Accepted Manuscript Mapping the Mirror Neuron System in Neurosurgery: Case Report Julio Plata Bello, PhD, Cristián Modroño, PhD, Francisco Marcano, PhD, José Luis González–Mora, PhD PII:
S1878-8750(15)00929-8
DOI:
10.1016/j.wneu.2015.07.059
Reference:
WNEU 3087
To appear in:
World Neurosurgery
Received Date: 29 March 2015 Revised Date:
25 July 2015
Accepted Date: 28 July 2015
Please cite this article as: Plata Bello J, Modroño C, Marcano F, González–Mora JL, Mapping the Mirror Neuron System in Neurosurgery: Case Report, World Neurosurgery (2015), doi: 10.1016/ j.wneu.2015.07.059. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title Mapping the Mirror Neuron System in Neurosurgery: Case Report.
RI PT
Authors Julio Plata Bello (PhD)1,2, Cristián Modroño (PhD)1, Francisco Marcano (PhD)1, José Luis González–Mora (PhD)1.
Affiliation Department of Physiology, Faculty of Medicine, University of La Laguna, Spain. 2 Hospital Universitario de Canarias (Department of Neurosurgery), S/C de Tenerife, Spain.
SC
1
AC C
EP
TE D
M AN U
Corresponding author Julio Plata Bello Address: Hospital Universitario de Canarias (Neuroscience department), Calle Ofra s/n La Cuesta. CP 38320. La Laguna, S/C de Tenerife. Spain. Phone number: +34 922 255 544 / +34 646 625 973. E – mail address:
[email protected]
1
ACCEPTED MANUSCRIPT Abstract Background Brain mapping is considered an important approach in neurosurgery to achieve better functional outcomes. The Mirror Neuron System (MNS) is a brain network implicated in action understanding and imitation. No previous study has focused on identifying
RI PT
and monitoring the MNS function during the peri-operative period in brain lesions
The aim of this study is to describe the application of an fMRI protocol to identify the MNS in a patient with a lesion in the premotor region.
SC
Case description
A specific fMRI protocol to identify regions belonging to the MNS was performed in a
M AN U
19-year-old-female patient who presented a cavernous angioma in the premotor region. The patient showed signs of impairment when imitating simple and complex hand movements. The fMRI protocol was performed prior to surgery and 3 months after the surgical procedure. The protocol consisted of an observation and an execution condition of a simple intransitive finger movement (precision grasping).
TE D
MNS regions were identified during both, pre- and post-surgical fMRI trials. Such mirror areas were respected during the procedure. The activation of those regions notably improved after the procedure, with a correlation between the recovery of the ability to imitate simple and complex hand movements and a higher and better-
AC C
Conclusion
EP
defined MNS activity.
The use of an fMRI protocol with observation and execution conditions based on simple intransitive finger actions allows the easy identification and preservation of the MNS. An increased activity in post-operative fMRI may be associated with improvement in motor functions.
Keywords Action observation; brain mapping; mirror neurons.
2
ACCEPTED MANUSCRIPT Introduction Brain mapping is considered an important approach in neurosurgery to achieve better functional outcomes. This approach gives a precise estimation of the location of the functional areas in relation to a lesion (e.g. a tumor), thus decreasing the surgical risk (1).
RI PT
One of the most widely-used methods for pre-operative brain mapping is the functional magnetic resonance imaging (fMRI). Many brain functions have been mapped using this technique (e.g. language and other motor-related conditions) and there are studies where the usefulness of brain mapping has been demonstrated in
SC
neurosurgery (for an extensive review see Duffau, 2011 (2)). However, no one has focused on mapping the functioning of the mirror neuron system (MNS). The MNS is a
M AN U
brain network which is activated during both, the execution and the observation of a motor action. The core of the MNS is extended over parietal regions (Superior Parietal Lobule [SPL], Inferior Parietal Lobule [IPL] and Intraparietal Sulcus [IPS]) and frontal regions (Dorsal and Ventral Premotor Cortex [dPMC and vPMC] and Inferior Frontal Gyrus [IFG]) (3–5). The MNS is associated with the capacity to understand the actions
TE D
performed by others. In this sense, the MNS integrates the motor action that is being observed with a motor action repertoire, and it allows the recognition of the action as well as its meaning (3,6). Bearing this function in mind, the MNS has also been associated with action imitation (7) and action prediction (8). Disturbance of the MNS
EP
may be related with significant cognitive impairment (9). fMRI has also been extensively used to investigate the features of the MNS and it is
AC C
accepted as an appropriate method for studying this brain network (10). Considering the lack of studies about the MNS in neurosurgical patients, the aim of the present report is to describe the application of an fMRI protocol to identify the MNS in a patient with a mass lesion in the premotor region.
