Cognitive resource limitations during sentence comprehension in Parkinson's disease

We report a single-case study of peripherally acquired dyslexia that meets the clinical criteria of "alexia without agraphia." The patient, AA, has a large infarct involving the left posterior cerebral artery. The most striking feature is a severe impairment in recognizing single visually presented letters that precludes explicit or implicit access to reading, even in a letter-by-letter fashion. AA can, however, differentiate letters from similar nonsense characters and digits, and he is also able to identify alphanumeric signs when the visual channel is bypassed (through somesthesic or kinesthesic presentation). Spelling tasks are also well performed. Since there is a breakdown in mapping a visually presented letter to its abstract graphemic representation, we propose the term "visuographemic alexia" for this kind of reading disorder. The pattern of deficits is interpreted following theoretical models previously developed in cognitive neuropsychology. An alexia for arabic numerals with preserved comprehension lends additional support for the crucial processing of different notational systems (e.g., phonographic vs logographic). More general perceptive disorders do not seem to account for these patterns; they are material-specific. Finally, we attempt to specify functional correlations with the implied neural networks.     

Impaired frontostriatal cognitive functioning following posteroventral pallidotomy in advanced Parkinson's disease

We investigated the long-term effects of posteroventral pallidotomy on tests sensitive to the functional integrity of frontostriatal neural systems in a sample of 11 patients with advanced Parkinson's disease (PD). Patients were assessed within 1 month prior to surgery and at 12 months following pallidotomy. Changes in outcome measures were compared to a control sample of equally performing PD patients receiving nonsurgical medical management assessed over a 12-month period. Measures of cognitive abilities sensitive to frontostriatal functional integrity tested psychomotor processing speed, executive components of working memory, and reasoning. Additional tests of general mental status and semantic memory ability were utilized to assess the specificity of the effect of pallidotomy on cognitive function. Significant declines in performance on all measures sensitive to frontostriatal integrity were found for the surgery group but not the PD control group. No significant changes in performance were found on the measures of general mental status or semantic memory for either the surgery or PD control samples. These results suggest that the posteroventral pallidotomy selectively impairs performance on tests of frontostriatal cognitive abilities.     

Impaired finger dexterity in Parkinson's disease is associated with praxis function

A controversial concept suggests that impaired finger dexterity in Parkinson’s disease may be related to limb kinetic apraxia that is not explained by elemental motor deficits such as bradykinesia. To explore the nature of dexterous difficulties, the aim of the present study was to assess the relationship of finger dexterity with ideomotor praxis function and parkinsonian symptoms. Twenty-five patients with Parkinson’s disease participated in the study. Their left and right arms were tested independently. Testing was done in an OFF and ON state as defined by a modified version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Finger dexterity was assessed by a coin rotation (CR) task and ideomotor praxis using a novel test of upper limb apraxia (TULIA), in which the patients were requested to imitate and pantomime 48 meaningless, as well as communicative and tool-related gestures. Coin rotation significantly correlated with TULIA irrespective of the motor state and arm involved, but not with the MDS-UPDRS. This association was significantly influenced by Hoehn and Yahr stage.The strong association of finger dexterity with praxis function but not the parkinsonian symptoms indicates that impaired finger dexterity in Parkinson’s disease may be indeed apraxic in nature, yet, predominantly in advanced stages of the disease when cortical pathology is expected to develop. The findings are discussed within a cognitive-motor model of praxis function.     

Impaired sequential and partially compensated probabilistic skill learning in Parkinson's disease

The striatal dopaminergic dysfunction in Parkinson's disease (PD) has been associated with deficits in skill learning in numerous studies, but some of the findings remain controversial. Our aim was to explore the generality of the learning deficit using two widely reported skill learning tasks in the same group of Parkinson's patients. Thirty-four patients with PD (mean age: 62.83 years, SD: 7.67) were compared to age-matched healthy adults. Two tasks were employed: the Serial Reaction Time Task (SRT), testing the learning of motor sequences, and the Weather Prediction (WP) task, testing non-sequential probabilistic category learning. On the SRT task, patients with PD showed no significant evidence for sequence learning. These results support and also extend previous findings, suggesting that motor skill learning is vulnerable in PD. On the WP task, the PD group showed the same amount of learning as controls, but they exploited qualitatively different strategies in predicting the target categories. While controls typically combined probabilities from multiple predicting cues, patients with PD instead focused on individual cues. We also found moderate to high correlations between the different measures of skill learning. These findings support our hypothesis that skill learning is generally impaired in PD, and can in some cases be compensated by relying on alternative learning strategies.     

