Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Inhibitory control is not lateralized in Parkinson's patients.

Parkinson's disease (PD) is often characterized by asymmetrical symptoms, which are more prominent on the side of the body contralateral to the most extensively affected brain hemisphere. Therefore, lateralized PD presents an opportunity to examine the effects of asymmetric subcortical dopamine deficiencies on cognitive functioning. As it has been hypothesized that inhibitory control relies upon a right-lateralized pathway, we tested whether left-dominant PD (LPD) patients suffered from a more severe deficit in this key executive function than right-dominant PD patients (RPD). To this end, via a countermanding task, we assessed both proactive and reactive inhibition in 20 LPD and 20 RPD patients, and in 20 age-matched healthy subjects. As expected, we found that PD patients were significantly more impaired in both forms of inhibitory control than healthy subjects. However, there were no differences either in reactive or proactive inhibition between LPD and RPD patients. All in all, these data support the idea that brain regions affected by PD play a fundamental role in subserving inhibitory function, but do not sustain the hypothesis according to which this executive function is predominantly or solely computed by the brain regions of the right hemisphere.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Does the cerebellum intervene in the abnormal somatosensory temporal discrimination in Parkinson's disease?

INTRODUCTION: somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Altered STDT has been reported in Parkinson's disease (PD). The cerebellum seems to play a role in the pathophysiology of PD, and may consequently be involved in the pathophysiology of STDT abnormalities. METHODS: STDT was investigated in fifteen PD patients who underwent real and sham cerebellar continuous theta burst stimulation (cTBS) in the OFF condition. Eight patients underwent a further real cTBS session in ON condition. STDT was measured on both hands before, 5 and 25 min after real and sham cTBS delivered over the cerebellar hemisphere ipsilateral to the more affected side. We controlled the efficacy of our protocol by monitoring primary motor cortex (M1) excitability. Ten healthy subjects acted as control group. RESULTS: STDT values were increased in PD patients in the OFF condition compared with healthy subjects and PD patients in the ON condition. In PD patients OFF condition, real but not sham cerebellar cTBS, significantly reduced STDT values only in the hand ipsilateral to the stimulated cerebellar hemisphere. Cerebellar cTBS also decreased motor evoked potentials (MEP) size in the contralateral M1. When PD patients were tested in the ON condition, cerebellar cTBS failed to modify STDT values. CONCLUSION: cerebellar cTBS improved STDT values in PD patients exclusively in OFF condition. We hypothesize that cerebellar stimulation partially compensates for increased STDT values only when patients are OFF dopaminergic therapy. This suggests that the cerebellum may act as compensatory system in PD.

Intrajejunal levodopa infusion in advanced Parkinson's disease: long-term effects on motor and non-motor symptoms and impact on patient's and caregiver's quality of life.

BACKGROUND: Continuous infusion of intrajejunal levodopa/carbidopa gel (CIILG) for advanced Parkinson's disease (PD) has been proved to be beneficial on motor complications, non-motor symptoms and quality of life in the short-term follow-up. Aim of this two-center, retrospective, open-label study was to evaluate the long-term effect of CIILG on patients' condition and caregivers' quality of life. MATERIALS AND METHODS: The assessments (performed at baseline and at latest follow-up available after CIILG) included: the unified PD rating scale (UPDRS I-IV), the non-motor symptoms scale (NMSS), the PD questionnaire (PDQ-8), the PD sleep scale (PDSS), and a battery assessing the cognitive and psychiatric status as well as caregiver's quality of life. Medications were expressed as levodopa equivalent daily dose (LEDD). RESULTS: 14 advanced PD patients (age: 67.0 +/- 11.5 years, disease duration: 12.9 +/- 4.8 years) were followed for 24.9 +/- 14.4 months after CIILG. Total LEDD was unchanged at follow-up, however therapy was globally simplified by reducing dopamine agonists (DAs). A statistically significant beneficial effect was shown on motor complications while the severity of motor symptoms did not change over time. A significant improvement of depressive symptoms and psychiatric side effects caused by DAs was detected. Sleep quality and diurnal somnolence ameliorated as revealed by the significant reduction of PDDS. Caregivers' stress and patients' quality of life were not significantly improved. However, when categorized according to their outcome, patients with improvement of motor condition and functionality gained an improvement of quality of life. Apart from the severity of motor impairment at baseline, no other predicting factors were detected. CONCLUSIONS: CIILG is an effective treatment option for patients with advanced PD over the long-term period as it may improve both the motor complications and the psychiatric side effects caused by other dopaminergic therapies.

