Kristen A. Pickett

The effect of subthalamic nucleus stimulation on kinaesthesia in Parkinson’s disease

Background: Parkinson’s disease is accompanied by deficits in passive motion and limb position sense. Objective: To investigate whether deep brain stimulation of the subthalamic nucleus (STN-DBS) reverses these proprioceptive deficits. Methods and results: A passive movement task was applied to nine patients with Parkinson’s disease and bilateral chronic STN-DBS and to seven controls. Thresholds for 75% correct responses were 0.9° for controls, 2.5° for Parkinson’s disease patients when stimulation was OFF, and 2.0° when stimulation was ON. Conclusions: STN-DBS improves kinaesthesic deficits in Parkinson’s disease, but does not lead to a full recovery of proprioceptive function.

Gait-Related Brain Activity in People with Parkinson Disease with Freezing of Gait

Approximately 50% of people with Parkinson disease experience freezing of gait, described as a transient inability to produce effective stepping. Complex gait tasks such as turning typically elicit freezing more commonly than simple gait tasks, such as forward walking. Despite the frequency of this debilitating and dangerous symptom, the brain mechanisms underlying freezing remain unclear. Gait imagery during functional magnetic resonance imaging permits investigation of brain activity associated with locomotion. We used this approach to better understand neural function during gait-like tasks in people with Parkinson disease who experience freezing- “FoG+” and people who do not experience freezing- ”FoG−“. Nine FoG+ and nine FoG− imagined complex gait tasks (turning, backward walking), simple gait tasks (forward walking), and quiet standing during measurements of blood oxygen level dependent (BOLD) signal. Changes in BOLD signal (i.e. beta weights) during imagined walking and imagined standing were analyzed across FoG+ and FoG− groups in locomotor brain regions including supplementary motor area, globus pallidus, putamen, mesencephalic locomotor region, and cerebellar locomotor region. Beta weights in locomotor regions did not differ for complex tasks compared to simple tasks in either group. Across imagined gait tasks, FoG+ demonstrated significantly lower beta weights in the right globus pallidus with respect to FoG−. FoG+ also showed trends toward lower beta weights in other right-hemisphere locomotor regions (supplementary motor area, mesencephalic locomotor region). Finally, during imagined stand, FoG+ exhibited lower beta weights in the cerebellar locomotor region with respect to FoG−. These data support previous results suggesting FoG+ exhibit dysfunction in a number of cortical and subcortical regions, possibly with asymmetric dysfunction towards the right hemisphere.

Perception of heaviness in Parkinson's disease.

The present study investigated whether a specific aspect of proprioception, the sense of heaviness or weight is affected in PD. We determined detection thresholds for the perception of a gravito‐inertial load in 10 PD patients and 11 age‐matched control subjects. A gradually increasing weight was applied to the index finger by means of two slings of different width (low vs. high skin pressure). For the controls, mean detection thresholds were 31.3 g at skin high pressure and 33.0 g under low pressure. PD patients revealed significantly higher thresholds than the control group in both pressure conditions (mean high pressure,47.7 g; mean low pressure, 52.3 g; group effect, P = 0.001). Thresholds of PD patients tended to increase with disease severity as measured by the Unified Parkinsons Disease Rating Scale Motor score (r = 0.55) but did not correlate significantly with levodopa equivalent dosage. The results demonstrate that the perception of heaviness or weight is already affected in the early stages of PD. These findings underline the growing evidence that proprioceptive and possibly haptic dysfunction is a common feature of PD.

Brain activity during complex imagined gait tasks in Parkinson disease

OBJECTIVE Motor imagery during functional magnetic resonance imaging (fMRI) allows assessment of brain activity during tasks, like walking, that cannot be completed in an MRI scanner. We used gait imagery to assess the neural pathophysiology of locomotion in Parkinson disease (PD). METHODS Brain activity was measured in five locomotor regions (supplementary motor area (SMA), globus pallidus (GP), putamen, mesencephalic locomotor region, cerebellar locomotor region) during simple (forward) and complex (backward, turning) gait imagery. Brain activity was correlated to overground walking velocity. RESULTS Across tasks, PD exhibited reduced activity in the globus pallidus compared to controls. People with PD, but not controls, exhibited more activity in the SMA during imagined turning compared to forward or backward walking. In PD, walking speed was correlated to brain activity in several regions. CONCLUSIONS Altered SMA activity in PD during imagined turning may represent compensatory neural adaptations during complex gait. The lowered activity and positive correlation to locomotor function in GP suggests reduced activity in this region may relate to locomotor dysfunction. SIGNIFICANCE This study elucidates changes in neural activity during gait in PD, underscoring the importance of testing simple and complex tasks. Results support a positive relationship between activity in locomotor regions and walking ability.

