Impaired automatic and unconscious motor processes in Parkinson's disease.

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson's disease has received little attention to date. Here, we administered a subliminal masked prime task to 15 Parkinson's disease patients and 15 age-matched healthy elderly subjects. Compatibility effects were examined by manipulating the direction of the arrows and the interstimuli interval. Analysis of the positive compatibility effect revealed performance differences between the most and the least affected hand in Parkinson's disease patients. Additionally, patients did not show the same tendency toward a negative compatibility effect as compared to elderly controls. These novel findings provide evidence supporting the role of basal ganglia circuits in controlling the balance between automatic motor response facilitation and inhibition.

Role of the supplementary motor area in the automatic activation of motor plans in de novo Parkinson's disease patients.

The role of the basal ganglia-cortical motor loop in automatic and unconscious motor processes is poorly understood. Here, we used event-related functional magnetic resonance imaging in 11 de novo Parkinson's disease patients as they performed a visuomotor masked priming task. The stronger subliminal priming effect for the non-dominant side of motor symptoms than for the dominant side was paralleled by stronger supplementary motor area proper activity in response to lateralized visual stimuli presented below the threshold of awareness. This novel result supports the prediction that this area is involved in the automatic activation of motor plans as a function of striatal dopamine levels.

Finger tapping clinimetric score prediction in Parkinson's disease using low-cost accelerometers.

The motor clinical hallmarks of Parkinson's disease (PD) are usually quantified by physicians using validated clinimetric scales such as the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, clinical ratings are prone to subjectivity and inter-rater variability. The PD medical community is therefore looking for a simple, inexpensive, and objective rating method. As a first step towards this goal, a triaxial accelerometer-based system was used in a sample of 36 PD patients and 10 age-matched controls as they performed the MDS-UPDRS finger tapping (FT) task. First, raw signals were epoched to isolate the successive single FT movements. Next, eighteen FT task movement features were extracted, depicting MDS-UPDRS features and accelerometer specific features. An ordinal logistic regression model and a greedy backward algorithm were used to identify the most relevant features in the prediction of MDS-UPDRS FT scores, given by 3 specialists in movement disorders (SMDs). The Goodman-Kruskal Gamma index obtained (0.961), depicting the predictive performance of the model, is similar to those obtained between the individual scores given by the SMD (0.870 to 0.970). The automatic prediction of MDS-UPDRS scores using the proposed system may be valuable in clinical trials designed to evaluate and modify motor disability in PD patients.

Brain activation pattern related to gait disturbances in Parkinson's disease.

Gait disturbances represent a therapeutic challenge in Parkinson's disease (PD). To further investigate their underlying pathophysiological mechanisms, we compared brain activation related to mental imagery of gait between 15 PD patients and 15 age-matched controls using a block-design functional MRI experiment. On average, patients showed altered locomotion relatively to controls, as assessed with a standardized gait test that evaluated the severity of PD-related gait disturbances on a 25-m path. The experiment was conducted in the subjects as they rehearsed themselves walking on the same path with a gait pattern similar as that during locomotor evaluation. Imagined walking times were measured on a trial-by-trial basis as a control of behavioral performance. In both groups, mean imagined walking time was not significantly different from that measured during real gait on the path used for evaluation. The between-group comparison of the mental gait activation pattern with reference to mental imagery of standing showed hypoactivations within parieto-occipital regions, along with the left hippocampus, midline/lateral cerebellum, and presumed pedunculopontine nucleus/mesencephalic locomotor area, in patients. More specifically, the activation level of the right posterior parietal cortex located within the impaired gait-related cognitive network decreased proportionally with the severity of gait disturbances scored on the path used for gait evaluation and mental imagery. These novel findings suggest that the right posterior parietal cortex dysfunction is strongly related to the severity of gait disturbances in PD. This region may represent a target for the development of therapeutic interventions for PD-related gait disturbances.

Construction and validation of the Dynamic Parkinson Gait Scale (DYPAGS).

