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Original Paper

Received: February 10, 2010


Accepted after revision: April 19, 2010
Published online: June 19, 2010

Eur Neurol 2010;64:914


DOI: 10.1159/000313976

Cortical Activation Pattern in


Hemiparetic Patients with Pontine Infarct
YongHyunKwon a SungHoJang b

Department of Physical Therapy, Yeungnam College of Science and Technology, and b Department of Physical
Medicine and Rehabilitation, College of Medicine, Yeungnam University, Taegu, Republic of Korea

Key Words
Magnetic resonance imaging, functional Pons Stroke
Infarct Motor recovery

Abstract
Objectives: No prior study has reported on the cortical activation pattern in hemiparetic patients with a pontine infarct.
The aim of this study was to investigate the cortical activation pattern of hemiparetic patients with a pontine infarct,
using functional MRI scanning (fMRI). Subjects and Method:
Fifteen consecutive patients who showed severe weakness
at onset due to a pontine infarct were recruited. The motor
function was assessed at the time of the onset of stroke and
fMRI scanning was performed (on average 8.9 months after
stroke onset). The fMRI was performed during a motor task
of timed hand grasp-release movements. From the fMRI, the
laterality index was calculated to assess the relative activity
in the ipsilateral versus the contralateral primary sensorimotor cortex (SM1). Results: All patients except for 2 (bilateral
SM1 activation) showed contralateral SM1 activation without
ipsilateral SM1 activation associated with the affected hand
movements. The average laterality index for the affected
hand movements among all patients was 0.97. Conclusions:
The fMRI results showed that primarily the contralateral SM1

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was activated during affected hand movements. Therefore,


it appears that the motor function of the affected hand, in
patients with a pontine infarct, recovers mainly via the lateral corticospinal tract.
Copyright 2010 S. Karger AG, Basel

Introduction

Current stroke rehabilitation focuses on the concept of


brain plasticity [13]. Therefore, elucidation of the mechanisms involved in motor recovery is likely to aid in the
approach to stroke rehabilitation. With the development
of functional neuroimaging techniques, several motor recovery mechanisms have been suggested by cortical activation patterns identified using functional neuroimaging
studies [48]. However, little is known about the motor
recovery mechanisms that are associated with the location of the lesions. Some studies have reported that cortical activation patterns and motor outcome vary accord-

This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (KRF-2008-314-E00173).

Sung Ho Jang, MD
Department of Physical Medicine and Rehabilitation, College of Medicine
Yeungnam University
317-1 Daemyungdong, Namku, Taegu 705-717 (Republic of Korea)
Tel./Fax +82 53 620 3269, E-Mail strokerehab@hanmail.net

ing to the lesion location in stroke patients [912]. These


results suggest the possibility that the mechanisms associated with motor recovery might be different based on
the lesion location. However, no prior study has evaluated
the cortical activation patterns in hemiparetic patients
with a pontine infarct.
In the current study, we tried to elucidate the motor
recovery mechanism in hemiparetic patients with a pontine infarct, by analyzing the cortical activation pattern
using functional MRI (fMRI).

Subjects and Methods


Fifteen consecutive patients (6 men mean age 61.6 8 2.4,
range 4275 years) with a pontine infarct were recruited according to the following criteria: (1) first-ever stroke, (2) at least 5
months had elapsed since the onset of stroke, (3) the infarct was
confined to the pontine base including the corticospinal tract
(CST), (4) the Medical Research Council (MRC) scale of finger
extensors in the affected hand at onset was 0, and at least 4 weeks
were required for the MRC scale to improve to 3, to eliminate the
possibility of motor recovery due to resolution of local factors
such as edema [13, 14], (5) the absence of serious cognitive problems (Mini-Mental State Examination 125), evident sensory
problems, or ataxia, and (6) no history of neurological diseases
other than the stroke. This study was approved by the institutional review board of Yeungnam University Hospital. All subjects gave written informed consent to participate in the study,
and were confirmed to be right-handed by the Edinburg Handedness Inventory [15].
Experimental Procedures
Motor Function Evaluation. Motor function was assessed by
the motricity index (MI), the MRC, the modified Brunnstrom
classification (MBC), and the functional ambulation category
(FAC) at the time of stroke onset and fMRI scanning (average 8.9
months after stroke onset). The MI was used to measure motor
function with a maximum score of 100 [16]. The MRC score for
the finger extensors was used as a parameter of hand motor function: 0 = no contraction; 1 = palpable contraction, but no visible
movement; 2 = movement without gravity; 3 = movement against
gravity; 4 = movement against a resistance lower than the resistance overcome by the healthy side, and 5 = movement against a
resistance equal to the maximum resistance overcome by the
healthy side [17]. The function of the affected hand was categorized according to the MBC: 0 = unable to move fingers voluntarily; 1 = able to move fingers voluntarily; 2 = able to close hand
voluntarily, but unable to open hand; 3 = able to grasp a card between thumb and medial side of index finger, able to extend fingers slightly; 4 = able to pick up and hold a glass, able to extend
fingers, and 5 = able to catch and throw a ball in a near-normal
fashion, able to button and unbutton a shirt [18]. Walking ability
was determined by the FAC [19]. Six categories are included in the
FAC: 0 = non-ambulatory; 1 = needs continuous support from
one person; 2 = needs intermittent support from one person; 3 =
needs only verbal supervision; 4 = help is required on stairs and

