Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study

OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement.     

Motor imagery in normal subjects and Parkinson's disease patients: an H215O PET study

Motor imagery paradigms can be used to investigate motor preparation. We used positron emission tomography to compare regional cerebral blood flow (rCBF) in patients with Parkinson's disease and normal controls under three conditions: rest, motor imagery and motor execution. In controls, imagery activated bilateral dorsolateral and mesial frontal cortex, inferior parietal cortex and precuneus. Motor execution additionally activated primary motor cortex (p < 0.001). Between-group, for imagery there was relative reduction in dorsolateral and mesial frontal activation in the patient group (p<0.01). For execution, there was impaired activation of right dorsolateral frontal cortex and basal ganglia (p<0.01). Our results support the notion that underfunctioning of mesial frontal and dorsolateral prefrontal cortex may underlie motor preparation in Parkinson's disease but also suggest that akinesia may occur in the absence of impaired mesial frontal cortex activation.     

Brain metabolic correlates of fatigue in Parkinson's disease: a PET study

Purpose: The neural bases of fatigue in Parkinson's disease (PD) remain uncertain. We aimed to assess the brain metabolic correlates of fatigue in patients with PD.

Patients and methods: Twenty-seven PD patients without clinically relevant depression (17-item Hamilton Depression Rating Scale (HAMD) score ≥ 14), apathy (Apathy Scale (AS) score ≥ 14) and excessive daytime somnolence (Epworth Sleepiness Scale (ESS) score ≥ 10) were evaluated with Fatigue Severity Scale (FSS). Each patient had an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale motor part. Levodopa equivalent daily dose for each patient was also calculated. The PET images were analyzed using statistical parametric mapping software. We introduced the age, educational level, HAMD scores, AS scores and ESS scores as covariates.

Results: High FSS scores were associated with brain hypermetabolism in areas including the right middle temporal gyrus (Brodmann area (BA) 37) and left middle occipital gyrus (BA 19). Increased FSS scores correlated with hypometabolism in regions such as the right precuneus (BA 23), left inferior frontal gyrus (BA 45) and left superior frontal gyrus (orbital part, BA 11).

Conclusion: This study demonstrates that brain areas including frontal, temporal and parietal regions indicative of emotion, motivation and cognitive functions are involved in fatigue in PD patients.     

Motor imagery evokes increased somatosensory activity in Parkinson's disease patients with tremor

Parkinson's disease (PD) is surprisingly heterogeneous: some patients have a prominent resting tremor, while others never develop this symptom. Here we investigate whether the functional organization of the voluntary motor system differs between PD patients with and without resting tremor, and whether these differences relate to the cerebral circuit producing tremor. We compared 18 PD patients with marked tremor, 20 PD patients without tremor, and 19 healthy controls. Subjects performed a controlled motor imagery task during fMRI scanning. We quantified imagery-related cerebral activity by contrasting imagery of biomechanically difficult and easy movements. Tremor-related activity was identified by relating cerebral activity to fluctuations in tremor amplitude, using electromyography during scanning. PD patients with tremor had better behavioral performance than PD patients without tremor. Furthermore, tremulous PD patients showed increased imagery-related activity in somatosensory area 3a, as compared with both healthy controls and to nontremor PD patients. This effect was independent from tremor-related activity, which was localized to the motor cortex, cerebellum, and thalamic ventral intermediate nucleus (VIM). The VIM, with known projections to area 3a, was unique in showing both tremor- and imagery-related responses. We conclude that parkinsonian tremor influences motor imagery by modulating central somatosensory processing through the VIM. This mechanism may explain clinical differences between PD patients with and without tremor.     

Motor blocks in Parkinson's disease.

Freezing episodes and related phenomena (as a general term, motor blocks [MBs]) are poorly understood, particularly disabling, and a therapeutically frustrating problem in Parkinson's disease (PD). Epidemiologic and clinical characteristics of MBs, as well as risk factors to develop MBs, have never been fully addressed. Herein, we report our database survey on 990 PD patients, of whom 318 (32%) had MBs. The majority of MBs were linked to gait. Start hesitation occurred in 86%, blocking on turning in 45%, and blocking in narrow spaces in 25% of patients. Initial parkinsonian symptoms in the upper body and tremor as the initial motor symptom were less likely to be associated with the presence of MBs (odds ratios [OR] 0.6 and 0.7, respectively), while initial symptoms affecting gait or trunk had higher association with MBs (OR = 1.58). Longer disease duration, higher Hoehn and Yahr stage, and longer duration of levodopa treatment are all significantly associated with the presence of MBs. We observed significant association between the existence of MBs and levodopa-induced dyskinesias to suggest similar pathophysiology. We propose that MBs in PD are abnormal retrieval or execution of complex motor tasks that can occur as a result of disease progression or as short- or long-term side effects of levodopa treatment.     

