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Neuroplasticity Dr. Michael P. Gillespie 2 Neuroplasticity Neuroplasticity is the ability of the brain to change, for better or for worse, throughout the individual’s life span. It involves forming neuronal connections in response to information derived from experiences in the environment, sensory stimulation, and normal development (Doidge, 2007; Merzenich, 2001; Nudo, 2008). Dr. Michael P. Gillespie 3 Neuroplasticity Neuroplasticity refers to the moldable structure of the brain and nerves that results from changes in neural pathways and synapses. These changes stem from changes in behavior, environment, neural processes as well as changes from bodily injury. The brain does change throughout life. Dr. Michael P. Gillespie 4 Neuroplasticity Dr. Michael P. Gillespie 5 Girl Living With Half Her Brain http://www.youtube.com/watch?v=2MKNsI5CWoU Dr. Michael P. Gillespie 6 Positive Outcomes of Neuroplasticity New skills Better cognition More efficient communication between sensory and motor pathways Improved function of the aging brain Slowing down pathological processes Promoting recovery of sensory losses Improved motor control Improved memory (Mahncke, Bronstone & Merzenich, 2006; Mahucke & Merzenich, 2006; Nudo 2007; Stein & Hoffman, 2003). Dr. Michael P. Gillespie 7 Negative Outcomes of Neuroplasticity Decline in brain function Altered motor control Impaired performance of activities of daily living Amplified perception of pain Dr. Michael P. Gillespie 8 Neuroplasticity http://www.youtube.com/watch?v=iAzmyB9PFt4 Dr. Michael P. Gillespie 9 Structural Changes in the Brain Synaptic plasticity Synaptogenesis Neuronal migration Neurogenesis Neural cell death Dr. Michael P. Gillespie 10 Synaptic Plasticity Synaptic plasticity refers to changes in the strength of connections between synapses. Long-term potentiation (LTP) Long-term depression (LTD) Changes in the number of receptors for specific neurotransmitters Up-regulation Down-regulation Changes in which proteins are expressed inside the cell Dr. Michael P. Gillespie 11 Neuroplasticity – Brain Remodeling Steps to remodel the brain based upon experiences: 1. Repetition 2. Correct fundamentals 3. Authentic environment Dr. Michael P. Gillespie 12 Neuroplasticity – Brain Remodeling http://www.youtube.com/watch?v=VvZ9ofM7Go&feature=related Dr. Michael P. Gillespie 13 Synaptogenesis & Synaptic Pruning The creation and removal of entire groups of synapses. This builds and destroys connections between neurons respectively. Dr. Michael P. Gillespie 14 Neuronal Migration Neuronal migration is a process whereby neurons extend from their place of birth to connect to far reaching areas of the brain. Dr. Michael P. Gillespie 15 Neurogenesis Neurogenesis is the creation of new neurons. It largely occurs in the developing brain. Limited neurogenesis occurs in the adult brain. Dr. Michael P. Gillespie 16 Neural Cell Death Neurons die. This can happen from either damage, over-excitation, or disease. Natural programmed cell death including apoptosis also occurs. Dr. Michael P. Gillespie 17 Functional Reorganization As the brain develops, certain areas of the brain become specialized for specific tasks. If your experience changes dramatically or parts of the brain are damaged, areas previously specialized for a certain function can take on the work of other areas. Dr. Michael P. Gillespie 18 Brain Functions / Brain Regions Contrary to common understanding, brain functions are not strictly confined to specific fixed locations as identified in this picture. Dr. Michael P. Gillespie 19 Previously Held Beliefs Brain functions were confined to specific fixed locations of brain tissue. Brain structure is relatively immutable after a critical period during early childhood. * New research reveals that many aspects of the brain remain plastic in adulthood. * Dr. Michael P. Gillespie 20 Levels of Neuroplasticity Cellular changes (result of learning) Cortical remapping (response to injury) Dr. Michael P. Gillespie 21 Synaptic Pruning Synaptic pruning is a neurological regulatory process that facilitates a change in neural structure by reducing the overall number of neurons and synapses. The resulting synaptic connections are more efficient. Pruning is believed to represent the learning process. Synapses that are frequently used have strong connections whereas those that are rarely used are eliminated. “Neurons that fire together, wire together. Neurons that fire apart, wire apart”. Dr. Michael P. Gillespie 