124 M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130
have a greater impact in patients with longer disease 2. Methods
duration, for example, because of the associated long-term
changes in endogenous DA metabolism [8–10]. Research- 2.1. Subjects
ers have taken advantage of the predictably brief availabili-
ty of levodopa  to study cognitive functioning under We assessed 20 non-demented (Mini Mental State
conditions of full DA supplementation compared to rela- Examination  mean529.1, S.D.51.19, range526–30),
tive DA depletion in the same patient. This has involved right-handed, native English speakers with idiopathic PD.
withholding a patient’s medication in some studies, while The patients were mildly impaired (Hoehn and Yahr Stage
other studies have examined patients at mid-dose and 1 or Stage 2), and signs included mild resting tremor and
during an end-of-dose wearing-off period. Several studies rigidity, according to the Uniﬁed Parkinson’s Disease
have demonstrated improvements in cognitive measures of Rating Scale . Demographic characteristics and medi-
memory and attention when PD patients are relatively ‘on’ cations at the time of the study are provided in Table 1.
their levodopa [12–16], but other studies have reported Exclusionary criteria for participation in this study in-
mixed results [17–19]. Discrepancies across these studies cluded the presence of a primary psychiatric disorder such
may be due to differences in the extent of DA loss in PD as psychosis, another akinetic–rigid disorder such as
patients participating in different studies. The impact of progressive supranuclear palsy, another neurologic con-
endogenous DA metabolism on cognitive functioning thus dition such as head trauma or hydrocephalus, a dementing
has been demonstrated in the evaluation of PD patients condition such as Alzheimer’s disease or dementia with
‘on’ and ‘off’ levodopa: memory and executive func- lewy bodies, another movement disorder such as parkin-
tioning were generally better in the subgroup of patients sonism due to small vessel ischemic disease or neuroleptic
with a stable response to levodopa who had a shorter drug use, or a metabolic or systemic disorder that could
disease duration than the PD patient subgroup with end-of- interfere with intellectual functioning.
dose wearing-off associated with longer disease duration, The patients were examined under two conditions, i.e.,
despite equivalent serum DA levels . when they were fully supplemented by levodopa at an
Sentence comprehension is a complex cognitive process optimal clinical dosage, and when they had been without
that we use daily. A crucial component of sentence levodopa for at least 12 h. The two sessions occurred at the
comprehension is grammatical processing. Some have same time of day (in the early morning), were typically
argued that sentence comprehension impairments in PD are separated by less than a week (mean52.85 days, S.D.5
due directly to an impairment in grammatical processing, 2.45 days between sessions), and the order of ‘on’ and
such as difﬁculty with the long-distance syntactic depen- ‘off’ assessments was randomized. We did not ﬁnd an
dencies among words in a sentence [21–23]. Recent work effect for the order in which patients were tested
has indicated that sentence comprehension also is depen- [F(1,38)50.66; ns].
dent in part on executive resources [24–26]. For example,
information retained in short-term memory from the 2.2. Materials
beginning of a sentence must be retrieved instantaneously
as it becomes needed later in a sentence . In this PD patients performed a 24-item sentence–picture
context, sentence comprehension difﬁculty in PD has been matching task using orally presented sentences. Sentence
related to their limited executive resources [28–34]. Given stimuli were equally divided into simpler items containing
the important contribution of working memory to sentence terminal subordinate clauses (e.g. ‘The hawk chased the
comprehension and the apparent sensitivity of executive eagle that was fast’) and more complex items containing
functioning to DA, we hypothesized that the accuracy of center-embedded subordinate clauses (e.g. ‘The eagle that
sentence processing in PD patients would vary depending the hawk chased was fast’). All sentences were semantical-
on the level of levodopa supplementation. ly unconstrained in that the action could be performed with
Despite a consensus that executive resources contribute equal plausibility by either the agent or the recipient.
