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Reﬂections on Mirror Therapy: A Systematic Review of the Effect of Mirror

Visual Feedback on the Brain
Article in Neurorehabilitation and Neural Repair · August 2014

DOI: 10.1177/1545968314546134 · Source: PubMed
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Reflections upon mirror therapy!
Reflections upon mirror therapy –!a systematic review of the effect of mirror
visual feedback on the brain
Deconinck FJA1,2,*(PhD), Smorenburg ARP3(PhD), Benham A4(PhD), Ledebt
A5(PhD), Feltham MG6(PhD), Savelsbergh GJP5(PhD)!
1
Ghent University (Belgium), Department of Movement and Sports Sciences!
2
Manchester Metropolitan University (UK), School of Healthcare Sciences!
3
Burke-Cornell Medical Research Institute (USA)!
4
Bradford Institute for Health Research (UK)!
5
VU University Amsterdam (The Netherlands), Research Institute MOVE!
6
University of Birmingham (UK), Primary Care Clinical Sciences!
*Corresponding author:
Ghent University –!Faculty of Medicine and Health Sciences, Department of
Movement and Sports Sciences, Watersportlaan 2, 9000 Gent, Belgium!
Tel.: +32 (0)9 264 91 37!
E-mail: Frederik.Deconinck@UGent.be!
This paper is published in Neurorehabilitation and Neural Repair.
The final publication is available at Sage via
http://dx.doi.org/[DOI:10.1177/1545968314546134]
"!
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 papers, 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 MI 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.!
Key words
systematic review, sensorimotor control, visual feedback, mirror, hemiparesis, stroke,
cerebral palsy !
#!
Introduction
Often a source of fascination, or perhaps frustration, optical illusions have captivated
people since ancient times. For instance, curved surfaces and the absence of right
angles in archaic Greek temples suggest that its architects attempted to optically
correct the illusion of slanted columns or curved 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 neuroscientists optical illusions are
considered a backdoor into people’s mind and provide an excellent way to study the
neural mechanisms underlying perception and action.2
Interestingly, although optical illusions are known to deceive the individual, the
false reality may fool the brain, such that the outcome is beneficial. One such an
illusion is the mirror illusion, which has been found to have therapeutic benefits over
the past 2 decades. When a mirror is placed, along the midsagittal plane in between
the 2 limbs, the reflection of the limb in front of the mirror is superimposed on the
contralateral limb. Any motion of the limb in front of the mirror induces the illusion
of 2 synchronously moving limbs. After Ramachandran and his colleagues found that
this illusion could alleviate phantom pain in a proportion of the patients,3 mirror
visual feedback (MVF) was introduced as a neurorehabilitation tool to treat other
unilateral pain disorders, such as complex regional pain syndrome (CRPS). In
addition, the paradigm is now used to promote motor recovery (eg, in hemiparetic
patients or after hand surgery).
Despite its widespread use in neurorehabilitation and the claims that MVF
therapy would lead to neuroplastic changes, there is no consensus about the
underlying mechanism and speculation often lacks the neuroscientific proof. The
aim of this review is therefore to bring together current knowledge on the effect of
MVF on the brain as has been described in neuroimaging studies, in order to
explore potential processes underlying the beneficial clinical effects of MVF. To
acquaint the reader with MVF and its current applications, we will first revisit
Ramachandran’s rationale for MVF, followed by a narrative review of the clinical
neurorehabilitation research that followed in his footsteps. At the end of this
section, we introduce 3 hypotheses that have been proposed to explain the positive
effects related to MVF. Part 2 provides a systematic review and discussion of
studies that examined the effect of MVF on brain activation patterns using
neuroimaging or electrophysiological techniques. Finally, in Part 3 we discuss the
$!
findings of the systematic review in relation to the hypotheses introduced in Part 1

and we identify where further research is required.
Part 1: Mirror therapy – background, current applications, and potential