10

Eur Neurol 2010;64:914

uneven surfaces, and 5 = can walk independently anywhere. The


reliability and validity of the MRC, MI, MBC, and FAC are well
established [1619].
Functional MRI. Patients were examined in the supine position with their eyes closed, and were secured firmly with the forearm pronated. For the motor task, a grasp-release hand movement
was performed at a metronome-guided frequency of 1 Hz in a
manner with a repetitive alternating cycle of control (rest for 21 s)
and stimulation (activity for 21 s). Each task of control and stimulation (42 s) was repeated three times in both the affected and
the non-affected hand. The cerebral blood oxygen level dependent (BOLD) fMRI was carried out in the final test. Echo planar
images (EPI) were acquired using a 1.5T MR scanner (Vision; Siemens, Germany) with a standard head coil. For the anatomic base
images, conventional T1-weighted echo images (20 axial, 5 mm
thickness) were obtained with a matrix size of 128 ! 128 and a
field of view (FOV) of 210 mm, parallel to the bi-commissure line
of the anterior commissure-posterior commissure. EPI BOLD
images of 60 vol were acquired over the same 20 axial sections,
with a total of 1,200 images for each subject. Imaging parameters
consisted of TR/TE = 2 s/60 ms, FOV = 210 mm, matrix size =
64 ! 64 and slice thickness = 5 mm.
Data Analysis and Measurements
The fMRI data analysis was performed using SPM99 software
(Wellcome Department of Cognitive Neurology, UK) running in
the MATLAB environment (The Mathworks, USA). The functional data from each participant was motion-corrected. All images were realigned and co-registered. The images were smoothed
with an 8-mm isotropic Gaussian kernel. Statistical parametric
maps were obtained, and voxels were considered significant at an
uncorrected p ! 0.001. Below the predetermined p value, only
clusters of 15 voxels were analyzed. Regions of interest (ROIs)
were drawn around the primary sensorimotor cortex (SM1), supplementary motor area (SMA), and premotor cortex (PMC). The
SM1 centered to the precentral knob extended from the precentral
to the postcentral gyrus. The PMC extends horizontally from the
precentral sulcus to the rostral limit, which lies halfway between
the central sulcus and the anterior-most extent of the brain, and
from the sylvian fissure to the SMA. The SMA, which is anteriorly located with regard to the leg somatotopy of the primary motor cortex, extends from the brain vertex to the cingulate sulcus
[20, 21]. We analyzed the voxel count to estimate the cortical activation response to hand movement, because they are reliable
indicators of cortical activation and cerebral blood flow changes
[22, 23]. The laterality index (LI), calculated according to the formula (voxel of contralateral SM1 voxel of ipsilateral SM1)/(voxel of contralateral SM1 + voxel of ipsilateral SM1), ranged from 1.0
(all activity in the contralateral hemisphere) to 1.0 (all activity in
the ipsilateral hemisphere).
Lesion volume was measured on T2-weighted MRI images
through Picture Archived Communication System (PACS; Marotech, Korea). We measured maximum width (X), length (Y) and
height (Z) of the lesion at the level where the infracted area was
most large size [24]. Lesion volume was calculated according to
the formula: lesion volume (mV) = 4/3 ! ! X(cm) ! Y(cm) !
Z(cm) ! 1/16.

Kwon /Jang

Table 1. Demographic data and the motor function at onset and second evaluation in patients with pontine infarct
Patient
No.