to sentence processing, there is considerable debate about Patients responded in an untimed fashion by selecting one
the nature of these resources. While some studies are most of four color pictures. One choice was an accurate
consistent with the claim that executive resources are representation of the stimulus sentence. Picture foils
material-neutral and equally applicable to the processing of included: a different verb depicting the action (in the
any domain of knowledge [35–37], other work is more above example, the picture might illustrate ‘pecking’
consistent with a model of comprehension wherein the instead of ‘chasing’); a different agent performing the
cognitive resources are dedicated to sentence processing action (e.g. a picture showing an owl chasing an eagle);
[24,38]. To explore the nature of executive resources in the and a reversal of the agent role and the theme role
DA-mediated sentence comprehension difﬁculties of PD involved in the action (e.g. an eagle chasing a hawk instead
patients, we also obtained an independent measure of of a hawk chasing an eagle). The two former foils involve
verbal working memory capacity that does not involve a comprehension of a single word, are less resource-demand-
speciﬁc syntactic manipulation during the different states ing, and appear to depend in large part on left temporal
of DA supplementation. brain regions that are sparsely innervated by DA projec-
M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130 125
Mean (6S.D.) clinical and demographic characteristics and medication regimens of patients with Parkinson’s disease
All PD PD patient subgroups
Group size 20 9 11
Age (years) 66.5 (11.2) 65.4 (12.1) 67.4 (10.8)
Education (years) 16.1 (2.4) 16.9 (2.1) 15.4 (2.5)
Duration (years) 9.6 (5.7) 8.8 (4.5) 10.6 (6.6)
Stage 1 ([ pts)† left54; right55 left53; right51 left51; right54
Stage 2 ([ pts) 11 5 6
— right 0.13 (0.24) 0.14 (0.22) 0.11 (0.26)
— left 0.24 (0.41) 0.33 (0.63) 0.13 (0.32)
— right 0.22 (0.41) 0.14 (0.33) 0.27 (0.45)
— left 0.25 (0.46) 0.25 (0.53) 0.23 (0.41)
levodopa 678 (436) 794 (464) 582 (408)
selegiline 5.5 (5.1) 6.7 (5.0) 4.5 (5.2)
bromocriptine 3.6 (4.4) 4.0 (5.5) 3.2 (3.4)
The medications are tabulated as the total mg dosage / day. All patients were taking levodopa in combination with carbidopa as Sinemet, ten patients
were taking selegiline, four patients were taking bromocriptine, and ﬁve patients were taking pergolide (pergolide daily dosage was multiplied by ten to be
roughly equated with bromocriptine). In addition to the medications listed in the table, three patients were taking amantadine (at 200 mg qd or 300 mg qd),
one patient was taking amitryptiline (50–75 mg qhs), one patient was taking doxepin (100 mg qhs), one patient was taking trihexyphenidyl (1 mg qid), one
patient was taking benztropine (1.5 mg tid), one patient was taking alprazolam (0.25 mg qhs), and one patient was taking triazolam (0.125 mg qhs)
(qd5daily, qhs5nightly, tid5three times each day, qid5four times each day).
With lateralized tremor.
tions; the latter foil involves mapping thematic roles (who a repeated-measures analysis of variance (ANCOVA) with
is doing what to whom) on to grammatical roles (sentence a DA status (on vs. off) 3 type of sentence (terminal
subject and object), a process that requires considerable subordinate vs. center-embedded subordinate) design to
working memory resources and appears to be dependent on assess differences in sentence comprehension. To control
left frontal brain regions that are mediated in part by DA.
These choices were equally distributed across trials in each
of four possible positions that were arrayed in a 232
conﬁguration. None of the patients had visual–perceptual
difﬁculty that could have interfered with picture interpreta-
To explore the nature of the executive resources that
contribute to sentence processing difﬁculty in PD, we
examined these patients on a measure of verbal working
memory — the reading span procedure . The reading
span procedure requires a subject to read a list of complex
sentences orally, and to recall the ﬁnal words of the list of
sentences when ﬁnished reading them. The list of sent-
ences presented in a block becomes progressively longer,
analogous to a digit span procedure. A subject’s reading
span is equal to the number of sentences whose ﬁnal words
are correctly reproduced after reading these lists.
