Cell-specific Dyt1 ∆GAG knock-in to basal ganglia and cerebellum reveal differential effects on motor behavior and sensorimotor network function.

Dystonia is a neurological movement disorder characterized by repetitive, unintentional movements and disabling postures that result from sustained or intermittent muscle contractions. The basal ganglia and cerebellum have received substantial focus in studying DYT1 dystonia. It remains unclear how cell-specific ∆GAG mutation of torsinA within specific cells of the basal ganglia or cerebellum affects motor performance, somatosensory network connectivity, and microstructure. In order to achieve this goal, we generated two genetically modified mouse models: in model 1 we performed Dyt1 ∆GAG conditional knock-in (KI) in neurons that express dopamine-2 receptors (D2-KI), and in model 2 we performed Dyt1 ∆GAG conditional KI in Purkinje cells of the cerebellum (Pcp2-KI). In both of these models, we used functional magnetic resonance imaging (fMRI) to assess sensory-evoked brain activation and resting-state functional connectivity, and diffusion MRI to assess brain microstructure. We found that D2-KI mutant mice had motor deficits, abnormal sensory-evoked brain activation in the somatosensory cortex, as well as increased functional connectivity of the anterior medulla with cortex. In contrast, we found that Pcp2-KI mice had improved motor performance, reduced sensory-evoked brain activation in the striatum and midbrain, as well as reduced functional connectivity of the striatum with the anterior medulla. These findings suggest that (1) D2 cell-specific Dyt1 ∆GAG mediated torsinA dysfunction in the basal ganglia results in detrimental effects on the sensorimotor network and motor output, and (2) Purkinje cell-specific Dyt1 ∆GAG mediated torsinA dysfunction in the cerebellum results in compensatory changes in the sensorimotor network that protect against dystonia-like motor deficits.

Cell-specific effects of Dyt1 knock-out on sensory processing, network-level connectivity, and motor deficits.

DYT1 dystonia is a debilitating movement disorder characterized by repetitive, unintentional movements and postures. The disorder has been linked to mutation of the TOR1A/DYT1 gene encoding torsinA. Convergent evidence from studies in humans and animal models suggest that striatal medium spiny neurons and cholinergic neurons are important in DYT1 dystonia. What is not known is how torsinA dysfunction in these specific cell types contributes to the pathophysiology of DYT1 dystonia. In this study we sought to determine whether torsinA dysfunction in cholinergic neurons alone is sufficient to generate the sensorimotor dysfunction and brain changes associated with dystonia, or if torsinA dysfunction in a broader subset of cell types is needed. We generated two genetically modified mouse models, one with selective Dyt1 knock-out from dopamine-2 receptor expressing neurons (D2KO) and one where only cholinergic neurons are impacted (Ch2KO). We assessed motor deficits and performed in vivo 11.1 T functional MRI to assess sensory-evoked brain activation and connectivity, along with diffusion MRI to assess brain microstructure. We found that D2KO mice showed greater impairment than Ch2KO mice, including reduced sensory-evoked brain activity in key regions of the sensorimotor network, and altered functional connectivity of the striatum that correlated with motor deficits. These findings suggest that (1) the added impact of torsinA dysfunction in medium spiny and dopaminergic neurons of the basal ganglia generate more profound deficits than the dysfunction of cholinergic neurons alone, and (2) that sensory network impairments are linked to motor deficits in DYT1 dystonia.

Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor.

OBJECTIVE: Essential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET. METHODS: We performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks. RESULTS: VIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4-8 Hz) across all effectors during seated and standing tasks. CONCLUSIONS: VIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors. SIGNIFICANCE: This study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.

Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity.

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.

Continuous in-home monitoring of essential tremor.

