Parkinson's disease impacts brain's centers of touch and vision

Movement disorder affects more than just motor control

Public release date: 17-Oct-2006
http://www.eurekalert.org/pub_releas...-pdi101306.php

Although Parkinson's disease is most commonly viewed as a "movement disorder," scientists have found that the disease also causes widespread abnormalities in touch and vision Ð effects that have now been verified using functional magnetic resonance imaging (fMRI) of the brain. The new findings, by scientists at Emory University School of Medicine and Zhejiang University Medical School in Hangzhou China, will be presented on Oct. 17 at the Society for Neuroscience meeting in Atlanta.

Scientists studying Parkinson's disease (PD) previously have focused on the brain's motor and premotor cortex, but not the somatosensory or the visual cortex. But Emory neurologist Krish Sathian, MD, PhD, and colleagues had earlier discovered, through tests of tactile ability, that PD patients have sensory problems with touch. They designed a study using fMRI to investigate the brain changes underlying these sensory abnormalities.

Dr. Sathian's research group studied six patients with moderately advanced PD and six age-matched healthy controls. After documenting the typical movement problems of PD and ruling out dementia and nerve problems in the PD patients, they administered a common test of tactile ability to both groups, asking the participants to use their fingers to distinguish the orientation of ridges and grooves on plastic gratings. At the same time, they conducted a brain-scanning study using fMRI. This technology measures activations of neurons in different areas of the brain by means of variations in blood flow as an individual does a particular task.

The fMRI scans showed that the PD patients had much less activation of the somatosensory areas in the brain's cortex than did the healthy controls. The scientists also were surprised to find similar widespread differences in the visual cortex, although the task involved touch, not vision.

"Our finding that the visual cortex is affected in Parkinson's disease, while surprising, makes sense given that our laboratory and many others have shown previously that areas of the brain's visual cortex are intimately involved in the sense of touch," Dr. Sathian notes. "Although the reasons for this are uncertain, they may involve a process of mental visualization of the tactile stimuli and may also reflect a multisensory capability of the visual cortex."

Dr. Sathian believes the study shows that the traditional boundaries between brain systems involved in touch and vision, and between those involved in sensation and movement, are artificial constructs that break down with more in-depth study. From a practical standpoint, it shows that patients with PD and other movement disorders have considerable problems in addition to movement control.

"These problems need to be appreciated in caring for these patients and in designing newer strategies for treatment and rehabilitation," Dr. Sathian emphasizes.

....couldn't they have just asked us? I could certainly have told them that touch was affected. After all, that's what the banding experiments are all about.

I love functional scans. They're fascinating.

This is an old study:


Research Article
Perception of heaviness in Parkinson's disease
Matthias Maschke, MD 1 2 *, Paul J. Tuite, MD 3, Kim Krawczewski, BS 1, Kristen Pickett, BS 1, Jürgen Konczak, PhD

Movement Disorders

RSS feed for Movement Disorders What is RSS?
Volume 21, Issue 7 , Pages 1013 - 1018

Published Online: 6 Apr 2006

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 Parkinson's 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. © 2006 Movement Disorder Society


(haptic sensation - a sensation localized on the skin)

FULL ARTICLE:

http://www3.interscience.wiley.com/c...8336/HTMLSTART

From the article I posted:

Article Text

The seminal work by Goldscheider (1898) distinguished four aspects of muscle sense: (1) passive motion sense, (2) active motion sense, (3) position sense, and (4) the appreciation of heaviness and resistance.[1] The last sense has also been called dynamesthesia, or sense of tension.[2] The perception of heaviness was first studied experimentally by the German psychologist Gustav Fechner in 1889, who investigated the human ability to detect and to discriminate between different weights.[3] Most of the subsequent work in this field addressed the question, which psychophysical mechanisms underlie the correct discrimination of two different weights. It has been shown that visual and haptic information is relevant for correct estimation of weights and might be altered by size-weight illusions.[4-6] Anesthesia to skin and joints causes changes in the perceived heaviness of weights, indicating that the sensation relies on an intact peripheral nervous systems.[7][8]

Although Parkinson's disease (PD) is predominately characterized by motor deficits, increasing evidence shows that processing of sensory signals might be altered in patients with PD. With respect to proprioception, we and others have shown that PD patients exhibit deficits in the conscious awareness of limb position and passive limb movements (kinesthesia) that can be partially reversed by deep brain stimulation of the subthalamic nucleus.[9-14] It is also known that proprioceptors next to cutaneous mechanoreceptors mediate the conscious perception of heaviness and tension. Thus, it seems plausible that such perception is affected in PD patients, although the psychophysical thresholds for load detection in PD are not known. Consequently, the purpose of the present study was to examine whether mild to moderately impaired PD patients show elevated detection thresholds for a gravitational load and to correlate possible perceptual deficits with markers of disease severity and medication.