mechanisms
The idea of using MVF for the management of phantom limb pain was inspired by
early findings on the integration of perception and action, in particular the
principle of reafference.4,5 Reafference is afferent sensory information caused by a
motor command (eg, signals from muscle spindles in M. biceps brachii when the
arm is actively flexed), as opposed to exafferent information, which results from
factors outside the individual (eg, signals from muscle spindles in M. biceps
brachii when the arm is flexed passively). To distinguish between these 2 sensory
stimuli, it is maintained that the generation of a motor command is accompanied
by a parallel signal, termed efference copy, which contains the sensory feedback to
be expected due to this command. Comparison of all afferent signals with the
efference copy provides a way to separate signals that originate from bodily
movements and those from outside the individual. As a consequence, motor
commands that are not instantaneously followed by the expected reafferent
feedback will be modified in an attempt to evoke the expected sensory afference.5
It is this conflictive state that, according to some,6,7 may evolve into a form of
“learned paralysis” accompanied by a feeling of painful spasms,* as experienced
by a proportion of patients who have had an arm or leg amputated. The goal of
MVF is to restore the efference–afference loop that has been interrupted. MVF of
the intact limb deceives the individual and elicits the awareness that the amputated
limb is still intact, not at least due to the dominance of the visual system over
other modalities.8,9 Indeed, when the illusion was tested in arm amputees with
complaints of “clenching spasms” and phantom limb pain, the spasms were
&!Intheir recent review article, Ramachandran and Altshuler9 rec- ognize that the origin of phantom
pain is still poorly understood and may be related to other factors, for example, persistence of
preamputation pain and pathological “remapping” among others (see also Ramachandran and
Hirstein6). The rationale to use MVF, however, is based on the notion of a mismatch between motor
output and visual and/or proprioceptive feedback.!
%!
eliminated and the pain was relieved immediately after exposure to MVF in a
proportion of the sample.3
The novelty and simplicity of the idea, in combination with the far-reaching
potential of MVF, prompted clinicians and researchers to replicate the initial
findings of Ramachandran and colleagues. Consistent with the earlier
observations, follow-up studies have confirmed that MVF treatment has the
capacity to reduce phantom limb pain intensity and duration.10,11 Moreover, the
notion that many neurological disorders with unilateral pain and motor symptoms
may be (partly) caused by maladaptive cortical reorganization involving a
disruption of the efference–afference loop, led others to apply MVF to a wide
range of conditions. Hemiparesis after stroke is perhaps the most striking example.
In a proportion of the patients the paresis is thought to be a form of “learned
paralysis” due to a nonpermanent blocking of corticofugal fibers by swelling after
the trauma.12 A recent Cochrane Review exploring the effectiveness of MVF
therapy in patients after stroke (13 randomized controlled trials, 506 patients)
concluded that mirror therapy indeed might be more effective in promoting motor
function than a control intervention † when used as an adjunct to conventional
therapy.13 Furthermore, the meta-analysis indicated that the effects were retained,
up to 6 months after the intervention, and that MVF therapy had a significantly
greater effect than control interventions on activities of daily living and on pain,
though the latter was found only in a subgroup with CRPS after stroke.
To date, MVF is administered to treat various unilateral pain and/or motor
disorders, including CRPS,14-18 hemiparesis after stroke,19,20 reduced mobility after
wrist fracture,21 and spastic hemiparetic cerebral palsy (SHCP).22,‡ The findings of
these studies tend to corroborate the initial work, that is, a reduction in pain and
improvement in motor function. Still, it should be noted that publication bias toward a
selection of positive results may be likely and additional placebo-controlled studies
are needed for all conditions or symptoms. In this respect, it is worth mentioning that
Brodie et al found that the attenuating effect of MVF on pain was not stronger than a
control condition in lower limb amputees.23
(The effect of MVF therapy was significantly larger than control interventions.!!
)See Ramachandran and Altschuler9 for a list of clinical cases where the use of MVF has been
observed informally but has not been described in the literature.!
'!
Despite the fact that there appear to be parallels in the pathophysiology of unilateral
pain and motor disorders as described by Ramachandran and Altschuler,12 the 2
phenomena should be considered separately, hence the focus of this review will be on
the effects of MVF on sensorimotor control. To fully exploit the potential of MVF, a
better insight into the processes that underlie the beneficial effects on motor function
is required. Not only would this knowledge advance our theoretical understanding of
the brain, it may also provide guidelines as to when MVF may be useful and how it
should be applied.
When the individual is required to perform bilateral, symmetrical motor tasks,
MVF therapy may be considered a special form of bilateral training, and hence exploit
similar mechanisms (see Cauraugh and Summers for a review24). However, in search
of the added value of MVF researchers have invoked 3 (not mutually exclusive)
hypotheses to account for the positive effects of MVF on motor recovery. A first
hypothesis relates to the mirror neuron system.17,19,20 Mirror neurons fire both when
an individual observes an action and when he/she performs a similar action. The
network, including the premotor cortex, supplementary motor area, inferior frontal
gyrus, and inferior parietal lobule of the brain, is thought to play an important role in
action recognition and motor learning or rehabilitation.25 An observation/execution
matching mechanism, whereby action observation activates crucial parts of the motor
system, is hypothesized to induce motor learning.25,26 It is known that action
observation facilitates the corticospinal pathway and this paradigm is already used in
neurorehabilitation as mental practice aimed at improving motor function.27
According to this hypothesis, a “mirror box” is a means to facilitate action
observation and therefore MVF is thought to activate the mirror neuron system in a
similar way to action observation (Hypothesis 1). In line with this is the notion that
MVF may elicit or enhance motor imagery,28 that is, internal simulation of movement
without overt action. Just like action observation motor imagery has been attributed
therapeutic capacities because it activates neural circuits involved in motor control.29
Second, MVF might promote recruitment of ipsilateral motor pathways.30 These
motor pathways, originating in the unaffected hemisphere and projecting ipsilaterally
to the paretic body-side, have been attributed a nontrivial role in the restoration of
motor function in hemiparesis.31-34 It is hypothesized that MVF might facilitate the
unmasking of “dormant” ipsilateral projections, which are normally inhibited
(Hypothesis 2).
*!
Finally, MVF or the associated illusion is thought to increase an individual’s

