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research-article2014
NNRXXX10.1177/1545968314546134Neurorehabilitation and Neural RepairDeconinck et al

Clinical Research Article


Neurorehabilitation and

Reflections on Mirror Therapy:


Neural Repair
2015, Vol. 29(4) 349­–361
© The Author(s) 2014
A Systematic Review of the Effect of Reprints and permissions:
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Mirror Visual Feedback on the Brain DOI: 10.1177/1545968314546134


nnr.sagepub.com

Frederik J. A. Deconinck, PhD1,2, Ana R. P. Smorenburg, PhD3,


Alex Benham, PhD4, Annick Ledebt, PhD5, Max G. Feltham, PhD6,
and Geert J. P. Savelsbergh, PhD5

Abstract
Background. Mirror visual feedback (MVF), a phenomenon where movement of one limb is perceived as movement of
the other limb, has the capacity to alleviate phantom limb pain or promote motor recovery of the upper limbs after
stroke. The tool has received great interest from health professionals; however, a clear understanding of the mechanisms
underlying the neural recovery owing to MVF is lacking. Objective. We performed a systematic review to assess the
effect of MVF on brain activation during a motor task. Methods. We searched PubMed, CINAHL, and EMBASE databases
for neuroimaging studies investigating the effect of MVF on the brain. Key details for each study regarding participants,
imaging methods, and results were extracted. Results. The database search yielded 347 article, of which we identified 33
suitable for inclusion. Compared with a control condition, MVF increases neural activity in areas involved with allocation
of attention and cognitive control (dorsolateral prefrontal cortex, posterior cingulate cortex, S1 and S2, precuneus). Apart
from activation in the superior temporal gyrus and premotor cortex, there is little evidence that MVF activates the mirror
neuron system. MVF increases the excitability of the ipsilateral primary motor cortex (M1) that projects to the “untrained”
hand/arm. There is also evidence for ipsilateral projections from the contralateral M1 to the untrained/affected hand as a
consequence of training with MVF. Conclusion. MVF can exert a strong influence on the motor network, mainly through
increased cognitive penetration in action control, though the variance in methodology and the lack of studies that shed light
on the functional connectivity between areas still limit insight into the actual underlying mechanisms.

Keywords
systematic review, sensorimotor control, visual feedback, mirror, hemiparesis, stroke, cerebral palsy

Introduction reflection of the limb in front of the mirror is superimposed


on the contralateral limb. Any motion of the limb in front of
Often a source of fascination, or perhaps frustration, optical the mirror induces the illusion of 2 synchronously moving
illusions have captivated people since ancient times. For limbs. After Ramachandran and his colleagues found that
instance, curved surfaces and the absence of right angles in this illusion could alleviate phantom pain in a proportion of
archaic Greek temples suggest that its architects attempted the patients,3 mirror visual feedback (MVF) was introduced
to optically correct the illusion of slanted columns or curved as a neurorehabilitation tool to treat other unilateral pain
tympanums; however, others believe these features may
serve engineering purposes or reflect aesthetic preference.1
As much as they are a source of excitement, for neuroscien- 1
Ghent University, Ghent, Belgium
2
tists optical illusions are considered a backdoor into peo- Manchester Metropolitan University, Manchester, UK
3
ple’s mind and provide an excellent way to study the neural Burke-Cornell Medical Research Institute, White Plains, NY, USA
4
Bradford Institute for Health Research, Bradford, UK
mechanisms underlying perception and action.2 5
VU University, Amsterdam, Netherlands
Interestingly, although optical illusions are known to 6
University of Birmingham, Birmingham, UK
deceive the individual, the false reality may fool the brain,
such that the outcome is beneficial. One such an illusion is Corresponding Author:
Frederik J. A. Deconinck, Ghent University, Faculty of Medicine and
the mirror illusion, which has been found to have therapeu- Health Sciences, Department of Movement and Sports Sciences,
tic benefits over the past 2 decades. When a mirror is placed, Watersportlaan 2, Gent 9000, Belgium.
along the midsagittal plane in between the 2 limbs, the Email: Frederik.Deconinck@UGent.be
350 Neurorehabilitation and Neural Repair 29(4)