BACKGROUND: Essential tremor (ET) is typically measured in the clinic with subjective tremor rating scales which require the presence of a clinician for scoring and are not appropriate for measuring severity throughout the day. Motion sensors can accurately rate tremor severity during a set of predefined tasks in a laboratory. METHODS: We evaluated the ability of motion sensors to quantify tremor during unconstrained activities at home. 20 ET subjects wore a wireless sensor continuously for up to 10 h daily on two days and completed hourly standardized tremor assessments involving pre-defined tasks. Mathematical models were used to predict tremor rating scores from the sensor data. RESULTS: At home tremor scores from hourly standardized assessments correlated with at home tremor scores estimated during unconstrained activities immediately following the standardized assessments. The hourly standardized assessments did not significantly fluctuate throughout the day, while fluctuations in the continuous assessments tended to follow changes in voluntary activity level. Both types of tremor ratings (standardized and continuous) showed high day-to-day test-retest reliability with intraclass correlation coefficients ranging from 0.67 to 0.90 for continuous ratings and 0.77 to 0.95 for standardized ratings. CONCLUSIONS: Results demonstrate the feasibility of continuous monitoring of tremor severity at home, which should provide clinicians with a measure of the temporal pattern of tremor in the context of daily life and serve as a useful tool for the evaluation of novel anti-tremor medications in clinical trials.

Increased REM sleep without atonia in Parkinson disease with freezing of gait.

OBJECTIVE: The objective of this cross-sectional study was to test the hypothesis that patients with Parkinson disease (PD) and freezing of gait (PD+FOG) would demonstrate sleep disturbances comparable to those seen in patients with REM sleep behavior disorder (RBD) and these changes would be significantly different from those in PD patients without FOG (PD-FOG) and age-matched controls. METHODS: We conducted overnight polysomnography studies in 4 groups of subjects: RBD, PD-FOG, PD+FOG, and controls. Tonic and phasic muscle activity during REM sleep were quantified using EMG recordings from the chin, compared among study groups, and correlated with disease metrics. RESULTS: There were no significant differences in measures of disease severity, duration, or dopaminergic medications between the PD+FOG and PD-FOG groups. Tonic muscle activity was increased significantly (p < 0.007) in the RBD and PD+FOG groups compared to the PD-FOG and control groups. There was no significant difference in tonic EMG between the PD+FOG and RBD group (p = 0.364), or in tonic or phasic EMG between the PD-FOG and control group (p = 0.107). Phasic muscle activity was significantly increased in the RBD group compared to all other groups (p = 0.029) and between the PD+FOG and control group (p = 0.001), but not between the PD+FOG and PD-FOG groups (p = 0.059). CONCLUSIONS: These findings provide evidence that increased muscle activity during REM sleep is a comorbid feature of patients with PD who exhibit FOG as a motor manifestation of their disease.

Thalamic projection fiber integrity in de novo Parkinson disease.

BACKGROUND AND PURPOSE: Postmortem studies of advanced PD have revealed disease-related pathology in the thalamus with an apparent predilection for specific thalamic nuclei. In the present study, we used DTI to investigate in vivo the microstructural integrity of 6 thalamic regions in de novo patients with PD relative to healthy controls. MATERIALS AND METHODS: Forty subjects (20 with early stage untreated PD and 20 age- and sex-matched controls) were studied with a high-resolution DTI protocol at 3T to investigate the integrity of thalamic nuclei projection fibers. Two blinded, independent raters drew ROIs in the following 6 thalamic regions: AN, VA, VL, DM, VPL/VPM, and PU. FA values were then calculated from the projection fibers in each region. RESULTS: FA values were reduced significantly in the fibers projecting from the AN, VA, and DM, but not the VPL/VPM and PU, in the PD group compared with the control group. In addition, there was a reduction in FA values that approached significance in the VL of patients with PD. These findings were consistent across both raters. CONCLUSIONS: The present study provides preliminary in vivo evidence of thalamic projection fiber degeneration in de novo PD and sheds light on the extent of disrupted thalamic circuitry as a result of the disease itself.

Comparison of a leukocyte esterase test with endometrial cytology for diagnosis of subclinical endometritis in postpartum dairy cows.

