I'm currently waiting on an appointment with a librarian to discuss and refine my systematic review, so for now it's more reading and consolidating, I guess...
Effects of rehabilitation on the brain
You've probably heard the old axiom: "if you don't use it, you lose it." In unilateral cerebral palsy (i.e. cerebral palsy only affecting one side of the body), there are delays in motor development on the affected side. If the limbs on that side are not used, they can become deconditioned, and development of cortical representation of that side of the body can be likewise suppressed. In turn, the affected limb becomes more limited in function, thus creating a vicious cycle of sorts.
Thankfully, there is some good news: motor control of the affected limb can be maintained. Maintenance may occur either via using the spared tissue of the affected hemisphere (a process known as "ipsilesional reorganisation") or via withdrawal of crossing fibres from the affected hemisphere and survival of fast-conducting ipsilateral motor projections (a process known as "contralesional reorganisation"). The type of reorganisation may have implications for treatment: subjects with ipsilesional reorganisation tend to experience an increase in motor cortex excitability following treatment, whereas subjects with contralesional reorganisation tend to experience a decrease in motor cortex excitability.
Studies involving combinations of constraint-induced movement therapy (CIMT), neurodevelopmental treatment (NDT), occupational therapy (OT), intensive motor training and/or training camps have shown that the brain can undergo reorganisation following such rehabilitative activities. In the affected hemisphere, the primary motor cortex and/or primary somatosensory cortex may undergo greater activation during active motor tasks (evidence is less consistent for passive motor tasks). However, these effects only take place if such tasks are done with the affected hand. Other functional effects also take place in the affected hemisphere: for instance, there is an increase in somatosensory evoked magnetic fields (SEFs) elicited by tactile stimulation. In patients with ipsilesional reorganisation (but not contralateral reorganisation), SEF latency may decrease and motor evoked potentials (MEPs) may increase in the primary motor cortex. Aside from functional changes, there are also structural changes in the affected hemisphere: the primary motor cortex, primary somatosensory cortex and hippocampus have all been found to increase as a result of rehabilitation.
The unaffected hemisphere also undergoes some changes. While there are no clear functional changes at a population level (some changes have been seen at a single-subject level), there are structural changes: both the primary motor cortex and hippocampus increase in volume.
Important factors in neurorehabilitation
Nielsen et al. (2015) identified many important factors in neurorehabilitation programs. They are as follows:
Active patient participation
It is important that patients participate actively in treatment, as sensory feedback via passive manipulation is not the same as via active manipulation. When muscles are contracted actively, gamma motor neurons are activated, causing greater deviations in the activity of muscle spindle afferents as opposed to passive movement. Furthermore, active contraction increases the load on the muscle tendon, which causes activation of Golgi tendon organ afferents. Joint afferents may result in different types of feedback depending on whether movement is active or passive.
I'm not done yet! During active manipulation, spinal motoneurones can influence spinal neural networks via Renshaw cell inhibition. Active manipulation is also a factor in influencing presynaptic inhibition of sensory input to spinal networks. Perception of sensory stimuli tends to be reduced when performing an active movement at the same time. (For example, when you move your arm, unless you are focusing on it, you generally don't tend to notice that your arm is moving. My understanding is that's because your brain is expecting that arm to move, so it blocks out a degree of sensory input pertaining to movement.)
What about those who are paralysed? There is hope that mental training and imagination may activate the same areas of the brain as voluntary movements. Current studies, however, are unconvincing. Mental training tends to be more effective in people who practise such techniques regularly, such as elite athletes. Other alternatives are virtual reality therapy and mirror therapy.
Physical aids only when necessary
Nielsen et al. recommend against the use of physical aids unless absolutely necessary, as a) time spent using a physical aid (e.g. a wheelchair) takes away from opportunities to practice a skill (e.g. walking), and b) external sensory feedback (e.g. training in a robotic device) may disrupt learning. There are, however, newer devices that allow a patient to contribute to the movement to an ever-increasing extent.
Challenges that support learning
It is important to keep the patient challenged and learning new things. If a patient learns something once, they get a short-lived increased representation of muscles in the corresponding brain areas. If training is repeated, they gain more long-lasting changes in cortical representation. However, if they keep repeating the same thing over and over, performance increases by a lesser amount each time, and cortical representation may even decrease. Cortical expansion only occurs when difficulty increases, so it is important to keep up the challenge. It might be helpful to have goals in mind to work towards.
Patient responsibility
It takes many hours to learn new skills, so it is important that patients have ways to train at home.
Every day, as long as possible
One study showed that no plastic changes occurred after training for 15 minutes, so blocks of 20 minutes or more may be necessary. On the other hand, another study suggested that multiple short bouts might be just as effective as one long bout.
Motivation and reward
When dopamine is released by the "reward system," there is increased consolidation of the motor program in the motor cortex and basal ganglia. There are also increased influences on the prefrontal areas, which facilitate the decision to perform similar behaviours in order to get that sweet, sweet dopamine. The effect of rewards and feedback are most optimal if given immediately.