disorders, such as complex regional pain syndrome (CRPS). leg amputated. The goal of MVF is to restore the efference–
In addition, the paradigm is now used to promote motor afference loop that has been interrupted. MVF of the intact
recovery (eg, in hemiparetic patients or after hand limb deceives the individual and elicits the awareness that
surgery). the amputated limb is still intact, not at least due to the dom-
Despite its widespread use in neurorehabilitation and inance of the visual system over other modalities.8,9 Indeed,
the claims that MVF therapy would lead to neuroplastic when the illusion was tested in arm amputees with com-
changes, there is no consensus about the underlying mech- plaints of “clenching spasms” and phantom limb pain, the
anism and speculation often lacks the neuroscientific proof. spasms were eliminated and the pain was relieved immedi-
The aim of this review is therefore to bring together current ately after exposure to MVF in a proportion of the
knowledge on the effect of MVF on the brain as has been sample.3
described in neuroimaging studies, in order to explore The novelty and simplicity of the idea, in combination
potential processes underlying the beneficial clinical with the far-reaching potential of MVF, prompted clinicians
effects of MVF. To acquaint the reader with MVF and its and researchers to replicate the initial findings of
current applications, we will first revisit Ramachandran’s Ramachandran and colleagues. Consistent with the earlier
rationale for MVF, followed by a narrative review of the observations, follow-up studies have confirmed that MVF
clinical neurorehabilitation research that followed in his treatment has the capacity to reduce phantom limb pain
footsteps. At the end of this section, we introduce 3 hypoth- intensity and duration.10,11 Moreover, the notion that many
eses that have been proposed to explain the positive effects neurological disorders with unilateral pain and motor symp-
related to MVF. Part 2 provides a systematic review and toms may be (partly) caused by maladaptive cortical reorga-
discussion of studies that examined the effect of MVF on nization involving a disruption of the efference–afference
brain activation patterns using neuroimaging or electro- loop, led others to apply MVF to a wide range of conditions.
physiological techniques. Finally, in Part 3 we discuss the Hemiparesis after stroke is perhaps the most striking exam-
findings of the systematic review in relation to the hypoth- ple. In a proportion of the patients the paresis is thought to
eses introduced in Part 1 and we identify where further be a form of “learned paralysis” due to a nonpermanent
research is required. blocking of corticofugal fibers by swelling after the
trauma.12 A recent Cochrane Review exploring the effec-
tiveness of MVF therapy in patients after stroke (13 ran-
Part 1: Mirror Therapy—Background, domized controlled trials, 506 patients) concluded that
Current Applications, and Potential mirror therapy indeed might be more effective in promoting
Mechanisms motor function than a control intervention† when used as an
The idea of using MVF for the management of phantom adjunct to conventional therapy.13 Furthermore, the meta-
limb pain was inspired by early findings on the integration analysis indicated that the effects were retained, up to 6
of perception and action, in particular the principle of reaf- months after the intervention, and that MVF therapy had a
ference.4,5 Reafference is afferent sensory information significantly greater effect than control interventions on
caused by a motor command (eg, signals from muscle spin- activities of daily living and on pain, though the latter was
dles in M. biceps brachii when the arm is actively flexed), found only in a subgroup with CRPS after stroke.
as opposed to exafferent information, which results from To date, MVF is administered to treat various unilateral
factors outside the individual (eg, signals from muscle spin- pain and/or motor disorders, including CRPS,14-18 hemipa-
dles in M. biceps brachii when the arm is flexed passively). resis after stroke,19,20 reduced mobility after wrist fracture,21
To distinguish between these 2 sensory stimuli, it is main- and spastic hemiparetic cerebral palsy (SHCP).22,‡ The find-
tained that the generation of a motor command is accompa- ings of these studies tend to corroborate the initial work,
nied by a parallel signal, termed efference copy, which that is, a reduction in pain and improvement in motor func-
contains the sensory feedback to be expected due to this tion. Still, it should be noted that publication bias toward a
command. Comparison of all afferent signals with the effer-
ence copy provides a way to separate signals that originate
from bodily movements and those from outside the indi- *In their recent review article, Ramachandran and Altshuler9 rec-
ognize that the origin of phantom pain is still poorly understood
vidual. As a consequence, motor commands that are not
and may be related to other factors, for example, persistence of
instantaneously followed by the expected reafferent feed-
preamputation pain and pathological “remapping” among others
back will be modified in an attempt to evoke the expected (see also Ramachandran and Hirstein6). The rationale to use MVF,
sensory afference.5 It is this conflictive state that, according however, is based on the notion of a mismatch between motor out-
to some,6,7 may evolve into a form of “learned paralysis” put and visual and/or proprioceptive feedback.
accompanied by a feeling of painful spasms,* as experi- †
The effect of MVF therapy was significantly larger than control
enced by a proportion of patients who have had an arm or interventions.
Deconinck et al 351

