David E. Vaillancourt

Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: a meta-analysis.

The mesial premotor cortex (pre-supplementary motor area and supplementary motor area proper), lateral premotor cortex (dorsal premotor cortex and ventral premotor cortex), and primary sensorimotor cortex (primary motor cortex and primary somatosensory cortex) have been identified as key cortical areas for sensorimotor function. However, the three-dimensional (3-D) anatomic boundaries between these regions remain unclear. In order to clarify the locations and boundaries for these six sensorimotor regions, we surveyed 126 articles describing pre-supplementary motor area, supplementary motor area proper, dorsal premotor cortex, ventral premotor cortex, primary motor cortex, and primary somatosensory cortex. Using strict inclusion criteria, we recorded the reported normalized stereotaxic coordinates (Talairach and Tournoux or MNI) from each experiment. We then computed the probability distributions describing the likelihood of activation, and characterized the shape, extent, and area of each sensorimotor region in 3-D. Additionally, we evaluated the nature of the overlap between the six sensorimotor regions. Using the findings from this meta-analysis, along with suggestions and guidelines of previous researchers, we developed the Human Motor Area Template (HMAT) that can be used for ROI analysis. HMAT is available through e-mail from the corresponding author.

Changing complexity in human behavior and physiology through aging and disease

Lipsitz and Goldberger proposed that there is a loss in the complexity of physiological and behavioral systems with aging and disease. Here, we show that this unidirectional view of the change in system complexity is too narrow in its consideration of the actual changes that occur with aging and disease. An increase or decrease in the complexity of a behavioral or physiological system output can occur and the direction of change is dependent on the confluence of constraints that channel the system dynamics. It is postulated that the observed increase or decrease in complexity with aging and disease is dependent on the nature of both the intrinsic dynamics of the system and the short-term change required to realize a local task demand.

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.

Role of hyperactive cerebellum and motor cortex in Parkinson's disease.

Previous neuroimaging studies have found hyperactivation in the cerebellum and motor cortex and hypoactivation in the basal ganglia in patients with Parkinsons disease (PD) but the relationship between the two has not been established. This study examined whether cerebellar and motor cortex hyperactivation is a compensatory mechanism for hypoactivation in the basal ganglia or is a pathophysiological response that is related to the signs of the disease. Using a BOLD contrast fMRI paradigm PD patients and healthy controls performed automatic and cognitively controlled thumb pressing movements. Regions of interest analysis quantified the BOLD activation in motor areas, and correlations between the hyperactive and hypoactive regions were performed, along with correlations between the severity of upper limb rigidity and BOLD activation. There were three main findings. First, the putamen, supplementary motor area (SMA) and pre-SMA were hypoactive in PD patients. The left and right cerebellum and the contralateral motor cortex were hyperactive in PD patients. Second, PD patients had a significant negative correlation between the BOLD activation in the ipsilateral cerebellum and the contralateral putamen. The correlation between the putamen and motor cortex was not significant. Third, the BOLD activation in the motor cortex was positively correlated with the severity of upper limb rigidity, but the BOLD activation in the cerebellum was not correlated with rigidity. Further, the activation in the motor cortex was not correlated with upper extremity bradykinesia. These findings provide new evidence supporting the hypothesis that hyperactivation in the ipsilateral cerebellum is a compensatory mechanism for the defective basal ganglia. Our findings also provide the first evidence from neuroimaging that hyperactivation in the contralateral primary motor cortex is not a compensatory response but is directly related to upper limb rigidity.

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 Bernsteins 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.

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

OBJECTIVE The study examines the time and frequency structure of Parkinsons disease tremor in patients that exhibit no clinical signs of tremor. METHODS Eight mild to moderate Parkinsons 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 Parkinsons 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 Parkinsons disease.

Effects of aging on force variability, single motor unit discharge patterns, and the structure of 10, 20, and 40 Hz EMG activity.

The purpose of this investigation was to examine the discharge properties of single motor units and the structure of the rectified 10, 20, and 40 Hz electromyographic (EMG) activity to determine a physiological correlate for the greater force variability with aging. Young (n=10; mean: 22+/-1 years), old (n=10; mean: 67+/-2 years), and older-old (n=10; mean: 82+/-5 years) adult humans produced isometric second finger abduction force in both constant and sine-wave tasks at 5, 10, 20, and 40% of their maximal voluntary contraction. Force and fine-wire intramuscular electromyography were recorded from the first dorsal interosseous muscle. The amount and time-dependent structure of the discharge rate variability of single motor units and Fourier analysis of the rectified intramuscular EMG was performed. Force output variability increased across the young, old, and older-old groups. The amount and time-dependent structure of the discharge rate variability of single motor units did not differ between the young and aging groups. There was a progressive decrease in the relative power of approximately 40 Hz EMG activity from the young>old>older-old subjects across the 5, 10, 20, and 40% maximum voluntary contraction (MVC) force levels. There was also a progressive increase in the relative power of the approximately 10 Hz EMG activity from young<old<older-old subjects at each target force level. The findings showed that a shift in the relative contribution of approximately 40 Hz to approximately 10 Hz neural activity is related to the reduced capacity of older adults to maintain optimal force control.

A two-year randomized controlled trial of progressive resistance exercise for Parkinson's disease

The effects of progressive resistance exercise (PRE) on the motor signs of Parkinsons disease have not been studied in controlled trials. The objective of the current trial was to compare 6‐, 12‐, 18‐, and 24‐month outcomes of patients with Parkinsons disease who received PRE with a stretching, balance, and strengthening exercise program. The authors conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients matched by sex and off‐medication scores on the Unified Parkinsons Disease Rating Scale, motor subscale (UPDRS‐III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight‐lifting program. The modified fitness counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised 2 days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first 6 months and 1 weekly session after 6 months. The primary outcome was the off‐medication UPDRS‐III score. Patients were followed for 24 months at 6‐month intervals. Of 51 patients, 20 in the PRE group and 18 in the mFC group completed the trial. At 24 months, the mean off‐medication UPDRS‐III score decreased more with PRE than with mFC (mean difference, −7.3 points; 95% confidence interval, −11.3 to −3.6; P<0.001). The PRE group had 10 adverse events, and the mFC group had 7 adverse events. PRE demonstrated a statistically and clinically significant reduction in UPDRS‐III scores compared with mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs.

Temporal capacity of short-term visuomotor memory in continuous force production

The focus of this article is on the temporal capacity of short-term visuomotor memory as reflected by changes in the time and frequency patterns of force output. In experiment 1, subjects produced continuous force output (isometric index finger flexion) to a target force level (from 5 to 75% of maximum voluntary contraction, MVC) displayed on a video monitor for 20 s. In the full visual feedback condition, visual feedback was displayed throughout each trial, while, for the visual feedback-withdrawal condition, visual feedback was occluded for the final 12 s of each trial. With visual feedback present, subjects matched their force output to the target force level for 20 s. When visual feedback was removed, participants continued to match the target force level for approximately 0.5–1.5 s; thereafter force output decayed exponentially. In line with this decay, short time-frequency analysis revealed a decrease in force intensity in the 0- to 5-Hz band. Force level did not influence the time before decay; however, greater forces led to larger decay. Experiment 2 assessed whether the force decay in experiment 1 was a property of visual or motor short-term memory by having participants set their own target force levels with no visual information provided throughout. In agreement with the findings of experiment 1, force output decayed, emphasizing the importance of a motor memory source. It is concluded that the 0.5- to 1.5-s time period represents a limit on the temporal capacity that precise visuomotor information is held in short-term memory.

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 Parkinsons 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 Parkinsons 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.