Surgical Neurology 63 (2005) 249 – 253

www.surgicalneurology-online.com

Correspondence of microelectrode mapping with magnetic resonance

imaging for subthalamic nucleus procedures
Clement Hamani, MD, PhDa, Erich O. Richter, MDb, Yuri Andrade-Souza, MDa,
William Hutchison, PhDa, Jean A. Saint-Cyr, PhDa, Andres M. Lozano, MD, PhDa,*
a
Division of Neurosurgery, University of Toronto, Toronto, ON M5T 2S8, Canada
b
Department of Neurosurgery, University of Florida, Gainesville, FL 32601, USA
Received 22 December 2003; accepted 25 May 2004

Abstract Background: Magnetic resonance imaging (MRI) and microelectrode recording (MER) are
commonly used to guide stereotactic procedures on the subthalamic nucleus (STN). Little is known
about the correlation between the position of the STN as seen on MRI and that as determined by
MER mapping. We compared these in 10 patients with Parkinson’s disease.
Methods: The position of the STN was determined by intraoperative MER findings and stereotactic
axial T2 magnetic resonance images with 2-mm slice thickness. Images were reconstructed in a 3-
dimensional workstation. The anterior, posterior, medial, lateral, dorsal, and ventral borders of the
STN defined with the MRI were measured relative to the midcommissural point. The location of
STN activity during MER was reconstructed relative to the midcommissural point for comparison.
Results: Twenty-nine tracks recorded with microelectrodes provided clear spans of STN-like activity
in 18 STN nuclei. The coordinates of MER were, in general, within the borders of the STN defined
with the MRI. However, when analyzed individually, some of the tracks had STN-like activity
outside the borders of the MRI-defined nucleus (mostly b1 mm). Three tracks had STN-like activity
recorded between 2 and 3 mm more anterior than the anterior border of the nucleus defined with the
MRI.
Conclusions: There was a good correlation between MER and the borders of the STN defined in the
MRI, except for the anterior-posterior axis, in which MER indicated that the STN extended more
anteriorly than as suggested by MRI. This should be taken into account in STN surgery.
D 2005 Elsevier Inc. All rights reserved.
Keywords: Microelectrode recording; Subthalamic nucleus; MRI; Surgery; Parkinson’s disease

1. Introduction imaging (MRI) using either T2 or inversion recovery

sequences [3-5,13,14,16]. However, because of the distor-
Several centers that report their clinical experience with
tions reported with this technique, the reliability of its use as
deep brain stimulation (DBS) for Parkinson’s disease (PD)
an isolated method to target the STN is in question.
combine imaging techniques and microrecording mapping
To address this issue, we reconstructed the final target
to target the subthalamic nucleus (STN). Nevertheless, some
coordinates and the angle of entry of the trajectories of the
centers rely exclusively on imaging studies and macro-
microelectrode tracks in reformatted magnetic resonance
stimulation mapping. The most commonly used imaging
images and compared them with the borders of the STN
method for direct STN targeting is magnetic resonance
seen in reconstructed stereotactic MRI sequences.