Deep brain stimulation of subthalamic nuclei affects arm response inhibition in Parkinson's patients.

The precise localizations of the neural substrates of voluntary inhibition are still debated. It has been hypothesized that, in humans, this executive function relies upon a right-lateralized pathway comprising the inferior frontal gyrus and the presupplementary motor area, which would control the neural processes for movement inhibition acting through the right subthalamic nucleus (STN). We assessed the role of the right STN, via a countermanding reaching task, in 10 Parkinson's patients receiving high-frequency electrical stimulation of the STN of both hemispheres (deep brain stimulation, DBS) and in 13 healthy subjects. We compared the performance of Parkinson's patients in 4 experimental conditions: DBS-ON, DBS-OFF, DBS-OFF right, and DBS-OFF left. We found that 1) inhibitory control is improved only when both DBS are active, that is, the reaction time to the stop signal is significantly shorter in the DBS-ON condition than in all the others, 2) bilateral stimulation of STN restores the inhibitory control to a near-normal level, and 3) DBS does not cause a general improvement in task-related motor function as it does not affect the length of the reaction times of arm movements, that is, in our experimental context, STN seems to play a selective role in response inhibition.

Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (p<0.01 at all time-points) but in PD patients with and without LIDs, on and off therapy, remained unchanged. In PD patients with and without LIDs, on and off therapy iTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features.

Dopamine influences primary motor cortex plasticity and dorsal premotor-to-motor connectivity in Parkinson's disease.

We investigated abnormal premotor to motor (PMd-to-M1) connectivity in Parkinson's disease (PD) with repetitive transcranial magnetic stimulation (rTMS). We studied 28 patients off and on dopaminergic therapy and 28 healthy subjects. We delivered 5 Hz rTMS over M1 before and after conditioning PMd with 5 Hz rTMS. In healthy subjects, motor-evoked potentials (MEPs) elicited by M1-rTMS were facilitated and PMd-rTMS left MEPs unchanged. In patients, before PMd-rTMS, M1-rTMS induced no MEP facilitation, whereas after PMd-rTMS, it significantly facilitated MEPs only when patients were on therapy. In the second experiment, we delivered M1-rTMS under 3 different attention-demanding tasks: eyes closed, attention directed to the stimulated hand, and attention directed to the nonstimulated hand. In healthy subjects, a more pronounced MEP facilitation was present when subjects directed attention to the stimulated hand. In patients, the MEP facilitation was present when attention was directed to the stimulated hand only when patients were on therapy. Finally, we delivered M1-rTMS in patients on therapy while they were looking at the stimulated hand, before and after 1 Hz PMd-rTMS. PMd-rTMS reduced the attention-induced MEP facilitation. We conclude that in addition to abnormal M1 plasticity, the reduced MEP facilitation in PD also reflects altered PMd-to-M1 connectivity.

Atlas-based functional radiosurgery: early results.

