Additional Info
Sample size/power
Sample size estimation has been performed, for all the proposed experiments, using a series of simulations in order to overcome the limitation of typical power estimation procedures, which are not suitable for studies employing a non-parametric statistical framework, as the one to be employed in this project. These simulations consisted in generating, for varying sample sizes, n =5 00 datasets with an expected effect magnitude, performing the non-parametric permutation-based statistical contrasts and counting how many times a significant difference was observed, i.e. the power. Based on preliminary data collected on Moebius patients the effect size was fixed at Cohen’s d = 0.9, for experiment 1 and 2. For the Bell’s patients, for whom there was no preliminary data at hand, the effect size was fixed at Coehn’s d = 0.8, for experiment 3 and 4. The same effect size was used for power simulations for experiment 5 and 6. This procedure revealed that for the studies involving the Moebius patients a sample size of 18 is enough to detect a significant effect in 80% of the simulations (power = 80%). For the studies involving Bell’s patients a sample size of ~25 is necessary to achieve a power of 80%. Finally, for the experiments involving healthy participants the required sample size is ~40 to achieve 80% statistical power (Exp. 5 and 6).
Proposal for a new rehabilitative protocol
Note: This protocol has been tested in MBS individuals following surgery. We intend to adapt this protocol for rehabilitation of individuals with Bell's palsy.
Peripheral facial palsy (PFP) is a neurological condition in which the function of the facial nerve is partially or completely lost. This leads to impairment of the mimic muscles resulting in a disfiguring condition [1–4].
The treatment of facial paralysis is determined by the etiology and what portions of the face are affected. In patients presenting congenital or acquired long term peripheral facial paralysis, neuromuscular transplantation (free gracilis muscle graft, FGMG) is the optimal option in order to restore a dynamic smile[5–11]. A portion of Gracile muscle is taken from the patients’ leg with its own nerve and blood vessels and transferred into the face and connected to the masseteric nerve which is responsible for activating the bite via the masseter muscle[5,7,8,10]. Right after the surgery, the patient is not yet able to use the transplanted muscle to smile and it is necessary to train the muscle by undergoing rehabilitation treatment[1,12].
Combining the most recent discoveries from the world of neuroscience with the needs of clinical practice, we have proposed a “dedicated” neurorehabilitative treatment (FIT-SAT) for patients who undergo FGMG with gracilis muscle transplantation re-innervated by the masseteric nerve. FIT-SAT includes the observation and execution of corner-of-the-mouth smile (facial “smile” imitation treatment, FIT) accompanied by the closing of the hand (synergistic-activity treatment, SAT)[12,13]
We hypothesized that motor recovery in patients undergoing FGMG might improve through action observation therapy, a specific treatment based on mirror neuron system literature[14–21]. From a theoretical point of view, motor and premotor activations during action observation (AO) should be at least in part similar to those in action execution[15,17,22,23]. AO therapy is defined as a motor training that involves the observation of specific actions performed by others and it may offer an effective adjunct to physical practice[15]. Thus, through FIT, patients who are asked to observe video clips in which an actor performs a smile, should be facilitated in their movements. In addition, hand closing might further facilitate the transplanted muscle recruitment. In fact, numerous neuroscientific researches demonstrated that hand and mouth cortical fields in the motor and somatosensory cortex partially overlap[24–26]. Specifically, some researchers demonstrated that the grasping action and the mouth opening movement are represented as motor synergies for which the closure of the hand is accompanied by the opening of the mouth. These hand/mouth movements are synchronous and coordinated to maximize their efficacy[24–28]. Thus, the simultaneous activity of hand closing during smile production would facilitate the recruitment of mouth motor neurons in the cerebral cortex[12,13,29].
The FIT-SAT treatment includes videos containing instructions and daily exercises to be performed at home for up to six months.
The protocol is divided into two phases.
