Grammatical and resource components of sentence processing in Parkinson’s
disease: An fMRI study
M. Grossman, A. Cooke, C. DeVita, C. Lee, D. Alsop, J. Detre, J. Gee, W. Chen, M. B.
Stern and H. I. Hurtig
Neurology 2003;60;775-781
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Grammatical and resource components
of sentence processing in
Parkinson’s disease
An fMRI study
M. Grossman, MD, EdD; A. Cooke, MD, PhD; C. DeVita, BA; C. Lee, BA; D. Alsop, PhD; J. Detre, MD;
J. Gee, PhD; W. Chen, BA; M.B. Stern, MD; and H.I. Hurtig, MD
Abstract—Background: Sentence comprehension requires linguistic processing as well as cognitive resources such as
working memory (WM) and information-processing speed (IPS). The authors hypothesize that sentence comprehension
difficulty in patients with mild PD is due to degradation of the large-scale neural network that supports cognitive
resources during sentence processing. Objective: To understand the neural basis for sentence comprehension difficulty in
PD. Method: Regional brain activity with blood oxygenation level– dependent fMRI was monitored while seven PD patients
and nine healthy seniors answered a simple probe about written sentences that vary in their grammatical and cognitive
resource properties. Results: Healthy seniors recruited posterolateral temporal and ventral inferior frontal regions of the
left hemisphere, brain regions associated with grammatical processing that were also activated by PD patients. Healthy
seniors also recruited left dorsal inferior frontal, right posterolateral temporal, and striatal regions that are associated
with cognitive resources during sentence processing. Direct contrasts showed that striatal, anteromedial prefrontal, and
right temporal regions are recruited to a significantly lesser degree in PD, but these patients have increased activation of
right inferior frontal and left posterolateral temporal–parietal areas during sentence comprehension. Conclusions: These
findings associate impaired sentence comprehension in PD with interruption of a large-scale network important for
cognitive resources during sentence processing. These results also imply compensatory up-regulation of cortical activity
that allows patients with mild PD to maintain sentence comprehension accuracy.
NEUROLOGY 2003;60:775–781
Nondemented PD patients are impaired at understanding grammatically complex sentences.1,2 Although
some attribute this to a grammatical deficit,3,4 recent
work relates comprehension difficulty in PD to a limitation in cognitive resources such as working memory
(WM) and information-processing speed (IPS) that contribute to sentence comprehension.5,6
FMRI studies suggest that sentence comprehension requires activation of brain regions supporting
both grammatical processes7,8 and the resource demands associated with complex language materials.9,10
In studies manipulating WM and grammatical demands factorially, left posterolateral temporal cortex
(PLTC) was recruited for all sentences, ventral portions of left inferior frontal cortex (vIFC) were associated with grammatical complexity, dorsal left inferior
frontal cortex (dIFC) and right PLTC contributed to
verbal WM, and striatal recruitment was related to
IPS.11-13
A frontal–striatal loop is compromised in patients
with PD.14 Previous work has shown reduced activation of prefrontal and striatal regions in PD when
performing nonlinguistic tasks that require problem
solving or generation of novel motor sequences.15-17 In
the current study, we used fMRI to monitor regional
brain activation while PD patients were presented
complex sentences manipulating grammatical and WM
demands (table 1). We expected PD patients to have
difficulty recruiting frontal–striatal brain regions that
support cognitive resources during sentence comprehension. Moreover, based on our observations of sentence comprehension in healthy seniors with WM
limitations,13 we expected increased activation of other
brain areas that might help patients with mild PD
maintain sentence comprehension accuracy.
Additional material related to this article can be found on the Neurology
Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 11 issue to find the title link for this article.
Methods. Subjects. We evaluated brain activation patterns
in seven right-handed, minimally medicated patients with mild
idiopathic PD (Hoehn and Yahr stage 1). The patients were not
From the Departments of Neurology (Drs. Grossman, Cooke, Detre, Stern, and Hurtig and C. DeVita, C. Lee and W. Chen) and Radiology (Drs. Alsop, Detre,
and Gee), University of Pennsylvania Medical Center, Philadelphia.
