**1. Introduction**

Stroke is a central nervous system condition that is prevalent worldwide. According to a report from the World Health Organization [1], approximately 15 million people experience a stroke each year globally, and stroke is the third leading cause of death after heart disease and cancer. As impairment of motor function after a stroke drastically impedes activities of daily living (ADL) and reduces the quality of life [2], the development of effective rehabilitation methods, which encourage the recovery of motor function in patients who have sustained a stroke, is an important task.

Although the 2014 Cochrane Stroke Systematic Review reported several rehabilitation methods demonstrating moderate results in the recovery of upper limb motor function after a stroke, a highly effective method is yet to be established [3]. Understanding the neural mechanisms underlying motor function recovery after brain injury is indispensable for the development of highly effective poststroke rehabilitation strategies. Therefore, in this chapter we will outline these mechanisms and introduce strategies based on these mechanisms as well as on the functional characteristics of the brain.

### **2. Brain reorganization after brain injury**

The brain is a highly plastic organ with the ability to reorganize as a result of learning or injury. In cases of injury in the motor cortex or corticospinal tract, the recovery of motor function is taken care of by the surviving brain regions. Dancause [4] has reported on cortical reorganization accompanying injury in the primary motor cortex. Neurons in the hand area of the primary motor cortex receive input from the fingers as well as the wrist/forearm, and signals are sent from the hand area of the primary motor cortex to the corresponding ipsilateral premotor area. If the hand area of the primary motor cortex is injured, elimination of the inhibitory neurons in the primary motor cortex leads to an increase in the input to the hand area from the wrist/forearm. This results in an enlargement of the wrist/forearm area and shrinking of the hand area of the ipsilateral premotor area. However, as inhibitory neurons at the non-injured side are eliminated, the hand area of the premotor area and the primary motor cortex at the non-injured side also enlarge. Subsequently, reorganization leading to functional recovery occurs through learning and practice. The hand area of the primary motor cortex continues to enlarge as networks are stimulated or adjacent areas are inhibited through changes in synaptic receptor density or the creation of new synapses due to neuroplasticity. Neural networks are also reorganized through the formation of new connections between neurons and axonal sprouting. Thus, brain areas in both the injured and non-injured hemispheres are involved in the functional repair process accompanying recovery after brain injury.

Premotor area activity is also important for the recovery of motor function after a brain injury. Apart from being responsible for certain functions of the motor network, the premotor area is also involved in the integration of sensory and cognitive information in the course of goal-oriented behavior (actions carried out with a clearly established goal or aim, such as ADL). It receives sensory information from the parietal lobe and cognitive information from the dorsolateral prefrontal cortex and the supplementary motor cortex, which are then integrated and sent to the primary motor cortex. This information is also sent directly to the spinal cord via the corticospinal tract. These neural network connections are highly susceptible to plastic changes resulting from injury, learning, training, or therapy. Kantak et al. [5] discuss the reorganization of the premotor area involved in promoting motor function recovery after a brain injury. Reorganization of the premotor area on the injured/non-injured sides in the context of motor function recovery is influenced by the extent and site of the damage. For example, in cases of localized damage to the primary motor cortex or corticospinal tract, patients experience mild functional impairment. In this event, the premotor area on the injured side assists in the recovery of motor function, simultaneously increasing direct input to the corticospinal tract and to the remaining area of the primary motor cortex on the injured side. In cases of extensive damage to the primary motor cortex or

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phase after a stroke.

*Rehabilitation Strategies and Key Related Mechanisms Involved in Stroke Recovery*

corticospinal tract, patients exhibit severe functional impairment. In contrast to cases of localized injury, in these cases, the premotor area on the non-injured side increases input to the surviving sensorimotor area of the injured side. Thus, the premotor areas of the injured and non-injured sides are involved in reorganization contributing to motor function recovery post-brain injury by way of two different

It is known that reorganization of the brain after an injury changes over time along with recovery of motor function. Nishimura et al. [6] caused injury to the corticospinal tracts of monkeys and then carried out rehabilitation to examine the changes in brain activity during the initial phase (1 month) and the stable phase (3 months) of motor function recovery. The study confirmed activity in both the contralateral and ipsilateral primary motor cortices during the initial recovery phase, during which the pinching motion success rate was 80%. Meanwhile, when the success rate reached 100% for the same motion during the stable recovery phase, ipsilateral primary motor cortex activity decreased, while contralateral activity increased and the contralateral area expanded. Based on this study, although the activity of ipsilateral brain regions is inhibited when using the hands or feet under normal situations, it is thought that a decrease in this inhibition and the subsequent activity in the ipsilateral brain areas post-injury promote recovery in the damaged contralateral neural network. Furthermore, it can be concluded that when the injured neural network has recovered substantially, either through repair of the original network or the mobilization of an adjacent network, the ipsilateral brain area returns to a state of inhibition similar to that observed before