(spatial) attention toward the unseen (affected) limb.35 It is known that hemiparetic
patients may end up in a state of “learned nonuse,” by continuously avoiding the use
of the paretic hand or by pathophysiological disruption of the efference–afference
loop.36 In keeping with the rationale for using constraint-induced movement therapy,36
the increased attention toward the affected limb, mediated by the illusory image of a
“healed” paretic limb, may activate motor networks (Hypothesis 3).
In sum, an increasing body of evidence underpins the potential of MVF to facilitate
recovery of motor function. Still, the neural mechanism of MVF, whether the
behavioral effect is accompanied by neuroplastic changes, and what this
reorganization would involve is unclear. The hypotheses invoked to explain MVF
effects are based on known concepts in neurorehabilitation, but they remain
speculative. Recent experimental neuroimaging research has begun to reveal the
extent of brain activation during movement with MVF, and its modulatory effects on
brain processes compared with normal visual conditions. In the following part of this
article, the findings of these studies will be systematically reviewed. This will serve as
a validity test of the proposed hypotheses.
Part 2: The neural correlates of mirror visual feedback

2.1. Purpose
The purpose of this systematic review was to identify the areas in the brain that are
differentially affected or modulated by MVF compared with a condition with normal
or without visual feedback.
2.2. Literature search

A literature search using the electronic databases PubMed, CINAHL, and EMBASE
(1972 to January 2014) was conducted. Search terms included “mirror therapy” or
“mirror visual feedback” combined with “functional magnetic resonance imaging
(fMRI),” “positron emission topography (PET),” “transcranial magnetic stimulation
(TMS),” “magnetoencephalography (MEG),” “electroencephalography (EEG),” or “near
infra-red spectrometry (NIRS).” In addition, we checked our personal database and the
reference list of included articles. Our search was restricted to peer-reviewed full articles
written in English.
+!
Inclusion criteria were the following:
• Experimental studies or clinical trials

• Normal and/or motor-impaired human participants
• Use of neuroimaging techniques (fMRI, PET, MEG, EEG, NIRS) or TMS to
study the effect of MVF§ on cortical activation (and related motor performance
or perceptual measures)
Exclusion criterion was the following:
• Studies that do not assess effect of MVF on sensorimotor control, but focus on
pain and/or tactile perception.
The records identified by this search were screened independently by 2 authors of

this systematic review (FD and AS) in 2 stages: a first stage screening of titles and
abstracts and a second stage using the full text of the remaining article. The lists of
eligible articles identified by the independent reviewers were compared, and any
disagreements were resolved through discussion (and referral to the text of the articles
in question).
2.3. Results
The electronic database search yielded 347 unique articles, of which 33 were
deemed eligible for this systematic review (see Figure 1 for an overview of the
selection process). Across the selected articles, the most commonly used scanning
technique was fMRI (12 studies).37-47 MEG was the neuroimaging modality in 5
article,48-52 EEG in 4,53-56 PET in 2,57,58 and NIRS in 2.59,60 Nine studies
investigated the effect of MVF on cortical activation with TMS47,61-68; 1 study
used both TMS and fMRI.47 In Tables 1 to 4, the included articles and their
methodologies are listed according to modality. The majority of the studies (n =
27) examined immediate modulatory effects when exposed to MVF, of which 22
focused on healthy individuals and 5 on stroke patients (Tables 1-3). In 16 studies,
MVF was provided in a bilateral fashion, that is, not obscuring the active hand.
Six studies assessed neuroplastic changes in response to a bout of practice or an
-Mirror visual feedback could be induced by a real mirror or using a virtual reality environment.!
,!
intervention in healthy individuals (n = 3) or stroke patients (n = 3). Here, bilateral

MVF was used in all but one study (Table 4 and Supplementary Material). The
variance in methodology and motor task, which may be unilateral or contralateral,
complicates the overall interpretation of the observations. A factor that adds to this
difficulty is the absence of a standard control condition. In some studies, MVF is
contrasted with normal full vision of the 2 limbs, whereas in others visual
feedback of the active or static limb only is used as a control. Furthermore, to
isolate the effect of MVF on brain activation it is crucial to keep the movement
(range, frequency, intensity) constant across MVF and control conditions, which a
number of studies have failed to do or to control for (see Table 1-4 for details).
Instant Neuromodulatory Effects of MVF. The neuromodulatory effects of MVF