* Corresponding author. Division of Neurosurgery, Toronto Western

Hospital, Toronto, ON, Canada M5T 2S8. Tel.: +1 416 603 6200; fax: +1 2. Materials and methods
416 603 5298.
E-mail addresses: c.hamani@sympatico.ca (C. Hamani)8 We reviewed 10 patients who had an implantation of
lozano@uhnres.utoronto.ca (A.M. Lozano). DBS electrodes for PD (8 bilateral and 2 unilateral), in
0090-3019/$ – see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.surneu.2004.05.036
250 C. Hamani et al. / Surgical Neurology 63 (2005) 249 –253
which the borders of the STN could be identified (18
subthalamic targets). Patient selection criteria are discussed
elsewhere [8,9].
2.1. Surgical procedure
The surgical procedure for microelectrode-guided STN
localization and the placement of DBS electrodes has been
previously described in detail [10,11]. Briefly, a stereotactic
frame (Leksell G, Elekta, Inc, Atlanta, Ga) was affixed to
each patient’s head on the morning of surgery and
preoperative magnetic resonance images were obtained
(Signa, 1.5 T, General Electric, Milwaukee, Wis). The x, y,
and z coordinates of the anterior commissure (AC) and
posterior commissure (PC) were determined using axial T2
magnetic resonance images. The coordinates of the STN
target were chosen on axial and coronal T2-weighted images.
In the operating room, a burr hole was drilled 2 cm from
the midline in front of the coronal suture. The underlying dura
mater was opened, and the exposed pial surface was
coagulated. The Leksell arc was attached to the head frame
and set to the target coordinates. Microrecordings were
started 10 mm above the target. Microelectrodes were
assembled from parylene C–insulated tungsten wires (Micro
Probe Inc., Potomac, MD) and were plated with gold and
platinum. Tip lengths ranged from 15 to 40 lm, and
impedances ranged from 0.2 to 1.5 MV. Manual hydraulic
microdrives were used to drive the microelectrodes through
the brain.
2.2. Electrophysiologic identification of the STN
Single and multiunit neuronal discharges were amplified,
filtered, displayed on an oscilloscope, and fed into an audio
monitor as previously described [10]. The dorsal border of
the STN was marked by an increase in background activity
and the presence of movement-related cells [1]. The ventral
border of the STN was characterized by a decrease in
neuronal activity. As the electrode progressed, an additional
increase in background activity was noticed upon its
entrance into the substantia nigra reticulata.
After microrecording and microstimulation mapping, a
DBS quadripolar electrode (Medtronic 3387, Medtronic,
Inc, Minneapolis, Minn) was implanted.
The electrodes were internalized usually between 3 and 7
days after surgery and connected to a pulse generator
(Medtronic, Kinetra or Soletra) in the infraclavicular region.
2.3. Magnetic resonance image analysis
Axial stereotactic T2-weighted images (reception time,
4000 milliseconds; echo time, 90 milliseconds; slice
thickness, 2 mm, with no gaps; matrix, 256  256 pixels;
bandwidth, 3.29 kHz) were transferred to the StealthStation
(Medtronic SNT). With the use of the FrameLink 4.1
software (Mach 4.1, StealthStation), the fiducial markers of
the frame were recognized and the mean rod marking error
was calculated and registered. Thereafter, the coronal and
sagittal planes were reconstructed based on the axial images.
Both AC and PC were targeted in the axial plane, and 3
additional points were plotted in the midline. The images
were reformatted parallel to the AC-PC line and orthogonal
to the midline. Pitch, roll, and yaw were corrected in the
StealthStation.
Two independent observers determined the borders of the
STN on magnetic resonance images and the measurements
were averaged. The most anterior extent of the STN was
measured relative to the midcommissural point (MCP) on each
axial T2 slice, and the most anterior of these measurements was
recorded. The posterior border was similarly evaluated on axial
T2 series. The most dorsal and ventral measurements obtained
from coronal T2 images were recorded relative to the
intercommissural plane (ICP). Medial and lateral border
measurements in millimeters from the midline were obtained
from T2 coronal series.
The superior and inferior limits of the STN as recorded
with electrophysiologic techniques were compared with
those obtained in the reconstructed MRI sequences. During
microelectrode mapping, the STN was traversed from lateral
to medial, anterior to posterior, and dorsal to ventral. In all
tracks, the superior and inferior electrophysiologic limits of
the STN were recorded. The coordinates of these 2 points
for each track and the angle of entry of the trajectories of the
microelectrode tracks were reconstructed in the reformatted
images to evaluate their position relative to the MCP, ICP,
midline, and the borders of the STN on the magnetic
resonance image. Tracks that had STN-like activity outside
the MRI-defined nucleus were subdivided according to their
distance from the borders of the STN into b1, 1 to 2, or 2 to
3 mm. The coordinates of the microelectrode tracks of
specific patients were compared with the borders of the STN
defined in their corresponding magnetic resonance images.
Measurements are reported as meanFSD.
3. Results
The position of the borders of the STN on the MRI
relative to the MCP, ICP, and midline are summarized in
Table 1. Twenty-nine microelectrode exploration tracks with
STN neuronal activity were analyzed. In most cases, there
was a good correspondence between the electrophysiolog-
Table 1
Position of the borders of the STN as seen in T2 MRI sequences relative to
the MCP, ICP, and midline
Borders of the STN Position
Medial 8.6 F 4.3 mm lateral to the midline
Lateral 13 F 6 mm lateral to the midline
Anterior 0.8 F 1.9 mm anterior to the MCP
Posterior 6.7 F 1.1 mm posterior to MCP
Dorsal 1.8 F 1.3 mm below the ICP
Ventral 7.4 F 0.9 mm below the ICP
The medial, lateral, dorsal, and ventral borders of the STN were determined
on coronal T2 images. The anterior and posterior borders were determined
on axial T2 images. ICP indicates intercommissural plane; MCP,
midcommissural point.
 C. Hamani et al. / Surgical Neurology 63 (2005) 249 –253 251

