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The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 1
The uses of mirror
therapy and ...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 2
can be used to describe similar...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 3
reported an increase in phantom...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 4
1.1 to stage 1.5 in hand recove...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 5
visible, the subject experience...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 6
mobility and decreasing pain in...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 7
with motor imagery.7 The combin...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 8
3 Boyd RN, Graham HK. Botulinum...
The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 9
22 Ramachandran VS, Blakeslee S...
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The uses of mirror therapy and theories of mechanisms regarding its effects on the brain

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The uses of mirror therapy and theories of mechanisms regarding its effects on the brain

  1. 1. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 1 The uses of mirror therapy and theories of mechanisms regarding its effects on the brain N. R. Walker Colorado State University, Department of Health and Exercise Science Abstract Mirror therapy, though recently developed, is a promising modality of treatment for a number of different disorders and syndromes. From phantom limb pain to fibromyalgia, evidence suggests the benefits of mirror visual feedback for restoring motor function and joint mobility, alleviating pain, and mediating discrepancies caused by afferent-efferent interruption. What is mirror therapy? Mirror therapy was first introduced in a 1996 publication entitled “Synaesthesia in phantom limbs induced with mirrors” by VS Ramachandran and D Rogers- Ramachandran.23 The original study employed the use of mirror visual feedback to reduce pain and increase mobility in the amputated limb of patients suffering from phantom limb pain. In a clinical setting, mirrors or mirror boxes are most often placed along the sagittal plane with the patient’s head turned to face the reflective side of the mirror. The functional side of the body is visible in the reflection, while the mirror covers or makes invisible the non- functional side. By observing the reflection of the functional body part in a mirror or reflective surface, while artificially superimposing the reflection of that functioning body part over the non- or minimally functional body part, an adjusted sense of reality and perception of oneself can be created and used to alter the subjective effects movement and sensation have on the mind and body.2 Much work has been completed since Ramachandran and Rogers-Ramachandran’s original publication to suggest a variety of uses for mirror therapy in addition to treating phantom limb pain. Mirror therapy for phantom limb syndrome Neuroscientist VS Ramachandran originally developed mirror therapy for the purpose of treating subjective pain and sensations experienced by individuals with phantom limb syndrome following amputation of an extremity.23 Studies show that 80-100% of amputees experience phantom limb sensation following amputation, and 60-80% of amputees report phantom limb pain in the early postoperative period.8 Most often, the more pain an individual is in before amputation, the more likely and more severe phantom pain becomes postoperatively.17 For most, phantom limb sensation or pain will alleviate itself soon after amputation, but for some, sensation and pain can become a long-term symptom. A 1985 study by Jensen et. al. followed 58 amputees from the day of their amputation to 2-years post operation. 71% of the patients still experienced phantom limb sensation two years after their operation, while 59% reported continuing phantom limb pain.17 Though the mechanisms by which phantom pain and sensation occur are not well understood, some trait characteristics
  2. 2. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 2 can be used to describe similarities between cases of individuals experiencing the phenomenon. For half of the participants in the Jensen et. al. study, phantom limb pain or sensation was constant, while for the other half, pain or sensation was intermittent. Patients often described their pain as knifelike, burning, squeezing, throbbing, or pricking.17 Another relatively common phantom sensation that occurs in approximately 30% of amputees is described as telescoping.13 Telescoping occurs over time in upper limb amputees, and is characterized by the sensation of having a full phantom arm that gradually “telescopes” into the stump, leaving a phantom hand that ectopically originates at the end of the stump.16 In 1996, VS Ramachandran gathered ten amputees suffering from a variety of different phantom sensations and pains and four control subjects. Using an inexpensive method that involved a mirror propped upright that allowed the amputee to visualize a reflection of their functioning hand superimposed over the phantom