refer to changes in activity or excitation that are evoked by MVF, that is, revealed
by direct comparison of MVF with a control condition (listed in Table 5). MVF
evokes a conflict between expected and actual feedback (cognitive conflict) and
between visual and kinaesthetic feedback (perceptual conflict). This conflict is
most obvious when performing unimanual or asymmetric bimanual tasks, although
even during symmetric bimanual actions, the perfect interlimb symmetry is
perceived as surreal. In this latter case, MVF is accompanied with an increase of
activity within the superior parietal lobe (precuneus [bilateral] and superior
posterior parietal cortex [contralateral]40), the posterior cingulate cortex,58 and
ipsilateral lateral sulcus51,52 compared to a condition with full vision of the 2
hands.
MVF inducing a more extreme conflict (during unimanual actions) stimulates
activity within primary visual and somatosensory areas, as well as higher order
processing areas in the occipital and parietal cortex ipsilateral to the moving
limb.38,39,42,43,46,60 In fact, the mirror inverts the lateralization that is normally
associated with the presentation of a right or left hand in these regions. Note,
however, that these observations stem from studies that contrasted virtual MVF of
the active hand with virtual VF displayed in the frontal plane (on a screen or onto
MRI-compatible goggles). Other studies show increased activation in the right
dorsolateral prefrontal cortex (DLPFC),58 the contralateral secondary sensory
cortex (SII),51 the ipsilateral superior temporal gyrus (STG),46 and the contralateral
insular cortex.52,57
.!
Finally, MVF modulates activity of the primary motor cortex, both ipsilateral and
contralateral to the active hand reflected into the mirror, though the findings are
somewhat inconsistent. The majority of the studies suggest an increase in ipsilateral
M1 excitability or increased ipsilateral activation as indicated by a change in laterality
index (vs a control condition).47,53,55,56,63,65-68 Hadoush et al claim that this effect is
more prominent for unimanual MVF, that is, when the active hand (reflected into the
mirror) is covered.48 Others show that the increase in excitability is observed
particularly when MVF and motor imagery are combined.66,68 Investigation of the
potential mediators of this effect suggests that MVF has the capacity to neutralize the
(interhemispheric) inhibition from contralateral to ipsilateral hemisphere. Still, it
should be noted that a number of studies could not find changes in activity within the
ipsilateral M1 evoked by MVF.39,60,64
Neuroplastic Effects Due to Practice or Intervention With MVF. Six studies have
examined the effect of a bout of practice or treatment with MVF on motor function
while also measuring the change in brain activity pre and post training (see Table 4
for details).44,45,54,61,62,69 Consistent with earlier reports training with MVF resulted in
a gain in motor function of the untrained or affected hand in all studies. This gain
seems to be related to an enhanced excitatory function of the (contralateral)
corticospinal pathway projecting to this hand (ie, decrease in motor threshold and
intracortical inhibition within M1 ipsilateral to the trained hand).61,62 After training the
activation balance when moving the affected hand has shifted toward M1 of the
affected hemisphere, indicating increased activation of the affected side and/or
decreased activation of the contralesional side.45,54,69 This would imply a
reestablishment the hemispheric balance that was disrupted by the insult. Another
study suggests, however, that the improvement of untrained hand is related to the
establishment of a functional connection between this hand and the ipsilateral motor
cortex (ie, M1 contralateral to the trained hand).44 Dynamic causal modeling and
functional connectivity analysis further indicates that this reorganization is mediated
by enhanced connectivity between the premotor cortices (both left and right) and the
ipsilateral supplementary motor area.
2.4. Discussion
"/!
This systematic review aimed to identify instant and long-term neuromodulatory

effects associated with MVF. The findings of the 33 articles indicate that MVF
engages a distributed network within the brain, including regions related to
perceptual, motor, and higher cognitive functions, though it is important to
acknowledge a number of limitations. Clearly, the variety of methodologies impedes
the ability to draw firm conclusions. In addition, a large number of studies had
relatively small sample sizes (N ! 10 in 17 out of 33 studies) and a number of studies
fail to meet all methodological requirements, for example, equal performance across
experimental manipulations or adequate control intervention (see Tables 1-3 and
Supplementary Material). These limitations highlight that future research should
primarily focus on isolating the effect of MVF from the mechanisms associated with
bilateral training. Despite these limitations, this first systematic review of the effect of
MVF on the brain reveals useful information with respect to the underlying
mechanisms of MVF for both researchers and practitioners in neurorehabilitation.
Overall, the findings suggest that MVF may affect perceptuo-motor control
processes via (parts of) 3 functional networks. First, the increase in activity in primary
and secondary visual and somatosensory areas suggests a rise in attentional resources
to resolve the perceptual incongruence.51,52 This is associated with conscious
awareness of sensory feedback or control of agency, as observed in the activity within
the insular cortex,70 and enhanced monitoring of the movement, as found in the
involvement of the right DLPFC.58,71 Furthermore, greater activation of the posterior
aspect of the parietal and cingulate cortex supports the notion of greater attentional
demands. The posterior cingulate cortex, highly interconnected with various brain
regions, is considered a hub for information exchange72 and a prominent role in the
cognitive control of behavior is attributed to this region.73 The nearby superior
posterior parietal cortex and its medial extension (precuneus) are known to be
involved in visuospatial information processing and directing spatial attention,
especially during bimanual coordination tasks.74,75 This probably explains why the
effect of MVF on the precuneus is primarily observed in studies that use virtual MVF
of the hand in the frontal plane.38,39,42,43,60 Notably, a number of studies have shown
that the precuneus is particularly active during motor imagery,76 which may account
for the combined effect of imagery and MVF.
""!
Second, MVF seems to cause increased immediate activation of STG46 and