Supported in part by the US Public Health Service (NS35867, AG15116, AG17586, and DC00237).
Received February 2, 2002. Accepted in final form October 11, 2002.
Address correspondence and reprint requests to Dr. Murray Grossman, Department of Neurology, 3 Gates, University of Pennsylvania, 3400 Spruce St.,
Philadelphia, PA 19104-4283.
Copyright © 2003 by AAN Enterprises, Inc. 775
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Table 1 Examples of sentence materials and accuracy during sentence comprehension challenges in healthy seniors and PD patients*
Sentence type
Stimulus example†
Healthy elderly, n " 9
PD, n " 7
MEAN (SD) % correct
Mean (SD) % correct
Subject-relative: short linkage
[The strange man]i in black who ti adored
Sue was rather sinister in appearance.
94.6 (4.9)
97.8 (3.2)
Subject-relative: long linkage
[The cowboy]i with the bright gold front tooth
who ti rescued Julia was adventurous.
91.1 (6.3)
86.1 (15.9)
Object-relative: short linkage
[The flower girl]i who Andy punched ti in the
arm was five years old.
88.5 (7.7)
75.4 (21.1)
Object-relative: long linkage
[The messy boy]i who Janet the very popular
hairdresser grabbed ti was extremely hairy.
90.7 (5.1)
84.1 (9.9)
* An analysis of variance comparing sentence comprehension accuracy in healthy seniors and PD patients revealed a significant main
effect for clausal grammatical structure (F[1,16] " 9.84, p $ 0.01) and a significant interaction effect for clausal structure # antecedent noun-trace distance (F[1,16] " 9.24, p $ 0.01). However, there was no main effect for group (F[1,16] " 3.68, NS), and group did
not interact significantly with any sentence comprehension factors.
† In sentences with a center-embedded clause, the subject or the object of the verb in the center-embedded clause that matches the
head noun has been displaced during sentence formulation, according to several linguistic accounts.50 The antecedent noun phrase (in
square brackets) is co-indexed (indicated by the subscript “i”) to a phonetically silent trace (indicated by “t”) in the “gap” in the
center-embedded clause from where the displaced subject or object was taken. For example, “The strange man” is the subject of the
main sentence in the first example above and is also the subject of the verb in the center-embedded clause “the strange man adored
Sue.” In English, the subject of the center-embedded clause “the strange man” is not repeated and instead is phonetically silent. We
keep track of this arrangement by linking the subject of the main sentence “the strange man” that we actually hear to a phonetically
silent trace positioned where “the strange man” should occur a second time, that is, in the center-embedded clause. According to the
model of gap filling,51 the antecedent noun phrase must be reaccessed as soon as the trace in the gap is encountered so that the sentence can be interpreted accurately. Subtle variations in this schema for subject-relative sentences and object-relative sentences are
likely to account for differences in the comprehension of these types of sentences. Regardless of the grammatical structure of the sentence, the linkage distance between the antecedent noun and the gap stresses working memory in proportion to the number of words
occupying this portion of the sentence.52
demented, based on extensive neuropsychological testing and
Mini-Mental State Examination scores (mean ! SD score " 28.3
! 1.4), and they were not depressed, based on clinical interview
and the Beck Depression Inventory (mean ! SD score " 8.1 !
5.5). There was no evidence for visual–spatial difficulty that could
have compromised performance on a reading task. Other causes of
parkinsonism were ruled out on the basis of clinical and laboratory exams. These patients were compared with nine healthy,
right-handed seniors who were age matched (means ! SD: PD "
71.0 ! 10.2 years; controls " 65.7 ! 10.2 years; t[12] " 0.91, NS)
and education matched (means ! SD: PD " 15.6 ! 1.1 years;
controls " 15.8 ! 2.1 years; t[12] " 0.27, NS) with the PD patients. All subjects had normal structural MRI scans. These seniors were selected from among 13 healthy older control subjects13
so that they matched the mean sentence comprehension accuracy
of PD patients during imaging, as summarized in table 1. Because
of a technical malfunction, sentence comprehension accuracy had
to be reassessed in two of the PD patients and one healthy senior
outside of the magnet bore.