limb, each participant was instructed to begin to move their functioning hand or arm while observing its reflection and consciously attempting to perceive the reflection as their restored limb. The protocol varied slightly between subjects depending on how much of the limb they had remaining and what type of sensation they felt. 23 Results between subjects varied depending on the type of phantom sensation they had and how long it had been since their operation, but each reported significant improvement in alleviating the symptoms felt within their phantom limb. One subject initially noted an irreversible, strong sensation of having a tightly clenched phantom hand 7 months following amputation 6 inches above the elbow. Upon placing his good hand next to the mirror and opening and closing his hand, as well as flexing, extending and circumducting the wrist, he immediately felt the tension in the phantom hand release and gained the ability to complete bilateral movement using both his functional and phantom hands. A second subject used the mirror technique 9 years post-amputation. While the participant first reported a paralyzed, lifeless, but painful phantom arm, after using the mirror apparatus once, he immediately reported the ability to feel his arm as if the phantom limb had been “plugged in again”. An addition to being able to produce movement, Ramachandran also experimented and noted that some of the participants could refer touch from their functioning hand to the phantom hand simply by observing the would-be restored hand being touched. Using a cotton swab, Ramachandran lightly touched the backside of one participant’s right hand while he observed the reflection superimposed on his phantom hand. Instantly, the subject reported feeling the cotton swab in the symmetric location on his phantom hand.23 A 2007 study conducted by Chan et. al. divided 18 lower limb amputees suffering from phantom limb pain into three different groups: (1) a mirror therapy group; (2) a covered mirror group; and (3) a mental visualization group. On a 100-point pain perception scale, baseline pain levels were similar across all three groups. After four weeks of 15-minute daily sessions attempting to perform movements with the amputated limb in congruence with the movement of the unaffected limb, 100% of the participants in the mirror therapy group reported a significant reduction in phantom limb pain (about -24 points on average). 17% of the participants in the covered mirror group reported a decrease in phantom limb pain, but 50% of subjects in this group reported an increase in pain. 33% of the subjects in the mental visualization group reported a decrease in pain, while 67%
  3. 3. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 3 reported an increase in phantom limb pain. Additionally, after the initial 4-week trial was completed, 9 of the participants in the covered mirror or mental visualization groups switched to using mirror therapy, and 8 of these subjects (89%) reported a decrease in phantom limb pain after an additional 4-weeks of mirror visual feedback treatment.9 An interesting application of mirror therapy tested by Hanling et. al. in 2010 suggested the use of pre-operational mirror therapy to reduce phantom limb pain following amputation. Four men in the armed forces preparing for lower limb amputation participated in the study. Each subject had participated in numerous limb reconstruction surgeries prior to the decision to amputate, placing the four subjects at a very high risk of developing phantom limb pain after amputation. 14 sessions of mirror therapy were completed by each of the four subjects before amputation. After amputation, one subject reported no phantom limb pain at all, two experienced rare episodes of mild phantom limb pain, and one reported daily, brief episodes of moderate phantom limb pain. None of the participants felt their phantom limb pain interfered with their quality of life or ability to participate in physical therapy post- operation. The benefits of preemptive mirror therapy are further supported by the idea that each of the subjects should have experienced high levels of phantom limb pain based on pre-operative limb pain.15 Mirror therapy for stroke recovery Mirror therapy has been utilized for a number of years in the treatment of individuals who have suffered from motor impairments following a stroke. In 1995, Bronner et. al. defined the word “stroke” to encompass a variety of blood brain barrier interruptions resulting in death of the neuronal tissue of the brain, including ischemic stroke (lack of oxygen to the brain), intracerebral hemorrhage (bleeding within neruronal tissue of the brain), and subarachnoid hemorrhage (blood within the subarachnoid space).4 A 2014 study by Samuelkamaleshkumar et. al. used three different measures of motor recovery to grade a post-stroke mirror therapy group versus a control group following a stroke to determine the outcomes for the use of mirror therapy as a modality of treatment for stroke sufferers. The three measures used by the researchers were: (1) the Fugl-Meyer Assessment (FMA) for testing shoulder, elbow, wrist