selection of positive results may be likely and additional Second, MVF might promote recruitment of ipsilateral
placebo-controlled studies are needed for all conditions or motor pathways.30 These motor pathways, originating in the
symptoms. In this respect, it is worth mentioning that unaffected hemisphere and projecting ipsilaterally to the
Brodie et al found that the attenuating effect of MVF on paretic body-side, have been attributed a nontrivial role in
pain was not stronger than a control condition in lower limb the restoration of motor function in hemiparesis.31-34 It is
amputees.23 hypothesized that MVF might facilitate the unmasking of
Despite the fact that there appear to be parallels in the “dormant” ipsilateral projections, which are normally inhib-
pathophysiology of unilateral pain and motor disorders as ited (Hypothesis 2).
described by Ramachandran and Altschuler,12 the 2 phe- Finally, MVF or the associated illusion is thought to
nomena should be considered separately, hence the focus of increase an individual’s (spatial) attention toward the
this review will be on the effects of MVF on sensorimotor unseen (affected) limb.35 It is known that hemiparetic
control. To fully exploit the potential of MVF, a better patients may end up in a state of “learned nonuse,” by con-
insight into the processes that underlie the beneficial effects tinuously avoiding the use of the paretic hand or by patho-
on motor function is required. Not only would this knowl- physiological disruption of the efference–afference loop.36
edge advance our theoretical understanding of the brain, it In keeping with the rationale for using constraint-induced
may also provide guidelines as to when MVF may be useful movement therapy,36 the increased attention toward the
and how it should be applied. affected limb, mediated by the illusory image of a “healed”
When the individual is required to perform bilateral, paretic limb, may activate motor networks (Hypothesis 3).
symmetrical motor tasks, MVF therapy may be considered In sum, an increasing body of evidence underpins the
a special form of bilateral training, and hence exploit simi- potential of MVF to facilitate recovery of motor function.
lar mechanisms (see Cauraugh and Summers for a Still, the neural mechanism of MVF, whether the behavioral
review24). However, in search of the added value of MVF effect is accompanied by neuroplastic changes, and what
researchers have invoked 3 (not mutually exclusive) this reorganization would involve is unclear. The hypothe-
hypotheses to account for the positive effects of MVF on ses invoked to explain MVF effects are based on known
motor recovery. A first hypothesis relates to the mirror concepts in neurorehabilitation, but they remain specula-
neuron system.17,19,20 Mirror neurons fire both when an tive. Recent experimental neuroimaging research has begun
individual observes an action and when he/she performs a to reveal the extent of brain activation during movement
similar action. The network, including the premotor cor- with MVF, and its modulatory effects on brain processes
tex, supplementary motor area, inferior frontal gyrus, and compared with normal visual conditions. In the following
inferior parietal lobule of the brain, is thought to play an part of this article, the findings of these studies will be sys-
important role in action recognition and motor learning or tematically reviewed. This will serve as a validity test of the
rehabilitation.25 An observation/execution matching proposed hypotheses.
mechanism, whereby action observation activates crucial
parts of the motor system, is hypothesized to induce motor
Part 2: The Neural Correlates of
learning.25,26 It is known that action observation facilitates
the corticospinal pathway and this paradigm is already Mirror Visual Feedback
used in neurorehabilitation as mental practice aimed at Purpose
improving motor function.27 According to this hypothesis,
a “mirror box” is a means to facilitate action observation The purpose of this systematic review was to identify the
and therefore MVF is thought to activate the mirror neu- areas in the brain that are differentially affected or modu-
ron system in a similar way to action observation lated by MVF compared with a condition with normal or
(Hypothesis 1). In line with this is the notion that MVF without visual feedback.
may elicit or enhance motor imagery,28 that is, internal
simulation of movement without overt action. Just like Literature Search
action observation motor imagery has been attributed ther-
apeutic capacities because it activates neural circuits A literature search using the electronic databases PubMed,
involved in motor control.29 CINAHL, and EMBASE (1972 to January 2014) was con-
ducted. Search terms included “mirror therapy” or “mirror
visual feedback” combined with “functional magnetic reso-

See Ramachandran and Altschuler9 for a list of clinical cases nance imaging (fMRI),” “positron emission topography
where the use of MVF has been observed informally but has not (PET),” “transcranial magnetic stimulation (TMS),” “mag-
been described in the literature. netoencephalography (MEG),” “electroencephalography
352 Neurorehabilitation and Neural Repair 29(4)

Search of bibliographic databases:


PubMed, CINAHL, EMBASE
+
Personal database

Outcome N = 347
Databases: N = 341 records
Personal databases: N = 6 records
Main reasons for exclusion:
1st stage screening of titles - Methodology did not
and abstracts by 2 involve MVF
independent reviewers - Methodology did not
involve neuroimaging
N = 41 records
Main reasons for exclusion:
2nd stage screening of full - Neuroimaging only for
texts by 2 independent diagnostic purposes, not
reviewers for measuring effect MVF
(N = 2)
Final selection: - Effect of MVF on pain or
N = 33, including 12 fMRI, 9 TMS, 5 MEG, 4 EEG, 2 tactile perception, not
PET, and 2 NIRS motor control (N = 4)
- See Supplementary
Material for details.

Figure 1.  Flow diagram of the article selection process.

(EEG),” or “near infra-red spectrometry (NIRS).” In addi- Results


tion, we checked our personal database and the reference
list of included articles. Our search was restricted to peer- The electronic database search yielded 347 unique articles,
reviewed full articles written in English. of which 33 were deemed eligible for this systematic review
Inclusion criteria were the following: (see Figure 1 for an overview of the selection process).
Across the selected articles, the most commonly used scan-
•• Experimental studies or clinical trials ning technique was fMRI (12 studies).37-47 MEG was the
•• Normal and/or motor-impaired human participants neuroimaging modality in 5 article,48-52 EEG in 4,53-56 PET
•• Use of neuroimaging techniques (fMRI, PET, MEG, in 2,57,58 and NIRS in 2.59,60 Nine studies investigated the
EEG, NIRS) or TMS to study the effect of MVF* on effect of MVF on cortical activation with TMS47,61-68; 1
cortical activation (and related motor performance or study used both TMS and fMRI.47 In Tables 1 to 4, the
perceptual measures) included articles and their methodologies are listed accord-
ing to modality. The majority of the studies (n = 27) exam-
Exclusion criterion was the following: ined immediate modulatory effects when exposed to MVF,
of which 22 focused on healthy individuals and 5 on stroke
•• Studies that do not assess effect of MVF on senso- patients (Tables 1-3). In 16 studies, MVF was provided in
rimotor control, but focus on pain and/or tactile a bilateral fashion, that is, not obscuring the active hand.
perception. Six studies assessed neuroplastic changes in response to a
bout of practice or an intervention in healthy individuals (n
The records identified by this search were screened inde- = 3) or stroke patients (n = 3). Here, bilateral MVF was
pendently by 2 authors of this systematic review (FD and used in all but one study (Table 4 and Supplementary
AS) in 2 stages: a first stage screening of titles and abstracts Material). The variance in methodology and motor task,
and a second stage using the full text of the remaining which may be unilateral or contralateral, complicates the
article. The lists of eligible articles identified by the indepen- overall interpretation of the observations. A factor that
dent reviewers were compared, and any disagreements were
resolved through discussion (and referral to the text of the *Mirror visual feedback could be induced by a real mirror or using
articles in question). a virtual reality environment.
Deconinck et al 353