Materials. Table 1 summarizes the four types of sentences
presented to the subjects. In brief, we assessed grammatical features of comprehension by administering sentences with a centerembedded clause that is subject-relative or object-relative. WM
was evaluated in each of these sentences by including a short,
three-word series of words between the head noun phrase and the
gap where the displaced noun phrase is interpreted in the centerembedded clause or a longer, seven-word series between the head
noun phrase and the gap. Each written sentence was presented in
a word-by-word fashion, and the types of sentences were matched
in word frequency, word length, and syllable length. Subjects responded to each sentence with a button press as soon as they felt
they knew the answer to the single probe provided at the beginning of each run: “Did a male or female perform the action described in the sentence?” All sentences contained a male and a
female equally distributed in each noun position in each type of
sentence, so that the male was the correct response in 50% of each
type of sentence. The button press initiated the presentation of
the next sentence following a 1,000-millisecond break. We presented two 40-second blocks of each type of sentence in a pseudorandom order in each run, together with two 40-second blocks of a
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NEUROLOGY 60 March (1 of 2) 2003
pseudo-font control task requiring similar sensory–motor processes. The pseudo-font stimuli consisted of brief (two to eight
units in length) strings of simple, letter-like geometric shapes
presented in a string-by-string manner, paralleling the word-byword presentation of sentences. Subjects responded with a button
press as soon as they saw one of two target geometric designs that
were presented at the beginning of the run. The blocks of stimuli
were presented continuously, and subjects were not informed that
blocks of different types of sentences were being administered.
Healthy subjects performed four runs alternating at presentation
rates of 750 or 500 ms/word, and we grouped data across levels of
this factor in the analyses presented below. PD patients performed the task only at the 750-ms/word presentation rate as they
were less reliable at performing the task at the faster rate. Forcing PD patients to perform the task at the faster rate would have
introduced resource-related interpretive confounds due to relative
task difficulty and would have prevented equating performance
accuracy across groups because of increased errors in PD. Subjects
were familiarized with the word-by-word presentation technique
and the gender probe prior to entering the magnet bore, and the
task was practiced by each subject.
Procedures. An LCD projector (Epson 5000, Long Beach, CA)
compatible with high magnetic fields was used to back-project
visual stimuli onto a screen at the magnet bore. The subject
viewed the screen through a system of mirrors available on the
GE head coil (Milwaukee, WI). A portable computer (Macintosh
1400C, Cupertino, CA) outside the magnet room used PsyScope
presentation software18 to present stimuli and record response
accuracy.
This experiment was carried out at 1.5 T on a GE Echospeed
scanner. We used the standard clinical quadrature radiofrequency
head coil. Foam padding was used to restrict head motion. Each
imaging protocol began with a 10- to 15-minute acquisition of
5-mm-thick adjacent slices for determining regional anatomy, including sagittal localizer images (repetition time [TR] " 500 ms,
echo time [TE] " 10 ms, 192 # 256 matrix), T2-weighted axial
images (fast spin echo, TR " 2,000 ms, TEeff " 85 ms), and
T1-weighted axial images of slices used for fMRI anatomic localization (TR " 600 ms, TE " 14 ms, 192 # 256 matrix). Gradient
echo echo-planar images were acquired for detection of alterations
Downloaded from www.neurology.org at University of Colorado Health Sciences Center on August 20, 2007
of blood oxygenation accompanying increased mental activity. All
images were acquired with fat saturation, a rectangular field of
view of 20 # 15 cm, flip angle of 90°, 5 mm slice thickness, an
effective TE of 50 milliseconds, and a 64 # 40 matrix, resulting in
a voxel size of 3.75 # 3.75 # 5 mm. The echo-planar acquisitions
consisted of 24 contiguous axial slices covering the entire brain
every 2 seconds. A separate acquisition lasting 1 to 2 minutes was
needed for phase maps to correct for distortion in echo-planar
images. Raw data were stored by the MRI computer on DAT tape
and then processed off-line.