Sentence comprehension in Parkinson's disease: the role of attention and memory.

Sentence comprehension is a complex process involving at least attentional, memory, grammatical, and semantic components. We report three experiments designed to evaluate the impairments underlying sentence comprehension difficulties in nondemented patients with Parkinson's disease (PD). In the first experiment, we asked patients to answer simple questions about sentences which varied in terms of grammatical complexity and semantic constraint. We found that PD patients are significantly compromised in their ability to perform this task. Their difficulties became more prominent as grammatical complexity increased, but they were significantly assisted by semantic constraints that limited possible interpretations of a sentence. Analyses of individual patient profiles revealed heterogeneous performance across the group of PD patients and somewhat inconsistent performance for patients across testing sessions. In the second experiment, we tested the possibility that patients' heterogeneous performance on the sentence comprehension task is due to an impairment in memory or attention, cognitive domains known to be compromised in some PD patients. Although PD patients and control subjects differed on one memory measure, there were no significant correlations between attention and memory performance and the results of the sentence comprehension task. In the final experiment, we manipulated the sentences used in the first experiment in a fashion that stressed the need for memory and attention in a sentence. The results indicated that PD patients are significantly compromised in their ability to attend to certain critical grammatical features of a sentence. A regression analysis identified specific grammatical, semantic, and attentional mechanisms as significant contributors to PD patients' overall sentence comprehension, accounting for over 97% of the variance in their performance. We conclude that there are multiple sources of cognitive difficulty underlying PD patients' sentence comprehension impairment.     

Speech production, syntax comprehension, and cognitive deficits in Parkinson's disease.

Speech samples were obtained that were analyzed for voice onset time (VOT) for 40 nondemented English speaking subjects, 20 with mild and 20 with moderate Parkinson's disease. Syntax comprehension and cognitive tests were administered to these subjects in the same test sessions. VOT disruptions for stop consonants in syllable initial position, similar to those noted for Broca's aphasia, occurred for nine subjects. Longer response times and errors in the comprehension of syntax as measured by the Rhode Island Test of Sentence Comprehension (RITLS) also occurred for these subjects. Anovas indicate that the VOT overlap subjects had significantly higher syntax error rates and longer response times on the RITLS than the VOT nonoverlap subjects--F(1, 70) = 12.38, p less than 0.0008; F(1, 70) = 7.70, p less than 0.007, respectively. The correlation between the number of VOT timing errors and the number of syntax errors was significant. (r = 0.6473, p less than 0.01). VOT overlap subjects also had significantly higher error rates in cognitive tasks involving abstraction and the ability to maintain a mental set. Prefrontal cortex, acting through subcortical basal ganglia pathways, is a component of the neural substrate that regulates human speech production, syntactic ability, and certain aspects of cognition. The deterioration of these subcortical pathways may explain similar phenomena in Broca's aphasia. Results are discussed in relation to "modular" theories.     

Effects of verbal working memory deficits on metaphor comprehension in patients with Parkinson's disease

This research studied one aspect of pragmatic language processing, the ability to understand metaphorical language, to determine whether patients with Parkinson disease (PD) are impaired for these abilities, and whether cognitive resource limitations/fronto-striatal dysfunction contributes to these deficits. Seventeen PD participants and healthy controls (HC) completed a series of neuropsychological tests and performed a metaphor comprehension task following the methods of Gernsbacher and colleagues [Gernsbacher, M. A., Keysar, B., Robertson, R. R. W., & Werner, N. K. (2001). The role of suppression and enhancement in understanding metaphors. Journal of Memory and Language, 45, 433-450.] When participants in the PD group were identified as "impaired" or "unimpaired" relative to the control group on a measure of verbal working memory span, we found that only PD participants with impaired working memory were simultaneously impaired in the processing of metaphorical language. Based on our findings we argue that certain "complex" forms of language processing such as metaphor interpretation are highly dependent on intact fronto-striatal systems for working memory which are frequently, although not always, compromised during the early course of PD.     