22 Synaptogenesis / Synaptic Pruning http://www.youtube.com/watch?v=tJ93qXXYRpU&feature=re lated Dr. Michael P. Gillespie 23 Cortical Maps Sensory information from certain parts of the body projects to specific regions of the cerebral cortex. As a result of this somatotrophic organization of sensory inputs to the cortex, cortical representation of the body resembles a map (or a homonculus). Dr. Michael P. Gillespie 24 The Learning Brain http://www.youtube.com/watch?v=cgLYkV689s4&feature=rel ated Dr. Michael P. Gillespie 25 Homunculus Dr. Michael P. Gillespie 26 Removing Sensory Inputs If a cortical map is derived of sensory input, the adjacent segments it will become activated by adjacent sensory inputs. Merzenich’s 1984 study involved the mapping of owl monkey hands before and after amputation of the third digit. Before amputation, there were five distinct areas corresponding to each individual digit. After amputation of the third digit, the area of the cortical map formerly occupied by the third digit was invaded by the previously adjacent second and fourth digit zones. Only the regions bordering a certain area will invade it will alter the cortical map. Dr. Michael P. Gillespie 27 Sensory Site Activation Sensory sites that are activated in an attended operant behavior increase their cortical representation (Merzenich and William Kenkins (1990)). When a stimulus is cognitively associated with reinforcement, its cortical representation is strengthened and enlarged (Merzenich and DT Blake (2002, 2005, 2006). Cortical representations can increase two to threefold in 1-2 days at the time in which a new sensory motor behavior is first acquired and changes are largely finished within a few weeks. Dr. Michael P. Gillespie 28 Phantom Limbs Phantom limbs are experienced by people who have undergone amputations. Cortical reorganization appears to play an important role in phantom limb sensation. Mirror box therapy developed by Vilayanur Ramachandran has shown great promise in treating phantom limb pain. Dr. Michael P. Gillespie 29 Phantom Limb Pain Dr. Michael P. Gillespie 30 Mirror Box A diagrammatic explanation of the mirror box. The patient places the good limb into one side of the box (in this case the right hand) and the amputated limb into the other side. Due to the mirror, the patient sees a reflection of the good hand where the missing limb would be (indicated in lower contrast). The patient thus receives artificial visual feedback that the "resurrected" limb is now moving when they move the good hand. Dr. Michael P. Gillespie 31 Mirror Visualization Therapy http://www.youtube.com/watch?v=Pe8Y3YETnuY&feature=r elmfu http://www.youtube.com/watch?v=hMBA15Hu35M&feature= related Dr. Michael P. Gillespie 32 Spatial Coupling Marian Michielsen suggested that Ramachandran’s Mirror Box therapy worked by enhancing spatial coupling between limbs. Dr. Michael P. Gillespie 33 Treatment of Brain Damage Brain activity associated with a given function can move to a different location. This concept allows for the treatment of acquired brain injury. The adult brain is not hard-wired with fixed neuronal circuits. Cortical and subcortical rewiring of neuronal circuits happens in response to training and in response to injury. Dr. Michael P. Gillespie 34 Neurogenesis Neurogenesis is the process by which neurons are generated from neural stem cells. Recent studies show that neurogenesis occurs in the adult mammalian brain and can persist well into old age. This appears to occur in the hippocampus, olfactory bulb, and cerebellum. In the rest of the brain, neurons can dies, but cannot be recreated. Dr. Michael P. Gillespie Rehabilitation Techniques That Precipitate Cortical Reorganization Constraint-induced movement therapy Functional electrical stimulation Treadmill training with body weight support Virtual reality therapy Dr. Michael P. Gillespie 35 Constraint-induced Movement Therapy (CIMT) 36 This therapy improves upper extremity function in stroke victims and other victims with central nervous system damage. The purpose is to combine restraint of the unaffected limb and intensive use of the affected limb. Types of restraints: Sling Triangular bandage Splint Half glove Mitt Dr. Michael P. Gillespie Constraint-induced Movement Therapy (CIMT) 37 The use of the affected limb is called shaping. Training typically involves restraining the unaffcted limb and using the affected limb for 90% of waking hours. Receiving CIMT early (3-9 months post-stroke) results in greater functional gains than