Table 1.  Outline of the Methodology, Type of MVF, Measures to Avoid Systematic Variation in Movement Across Conditions, and
Known Potential Confounds in All Experimental Studies Using fMRI Included in the Systematic Review.
Outline of Experimental Methodology Relevant to (a) Measures to Avoid Systematic
Study Reference Participants This Review Type of MVF Variation (b) Potential Confounds

Diers et al (2010)37 9 healthy individuals aged Repetitive clenching of the fist at dominant side Bilateral (a) Metronome paced
51.9 ± 6.9 with (1) normal VF, (2) MVF of active hand, or (b) No statistical comparison
(3) during motor imagery between conditions
Dohle et al (2004)38 6 healthy individuals aged Static condition vs finger-thumb opposition with Unilateral (a) Metronome paced
29.0 ± 1.5 (1) virtual VF of hand; (2) virtual MVF of hand
Fritzsch et al (2013)39 15 healthy individuals aged Unilateral index finger-thumb opposition of either Unilateral (a) Metronome paced
22-56 left or right hand with (1) virtual VF, (2) virtual
MVF
Matthys et al (2009)46 18 healthy individuals aged Tapping right index finger with (1) VF active hand; Bilateral (a) None
22-48 (2) MVF active hand
Merians et al (2009)47 3 healthy individuals aged 26.8 and Finger tapping right hand with (1) virtual VF active Unilateral (a) None
1 stroke patient aged 70.0 hand; (2) virtual MVF active hand (b) Lack of control condition
Michielsen et al (2011)40 18 stroke patients aged Unimanual (nonaffected hand) and bimanual Bilateral (a) Metronome paced
54.7 ± 9.9 clenching movement with (1) VF; (2) MVF
Shinoura et al (2008)41 5 healthy individuals aged 21-57 and Unimanual and bimanual clenching of hand(s) with Bilateral (a) None
2 patients with brain tumor aged (1) eyes closed; (2) MVF of (one of the) active (b) No statistical comparison
47 and 67 hand(s) between conditions
Wang et al (2013)42 15 healthy individuals aged Movement performance task: Unilateral index Unilateral (a) Number of repetitions
22-56 finger-thumb opposition of either left or right counted post hoc
hand with (1) virtual VF, (2) virtual MVF.
Movement observation task: Observation of
similar action on video
Wang et al (2013)43 15 healthy individuals aged 22-56 Unilateral index finger-thumb opposition of either Unilateral (a) Number of repetitions
and 5 stroke patients aged 50-72 left or right hand with (1) virtual VF, (2) virtual counted post hoc
MVF

Abbreviations: MVF, mirror visual feedback; VF, normal visual feedback. Bilateral MVF, active hand and its mirror reflection; Unilateral MVF, MVF of active hand only. MVF
was generated by a mirror placed in between the arms in the sagittal plane, except when stated otherwise.

adds to this difficulty is the absence of a standard control somatosensory areas, as well as higher order processing
condition. In some studies, MVF is contrasted with normal areas in the occipital and parietal cortex ipsilateral to the
full vision of the 2 limbs, whereas in others visual feedback moving limb.38,39,42,43,46,60 In fact, the mirror inverts the lat-
of the active or static limb only is used as a control. eralization that is normally associated with the presentation
Furthermore, to isolate the effect of MVF on brain activa- of a right or left hand in these regions. Note, however, that
tion it is crucial to keep the movement (range, frequency, these observations stem from studies that contrasted virtual
intensity) constant across MVF and control conditions, MVF of the active hand with virtual VF displayed in the
which a number of studies have failed to do or to control frontal plane (on a screen or onto MRI-compatible goggles).
for (see Table 1-4 for details). Other studies show increased activation in the right dorso-
lateral prefrontal cortex (DLPFC),58 the contralateral sec-
Instant Neuromodulatory Effects of MVF.  The neuromodula- ondary sensory cortex (SII),51 the ipsilateral superior
tory effects of MVF refer to changes in activity or excitation temporal gyrus (STG),46 and the contralateral insular
that are evoked by MVF, that is, revealed by direct compari- cortex.52,57
son of MVF with a control condition (listed in Table 5). Finally, MVF modulates activity of the primary motor
MVF evokes a conflict between expected and actual feed- cortex, both ipsilateral and contralateral to the active hand
back (cognitive conflict) and between visual and kinaes- reflected into the mirror, though the findings are somewhat
thetic feedback (perceptual conflict). This conflict is most inconsistent. The majority of the studies suggest an increase
obvious when performing unimanual or asymmetric biman- in ipsilateral M1 excitability or increased ipsilateral activa-
ual tasks, although even during symmetric bimanual actions, tion as indicated by a change in laterality index (vs a control
the perfect interlimb symmetry is perceived as surreal. In condition).47,53,55,56,63,65-68 Hadoush et al claim that this
this latter case, MVF is accompanied with an increase of effect is more prominent for unimanual MVF, that is, when
activity within the superior parietal lobe (precuneus [bilat- the active hand (reflected into the mirror) is covered.48
eral] and superior posterior parietal cortex [contralateral]40), Others show that the increase in excitability is observed
the posterior cingulate cortex,58 and ipsilateral lateral sul- particularly when MVF and motor imagery are com-
cus51,52 compared to a condition with full vision of the 2 bined.66,68 Investigation of the potential mediators of this
hands. effect suggests that MVF has the capacity to neutralize the
MVF inducing a more extreme conflict (during uniman- (interhemispheric) inhibition from contralateral to ipsilat-
ual actions) stimulates activity within primary visual and eral hemisphere. Still, it should be noted that a number of
354 Neurorehabilitation and Neural Repair 29(4)