The roles of sequencing and verbal working memory in sentence comprehension deficits in Parkinson's disease

Studies of sentence comprehension deficits in Parkinson's disease (PD) patients suggest that language processing involves circuits connecting subcortical and cortical regions. Anatomically segregated neural circuits appear to support different cognitive and motor functions. To investigate which functions are implicated in PD comprehension deficits, we tested comprehension, verbal working memory span, and cognitive set-switching in a non-linguistic task in 41 PD patients; we also obtained speech measurements reflecting motor sequencing processes that may be involved in articulatory rehearsal within working memory. Comprehension of sentences with center-embedded or final relative clauses was impaired when they could not be understood from lexical semantic content alone. Overall comprehension error rates correlated strongly with impaired set-switching and significantly with reduced working memory span and speech motor sequencing deficits. Correlations with comprehension of different sentence structures indicate that these impairments do not represent a single deficit; rather, PD comprehension deficits appear to arise from several independent mechanisms. Deficits in cognitive set-switching or underlying inhibitory processes may compromise the ability to process relative clauses. Deficits in verbal working memory appear to impair comprehension of long-distance dependencies. Speech sequencing correlated with neither set-switching nor verbal working memory span, consistent with their being supported by independent, segregated cortico-subcortical circuits.     

Past tense formation and comprehension of passive sentences in Parkinson's disease: evidence from Greek

The present study investigates the production of regular and irregular verbs in the past tense and the comprehension of passive sentences by Greek-speaking PD patients, and compares their behavior to that of normal speakers. Although the two groups manifest large scale differences at all the above constructions, the behavior of PDs is not different at regular vs. irregular past tense formation neither did we obtain strong evidence that they do not comprehend passives, most importantly, they certainly do not perform at chance. On the basis of the above, we conclude that there are no indications for a clearly linguistic deficit of the PD group, hence, their difference with the control group should be attributed to other factors, such as the computational demands of the tasks.     

Impaired perception of vocal emotions in Parkinson's disease: influence of speech time processing and executive functioning

Little is known about the underlying dimensions of impaired recognition of emotional prosody that is frequently observed in patients with Parkinson's disease (PD). Because patients with PD also suffer from working memory deficits and impaired time perception, the present study examined the contribution of (a) working memory (frontal executive functioning) and (b) processing of the acoustic parameter speech rate to the perception of emotional prosody in PD. Two acoustic parameters known to be important for emotional classifications (speech duration and pitch variability) were systematically varied in prosodic utterances. Twenty patients with PD and 16 healthy controls (matched for age, sex, and IQ) participated in the study. The findings imply that (1) working memory dysfunctions and perception of emotional prosody are not independent in PD, (2) PD and healthy control subjects perceived vocal emotions categorically along two acoustic manipulation continua, and (3) patients with PD show impairments in processing of speech rate information.     

Syntactic comprehension deficits in Alzheimer's disease

Syntactic comprehension of German patients with dementia of the Alzheimer type was investigated and compared to healthy controls matched with respect to age, sex, and education. Special attention was directed at syntactic structures, which, in contrast to a language like English, are feasible in a grammatically rich language like German. In a sentence picture matching paradigm, only semantically reversible sentences were used. Syntactic complexity ranged from simple active voice sentences to more complex sentences like center-embedded object relative sentences. In comparison to their controls, patients showed a deficit in nearly all categories. Their performance was not influenced by age, but was heavily influenced by the degree of cognitive impairment. Patients with mild cognitive impairment, as defined by a MMSE score of 20 or higher, showed only slight difficulties in syntactic processing, whereas patients with moderate to severe impairment (MMSE < 20) did not perform above chance limits in most syntactic categories. It appears as though syntactic comprehension is only mildly affected in the early stages of Alzheimer's disease and is rather severely impaired in more advanced stages. In the present report, results are discussed in terms of working memory demands for syntactic processing.     

Source memory in Parkinson's disease

Three experiments (ns = 14 per group) are reported which investigated the ability of Parkinson patients to remember the characteristics of conditions under which a memory was acquired. In Exp. 1, subjects were required to indicate for each item in a recognition memory test whether it was spoken by Experimenter 1 or by Experimenter 2 (external-external source memory). In Exp. 2, subjects had to indicate for each item whether it was generated by themselves or by the experimenter (internal-external source memory). In Exp. 3, subjects had to judge whether an item was generated by themselves in saying or in thinking (internal-internal source memory). We found that patients with Parkinson's disease were not impaired in the previous two kinds of source memory (Exp. 1 and 2) but were impaired in internal-internal source memory (Exp. 3) relative to the age-matched control groups. In addition, both groups' performance could be improved when given distinctive cues, i.e., perceptual cues in Exp. 1 and different-domain cues in Exp. 2. These results suggest that the availability of cues was critical for Parkinson's disease in source memory. Finally, the result of Exp. 2 also showed generation effects for patients with Parkinson's disease. The generation effect refers to better memory of information by people when they had to produce it, e.g., producing associates to a word, compared with memory of information given to them.     