Case presentation A 19-year-old right-handed woman was admitted to the Emergency Department after presenting a secondary generalized tonic-clonic seizure. She was affected by hereditary multiple cavernous angiomas. Three months previously, she had another 3
ACCEPTED MANUSCRIPT epileptic seizure associated with radiological signs of bleeding in a left temporal lobe cavernous angioma. The patient refused any surgical treatment for this lesion. The neurological examination revealed the presence of a slight left hemiparesis (4/5) and numbness predominantly in the left arm. No other neurological signs were identified, although she showed signs of impairment when imitating simple finger actions with
RI PT
her left hand. The Purdue Pegboard test, used for evaluating the ability to perform precision grasping actions (11), was applied in the same manner as previous studies (12), she scored 15.3 with the right hand and 8.7 with the left hand.
A computed tomography (CT) scan was performed, showing the presence of a right
SC
frontal hematoma without significant mass effect (figure 1a). Previous imaging studies had shown the presence of a cavernous angioma in that location, thus the bleeding
M AN U
was considered to be related. Conservative treatment was considered and the patient progressively presented a deterioration of the left hemiparesis and a worsening in the Purdue Pegboard test scores. This was coherent with a chronically intratumoral evolution of the bleeding monitored by CT scan (Figure 1b) and MRI (figure 1c and 1d). Furthermore,
important
vasogenic
oedema
was
identified,
which
is
why
TE D
dexamethasone therapy (4mg each 6 hours) was initiated and whose response after 5 days of treatment was unsatisfactory. Therefore, the patient finally gave her consent to perform a surgical procedure in which the haematoma and the cavernous angioma were both removed via a frontal craniotomy. Preoperative fMRI with a specific
EP
protocol for determining the MNS was performed (see below) and the identified regions were easily respected.
AC C
The postsurgical evolution was uneventful and standard motor rehabilitation program was initiated and no observation based rehabilitation approaches were included. The same preoperative fMRI protocol was performed in order to identify differences in the MNS activation. When this fMRI was performed (3 months after the procedure), the patient had recovered almost normal function in the left side of the body with the persistence of a slight numbness. She was able to imitate simple movements with the left hand without any difficulty and her Purdue Pegboard Test score was 16.4 with the right hand and 13.8 with the left hand. At this moment in time, after one year’s follow up, the patient presents normal motor and sensory function. Conservative management has been prescribed for the remaining cavernous angiomas. 4
ACCEPTED MANUSCRIPT
Materials and Methods Study protocol In order to identify regions with common activation during the execution and the
RI PT
observation of a motor action, the fMRI protocol from another study was used (12). In brief, two fMRI runs were performed, one for each condition (execution or observation). Both studies were structured with block designs. Execution and observation blocks lasted 15 seconds and after a period of fixation (3 seconds for the
SC
execution study and 5 for the observation study) a control condition was displayed for each fMRI run. For the execution the control condition consisted of a static white cross
M AN U
in the middle of the screen; for the observation the control condition consisted of static photographs of a hand. The execution was performed with only the left hand with a 1Hz visual-guided frequency. Observation blocks consisted of the observation of videos where a right or left hand performed the index to thumb opposition task in a first or a third person perspective. Each fMRI run consisted of 12 blocks for each
TE D
condition.
Arms were positioned beside the body and the left hand was with the palm facing upward with the wrist in a neutral position during the procedure.