Optimise acquisition and retention
Acquisition and retention can be optimised by optimising the practice structure. In this area, there is a bit of a trade-off between increased performance in the practice session (which can lead to increased motivation) and increased performance in the long-term. Practising a single skill during constant conditions or practising multiple skills in a "blocked" format (i.e. practise skill A and only skill A for x minutes, and then skill B and only skill B for y minutes) can increase performance short-term, as well as motivation. On the other hand, varying the conditions and using random or interleaved practise is better for long-term retention.
Consolidation
Failure to consolidate a new skill is most likely if the patient learns another task or is subjected to competing external stimuli (i.e. stimuli that activate the same neural circuits) within 3-4 hours of learning. It has been suggested that it may help to schedule the timing of sessions so that patients can sleep afterwards. This way, patients won't be affected by external stimuli during the critical 3-4 hour period. Furthermore, certain phases of sleep may influence consolidation of new skills.
Dopamine, as well as being important in motivation, is also essential for the late phase of long-term potentiation. It is related to consolidation and structural network changes. As such, maybe it might be important to increase dopamine levels, through methods such as aerobic exercise towards the end of a session. (Amphetamines also increase levels of monoamines such as dopamine, thus increasing consolidation, but please don't try this at home.)
Focus on paresis (muscular weakness), not spasticity
Many interventions focus on spasticity (muscle stiffness), but this focus may be misplaced. The abnormal stretch reflexes that are the hallmark of spasticity only occur in the resting state, not during movement. Also, it has been suggested that spasticity may be an adaptive change aimed at maintaining functional output despite diminished descending drive. Nielsen et al. suggest teaching patients how to optimally integrate sensory feedback, rather than focus on eliminating spasticity.
Other influences on learning and memory
Since the brain lives off glucose, increasing sugar intake prior to learning may be helpful. (Of course, you shouldn't overdo it, and you need to be careful if the patient has diabetes or some other dietary requirement.) Another supplement that might be important is DHA (docosahexaenoic acid), which is a component of the neural membrane. Yet another important component is exercise.
Individualisation
We're all individuals, so rehabilitation needs to be individualised :)
Neurorehabilitation still has effects late in life
Old brains still maintain considerable plastic potential: motor learning and consolidation are only slightly slower as compared to younger brains. Therefore, even older patients can stand to benefit from neurorehabilitation. In a similar vein, while the 3-4 months following an injury is the optimal period for rehabilitation, rehabilitation can still occur afterwards. The main take-home point from this is that patients can't use "I'm too old"/"It's been too long, there's no hope for me any more" as excuses for not doing their exercises :D
Virtual reality training
As my project will (hopefully) incorporate elements of virtual reality, I decided to have a look at some virtual reality stuff as well. Virtual reality can provide rich sensory environments for mass practice of skills. The ability to make simple alterations in graphics and sound effects can influence attention levels, which is especially important in rehabilitation of children.
One of the easiest components to implement in virtual reality is vision, so let's start there. Many motor, premotor and parietal neurons are modulated by visual information, and movement errors in the visual domain can influence motor control areas during motor learning. Interacting with a virtual representation of hands can recruit the angular gyrus, precuneus and extrastriate body area, which are all regions of the brain involved in attribution of agency (subjective awareness of initiating, executing and controlling one's own actions). Furthermore, when actions are observed, motor evoked potentials (MEPs) may increase in magnitude, and there may also be influences in corticocortical interactions in the motor and premotor areas. Visually-stimulated motion also has an effect on postural responses.
A component of virtual reality that is perhaps more difficult to implement is haptic (tactile) feedback. Tactile feedback can assist with advanced skill learning, and forces that augment errors are more effective in teaching desired movements.
Virtual reality treatments have been found to alter brain activation in at least one child with cerebral palsy. Before a virtual reality treatment, the child had predominantly bilateral activation of sensorimotor cortices. After the treatment, the bilateral activation disappeared, leaving only contralateral activation. These changes were associated with an increased ability of the child to perform reaching, dressing and self-feeding tasks.
References
Adamovich, S 2009, 'Sensorimotor training in virtual reality: A review', NeuroRehabilitation, vol. 25, no. 1, pp. 29-44
Inguaggiato, E, Sgandurra, G, Perazza, S, Guzzetta, A, Cioni, G, Sale, A 2013, 'Brain reorganization following intervention in children with congenital hemiplegia: A systematic review', Neural Plasticity, vol. 2013.
Nielsen, JB, Willerslev-Olsen, M, Christiansen, L, Lundbye-Jensen, J, Lorentzen, JR 2015, 'Science-based neurorehabilitation: Recommendations for neurorehabilitation from basic science', Journal of Motor Behaviour, vol. 47, no. 1, pp. 7-17
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