Similarly, the abovementioned phenomenon can be observed in the process of motor function recovery in stroke patients. Using functional magnetic resonance imaging (fMRI), Ward et al. [7] explored the correlation between stroke patient motor outcomes (motor function evaluations) 3 months after the onset and brain activity when performing a visually induced motor task with the paretic hand,. The results demonstrated that the number of motor-related brain areas utilized during the motor task was higher in patients with a poor outcome, while patients with a favorable outcome utilized fewer of these areas—a pattern of brain activity close to that of healthy individuals. Further, a negative correlation between motor outcome and the activity of task-related brain areas, such as the supplementary motor area, cingulate motor area, premotor cortex, posterior parietal cortex, and cerebellum, was shown. This negative correlation was confirmed for both the non-injured and injured primary motor cortices. Thus, it was understood that when performing motions with the paretic hand, the worse a patient's poststroke motor function, the more bilateral their brain activity. In a similar study, Rehme et al. [8] used fMRI to investigate longitudinal changes in motor network activity during the recovery of motor function in the initial phase after stroke onset. The authors measured the motor function recovery score and brain activity during movement of the nonparetic and paretic hands in stroke patients 2, 5, and 10 days after onset. The results demonstrated activity of the bilateral primary motor cortex, dorsal and ventral premotor area, and supplementary motor cortex during movement of the paretic hand in stroke patients (**Figure 1B**). Further, when the results were compared by level of motor function impairment, patients with mild impairment showed activity resembling that of healthy individuals at 2, 5, and 10 days, whereas patients with severe impairment showed increased bilateral activity over time (**Figure 1C**). As this bilateral activity demonstrated a positive correlation with motor function recovery (**Figure 1D**), it is thought to reflect neural restructuring in the initial

*DOI: http://dx.doi.org/10.5772/intechopen.91025*

strategies.

the injury.

#### *Rehabilitation Strategies and Key Related Mechanisms Involved in Stroke Recovery DOI: http://dx.doi.org/10.5772/intechopen.91025*

corticospinal tract, patients exhibit severe functional impairment. In contrast to cases of localized injury, in these cases, the premotor area on the non-injured side increases input to the surviving sensorimotor area of the injured side. Thus, the premotor areas of the injured and non-injured sides are involved in reorganization contributing to motor function recovery post-brain injury by way of two different strategies.

It is known that reorganization of the brain after an injury changes over time along with recovery of motor function. Nishimura et al. [6] caused injury to the corticospinal tracts of monkeys and then carried out rehabilitation to examine the changes in brain activity during the initial phase (1 month) and the stable phase (3 months) of motor function recovery. The study confirmed activity in both the contralateral and ipsilateral primary motor cortices during the initial recovery phase, during which the pinching motion success rate was 80%. Meanwhile, when the success rate reached 100% for the same motion during the stable recovery phase, ipsilateral primary motor cortex activity decreased, while contralateral activity increased and the contralateral area expanded. Based on this study, although the activity of ipsilateral brain regions is inhibited when using the hands or feet under normal situations, it is thought that a decrease in this inhibition and the subsequent activity in the ipsilateral brain areas post-injury promote recovery in the damaged contralateral neural network. Furthermore, it can be concluded that when the injured neural network has recovered substantially, either through repair of the original network or the mobilization of an adjacent network, the ipsilateral brain area returns to a state of inhibition similar to that observed before the injury.

