AJR 2001; 176:541-544
© American Roentgen Ray Society
Neuropsychologic Performance After Resection of an Activation Cluster Involved in Cognitive Memory Function
Joseph A. Maldjian1,
John A. Detre2,
William D. Scott Killgore2,
Kevin Judy3,
David Alsop1,
Murray Grossman2 and
Guila Glosser2
1
Department of Radiology, Hospital of the University of Pennsylvania, Ground
Floor Founders, 3400 Spruce St., Philadelphia, PA 19104.
2
Department of Neurology, Hospital of the University of Pennsylvania,
Philadelphia, PA 19104.
3
Department of Neurosurgery, Hospital of the University of Pennsylvania,
Philadelphia, PA 19104.
Received June 5, 2000;
accepted after revision August 3, 2000.
J. Maldjian is a 1999-2000 American Roentgen Ray Society Scholar.
Address corresspondence to J. A. Maldjian
Introduction
The advent of functional MR imaging (fMRI) has made it possible to map
regional brain function in patients with brain tumors. Several studies have
shown a good correlation between fMRI and invasive mapping for identifying the
primary motor cortex
[1,2,3].
The extension of this approach to more subtle cognitive functions, however,
remains to be established. In general, fMRI studies of cognitive tasks reveal
activation in a distributed network of brain regions. Although it may be
tempting to assume that each of these regions plays a critical role in task
performance, we present a case suggesting that resections coinciding with some
activated regions do not result in neuropsychologic deficit.
Case Report
A previously healthy 29-year-old right-handed woman presented with a
6-month history of brief episodes of numbness in her left face, arm, torso,
and leg. MR imaging revealed a 5 x 4 x 4 cm mass in the right
basal ganglia extending into the right frontal lobe. Conventional imaging was
performed 1 day before surgery and 2 days after near-total surgical resection.
One week before surgery and approximately 6 months after surgery, fMRI was
performed. In addition, the patient underwent detailed neuropsychologic
testing on the day of the fMRI and 6 weeks after the surgery. On pathology,
the mass was found to be an anaplastic astrocytoma. Postoperative MR imaging
showed hemorrhage within the operative bed with some residual peripheral
enhancement. The patient experienced transient left upper extremity weakness
that resolved almost completely.
The neuropsychologic testing consisted of motor, sensory, and cognitive
screening using standardized tests (Table
1). The patient performed within normal limits on all tests
preoperatively and showed no significant decrease in performance on the same
tests postoperatively, except a decline in left-sided motor speed. Slight
improvement in scores on several tasks reflects the expected effects of
practice with repeated administration.
The cognitive episodic fMRI memory paradigm
[4] consisted of alternating
40-sec blocks of scenes (task) and scrambled color-matched images (baseline)
for a total of 8 min, presented via a liquid crystal display projector. The
patient was instructed to remember the scenes for a subsequent recall test.
Imaging consisted of a sagittal T1-weighted localizer, followed by an axial
T1-weighted acquisition of the entire brain (24-cm field of view, 256 x
256 matrix, 3-mm slice thickness). Functional imaging was performed in the
axial plane using multislice gradient-echo echoplanar imaging with a field of
view of 24 x 15 cm and an acquisition matrix of 64 x 40 (21
slices; 5-mm thickness; no skip; TR/TE, 2000/70).
The fMRI data were processed using previously described methods
[5]. Statistical parametric
maps were generated using SPM97 (Wellcome, London, United Kingdom)
[6,
7] implemented in MatLab
(Mathworks, Sherborn, MA), with an IDL interface (Research Systems, Boulder,
CO). The motion-corrected data sets were normalized to a standard Talairach
atlas [8] and smoothed using an
8 x 8 x 10 mm smoothing kernel. Statistical maps were generated
using the general linear model and a threshold p value of less than
0.001, corrected for spatial extent (p < 0.05) using the theory of
Gaussian fields.
The postoperative anatomic images were also normalized to a standard atlas
within SPM97 using a rigid body transformation. Although the presence of a
brain tumor distorts local anatomy, visual inspection by a neuroradiologist
showed good agreement between the atlas and the normalized data sets using
known anatomic landmarks. Direct visual comparisons using the pre- and
postoperative anatomic images, with overlaid preoperative functional data, was
performed to determine whether any activated tissue was removed during
surgery.
The scene memory task revealed activation of bilateral frontal lobes (right
> left) and bilateral parietooccipital visual association areas
(Fig. 1A). Within the
dorsolateral right frontal lobe, a large activation cluster involving the
anterolateral aspect of the lesion was present. Direct comparison of the pre-
and postoperative scans, with the overlaid preoperative fMRI data, showed that
this region had been removed during surgery
(Fig. 1B). The activation
within this region was highly significant, both at the cluster level and at
the voxel level, achieving a maximum Z score of 6.7. There was also a large
activation present in the left frontal lobe.
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Fig. 1A. —Episodic scene memory functional MR imaging (fMRI) task.
Images are displayed in Talairach space (right of image is right of subject).
Preoperative fMR images show activation cluster within right dorsolateral
prefrontal cortex, which is adjacent to tumor.
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Fig. 1B. —Episodic scene memory functional MR imaging (fMRI) task.
Images are displayed in Talairach space (right of image is right of subject).
Same functional data as that shown in A overlaid on postoperative fMR
images reveal activation cluster to reside within operative bed. High signal
intensity within surgical bed represents hemorrhage.