The dynamic evaluation of Parkinson's disease (PD)-related episodic gait disturbances in routine is challenging. Therefore, the aim of our study was to assess the reliability/validity of the Dynamic Parkinson Gait Scale (DYPAGS) composed of eight relevant items for the objective quantification of PD gait features: walking forwards/backwards/with dual-task, turning to both sides, imaginary obstacle avoidance with both legs and passing through narrow spaces. The scale was validated on thirty-five patients with mild to severe parkinsonism in their habitual "on-state". A shorter 6 item-version was designed on the basis of a principal component analysis. No significant floor/ceiling effect was detected. The internal consistency was excellent. The levels of interrater agreement, precision and minimal detectable change were adequate. The criterion-related validity was demonstrated by strong correlations with the DYPAGS scores and those at the gait subscales of the Tinetti Mobility Test and MDS-UPDRS. The construct validity was assessed by moderate-strong correlations with the Freezing of Gait Questionnaire, mobility index of the PD Questionnaire (PDQ-39), disease duration and levodopa equivalent daily doses. Statistical analyses using the coefficient of determination showed that both DYPGAS versions were superior to the other instruments to identify patients with gait disturbances with poorer response to dopaminergic treatment. Full and short DYPAGS are reliable instruments for the quantification of "on" PD-related episodic gait disturbances. The full version is sensitive to detect subtle disturbances in mild parkinsonism. The shorter one is easily administered and reliably quantifies gait disturbances in moderate to severe parkinsonism. We recommend their use for research and clinical practice.

Hemispheric specialization during mental imagery of brisk walking.

OBJECTIVES: Brisk walking, a sensitive test to evaluate gait capacity in normal and pathological aging such as parkinsonism, is used as an alternative to classical fitness program for motor rehabilitation and may help to decrease the risk of cognitive deterioration observed with aging. In this study, we aimed to identify brain areas normally involved in its control. METHODS: We conducted a block-design blood oxygen level dependent function magnetic resonance imaging (BOLD fMRI) experiment in 18 young healthy individuals trained to imagine themselves in three main situations: brisk walking in a 25-m-long corridor, standing or lying. Imagined walking time (IWT) was measured as a control of behavioral performance during fMRI. RESULTS: The group mean IWT was not significantly different from the actual walking time measured during a training session prior to the fMRI study. Compared with other experimental conditions, mental imagery (MI) of brisk walking was associated with stronger activity in frontal and parietal regions mainly on the right, and cerebellar hemispheres, mainly on the left. Presumed imagined walking speed (2.3 ± 0.4 m/s) was positively correlated with activity levels in the right dorsolateral prefrontal cortex and posterior parietal lobule along with the vermis and the left cerebellar hemisphere. INTERPRETATIONS: A new finding in this study is that MI of brisk walking in young healthy individuals strongly involves processes lateralized in right fronto-parietal regions along with left cerebellum. These results show that brisk walking might be a non automatic locomotor activity requiring a high-level supraspinal control.

Effects of light deprivation on visual evoked potentials in migraine without aura.

BACKGROUND: The mechanisms underlying the interictal habituation deficit of cortical visual evoked potentials (VEP) in migraine are not well understood. Abnormal long-term functional plasticity of the visual cortex may play a role and it can be assessed experimentally by light deprivation (LD). METHODS: We have compared the effects of LD on VEP in migraine patients without aura between attacks (MO, n = 17) and in healthy volunteers (HV, n = 17). Six sequential blocks of 100 averaged VEP at 3.1 Hz were recorded before and after 1 hour of LD. We measured VEP P100 amplitude of the 1st block of 100 sweeps and its change over 5 sequential blocks of 100 responses. RESULTS: In HV, the consequence of LD was a reduction of 1st block VEP amplitude and of the normal habituation pattern. By contrast, in MO patients, the interictal habituation deficit was not significantly modified, although 1st block VEP amplitude, already lower than in HV before LD, further decreased after LD. CONCLUSIONS: Light deprivation is thought to decrease both excitatory and subsequent inhibitory processes in visual cortex, which is in line with our findings in healthy volunteers. The VEP results in migraine patients suggest that early excitation was adequately suppressed, but not the inhibitory mechanisms occurring during long term stimulation and habituation. Accordingly, deficient intracortical inhibition is unlikely to be a primary factor in migraine pathophysiology and the habituation deficit.

Gait feature extraction in Parkinson's disease using low-cost accelerometers.

The clinical hallmarks of Parkinson's disease (PD) are movement poverty and slowness (i.e. bradykinesia), muscle rigidity, limb tremor or gait disturbances. Parkinson's gait includes slowness, shuffling, short steps, freezing of gait (FoG) and/or asymmetries in gait. There are currently no validated clinical instruments or device that allow a full characterization of gait disturbances in PD. As a step towards this goal, a four accelerometer-based system is proposed to increase the number of parameters that can be extracted to characterize parkinsonian gait disturbances such as FoG or gait asymmetries. After developing the hardware, an algorithm has been developed, that automatically epoched the signals on a stride-by-stride basis and quantified, among others, the gait velocity, the stride time, the stance and swing phases, the single and double support phases or the maximum acceleration at toe-off, as validated by visual inspection of video recordings during the task. The results obtained in a PD patient and a healthy volunteer are presented. The FoG detection will be improved using time-frequency analysis and the system is about to be validated with a state-of-the-art 3D movement analysis system.