Initial image processing was carried out with Interactive Data
Language (Research Systems) on a Sun Ultra 60 workstation.
Raw image data were reconstructed using a two-dimensional fast
Fourier transform with a distortion correction to reduce artifact
due to magnetic field inhomogeneities.19 Individual subject data
were then prepared and analyzed statistically using statistical
parametric mapping (SPM99), operating on a MatLab platform,
developed by the Wellcome Department of Cognitive Neurology.20
In brief, the images in each subject’s time series were registered to
the initial image in the series. The images were then aligned to a
standard coordinate system.21 The data were scaled to equate global
blood oxygenation level–dependent signal across groups and spatially smoothed with a 12-mm Gaussian kernel to account for small
variations in the location of activation and gyral anatomy across
subjects, and low-pass temporal filtering was implemented to control auto-correlation with a first-order auto-regressive method.
The data were pooled across subjects within groups prior to parametric analysis with a fixed effects model using t-test comparisons
converted to z-scores for each compared voxel. As we are testing
specific hypotheses, we provide contrasts that are significant at
the p $ 0.001 level uncorrected for multiple comparisons that are
in a cluster of at least 20 voxels. For convenience and readability,
we refer to activated regions provided in the tables and figure
with shorthand anatomic terms such as PLTC and dIFC, and
these terms do not refer to fixed regions of interest with independent anatomic boundaries.
Results. The regional anatomic distribution of activation in
healthy seniors during comprehension of the four types of sentences, compared with a pseudo-font baseline, are illustrated in
figure 1A. The coordinates and magnitude of peaks associated
with these activations are also summarized (additional material
can be found on the Neurology Web site; go to www.neurology.
org). Brain regions recruited significantly for all types of sentences in healthy seniors included left PLTC (Brodmann area [BA]
21/22), left dIFC extending into premotor cortex (BA 6/44), and
bilateral occipital cortex. Healthy seniors also recruited right
PLTC (BA 21/22) for all types of sentences and adjacent portions
of right parietal cortex (BA 40/7) for WM-demanding sentences
with a long noun-gap linkage. Direct contrasts of activation patterns in sentences with long and short noun-gap linkages indicated that sentences with a long linkage recruit right PLTC and
right parietal cortex to a significantly greater extent than sentences with a short linkage (additional material can be found on
the Neurology Web site). This emphasizes the role of right temporal–parietal cortex in WM demands during sentence processing.
We also found striatal activation for sentences with a long noungap linkage compared with sentences with a short linkage (additional material can be found on the Neurology Web site). Left
vIFC (BA 47/45) was significantly activated for the object-relative
sentences with a long noun-gap linkage. Direct contrasts of the
different types of sentences emphasized the role of this left vIFC
region in sentences with combined grammatical and WM demands
(additional material can be found on the Neurology Web site).
Regional brain activation patterns during sentence comprehension in PD, compared with a pseudo-font baseline, are illustrated
in figure 1B. The coordinates and magnitude of peaks associated
with these activations are also summarized (additional material
can be found on the Neurology Web site). As for healthy seniors,
we found significant activation in left PLTC, left dIFC/premotor,
right PLTC, and bilateral occipital cortices for all sentence conditions and in right parietal cortices for WM-demanding sentences
with a long noun-gap linkage. Direct contrasts of sentences with
long and short noun-gap linkages again indicated that sentences
with a long linkage recruit right temporal–parietal cortex to a
significantly greater extent than sentences with a short linkage
(additional material can be found on the Neurology Web site). We
also found activation of left IFC in PD. Direct contrasts of the
different types of sentences emphasized the role of this brain
region in grammatically demanding sentences in PD (additional
material can be found on the Neurology Web site). We did not see
activation of the striatum in PD as we did in healthy seniors.