elevated engagement of PMC44 after training. Both areas have been associated with
the mirror neuron system. STG is often linked to its neighboring superior temporal
sulcus and is involved in the visual identification of biological motion.77 Combined
with the PMC, it forms a network that subserves the imitation of biological motion
and the acquisition of motor skills.25,78,79 The activation of PMC, especially at the side
of the lesion, is in keeping with earlier research that has attributed a prominent role to
this region in motor recovery after stroke.80,81
A third functional network on which MVF appears to exert a modulatory effect
is the motor network. The primary motor cortex (M1) ipsilateral to the active
(reflected) hand, that is, M1 projecting to the unseen hand behind the mirror, is
considered the final common pathway for the beneficial effect of MVF according
to various studies. A complete reversal of lateralization when moving a limb that
is reflected by a mirror (ie, the ipsilateral side taking over control), as put forward
by some,53,56,59 is unlikely; however, there is accumulating evidence that MVF
decreases the motor threshold and enhances corticospinal output of the ipsilesional
M1 in stroke patients.55,63,65-68 This is probably mediated through a reduction in
interhemispheric inhibition (from contralateral/lesional to ipsilateral/lesional)63
and/or a reduction of intracortical inhibition.61 In view of the notion that
functional recovery is correlated with the extent of involvement of the ipsilesional
(here: contralateral) motor network,82 this seems a promising therapeutic effect of
MVF. Other findings in healthy adults, however, indicate that improved motor
skill of the untrained hand is achieved by establishing a functional connection with
the ipsilateral motor cortex via MVF, a mechanism that has been associated with
poorer motor recovery compared with normalization of the hemispheric balance.83
This discrepancy might reflect 2 stages in the recovery process or a population-
specific response and warrants further investigation.
The effect of MVF on brain activation is likely dependent on the specific nature of
the feedback. In this respect it is remarkable that the effect on primary and secondary
visual processing areas is primarily related to unilateral MVF. Bimanual MVF, in
contrast, seems to engage more frontal and parietal regions related to higher cognitive
functions like attention and monitoring (see Table 5).
Finally, it is noteworthy that the findings for individuals with stroke are in
accordance with those for healthy people, insofar as the limited number of studies
"#!
allows this comparison (see Table 5). There is evidence of increased activation of
higher order areas involved with attentional processes (precuneus and posterior
cingulate cortex) and the ipsilateral M1.
Part 3: Summary and future directions

Convergent evidence suggests that MVF may be used as a tool to promote
functional recovery in patients with unilateral motor impairments. A systematic
review of neuroimaging research was conducted to test the validity of the 3
hypotheses proposed to explain the positive effects associated with MVF. The
findings of this review, suggesting substantial overlap between MVF-related
activity and regions subserving attention-related processes, confirm that MVF
activates a broad network dedicated to attention and action monitoring (Hypothesis
3). This is consistent with known motor learning principles, which attribute
success of motor practice to attentional focus and cognitive processing.
Furthermore, the positive effect on motor function is associated with facilitation of
M1 contralateral to the affected or untrained hand (here: referred to as ipsilateral
to the moving hand that is mirrored). However, there is also evidence to support a
mechanism that exploits ipsilateral control of the affected limb, which has been
associated with suboptimal recovery after other therapeutic interventions
(Hypothesis 2). Regions that have been linked with the mirror neuron system
(PMC, STG) may play a mediating role in connecting perceptual and motor areas
(Hypothesis 1). Still, the current evidence indicates that MVF therapy is certainly
not a substitute for observational therapy or motor imagery, given that MVF
activates only isolated parts of the MNS. Future research using recent advances in
graph theory may elucidate functional connectivity within and between the
involved networks.84
To date the majority of evidence stems from studies in healthy adult
individuals and the few studies that have examined a patient population only
considered people who survived a stroke. It remains unclear to what extent these
hypotheses may be valid for other clinical conditions for which MVF has been
suggested an adjunct to conventional therapy (eg, SHCP22,85-87 and CRPS14-18).
The finding that MVF may have an impact on multiple functional networks may
"$!
mean it can serve as a versatile tool to promote motor recovery, of which the
actual mechanism is dependent on the specific condition or damage. Large-scale
clinical trials that include measurement of brain function and structure are to
examine the efficacy and the underlying mechanisms of MVF in different
populations, and potential differences between them. Although further research is
warranted to fully understand and exploit the potential of MVF in
neurorehabilitation, it is indisputable that MVF can exert a strong modulatory
influence on the motor system.
"%!
Acknowledgements
The authors wish to thank Prof. Karen Caeyenberghs and 2 anonymous reviewers for
their advice and suggestions.
Declaration of Conflicting Interest