The first (unilateral rehabilitation) phase aims at increasing muscle strength with unilateral exercises and begins when the patient starts to recruit the transplanted muscle. This phase consists of a series of video clips of an actor performing only unilateral smiles which are then imitated by the patient. Each video clip contains instructions concerning both the co-activation of hand closed as a fist and the specific number of repetitions that patients must perform each day. The duration of the first phase varies from patient to patient depending on the muscle recruitment.
The second phase of the treatment begins only after the patient is able to perform multiple repetitions of the unilateral movement maintaining the posture for at least three seconds. The second (bilateral rehabilitation) phase aims at synchronizing the contraction of both sides in order to obtain a harmonious movement and a natural smile. This is achieved by presenting clips of an actor smiling bilaterally and by giving instruction about the co-activation of the hands. Bilateral exercises include modulation tasks in which the patient is asked to perform maximum and small (gentle) smiles in order to train and control the contraction force of the transplanted muscle/s. The second phase of the FIT-SAT ends when the speech therapist determines that the patient is able to synchronize the contraction of both sides in order to obtain a harmonious movement and a natural smile.
To test the efficacy of the FIT-SAT two experiments were conducted.
In the first experiment four patients with bilateral and congenital facial nerve paralysis (Moebius syndrome) were included. They underwent two FGMG, one year apart from each other. The side of the face first operated was rehabilitated with the traditional treatment which involves spontaneous muscle recruitment through teeth grinding[13,30], while the second side was rehabilitated with FIT-SAT.
As soon as an initial activation of the transplanted muscle was observed participants began FIT-SAT at home (or traditional treatment) and took part in an experimental session in which the three-dimensional (3D) kinematics of mouth was registered (SMART-DX-100 system, BTS Bioengineering, Milan, Italy) at the beginning (T1) and at the end (T2) of the rehabilitation process. The experimental conditions required participants to: imitate the unilateral smile observed on video-clips by closing the ipsilateral hand (SO-HC); imitate the movement observed on video-clips without closing the hand (SO); perform a unilateral smile without observing it on video-clips and close the ipsilateral hand (HC); perform a unilateral smile without observing it and without closing the ipsilateral (BC) hand. Two markers were applied at the corners of the mouth and a further additional marker was placed on the nose (reference point). Bilateral amplitude was calculated as the maximal intercommissural distance (maximal mouth aperture MMA), that is, the Euclidian distance in millimeters between the two lip corner markers. Left (or right) smile excursions (Left/Right SIDE) were also calculated as the Euclidian distances in millimeters between the left (right) lip corner marker and the nose marker. Finally, we also calculated the Asymmetry Index of the bilateral blocks (AI%), which provides information to evaluate the attainment of a harmonious and natural movement.
We used linear mixed-effects models fit by maximum likelihood (LMM) to test the efficacy of the FIT-SAT conditions (SO-HC, HC, SO) on the excursion of the patients’ smile. Results suggest that the observation of a smile and its subsequent reproduction associated with hand closure (SO-HC, figure 1) increased patients’ unilateral smile excursion with respect to the baseline condition. We also observed a reduction in asymmetry and a greater excursion of the bilateral smile (figure 2). Last, but not least, in bilateral task we did not find significant differences comparing the excursion of the right side at T1 (side of the face rehabilitated with traditional treatment) and the left side at T2 (side of the face rehabilitated with FIT-SAT treatment). This result supports the conclusion that FIT-SAT treatment may be as effective as the traditional treatment in recruiting muscles involved in smiling after smile surgery.
In the second experiment 30 patients with congenital or acquired facial paralysis were included. Patients were divided into two groups: experimental group (EG) and control group (CG). EG rehabilitated their smile with FIT-SAT whereas CG underwent traditional treatment[13,30].
Frontal-view photographs were captured while participants maintained the following posture: a rest condition (baseline), gentle and maximal smile. The photos were uploaded and analyzed using Emotrics (Emotrics Software, Mass Eye and Ear, Boston, MA32) an open source software based on a machine learning algorithm that calculates a full set of measurements relevant to quantify facial symmetry. Emotrics measurements were: commissure excursion (CE, the distance from the midline of the vertical/lower lip vermilion junction to the oral commissure)6, commissure height deviation (CHD, vertical distance between the horizontal plane of the left and the right oral commissure), upper/lower lip height deviation (ULHD/LLUD, vertical distance between horizontal planes taken from the upper/lower lip vermillion border points where they intersect with a vertical plane taken midway between the mid-vertical and the oral commissure) and smile angle (SA, the angle between the horizontal plane at the midline vertical/lower lip vermilion junction and the oral commissure).