EP
Data acquisition and processing
Data for the experiment were collected at the Magnetic Resonance for Biomedical
AC C
Research Service of the University of La Laguna (SRMIB). Functional images were obtained on a 3T General Electric (Milwaukee, WI, USA) scanner using an echo-planar imaging gradient-echo sequence and an 8 channel head coil (TR = 3000ms, TE = 21ms, flip angle = 90◦, matrix size = 64 × 64 pixels, 57 slices/volume, spacing between slices = 1 mm, slice thickness = 3 mm). The slices were aligned to the anterior commissure – posterior commissure line and covered the whole cranium. Functional scanning was preceded by 18 s of dummy scans to ensure tissue steady-state magnetization. A whole-brain three-dimensional structural image was acquired for anatomical reference. A 3D fast spoiled gradient – recalled pulse sequence was obtained with the following acquisition parameters: TR = 10.4 ms, TE = 4.2 ms, flip angle = 20, matrix size 5
ACCEPTED MANUSCRIPT = 512 × 512 pixels, .5 × .5 mm in plane resolution, spacing between slices = 1 mm, slice thickness = 2 mm. After checking the images for artefacts, data were preprocessed and analyzed using Statistical Parametric Mapping software SPM8 (Wellcome Trust Centre for Neuroimaging; http://www.fil.ion.ucl.ac.uk/spm/) and displayed using xjView 8.1
RI PT
(http://www.alivelearn.net/xjview8/). The images were spatially realigned, unwarped, and normalized to the Montreal Neurological Institute (MNI) space using standard SPM8 procedures. The normalized images of 2 × 2 × 2 mm were smoothed by a full
SC
width at half maximum (FWHM) 8 × 8 × 8 Gaussian kernel.
Simple T contrasts
M AN U
A block design in the context of a general linear model was used, for individual subject analyses (first level), to look for differences in brain activity during the periods of observation and the control condition. The considered contrasts in the analysis were as follows: Index Observation > Control and Index Execution > Control. Significance was considered with a p-value of 0.001 uncorrected thresholds with a minimum cluster size
Conjunction analysis
TE D
of ten voxels.
A conjunction analysis using the Minimum Statistic compared with the Conjunction
EP
Null method (13) was performed to determine voxels activated by observation and execution. The assumption is that brain regions with mirror properties are among
AC C
those activated during both conditions. Significance was considered with a p-value of 0.005 uncorrected threshold with a minimum cluster size of ten voxels.
Results
Preoperative fMRI Mirror activity in the presurgical fMRI was confined to bilateral parietal lobes and corresponded to posterior parietal regions (i.e. IPL and SPL). Right parietal activation appeared to be displaced due to the lesion itself and the associated-oedema, which laterally pushed the normal brain structures (figure 2a). Another interesting finding is 6
ACCEPTED MANUSCRIPT that the observation condition did not lead to significant activity in premotor regions that are associated with the MNS (i.e. IFG). Furthermore, higher activity in prefrontal regions and medial frontal areas (cingulate gyrus) was observed during the observation condition (see supplementary material).
RI PT
Postoperative fMRI
In the postsurgical fMRI (three months after the procedure) important differences were seen compared with the presurgical fMRI. Mirror activity was higher and better defined and extended into bilateral premotor regions (clusters of activity in the IFG)
SC
and in the sensorimotor cortex (SMC) and posterior parietal regions (the cluster included regions belonging to the IPL) (figure 2b). Much less activity in prefrontal
M AN U
regions was observed during observation conditions (see supplementary material).
Discussion
The main finding of the present report is the notable change in the MNS activity after a
TE D
surgical procedure to remove a carvernous angioma. MNS regions showed very low activity during the execution and the observation of a simple finger action before surgery. However, three months after the procedure, the fMRI showed a significant increase of activity in the MNS. These findings and their possible significance in brain
EP
mapping will be discussed below.
A notable increase of activity in posterior parietal regions, as well as, in the premotor
AC C
regions in the right hemisphere was identified 3 months after the surgical procedure, as can be seen in figures 2a and 2b. This greater activity in the MNS also correlated with an improvement in the neurological status, with an almost complete recovery of the left hemiparesis. However, this study is not able to demonstrate that the functional recovery was directly related with the increase in MNS activity. In fact, this might be a consequence and not a cause of the motor recovery. In order to identify the activity of the MNS, we used a simple fMRI protocol, based on an observation condition and an execution condition. Mirror activity (i.e. common activity between observation and execution) was identified using a conjunction analysis (13). The index to thumb opposition task was chosen as the motor action 7
ACCEPTED MANUSCRIPT because it is a simple intransitive (i.e. with no object interaction) motor action, which can be considered as the pantomime of a precision grasping action (14). This action is performed in the daily activities of primates and its impairment leads to noticeable disability (15). The simplicity of the selected action and the fact that object interaction is unnecessary makes this a suitable protocol to apply in fMRI studies where significant
RI PT
space limits exist. Furthermore, it may also be useful in patients with some degree of weakness, because it is a common action and it does not require much cognitive effort to perform the action.
