Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brain’s ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bell’s palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations.
Neuroplasticity is a common, yet complex phenomenon that occurs in both animals and humans [
Bell’s palsy (BP) offers an ideal human model to investigate neuroplasticity following peripheral nerve injury [
The primary somatosensory cortex (S1) and the primary motor cortex (M1) are well known for their precise physical representation of the body on the cortex, thereby providing a perfect location to explore the reorganization of the brain caused by BP. Brain imaging tools such as MRI/fMRI, MEG, and PET and neuromodulation methods have allowed investigators to explore changes in the brain’s structure, function, and excitability at S1 and M1 following different disorders [
Recently, intrinsic resting-state functional connectivity (rsFC) has drawn the attention of investigators, and been applied to investigate neural plasticity [
In this study we first used task-related fMRI (hand movement and mouth movement) to define subject’s cortical map at S1 and M1 and then investigated and compared the regional brain functional status in the early period of BP to healthy controls using ReHo [
Twenty-five right-handed patients with left or right side Bell’s palsy (House-Brackmann Scale (HBS) ≥3, age
There were a total of 5 tasks in our design: a facial movement task, left and right hand movement tasks, and left and right facial sensory stimulation task. We used a block design in our 5 tasks (Figure
The block design paradigm used in this study.
All scans were performed on the same 3.0 Tesla MR scanner (Magnetom Verio, Siemens, Germany) in order to obtain T1-weighted structural images and echo-planar
All functional data preprocessing and analyses were performed using Data Processing Assistant for Resting-State fMRI (DPARSF) software (
Before we processed the images, all BP patients with left side palsy and matched healthy controls were flipped along the
For each subject, all images were realigned using a six-parameter rigid-body transformation that corrected for motion artifacts. The images were then coregistered with the subjects’ corresponding anatomical (T1-weighted) images, normalized by using structural images unified segmentation, resampled to 3 mm cubic voxels, and spatially smoothed with a 6 mm full width at half maximum (FWHM) Gaussian kernel.
A multiple regression analysis using a general linear model was performed to obtain statistical parametric maps calculated for all 5 conditions (facial movement, right/left side hand movement and right/left side facial sensory). Functional MRI signal time courses were high-pass filtered (128 s) and modeled as an experimental stimulus onset function, and convolved by the canonical hemodynamic response function (low-pass filter). Individual contrast images for each task were entered into a 2nd level random effects analysis to make inferences at the group level. For our one sample
For each subject, the first 10 volumes of functional data were discarded because of the signal equilibrium and subjects’ adaptation to the imaging noise. The remaining volumes were then slice timing corrected, spatially realigned, and coregistered with the subject’s corresponding anatomical (T1-weighted) images and segmented. Friston 24 head motion parameters [
fALFF data was smoothed after normalization, and then, temporal filtering was performed so that only the low frequency band (0.01–0.08) was examined in subsequent analyses of the low frequency fluctuations (LFF) amplitude.
After normalization, the ICC data underwent ART (
To explore the ReHo/fALFF/ICC differences between the BP patient group and healthy control group, a two-sample
All patients showed impairments in their left or right facial muscle function due to BP, with the HBS grades ≥3. All MR scans were performed 3–14 days after BP onset (Table
Clinical data for all BP patients.
Number | Gender | Age (years) | Paralyzed side | Duration (days) | HBS |
---|---|---|---|---|---|
1 | M | 44 | R | 7 | 4 |
2 | M | 42 | R | 10 | 3 |
3 | M | 38 | R | 7 | 3 |
4 | M | 25 | L | 14 | 5 |
5 | M | 39 | R | 7 | 4 |
6 | M | 34 | L | 9 | 4 |
7 | F | 34 | R | 5 | 4 |
8 | F | 34 | R | 6 | 5 |
9 | F | 23 | R | 5 | 4 |
10 | M | 28 | L | 8 | 5 |
11 | M | 40 | L | 8 | 5 |
12 | M | 33 | R | 7 | 5 |
13 | F | 39 | L | 4 | 5 |
14 | M | 39 | L | 6 | 5 |
15 | F | 45 | L | 6 | 4 |
16 | F | 33 | R | 3 | 4 |
17 | M | 26 | L | 9 | 4 |
18 | M | 26 | R | 10 | 4 |
19 | M | 43 | R | 8 | 5 |
20 | F | 35 | L | 8 | 6 |
21 | M | 42 | R | 9 | 6 |
22 | M | 31 | R | 5 | 6 |
23 | F | 50 | L | 8 | 4 |
24 | F | 39 | L | 8 | 6 |
25 | F | 34 | R | 5 | 4 |
F, female; HBS, House-Brackmann Scale; L, left side; M, male; R, right side.