Table 3
Distance of the superior and inferior electrophysiologic limits of the STN
from the MRI borders of the nucleus in tracks with activity outside the
imaging-defined STN
Superior limit of Inferior limit of
STN-like activity (mm) STN-like activity (mm)
Medial tracks 1.2 F 0.6 1.1 F 0.5
Anterior tracks 1.8 F 1.0 1.0 F 0.9
Posterior tracks – 0.9 F 0.2
Dorsal tracks 0.7 F 0.5 –
Ventral tracks – 0.6 F 0.8
In the first column, the positions of the tracks relative to the MRI borders of
the nucleus are represented.
Results are in mean F SD.
There were no tracks with activity lateral to the MRI-defined border of the
nucleus. There were no tracks with the upper portion of the microrecordings
Fig. 1. Schematic representation of the region of the STN in coronal and posterior to the MRI border. In the dorsal-ventral axis, none of the tracks
sagittal sections. The contours of the STN represent the borders defined in that had activity outside the STN defined with the MRI had STN-like
the MRI. The 2 black dots in each section represent the average coordinates recordings in both directions (dorsal and ventral).
of the upper and lower limits of the STN-like electrophysiologic recordings.
Vertical and horizontal lines represent standard deviations. RED indicates
red nucleus; SN, substantia nigra; STN, subthalamic nucleus; Thal, In tracks that showed discrepancies between MER and
thalamus; and ZI, zona incerta. MRI, the superior and inferior limits of STN-like recordings
were, on average, 1.2 F 0.6 and 1.1 F 0.5 mm more medial
ically defined STN and the borders of the nucleus on the than the medial border of the MRI-defined nucleus,
magnetic resonance image (Fig. 1). In the trajectories respectively (Table 3).
sampled, the superior limit of the STN-like electrophys-
iologic activity was, on average, 10.9 F 5.9 mm from the 3.2. Anterior and posterior borders of the STN
midline, 1.1 F 2.2 mm posterior to the MCP, and 3.2 F 1.4 Fifteen tracks revealed a good correspondence between
mm below the ICP. The inferior limit of the STN-like MER and the anterior-posterior extent of the STN in T2
electrophysiologic activity was, on average, 10.2 F 5.5 mm axial images.
from the midline, 2.7 F 2.2 mm posterior to the MCP, and Fourteen tracks had STN-like activity recorded outside
6.7 F 1.2 mm below the ICP. the MRI-defined anterior-posterior limits of the STN. In 5 of
3.1. Medial and lateral borders of the STN these tracks, STN-like activity was recorded within 1 mm
from the MRI borders (in 3, more anterior than the anterior
Twenty-three tracks revealed STN-like electrophysiolog- MRI border; in 2, more posterior than the posterior MRI
ic activity within the medial-lateral extent of the STN in T2 border). In 6 tracks, STN-like activity was recorded between
coronal images. 1 and 2 mm more anterior than the anterior border of the
In 6 tracks, the position of the STN as seen with MRI-STN. In 3 tracks, this distance was between 2 and 3
microelectrode recording (MER) and that as seen with MRI mm (Table 2).
did not match. In 3 of these tracks, STN-like activity was In tracks with STN recordings anterior to the anterior
recorded within a distance of b1 mm from the medial MRI border of the magnetic resonance image, the superior and
border. In 3 others, this distance was between 1 and 2 mm. inferior limits of STN-like recordings were, on average,
No STN electrophysiologic activity was found lateral to the 1.8 F 1 and 1 F 0.9 mm more anterior than the imaging-
MRI-defined lateral border of the STN (Table 2). defined nucleus, respectively. In tracks with STN record-
Table 2
Number of tracks with STN-like activity recorded inside and outside the borders of the STN defined with the MRI
Tracks with recordings Tracks with recordings Tracks with recordings Tracks with recordings