Analyses of covariance (ANCOVAs) were performed adjusted for participants’age to test for differences in symmetry between groups (EG vs. CG). We were interested to test for any statistically significant differences on Emotrics measurements (CE, CHD, ULHD/LLUD and SA) between the two treatments.
Except for ULHD, in the maximum smile both treatments did not differ in terms of symmetry; on the contrary, in the gentle smile the EG group obtained a better symmetry than the CG, figure 4. These results suggested that the FIT-SAT allows patients to better modulate the smile making them aware of the force necessary to contract the muscles of the face. This, in turn, permits to control the extent of the lips excursion and adapt the smile to the various social contexts.
DISCUSSION
FIT-SAT treatment for patients who underwent FGMG is aimed at combine neuroscientific knowledge relating to the organization of the somatosensory cortex with the needs of clinical practice. Specifically, FIT-SAT exploits hand/mouth synergies and the principles of action observation therapy (observe to imitate) to facilitate the activation of motor programs involved in the control of transplanted muscle for smiling. Such rehabilitative treatment is based on two main hypotheses:
1. observation of smile movement activates an action-observation (AO) network which facilitates the correspondent motor programs as already demonstrated for the superior arms[14–17,22,31];
2. the activation of the motor programs controlling the transplanted muscles is facilitated by the contingent activation of the hand. Such synergy is supported by the notion that hand and mouth motor representation at the cortical level (both in M1 and premotor cortex) do overlap. Hence, activity of neurons of the hand could facilitate the recruitment of the cortical motor commands involved in the control of facial muscles[24,26–29,32,33]. Results support FIT-SAT as a viable alternative for smile rehabilitation after FGMG. Specifically, results of experiment one suggested that the combined use of smile observation and hand closure determined a greater recruitment of the transplanted muscle with respect to baseline condition at the initial phase of the rehabilitation process. Furthermore, results of experiment two also suggested that FIT-SAT allows patients to better modulate the smile making them aware of the force necessary to contract the muscles of the face. This, in turn, permits to control the extent of the lips excursion and adapt the smile to the various social contexts. This is a crucial aspect to improve reciprocal interactions and one's emotions expressions through the face.
References
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Contacts and Info:
Elisa De Stefani (Psychologist-psychotherapist, Ph. D. postdoctoral researcher)
E-mail: elidestefani@gmail.com
Pier Francesco Ferrari (Director at the "Marc Jeannerod" Institute of Cognitive Sciences of the National Center for Scientific Research (CNRS) in Lyon and Associate Professor at the University of Parma)
Anna Barbot (Speech Therapist, the idea of the protocol was born from her experience and professional intuition. Anna is available for any information or further information about Bell's palsy or acquired palsies in general)
Cecilia Zannoni (Speech Therapist)
Chiara Bertolini (Speech Therapist)
Mauro Belluardo (Psychologist, Ph. D. postdoctoral researcher)
Dr. Bernardo Bianchi (Surgeon, Maxillofacial Surgery Unit, University Hospital of Parma)
Dr. Andrea Ferri (Surgeon, Maxillofacial Surgery, University Hospital of Parma)
STRUCTURES INVOLVED:
Neuroscience Unit, Department of Medicine and Surgery, University of Parma
Head-Neck Department, UOC Maxillofacial Surgery, University Hospital of Parma
Institut des Sciences Cognitives Marc Jeannerod, CNRS, Université de Lyon, Bron, France
PROJECT SUPPORTED BY:
AISMo - Italian Association of Moebius Syndrome
Cariparma Foundation
European Diagnostic Center Dalla Rosa Prati
Filippo Bassignani Foundation