We found significantly increased activation at the bilateral S1/M1, supplementary motor area (SMA), and cerebellum in healthy controls during the facial movement task.
During the hand movement task, we found significantly increased activation at the contralateral S1/M1, thalamus, putamen, insula, bilateral SMA, and cerebellum in both BP patients and healthy controls. There was no significant difference between the two groups.
During facial sensory stimulation, we found significantly increased activation at the contralateral S1/M1, insula and S2 in both BP patients and healthy controls. We also found that in the healthy control group the (1) left facial sensory stimulation provoked significantly increased activation at the ipsilateral S1 and the (2) right facial sensory stimulation provoked significantly increases activation at the ipsilateral cerebellum (Table
Task-related fMRI results for healthy controls.
Tasks | Brain region | Cluster size | Peak |
MNI coordinates (mm) | ||
---|---|---|---|---|---|---|
|
|
| ||||
Facial movement | L S1/M1 | 346 | 7.38 | −51 | −12 | 42 |
R S1/M1 | 273 | 6.65 | 48 | −9 | 45 | |
R SMA | 175 | 6.42 | 6 | −3 | 63 | |
B cerebellum | 126 | 6.34 | 12 | −63 | −18 | |
|
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Right hand movement | L S1/M1 | 1216 | 7.58 | −33 | −24 | 54 |
B cerebellum | 505 | 7.27 | 12 | −54 | −15 | |
L thalamus | 535 | 7.01 | −15 | −21 | 6 | |
|
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Left hand movement | R S1/M1 | 533 | 7.50 | 36 | −21 | 51 |
L cerebellum | 552 | 7.14 | −18 | −54 | −18 | |
B SMA | 434 | 6.96 | 6 | 0 | 45 | |
R thalamus | 531 | 6.75 | 15 | −21 | 6 | |
R putamen | 6.02 | 24 | 3 | 6 | ||
R S2 | 149 | 6.05 | 48 | −21 | 24 | |
|
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Right facial sensory | L S2/S1/M1 | 744 | 6.84 | −39 | −15 | 18 |
R cerebellum | 42 | 5.84 | 6 | −66 | −12 | |
|
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Left facial sensory | R S2/S1/M1 | 201 | 6.74 | 60 | −18 | 24 |
L S1 | 29 | 5.47 | −60 | −18 | 30 |
B, bilateral; L, left; M1, primary motor cortex; R, right; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; SMA, supplementary motor area.
Compared to healthy controls, BP patients showed (1) significant ReHo decreases in the bilateral S1/M1 and contralateral cingulate motor area (CMA), (2) significant fALFF decreases in the contralateral S1/M1, and (3) significant ICC decreases in the bilateral S1/M1 (Table
Comparisons of ReHo, fALFF, and ICC values in resting-state between BP patients and healthy controls using small volume FWE correction.
Resting-state | Brain region | Cluster size | Peak |
MNI coordinates (mm) | ||
---|---|---|---|---|---|---|
|
|
| ||||
ReHo | L S1/M1 | 500 | 4.59 | −33 | −24 | 63 |
R S1/M1 | 234 | 4.09 | 24 | −36 | 60 | |
fALFF | L S1/M1 | 40 | 3.36 | −30 | −27 | 63 |
ICC | L S1/M1 | 224 | 4.33 | −48 | −18 | 48 |
R S1/M1 | 140 | 4.60 | 15 | −21 | 69 |
B, bilateral; L, left; M1, primary motor cortex; R, right; S1, primary somatosensory cortex.
To explore the association between the above measurements and the duration of the patients’ Bell’s palsy, we also performed regression analyses across all patients using SPSS 18.0 Software (SPSS Inc., Chicago, IL, USA), including age, gender, and HBS as covariates. We found a significant positive association between the ICC values of the contralateral S1/M1 and the duration of the patient’s BP (
Intrinsic connectivity contrast (ICC) results. (a) ICC value was decreased in the contralateral S1/M1 in Bell’s palsy patients. (b) There was a positive association between the duration of a subject’s BP and the ICC value (
Contralateral hemisphere to the side of the affected nerve injury. (a) ReHo resting-state fMRI result. (b) ICC resting-state fMRI result. (c) fALFF resting-state fMRI result. (d) Increased activation evoked by ipsilateral hand movement in BP patients. (e) Increased activation evoked by ipsilateral hand movement in healthy controls. (f) Increased activation evoked by ipsilateral facial sensory stimulation in BP patients. (g) Increased activation evoked by ipsilateral facial sensory stimulation in healthy controls. (h) Increased activation evoked by mouth movement in healthy controls.