Functional disorders of the brain, such as dystonia and neuropathic pain, may respond poorly to medical therapy. Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the centromedian nucleus of the thalamus (CMN) may alleviate dystonia and neuropathic pain, respectively. A noninvasive alternative to DBS is radiosurgical ablation [internal pallidotomy (IP) and medial thalamotomy (MT)]. The main technical limitation of radiosurgery is that targets are selected only on the basis of MRI anatomy, without electrophysiological confirmation. This means that, to be feasible, image-based targeting must be highly accurate and reproducible. Here, we report on the feasibility of an atlas-based approach to targeting for functional radiosurgery. In this method, masks of the GPi, CMN, and medio-dorsal nucleus were nonrigidly registered to patients' T1-weighted MRI (T1w-MRI) and superimposed on patients' T2-weighted MRI (T2w-MRI). Radiosurgical targets were identified on the T2w-MRI registered to the planning CT by an expert functional neurosurgeon. To assess its feasibility, two patients were treated with the CyberKnife using this method of targeting; a patient with dystonia received an IP (120 Gy prescribed to the 65% isodose) and a patient with neuropathic pain received a MT (120 Gy to the 77% isodose). Six months after treatment, T2w-MRIs and contrast-enhanced T1w-MRIs showed edematous regions around the lesions; target placements were reevaluated by DW-MRIs. At 12 months post-treatment steroids for radiation-induced edema and medications for dystonia and neuropathic pain were suppressed. Both patients experienced significant relief from pain and dystonia-related problems. Fifteen months after treatment edema had disappeared. Thus, this work shows promising feasibility of atlas-based functional radiosurgery to improve patient condition. Further investigations are indicated for optimizing treatment dose.

Effects of unilateral subthalamic deep brain stimulation on contralateral arm sequential movements in Parkinson's disease.

In Parkinson's disease, unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN), unlike bilateral stimulation, excludes ipsilateral confounding effects so that the contralateral effects of DBS on motor performance can be investigated alone. Because no kinematic study has yet investigated how unilateral STN-DBS affects the performance of a contralateral fast sequential motor act, we performed a kinematic analysis of the movement duration, switching time and spatial accuracy of a motor arm sequence in 10 parkinsonian patients. Patients were studied without dopaminergic therapy and when they were OFF and ON unilateral STN-DBS. We found that unilateral STN-DBS significantly improved movement time of a motor sequence and the switching time from one sequential step to the next, whereas accuracy deteriorated. We conclude that unilateral STN-DBS improves the performance of contralateral sequential arm movements in patients with Parkinson's disease.

Neither simple nor sequential arm movements are bradykinetic in parkinsonian patients with peak-dose dyskinesias.

OBJECTIVE: To find out whether parkinsonian patients with levodopa-induced peak-dose dyskinesias are bradykinetic. METHODS: The performance of a sequential internally determined arm movement and a simple externally triggered arm movement was studied in a group of dyskinetic parkinsonian patients during their best clinical condition and when they were OFF treatment. Patients' performance was compared with that of an age-matched control group. Movements in the three-dimensional space were recorded by the ELITE motion analysis system. Kinematic variables analysed for the sequential motor task were total movement duration and total pause duration; for the simple motor task, movement duration and reaction time; and for both tasks, movement inaccuracy. RESULTS: When patients were OFF therapy they performed sequential and simple movement tasks slower than healthy subjects whereas when they were dyskinetic they did not. During the sequential task, when the patients were dyskinetic total pause duration shortened and movement inaccuracy increased. CONCLUSIONS: Our kinematic finding indicates that parkinsonian patients' with peak-dose dyskinesias are not bradykinetic. SIGNIFICANCE: Parkinsonian patients with peak-dose dyskinesias are not bradykinetic, probably because dopamine at peak doses functionally normalizes the mechanisms controlling movement speed.

One-hertz subthreshold rTMS increases the threshold for evoking inhibition in the human motor cortex.

Despite indisputable evidence that repetitive transcranial magnetic stimulation (rTMS) modulates motor cortical excitability, the effects of subthreshold low-frequency rTMS on intracortical inhibition (ICI) are controversial. In this paper we investigated whether increasing the level of baseline ICI increases the sensitivity of ICI for disclosing the after-effects of rTMS on cortical excitability. In experiment 1, we studied changes in ICI, tested at two different baseline levels, after a train of 900 subthreshold rTMS pulses delivered at 1 Hz. In experiment 2, we studied whether the same conditioning rTMS train changed the ICI threshold, and in experiment 3 whether it changed the facilitatory I-wave interaction. Conditioning rTMS reduced ICI tested at a baseline level of 75% but left ICI tested at a baseline level of 50% unchanged. It also increased the ICI threshold but left the facilitatory I-wave interaction unchanged. These findings suggest that conditioning rTMS selectively reduced ICI tested at a baseline level of 75% by increasing the threshold for evoking inhibition in the motor cortex. The inhibitory system mediating ICI may therefore be more efficient than other motor cortical systems in reducing high cortical excitability after external intervention. Hence studies investigating the after-effects of rTMS should standardize ICI levels at baseline.