and hand motor recovery following a stroke on a point scale from 0 to 66 (based on the sum of individual subsections); (2) the Brunnstrom stages of motor recovery, a motor recovery assessment consisting of six sequential stages that must be accomplished in order; and (3) the Box and Block test (BBT) which consists of moving blocks from one box to another divided by a wall and measures dexterity based on the number of blocks moved per.25 The participants completed 30, 15- minute mirror box sessions spanning 3 weeks time (2 sessions per day, 5 days per week, 3 weeks duration) consisting of observing their unaffected limb move, stretch, and perform simple tasks like grabbing small objects or writing their name. Following the mirror visual feedback therapy, participants in the mirror therapy group improved their Fugl-Meyer scores from 9.7 to 30.8 on average, while the control group improved from 4.3 to 8.8. Participants in the mirror group went from reaching stage 2.5 to stage 4.5 on average in arm recovery and from stage 1.6 to stage 3.2 in hand recovery. The control group improved from stage 1.7 to stage 2.6 in the arm recovery measurement, and from stage
  4. 4. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 4 1.1 to stage 1.5 in hand recovery. Finally, the mirror therapy group went from moving 1.1 blocks per minute to 6.6 blocks per minute in the BBT test, while the control group improved from 0 blocks per minute to 0.7 blocks per minute on average.25 Though both the control and mirror therapy groups saw improvement in the categories they were tested in using the measurements the researchers used, it is clear that motor recovery using mirror therapy was accelerated as compared to recovery without mirrors, speedy improvement necessary to getting an individual back to a functioning and independent lifestyle as quickly as possible. Mirror therapy for chronic regional pain syndrome (CRPS) Complex regional pain syndrome encompasses several different pain disorders including reflex sympathetic dystrophy, causalgia, and algodystrophy. Clinical characteristics include sensory and motor disturbances, changes in vascular tone and temperature, and pain seemingly disproportionate to the insult.20 A 2003 study by McCabe et. al. determined the potential use of mirror therapy for treating CRPS type 1, which occurs either spontaneously or following trauma and is not associated with peripheral nerve damage as CRPS type 2 is. Of the 8 participants who began the study, 5 completed the study all the way through. During the initial assessment, each participant completed a routine of movement consisting of two control trials using a non-reflective surface and one test trial using a reflective surface to view their functioning limb and its reflection. Each participant graded their pain on a scale of 0 to 10, with zero being no pain at all and ten being the greatest amount of pain imaginable, at the beginning of the first session and at the end. Following the first session, the participant was asked to complete mirror therapy at home as often as desired with sessions lasting no longer than 10 minutes in order to maintain concentration. At the beginning of the first session, participants reported an average pain rating at rest of 7.2 on a 10-point scale. Following mirror therapy during the first session, participants reported a decrease in pain, reporting a pain rating of only 3.2 on average. Additionally, after completing a 6- week mirror therapy regimen, participants reported an average pain rating of 0.6 at rest on a 10-point scale.20 Mirror therapy for fibromyalgia Fibromyalgia is a disorder of unknown etiology characterized by chronic widespread pain, muscle and joint tenderness upon palpation, sleep disturbance, fatigue, morning stiffness and depression. The American College of Rheumatology criterion for the diagnosis of fibromyalgia consists of pain within all four quadrants of the body, as well as tenderness upon palpation of at least 11 of 18 specific points.27 Mirror therapy as a possible treatment for fibromyalgia is based on the use of mirrors to create a body image illusion and the feeling of “standing outside oneself”.2 Evidence suggests such dissociative states are evolutionary adaptive mechanisms to disconnect the physical sensation of pain from the emotional state of “being in pain”.22 In a study conducted by Ramachandran and Seckle, a subject who suffered from lower limb pain caused by fibromyalgia was placed in front of a mirror arrangement that allowed her to see the reflection of her left leg in a far mirror and a superimposed image of her left leg (appearing as her right leg) in a second, perpendicular mirror. By lifting her left leg with her right leg grounded though not