Fig. 1. Mean (6S.E.) sentence comprehension accuracy of terminal
Fig. 1 summarizes PD patients’ sentence comprehension subordinate and center-embedded subordinate sentences in Parkinson’s
accuracy during ‘on’ and ‘off’ assessment phases. We used disease when ‘off’ and ‘on’ levodopa medication.
126 M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130
for the effects of endogenous DA metabolism, we covaried with more errors only for the resource-demanding reversal
for disease duration on the assumption that longer disease foil.
duration is associated with greater DA depletion. We did We found that the reading span of PD patients ‘off’
not ﬁnd any signiﬁcant main effects, but the DA status 3 levodopa (mean reading span score ‘off’ levodopa533.05;
type of sentence interaction effect was highly signiﬁcant S.D.5610.32) did not differ substantially from their
[F(1,18)57.82; P,0.01]. We did not observe a similar reading span performance when ‘on’ levodopa (mean
interaction effect when we covaried for other clinical reading span score ‘on’ levodopa528.45; S.D.5610.17).
factors such as age [F(1,18)51.94; P50.18] and education We related PD patients’ executive resources ‘off’ levodopa
[F(1,18)50.17; P50.68]. t-Tests demonstrated that com- to their comprehension of sentences during levodopa
prehension of center-embedded subordinate sentences was supplementation. Individual patient’s performance proﬁles
signiﬁcantly worse than terminal subordinate sentences are summarized in Table 2. We found that reading span
only during the ‘off’ phase of testing [t(19)52.17; P, ‘off’ levodopa is signiﬁcantly correlated with the com-
0.05], but comprehension of center-embedded subordinate prehension of center-embedded subordinate sentences ‘on’
sentences did not differ from comprehension of terminal levodopa [r(18)50.647; P,0.002], but is not correlated
subordinate sentences during the ‘on’ phase of testing. with the comprehension of terminal subordinate sentences
To learn more about the basis for the effect of DA on ‘on’ levodopa [r(18)50.425; ns]. Reading span ‘off’
sentence comprehension, we examined the errors that levodopa was not correlated with sentence comprehension
patients made when they chose an incorrect picture. The ‘off’ levodopa, and reading span ‘on’ levodopa was not
results are summarized in Fig. 2. Separate ANCOVAs were correlated with sentence comprehension under ‘on’ or ‘off’
performed for verb, agent, and reversal foils, comparing conditions.
the frequency of selecting a foil during the comprehension We also used a ‘median split’ to divide the patients into
of terminal subordinate and center-embedded subordinate two subgroups according to their cognitive resources ‘off’
sentences while ‘on’ and ‘off’ levodopa, covarying for levodopa, i.e., into those with ‘greater executive resources’
disease duration. This revealed a signiﬁcant drug effect (n59; mean reading span score537.56; S.D.566.23) and
only for the reversal error [F(1,18)512.69; P,0.002]. The those with ‘limited executive resources’ (n511; mean
impairment in PD patients’ performance on center-embed- reading span score522.72; S.D.566.10) (because of ties,
ded sentences while ‘off’ levodopa thus was associated the median split could not be used to divide the PD
Fig. 2. Mean (6S.E.) proportion of foils selected when patients with Parkinson’s disease erred in their sentence–picture matching. * indicates a
statistically signiﬁcant difference.