The objective was to compare a leukocyte esterase (LE) test with endometrial cytology (EC) for diagnosis of subclinical endometritis in dairy cows. The relationship between subsequent fertility and the uterine (Ut) and cervical (Cx) leukocyte esterase activity was determined by the odds of pregnancy by 90 days in milk (DIM). Holstein cows (N = 218) without clinical endometritis and between 21 and 47 DIM from five commercial dairy herds were sampled for uterine and cervical leukocyte esterase activity and EC by cytobrush. To test the effect of time, cows were grouped into early (21-31 DIM) and late (32-47 DIM) animals. There was a slight agreement between UtLE and CxLE (weighted κ = 0.37). The percentage of neutrophils was correlated with esterase score either from the uterus (UtLE; P = 0.0001) or cervix (CxLE; P = 0.002). The percentage of neutrophils on EC (P < 0.001), the UtLE score (P < 0.0001), and the CxLE (P = 0.0009) diminished as DIM increased. Neither CxLE nor UtLE were statistically associated with pregnancy at 90 DIM. However, between 32 and 47 DIM, the percentage of neutrophils on EC and odds of pregnancy at 90 DIM were associated (P = 0.04). For the same interval, based on receiver/response operating characteristics analysis, the optimal cutoff was >6.7% neutrophils to classify cows with subclinical endometritis. In conclusion, uterine LE activity was correlated with percentage of neutrophils as determined by EC, but not with odds of pregnancy. Subclinical endometritis (>6.70% neutrophils) diagnosed by EC between 32 and 47 DIM was associated with reduced odds of pregnancy.

Specific cerebellar regions are related to force amplitude and rate of force development.

The human cerebellum has been implicated in the control of a wide variety of motor control parameters, such as force amplitude, movement extent, and movement velocity. These parameters often covary in both movement and isometric force production tasks, so it is difficult to resolve whether specific regions of the cerebellum relate to specific parameters. In order to address this issue, the current study used two experiments and SUIT normalization to determine whether BOLD activation in the cerebellum scales with the amplitude or rate of change of isometric force production or both. In the first experiment, subjects produced isometric pinch-grip force over a range of force amplitudes without any constraints on the rate of force development. In the second experiment, subjects varied the rate of force production, but the target force amplitude remained constant. The data demonstrate that BOLD activation in separate sub-areas of cerebellar regions lobule VI and Crus I/II scales with both force amplitude and force rate. In addition, BOLD activation in cerebellar lobule V and vermis VI was specific to force amplitude, whereas BOLD activation in lobule VIIb was specific to force rate. Overall, cerebellar activity related to force amplitude was located superior and medial, whereas activity related to force rate was inferior and lateral. These findings suggest that specific circuitry in the cerebellum may be dedicated to specific motor control parameters such as force amplitude and force rate.

Comparison of three methods of sampling for endometrial cytology in the mare. Preliminary study.

OBJECTIVE: This prospective study aims to compare three different sampling techniques for the collection of endometrial cytological specimens in the mare: the guarded culture swab, the uterine cytobrush and the low volume uterine flush. MATERIAL AND METHODS: The study population consisted of six healthy Standardbred mares in dioestrus. In each mare an acute endometritis was induced by performing a low- volume uterine flush 6days after ovulation using a sterile isotonic solution (lactated Ringer's solution or ViGro™ Complete Flush Solution). Two days after initiating inflammation, samples were collected from each mare using the three compared techniques: the double guarded cotton swab, the uterine cytobrush and the low volume uterine flush. The cytological evaluation of the samples was based on following criteria: the quality and cellularity of the samples and the number of neutrophils recovered. RESULTS: The uterine cytobrush yielded slides of significantly (p=0.02) better quality than the low volume uterine flush. There was no significant difference between the cytobrush and the double guarded swab technique for the quality. There was no difference between techniques in the number of endometrial cells (p=0.55) and neutrophils recovered (p=0.28). CONCLUSION AND CLINICAL RELEVANCE: Endometrial cytology is a practical method for the diagnosis of acute endometrial inflammation in the mare. Since no difference in the number of neutrophils was found between the three techniques, the choice of the sampling method should be based on other factors such as practicability, costs and disadvantages of each technique.

High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease.