The direct contrast of brain activation patterns in PD patients
and healthy seniors is summarized in table 2. PD patients had
less activation than healthy control subjects in the striatum for
sentences with a long noun-gap linkage. PD patients also demonstrated less anteromedial prefrontal (BA 32/10) and right PLTC
activation in all sentence conditions compared with healthy seniors. These observations are illustrated in figure 2A. PD patients
also showed somewhat less activation than healthy seniors in left
PLTC and occipital regions for all sentences and vIFC for the
object-relative sentences with a long noun-gap linkage.
To achieve levels of comprehension accuracy equal to older
control subjects, PD patients apparently engaged several brain
regions associated with WM in a significantly increased manner
relative to healthy seniors. This is illustrated in figure 2B. In all
sentence conditions, left posterolateral temporal parietal cortex
(BA 22/40), right IFC (BA 45/47), and right parietal cortex (BA
19/39) were recruited in a significantly greater manner in PD
patients than in healthy seniors.
Discussion. In the current study, we sought to determine whether linguistic or cognitive resource components of a large-scale neural network for sentence
processing are interrupted in patients with mild PD
by examining regional brain activation during the
comprehension of several types of sentences. Our
findings suggest that neural activation in PD during
sentence comprehension differs in subtle but important ways from the pattern seen in healthy seniors.
For example, there appear to be changes in the recruitment of components of a frontal–striatal–thalamic loop that may be one source of cognitive
difficulty in PD.14 We found that PD patients have
significantly reduced striatal recruitment during
sentence processing compared with age-matched control subjects. The striatum appears to contribute to
cognitive resources such as WM and IPS. In the current study, for example, healthy seniors recruited
the striatum during comprehension of long-linkage
sentences. Other fMRI work with nonlinguistic material in healthy young subjects has associated striatal recruitment with cognitive resources such as
WM22,23 and IPS,24,25 and an fMRI assessment of sentence processing in young adults showed that the
striatum contributes to IPS during comprehension.11
Studies of PD patients using nonlinguistic materials
have reported limited WM26,27 and slowed IPS,28,29
and functional neuroimaging studies in PD have
shown reduced striatal recruitment during similar
nonlinguistic tasks.15,16 Ischemic insult to the caudate did not interfere with an early left anterior negativity shift in electrocortical activity, according to
one evoked potential study of sentence processing,30
and follow-up work has related striatal disease instead to late electrocortical changes associated with
an effort-related integrative component of sentence
interpretation. In the context of PD patients’ cognitive resource limitations during sentence processing,5,6,31 our observations are consistent with the
claim that the sentence comprehension pattern seen
in PD is due in part to their restricted striatal
recruitment.
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777
Figure 1. Regional activation patterns associated with contrasts of each type of sentence minus the pseudo-font baseline
in healthy seniors (A) and PD patients (B). Left hemisphere and right hemisphere lateral views of each type of sentence in
each group of subjects: 1 " subject-relative short-linkage sentences; 2 " subject-relative long-linkage sentences; 3 " objectrelative short-linkage sentences; 4 " object-relative long-linkage sentences.
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Table 2 Magnitude of peak brain changes in direct contrasts of PD patients and healthy seniors during sentence comprehension*
Coordinates
Brain region (Brodmann area; coordinates)†
Subject-relative
X
Y
Z
Short
&56
&40
&4
36
&52
12
Object-relative
Long
Short
Long
3.83
3.10
3.33
4.32
4.19
2.87§
3.68
3.68
Recruitment less in PD than healthy seniors‡
Left posterolateral temporal (BA 21/22)
Right posterolateral temporal (BA 21/22/39)
Bilateral striatum
20
12
20
—
3.82
—
3.79
Bilateral anteromedial prefrontal (BA 32/10)
&16
52
28
3.46
3.48
3.08
3.66
Left ventral inferior frontal (BA 47)
&48
24
&4
—
—
—
3.14
&4
&72
20
5.71
3.79
4.98
4.36
&44
&56
32
4.65
4.00
4.57
4.32
Right inferior frontal (BA 45/47)
24
44
28
5.05
3.34
3.50
3.46
Right parietal occipital (BA 19/39)
20
&72
44
4.65
4.28
3.57
3.96
Bilateral occipital (BA 17/18)
Recruitment greater in PD than healthy seniors
Left posterolateral temporal parietal (BA
22/40)
* Data refer to z-scores indicating height of peak activation in a cluster. All values are significant at least at the p $ 0.001 level uncorrected for multiple comparisons, except where § indicates a peak approaching significance. Dashes indicate a region that did not show
activation for the indicated type of sentence.