M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130 127
Individual patient’s executive resource and sentence comprehension proﬁles ‘off’ and ‘on’ levodopa medication a
Patient Reading Terminal subordinate Center-embedded subordinate
Off On Off On
Greater executive resources
205 49 88 100 100 100
217 48 75 100 88 88
237 43 88 75 100 88
241 42 88 88 75 88
075 41 88 63 75 88
171 41 88 63 75 88
257 40 100 88 75 88
246 35 75 75 88 75
248 34 100 88 63 88
Limited executive resources a
133 31 100 75 88 75
194 31 88 75 100 63
227 31 88 75 88 75
236 30 88 88 75 75
216 29 75 88 100 88
253 29 75 75 75 50
013 27 75 88 38 75
266 21 100 100 100 100
269 21 88 63 38 63
258 16 75 100 63 100
260 4 75 63 50 63
Executive resources were established by performance on a reading span task. Reading span is scored as the total number of sentences with correctly
recalled terminal words, and subjects with larger reading spans have greater executive resources. See text for additional details. Comprehension of terminal
subordinate and center-embedded sentences is reported as percent correct.
patients into two equal subgroups). These subgroups thematic relations in a sentence, i.e., who is doing what to
differed signiﬁcantly in their reading span scores (t(18)5 whom. This aspect of sentence comprehension is depen-
5.35; P,0.001), but they did not differ statistically in their dent on executive resources. The results of an independent
age, education, disease duration, forward digit span, or measure of verbal working memory suggest that cognitive
medication regimen, as summarized in Table 1. Consistent resources dedicated to sentence processing and material-
with the correlation analysis, inspection of non-zero differ- neutral executive resources both contribute to the com-
ences revealed that 72% of PD patients with greater prehension of complex sentences.
executive resources were superior during ‘on’ compared to Previous studies have attempted to assess whether or not
‘off’ conditions in their comprehension of center-embed- DA levels inﬂuence cognitive performance in PD [4–7].
ded subordinate sentences. Only 44% of PD patients with The results of studies using a between-patient design have
limited executive resources showed this advantage during been difﬁcult to interpret since they have not been able to
‘on’ compared to ‘off’ conditions for center-embedded control for differences in disease severity and CNS DA
subordinate sentences. These subgroups did not differ in levels across the groups of PD patients being compared
the relative ‘on’ vs. ‘off’ advantage for their comprehen- [18,20]. Studies using a within-patient design have demon-
sion of terminal subordinate sentences (greater executive strated some levodopa-associated improvement in mea-
resource subgroup528%; limited executive resource sures of attention, memory, and executive functioning. For
subgroup538%). example, several reports have described improved verbal
memory when patients receive their dopaminergic medica-
tion compared to performance during an unmedicated
4. Discussion period [13,15]. Brown et al.  observed improvement in
measures of intelligence and general reasoning during the
Our observations suggest that sentence comprehension is ‘on’ phase of medication response compared to the ‘off’
inﬂuenced by levodopa levels in PD. In particular, we phase. A report of uncued and cued choice reaction time
found that differences in understanding grammatically found that DA supplementation helps patients take advan-
simple and grammatically complex sentences when ‘off’ tage of the predictability of a stimulus . Owen et al.
levodopa are diminished by DA supplementation in PD  found reduced planning accuracy in unmedicated
patients. An error analysis revealed that this effect is patients that improved with levodopa treatment, although
speciﬁcally associated with more accurate grasp of the the patients’ response latencies did not change. Improved
128 M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130
cognitive functioning while ‘on’ levodopa, however, has speciﬁc grammatical manipulations. Several aspects of our
not been a universal ﬁnding in assessments using a within- study are consistent with the hypothesis that the DA-
patient design. Several studies have reported mixed results, mediated effects impact on a speciﬁc, resource-dependent
associating some measures of executive functioning and component of sentence comprehension. An error analysis
learning with relatively impaired performance during DA thus associated impaired sentence comprehension during
supplementation but other measures with improved per- limited DA supplementation with difﬁculty mapping gram-
formance [18,19]. Another study failed to ﬁnd any DA- matical roles on to thematic roles in sentences. Grammati-
associated differences in measures of verbal memory, cal–thematic mapping requires intensive working memory
visuospatial orientation, attention, and executive function- support, and this aspect of sentence comprehension has
ing . proven quite difﬁcult for PD patients [28–30,33]. More-
Several factors may have contributed to discrepant over, unlike the comprehension of grammatically demand-
results across these studies, such as differences in disease ing sentences, we found comparatively little change in
duration and severity. We covaried for disease duration, reading span during ‘on’ and ‘off’ conditions. These
reasoning that patients with a longer disease duration observations are more consistent with the hypothesis that
should have relatively limited endogenous DA metabolism. the executive resource component of sentence comprehen-
This analysis revealed a signiﬁcant effect of DA on sion is different from the material-neutral form of execu-
sentence comprehension: there was a signiﬁcant dis- tive resources that may support other cognitive tasks .
