statistically compared. In a different NIRS study, Suzuki et al. (2004) examined the effect of various walking speeds on cerebral activity. They demonstrated that cerebral activity in the prefrontal cortex and premotor cortex tended to increase as the locomotion speed increased, whereas cerebral activity in the medial sensorimotor cortex was not influenced by the locomotion speed. In summary, NIRS is particularly useful for studying the cortical bases of locomotion control. Unfortunately, given the limited depth penetration of the infrared light (a few centimetres from the skull surface), the NIRS

whole-body motor activities (Maki et al., 1995; Obrig et al., 1996).

**4.2 Brain activity and motor performance** 

Subudhi et al., 2007; Suzuki et al., 2004).

technique can only assess the responses of the most superficial portions of the cerebral cortex.

Neuroimaging studies have reported a proportional relationship between cortical signals and exerted joint force in humans, indicating that brain signals are positively correlated to voluntary efforts, as a high level of effort is required for exerting greater muscle force (Liu et al., 2007; Liu et al., 2003). Recently several authors have proposed combining neuroimaging techniques with the classical twitch interpolation to investigate the central aspects of fatigue after and during ongoing exercise. Most studies on central fatigue have investigated isometric contractions of isolated muscle groups. Post et al. (2009) showed, during a sustained high force contraction, that the hemodynamic response (BOLD signal) in the most important motor (output) areas increased (primary sensorimotor cortex, supplementary motor area, premotor area), whereas the voluntary activation (accessed via the twitchinterpolation technique) of the index finger muscle during a unilateral task decreased with time. This finding suggests that although the central nervous system (CNS) increased its input to the motor areas, these increases did not overcome fatigue-related changes in the voluntary drive to the motor units. During a progressive maximal cycling exercise, Rupp and Perrey (2008) showed a decrease in prefrontal cortical oxygenation before motor performance failure, which may be compatible with the notion of a role for the prefrontal cortex in the reduction of motor output by the cessation of exercise. However, this finding was not associated with a decrease in voluntary activation, but measured 6 min postexercise. Support for the role of a failure of the CNS to excite the motor neurons adequately (i.e., central fatigue) in fatigue during challenging exercises has been provided by the finding that voluntary activation of skeletal muscles is reduced after fatiguing exercise.

This suboptimal muscle activation has also been functionally observed via lowered surface electromyographic (EMG) activity on several occasions during fatiguing exercises (Mendez-Villanueva et al., 2007). However, what triggers these acute changes in the CNS behaviour remains to be determined. Central fatigue may be elicited by low brain oxygenation, i.e., by insufficient O2 delivery and/or low pressure gradient to drive the diffusion of O2 from the capillaries to the mitochondria. Direct and indirect evidences support the contention that inadequate cerebral oxygenation depresses cortical neuron excitability, although the mechanisms remain debated (for review see Nybo and Rasmussen, 2007). The non-invasive technique of NIRS offers real-time measurement of oxygenation and hemodynamic responses in tissues, and thus, constitutes a relevant tool to enhance our current knowledge of central (CNS) and peripheral (muscle) determinants of whole-body exercise performance. Some studies have reported that muscle deoxygenation occurs during repeated cycling tests (Racinais et al., 2007). However, exercises of this nature appear to induce a fairly constant level of deoxygenation in prime mover muscles across repetitions, and therefore authors have suggested that muscle O2 uptake was well preserved and was not likely to represent a limiting factor. Data on cerebral oxygenation changes during fatiguing tests are currently presented in the literature. Based on studies conducted during constant workload exercise, incremental test to maximal effort (Rupp and Perrey, 2008), and supramaximal exercise (Shibuya et al., 2004b), the deoxygenation of the cerebral cortex has, in general, been incriminated in the cessation of exercise, or at least in the reduction of exercise intensity. This finding, however, is confounded by the availability of O2 (Subudhi et al., 2007). Although an association exists between cerebral oxygenation and performance in various

What Does Cerebral Oxygenation Tell Us About Central Motor Output? 311

To date based on recent evidences; we may propose that reductions in cerebral oxygenation during exhaustive intensities are caused by decreased cerebral blood flow coupled with increased cerebral oxygen uptake (Gonzalez-Alonso et al., 2004). It has also been proposed that this change in flow and metabolism at high intensities is sensed or controlled by a 'central governor' so that during oxygen availability reduction, peak exercise performance is reduced to prevent the development of ischemia in vital organs including the brain (Noakes et al., 2005). In this way, an increase in Hbtot and a decrease in cerebral oxygenation represent potential metabolic indicators, signalling either directly or indirectly to subcortical and cortical motor areas of the brain to reduce muscle unit recruitment and thus

NIRS utilises light to measure cortical haemoglobin concentration changes associated with neural activity. This technique is more tolerant compared with other comparable techniques, regarding the subjects' movements, thus allowing a wider range of experimental tasks in the range of dynamic exercises. However, it has some shortcomings that need to be addressed. In this chapter, we showed how technical obstacles could be overcome, how NIRS contributes to the mapping of exercise-related brain functions, and further promotes the understanding of human movement and motor performance. In this context, we propose NIRS as a potential mediator between physiology and neuroscience. Beside these advances in technique and analysis of the data, we believe that users should consider the

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protect the brain and peripheral organs.

**5. Conclusion** 

**6. References** 

Munich.

und Sohn.

exercises, no studies have yet determined if a critical level of cerebral deoxygenation impairs whole body exercise. Shibuya and colleagues Shibuya et al. (2004a) reported a progressive cerebral deoxygenation during intermittent exercises. Specifically, these authors observed a reduction in Δ[O2Hb] and Δ[Hbtot], while Δ[HHb] increased, over the course of seven, 30s cycling exercises performed at an intensity corresponding to 150% V� O2max and interspersed with 15s of rest. It was concluded that fatigue, resulting from such intermittent supramaximal exercises, was related to a decrease in the cerebral oxygenation level.

Fig. 6. Example of a NIRS setting while the subject is walking on a treadmill.

To date based on recent evidences; we may propose that reductions in cerebral oxygenation during exhaustive intensities are caused by decreased cerebral blood flow coupled with increased cerebral oxygen uptake (Gonzalez-Alonso et al., 2004). It has also been proposed that this change in flow and metabolism at high intensities is sensed or controlled by a 'central governor' so that during oxygen availability reduction, peak exercise performance is reduced to prevent the development of ischemia in vital organs including the brain (Noakes et al., 2005). In this way, an increase in Hbtot and a decrease in cerebral oxygenation represent potential metabolic indicators, signalling either directly or indirectly to subcortical and cortical motor areas of the brain to reduce muscle unit recruitment and thus protect the brain and peripheral organs.