Brain mapping for indentifying the relationship between brain lesions and functional
SC
areas is now considered a standard in brain surgery (for an extensive review see (2)). However, no previous study has focused on mapping the MNS. In this sense,
M AN U
disturbances in the MNS have been related with different pathological conditions. Lesions in the posterior parietal regions (belonging to the MNS) have been associated with deficits in comprehension of motor acts and in object-related gesture recognition (16,17). On the other hand, MNS dysfunctions are associated with complex psychiatric conditions, including mood disorders (18). Bearing this in mind, as has been previously
TE D
proposed (9), injuring MNS regions could lead to a cognitive disturbance that may worsen the functional outcome of neurosurgical patients. Therefore, it would seem to be of interest to monitor the functioning of this system throughout the management of a brain lesion.
EP
On the one hand, pre-surgical mapping will allow the identification of regions belonging to the MNS in a distorted brain parenchyma due to primary lesion (e.g. brain
AC C
tumor) or oedema. The functioning of the MNS can be tested and an association between the pattern of activity and neurological disturbances can be identified or made with the approach presented here. In this case, it should be stressed that the patient presented signs of impairment when imitating simple finger actions with the left hand. This may be associated with disturbances in the MNS, bearing in mind the implication of this brain network in imitation (4,5,7). To this effect, when the MNS is affected motor learning might be impaired because of the importance of imitative behaviour in these processes (19). On the other hand, preoperative use of this sort of brain mapping procedure may be useful to identify regions with mirror properties which should be respected during the 8
ACCEPTED MANUSCRIPT surgical procedure. This point would be even more important if an observation-based rehabilitation program is considered (9), in view of the benefits that action observation based rehabilitation showed in stroke and other pathological conditions (20,21). In the present case, regions with mirror properties were respected using a neuronavigation system. The postoperative standard rehabilitation program was enough to achieve a
RI PT
good recovery of the MNS functioning. In this sense, the use of the same protocol after surgery may allow the monitoring of the effectiveness of the treatment in recovering the MNS function, since there is no specific test for assessing the function of this brain network.
SC
This case report clearly presents various limitations for extending the consideration of using this sort of fMRI protocol (i.e. MNS mapping) in neurosurgery. Larger series of
M AN U
cases and other types of brain lesions may be necessary to demonstrate the usefulness of this approach. Furthermore, clinical correlations with MNS disturbances should be better defined and the possible impact of observation based rehabilitation programs in
TE D
neurosurgical patients should be measured.
Conclusion
MNS disturbances have not been explored in neurosurgical patients to date. The presence of motor deficits may be associated with impairment in the MNS activity and
EP
a correlation between motor recovery and MNS activity may exist. Therefore, the use of fMRI protocols to identify MNS regions before a surgical procedure or for
AC C
monitoring the rehabilitation evolution may be useful in neurosurgical patients.
Acknowledgments
We would like to thank our volunteers for their participation in this study. We also thank Miguel Angel León Ruedas for his assistance with data acquisition and Silvia Acosta López for her valuable contribution in the video recordings.
9
ACCEPTED MANUSCRIPT References Duffau H: Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity. Lancet Neurol 4(8):476– 86, 2005. Doi: 10.1016/S1474-4422(05)70140-X.
2.
Duffau H, editor.: Brain Mapping. From Neural Basis of Cognition to Surgical Applications. 1st ed. SpringerWienNewYork; 2011.
3.
Cattaneo L, Rizzolatti G: The mirror neuron system. Arch Neurol 66(5):557–60, 2009.
4.
Rizzolatti G: The mirror neuron system and its function in humans. Anat Embryol (Berl) 210(5-6):419–21, 2005. Doi: 10.1007/s00429-005-0039-z.
5.
Iacoboni M, Mazziotta JC: Mirror neuron system: basic findings and clinical applications. Ann Neurol 62(3):213–8, 2007. Doi: 10.1002/ana.21198.