crepancy in the ability to understand grammatically simple However, this cannot entirely explain the DA-dependent
and grammatically complex sentences when patients were change in sentence comprehension since we also found
‘off’ levodopa due to the relatively poor comprehension of that an independent measure of verbal working memory
complex grammatical sentences during limited DA supple- correlated with the comprehension of the most complex
mentation. This discrepancy in understanding simple and sentences during the ‘on’ condition, but did not correlate
complex grammatical sentences was not evident when the with the comprehension of simpler sentences. This ob-
patients were ‘on’ levodopa. Other observations have also servation is more consistent with the hypothesis that
demonstrated a relationship between the performance of material-neutral resources contribute to sentence com-
complex cognitive tasks and DA metabolism in PD, prehension as well. Taken together, these ﬁndings suggest
consistent with the hypothesis that improvement in cogni- that the DA-mediated cognitive resources contributing to
tive functioning during levodopa supplementation in PD is sentence comprehension in PD are multifaceted in nature.
mediated in part by disease duration . The mechanism by which DA supplementation impacts
Another factor that may explain some of the discrepan- working memory and executive resources during sentence
cies across previous studies of DA-dependent cognitive comprehension in PD remains to be elucidated. One
functioning has to do with the model of executive re- possibility is that speciﬁc brain regions have different
sources under examination. The results described above sensitivities to DA [18,44], and that the network of brain
thus are discrepant only if one assumes that there is a regions responsible for working memory resources in
single, material-neutral executive resource underlying all language is particularly sensitive to DA because of its
aspects of cognitive functioning. For example, slowed neuroanatomic distribution. Recent work has shown that an
information processing speed  or a limitation in total interaction of grammatically complex sentence structure
processing space  have each been cited as a uniﬁed and increased working memory demands is crucial to the
source of limited cognitive resources in the healthy elderly. recruitment of left inferior frontal regions during an fMRI
An alternative account is that executive resources support a activation study of sentence comprehension in healthy
relatively narrow range of cognitive functions, and that adults . This frontal area is part of a dopamine-
there may be cognitive resources that are speciﬁcally modulated frontal-striatal network that is thought to play a
dedicated to sentence processing . Studies of sentence role in the cognitive deﬁcits of PD patients , and this
processing in PD, beyond conﬁrming the contribution of area also appears to receive mesocortical projections from
cognitive resources, raise the possibility that limitations of the substantia nigra that contribute to cognitive functioning
several different types of resource are associated with in PD . The regional speciﬁcity of DA-mediated neural
comprehension difﬁculty. For example, information pro- systems may also explain the non-signiﬁcant decline in
cessing speed , working memory , and planning performance on terminal-subordinate sentences and in-
 each appear to be related to comprehension difﬁculty creased selection of a different agent and a different verb
in PD, and it has been hypothesized that each of these when ‘on’ DA, since these less-demanding grammatical
resources supports a speciﬁc aspect of sentence processing and lexical semantic features of sentences are reliant on
that may be compromised in PD . non-frontal regions [45,48] where DA projections are
We investigated the nature of the executive resource relatively sparse.