within the borders of within a b1-mm within a 1- to 2-mm within a 2- to 3-mm
the MRI-defined STN distance from the MRI distance from the MRI distance from the MRI
borders of the STN borders of the STN borders of the STN
Medial-lateral plane 23 3 3 –
in coronal
T2 images
Anterior-posterior 15 5 6 3
plane in axial
T2 images
Dorsal-ventral plane 13 13 3 –
in coronal
T2 images
252 C. Hamani et al. / Surgical Neurology 63 (2005) 249 –253
ings posterior to the posterior border of the magnetic
resonance image, the inferior limit of the STN-like
recordings was, on average, 0.9 F 0.2 mm more posterior
than the imaging-defined nucleus (Table 3). The superior
limit of the electrophysiologically defined STN in posterior
tracks was always within the borders of the MRI nucleus.
3.3. Dorsal and ventral borders of the STN
Thirteen tracks revealed STN-like electrophysiologic
activity within the dorsal-ventral extent of the STN as seen
on T2 coronal images.
In 16 tracks, MER and MRI did not match. Thirteen of
these tracks presented STN-like activity within a distance of
b 1 mm from the MRI-STN (in 10, more dorsal than the
dorsal MRI border; in 3, more ventral than the ventral MRI
border). Three tracks had STN-like activity within a
distance of 1 to 2 mm from the MRI-STN (in 2, more
dorsal than the dorsal MRI border; in 1, more ventral than
the ventral MRI border; Table 2).
Tracks in which STN-like activity was recorded
outside the dorsal and ventral borders of the MRI-
defined nucleus revealed STN-like activity that was, on
average, 0.7 F 0.5-mm dorsal and 0.6 F 0.8-mm ventral to
the imaging borders (Table 3).
4. Discussion
There was, in general, a good correspondence between
the position of the STN seen on the MRI and that seen on
the MER. Discrepancies of N2 mm were observed in 17% of
the nuclei (3 of 18), in which electrophysiologic STN-like
activity was recorded anterior to the border defined with the
MRI, and 20% of the patients (2 of 10).
A limitation of this study was the resolution of the STN
on imaging. The delineation of the borders of the STN,
which are hypointense in T2, is not always clear in MRI
scans [13]. In fact, it is estimated that in approximately 10%
of the cases, the definition of the STN cannot be fully
appreciated [13]. In T2 MRI scans, the substantia nigra, the
globus pallidus, the striatum, and some of the fiber systems
that run close to the STN also have hyposignal intensity in
T2 sequences. This seems to be partly because of the high
iron content within these structures [2,17]. Histochemical
studies on nonhuman primates revealed that the iron content
within the basal ganglia is localized in the globus pallidus,
substantia nigra, striatum, and some fascicles of fibers,
including part of the ansa lenticularis [6]. The STN per se
does not contain iron but has a high neuronal density, which
could partially account for its signal in MRI scans [7].
Previous studies from our group have found that the
anterior border of the STN was the boundary of the nucleus
with the highest variability [11]. The anterior border of the
STN on axial and coronal T2 MRI sections is difficult to
distinguish inferomedially from the substantia nigra and
anterosuperiorly from the pallidofugal fiber pathways,
which are also hypointense in T2 sequences. In addition
to these anatomic features, the anterior-posterior axis is
more prone to MRI distortions because it is usually the
frequency-encoded plane of image acquisition [10,14,15]. In
a previous study, Starr et al [14] have shown that
coordinates obtained in MRI scans are more prone to errors
in the anterior-posterior plane, with a trend for the MRI
coordinates to be more posterior than the real ones. These
observations help to explain the discrepancies observed in
the present study when the anterior border of the STN was
defined with electrophysiology or MRI.