receiving delayed treatment (15-21 months post-stroke). Factors for success of CIMT Concentrated and repetitive practice of the affected limb. The unaffected limb must be constrained 90% of the waking hours. Dr. Michael P. Gillespie Constraint-induced Movement Therapy (CIMT) Dr. Michael P. Gillespie 38 Constraint-induced Movement Therapy (CIMT) http://www.youtube.com/watch?v=MMTh2hWvB2g Dr. Michael P. Gillespie 39 40 Functional Electrical Stimulation Functional electrical stimulation uses electrical currents to activate nerves innervating extremities affected by paralysis resulting from spinal cord injury, head injury, stroke, and other neurological disorders. Sometimes it is referred to as Neuromuscular electrical stimulation (NMES). Dr. Michael P. Gillespie 41 Functional Electrical Stimulation Dr. Michael P. Gillespie Contralaterally Controlled Functional Electrical Stimulation Stroke Therapy http://www.youtube.com/watch?v=boz0HQXQhKg Dr. Michael P. Gillespie 42 43 Treatment of Learning Difficulties Michael Merzenich developed a series of plasticity based computer programs known as Fast ForWord. The programs consist of seven brain exercises to help with the language and learning deficits of dyslexia. The software also improved cognitive function in adults with age related cognitive decline (ARCD). Dr. Michael P. Gillespie 44 Chronic Pain Some people suffer chronic pain at sites that were previously injured, but are currently healthy. Chronic pain happens as a result of maladaptive reorganization of the nervous system both peripherally and centrally. During the period of tissue damage, prolonged nociceptive input from the periphery to the central nervous system results in somatotopic organization and central sensitization. Dr. Michael P. Gillespie 45 Meditation Meditation has been linked to cortical thickness and the density of gray matter. Richard Davidson performed experiments with H.H. the Dalai Lama to examine the effects of mediation on the brain. Long term and short term practice of meditation resulted in different levels of activity in brain regions associated with qualities such as attention, anxiety, depression, fear, and anger. Mediation also demonstrated an effect on the ability of the body to heal itself. Changes in the physical structure of the brain appear to be responsible for these differences. Dr. Michael P. Gillespie 46 Exercise Induced Neuroplasticity All forms of exercise appear to produce neuronal changes in the brain; however, different forms of exercise produce changes in different brain regions. More demanding forms of exercise seem to promote change in more diverse areas of the brain. Dr. Michael P. Gillespie 47 Neuroplasticity & Occupational Therapy Learning and memory are the result of experience driven alterations of the synaptic structures of neurons. “Occupational Therapy practitioners set up the circumstances and situations that modify the environment and the degree of challenge for a skill set (just the right challenge) that creates an adaptive response that originates at the cellular and molecular level” (McCormack, 2009). Neuroplasticity reflects the brain’s ability to grow and change into old age as long as it is engaged in meaningful occupations. This is the basis of occupational therapy (Christiansen & Baum, 2005). Dr. Michael P. Gillespie 48 Types of Neuroplasticity Practice-Dependent Plasticity Competitive Plasticity Positive Plasticity Negative Plasticity Dr. Michael P. Gillespie 49 Practice-Dependent Plasticity A person performs a task repeatedly to learn or re-learn a skills set. “The neurons that fire together, wire together” (Hebb’s concept). http://www.youtube.com/watch?v=5iyodWeFkLE You can incorporate constraint induced OT as well to “force” neurons to fire together and “unmask” latent neurons to activate those neuronal pathways. Dr. Michael P. Gillespie 50 Competitive Plasticity Use or disuse of a neuronal pathway will lead to natural selection of the pathways utilized. “Use it or lose it” The cerebral cortex is constantly remodeling itself according to influences from the environment (Bear et al, 2007; Mahncke, Bronstone et al, 2006). Dr. Michael P. Gillespie 51 Positive Plasticity Compensatory changes occuring at the cellular and molecular levels (dendritic sprouting). Temporal changes (speed of action potentials). Release of neuromodulators. Influence of second messengers (i.e. producing new postsynaptic membrane receptors). Formation of alternative pathways that make new functional connections in the cortex and tract