† Representative coordinates refer to X-, Y-, and Z-axes in Talairach space,21 taken from object-relative sentences with a long linkage.
‡ Reduced activations in PD patients relative to healthy seniors for object-relative sentences with a long linkage are illustrated in axial
slices in figure 2A with the following distribution: 1-bilateral anteromedial prefrontal; 2-left ventral inferior frontal; 3- bilateral striatum; 4-left posterolateral temporal; 5-right posterolateral temporal; 6- bilateral occipital.
BA " Brodmann area.
We also found reduced activation of left anteromedial prefrontal cortex in PD, another component of a
frontal–striatal–thalamic loop.14 Several studies
have shown reduced resting brain activity in this
distribution in PD.32,33 Much work has related medial
frontal activation in a superior distribution to cognitive resources such as selective attention and performance monitoring in fMRI activation studies of
healthy adults,34,35 and frontal activation also has
been associated with IPS.36 Although we are not
aware that anteromedial prefrontal cortex has been
related previously to sentence comprehension, fMRI
studies have associated activation of this brain region
with a form of WM important for processing the structure of complex configurations of verbal information37,38 and the processing of subgoals during complex
problem solving.39 Additional work is needed to specify
the relationship between this anterior prefrontal distribution of changed activation and sentence
processing.
We also found reduced activation of right PLTC in
PD patients relative to healthy seniors. In the current study, direct contrasts of sentences with long
linkages compared with those with short linkages
suggested that healthy seniors recruit right PLTC to
support comprehension of sentences with greater
WM demands. We have associated right PLTC activation with sentence WM in young adults as well.12
Other labs also have related right PLTC activation
to WM demands during sentence processing.40,41
Many reports have described sentence-processing
impairments following right hemisphere stroke,42,43
and some of this work (e.g., syllogistic reasoning)
seems to involve considerable resource demands that
have been associated with right hemisphere activation.44,45 These findings are consistent with the claim
that brain regions supporting cognitive resources
during comprehension have limited activation in PD.
Reduced right PLTC activation in PD may be related
indirectly to the visual–spatial impairments that are
seen in mildly impaired PD patients.46 Although obvious visual–spatial difficulty was not evident in this
group of PD patients, we cannot rule out that visual
sentence presentation made the task more difficult for
PD patients. Subtle differences in the anatomic distribution of left perisylvian activation have been reported
in the one study directly comparing visual and auditory modalities of sentence presentation, although this
work did not find any evidence that the modality of
presentation interacted with resource-related process-
Figure 2. Regional activation patterns in direct contrasts of PD patients and healthy seniors. (A) Areas of reduced activation in PD patients relative to healthy seniors for object-relative long-linkage sentences, including lateral views and
representative transaxial views (left hemisphere on the left) at z " 0 mm (a), z " %8 mm (b), and z " %16 mm (c). 1 "
Bilateral anteromedial prefrontal; 2 " left ventral inferior frontal; 3 " bilateral striatum; 4 " left posterolateral temporal; 5 " right posterolateral temporal; 6 " bilateral occipital. (B) Areas of increased activation in PD patients relative to
healthy seniors for object-relative long-linkage sentences.
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779
ing demands during sentence comprehension in
healthy subjects.41 Additional work is needed to evaluate the role of presentation modality and resource demands during sentence processing in PD.