Sex/
age

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15

M/69
M/61
M/53
M/42
M/62
M/57
F/72
F/69
F/69
F/75
F/54
F/52
F/52
F/69
F/69

Avg
SEM

61.6
2.4

Lesion lesion
Duration
side
volume to fMRI
mV
months
Rt
Rt
Rt
Rt
Rt
Rt
Lt
Rt
Lt
Rt
Rt
Lt
Lt
Rt
Lt

1.19
0.74
1.00
0.49
2.40
2.51
1.74
3.05
2.64
0.96
3.22
1.72
2.60
2.46
1.50
1.88
0.23

13
7
9
12
5
21
5
6
5
14
12
6
6
6
7
8.9
1.1

p value

Total MI (arm/leg)

MRC (finger
extensor)

MBC

FAC

LI Aff
voxel

onset

fMRI

onset fMRI

onset fMRI

onset fMRI

fMRI

24 (30 /17)
26 (19/33)
34 (30/37)
34 (39/28)
29 (30/28)
0 (0/0)
19 (19/19)
26 (19/33)
29 (30/28)
25 (30/19)
0 (0/0)
28 (0/56)
36 (34/37)
29 (30/28)
0 (0/0)

100 (100/100)
100 (100/100)
100 (100/100)
100 (100/100)
75 (76/74)
72 (75/68)
100 (100/100)
75 (76/74)
100 (100/100)
91 (91/91)
70 (76/63)
100 (100/100)
100 (100/100)
100 (100/100)
100 (100/100)

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

5
5
5
5
4
4
5
3
5
4
4
5
5
5
5

1
1
1
2
1
1
1
1
1
1
1
1
1
1
1

6
6
6
6
5
5
6
5
6
5
5
5
6
6
6

1
0
0
1
0
0
0
0
0
0
0
2
2
0
1

5
5
5
5
4
4
5
5
5
4
4
5
5
5
4

1 (68/0)
1 (46/0)
1 (135/0)
1 (28/0)
1 (770)
0.9 (100/5)
1 (78/0)
0.6 (39/9)
1 (97/0)
1 (78/0)
1 (116/0)
1 (50/0)
1 (56/0)
1 (108/0)
1 (31/0)

0
0

4.6
0.1

1.0
0.0

5.6
0.1

0.4
0.1

4.6
0.1

0.97 (73.8/0.93)
0.25 (8.39/0.67)

22.6 (20.6/24.2)
3.2 (3.6/4.0)

92.2 (92.9/91.3)
3.16 (2.8/3.5)

0.001 (0.001/0.001)*

0.000*

0.000*

0.001*

fMR I = Functional MRI; MI = motricity index; MRC = Medical Research Council; MBC = modified Brunnstrom classification; FAC = functional
ambulatory category; LI aff = laterality index during affected hand movements. Voxel is expressed as (voxel of contralateral primary motor cortex/voxel
of ipsilateral primary motor cortex). * p < 0.05.

Statistical Analysis
All dependent variables (MI, MRC, MBC, FAC) were analyzed
with a paired t test, to compare the motor function between stroke
onset and fMRI scanning. The 2 test was used to analyze the difference in distribution of the cortical activation patterns on the
affected and non-affected side at the predetermined ROIs (SM1,
SMA, PMC). All statistical analyses were performed with SPSS
Ver 14.0, and the criterion for statistical significance was set at a
p ! 0.05.

Results

Table1 shows the demographic data, the changes in


motor function, lesion volume, and the LI of the affected hand. On all scales of motor function, there was a
significant difference between stroke onset and fMRI
findings (p ! 0.05). The MI score improved from an average of 22.6 at stroke onset to an average of 92.2 at fMRI
scanning. In terms of the MRC of the affected finger extensor, all patients recovered to the extent that they
could move against gravity (more than MRC 3) and 10
of 15 (67%) patients to the full mark (MRC 5). As for
hand function (fig.1), all patients were able to grasp and
CAP in Hemiparetic Patients with
Pontine Infarct

release an object (more than MBC 5) and 9 of 15 (60%)


patients could carry out fine motor activities (MBC 6).
With regard to gait, all patients could walk independently (more than FAC 4) and 10 of 15 (67%) patients
could walk anywhere (FAC 5).
Table 2 shows the distribution of cortical activation
patterns at each of the ROIs. The 2 analysis showed no
statistically significant differences in the proportion of
cortical activation patterns in the SM1, SMA, and PMC
(p 1 0.05). All patients except 2 (bilateral SM1 activation)
showed contralateral SM1 activation without ipsilateral
SM1 activation. The LI for the affected hand was 0.97.
SMA activation was observed in 3 patients and PMC activation in 2.

Discussion

In the current study, we investigated the cortical activation patterns in hemiparetic patients with a pontine infarct. Moreover, we compared the results with those of
our previous study on cortical activation patterns in patients with cortical and corona radiata infarcts [9]. In this
Eur Neurol 2010;64:914

11

Fig. 1. Functional MRI findings show the two different types

of cortical activation patterns in the representative cases. T2weighted brain MR images show infarcts in the right pons (arrows). A Functional MRI images show the contralateral primary
sensorimotor cortex activation during either hand movement.