Do Cerebro-Basal-Ganglia Loops Play a Role in Perception of Heaviness?

The significant group difference in weight perception thresholds between PD patients and control subjects indicates that intact cerebro-basal-ganglia loops are essential for an intact gravito-inertial sense that Goldscheider called the sensation of heaviness.

The critical role of this functional loop in proprioceptive processing has been documented by several psychophysical studies investigating kinesthesia in PD and focal dystonia patients.[9-15]

Taken together, all these reports indicate that the cerebro-basal-ganglia loops are more involved in proprioceptive signal processing than previously known. Recent anatomical and neurophysiological data corroborate these behavioral findings.

First, neuronal activity elicited by passive movements and somatosensory evoked potentials can be recorded within the subthalamic nucleus and pallidal globe.[16-18]

Second, the basal ganglia receive inputs not only from motor cortical areas but also from numerous other cortical areas, including the sensory cortex.[19] Third, with respect to patients, who have a dysfunction of the cerebro-basal ganglia loop, it is known that they exhibit an altered distribution proprioceptive-evoked cortical potentials in PD and in Huntington's disease.[20]

The functional significance of these proprioceptive deficits is still not fully understood. However, the reported kinesthetic deficits likely contribute to the endpoint errors in goal-directed movements of PD patients,[21] whereas the consistent hypometria of pointing movements against gravity becomes explainable on the basis of our findings that the thresholds for gravitational loads are altered.

In fact, PD patients have been demonstrated to exhibit disturbances in lifting an object in a precision grip between the thumb and the index finger.[22]

Could Other Factors Account for Deficits in PD Patients?

PD is a neurodegenerative disease that does not solely affect dopaminergic pathways but also cholinergic and serotoninergic circuits. Thus, one needs to consider other factors that possibly contributed to an impaired weight perception.

First, peripheral neuropathy or sensory tract involvement are known to affect weight perception.[23]

However, clinical examination did not reveal any clinical signs of sensory impairments in our PD patient sample. In addition, peripheral neuropathy is an uncommon feature of idiopathic Parkinson's disease and, if present, is due to nerve compression or rare side-effects of medication in advanced stages rather than to the disease itself.

Second, the dopaminergic medication could have induced a proprioceptive deficit since one study reported a suppressed position sense after administration of L-dopa and dopamine agonists.[24]

However, in our study, individual thresholds of PD patients did not correlate significantly with their L-dopa equivalent dose but increased with disease severity, indicating that the disease itself and not the medication was causative.

Third, attention, decision-making, or other cognitive deficits of PD patients might have led to the observed perceptual deficits. However, our neuropsychological results speak against such assumption. The MMSE and Tower of Hanoi scores were not different between our PD patients and controls.

As a caveat, we cannot completely rule out that subtle cognitive deficits have contributed to the perceptual deficits in our group of PD patients, because we did not administer a detailed neuropsychological test battery.

Lastly, fatigue might have influenced the results in PD patients but not in controls. However, both in controls and in PD patients, the performance recorded at the end of the experiment did not significantly differ from that at the beginning of the experiment. Therefore, it is unlikely that fatigue was a key factor in our experiment.

In summary, our results demonstrate that the perception of heaviness or weight is already affected in the early stages of PD. The findings of the current study underline growing evidence that proprioceptive and possibly haptic dysfunction is a common feature of PD and confirm the importance of the cerebro-basal-ganglia loops for proprioception.

J Neuroengineering Rehabil. 2006; 3: 9.
Published online 2006 May 4. doi:

Effect of step-synchronized vibration stimulation of soles on gait in Parkinson's disease: a pilot study

Peter Novakcorresponding author1 and Vera Novak2
1Department of Neurology, Boston University School of Medicine; 715 Albany Street, C315, Boston, MA 02118, USA
2Division of Gerontology2, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA


Background
Previous studies have suggested that impaired proprioceptive processing in the striatum may contribute to abnormal gait in Parkinson's disease (PD).

Parkinson's disease (PD) is caused by a dopamine deficiency in the basal ganglia that results in characteristic motor abnormalities including postural instability and gait impairment. Short shuffling steps, slow walking speed, and increased stride variability characterize abnormal gait in PD.

Although PD is primarily a motor disease, accumulating evidence suggests that abnormal proprioception and kinesthesia contribute to the parkinsonian gait. PD patients have reduced sensation on the plantar feet [1] and impaired joint position sense [2], movement perception [3], and movement accuracy [4-6].