Table 2.  Outline of the Methodology, Type of MVF, Measures to Avoid Systematic Variation in Movement Across Conditions, and
Known Potential Confounds in All Experimental Studies Using TMS Included in the Systematic Review.
(a) Measures to Avoid
Systematic Variation
Outline of Experimental Methodology Type of
Study Reference Participants Relevant to This Review MVF (b) Potential Confounds
63
Carson and Ruddy (2012) 12 healthy individuals aged Exp 1: Flexion-extension of left wrist with Bilateral (a) Metronome paced,
21.5 ± 3.4 (1) VF of nonmoving right hand; (2) MVF of EMG recording
moving left hand; (3) no VF
Fukumura et al (2007)68 6 healthy individuals aged Flexion-extension of left wrist with (1) VF Bilateral (a) Metronome paced
20-39 left hand; (2) VF left + motor imagery right
hand; (3) MVF left hand; (4) MVF left +
motor imagery right hand; (5) MVF left +
passive movement right hand; (6) MVF +
passive movement and motor imagery right
hand
Funase et al (2007)64 12 healthy individuals aged Flexion-extension left hand or left index finger Bilateral (a) Metronome paced
19-40 and wrist with (1) VF left side; (2) MVF left
side
Garry et al (2005)65 8 healthy individuals aged Finger-thumb opposition with (1) VF active Bilateral (a) Metronome paced,
39.6 ± 14.5 hand; (2) VF inactive hand; (3) neutral VF; EMG recording
(4) MVF active hand
Kang et al (2011)66 30 healthy individuals aged Thumb abduction/adduction with (1) VF active Bilateral (a) Metronome paced
28.0 ± 2.4 and 30 stroke hand + motor imagery; (2) MVF active hand
patients aged 66.0 ± 11.0 + motor imagery inactive hand; (3) MVF
active hand + motor imagery of asymmetric
movements inactive hand
  Passive task with (1) motor imagery of right  
hand; (2) AO other hand + motor imagery
own right hand; (3) MVF + motor imagery
other hand
Kang et al (2012)67 18 healthy individuals aged Exp 1: TMS across nondominant/affected Bilateral (a) Metronome paced
30.9 ± 2.2 and 18 stroke hemisphere during unilateral flexion-
patients aged 61.3 ± 11.6 extension of the dominant/unaffected wrist
with (1) MVF, (2) virtual MVF, or during (3)
relaxation
  Exp 2: TMS across nondominant/affected  
hemisphere during unilateral flexion-
extension of the dominant/unaffected
wrist with (1) continuous virtual MVF, (2)
intermittent virtual MVF
Merians et al (2009)47 1 healthy individual Finger tapping right hand with (1) virtual VF Bilateral (a) None
active hand; (2) virtual MVF active hand

Abbreviations: MVF, mirror visual feedback; VF, normal visual feedback; AO, action observation; Exp, experiment. Bilateral MVF, active hand and its mirror reflection;
Unilateral MVF, MVF of active hand only. MVF was generated by a mirror placed in between the arms in the sagittal plane, except when stated otherwise.

studies could not find changes in activity within the ipsilat- After training the activation balance when moving the
eral M1 evoked by MVF.39,60,64 affected hand has shifted toward M1 of the affected hemi-
sphere, indicating increased activation of the affected side
Neuroplastic Effects Due to Practice or Intervention With and/or decreased activation of the contralesional side.45,54,69
MVF.  Six studies have examined the effect of a bout of prac- This would imply a reestablishment the hemispheric bal-
tice or treatment with MVF on motor function while also ance that was disrupted by the insult. Another study sug-
measuring the change in brain activity pre and post training gests, however, that the improvement of untrained hand is
(see Table 4 for details).44,45,54,61,62,69 Consistent with earlier related to the establishment of a functional connection
reports training with MVF resulted in a gain in motor func- between this hand and the ipsilateral motor cortex (ie, M1
tion of the untrained or affected hand in all studies. This contralateral to the trained hand).44 Dynamic causal model-
gain seems to be related to an enhanced excitatory function ing and functional connectivity analysis further indicates
of the (contralateral) corticospinal pathway projecting to that this reorganization is mediated by enhanced connectiv-
this hand (ie, decrease in motor threshold and intracortical ity between the premotor cortices (both left and right) and
inhibition within M1 ipsilateral to the trained hand).61,62 the ipsilateral supplementary motor area.
Deconinck et al 355