Motor fluctuations in Parkinson's disease.

OBJECTIVES: To assess patterns, prevalence, and risk factors of motor fluctuations in an unselected population of Parkinson's disease patients attending Movement Disorders Clinic of a tertiary hospital. MATERIAL AND METHODS: Eighty patients with Parkinson's disease were interviewed and data about their clinical characteristics, motor fluctuations, i.e. dyskinesia, dystonia, motor blocks and details of drug therapy, were collected. RESULTS: Forty patients had at least one type of motor fluctuation. Twenty three patients had motor blocks, 20 had dyskinesia and 11 had dystonia. Interval between onset of symptom and start of levodopa therapy and duration of levodopa therapy correlated with presence of motor fluctuations in general and to dyskinesia in particular. Patients with dyskinesia had younger age of onset of disease. Motor blocks showed a positive relationship to duration of disease. CONCLUSIONS: Fifty percent of unselected patients of Parkinson's disease had motor fluctuations after a mean duration of 5 years of illness. Early initiation and longer duration of levodopa therapy were identified as risk factors for motor fluctuations. Younger patients had more risk of developing dyskinesias. Motor blocks were more common in patients with a longer duration of illness.     

Motor imagery in Huntington's disease

We investigated the role of the basal ganglia (BG) in motor imagery in patients with Huntington's disease (HD). A visually guided pointing task assessed whether patients could predict actual movement time (MT) through motor imagery. Executed and imagined movements were performed when vision was constrained centrally, or was free to move. Participants completed a series of imagined and actual movements, with and without central fixation, between two target circles. Patients with HD and controls' imagined MTs were significantly faster than their executed MTs. In compliance with Fitt's law, both actual and imagined MTs increased as a function of increasing task difficulty. We conclude that motor imagery is relatively preserved in HD.     

Motor cortex reorganisation in Parkinson's disease.

Transcranial magnetic stimulation mapping of the motor cortical projection to the hand was performed in a group of patients with Parkinson's disease (PD) of variable duration to determine whether there is evidence of cortical reorganisation. Map shifts were found in the majority of PD cases (12/15), in untreated early cases as well as treated cases of longer duration, and there was a correlation between inter-side difference in the severity of PD symptoms (Unified Parkinson's Disease Rating Scale) and interhemispheric map displacement (r=0.60; P=0.018). These findings indicate that there is reorganisation of the corticomotor representation of the hand in PD, even at a relatively early stage of the disease, and suggest a dynamic process of reorganisation in the motor cortex due to an increase in the pallidal inhibitory inputs to the thalamo-cortical projections.     

Sleepiness in Parkinson's disease: a controlled study.

Sudden-onset sleep episodes while driving have been reported in Parkinson's disease (PD) patients, and termed sleep attacks because they were reported to be irresistible and to occur without warning. We postulate that these episodes are due to excessive daytime sleepiness secondary to the high frequency of sleep disorders in PD patients and the sedative effects of dopaminergic medications. We assessed the frequency and relationship between excess daytime sleepiness and sleep episodes while driving (SE) in patients with PD. We evaluated 101 consecutive PD patients presenting to the Movement Disorder Center at the Mount Sinai School of Medicine using a questionnaire that incorporated a subjective estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on disease severity and dopaminergic medications. One hundred age-matched respondents without PD served as a control population. Excess daytime sleepiness was reported in 76% of PD patients compared to 47% of controls (P < 0.05). The mean ESS scores for PD patients was 9.1 +/- 6.1 versus 5.7 +/- 4.4 in controls (P < 0.001). ESS scores > or =10 were observed in 40.6% of PD patients compared to 19% of controls (P < 0.01) and 24% of PD patients had scores > or =15, compared to 5% of controls (P < 0.001). Sleep episodes while driving were experienced by 20.8% of PD drivers compared to 6% of control drivers (P < 0.05). The mean daily levodopa (L-dopa) dose equivalent was 1,142 +/- 858 mg in PD drivers who experienced a SE while driving compared to 626 +/- 667 mg in those who had not (P < 0.05). Similarly, ESS was significantly greater in drivers with a SE than in those without (11.6 +/- 6.4 vs. 8.4 +/- 4.1; P < 0.05). Logistic regression analysis demonstrated that ESS and mean daily L-dopa dose equivalents were predictors of sleep episodes while driving, whereas age, gender, disease severity, and individual dopaminergic agents were not. These findings support the notion that sleep episodes while driving in PD patients are related to excess daytime sleepiness and dopaminergic load. Physicians should advise and treat patients accordingly.     