Impulse-control disorders in Parkinson's disease

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.     

Emotional dysfunction in Parkinson's disease

In addition to motor symptomatology, idiopathic Parkinson's disease is characterized by emotional dysfunction. Depression affects some 30 to 40 percent of Parkinson patients and other psychiatric co-morbidities include anxiety and apathy. Neuropsychological and neuroimaging studies of emotional dysfunction in Parkinson patients suggest abnormalities involving mesolimbic and mesocortical dopaminergic pathways. There is also evidence suggesting that the interaction between serotonin and dopamine systems is important in the understanding and treatment of mood disorders in Parkinson's disease. In this review we discuss the neuropsychiatric abnormalities that accompany Parkinson's disease and describe their neuropsychological, neuropharmacologic, and neuroimaging concomitants.     

Control of saccades in Parkinson's disease

Parkinson's patients (PD) made pro- and antisaccades: In the no-delay condition, the target appeared concurrent with the GO signal. In the delay condition, the target appeared before the signal for movement. Second, we probed spatial working memory in PD. Subjects looked to the remembered locations of sequential targets. In the no-delay prosaccade condition, PD had faster reaction times, made more express saccades, and exhibited hypometria. In the no-delay antisaccade condition, PD had longer reaction times and made more direction errors. In the delay tasks, PD made more direction errors and had more difficulty withholding a movement. PD made more sequencing errors in the spatial working memory task. These findings are consistent with a basal ganglia pathophysiology influencing eye movement processing in the frontal cortex.     

Metaphor comprehension in Alzheimer's disease: novelty matters

The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of non-conventional (novel) metaphor comprehension. This ability was not related to global cognitive deterioration or to deficits in the cognitive domains of attention, memory and language comprehension. On the other hand, the impairment in verbal reasoning appeared to be relevant for both novel and conventional metaphor comprehension. The relationship between novel metaphor comprehension and performance in the visual-spatial planning task of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) suggests that executive impairment, possibly related to prefrontal dysfunction, may be responsible for the pAD patients' poor performance in novel metaphor comprehension. The present findings suggest a role of the prefrontal cortex in novel metaphor comprehension.     

Ideational fluency in Parkinson's disease.

Recent research on Parkinson's disease (PD) suggests that executive functions are impaired but that visuospatial functions may be spared. This dissociation has been attributed to dysfunction in ascending dopaminergic pathways affecting the prefrontal cortex. We investigated these ideas in a sample of intellectually intact patients with idiopathic, optimally treated PD (N = 20) and in spouse controls (N = 15); the groups were divided into young (age < 60) and old subgroups, each comparable on education, vocabulary level, and Mini-Mental State scores. Six tasks were selected from a set of factor-referenced cognitive tests to measure three abilities: (1) ideational fluency (ability to generate ideas), (2) flexibility of use (ability to shift mental set), and (3) spatial orientation (ability to perceive spatial patterns). PD patients were impaired only on the ideational fluency factor (p = .01). An age-related deficit was seen on the spatial factor (p < .05) with a trend on the flexibility factor (.05 < p < .10). No interactions were significant. The findings suggest that when age and verbal intelligence are controlled, PD patients show no deficit on purely spatial tasks; in contrast, patients seem less able to generate ideas though capable of shifting from one idea to another.     

Sentence processing in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative condition that is associated with the depletion of dopamine (DA)-containing neurons in specific brain regions. This article reviews one consequence of this defect-sentence comprehension difficulty in nondemented patients with PD. The first section describes the pattern of cognitive deficits seen in patients with PD, focusing specifically on their difficulties with language processing. Subsequent sections relate the profile of cognitive impairments in PD to studies investigating compromised DA metabolism in fronto-striatal brain regions. The findings suggest that the sentence comprehension deficit in PD is due in large part to limitations in the strategic distribution of cognitive resources such as selective attention that contribute to the processing of complex material. The physiological basis for this deficit appears to be associated with the disruption of a fronto-striatal cerebral network that is compromised following degradation of the DA projection system.     

Noun verb dissociation in Parkinson's disease

A noun/verb dissociation with a relative verb deficit was found in patients affected by Parkinson's disease, even in relatively early stages, when mental deterioration is not severe. This finding is compatible with earlier observations, according to which verbs are dealt with in more anterior regions with respect to nouns. It also supports the speculation that the co-ordination and the manipulation of information associated with a verb world rely on the frontostriatal system.     

Non-motor aspects of Parkinson's disease

Parkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.