limitation during sentence comprehension in PD by ex- Another possible mechanism for the DA-mediated ef-
amining the errors seen during the patients’ comprehension fects in PD patients’ sentence comprehension and execu-
performance and by assessing performance on a working tive functioning is related to the amount of DA . From
memory measure that is verbal but does not involve this perspective, the resource component of sentence
M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130 129
comprehension may have been more sensitive to DA  Lieberman P, Friedman J, Feldman LS. Syntax comprehension in
dosage than reading span. Similarly, the substrate for Parkinson’s disease. Journal of Nervous and Mental Disease
cognitive resources in sentence comprehension may have  Natsopoulos D, Katsarou Z, Bostantzopoulos S, Grouios G, Men-
been so compromised in the subgroup of PD patients with tenopoulos G, Logothetis J. Strategies in comprehension of relative
limited cognitive resources that they would have required clauses in Parkinsonian patients. Cortex 1991;27:255–68.
more levodopa supplementation to derive any beneﬁt. If  Zimmermann P, Sprengelmeyer R, Fimm B, Wallesch C-W. Cogni-
DA supplementation has an inverted-U-shaped effect on tive slowing in decision tasks in early and advanced Parkinson’s
cognitive functioning , the PD patients may have been disease. Brain and Cognition 1992;18:60–9.
 Cooper JA, Sagar HJ, Sullivan EV. Short-term memory and temporal
receiving a relative excess of DA supplementation in the ordering in early Parkinson’s disease: Effects of disease chronicity
‘on’ state for aspects of sentence comprehension with few and medication. Neuropsychologia 1993;31:933–49.
resource demands such as grammatically simpler sentences  Downes JJ, Roberts AC, Sahakian BJ, Evenden JL, Morris RG,
and single word meaning. Additional research is necessary Robbins TW. Impaired extra-dimensional shift performance in
to establish the speciﬁc basis for the DA-mediated impact medicated and unmedicated Parkinson’s disease: Evidence for a
of working memory resources during sentence comprehen- speciﬁc attentional dysfunction. Neuropsychologia 1989;27:1329–
sion.  Owen AM, James M, Leigh PN, Summers BA, Marsden CD, Quinn
Several caveats should be kept in mind when interpret- NP, Lange KW, Robbins TW. Fronto-striatal cognitive deﬁcits at
ing the results of this report. We studied mildly impaired, different stages of Parkinson’s disease. Brain 1992;115:1727–51.
high-school-educated PD patients and caution should be  Melamed E, Hefti F, Pettibone DJ, Liebman J, Wurtman RJ.
used in generalizing our results to other groups of PD Aromatic L-amino acid decarboxylase in rat corpus striatum: Impli-
patients. PD patients were assessed with a limited variety cations for action of L-dopa in parkinsonism. Neurology
of sentences using only one kind of comprehension  Zhang W, Tilson HA, Nanry KP, Hudson PM, Hong JS, Stachowiak
measure, and our observations must be replicated with MK. Increased dopamine release from striata of rats after unilateral
other linguistic techniques in a larger group of patients. We nigrostriatal bundle damage. Brain Res 1988;461:335–42.
focused on levodopa supplementation in a relatively small  Fabbrini G, Juncos JL, Mouradian MM, Serrati C, Chase TN.
group of PD patients with a limited range of disease Levodopa pharmacokinetic mechanisms and motor ﬂuctuations in
duration, and additional work is necessary to establish the Parkinson’s disease. Ann Neurol 1987;21:370–6.
 Wooten GF, Marsden CD, Fahn S, editors, Movement Disorders 2,
contribution of disease duration to cognitive difﬁculty in 1st ed, Pharmacokinetics of levodopa, Vol. 11, London: Butter-
PD. The effect of withholding levodopa was limited, given worths, 1987, pp. 231–48.
the relatively brief period that this medication was with-  Brown RG, Marsden CD, Quinn N, Wyke MA. Alterations in
held and the fact that patients continued to take other cognitive performance and affect arousal state during ﬂuctuations in
dopaminergic medications. We could not assess the impact motor function in Parkinson’s disease. J Neurol Neurosurg Psychi-
of other classes of medication on sentence comprehension, atry 1984;47:454–65.