The author(s) declared no potential conflicts of interest with respect to the research,
authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research,
authorship, and/or publication of this article: This work was partly supported by a
research grant from Sparks, registered charity 1003825 (England & Wales), to Geert
Savelsbergh and Frederik Deconinck (Grant 09MMU01).
"'!
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Reflections upon mirror therapy
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.
Study reference Participants Outline of experimental methodology relevant to this review Type of MVF (a) Measures to avoid systematic variation
(b) Potential confounds
Diers et al. (2010)37 9 healthy individuals aged Repetitive clenching of the fist at dominant side with (1) normal Bilateral (a) Metronome paced
51.9±6.9 VF, (2) MVF of active hand, or (3) during motor imagery. (b) No statistical comparison between conditions
Dohle et al. (2004)38 6 healthy individuals aged Static condition vs. finger-thumb opposition with (1) virtual VF Unilateral (a) Metronome paced
29.0±1.5 of hand; (2) virtual MVF of hand
Fritzsch et al. (2013)39 15 healthy individuals aged Unilateral index finger-thumb opposition of either left or right Unilateral (a) Metronome paced
22-56 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; (2) MVF Bilateral (a) None
22-48 active hand
Merians et al. (2009)47 3 healthy individuals aged Finger tapping right hand with (1) virtual VF active hand; (2) Unilateral (a) None
26.8 and 1 stroke patient virtual MVF active hand (b) Lack of control condition
aged 70.0
Michielsen et al. (2011a)40 18 stroke patients aged Unimanual (non-affected hand) and bimanual clenching Bilateral (a) Metronome paced
54.7±9.9 movement with (1) VF; (2) MVF
Shinoura et al. (2008)41 5 healthy individuals aged Unimanual and bimanual clenching of hand(s) with (1) eyes Bilateral (a) None
21-57 and 2 patients with closed; (2) MVF of (one of the) active hand(s) (b) No statistical comparison between conditions
brain tumor aged 47 & 67
Wang et al. (2013a)42 15 healthy individuals aged Movement performance task: Unilateral index finger-thumb Unilateral (a) Number of repetitions counted post-hoc
22-56 opposition of either left or right hand with (1) virtual VF, (2)
virtual MVF. Movement observation task: Observation of
similar action on video
Wang et al. (2013b)43 15 healthy individuals aged Unilateral index finger-thumb opposition of either left or right Unilateral (a) Number of repetitions counted post-hoc
22-56 and 5 stroke patients hand with (1) virtual VF, (2) virtual MVF.
aged 50-72
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.
! 22
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.
Carson & Ruddy (2012)63 12 healthy individuals aged Exp1: Flexion-extension of left wrist with (1) VF of non-moving Bilateral (a) Metronome paced, EMG recording
21.5±3.4 right hand; (2) MVF of moving left hand; (3) no VF.
Fukumura et al. (2007)68 6 healthy individuals aged Flexion-extension of left wrist with (1) VF left hand; (2) VF left Bilateral (a) Metronome paced
20-39 + 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 & wrist with (1) Bilateral (a) Metronome paced
19-40 VF left side; (2) MVF left side
Garry et al. (2005)65 8 healthy individuals aged Finger-thumb opposition with (1) VF active hand; (2) VF Bilateral (a) Metronome paced, EMG recording
39.6±14.5 inactive hand; (3) neutral VF; (4) MVF active hand
Kang et al. (2011)66 30 healthy individuals aged Thumb abduction/adduction with (1) VF active hand + motor Bilateral (a) Metronome paced
28.0±2.4 and 30 stroke imagery; (2) MVF active hand + motor imagery inactive hand;
patients aged 66.0±11.0 (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 Exp1: TMS across nondominant/affected hemisphere during Bilateral (a) Metronome paced
30.9±2.2 and 18 stroke unilateral flexion-extension of the dominant/unaffected wrist
patients aged 61.3±11.6 with (1) MVF, (2) virtual MVF, or during (3) relaxation.
Exp2: TMS across nondominant/affected hemisphere during
unilateral flexion-extension of the dominant/unaffected wrist
with (1) continuous virtual MVF, (2) internmittent virtual MVF
Merians et al. (2009)47 1 healthy individual Finger tapping right hand with (1) virtual VF active hand; (2) Bilateral (a) None
virtual MVF active hand
Abbreviat
ions: 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.
! 23
Confounds in All Experimental Studies Using PET, MEG, EEG, and NIRS Included in the Systematic Review.
Study reference Modality Participants Outline of experimental methodology relevant to this review Type of MVF (a) Measures to avoid
systematic variation
Dohle et al. (2011)57 PET 10 healthy individuals aged PET; Unilateral circular movement of left or right arm with (1) Unilateral (a) Metronome paced
19-42 VF; (2) virtual MVF
Fink et al. (1999)58 PET 10 healthy individuals aged PET; Luria’s bimanual circle drawing task: (1) in phase with VF; Bilateral (a) None