6.
Press C, Bird G, Walsh E, Heyes C: Automatic imitation of intransitive actions. Brain Cogn 67(1):44–50, 2008. Doi: 10.1016/j.bandc.2007.11.001.
7.
Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziotta JC, Rizzolatti G: Cortical mechanisms of human imitation. Science 286(5449):2526–8, 1999.
8.
Iacoboni M, Molnar-Szakacs I, Gallese V, Buccino G, Mazziotta JC, Rizzolatti G: Grasping the intentions of others with one’s own mirror neuron system. PLoS Biol 3(3):e79, 2005. Doi: 10.1371/journal.pbio.0030079.
9.
Plata Bello J, Modroño C, González-Mora JL: The role of mirror neurons in neurosurgical patients: A few general considerations and rehabilitation perspectives. NeuroRehabilitation, 2014. Doi: 10.3233/NRE-141167.
10.
Glenberg AM: Introduction to the Mirror Neuron Forum. Perspect Psychol Sci 6(4):363–8, 2011. Doi: 10.1177/1745691611412386.
12.
SC
M AN U
TE D
EP
AC C
11.
RI PT
1.
Tiffin J, Asher EJ: The Purdue pegboard; norms and studies of reliability and validity. J Appl Psychol 32(3):234–47, 1948.
Plata Bello J, Modroño C, Marcano F, González-Mora JL: The mirror neuron system and motor dexterity: What happens? Neuroscience 275:285–95, 2014.
13.
Nichols T, Brett M, Andersson J, Wager T, Poline J-B: Valid conjunction inference with the minimum statistic. Neuroimage 25(3):653–60, 2005.
14.
Plata Bello J, Modroño C, Marcano F, González-Mora JL: Observation of simple intransitive actions: the effect of familiarity. PLoS One 8(9):e74485, 2013.
10
ACCEPTED MANUSCRIPT Johanson ME, Valero-Cuevas FJ, Hentz VR: Activation patterns of the thumb muscles during stable and unstable pinch tasks. J Hand Surg Am 26(4):698–705, 2001.
16.
Heilman KM, Rothi LJ, Valenstein E: Two forms of ideomotor apraxia. Neurology 32(4):342–6, 1982.
17.
Buxbaum LJ, Kyle KM, Menon R: On beyond mirror neurons: internal representations subserving imitation and recognition of skilled object-related actions in humans. Brain Res Cogn Brain Res 25(1):226–39, 2005. Doi: 10.1016/j.cogbrainres.2005.05.014.
18.
Yuan T-F, Hoff R: Mirror neuron system based therapy for emotional disorders. Med Hypotheses 71(5):722–6, 2008. Doi: 10.1016/j.mehy.2008.07.004.
19.
Higuchi S, Holle H, Roberts N, Eickhoff SB, Vogt S: Imitation and observational learning of hand actions: prefrontal involvement and connectivity. Neuroimage 59(2):1668–83, 2012. Doi: 10.1016/j.neuroimage.2011.09.021.
20.
Ertelt D, Small S, Solodkin A, Dettmers C, McNamara A, Binkofski F, Buccino G: Action observation has a positive impact on rehabilitation of motor deficits after stroke. Neuroimage 36 Suppl 2:T164–73, 2007. Doi: 10.1016/j.neuroimage.2007.03.043.
21.
Small SL, Buccino G, Solodkin A: The mirror neuron system and treatment of stroke. Dev Psychobiol 54(3):293–310, 2012. Doi: 10.1002/dev.20504.
AC C
EP
TE D
M AN U
SC
RI PT
15.
11
ACCEPTED MANUSCRIPT Figure legends Figure 1. Preoperative imaging studies. a) Initial CT scan showing a frontal haematoma without significant mass-effect; b) 7-days post-initial CT scan showing that the haematoma is larger with a chronic evolution and with vasogenic oedema surrounding
RI PT
the lesion; c) axial T1-weighted and d) coronal FLAIR MRI images showing the cavernous angioma with the associated bleeding. Another cavernous angioma is
SC
shown in the right inferior cerebellar peduncle.
Figure 2. Functional magnetic resonance imaging (fMRI) showing the shared brain
M AN U
activity between action execution and action observation (p