Inhibitory interactions between pairs of subthreshold conditioning stimuli in the human motor cortex.

OBJECTIVE: These experiments examined short interval paired-pulse paradigms for intracortical inhibition (ICI) and facilitation (ICF). We tested whether pairs of subthreshold conditioning stimuli interact, and whether they showed rapid periodicity similar to that observed in subthreshold I-wave interaction. METHODS: Transcranial magnetic stimulation (TMS) was given over left M1 to evoke a motor-evoked potential (MEP) of approximately 1 mV peak-to-peak amplitude in the contralateral first dorsal interosseous (FDI) muscle. Each test shock (TS) was preceded by single or paired subthreshold conditioning stimuli (CS(1) and CS(2)) at short interstimulus intervals (ISIs 1-15 ms). Intensities of CS were set just below thresholds for intracortical inhibition (ICI) or intracortical facilitation (ICF). RESULTS: Each CS(single) alone had no effect on the test MEP, but with two CS, clear inhibition was elicited at certain intervals. With a CS(2)-TS interval of 2 ms, maximum suppression occurred if CS(1) was applied 1-2.5 ms before CS(2). This inhibitory effect tapered off gradually as the CS(2)-CS(1) interval was increased up to 13 ms. When facilitation was present with a CS(single)-TS interval of 10 ms, a small but non-significant extra-facilitation occurred at ISIs between CS(2) and CS(1) of 6-15 ms. CONCLUSIONS: Two subthreshold conditioning stimuli facilitate inhibition that lacks the rapid periodicity typical of I-wave interaction. The data would be compatible with a model in which synaptic inputs converge on a common inhibitory interneurone.

BOLD signal sign and transient vessels volume variation.

The purpose of this work was to investigate the relation between BOLD signal sign and transient vessels volume variation induced by apnea. This stimulus consisting of breath holding after inspiration is able to induce a light slowing down in venous blood flow like in a sort of Valsalva maneuver. We observed diffuse negative BOLD responding areas at cortical level and a stronger negative response in correspondence of the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in the hemodynamics. Our study suggests that particular care must be considered in the interpretation of fMRI findings, especially when patients with vascular-related cerebral diseases are involved.

Transcranial magnetic stimulation techniques in clinical investigation.

Transcranial magnetic stimulation (TMS) is a technique that can activate cortical motor areas and the corticospinal tract without causing the subject discomfort. Since TMS was introduced, numerous applications of the technique have been developed for the evaluation of neurologic diseases. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of motor conduction in the CNS. Conduction studies provide specific information in neurologic conditions characterized by clinical and subclinical upper motor neuron involvement. In addition, they have proved useful in monitoring motor abnormalities and the recovery of motor function. TMS also gives information on the pathophysiology of the processes underlying the various clinical conditions. More complex TMS applications (paired-pulse stimulation, silent period, ipsilateral silent period, input-output curve, and evaluation of central fatigue) allow investigation into the mechanisms of diseases causing changes in the excitability of cortical motor areas. These techniques are also useful in monitoring the effects of neurotrophic drugs on cortical activity. TMS applications have an important place among the investigative tools to study patients with motor disorders.

Combination of two different dopamine agonists in the management of Parkinson's disease.

An alternative approach to the symptomatic treatment of parkinsonian patients with and without motor fluctuations is to use dual dopamine agonists. The aim of this study was to investigate the symptomatic effect of administrating a second dopamine agonist to parkinsonian patients already assuming pramipexole or ropinirole. As the second dopamine agonist we chose cabergoline, a drug with a long half life, whose pharmacological profile differs from that of the newer non-ergot-derived dopamine-receptor agonists. In this pilot study we enrolled 27 patients: 21 patients had motor fluctuations and were receiving levodopa plus a dopamine agonist, and 6 patients without motor fluctuations were receiving a dopamine agonist without levodopa. This open study shows that dual dopamine agonist therapy (cabergoline plus pramipexole or ropinirole) may be used in the symptomatic treatment of patients with Parkinson's disease receiving therapy with or without levodopa.