Measuring kinaesthetic sensitivity in typically developing children

This study presents a method to quantify a child’s sensitivity to passive limb motion, which is an important aspect of kinaesthesia not easily examined clinically. Psychophysical detection thresholds to passive forearm motion were determined in a group of 20 typically developing pre‐adolescent children (mean age 12y 6mo, SD 10mo, range 11−13y) and a group of 10 healthy adults (mean age 29y 10mo, SD 10y 7mo, range 18−50y). A newly designed passive motion apparatus was used to measure the time to detection of forearm motion and the errors in determining movement direction. Results showed that limb motion sensitivity became increasingly variable below 0.3°/s in children and adults. In comparison with adults, movement detection times in the pediatric group were increased by between 4% and 108% for the range of tested velocities (0.075−1.35°/s). At 0.075°/s, 5% of the children, but 50% of the adults, made no directional error, indicating that motion perception became unreliable at such low velocity in both groups. The findings demonstrate that sensitivity to passive forearm motion in children should be tested at a range between 0.075 and 0.3°/s. They further suggest that passive motion sensitivity may not be fully developed in pre‐adolescent children.

Upper Extremity Freezing and Dyscoordination in Parkinson's Disease: Effects of Amplitude and Cadence Manipulations

Purpose. Motor freezing, the inability to produce effective movement, is associated with decreasing amplitude, hastening of movement, and poor coordination. We investigated how manipulations of movement amplitude and cadence affect upper extremity (UE) coordination as measured by the phase coordination index (PCI)—only previously measured in gait—and freezing of the upper extremity (FO-UE) in people with Parkinsons disease (PD) who experience freezing of gait (PD + FOG), do not experience FOG (PD-FOG), and healthy controls. Methods. Twenty-seven participants with PD and 18 healthy older adults made alternating bimanual movements between targets under four conditions: Baseline; Fast; Small; SmallFast. Kinematic data were recorded and analyzed for PCI and FO-UE events. PCI and FO-UE were compared across groups and conditions. Correlations between UE PCI, gait PCI, FO-UE, and Freezing of Gait Questionnaire (FOG-Q) were determined. Results. PD + FOG had poorer coordination than healthy old during SmallFast. UE coordination correlated with number of FO-UE episodes in two conditions and FOG-Q score in one. No differences existed between PD−/+FOG in coordination or number of FO-UE episodes. Conclusions. Dyscoordination and FO-UE can be elicited by manipulating cadence and amplitude of an alternating bimanual task. It remains unclear whether FO-UE and FOG share common mechanisms.

Depth perception in cerebellar and basal ganglia disease

There is increasing evidence that the cerebellum and the basal ganglia serve not only a role in motor control but also in visual perception. Patients with Parkinson’s disease (PD) as well as patients with cerebellar lesions exhibit impairments of vision that are not fully explained by ocular motor deficits. It is less clear to which extent these visual deficits contribute to an impaired control of visually guided movements. This study examined whether a dysfunction of the cerebellum or the basal ganglia induces impairments in depth perception, which affect action. We employed an illusionary display, the Ames trapezoidal window, to determine the ability of PD patients (n=10) and patients with spinocerebellar ataxia (SCA) (n=6) to process depth cues when estimating object slant. Participants either pointed to the edges of the window (motor judgement) or verbally indicated the perceived orientation of the display (verbal judgement). To control for ocular and limb motor deficits, participants judged the slant of a non-illusionary display in a second task. Slant estimation of the non-illusionary window was not impaired in either patient group when compared to control subjects (all P>0.2). In contrast, SCA as well as PD patients exhibited significantly greater slant estimation errors than controls when pointing to the illusionary window (P=0.005). In addition, both patient groups made larger errors than controls in their verbal judgements during binocular viewing of the illusion (P=0.005), but not during monocular viewing (P>0.2). In sum, the present findings point towards a role for both the basal ganglia and cerebellum for the processing of visual information about depth. Since the deficits were seen both in the context of action and perception and were only partially reconciled by the availability of binocular depth cues, we conclude that basal ganglia as well as cerebellar disease may affect the visual perception of depth.