Table 3.  Outline of the Methodology, Type of MVF, Measures to Avoid Systematic Variation in Movement Across Conditions, and
Known Potential Confounds in All Experimental Studies Using PET, MEG, EEG, and NIRS Included in the Systematic Review.
(a) Measures to Avoid
Systematic Variation
Outline of Experimental Methodology
Study Reference Modality Participants Relevant to This Review Type of MVF (b) Potential Confounds
57
Dohle et al (2011) PET 10 healthy individuals Unilateral circular movement of left or right Unilateral (a) Metronome paced
aged 19-42 arm with (1) VF; (2) virtual MVF
Fink et al (1999)58 PET 10 healthy individuals Luria’s bimanual circle drawing task: (1) Bilateral (a) None
aged 20-73 in-phase with VF; (2) in- phase with MVF;
(3) out-of-phase with VF; (4) out-of-phase
with MVF
Hadoush et al (2013)48 MEG 10 healthy individuals Index finger extension with MVF of active Bilateral (a) None
aged 22-35 hand, (1) with VF of active hand or (2)
without VF of active hand
Tominaga et al (2009)49 MEG 11 healthy individuals Stimulation of right median nerve at wrist Unilateral (a) N/A
aged 19-34 while holding a pencil with (1) MVF of right
hand; (2) VF of right hand; (3) MVF of left
hand; (4) VF of left hand
Tominaga et al (2011)50 MEG 13 healthy individuals Stimulation of right or left median nerve at Unilateral (a) N/A
aged 19-34 wrist while holding a pencil with (1) MVF
of right hand; (2) VF of right hand; (3) MVF
of left hand; (4) VF of left hand
Wasaka and Kakigi MEG 10 healthy individuals Stimulation of left median nerve at wrist Bilateral (a) None
(2012)52 aged 24-46 while flexing-extending left thumb
repetitively or at rest with (1) MVF of
stationary right hand; (2) VF of both hands
Wasaka and Kakigi MEG 10 healthy individuals Stimulation of left median nerve at wrist Bilateral (a) None
(2012)51 aged 28-46 while flexing-extending left and right
thumb repetitively symmetrically or
asymmetrically with (1) MVF of right hand;
(2) VF of both hands
Praamstra et al (2011)55 EEG 9 healthy individuals aged Extension-flexion right or left index finger Unilateral (a) Set number of trials,
32 ± 11 with (1) VF active finger; (2) MVF active EMG recording
finger
Touzalin-Chretien et al EEG 11 healthy individuals Key press with right hand [except (4)] with Unilateral (a) Set number of trials,
(2008)56 aged 27.7 (1) VF of right hand; (2) MVF of right hand; EMG recording
(3) MVF of right hand in a frontal mirror;
(4) VF of left hand
Touzalin-Chretien et al EEG 8 healthy individuals aged Key press with right hand [except (2)] with Unilateral (a) Set number of trials,
(2010)53 32.2 (1) VF of right hand; (2) VF of left hand; (3) EMG recording
MVF of right hand; (4,5) MVF of right hand
with left hand in incongruent position; (6)
MVF of right hand in a frontal mirror
Imai et al (2008)59 NIRS 5 healthy individuals aged Unilateral grasping movements with right or Bilateral (a) Metronome paced
21.1 ± 1.1 left hand with (1) VF of nonmoving hand,
(2) with MVF of moving limb
Mehnert et al (2013)60 NIRS 22 healthy individuals Unilateral index finger-thumb opposition of Unilateral (a) Metronome paced
aged 21-40 either left or right hand with (1) virtual VF,
(2) virtual MVF

Abbreviations: MVF, mirror visual feedback; VF, normal visual feedback; PET, positron emission topography; MEG, magnetoencephalography; EEG, electroencephalography;
NIRS, near infrared spectrometry.

Discussion draw firm conclusions. In addition, a large number of stud-


ies had relatively small sample sizes (N ≤ 10 in 17 out of 33
This systematic review aimed to identify instant and long-
studies) and a number of studies fail to meet all method-
term neuromodulatory effects associated with MVF. The
findings of the 33 articles indicate that MVF engages a dis- ological requirements, for example, equal performance
tributed network within the brain, including regions related across experimental manipulations or adequate control
to perceptual, motor, and higher cognitive functions, though intervention (see Tables 1-3 and Supplementary Material).
it is important to acknowledge a number of limitations. These limitations highlight that future research should pri-
Clearly, the variety of methodologies impedes the ability to marily focus on isolating the effect of MVF from the
356 Neurorehabilitation and Neural Repair 29(4)

Table 4.  Outline of the Methodology in All Clinical or Training Studies Included in the Systematic Review.
Outline of Experimental Methodology
Study Reference Modality Participants Nature of Training Frequency and Duration Relevant to This Review

