Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Speech production, syntax comprehension, and cognitive deficits in Parkinson's disease. 139 19

Posteroventral pallidotomy (PVP) was carried out in 86 patients with Parkinson's disease, who presented marked bradykinesia, freezing of gait and postural defect associated with rigidity and tremor in 82 patients (bradykinesia type), and similar gait and postural problems with minimum signs of rigidity and tremor in 4 (pure akinesia type). The stereotactic coordinates of Leksell's device were calculated from MRI and conventional ventriculography. The final target was defined by microelectrode techniques in the basal ganglia. The microrecording study revealed a very high background activity in the internal pallidum in patients of the bradykinetic type, however, a much lower pallidal activity in patients of the pure akinesia type. Fifty-eight patients underwent unilateral PVP, and 28 underwent bilateral surgery. Following PVP, rigidity tremor and poor reciprocal movements were significantly improved especially in the contralateral extremities. The most dramatic findings were the reversal of akinetic symptoms and wearing-off phenomena. The patients were followed up for 3-30 months (mean = 8) after surgery. Of the 82 bradykinesia type patients, good result were obtained in 48 (58%), fair results in 26 (32%), and minor improvement or no change in 8 (10%). In all the 4 patients of the pure akinesia type, recurrence of the akinetic symptoms occurred after a temporal improvement lasting a few days to 3 month after surgery. There was worst dysarthria in 3 patients, hemiparesis in 1 and partial motor aphasia in 1. The visual field problem was not complicated in any patients. These findings suggest that akinetic symptoms in PD are implicated in overactive pallidal outputs with putative GABAergic modulator by excessively inhibiting pedunculopontine nucleus activity (midbrain locomotor and posture regions) as well as thalamic activity. Partial interruption of the pallidal efferents eliminates the akinetic symptoms by disinhibitory effects on the target structures. The pathology of PD of the pure akinesia type is supposedly in the brainstem and should be excluded from indication of pallidotomy.
 ...
PMID:Surgical control of akinesia in Parkinson's disease. 879 Oct 23

The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/- 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/- 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia "off" scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.
 ...
PMID:Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis. 960 17

Stereotactic medial posteroventral pallidotomy for treatment of Parkinson's disease attracts increasing attention. We report on the preliminary results of 12 patients at 1 year after microelectrode-guided unilateral pallidotomy. The primary indications were severe bradykinesia and levodopa-induced dyskinesias. After radiofrequency lesioning all patients had immediate improvement of contralateral parkinsonian signs. Postoperative magnetic resonance imaging confirmed the localization of the lesions. At the 1-year follow-up, all patients had sustained benefit. The global improvement was rated as moderate in six cases, and as marked in six other cases. The mean values of various subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) showed highly significant changes in the "off" state (pre/postoperatively): UPDRS Motor score (60.3/31). UPDRS Activities of Daily Living (ADL) score (33.2/18.3), gait/postural stability score (13.8/7.0), and subscores for contralateral rigidity (4.9/2.1), tremor (7.1/1.4) and bradykinesia (11.6/5.3). There was also significant improvement of ipsilateral bradykinesia and rigidity. Furthermore, we found significant changes of the mean values of the UPDRS ADL and motor "on" scores, an increase of the percentage of "on" time with reduced on-off fluctuations, and a decrease of the percentage of levodopa-induced dyskinesias, with marked improvement or complete abolition of contralateral dyskinesias in particular. The preoperative levodopa regimen was maintained, in general, or only slightly modified, if necessary. Two patients had transient complications: one patient suffered postoperative pneumonia and altered mental status; another patient displayed mild Broca's aphasia secondary to a small stroke involving the dorsal thalamus and the adjacent white matter. There were no persistent side effects at the 1-year follow-up. Contemporary unilateral pallidotomy is an effective and promising therapeutical option for surgical treatment of advanced Parkinson's disease.
 ...
PMID:[Medial posteroventral pallidotomy for the treatment of Parkinson's disease]. 948 51

Research is reviewed concerning the performance of several neurological groups on the perception and production of voicing contrasts in speech. Patients with cerebellar damage, Parkinson's disease, specific language impairment, Broca's aphasia, apraxia, and Wernicke's aphasia have been reported to be impaired in the perception and articulation of voicing. The types of deficits manifested by these neurologically impaired groups in creating and discriminating voicing contrasts are discussed and the respective contributions of separate neural areas are identified. A model is presented specifying the level of phonemic processing thought to be impaired for each patient group and critical tests of the model's predictions are identified.
 ...
PMID:Relating selective brain damage to impairments with voicing contrasts. 1124 58

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.
 ...
PMID:On the nature and evolution of the neural bases of human language. 1265 8

While growing evidence reports changes in language use in non-demented individuals with Parkinson's disease (PD), the presence and nature of the deficits remain largely unclear. Researchers have proposed that dysfunctioning fronto-basal ganglia circuit results in impaired grammatical processes, predicting qualitatively similar language impairments between individuals with PD and agrammatic Broca's aphasia, whereas others suggest that PD is not associated with language-specific grammatical impairment. In addition, there is a paucity of research examining syntactic production in PD at the sentence-level. This study examined sentence production of individuals with PD, healthy older adults, and individuals with agrammatic Broca's aphasia. In Experiment 1, using a Cinderella story-telling task, proportion of grammatical sentences, number of embedded clauses and production of verb arguments in sentences were examined. In Experiment 2, a structured sentence elicitation task was used in which syntactic complexity of sentences (canonical vs. non-canonical word order) was systematically manipulated while minimizing demands for non-syntactic processing. Only the participants with agrammatic Broca's aphasia showed significantly impaired syntactic production in both experiments. Participants with PD did not show impaired syntactic production in either task, despite impairments in lexical retrieval, repetition of words and sentences, and speech production. These findings suggest that impaired syntactic processing may not be a core deficit underlying the changes in language use in non-demented PD. Changes in language use in PD are qualitatively different from language deficits in aphasia.
 ...
PMID:Sentence production in Parkinson's disease. 2949 61