BACKGROUND: In the midbrain of patients with Parkinson disease (PD), there is a selective loss of dopaminergic neurons in the ventrolateral and caudal substantia nigra (SN). In a mouse model of PD, investigators have administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and found that measures derived using diffusion tensor imaging (DTI) were correlated with the number of dopamine neurons lost following intoxication. METHODS: Twenty-eight subjects (14 with early stage, untreated PD and 14 age- and gender-matched controls) were studied with a high-resolution DTI protocol at 3 Tesla using an eight-channel phase array coil and parallel imaging to study specific segments of degeneration in the SN. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. RESULTS: Fractional anisotropy (FA) was reduced in the SN of subjects with PD compared with controls (p < 0.001). Post hoc analysis identified that reduced FA for patients with PD was greater in the caudal compared with the rostral region of interest (p < 0.00001). A receiver operator characteristic analysis in the caudal SN revealed that sensitivity and specificity were 100% for distinguishing patients with PD from healthy subjects. Findings were consistent across both raters. CONCLUSIONS: These findings provide evidence that high resolution diffusion tensor imaging in the substantia nigra distinguishes early stage, de novo patients with Parkinson disease (PD) from healthy individuals on a patient by patient basis and has the potential to serve as a noninvasive early biomarker for PD.

Effects of focal hand dystonia on visually guided and internally guided force control.

BACKGROUND: A fundamental feature underlying many movement disorders is increased variability in the motor response. Despite abnormalities of grip force control in people with dystonia, it is not clear whether dystonia is also associated with increased variability in force output and whether force variability in dystonia is affected by the presence or absence of visual feedback. OBJECTIVE: To examine force variability in 16 patients with writer's cramp and 16 matched controls. METHODS: The variability of force output at the wrist under conditions of both vision and no vision was examined. The underlying frequency structure of the force signal was also compared across groups. Participants produced isometric wrist flexion to targets at 25% and 50% of their maximum voluntary contraction strength under conditions of both vision and no vision. RESULTS: Similar levels of force variability were observed in patients with dystonia and controls at the lower force levels, but patients with dystonia were less variable in their force output than controls at the higher force level. This reduction in variability in people with dystonia at 50% maximum voluntary contraction was not affected by vision. Although a similar dominant frequency in force output was observed in people with dystonia and controls, a reduced variability in the group with dystonia at the higher force level was due to reduced power in the 0-4-Hz frequency bin. CONCLUSIONS: The first evidence of a movement disorder with reduced variability is provided. The findings are compatible with a model of dystonia, which includes reduced cortical activation in response to sensory input from the periphery and reduced flexibility in motor output.

EMG remains fractionated in Parkinson's disease, despite practice-related improvements in performance.

OBJECTIVE: We studied the ability of patients with Parkinson's disease to improve their performance in a motor task requiring both speed and accuracy in the execution of elbow flexion movements. Our goal was to investigate the changes in electromyographic activity associated with the changes in movement performance. METHODS: Eleven patients on anti-Parkinsonian medication were tested. The patients were selected for being bradykinetic, having little or no resting tremor or dyskinesias, and being in stages II or III of the Hoehn and Yahr rating scale. RESULTS: The untrained patients displayed multiple bursts of agonist activity, characteristic of Parkinsonian EMG recordings. All patients improved their performance by increasing peak velocity while maintaining movement accuracy within strict boundaries. With practice, the patients' performance changed in a manner similar to that which has been previously observed for performance curves in neurologically normal subjects. As movement duration decreased (i.e. peak velocity increased), we observed a slight decrease in the number of agonist bursts and an increase in the average burst duration. However, the patients continued to generate a fractionated, multi-burst agonist pattern. CONCLUSIONS: We conclude that Parkinsonian patients benefit from practice by improving their performance but remain fundamentally impaired in the generation of muscle activation patterns. This study has shown that the generation of fractionated, multiple short bursts of EMG activity that is characteristic of movements made by Parkinsonian patients is not normalized by practice.

Deep brain stimulation of the VIM thalamic nucleus modifies several features of essential tremor.