Early presentation of gait impairment in Wolfram Syndrome

BackgroundClassically characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities, Wolfram syndrome (WFS) is also associated with atypical brainstem and cerebellar findings in the first decade of life. As such, we hypothesized that gait differences between individuals with WFS and typically developing (TD) individuals may be detectable across the course of the disease.MethodsGait was assessed for 13 individuals with WFS (min 6.4 yrs, max 25.8 yrs) and 29 age-matched, typically developing individuals (min 5.6 yrs, max 28.5 yrs) using a GAITRite ® walkway system. Velocity, cadence, step length, base of support and double support time were compared between groups.ResultsAcross all tasks, individuals with WFS walked slower (p = 0.03), took shorter (p ≤ 0.001) and wider (p ≤ 0.001) steps and spent a greater proportion of the gait cycle in double support (p = 0.03) compared to TD individuals. Cadence did not differ between groups (p = 0.62). Across all tasks, age was significantly correlated with cadence and double support time in the TD group but only double support time was correlated with age in the WFS group and only during preferred pace forward (rs= 0.564, p = 0.045) and dual task forward walking (rs= 0.720, p = 0.006) tasks. Individuals with WFS also had a greater number of missteps during tandem walking (p ≤ 0.001). Within the WFS group, spatiotemporal measures of gait did not correlate with measures of visual acuity. Balance measures negatively correlated with normalized gait velocity during fast forward walking (rs = −0.59, p = 0.03) and percent of gait cycle in double support during backward walking (rs = −0.64, p = 0.03).ConclusionsQuantifiable gait impairments can be detected in individuals with WFS earlier than previous clinical observations suggested. These impairments are not fully accounted for by the visual or balance deficits associated with WFS, and may be a reflection of early cerebellar and/or brainstem abnormalities. Effective patient-centered treatment paradigms could benefit from a more complete understanding of the progression of motor and other neurological symptom presentation in individuals with WFS.

Selective BOLD Responses to Individual Finger Movement Measured with FMRI at 3T

Although the gross somatotopic organization of the posterior bank of the precentral gyrus is well established, a fine scale organization of the representations of the digits of the hand has not been fully characterized. Previous neuroimaging studies have failed to find clear evidence for a specificity of digit representations in motor cortex, but rather report a distributed network of control. Reported here are the results of two experiments; in Experiment 1 a sequential finger tapping task produced strong blood oxygen level dependent (BOLD) responses in the contralateral precentral gyrus, but there was a lack of specificity for distinguishing individual representations. A randomly ordered task did accomplish this goal. In the second experiment, a randomly ordered finger‐tapping task was used and the findings demonstrated BOLD responses in clusters of voxels specific to movement of a single digit. The region of interest defined for each digit comprised several noncontiguous clusters. A “selectivity index” was developed to quantify the magnitude of the BOLD response to the movement of a specific digit, relative to BOLD response associated with movement of other digits. Strong evidence of BOLD selectivity (albeit not exclusivity) was found in the hemisphere contralateral to the cued digit; however, there was no evidence for an orderly spatial topography. These findings demonstrate that a selectivity of activation is quantifiable, supports a theory of noncontiguous distribution of control, and provides a method for comparing between healthy and impaired populations and investigating changes following training or intervention. Hum Brain Mapp, 2011.

Motor imagery of gait tasks in individuals with Parkinson disease

We developed a questionnaire to assess motor imagery (MI) of gait and administered it to 33 controls and 28 individuals with PD. Our goals were: 1) compare gait MI in individuals with and without PD, 2) determine whether walking performance relates to gait MI and 3) compare gait MI in individuals with PD with and without freezing of gait. Gait MI was not different between PD and controls. There was no correlation between walking performance and gait MI, and no difference in gait MI between freezers and nonfreezers. The gait imagery questionnaire may be useful for imaging studies involving imagined gait.