Hallucinations in Parkinson's disease: a follow-up study.

To study prevalence of hallucinations in patients with Parkinson's disease (PD) during a 1-year period, and identify factors predictive of the onset of hallucinations in patients who were hallucination-free at baseline, 141 unselected outpatients with PD were evaluated prospectively for a set of demographic, clinical, and therapeutic variables and the presence of hallucinations during the previous 3 months. Patient groups were compared with nonparametric tests, and logistic regression was applied to significant data. Follow-up data were available for 127 patients. The hallucination prevalence rates (%) at the first and second evaluation were, respectively, 41.7 and 49.6 for hallucinations of all types (NS), 29.1 and 40.2 for minor hallucinations (i.e., presence or passage hallucinations, and illusions) (P = 0.02), 22.8 and 21.2 for formed visual hallucinations (NS), and 8.7 and 8.7 for auditory hallucinations (NS). Hallucinations rarely started or ceased during the study. The most labile forms were minor hallucinations, which developed in 20% of patients and ceased in 9%. During follow-up, 15% of patients started to hallucinate. Three factors, all present at the first evaluation, independently predicted the onset of hallucinations in patients previously free of hallucinations at baseline (odds ratio; 95% confidence interval): severe sleep disturbances (14.3; 2.5-80.9), ocular disorders (9.1; 1.6-52.0), and a high axial motor score (5.7; 1.2-27.4). Hallucinations have a chronic course in most parkinsonian patients. Factors predicting the onset of hallucinations point to a role of extranigral brainstem involvement and a nonspecific, facilitating role of ocular disorders.     

Parkinson's disease in twins: a follow-up study.

OBJECTIVE: To reevaluate concordance rates in 9 monozygotic (MZ) and 12 dizygotic (DZ) twin pairs with PD 8 years after the initial study. BACKGROUND: Longitudinal investigations increase accuracy in clinical diagnosis of PD. METHODS: Follow-up by personal interview and clinical examination. RESULTS: Concordance rates were not different between MZ (3/9) and DZ (5/12) twin pairs at follow-up, even when PD-associated dementia and isolated postural tremor were considered diagnostic of familial Lewy body parkinsonism. Evaluation of medical history, personality traits, and blink rate did not reveal putative early or premorbid parkinsonism in 9 co-twins who were motor-asymptomatic during the follow-up interval. However, these co-twins had reduced semantic fluency in comparison with a healthy control group of similar age. None of 7 co-twins without motor signs who underwent PET investigation 6 years previously showed signs of extrapyramidal disease at follow-up, but verbal memory continued to be reduced in 5 of these co-twins. CONCLUSION: Based on concordance rates only, the findings in our twin sample do not support a major genetic impact for the motor expression of PD.     

Motor complications in Parkinson's disease

Management of motor complications in advanced Parkinson's disease (PD) can be challenging. The main complications are inadequate dopaminergic tone ("off" time and dose failures) and excess dopaminergic tone (dyskinesia). These motor complications increase as PD progresses. Changing the dose and timing of L-dopa is the main strategy for both scenarios. Reducing "off" time can also be achieved by the addition of adjunctive therapies (dopamine agonists, catechol-O-methyl transferase inhibitors, and monoamine oxidase-B inhibitors). Dyskinesia can improve with amantadine and possibly several other medications. Surgical interventions such as lesioning and deep brain stimulation are considered when pharmacological strategies for motor complications are not satisfactory.     