Ipsilateral hemisphere to the side of the affected nerve injury. (a) ReHo resting-state fMRI result. (b) ICC resting-state fMRI result. (c) Increased activation evoked by contralateral hand movement in BP patients. (d) Increased activation evoked by contralateral hand movement in healthy controls. (e) Increased activation evoked by contralateral facial sensory stimulation in BP patients. (f) Increased activation evoked by contralateral facial sensory stimulation in healthy controls. (g) Increased activation evoked by mouth movement in healthy controls.
In this study, we explored neural plasticity in BP patients using task-related and resting-state fMRI. We found that the early stage of BP is associated with significant decreases in ReHo, fALFF and ICC values in the contralateral S1/M1, and with significant decreases in ReHo and ICC values in the ipsilateral S1/M1, compared to matched healthy controls. It is interesting to note that the regions with decreased ReHo, fALLFF and ICC values were not only in the cortical map representing the face, but also in the hand region of the cortex; regions defined by hand and mouth task-related fMRI. We also found that BP patients and healthy controls had similar increased activation during the hand movement task and facial sensory stimulation. There was no significant difference between the two groups in all tasks performed by both groups. Our results suggest functional neuroplasticity in S1/M1 following the onset of BP and that resting-state fMRI may be a sensitive tool to detect these early stages of neural plasticity in patient populations.
ReHo, ICC, and fALFF are methods used to investigate the regional brain functional status using resting-state fMRI. ReHo measures the homogeneity of a brain’s functional area in a specific condition, and has the ability to detect unpredicted hemodynamic responses that model-driven methods have failed to identify [
In a previous study, investigators compared the resting-state functional connectivity of the motor network as identified by facial movements. They found that compared to healthy controls, BP patients showed decreased connectivity, mainly in areas responsible for sensorimotor integration and supervision (SII, insula, thalamus and cerebellum) [
In our study, we used methods focused on the regional brain status, and found significant decreases in resting-state functional connectivity at the S1/M1. This is consistent with previous studies on nerve injury. For instance, Pawela and colleagues found that the contralateral S1 showed a decreased connectivity with the bilateral M1 and ipsilateral S1 in rats with transected the brachial plexus compared to the control rats [
We found decreased ReHo, fALFF, and ICC values not only at face representation areas, but also at hand representation areas of S1 and M1. These results are consistent with previous studies on neuroplasticity following peripheral nerve injury, in which researchers found the preservation of the original function of the invaded territory, as well as cohabitation with a newly acquired function [
We also found a significant decrease in ReHo and ICC values at the ipsilateral S1/M1, suggesting that unilateral nerve injury can affect bilateral S1/M1. Studies have suggested that the ipsilateral hemisphere also plays an important role in sensorimotor function. For instance, a TMS study showed that stimulation to one side of the M1 cortex can cause ipsilateral motor evoked potentials (MEPs) in BP patients [
We found there was a significant positive association between BP duration and ICC values at the contralateral S1 and M1. We speculate this may reflect the self-recovery process of BP patients, which usually begins about one week after the onset of BP. Further studies are needed to validate the above findings.
In this study, we found that hand movement evoked significantly increased activation at bilateral M1, SMA, and insula, which is consistent with findings from previous studies [
The present study had several limitations. The first is that we did not scan the patients at late stage or after recovery, so we were not able to provide dynamic neural plasticity changes of BP patients. Second, we did not test the facial motor condition in our BP patients, therefore we were unable to measure the motor cortical function during this task and compare it to the healthy controls. However, a previous study found no significant difference between BP patients and healthy controls during a mouth movement task [
We found that the period shortly following the onset of BP is associated with neural plasticity in both the face and hand region of the bilateral S1/M1 as measured by different regional functional connectivity methods. Our results imply that regional functional connectivity may be a useful tool to investigate neural plasticity in patient populations and may hold the potential to assess the severity of the injured nerve.
The authors declare that they have no competing interests.
Wenwen Song and Minhui Dai contributed equally to this work.
The study is supported by the Construction Funds of Key Subjects of Colleges and Universities in Zhejiang Province [Grant no. ZJGK2012-80-160]. Jian Kong is supported by R01AT006364, R01 AT008563, R21AT008707, and P01 AT006663 from NIH/NCCIH.