Motor cortex excitability following short trains of repetitive magnetic stimuli.

Trains of repetitive transcranial magnetic stimuli (rTMS) appear to have effects on corticospinal excitability that outlast the duration of the train. In order to investigate the mechanism of this effect in more detail we applied short periods of rTMS consisting of up to 20 stimuli at 5 Hz, 10 Hz or 20 Hz (rTMS) to the motor cortex at an intensity equal to resting threshold in 11 healthy, relaxed subjects. Spinal excitability, as judged by effects on the H-reflex or on transcranial anodal facilitation of the H-reflex, was not affected by the rTMS. However, cortical excitability, as judged by the effect on the size of EMG responses evoked by a suprathreshold TMS pulse, was decreased for up to 1 s after the end of rTMS. Post-train suppression was more powerful following longer trains or higher frequencies of rTMS. The predominant suppression contrasts with previous reports of facilitation, particularly after high-frequency rTMS. A second set of experiments, however, showed that this could be converted into facilitation if the intensity of rTMS was increased. We conclude that the after-effects of rTMS depend on its frequency, intensity and duration. The results are consistent with a model in which inhibition and facilitation build up gradually during the course of a conditioning train. Inhibition reaches its maximum effect after only a small number of stimuli, whereas facilitation takes longer. The threshold for evoking inhibition is lower than that for facilitation. Thus if moderate intensities of conditioning train are applied, inhibition is predominant after short trains, whereas facilitation dominates after long trains.

The prolonged cortical silent period in patients with Huntington's disease.

OBJECTIVES: In a group of patients with Huntington's disease and age-matched controls, we studied the cortical silent period (SP) elicited by single transcranial magnetic stimulation (TMS) pulses. METHODS: We measured the area of the pre-stimulus electromyographic (EMG) activity, the area of the motor evoked potentials (MEPs) and the duration of the SP induced by stimuli delivered at an intensity of 150% of motor threshold with a round coil placed over the vertex. We determined the cortical SP by sampling only the 5 traces containing the shortest SPs and by collecting 10 consecutive unselected traces without selecting trials. RESULTS: Patients and controls had normal EMG background areas, and MEP latencies and areas. Whereas data measured from selected trials gave a normal duration of the SP (patients, 154+/-58 ms; controls, 166+/-22 ms), data from unselected trials yielded a significantly longer SP duration in patients than in controls (356+/-251 vs. 159+/-44 ms) and also a larger variance and range. CONCLUSIONS: We conclude that in Huntington's disease, an abnormal cortical SP is best sought by collecting unselected consecutive traces. We suggest that the prolonged SP in HD originates from a dysfunction of the mechanisms controlling the restart of voluntary movement after TMS.

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia.

To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50-100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms.

Botulinum toxin restores presynaptic inhibition of group Ia afferents in patients with essential tremor.

We studied the effect of botulinum toxin A injection on the abnormal presynaptic phase of reciprocal inhibition between forearm antagonist muscles in patients with essential tremor. Ten patients with essential tremor were investigated before and 1 month after botulinum injection. Reciprocal inhibition was studied by conditioning the H reflex in forearm flexors with a radial-nerve stimulus delivered at a range of time intervals. Botulinum toxin produced a significant functional improvement in tremor (about 20%). Before botulinum toxin injection, patients had a reduced presynaptic phase of reciprocal inhibition. After botulinum toxin this phase was significantly more pronounced. The normal early disynaptic phase of reciprocal inhibition was normal before and after botulinum treatment. Although botulinum treatment reduced the size of the H reflex and the M wave to a similar extent, it left the H/M ratio unchanged. These findings show that botulinum toxin treatment restores presynaptic inhibition between forearm antagonist muscles. The results are also consistent with botulinum toxin having a beneficial effect in patients with essential tremor. Both effects probably depend upon the toxin's concurrent action on the extrafusal and intrafusal motor end-plates, the latter resulting in decreased spindle afferent input to the spinal cord.