Bae et al (2012)54 EEG MG: 10 stroke patients MG: bilateral movements 4 weeks, 5 sessions/ Observation of hand movements
aged 55.2 ± 8.5 with MVF week, 30 minutes/ during rest, while measuring µ-
CG: 10 stroke patients CG: unilateral session rhythm across left (C3), right (C4)
aged 52.6 ± 11.2 movements of paretic and (Cz) central fissure prior to and
side with VF of 2 limbs after training
Bhasin et al (2012)69 fMRI MG: 20 stroke patients Bilateral hand exercises 8 weeks, 5 sessions/ Repetitive clenching/extension of fist
aged 28-62 with virtual MVF on week, 30-60 minutes/ at the affected side without VF pre-
laptop screen session and posttraining
Hamzei et al (2012)44 fMRI MG: 13 healthy MG and CG: 5 4 days, 20 minutes/day fMRI during (1) AO of grasping
individuals aged 23.9; unimanual skills (RH movement during rest, (2) active
CG: 13 healthy only) with MVF or VF imitation of grasping movement
individuals aged 25.5 of RH only with left or right hand, pre- and
posttraining
Laeppchen et al (2012)61 TMS MG and CG: 10 MG and& CG: 5 4 days, 20 minutes/day Test of TMS parameters (MT, ICI,
healthy individuals unimanual skills (RH ICF, IHI left hemisphere) pre- and
aged 24.1 only) with MVF or VF posttraining
of RH only
Michielsen et al (2011)45 fMRI MG: 9 stroke patients MG and CG: bimanual 6 weeks, 5 sessions/ fMRI during clenching movement with
aged 51.9 ± 9.3 exercises with MVF or week, 60 minutes/day affected hand without VF pre- and
CG: 7 stroke patients VF of 2 hands posttraining
aged 59.0 ± 10.4
Nojima et al (2012)62 TMS Exp 1. MG and CG: 10 MG and CG: unimanual 10 sets of 30 minutes Test of TMS parameters (MT, ICI, IHI)
healthy individuals (RH only) ball handling each pre- and postpractice
(young adults) task with MVF or VF of
2 hands
  Exp 2. MG1 and MG2: MG1 = MG2: unimanual 10 sets of 30 minutes Similar to Exp 1. Practice was followed
8 healthy individuals (RH only) ball handling each by cTBS over M1 (MG1) or occipital
(young adults) task with MVF cortex (MG2)

Abbreviations: EEG, electroencephalography; fMRI, functional magnetic resonance imaging; TMS, transcranial magnetic stimulation; MG, mirror group; CG, control group;
MVF, mirror visual feedback; VF, normal visual feedback; Exp, experiment; AO, action observation; MT, motor threshold; ICI, intracortical inhibition; ICF, intracortical
facilitation; IHI, interhemispheric inhibition; cTBS, continuous theta burst stimulation. MVF was generated by a mirror placed in between the arms in the sagittal plane,
except when stated otherwise.

Table 5.  Brain Areas Differentially Activated With Mirror Visual Feedback (MVF) Compared to Control Conditions, Corresponding
Brodmann Area (BA) Where Known, Side of Activation Listed According to Populationa,b.

Population Area BA Side MVF Network


58
Healthy Dorsolateral prefrontal cortex 9/46 Right Bi Attention
  Precentral gyrus (M1) 4 Ipsi41,47,63,65-68 Uni and Bi Motor
  Postcentral sulcus, posterior wall (S1/S2) 2 Contra52 Uni and Bi Attention
  Lateral sulcus, upper wall (S2) Contra51,52 Bi Attention
  Superior posterior parietal cortex 7 Ipsi58 Bi Attention
  Precuneus (V6) 7 Ipsi38,42,43,60 Uni and Bi Attention
  Superior temporal gyrus 39 Ipsi46 Bi MNS
  Cuneus/Lingual gyrus (V1/V2) 17/18 Ipsi38,42 Uni Attention
  Superior/Middle occipital gyrus (V2, 3, 5) 19 Ipsi38,42,46 Uni and Bi Attention
  Fusiform gyrus (V4) 37 Ipsi38,42 Uni Attention
  Insular cortex, posterior region Contra57 Uni Attention
Stroke Precentral gyrus (M1) 4 Ipsi66,67 Bilateral Motor
  Precuneus (V6) 7 Contra40, Ipsi40,43 Uni and Bi Attention
  Posterior cingulate cortex 30 Contra40 Bi Attention

Abbreviation: MNS, mirror neuron system.


a
The 2 final columns indicate the type of MVF that elicits this observation and the network to which specific areas are considered to belong.
b
Contralateral (contra) and ipsilateral (ipsi) are defined with respect to the (moving) limb that is reflected in the mirror. MVF indicates the type of MVF
(unilateral or bilateral) that elicits this observation.
Deconinck et al 357