It has been proposed that an inadequate integration of sensory inputs at the striatum and a defective proprioceptive feedback underlie abnormal motor control movement in PD [6,7].

Sensory feedback is necessary for postural adjustments and facilitates control of compensatory stepping reactions evoked by postural perturbation [8-10]. Cutaneous, joint, and muscular mechanoreceptors provide the necessary proprioceptive inputs [11].

Mechanical stimulation of foot mechanoreceptors can be used to perturb the proprioceptive feedback and to assess its role in generation of parkinsonian gait. The foot pressure activates the plantar mechanoreceptors that mediate postural adjustment during the stance phases of the step [10].

Several studies explored the effects of mechanical stimulation upon static balance as a mean for proprioceptive feedback modulation. Subsensory mechanical noise applied to the soles has improved the quiet-standing balance in healthy controls [12] and in patients with diabetes and stroke [13]. This effect was attributed to enhanced proprioceptive feedback.

The effect of the suprathreshold stimulation is complex and depends on the frequency, amplitude, and location of the stimulation [14,15]. For example, during standing, the vibratory stimulation of the forefoot zones induces early electromyographic responses in the soleus muscle (mean latency 119 ms), followed by small forward center of pressure (CoP) displacement (mean latency 251 ms) and backward body tilt (mean latency 434 ms).

Vibratory stimulation of rear foot zones has a similar effect but with an opposite direction of the body tilt. Simultaneous activation of both forefoot and rear foot zones has no effect on body tilt but does cause CoP oscillations. These results imply that characteristic postural responses may be specific to the localization and character of a stimulus.

We hypothesized that a vibration stimulation of foot mechanoreceptors synchronized with the step improves gait in PD. In this study the step-synchronized vibration stimulation was used to enhance the proprioceptive input during walking in healthy and PD subjects.

The vibratory stimulus was delivered to the soles during the stance phase of the step, but not during the swing phase. Preliminary results were previously published as an abstract [16].

Study:

http://www.pubmedcentral.nih.gov/art...?artid=1471796

Brain, Vol. 126, No. 10, 2312-2322, October 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg230
Dysfunction of the basal ganglia, but not the cerebellum, impairs kinaesthesia
Matthias Maschke1,3, Christopher M. Gomez2, Paul J. Tuite2 and Jürgen Konczak1,2

Precise knowledge about limb position and orientation is essential for the ability of the nervous system to plan and control voluntary movement. While it is well established that proprioceptive signals from peripheral receptors are necessary for sensing limb position and motion, it is less clear which supraspinal structures mediate the signals that ultimately lead to the conscious awareness of limb position (kinaesthesia).

Recent functional imaging studies have revealed that the cerebellum, but not the basal ganglia, are involved in sensory processing of proprioceptive information induced by passive and active movements.

Yet psychophysical studies have suggested a prominent role of the basal ganglia in kinaesthesia. This study addresses this apparent dichotomy by investigating the contributions of the cerebellum and the basal ganglia to the perception of limb position.

Using a passive movement task, we examined the elbow position sense in patients with a dysfunction of the basal ganglia (Parkinson’s disease, n = 9), patients with cerebellar degeneration [spinocerebellar ataxia (SCA) types 6 and 8, n = 6] and age-matched healthy control subjects (n = 11).

In comparison with healthy control subjects, Parkinson’s disease patients, but not SCA patients, were significantly impaired in the ability to detect displacements correctly. A 1° forearm displacement was correctly recognized in >75% of trials by control subjects and SCA patients, but only in 55% of Parkinson’s disease patients. Only at 6° displacement did Parkinson’s disease patients exhibit a response rate similar to those of the two other groups. Thresholds for 75% correct responses were 1.03° for controls, 1.15° for cerebellar patients and 2.10° for Parkinson’s disease patients.

This kinaesthetic impairment significantly correlated with the severity of disease in Parkinson’s disease patients, as determined by the Unified Parkinson’s Disease Rating Scale (r = –0.7, P = 0.03) and duration of disease (r = –0.7, P = 0.05).

In contrast, there was no significant correlation between performance and the daily levodopa equivalent dose. These results imply that an intact cerebro-basal ganglia loop is essential for awareness of limb position and suggest a selective role of the basal ganglia but not the cerebellum in kinaesthesia.