Similarly, the abovementioned phenomenon can be observed in the process of motor function recovery in stroke patients. Using functional magnetic resonance imaging (fMRI), Ward et al. [7] explored the correlation between stroke patient motor outcomes (motor function evaluations) 3 months after the onset and brain activity when performing a visually induced motor task with the paretic hand,. The results demonstrated that the number of motor-related brain areas utilized during the motor task was higher in patients with a poor outcome, while patients with a favorable outcome utilized fewer of these areas—a pattern of brain activity close to that of healthy individuals. Further, a negative correlation between motor outcome and the activity of task-related brain areas, such as the supplementary motor area, cingulate motor area, premotor cortex, posterior parietal cortex, and cerebellum, was shown. This negative correlation was confirmed for both the non-injured and injured primary motor cortices. Thus, it was understood that when performing motions with the paretic hand, the worse a patient's poststroke motor function, the more bilateral their brain activity. In a similar study, Rehme et al. [8] used fMRI to investigate longitudinal changes in motor network activity during the recovery of motor function in the initial phase after stroke onset. The authors measured the motor function recovery score and brain activity during movement of the nonparetic and paretic hands in stroke patients 2, 5, and 10 days after onset. The results demonstrated activity of the bilateral primary motor cortex, dorsal and ventral premotor area, and supplementary motor cortex during movement of the paretic hand in stroke patients (**Figure 1B**). Further, when the results were compared by level of motor function impairment, patients with mild impairment showed activity resembling that of healthy individuals at 2, 5, and 10 days, whereas patients with severe impairment showed increased bilateral activity over time (**Figure 1C**). As this bilateral activity demonstrated a positive correlation with motor function recovery (**Figure 1D**), it is thought to reflect neural restructuring in the initial phase after a stroke.

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

tional characteristics of the brain.

ing recovery after brain injury.

**2. Brain reorganization after brain injury**

Although the 2014 Cochrane Stroke Systematic Review reported several rehabilitation methods demonstrating moderate results in the recovery of upper limb motor function after a stroke, a highly effective method is yet to be established [3]. Understanding the neural mechanisms underlying motor function recovery after brain injury is indispensable for the development of highly effective poststroke rehabilitation strategies. Therefore, in this chapter we will outline these mechanisms and introduce strategies based on these mechanisms as well as on the func-

The brain is a highly plastic organ with the ability to reorganize as a result of learning or injury. In cases of injury in the motor cortex or corticospinal tract, the recovery of motor function is taken care of by the surviving brain regions. Dancause [4] has reported on cortical reorganization accompanying injury in the primary motor cortex. Neurons in the hand area of the primary motor cortex receive input from the fingers as well as the wrist/forearm, and signals are sent from the hand area of the primary motor cortex to the corresponding ipsilateral premotor area. If the hand area of the primary motor cortex is injured, elimination of the inhibitory neurons in the primary motor cortex leads to an increase in the input to the hand area from the wrist/forearm. This results in an enlargement of the wrist/forearm area and shrinking of the hand area of the ipsilateral premotor area. However, as inhibitory neurons at the non-injured side are eliminated, the hand area of the premotor area and the primary motor cortex at the non-injured side also enlarge. Subsequently, reorganization leading to functional recovery occurs through learning and practice. The hand area of the primary motor cortex continues to enlarge as networks are stimulated or adjacent areas are inhibited through changes in synaptic receptor density or the creation of new synapses due to neuroplasticity. Neural networks are also reorganized through the formation of new connections between neurons and axonal sprouting. Thus, brain areas in both the injured and non-injured hemispheres are involved in the functional repair process accompany-

Premotor area activity is also important for the recovery of motor function after

a brain injury. Apart from being responsible for certain functions of the motor network, the premotor area is also involved in the integration of sensory and cognitive information in the course of goal-oriented behavior (actions carried out with a clearly established goal or aim, such as ADL). It receives sensory information from the parietal lobe and cognitive information from the dorsolateral prefrontal cortex and the supplementary motor cortex, which are then integrated and sent to the primary motor cortex. This information is also sent directly to the spinal cord via the corticospinal tract. These neural network connections are highly susceptible to plastic changes resulting from injury, learning, training, or therapy. Kantak et al. [5] discuss the reorganization of the premotor area involved in promoting motor function recovery after a brain injury. Reorganization of the premotor area on the injured/non-injured sides in the context of motor function recovery is influenced by the extent and site of the damage. For example, in cases of localized damage to the primary motor cortex or corticospinal tract, patients experience mild functional impairment. In this event, the premotor area on the injured side assists in the recovery of motor function, simultaneously increasing direct input to the corticospinal tract and to the remaining area of the primary motor cortex on the injured side. In cases of extensive damage to the primary motor cortex or

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#### **Figure 1.**

*Longitudinal changes in motor network activity in the initial phase after stroke onset [8]. (A) Brain activity during right/left hand movement in healthy adults. (B) Brain activity during non-paretic/paretic hand movement in stroke patients (2, 5, and 10 days after onset). Bilateral activation is expanded for the paretic hand. (C) Brain activity during paretic hand movement for mild and severe stroke patients (2, 5, and 10 days after onset). In patients with mild functional impairment, only the contralateral hemisphere is active, whereas the activity in both hemispheres expands for severe patients. (D) Map of brain regions involved in favorable motor function recovery.*