mechanisms associated with bilateral training. Despite mediated through a reduction in interhemispheric inhibition
these limitations, this first systematic review of the effect of (from contralateral/lesional to ipsilateral/lesional)63 and/or
MVF on the brain reveals useful information with respect to a reduction of intracortical inhibition.61 In view of the
the underlying mechanisms of MVF for both researchers notion that functional recovery is correlated with the extent
and practitioners in neurorehabilitation. of involvement of the ipsilesional (here: contralateral)
Overall, the findings suggest that MVF may affect per- motor network,82 this seems a promising therapeutic effect
ceptuo-motor control processes via (parts of) 3 functional of MVF. Other findings in healthy adults, however, indicate
networks. First, the increase in activity in primary and sec- that improved motor skill of the untrained hand is achieved
ondary visual and somatosensory areas suggests a rise in by establishing a functional connection with the ipsilateral
attentional resources to resolve the perceptual incongru- motor cortex via MVF, a mechanism that has been associ-
ence.51,52 This is associated with conscious awareness of ated with poorer motor recovery compared with normaliza-
sensory feedback or control of agency, as observed in the tion of the hemispheric balance.83 This discrepancy might
activity within the insular cortex,70 and enhanced monitor- reflect 2 stages in the recovery process or a population-spe-
ing of the movement, as found in the involvement of the cific response and warrants further investigation.
right DLPFC.58,71 Furthermore, greater activation of the The effect of MVF on brain activation is likely depen-
posterior aspect of the parietal and cingulate cortex sup- dent on the specific nature of the feedback. In this respect it
ports the notion of greater attentional demands. The poste- is remarkable that the effect on primary and secondary
rior cingulate cortex, highly interconnected with various visual processing areas is primarily related to unilateral
brain regions, is considered a hub for information exchange72 MVF. Bimanual MVF, in contrast, seems to engage more
and a prominent role in the cognitive control of behavior is frontal and parietal regions related to higher cognitive func-
attributed to this region.73 The nearby superior posterior tions like attention and monitoring (see Table 5).
parietal cortex and its medial extension (precuneus) are Finally, it is noteworthy that the findings for individuals
known to be involved in visuospatial information process- with stroke are in accordance with those for healthy people,
ing and directing spatial attention, especially during biman- insofar as the limited number of studies allows this com-
ual coordination tasks.74,75 This probably explains why the parison (see Table 5). There is evidence of increased activa-
effect of MVF on the precuneus is primarily observed in tion of higher order areas involved with attentional processes
studies that use virtual MVF of the hand in the frontal (precuneus and posterior cingulate cortex) and the ipsilat-
plane.38,39,42,43,60 Notably, a number of studies have shown eral M1.
that the precuneus is particularly active during motor imag-
ery,76 which may account for the combined effect of imag- Part 3: Summary and Future
ery and MVF.
Second, MVF seems to cause increased immediate acti-
Directions
vation of STG46 and elevated engagement of PMC44 after Convergent evidence suggests that MVF may be used as a
training. Both areas have been associated with the mirror tool to promote functional recovery in patients with unilat-
neuron system. STG is often linked to its neighboring supe- eral motor impairments. A systematic review of neuroimag-
rior temporal sulcus and is involved in the visual identifica- ing research was conducted to test the validity of the 3
tion of biological motion.77 Combined with the PMC, it hypotheses proposed to explain the positive effects associ-
forms a network that subserves the imitation of biological ated with MVF. The findings of this review, suggesting sub-
motion and the acquisition of motor skills.25,78,79 The activa- stantial overlap between MVF-related activity and regions
tion of PMC, especially at the side of the lesion, is in keep- subserving attention-related processes, confirm that MVF
ing with earlier research that has attributed a prominent role activates a broad network dedicated to attention and action
to this region in motor recovery after stroke.80,81 monitoring (Hypothesis 3). This is consistent with known
A third functional network on which MVF appears to motor learning principles, which attribute success of motor
exert a modulatory effect is the motor network. The primary practice to attentional focus and cognitive processing.
motor cortex (M1) ipsilateral to the active (reflected) hand, Furthermore, the positive effect on motor function is associ-
that is, M1 projecting to the unseen hand behind the mirror, ated with facilitation of M1 contralateral to the affected or
is considered the final common pathway for the beneficial untrained hand (here: referred to as ipsilateral to the moving
effect of MVF according to various studies. A complete hand that is mirrored). However, there is also evidence to
reversal of lateralization when moving a limb that is support a mechanism that exploits ipsilateral control of the
reflected by a mirror (ie, the ipsilateral side taking over con- affected limb, which has been associated with suboptimal
trol), as put forward by some,53,56,59 is unlikely; however, recovery after other therapeutic interventions (Hypothesis
there is accumulating evidence that MVF decreases the 2). Regions that have been linked with the mirror neuron
motor threshold and enhances corticospinal output of the system (PMC, STG) may play a mediating role in connect-
ipsilesional M1 in stroke patients.55,63,65-68 This is probably ing perceptual and motor areas (Hypothesis 1). Still, the
358 Neurorehabilitation and Neural Repair 29(4)

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Acknowledgments
patients with causalgia (complex regional pain syndrome type
The authors wish to thank Prof Karen Caeyenberghs and two II) following peripheral nerve injury: two cases. J Rehabil
anonymous reviewers for their advice and suggestions. Med. 2008;40:312-314. doi:10.2340/16501977-0158.
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Declaration of Conflicting Interests regional pain syndrome. Anaesthesia. 2006;61:412-413.
16. Tichelaar YIGV, Geertzen JHB, Keizer D, van Wilgen PC.
The author(s) declared no potential conflicts of interest with
Mirror box therapy added to cognitive behavioural therapy
respect to the research, authorship, and/or publication of this
in three chronic complex regional pain syndrome type I
article.
patients: a pilot study. Int J Rehabil Res. 2007;30:181-188.
doi:10.1097/MRR.0b013e32813a2e4b.
Funding 17. Rosen B, Lundborg G. Training with a mirror in rehabilita-
The author(s) disclosed receipt of the following financial support tion of the hand. Scand J Plast Reconstr Surg Hand Surg.
for the research, authorship, and/or publication of this article: This 2005;39:104-108.
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and Frederik Deconinck (Grant 09MMU01). visual feedback in the treatment of complex regional pain syn-
drome (type 1). Rheumatology. 2002;42:97-101. doi:10.1093/
Supplementary Material rheumatology/keg041.
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Supplementary material for this article is available on the
apy enhances lower-extremity motor recovery and motor
Neurorehabilitation & Neural Repair Web site at http://nnr.sage-
functioning after stroke: a randomized controlled trial.
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