Motor fluctuations in Parkinson's disease

Parkinson's disease is characterized by progressive slowness in activities of daily living and is the most common cause of parkinsonism, whose symptoms include resting tremor, cogwheel rigidity, and bradykinesia. The introduction of levodopa and its positive effect on motor dysfunction in Parkinson's disease has allowed neurologists to focus on motor fluctuations. "End-of-dose wearing-off" and "morning akinesia" are terms to describe the transition between a patient's relatively normal motor performance when levodopa is effective and when it has transiently lost its effect on motor responses and parkinsonian symptoms reemerge. The choices available to alleviate these motor fluctuations range from altering the patient's levodopa/carbidopa dosing schedule to the addition of other agents to the regimen, including dopamine receptor agonists, catechol-O-methyltransferase inhibitors, monoamine oxidase inhibitors, and amantadine, as well as implementing dietary changes. Therapeutic decisions can be difficult because older agents have not been compared in head-to-head trials to determine which drugs are better than others and the order in which they should be tried or added to the levodopa regimen; however, all of the available treatments provide a good possibility of benefit to the patient. Deep brain stimulation surgery is an option for patients with medically intractable severe motor fluctuations.     

Rate of progression in Parkinson's disease: a 6-[18F]fluoro-L-dopa PET study.

The aim of this study was to investigate the rate of progression in Parkinson's disease (PD) with 6-[(18)F]fluoro-L-dopa (FDOPA) positron emission tomography (PET). We investigated 21 patients with PD and eight healthy controls. Ten of the patients were de novo at the time of the first PET scan and antiparkinsonian medication was started thereafter, with a favourable response. A FDOPA PET scan was carried out twice at an approximately 5-year interval. The regions of interest were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images. At the first PET scan, in PD patients the mean k(i)(occ) (x 10(-3) min(-1)) in the anterior putamen was 5.6 +/- 2.7 (mean +/- S.D.; 55% of the control mean) and in the posterior putamen 4.5 +/- 2.4 (45% of the control mean). The k(i)(occ) value for the caudate nucleus was 7.5 +/- 2.1 (x 10(-3) min(-1); 76% of the control mean). The FDOPA uptake declined by the time of the second PET scan and the annual rate of decline was 8.3 +/- 6.3% (P < 0.001) of the baseline mean in the anterior putamen and 10.3 +/- 4.8% (P < 0.001) in the posterior putamen. In the caudate nucleus, FDOPA uptake decreased by 5.9 +/- 5.1% (P < 0.001) of the baseline mean per year. The estimated preclinical period was longest for the posterior putamen being 6.5 years. For the anterior putamen the preclinical period was 4.6 years. In the caudate nucleus, the estimated FDOPA uptake was at normal level at disease onset. In healthy controls, there was no significant decline in FDOPA uptake in any striatal subregion. Our results suggest that the disease process in PD first affects posterior putamen, followed by the anterior putamen and the caudate nucleus, but once started, the absolute rate of decline is the same. In healthy controls, no significant decline in FDOPA was detected.     

Motor fluctuations in Parkinson's disease

Journal of Neurology - Almost all patients with Parkinson's disease will eventually require levodopa during the course of their disease. The effectiveness of levodopa is evident, but earlier...     

Motor learning by imagery is differentially affected in Parkinson's and Huntington's diseases.

Studies of motor imagery and motor learning have thus far been concerned only with its effects on healthy subjects. Therefore, in order to investigate the possible involvement of the basal ganglia, the effectiveness of motor imagery in the acquisition of motor constants in a graphomotor trajectorial learning task was examined in 11 non-demented mildly affected Huntington's disease (HD) patients and 12 non-demented Parkinson's disease (PD) patients. The patients received, after baseline, 10 min of motor imagery training, followed by a motor practice phase. Additionally, a test battery for visual imagery abilities was administered in order to investigate possible relations between visual and motor imagery. The results showed that imagery training alone enabled the HD patients to achieve a significant approach to movement isochrony, whereas the PD patients showed no marked improvements, either with motor imagery or with motor practice. Furthermore, the PD patients had more difficulties than the HD patients in solving the visual imagery tasks. Subsequent correlational analysis revealed significant relationships between the degree of caudate atrophy in the HD patients and their performance in the visual imagery tasks. However, there were no substantial correlations between the performance on the visual imagery tasks and the improvement of motor performance through motor imagery, which indicates that visual and motor imagery are independent processes. It is suggested that the dopaminergic input to the basal ganglia plays an important role in the translation of motor representations into motor performance, whereas the caudate nucleus atrophy of the HD patients does not seem to affect motor imagery, but only the visual imagery process. Furthermore, the deficits found in PD patients might also be related to their limited attentional resources and difficulties in employing predictive motor strategies.     

Neuroinflammation in Parkinson's disease: a meta-analysis of PET imaging studies

Journal of Neurology - Increasingly, evidence implicates an important role of neuroinflammation in neurodegeneration progression. Yet, brain imaging has not reached a consistent conclusion that...