BACKGROUND: Pharmacologic interventions (e.g., beta blockers) and thalamic lesions have failed to alter the pathophysiology of essential tremor (ET) beyond a reduction in tremor amplitude. Deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus successfully reduces tremor rating scores. It is unknown how VIM DBS alters the pathophysiologic characteristics of ET. OBJECTIVE: To determine the effects of VIM DBS on the neurophysiologic characteristics of ET. METHODS: Hand tremor and EMG activity of forearm extensor and flexor muscles were recorded in six patients with ET ON-DBS and OFF-DBS and from six age- and sex-matched control subjects. Hand tremor was assessed across different inertial loads. The amplitude, frequency, regularity, and tremor-EMG coherence were analyzed. RESULTS: VIM DBS reduced the amplitude, increased the frequency, decreased the regularity, and reduced the 1 to 8 Hz tremor-EMG coherence of ET. ON-DBS, patients with ET had greater tremor amplitude, lower frequency, more regularity, and greater tremor-EMG coherence compared to control subjects. CONCLUSIONS: Whereas pharmacologic and thalamic lesions have previously failed to change characteristics of ET beyond amplitude reduction, VIM DBS modified multiple features of ET. The changes in ET after VIM DBS provide strong evidence for clinical efficacy.

Dimensional change in motor learning.

Bernstein (The Co-ordination and Regulation of Movements, Pergamon, London, 1967) outlined a theoretical framework for the degrees of freedom problem in motor control that included a 3-stage approach to the reorganization of the peripheral biomechanical degrees of freedom in motor learning and development. We propose that Bernstein's conception of change through the stages of learning is too narrow in its consideration of the degrees of freedom problem and the actual pathways of change evident in motor learning. It is shown that change in both the organization of the mechanical degrees of freedom and the dimension of the attractor dynamic organizing motor output can either increase or decrease, according to the confluence of constraints imposed on action. The central issue determining directional change in dimension is whether the dimensionality of the task relevant intrinsic dynamic needs to be increased or decreased to realize new task demands.

Visual control of isometric force in Parkinson's disease.

The current article reports an investigation of the influence of visual feedback on force production in Parkinson's disease (PD) that required subjects to maintain a constant amount of isometric force with their index finger and thumb with and without visual feedback. Eight PD and eight matched control subjects produced force at 5, 25 and 50% of their maximal voluntary contraction for 20 s. In conditions of full vision, the force trajectory and force target were viewed on the computer monitor. In the no visual feedback condition, visual feedback of the force trajectory vanished after the initial 8 s of the trial. The results showed that under the vision condition PD subjects produced levels of maximal and submaximal force that were similar to controls. Approximately 1.5-2.5 s following the removal of visual feedback, the force level in both subject groups decreased to steady-state levels. There was no difference in the time between visual feedback removal and the beginning of force decay in PD. There was a larger amount and faster rate of force decay after visual feedback removal in PD subjects compared to the controls. It is proposed that the increased force decay in PD does not result from sensory reflex deficits but from higher order sensory-motor memory processes.

Regularity of force tremor in Parkinson's disease.

OBJECTIVES: The study examines the time-dependent structure of force tremor to investigate two hypotheses: (1), the regularity of tremor can help in discriminating normal aging from that of Parkinson's disease (PD); and (2), there is increased tremor regularity with increases in the severity of PD. METHODS: Eight young (21-29 years), eight elderly (68-80 years), and eight PD (68-80 years) subjects produced constant grip force at 5, 25 and 50% of their maximal voluntary contraction by squeezing two load cells with their index finger and thumb under a vision and no vision condition. Spectral analysis and approximate entropy (ApEn) were used, respectively, to analyze the frequency and time-dependent structure of tremor. RESULTS: The analyses showed that there were no differences in the amplitude and modal frequency of force tremor between groups. The ApEn was significantly lower in the PD group compared with the controls. For the PD group, the linear relations between the total scores taken from the Unified Parkinson's Disease Rating Scale-motor section and the dependent variables were r(2)=0.71 (P<0.01) for ApEn, r(2)=0.20 (P>0.05) for the modal frequency, and r(2)=0.23 (P>0.05) for the standard deviation. Surrogate analyses revealed that the time-dependent structure of tremor provided additional information beyond that of amplitude and modal frequency analyses. CONCLUSIONS: These findings indicate that tremor analyses should not be limited to just the frequency and amplitude of the oscillation, and that the time-dependent structure of tremor is useful in differentiating tremor in healthy people from those with PD. The hypothesis that more regular tremor in PD is due to a loss of multiple neuronal oscillators contributing to the tremor output is discussed.