20-73 (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 aged MEG; Index finger extension with MVF of active hand, (1) with Bilateral (a) None
22-35 VF of active hand or (2) without VF of active hand
Tominaga et al. (2009)49 MEG 11 healthy individuals aged MEG; Stimulation of right median nerve at wrist while holding a Unilateral (a) N/A
19-34 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 aged MEG; Stimulation of right or left median nerve at wrist while Unilateral (a) N/A
19-34 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 & Kakigi MEG 10 healthy individuals aged MEG; Stimulation of left median nerve at wrist while flexing- Bilateral (a) None
(2012a)52 24-46 extending left thumb repetitively or at rest with (1) MVF of
stationary right hand; (2) VF of both hands
(2012b)51 28-46 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 EEG; Extension-flexion right or left index finger with (1) VF Unilateral (a) Set number of trials, EMG
32±11 active finger; (2) MVF active finger recording
Touzalin-Chretien et al. EEG 11 healthy individuals aged EEG; Key press with right hand [except (4)] with (1) VF of right Unilateral (a) Set number of trials, EMG
(2008)56 27.7 hand; (2) MVF of right hand; (3) MVF of right hand in a frontal recording
mirror; (4) VF of left hand
(2010)53 32.2 hand; (2) VF of left hand; (3) MVF of right hand; (4,5) MVF of recording
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 NIRS; Unilateral grasping movements with right or left hand Bilateral (a) Metronome paced
21.1±1.1 with (1) VF of non-moving hand (2) with MVF of moving limb
Mehnert et al. (2013)60 NIRS 22 healthy individuals aged NIRS; Unilateral index finger-thumb opposition of either left or Unilateral (a) Metronome paced
21-40 right hand with (1) virtual VF, (2) virtual MVF.
! 24
Abbreviations: MVF, mirror visual feedback; VF, normal visual feedback; PET, positron emission topography; MEG, magnetoencephalography; EEG, electroencephalography; NIRS, near infrared spectrometry.
! 25
Table 4. Outline of the Methodology in All Clinical or Training Studies Included in the Systematic Review.
Study reference Modality Participants Nature of training Frequency & Outline of experimental methodology
duration relevant to this review
Bae et al. (2012)54 EEG MG: 10 stroke patients MG: bilateral movements with MVF 4 weeks, 5 Observation of hand movements during rest,
aged 55.2±8.5 CG: unilateral movements of paretic side with VF of two sessions/week, while measuring µ- rhyrthm across left (C3),
CG: 10 stroke patients limbs 30’/session right (C4) and (Cz) central fissure prior to and
aged 52.6±11.2 after training.
Bhasin et al. (2012)69 fMRI MG: 20 stroke patients Bilateral hand exercises with virtual MVF on laptop 8 weeks, 5 Repetitive clenching/extension of fist at the
aged 28-62 screen sessions/week, affected side without VF pre and post training
30’-60’/session
Hamzei et al. (2012)44 fMRI MG: 13 healthy MG & CG: 5 unimanual skills (RH only) with MVF 4 days, 20’/day fMRI during (1) AO of grasping movement
individuals aged 23.9 or VF of RH only during rest (2) active imitation of grasping
CG: 13 healthy movement with left or right hand, pre and post
individuals aged 25.5 training
Laeppchen et al. TMS MG & CG: 10 healthy MG & CG: 5 unimanual skills (RH only) with MVF 4 days, 20’/day Test of TMS parameters (MT, ICI, ICF, IHI
(2012)61 individuals aged 24.1 or VF of RH only left hemisphere) pre and post training
Michielsen et al. fMRI MG: 9 stroke patients MG & CG: bimanual exercises with MVF or VF of two 6 weeks, 5 fMRI during clenching movement with
(2011b)45 aged 51.9±9.3 hands sessions/week, affected hand without VF pre and post training
CG: 7 stroke patients 60’/day
aged 59.0±10.4
Nojima et al. (2012)62 TMS Exp1. MG & CG: 10 MG & CG: unimanual (RH only) ball handling task with 10 sets of 30’’ Test of TMS parameters (MT, SICI, IHI) pre
healthy individuals MVF or VF of 2 hands each and post practice
(young adults)
Exp2. MG1 and MG2: 8 MG1 = MG2: unimanual (RH only) ball handling task 10 sets of 30’’ Similar to Exp1. Practice was followed by
healthy individuals with MVF each cTBS over M1 (MG1) or occipital cortex
(young adults) (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.
"#!
22-48 active hand
aged 70.0
aged 50-72
! 22
right hand
imagery other hand
Abbreviat
! 23
phase with MVF
hands
! 24
! 25
30’-60’/session
aged 59.0±10.4
(young adults)
"#!
22-48 active hand
aged 70.0
aged 50-72
! 22
right hand
imagery other hand
Abbreviat
! 23
phase with MVF
hands
! 24
! 25
30’-60’/session
aged 59.0±10.4
(young adults)
"#!
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!
Healthy! Dorsolateral prefrontal cortex! 9/46! Right58! Bi! Attention!
Precentral gyrus (M1)! 4! Ipsi41,47,63,65-68! Uni & Bi! Motor!
Postcentral sulcus, posterior wall (S1/S2)! 2! Contra52! Uni & 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 & 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 & 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 & Bi! Attention!
Posterior cingulate cortex! 30! Contra40! Bi! Attention!
Abbreviation: MNS, mirror neuron system.