  5. 5. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 5 visible, the subject experienced the feeling of floating and weightlessness, immediately decreasing the sensation of pain in her left leg. After 15 30-second trials, with 5 minutes of rest between each, the subject reported a reduction of pain from an average of 8.00 to 4.93 on a 1-10 point scale. A placebo study in which both the left and right legs were visible reported pain reduction from 8.00 to 7.33 on average, indicating the efficacy of mirror therapy and body image illusion on reducing the pain associated with fibromyalgia.24 Mirror therapy for joint mobility and pain reduction Based on M. MacLachlan’s theory that mirror therapy may decrease phantom limb pain due to an amputee’s ability to control his phantom limb, others have applied the idea of immobile joint control aided by mirrors to conditions that limit joint range of motion.19 Altschuler and Hu’s evidence regarding the benefits of mirror therapy in the restoration of range of motion in a woman recovering from a severe wrist fracture and resulting surgeries is outlined in a 2008 study on the topic. A 39–year-old woman slipped on ice in February of 2006, severely fracturing her left distal radius. Following surgery and a bone graft in early April, her plaster cast was removed in mid-May of 2006, at which point she was able to begin physical therapy. Upon presentation, she complained of extreme stiffness and pain in the joint, and both her active and passive wrist flexion and extension were 0°. A week of traditional physical therapy increased passive wrist extension to 20°, but she was still unable to actively extend the wrist. Mirror therapy as a modality for her wrist recovery was introduced to the patient in early June. A combination of electrical stimulation and mirror therapy at an outpatient occupational therapy facility for 15 minutes two to three times a week, as well as 15 minute bouts of mirror therapy alone at home five to six times a week increased her active extension of the wrist to 25° by early July 2006. After five additional weeks of mirror therapy, her active wrist extension was 30°, and by the time she was discharged from therapy in mid-August 2006, she could actively extend the wrist to 35° and actively flex the wrist to 80°. By viewing the active flexion and extension of her healthy right wrist in a mirror on a regular basis, over time the patient restored active control of her left wrist.1 A second study by Mohamed and Wong utilized mirror therapy in the treatment of a young girl with recurring right ankle sprains following a motor vehicle accident. Using traditional ankle sprain treatment, including strength exercises like ankle circles, ankle pumps, and step downs, as well as balance exercises like heel and toe raises, the patient reported a worsening in pain between pre- and post-treatment evaluation following two sessions of physical therapy. Mirror therapy was introduced during the third session of physical therapy. The patient was told to observe her left leg in the mirror and consciously imagine the reflection was her right leg performing the exercises in unison with her left. A home program involving mirror therapy and motor imagery was also prescribed, with the patient performing both twice a day. Following 3 sessions of mirror therapy treatment and adherence to the home program, the patient reported a pain rating of 1 on a 1-10 point scale at the beginning of the fifth session, and a pain rating of 0 at the end of the fifth session.21 Despite the fact that each of the studies discussed used only one participant, each provides strong evidence regarding mirror therapy utilization for increasing joint
  6. 6. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 6 mobility and decreasing pain in chronic ankle sprains. Mirror therapy for children with spastic hemiparesis Spastic hemiparesis is classified as a secondary effect of neural defect or injury (such as cerebral palsy, traumatic brain injury or cerebrovascular insult) and is characterized by excessive muscle contraction in an otherwise paralyzed limb. Over time, and especially in young children, the contractions can lead to muscular imbalance, bony torsional abnormalities and joint instability.3 Gygax, Schneider and Newman first described the use of mirror therapy in children with spastic hemiparesis in their 2011 publication “Mirror therapy in children with spastic hemiplegia: a pilot study”. Ten participants suffering from spastic hemiparesis aged 6 to 14 years were selected for the study, and each was taught a series of three symmetric upper limb exercises to be completed over 15-minutes daily at home. The ten participants were then divided randomly into two groups of five participants each. One group participated in 3 weeks of completing the exercises in a mirror, followed by 3 weeks of exercising without a mirror, while the opposite group started without a mirror and ended using mirrors for their exercise routine.14 Following the 6-week trial, maximal grip strength of the paretic hand increased on average by 23.4% (from 16.2 kPa to 20.0 kPa) between all ten participants, with the most improvement occurring during the period in which the child was using mirrors to complete their exercises. Additionally, improvement was documented in all three categories of evaluation of the Shriner’s Hospital for Children Upper Extremity Evaluation (SHUEE), an assessment for children with cerebral palsy that measures: (1) the spontaneous use of the paretic extremity; (2) the position of the limb during