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Six months after resection, fMRI was repeated using the same methodology
(Fig. 1C). This examination
showed activation of the right parahippocampal region and bilateral visual
association cortical regions. A small activation cluster was present in the
right frontal lobe, inferior to the operative bed. No frontal lobe activation
was seen adjacent to the operative site. The previously identified left
frontal lobe activation was no longer present.
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Fig. 1C. —Episodic scene memory functional MR imaging (fMRI) task.
Images are displayed in Talairach space (right of image is right of subject).
Same paradigm performed 6 months after surgery. Functional MR images reveal
right frontal activation adjacent to surgical bed is no longer present. There
is small activation cluster in right inferior frontal lobe, well removed from
operative bed. Bilateral occipital visual association cortical activation and
right parahippocampal activation are present.
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Immediately after each scene memory task, the patient was given a
recognition test in which she was asked to indicate whether the image had been
shown previously. A discrimination score was computed as the proportion of
correct "yes" responses (hit rate) minus the proportion of
incorrect "yes" responses (false-alarm rate)
[9]. Her performance on this
task improved slightly between the preoperative and postoperative fMRI
examinations (preoperative score, 0.983; postoperative score, 0.992). She
performed better than healthy control subjects on this task during both
sessions (mean score for 16 healthy control subjects, 0.8).
Discussion
Patients undergoing surgery for brain tumors frequently must have portions
of cortex removed to provide adequate margins or tumor debulking. In highly
malignant tumors such as glioblastomas, removal of a portion of the cortex is
often a necessary and unavoidable part of the surgery, providing a small but
measurable increase in longevity. When these resected areas involve eloquent
cortex, the small increase in survival may not outweigh the considerable
resulting morbidity. Functional MR imaging has held the promise of identifying
these eloquent areas preoperatively, potentially avoiding the surgical
morbidity. Although fMRI of simple sensorimotor tasks has been validated using
intraoperative invasive stimulation
[2,
3,
10,
11], more complex cognitive
and language tasks remain to be validated. Despite this fact, it is tempting
to ascribe functional significance to any activated regions in these patients.
This can be especially problematic with cognitive tasks, for which distributed
areas of activation are frequently observed. If these activated regions are
judged to be important for these cognitive functions, surgical treatment may
be unnecessarily altered on the basis of unvalidated assumptions. Furthermore,
recent evidence suggests that the presence of a brain tumor can affect the
fMRI response [12,
13].
A variety of hypotheses concerning mechanisms for memory function have been
suggested in the literature. The hippocampus is widely regarded to be the site
for object encoding, and regions in the frontal lobes (dorsolateral prefrontal
cortex) are believed to subserve working memory. Much of this literature is
based on lesion studies in primates and functional imaging studies of healthy
volunteers [14,
15]. Although lesion studies
in primates may offer a model for the relationship of memory systems, critical
differences in the anatomy of the frontal lobes and limitations in the nature
of cognitive testing make direct analogies with humans problematic. What has
been lacking thus far is an in vivo human model for evaluating functional
localization. Using fMRI in patients with brain tumors, this model is now
available. During surgical resection, portions of cortex surrounding the tumor
will unavoidably need to be removed. In some cases, this resection may involve
areas of activation on fMRI. This can provide a powerful in vivo lesion model
that can be used to establish the validity of ascribing function to specific
regions on the basis of fMRI and to determine the functional localization of
neural substrates in a variety of cognitive tasks.
In this patient, a large, highly significant activation cluster was seen in
the dorsolateral prefrontal cortex—that is, in the region of the tumor.
Despite having this area of brain removed, the patient showed no subsequent
cognitive memory deficits. In healthy subjects, the scene memory paradigm
reveals activation of bilateral parahippocampal structures and of frontal lobe
structures [4,
16]. A representative example
from our experience using this task in a group of 19 healthy right-handed
subjects is presented in Figure
2. Bilateral parahippocampal and visual association cortical
activation is shown. The right frontal lobe activation cluster in the healthy
subjects corresponds well to the resected right frontal activation cluster
seen in this patient. This finding suggests that all activation clusters on
cognitive memory paradigms cannot be assumed to represent structures critical
to the task. It is interesting that on the preoperative fMRI, activation
within the parahippocampal regions was not seen. The follow-up fMRI, however,
did reveal activation patterns similar to those observed in the healthy
subjects. The absence of parahippocampal activation preoperatively may reflect
a remote effect of the lesion.
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Fig. 2. —Episodic scene memory functional MR imaging task performed in
group of 19 healthy right-handed volunteers. Images are displayed in Talairach
space on standard pseudosubject structural image. Imaging and analysis were
performed as described in text. Group map was generated using random-effects
model in SPM97 (Wellcome, London, United Kingdom), threshold at
p<0.05, and corrected for spatial extent (p<0.05)
using theory of Gaussian fields, was implemented in SPM97. Bilateral
parahippocampal and visual-association cortical activation and right inferior
and right superior frontal lobe activation are shown.
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This case illustrates the potential pitfalls in ascribing cognitive
function on the basis of statistically significant changes in blood flow
observed on fMRI. More detailed evaluation of fMRI for complex cognitive and
language tasks is warranted before results of these studies are used to guide,
or to avoid, surgical treatment. Patients with brain tumors can provide a
much-needed in vivo lesion model for the evaluation of fMRI methods in
predicting postoperative deficit and for the general validation of the
technique with cognitive paradigms.
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Introduction
Case Report