aThe 2 final columns indicate the type of MVF that elicits this observation and the network to which specific areas are
considered to belong.
bContralateral (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.
"#!
Figure captions
Figure 1: Flow diagram of the article selection process.
"$!
"%!
Supplementary material to Figure 1
List of all 8 references excluded in 2nd stage and the reason for exclusion.
Study reference Imaging Reason for exclusion

modality
Egsgaard et al. (2011) EEG Examines effect of MVF on tactile perception, not on motor control
Llobera et al. (2013) EEG EEG used to control brain computer interface, not to examine effect of MVF
Nojima et al. (2011) TMS Conference proceeding. Full paper is included (Nojima et al. 2012)
Nojima et al. (2013) TMS Neuroimaging used for diagnostic purposes, not to examine effect of MVF
Ohtsuka et al. (2009) TMS Conference proceeding, limited data.
Papeo et al. (2011) EEG Examines effect of MVF on tactile perception, not on motor control
Ro et al. (2004) TMS Examines effect of MVF on tactile perception, not on motor control
Seidel et al. (2011) fMRI Examines effect of MVF on pain, not on motor control
Full bibliographic details of all 8 excluded references:
• Egsgaard LL, Petrini L, Christofferson G, Arendt-Nielsen L. Cortical responses to the mirror box
illusion: a high-resolution EEG study. Exp Brain Res. 2011;215:345-57.
• Llobera J, González-Franco M, Perez-Marcos D, Valls-Solé J, Slater M, Sanchez-Vives MV.
Virtual reality for assessment of patients suffering from chronic pain. A case study. Exp Brain
Res. 2013;225:105-17.
• Nojima I, Koganemaru S, Fukujama H, Kawamata T, Mima T. Effect of mirror visual feedback
on human motor plasticity. Neurosci Res. 2011;71S:e253.
• Nojima I, Oga T, Fukuyama H, Kawamata T, Mima T. Mirror visual feedback can induce motor
learning in patients with callosal disconnection. Exp Brain Res. 2013;227:79-83.
• Ohtsuka H, Matsuzawa D, Numata K, Yoshida S, Nakazawa K, Shimizu E. Reduced transcallosal
inhibition during watching unilateral movement through mirror. Neurosci Res. 2009;65:S217.
• Papeo L, Longo MR, Feurra M, Haggard P. The role of the right temporoparietal junction in
intersensory conflict: detection or solution? Exp Brain Res. 2010;206:129-39.
• Ro T, Wallace R, Hagedorn J, Farnè A, Pienkos E. Visual enhancing of tactile perception in the
posterior parietal cortex. J Cog Neurosci. 2004;16:24-30.
• Seidel S, Kasprian G, Furtner J, Schöpf V, Essmeister M, Sycha T, Auff E, Prayer D. Mirror
therapy in lower limb amputees – A look beyond primary motor cortex reorganization. Fortschr
Röntgenstr. 2011;183:1051-57.
&'!
Supplementary material to Table 1d - Outline of the type of MVF, and measures to
avoid systematic variation across conditions in all clinical or training studies included
in the systematic review.
Study reference Type of MVF (a) Measures to avoid systematic variation across conditions
Bae et al. (2012)54 Bilateral (a) no measures taken
(b) task in sham and mirror condition is different
Bhasin et al. (2012)69 Unilateral (a) visual monitoring of movement in fMRI
(b) no control group
Hamzei et al. (2012)44 Bilateral (a) set number of trials + EMG recording of movement
Laeppchen et al. Bilateral (a) set number of trials + EMG recording

(2012)61
Michielsen et al. Bilateral (a) movement is metronome paced
(2011b)45
Nojima et al. (2012)62 Bilateral (a) set number of trials + EMG recording
Abbreviation: Bilateral MVF = active hand and its mirror reflection; Unilateral MVF = MVF of active hand only.
&(!
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Reﬂections on Mirror Therapy: A Systematic Review of the Effect of Mirror

Article in Neurorehabilitation and Neural Repair · August 2014

Frederik J A Deconinck Ana Smorenburg

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Alex Benham Annick Ledebt

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visual feedback on the brain

Deconinck FJA1,2,*(PhD), Smorenburg ARP3(PhD), Benham A4(PhD), Ledebt

A5(PhD), Feltham MG6(PhD), Savelsbergh GJP5(PhD)!

Ghent University –!Faculty of Medicine and Health Sciences, Department of

Movement and Sports Sciences, Watersportlaan 2, 9000 Gent, Belgium!

Tel.: +32 (0)9 264 91 37!

This paper is published in Neurorehabilitation and Neural Repair.

The final publication is available at Sage via

findings of the systematic review in relation to the hypotheses introduced in Part 1

Part 1: Mirror therapy – background, current applications, and potential

Finally, MVF or the associated illusion is thought to increase an individual’s

Part 2: The neural correlates of mirror visual feedback

2.2. Literature search

Inclusion criteria were the following:

• Experimental studies or clinical trials

Exclusion criterion was the following:

The records identified by this search were screened independently by 2 authors of

intervention in healthy individuals (n = 3) or stroke patients (n = 3). Here, bilateral

Instant Neuromodulatory Effects of MVF. The neuromodulatory effects of MVF

This systematic review aimed to identify instant and long-term neuromodulatory

Second, MVF seems to cause increased immediate activation of STG46 and

Part 3: Summary and future directions

Declaration of Conflicting Interest

1. Thompson P, Papadopoulou G, Vassiliou E. The origins of entasis: illusion,

32. Staudt M, Grodd W, Gerloff C, Erb M, Stitz J, Krägeloh-Mann I. Two types of

randomized controlled trial. Neurorehabil Neural Repair. 2011;25(3):223–33.

61. Laeppchen CH, Ringer T, Blessin J, et al. Optical Illusion alters M1

of Activation Listed According to Populationa,b.

Population! Area! BA! Side! MVF! Network!

Healthy! Dorsolateral prefrontal cortex! 9/46! Right58! Bi! Attention!

Precentral gyrus (M1)! 4! Ipsi41,47,63,65-68! Uni & Bi! Motor!

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 & Bi! Attention!

Superior temporal gyrus! 39! Ipsi46! Bi! MNS!

Cuneus/Lingual gyrus (V1/V2)! 17/18! Ipsi38,42! Uni! 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 & Bi! Attention!

Posterior cingulate cortex! 30! Contra40! Bi! Attention!

Abbreviation: MNS, mirror neuron system.

Figure 1: Flow diagram of the article selection process.

Supplementary material to Figure 1

Study reference Imaging Reason for exclusion

Ohtsuka et al. (2009) TMS Conference proceeding, limited data.

Full bibliographic details of all 8 excluded references:

Supplementary material to Table 1d - Outline of the type of MVF, and measures to

in the systematic review.

Laeppchen et al. Bilateral (a) set number of trials + EMG recording

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