systems. Dr. Michael P. Gillespie 52 Dendritic Sprouting Dr. Michael P. Gillespie 53 Neurite Outgrowth http://www.youtube.com/watch?v=n_9YTeEHp1E&feature=r elated Dr. Michael P. Gillespie 54 Negative Plasticity Negative plasticity occurs when dendritic sprouting and proliferation of postsynaptic membrane receptors results in excessive production of excitatory impulses producing hypertonicity in muscles. Good motivation and attention release neuromodulators (dopamine and acetylcholine) that promote faster synapses and positive changes in cortical mapping. Poor motivation and lack of effort produces weak synaptic connections and synapses that are slower. These neurons sometimes undergo apoptosis. “Neurons that fire out of sync, fail to link” (Bear et al., 2007; Fillipi, 2002; Woolf & Salter, 2000). Dr. Michael P. Gillespie 55 Secondary Neural Pathways After a lesion in the central nervous system, the usual neuronal pathways are blocked or destroyed. We can develop secondary neuronal pathways to send neuronal signals around the blockage. We say that secondary neuronal pathways become “unmasked” and get stronger with use. This is analogous to a bridge going out. We can take secondary roads. This path may take longer, but shorter paths will be found. Dr. Michael P. Gillespie 56 Compensation If a person loses one sensory modality, other senses can compensate and take over. Teaching ways to adapt, modify, or change the method to perform the task. This may involve modifying the environment. It may involve training the family members or caregivers to assist. Compensation involves the brain’s ability to recruit other neurons in other regions of the nervous system. It is a form of neuroplasticity and not just a way to modify or adapt. Dr. Michael P. Gillespie 57 Neuroplasticity in Pain Syndromes Neuropathic pain and pain hypersensitivity are examples of negative plasticity. Activation of nociceptive pathways is the response of the system to repeated stimuli. Dr. Michael P. Gillespie 58 Neuroplasticity in Repetitive Strain Injuries Complex bio-psychosocial responses can cause undesirable outcomes in localized injuries (Nudo, 2007). Therefore, it is necessary to “treat the whole person”. OT practitioners should stimulate practice-dependent plasticity by facilitating adaptive responses that engage the cerebral cortex. Mental rehearsals and guided imagery techniques release neuromodulators such as dopamine, norepinephrine, and acetylcholine. These neuromodulators influence neuroplasticity and the formation of new cortical maps. Dr. Michael P. Gillespie 59 Mechanisms of Neuroplasticity 1. Diaschisis – neuronal structures that are anatomically connected to a lesion or region damaged by stroke undergo reduced blood supply and metabolism. 2. Behavioral compensation – occupational therapy directs the individual’s interaction with the environment to utilize viable neurons surrounding the area of the lesion in order to reorganize their capacity to compensate for damaged neurons. 3. Adaptive plasticity – dendritic growth and angiogenesis occurs near the damaged areas. Dendritic growth is an adaptive response to substitute for the lost function. This is a critical time of OT intervention. Positive plasticity happens through use or doing. Negative plasticity happens through disuse or doing little. Dr. Michael P. Gillespie 60 OT in Cognitive Rehabilitation Cognitive impairments are an example of negative plasticity that affects mood and the ability to problem solve. This in turn can reduce motivation. Interventions used in occupational therapy that stimulate change and repetition are important in strengthening connections between neurons (Meintzschel & Ziemann, 2006). If the practitioner uses a novel stimulus, it should be followed immediately by some reward or reinforcement. It should be repeated again and again to drive synaptic change. Dr. Michael P. Gillespie 61 Compensatory Cognitive Strategies Changes in environmental structure and support. Visual aids. Checklists. Step-by-step instructions. Remedial cognitive interventions include repetitively practicing tasks that require specific cognitive functions and challenges. Video games Virtual reality Neurofeedback training Brain-computer interface technology can deliver repetition, challenge, and motivation rapidly and consistently. Dr. Michael P. Gillespie 62 Neurofeedback Training http://www.youtube.com/watch?v=GJRWYxEEFv0 Dr. Michael P. Gillespie 63 Brain Computer Interface http://www.youtube.com/watch?v=ZwuMg0FsKzs Dr. Michael P. Gillespie