Proprioception in Parkinson's disease is acutely depressed by dopaminergic medications
P O'Suilleabhain, J Bullard, R B Dewey

J Neurol Neurosurg Psychiatry 2001;71:607-610 ( November )

OBJECTIVES---Impaired proprioception has been previously reported in patients with Parkinson's disease. It was hypothesised that dopaminergic medications transiently depress proprioception, with amplification of adventitious movements as a result. This study tested for effects on proprioception of dopaminergic drugs, and for associations between such effects and drug induced dyskinesias.


METHODS---In 17 patients with Parkinson's disease, arm proprioception was tested in the practically defined "off" state, and retested 1 hour after taking levodopa or dopamine agonist. Testing consisted of side to side comparison of elbow angle, matching the contralateral elbow angle, and spatial recall of an unrestrained arm.


RESULTS---Proprioception deteriorated as hypothesised, reaching significance by one tailed t test for each of the three tasks. The relative deterioration (and the 95% lower confidence bound for estimated deterioration) was 31% (4%) for side to side elbow comparison, was 27% (11%) for accuracy in matching the contralateral elbow angle, and was 11% (0%) for spatial recall. Dyskinetic (n=6) and non-dyskinetic (n=11) patients did not differ significantly in these effects on proprioception. Control subjects (n=6) and untreated parkinsonian subjects (n=5) did not significantly differ from the parkinsonian patients in the off state.


CONCLUSIONS---Administration of levodopa and dopamine agonists were associated with a modest acute suppression in central responsiveness to joint position. It is speculated that compensatory exaggerated movement could account in part for the phenomenon of drug induced dyskinesias.

For those of us with dystonia:

Klin Neurophysiol 2004; 35
DOI: 10.1055/s-2004-832129
Sensorimotor Integration in Basal Ganglia Disorders: New Findings on Impaired Kinaesthesia in Focal Dystonia and Parkinson's Disease
N Putzki1, P Stude2, K Graf3, M Maschke4

The term „movement disorders“ is often used to subsume conditions resulting from basal ganglia pathology and refers to the predominating motor symptoms. However, clinically unapparent sensory deficits were also found in these disorders.

Recent neurophysiological, neuroimaging and animal studies have revealed that sensory processing is impaired in Huntington's disease, Parkinson's disease and focal dystonia.

This raised the interesting question to what extent impaired sensorimotor integration contributes to the clinical symptoms in these disorders. We analyzed kinaesthesia, the conscious perception of limb position, in a passive movement task (repeated extension and flexion of the index finger between 0.2° and 4° in 45 trials of random order) and compared results of patients with idiopathic focal dystonia (blepharospasm n=3, torticollis n=6) and patients with idiopathic PD (n=8) to an age-matched group of healthy controls (n=5).

Patients and controls were without cognitive decline and did not show sensory deficits in routine clinical examination. PD patients detected the correct direction of a 0.2° displacement of the index finger in only 59% of the trials compared to 82% in healthy controls. Patients with focal dystonia also revealed a kinaesthetic deficit given that they responded correctly in only 76% of trials in the same task.

The overall differences for detecting the correct direction of index finger movements between patient groups and controls were statistically significant (β2, p=0.001 for PD group, p=0.002 for dystonia group). Calculated thresholds for 75% correct responses were 0.3° in PD patients, 0.2° in dystonia patients and 0.1° in control subjects.

Additionally, we analyzed the ability to judge the extent of a passive movement of the index finger by asking the patients to compare two consecutive passive movements.

PD patients appeared to be more impaired than dystonia patients and both groups were different from the control group. Our findings in PD patients confirm results of previous studies that revealed kinaesthetic deficits in PD.

Furthermore, the results of the present study suggest that a kinaesthetic impairment is also prevalent in focal dystonia. Together with previous findings the present results indicate that a deficit in processing multimodal sensory information might contribute to motor deficits in distinct basal ganglia disorders. Our results show the potential role of the basal ganglia as a sensory analyzer.

Zuchiniflower, very good indeed! This is touching on what we suspect as being behind the bands' effect. The light stimulation temporarily reopens the feedback loops (or so we think).

Now I understanad my initial symptoms of PD before Dx. I experienced attacks of "dizzziness" (confusion about which direction was down) without vertigo. I spent a lot of time with audiologists and ENT specialists trying to diagnose an inner ear problem. And all the time the problem was in the proprioception loop involving the basal ganglia.
I still have some degree constantly of the same sensation, and have been given meclazine by my neurologist to treat it. Meclazine does not touch it.
Gait instability was what tipped off the neuro as to my initial Dx.
One thing that doesn't fit is that DOPA greatly alleviated my gait problems within 36-48 hours after I started taking it, whereas it did not seem to affect the PD-associated proprioception problems in the studies ZF cited.
Robert