execution of specific tasks; and (3) the ability to perform grasp and release tasks.10 Theories on mechanisms by which mirror therapy affects the brain Though the mechanisms by which mirror therapy works within the brain are not completely clear or well understood, for the most part, studies on the effect of mirror therapy can be sorted under three main hypotheses: (1) mirror therapy activates networks dedicated to attention and action monitoring on the cortex of the brain; (2) mirror therapy utilizes mirror neuron systems the mediate connections between perceptual and motor areas of the brain; and (3) mirror therapy stimulates motor areas contralateral to the affected limb and may even utilize dormant ipsilateral motor pathways.11 In support of the first hypothesis, a variety of information suggests that mirror therapy may affect perceptuo-motor control processes in three main functional networks of the brain, with the first functional network being the insular cortex. The insular cortex is a division of the cerebral cortex, which functions in developing an individual’s sense of consciousness via perception, motor control, and self- awareness.12 In 2002, Farrer et. al. determined marked activity in the insular cortex could be attributed to a conscious awareness of visual feedback, as well as a feeling of control over ones actions.12 The second important brain region activated by mirror therapy is the posterior cingulate cortex, which is highly connected to a variety of brain centers and believed to be important center for cognitive control of behavior.18 Finally, mirror therapy activates the precuneus of the posterior parietal cortex, a region of the brain often associated
  7. 7. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 7 with motor imagery.7 The combination of an increased sense of self-awareness via activation in the insular cortex, cognitive control over behavior via activity in the posterior cingulate cortex, and motor imagery in the precuneus all suggest the utilization of cortical regions of the brain during mirror visual feedback therapy. The theory that mirror visual feedback activates mirror neurons in the brain can be derived from a number of studies involving two hypothesized mirror neuron pathways in the brain. The first mirror neuron pathway is found in the superior temporal gyrus, a region attributed to visual identification of biological movement.26 The second mirror neuron pathway is the pontine micturition center, an area of the brain found to be active during imitation of biological movement and motor learning.5 Activation in each of these brain centers suggests the method by which mirror visual feedback not only allows an individual to identify a specific movement being performed by a functional limb, but also attempt to imitate and complete a similar movement in a non- or low functioning limb. The final functional network utilized by mirror visual feedback is the primary motor cortex (abbreviated M1) ipsilateral to the affected limb. In a healthy individual, the M1 contralateral to the limb being used controls the movement of that limb, i.e. the movements of the left arm are controlled by the right primary motor cortex. Additionally, in a healthy individual, though some ipsilateral control of movement maybe present, it is inhibited by the contralateral motor cortex to prevent overlapping of signals and motor commands being sent to the limbs. During mirror visual feedback therapy, however, ipsilateral control of motor information is no longer inhibited, allowing bilateral movements to be duplicated on each side of the body.6 For example, if the left arm is affected, the motor threshold required to produce ipsilateral movement in the left arm is reduced, and motor function from the left M1 that creates movement for the right arm could also be used to create symmetrical movement in the left affected arm. Possible future directions for mirror therapy as a treatment modality Mirror therapy seems to work best for unilateral disorders and injuries, as it is necessary to have a healthy, well- functioning limb to observe in order to improve pain, mobility, control, etc. in the non-functioning limb. This being said, mirror therapy could surely be an inexpensive treatment for individuals who have undergone surgery. The illusion of a functional limb following surgery could aid in speeding the recovery of an limb post- operation. Preemptive mirror therapy may also aid in reducing the amount of time necessary before an individual could begin a physical therapy or occupational therapy treatment plan. Mirror therapy might also relieve symptoms of osteoarthritis via means similar to those utilized in the treatment of fibromyalgia. The illusion of floating or being weightless could give the illusion of the relief of pressure on the joints and alleviate the pain associated with the disorder. Citations 1 Altschuler EL, Hu J. Mirror therapy in a patient with a fractured wrist and no active wrist extension. Scand. J. Plas. Recon. Surg. & Hand Surg. 2008; 42(2): 110-111. 2 Altschuler EL, Ramachandran VS. A simple method to stand outside oneself. Perception. 2007; 36(4): 632-634.