 Cooper JA, Sagar HJ, Doherty SM, Jordan N, Tidswell P, Sullivan
such as anti-cholinergic medication, given the limited use EV. Different effects of dopaminergic and anticholinergic therapies
of these substances in the PD patients we assessed. on cognitive and motor function in Parkinson’s disease. Brain
Nevertheless, it is important to remember that other 1992;115:1701–25.
neurotransmitter systems contributing to PD can have an  Jahanshahi M, Brown RG, Marsden CD. The effect of withdrawal of
impact on sentence comprehension as well, and additional dopaminergic medication on simple and choice reaction time and the
use of advance information in Parkinson’s disease. J Neurol
work will be needed to manipulate these substances in Neurosurg Psychiatry 1992;58:1168–76.
other PD patients. With these shortcomings in mind, our  Mohr E, Fabbrini G, Williams J. Cognitive concomitants of dopa-
observations are consistent with the hypothesis that DA mine system stimulation in parkinsonian patients. J Neurol Neuro-
supports the working memory resources that contribute to surg Psychiatry 1987;50:1192–6.
sentence processing in PD.  Owen AM, Sahakian BJ, Hodges JR, Summers BA, Polkey CE.
Dopamine dependent frontostriatal planning deﬁcits in early Parkin-
son’s disease. Neuropsychology 1995;9:126–40.
 Girotti F, Carella F, Grassi MP, Soliveri P, Marano R, Caraceni T.
Acknowledgements Motor and cognitive performances of Parkinsonian patients in the on
and off phases of the disease. J Neurol Neurosurg Psychiatry
This work was supported in part by grants from the 1986;49:657–60.
 Gotham AM, Brown RG, Marsden CD. ‘Frontal’ cognitive function
US Public Health Service (N535867, AG15116, and
in patients with Parkinson’s disease ‘‘on’’ and ‘‘off’’ levodopa.
AG17586), and the American Health Assistance Founda- Brain 1988;111:299–321.
tion. We express our appreciation to Heather White for her  Taylor AE, Saint-Cyr JA, Lang AE. Parkinson’s disease: Cognitive
help with various aspects of this study. changes in relation to treatment response. Brain 1987;110:35–51.
 Kulisevsky J, Avila A, Barbanoj M, Antonijoan R, Berthier M,
Gironell A. Acute effects of levodopa on neuropsychological
performance in stable and ﬂuctuating Parkinson’s disease patients at
References different levodopa plasma levels. Brain 1996;119:2121–32.
 Lieberman P, Kako E, Friedman J, Tajchman G, Feldman LS,
 Grossman M, Carvell S, Gollomp S, Stern MB, Vemon G, Hurtig HI. Jiminez EB. Speech production, syntax comprehension, and cogni-
Sentence comprehension and praxis deﬁcits in Parkinson’s disease. tive deﬁcits in Parkinson’s disease. Brain Lang 1992;43:169–89.
Neurology 1991;41:1620–6.  Natsopoulos D, Grouios G, Bostantzopoulou S, Mentenopoulos G,
130 M. Grossman et al. / Journal of the Neurological Sciences 184 (2001) 123 – 130
Katsarou Z, Logothetis J. Algorithmic and heuristic strategies in  King J, Just MA. Individual differences in syntactic processing: The
comprehension of complement clauses by patients with Parkinson’s role of working memory. J Mem Lang 1991;30:580–602.
disease. Neuropsychologia 1993;31:951–64.  Miyake A, Carpenter PA, Just MA. A capacity approach to syntactic
 UlIman MT, Corkin S, Coppola M, Hickok G, Growdon JH, comprehension disorders: Making normal adults perform like
Koroshetz WJ, Pinker S. A neural dissociation within language: aphasic patients. Cognit Neuropsychology 1994;11:671–717.
Evidence that the mental dictionary is part of declarative memory,  Waters GS, Caplan D. Processing resource capacity and the com-
and that grammatical rules are processed by the procedural system. J prehension of garden path sentences. Mem Cogn 1996;24:342–55.