The main goal of our study was to evaluate the
relationship between the mapping of STN-like activity with
microelectrodes as recorded in the operating room and the
magnetic resonance images used for targeting. We found a
good correspondence between MRI and MER. However,
establishment of the anterior border of the STN with MRI
was inaccurate by 2 to 3 mm in 20% of the patients. This is of
relevance if we take into account that the preferred location
for the best contact to treat patients with PD is the
anterodorsal portion of the STN [12]. Microelectrode
recording is useful in identifying this portion of the nucleus
in 2 ways: (1) by identifying the population of movement-
responsive neurons that occupy this region [1] and (2) by
classifying the position of the track within the STN as
indicated by the span of STN neurons encountered in
parasagittal MER trajectories. Microelectrode recording
trajectories near the anterior and posterior limits of this
biconvex nucleus would give a 1- to 2- or 2- to 3-mm span of
STN activity, whereas trajectories through the middle of the
nucleus would encounter 5 to 6 mm of STN neuronal
activity. Thus, inaccuracies observed in MRI regarding the
anterior border of the STN could be easily corrected with
MER. This shows that microelectrode mapping is important
in increasing targeting precision during STN surgery.
Acknowledgments
We thank Arthur J. Ulm for his assistance.
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Commentary
In this study, the authors investigate the relationship
between the position of the STN as determined by
microelectrode recordings during deep brain stimulator
253
placement and that as determined from axial T2 MRI.
Specifically, the anterior, posterior, medial, lateral, dorsal,
and ventral limits of the STN were determined using MRI
and were compared with the analogous borders determined
from microelectrode recording. Ten patients were enrolled
into the study, and 29 STN microelectrode passes were
made. When the microelectrode recordings yielded a border
of the STN that fell outside the border determined from
MRI, the deviation was quantified into 1 of 3 types: b1, 1 to
2, or 2 to 3 mm.
In general, there was good concordance between the
positions of the STN as calculated by T2 MRI and as
determined from microelectrode recordings. In several
passes, however, STN activity was detected outside the
STN borders by magnetic resonance criteria. To illustrate,
nearly half (14/29) of the tracks fell outside the magnetic
resonance STN boundary in the anterior-posterior (AP)
direction, with 3 tracks by as much as 2 to 3 mm outside.
Similarly, more than half (16/29) of the tracks missed the
magnetic resonance–defined STN in the dorsal-ventral axis,
some by as much as 1 to 2 mm. The authors refer to
previous work reporting difficulties defining the anatomic
borders of the STN in the AP axis and to magnetic
resonance distortion effects most prominent in this plane
to explain the AP mismatch between magnetic resonance–
defined and microelectrode-defined STN borders.
This study highlights some of the technical limitations
inherent to deep brain stimulator procedures. Even with
meticulous attention to detail in planning these operations,
there exists a certain amount of error that blurs even the best
treatment plans. Until distortion-free MRI that permits
substantially finer neuroanatomic detail is developed and
brain shift can be accounted for, a certain degree of error
will inevitably be present in these procedures. Thus, the
take-home message of this study could be that one must be
cautioned not to rely entirely upon imaging alone for
placement of these electrodes.
Kim J. Burchiel, MD
Christopher J. Winfree, MD
Department of Neurosurgery
Oregon Health Sciences University
Portland, OR 97201, USA