B The bilateral primary sensorimotor cortices were activated during the affected hand movements while only the contralateral primary sensorimotor cortex was activated during movement of the
unaffected hand.

Table 2. The distribution of cortical activation in the regions of interest

SM1

Affected hand
Non-affected hand
Pearson 2 (p value)

SMA

PMC

contralateral

bilateral

contralateral

bilateral

no activation

contralateral

bilateral

no activation

13 (86.6%)
15 (100%)

2 (13.3%)
0 (0.0%)

2 (13.3%)
0 (0.0%)

1 (6.6%)
0 (0.0%)

12 (80.0%)
15 (100%)

1 (6.6%)
0 (0.0%)

1 (6.6%)
0 (0.0%)

13 (86.6%)
15 (100%)

2.143 (0.483)

3.333 (0.189)

2.143 (0.343)

SM1 = Primary sensorimotor cortex; SMA = supplementary motor area; PMC = premotor cortex.

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Eur Neurol 2010;64:914

Kwon /Jang

study, the LI for the affected hand movements was high


(0.97). This is a little lower than that of the unaffected
hand movements (1.0) among the patients studied, and a
little higher than that of the control group (0.96) of a previous study, and that of patients with a cortical infarct
(0.91); however, it is higher than that of patients with a
corona radiata infarct (0.59) [9]. An LI of 1.0 indicates
that all of the cortical activity is in the contralateral hemisphere and a score of 1.0 refers to all cortical activity in
the ipsilateral hemisphere. Therefore, a plus LI means
that the contralateral motor cortex activity was higher
than the ipsilateral motor cortex activity during affected
hand movements. The activation of the contralateral motor cortex without ipsilateral activation during affected
hand movements means that the motor function of the
affected hand was likely recovered by the lateral CSTs, the
most important motor pathway for motor control. It is
well known that patients who recover from damaged lateral CSTs have good motor function [4, 8, 25, 26]. The
patients in this study also had good motor function. All
patients could grasp and release objects using the affected
hand and walk independently. In addition, 60% of all patients could carry out fine motor activities using the affected hand, and 67% of all patients could walk independently anywhere. Compared to the results of our previous
study [9], the MRC (4.6) of the finger extensors was better
than that of patients with a cortical infarct (4.25) and a
corona radiata infarct (3.58). This good motor function
among the patients in this study is consistent with the
findings of previous studies on the motor outcome of patients with a pontine infarct [2729].
There have been no cortical activation studies reported on motor function in patients with a pontine infarct;
therefore little is known about the motor recovery mechanisms of patients with a pontine infarct. After the introduction of diffusion tensor imaging, two possible motor
recovery mechanisms in patients with a pontine infarct
have been reported [26, 30]. Ahn et al. [26] reported that
infarcted CST function of the pons was relocated to periinfarct CST areas in patients with a pontine infarct who
showed severe weakness at stroke onset using fMRI and
diffusion tensor tractography. Recently, 1 patient with a
pontine infarct was found to have recovered through aberrant CSTs in the brainstem [30]. In the current study,
13 of 15 patients showed only contralateral motor cortex
activation without ipsilateral motor cortex activation.
Therefore, it appears that the motor function of the affected hand in these patients recovered via a damaged
lateral CST. By contrast, 2 of 15 patients showed bilateral
motor cortex activation. In these 2 patients the motor

function of the affected hand might have recovered via


the ipsilateral motor pathway from the unaffected motor
cortex to the affected hand. The fMRI has limitations in
demonstrating neural pathways at the subcortical level
and in the ipsilateral motor pathway. Further combined
studies with diffusion tensor imaging or transcranial
magnetic stimulation are required to improve on the limitations of the fMRI.
In conclusion, we investigated the cortical activation
patterns of patients with a pontine infarct. The fMRI results showed that primarily the contralateral SM1 was activated during affected hand movements. Therefore, the
motor function of the affected hand appears to have recovered mainly via the lateral CSTs in patients with a
pontine infarct. This is the first functional neuroimaging
study to investigate the cortical activation patterns of
motor function in patients with a pontine infarct. These
findings have important implications for improving our
understanding of the mechanisms underlying motor recovery in patients with a pontine infarct. In addition, it
will help to develop strategies to facilitate motor recovery
in patients with a pontine infarct. However, the results of
this study have a generalized limitation due to the small
number of patients. Further studies with a larger patient
cohort are needed as well as a follow-up study from acute
to chronic stage along with the course of motor recovery
and combined studies with other brain mapping techniques such as diffusion tensor imaging and transcranial
magnetic stimulation.

CAP in Hemiparetic Patients with


Pontine Infarct

Eur Neurol 2010;64:914

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Kwon /Jang

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