  8. 8. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 8 3 Boyd RN, Graham HK. Botulinum toxin A in the management of children with cerebral palsy: indications and outcome. Eur. J. Neurol. 1997; 4:15-22. 4 Bronner LL, Kanter DS, Manson JE. Primary prevention of stroke. N. Engl. J. Med. 1995; 333: 1392-1400. 5 Buccino G, Solodkin A, Small SL. Functions of the mirror neuron system: implications for neurorehabilitation. Cogn. Behav. Neurol. 2006; 19: 55-63. 6 Carson RG, Ruddy KL. Vision modulates corticospinal suppression in a functionally specific manner during movement of the opposite limb. J. Neurosci. 2012; 32: 646-652. 7 Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006; 129(3): 564-583. 8 Chahine L, Kanazi G. Phantom limb syndrome: a review. M. E. J. Anesth. 2007; 19(2): 345-356. 9 Chan BL, Witt R, Charrow AP, Magee A, Howard R, Pasquina PF, Heilman KM, Tsao JW. Mirror therapy for phantom limb pain. N. Engl. J. Med. 2007; 357: 2206-2207. 10 Davids JR, Peace LC, Wagner LV, Gidewall MA, Blackhurst DW, Roberson WM. Validation of the Shriner’s Hospital for Children Upper Extremity Evaluation (SHUEE) for children with spastic hemiplegic cerebral palsy. J. Bone Joint Surg. Am. 2006; 88: 326-333. 11 Deconinck FJA, Smorenburg ARP, Benham A, Ledebt A, Feltham MG, Savelsbergh GJP. Reflections on mirror therapy: a systematic review of the effect of mirror visual feedback on the brain. Neurorahabil. Neural Repair. 2014; 1- 13. 12 Farrer C, Frith CD. Experiencing oneself vs another person as being the cause of an action: the neural correlates of the experience of agency. Neuroimage. 2002; 15: 596-603. 13 Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neuro. 2002; 1(3): 182-189. 14 Gygax MJ, Schneider P, Newman CJ. Mirror therapy in children with hemiplegia: a pilot study. Develop. Med. & Child Neurol. 2011; 53: 473-476. 15 Hanling SR, Wallace SC, Hollenbeck KJ, Belnap BD, Tulis MR. Preamputation mirror therapy may prevent development of phantom limb pain: a case series. Anesthes. & Analgesia. 2010; 110(2): 611-614. 16 Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain. 1983; 17(3): 243-256. 17 Jensen TS, Krebs B, Nielsen J, Rasmussen P. Immediate and long-term phantom limb pain in amputees: incidence, clinical characteristics and relationship to pre-amputation limb pain. Pain. 1985; 21(3): 267-278. 18 Leech R, Braga R, Sharp DJ. Echoes of the brain within the posterior cingulate cortex. J. Neurosci. 2012; 32: 215-222. 19 MacLachlan M, McDonald D, Waloch J. Mirror treatment of lower limb phantom pain: a case study. Disabil. Rehabil. 2004; 26(14-15): 901-4. 20 McCabe CS, Haihj RC, Ring EFJ, Halligan PW, Wall PD, Blake DR. A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1). Rheumatology. 2003; 42: 97- 101. 21 Mohamed M, Wong CK. More than meets the eye: clinical reflection and evidence-based practice in an unusual case of adolescent chronic ankle sprain. J. Amer. Phys. Ther. Assoc. 2011; 91(9): 1395-1402.
  9. 9. The uses of mirror therapy and theories of mechanisms regarding its effects on the brain 9 22 Ramachandran VS, Blakeslee S. Phantoms in the Brain: Probing the Mysteries of the Human Mind. New York: William Morrow; 1998. 208 p. 23 Ramachandran VS, Rogers- Ramachandran D. Synaesthesia in phantom limbs induced with mirrors. Proc. R. Soc. Lond. B. 1996; 263(1369): 377-386. 24 Ramachandran VS, Seckle EL. Using mirror visual feedback and virtual reality to treat fibromyalgia. Med. Hypot. 2010; 75(6): 495-496. 25 Sameulkamaleshkumar S, Reethajanetsureka S, Pauljebaraj P, Benshamir B, Padankatti S, David JA. Mirror therapy enhances motor performance in the paretic upper limb following stroke: a pilot randomized control study. Arch. Phys. Med. and Rehab. 2014; 95(11): 2000-2005. 26 Schultz J, Imamizu H, Kawato M, Frith CD. Activation of the human superior temporal gyrus during observation of goal attribution by intentional objects. J. Cogn. Neurosci.. 2004; 16: 1695-1705. 27 Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, Mccain GA, Reynolds WJ, Romano TJ, Russell IJ, Sheon RP. The american college of rheumatology 1990 criteria for the classification of fibromyalgia. Arth. & Rheum. 1990; 33(2): 160-172.

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