Cogn Neurosci 1997;9:266–76.  Folstein MF, Folstein SF, McHugh PR. ‘Mini Mental State’ A
 Caplan D, Waters GS. Verbal working memory and sentence practical method for grading the cognitive state of patients for the
comprehension. Behav Brain Sci 1999;22:77–126. clinician. J Psychiatric Res 1975;12:189–98.
 Grossman M. Sentence processing in Parkinson’s disease. Brain and  Quantiﬁcation of neurologic deﬁcit. In: Lang A, Fahn S, Munsat T,
Cognition, 2000;40:387–413. editors, Assessment of Parkinson’s disease, Boston: Butterworths,
 Just MA, Carpenter PA. A capacity theory of comprehension: 1989, pp. 285–309.
Individual differences in working memory. Psychol Rev  Daneman M, Carpenter PA. Individual differences in working
1992;99:122–49. memory and reading. J Verb Learn Verb Behav 1980;19:450–66.
 An invitation to cognitive science. In: Zurif EB, Osherson D,  Salthouse TA. The aging of working memory. Neuropsychology
editors, 2nd ed, 13, Brain regions of relevance to syntactic process- 1994;8:535–43.
ing, Cambridge: MIT Press, 1996, pp. 381–97.  Engle RW, Cantor J, Carullo JJ. Individual differences in working
 Geyer H, Grossman M. Investigating the basis for the sentence memory and comprehension: A test of four hypotheses. J Exp
comprehension deﬁcit in Parkinson’s disease. J Neurolinguistics Psychol: Learn Mem Cogn 1992;18:972–92.
1994;8:191–205.  Williams GV, Goldman-Rakic PS. Modulation of memory ﬁelds by
 Grossman M, CarvelI S, Stern MB, Gollomp S, Hurtig HI. Sentence dopamine D1 receptors in prefrontal cortex. Nature 1995;376:572–
comprehension in Parkinson’s disease: The role of attention and 5.
memory. Brain Lang 1992;42:347–84.  Cooke A, Zurif EB, DeVita C, Alsop D, Koenig P, Detre J, Gee JC,
 Grossman M, Kalmanson J, Bernhardt N, Stern MB, Hurtig HI. Pinango M, Balogh J, Grossman M. The neural basis for sentence
Cognitive resource limitations during sentence processing in Parkin- comprehension: Grammatical and short-term memory components.
son’s disease. Brain Lang 2000;73:1–16. Submitted to Human Brain Mapping.
 Grossman M, Lee C, Morris J, Stern MB, Hurtig HI. On-line  Alexander GE, Crutcher MD. Functional architecture of basal
sentence processing in Parkinson’s disease. Submitted to Brain and ganglia circuits: Neural substrates of parallel processing. Trends
Language. Neurosci 1990;13:266–71.
 Grossman M, Zurif EB, Prather P, Lee C, Kalmanson J, Stern MB,  German D, Manaye K, Smith W, Woodward D, Saper C. Midbrain
Hurtig HI. Information processing speed and sentence comprehen- dopaminergic cell loss in Parkinson’s disease: computer visualiza-
sion in Parkinson’s disease. Submitted to Neuropsychology. tion. Ann Neurol 1989;26:507–14.
 Kemmerer DL. Impaired comprehension of raising-to-subject con-  Martin A, Ungerleider L, Haxby JV, Gazzaniga MS, editors. The
structions in Parkinson’s disease. Brain Lang 1999;66:311–28. new cognitive neurosciences. Cambridge: MIT Press, 2000; 71,
 Waters GS, Caplan D. The role of working memory in sentence Category speciﬁcity and the brain: The sensory / motor model of
processing: Evidence from Parkinson’s disease. Brain Lang semantic representations of objects, pp. 1023–1036.
1997;60:64–6.  Saint-Cyr JA, Taylor AE, Lang AE. Neuropsychological and
 Just MA, Carpenter PA. The intensity dimension of thought: psychiatric side effects in the treatment of Parkinson’s disease.
Pupillometric indices of sentence processing. Can J Exp Psychology Neurology 1993;43(Suppl. 6):S47–52.