We also observed reduced activation in PD relative to healthy seniors in another region that is not
part of a frontal–striatal loop: occipital cortex. We presented sentences at two rates in healthy seniors but
only at the slower of these two rates in PD patients to
minimize potential resource-related confounds associated with task performance rather than sentence interpretation. Reduced occipital activation in PD may have
been due to the smaller number of words that these
patients read during this blocked design paradigm. Additional work is needed to establish the precise basis
for activation changes in this region in PD.
Our observations also showed that patients with
mild PD with good comprehension appear to increase
recruitment of several brain regions when directly
compared with healthy seniors. For example, unlike
the unilateral dIFC/premotor activation seen in
healthy seniors with good sentence comprehension,
we found bilateral IFC recruitment during sentence
comprehension in PD. Up-regulation of the IFC verbal WM network has been seen in other nonlinguistic47,48 and linguistic13 fMRI studies of healthy
seniors with age-related WM limitations. PD patients also showed increased activation in a portion
of frontal brain systems during resource-demanding
nonlinguistic tasks.15,17 These findings are consistent
with the hypothesis that activation of relatively preserved WM-related brain regions compensates in
part for cognitive resource limitations in PD. In the
current study, this may have allowed patients with
mild PD to achieve comprehension accuracy that is
equivalent to healthy seniors.
Left posterolateral temporal–parietal cortex was
upregulated in PD compared with healthy seniors in
the current study as well. This appears to be a portion of the large-scale network that is central to linguistic aspects of sentence processing,7,8 implying
that the neural substrate essential to sentence processing is relatively preserved in PD. Like healthy seniors, PD patients also recruit left vIFC and bilateral
occipital cortices. The patterns of relative activation
across specific types of sentences are remarkably similar in PD and healthy seniors, and the nonselective
decrease in activation levels in some of these regions in
PD does not appear to have any clinical consequences.
Several caveats must be kept in mind when considering our results. We examined a small number of
mildly impaired patients with PD, and we used a
fixed-effects model to assess brain activation profiles,
so our findings cannot be generalized beyond the
group of patients studied for this report. These issues emphasize the caution that must be adopted
when interpreting our observations, and additional
work is needed to confirm the results of this report.
We used a blocked design because of the relatively
robust data acquired with this technique, and this
appears to compensate for the reduced activation
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NEUROLOGY 60 March (1 of 2) 2003
that may be associated with repeated presentation of
the same type of sentence in a block.49-52 Functional
neuroimaging techniques for groups of subjects have
adopted several statistical conventions to compensate for the limited spatial resolution of the imaging
techniques, the minor interindividual differences in
regional sulcal anatomy, and the relatively weak
clinical magnet we used to collect data. For reasons
such as these, the data we report represent an approximation of the anatomic distribution of cerebral
activation associated with sentence processing, and
future work using techniques with better spatial resolution will be necessary.
With these caveats in mind, the observations described in the current report appear to be consistent
with our neural model of sentence processing. We
hypothesize two dynamically interactive, large-scale
processing networks during sentence comprehension.
One component appears to be concerned with written
comprehension and becomes modified depending on
the linguistic features of the sentence being processed. The anatomic distribution of these activated
regions appears to overlap considerably in young
adults, healthy seniors, and PD patients. Anatomic
elements include left PLTC and ventral portions of
left IFC. A second component is concerned with cognitive resources such as WM and IPS. As a sentence
emerges over time, this network temporarily retains
its constituents while processing these complex materials. This component includes dorsal portions of
left IFC, left parietal cortex, striatum, anteromedial
prefrontal cortex, and right PLTC. Portions of this
component appear to be interrupted in PD, consistent with the pattern of sentence comprehension difficulty in these patients, but other brain regions
appear to be up-regulated so that PD patients can
achieve reasonably accurate sentence comprehension
early in the course of their disease.
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March (1 of 2) 2003 NEUROLOGY 60
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781
Grammatical and resource components of sentence processing in Parkinson’s
disease: An fMRI study
M. Grossman, A. Cooke, C. DeVita, C. Lee, D. Alsop, J. Detre, J. Gee, W. Chen, M. B.
Stern and H. I. Hurtig
Neurology 2003;60;775-781
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