Intermittency in the visual control of force in Parkinson's disease.

Studies on the variability of motor output in Parkinson's disease have found contrasting results depending on the speed-accuracy constraints of the task. The first goal of this study was to determine if Parkinson's disease subjects are more variable than control subjects. The second goal of the study was to examine the limitations on visual and motor processing that contribute to the changes in force variability in Parkinson's disease. Eight mild to moderate Parkinson's disease (age: 68-80 years) and eight matched control (age: 68-80 years) subjects maintained a constant level of force at 25% of their maximum voluntary contraction with their index finger and thumb (grip precision task) for 20 s while online visual feedback of the total force was viewed on a computer monitor. During the force task, subjects received visual feedback at varying frequencies. The sampled visual feedback levels were presented at intervals as slow as every 5 s to as fast as every 0.04 s (0.2, 0.4, 0.8, 1.6, 3.2, 6.4, 12.8, 25.6 Hz). Force variability decreased over sampled visual feedback according to hyperbolic decay functions. The minimal visual processing time for both the Parkinson's disease and control subjects was approximately 160 ms. Motor output corrections were generated in both groups at a frequency of 1 Hz over a wide range of sampled visual feedback levels. However, the amplitude of the 1-2 Hz visuo-motor corrective process was amplified in Parkinson's disease, and this related to increases in force-output variability. The findings suggest that the basal ganglia are important for adjusting the amplitude of motor output at 1-2 Hz during visuo-motor feedback control.

The dynamics of resting and postural tremor in Parkinson's disease.

OBJECTIVE: The study examines the time and frequency structure of Parkinson's disease tremor in patients that exhibit no clinical signs of tremor. METHODS: Eight mild to moderate Parkinson's disease and 8 matched control subjects maintained their limb in a constant position (30 s) under a postural finger, postural hand and resting tremor condition. Finger acceleration from the middle phalange, electromyographic (EMG) activity from extensor digitorum communis and flexor digitorum superficialis (FDS) were recorded. RESULTS: The data confirmed that there were no differences in the amount of limb motion and the modal frequency was around 9 Hz for each subject group. The time-dependent organization of tremor was more regular (lower approximate entropy [ApEn]) in Parkinson's disease. Both time and frequency analyses between the acceleration and extensor EMG signals demonstrate a reduction in the 20-25 Hz tremor component and an increase in the 8-12 Hz region of tremor. CONCLUSIONS: The results are discussed in relation to the proposal that increased regularity results from an increase in motor unit synchronization at 8-12 Hz and a reduction in the amplitude of the 20-25 Hz tremor component. The time and frequency structure of tremor may be useful in assessing individuals with Parkinson's disease.

Intermittency in the control of continuous force production.

The purpose of the current investigation was to examine the influence of intermittency in visual information processes on intermittency in the control continuous force production. Adult human participants were required to maintain force at, and minimize variability around, a force target over an extended duration (15 s), while the intermittency of on-line visual feedback presentation was varied across conditions. This was accomplished by varying the frequency of successive force-feedback deliveries presented on a video display. As a function of a 128-fold increase in feedback frequency (0.2 to 25.6 Hz), performance quality improved according to hyperbolic functions (e.g., force variability decayed), reaching asymptotic values near the 6.4-Hz feedback frequency level. Thus, the briefest interval over which visual information could be integrated and used to correct errors in motor output was approximately 150 ms. The observed reductions in force variability were correlated with parallel declines in spectral power at about 1 Hz in the frequency profile of force output. In contrast, power at higher frequencies in the force output spectrum were uncorrelated with increases in feedback frequency. Thus, there was a considerable lag between the generation of motor output corrections (1 Hz) and the processing of visual feedback information (6.4 Hz). To reconcile these differences in visual and motor processing times, we proposed a model where error information is accumulated by visual information processes at a maximum frequency of 6.4 per second, and the motor system generates a correction on the basis of the accumulated information at the end of each 1-s interval.