Basal ganglia oscillations as biomarkers for targeting circuit dysfunction in Parkinson's disease.

Oscillations are a naturally occurring phenomenon in highly interconnected dynamical systems. However, it is thought that excessive synchronized oscillations in brain circuits can be detrimental for many brain functions by disrupting neuronal information processing. Because synchronized basal ganglia oscillations are a hallmark of Parkinson's disease (PD), it has been suggested that aberrant rhythmic activity associated with symptoms of the disease could be used as a physiological biomarker to guide pharmacological and electrical neuromodulatory interventions. We here briefly review the various manifestations of basal ganglia oscillations observed in human subjects and in animal models of PD. In this context, we also review the evidence supporting a pathophysiological role of different oscillations for the suppression of voluntary movements as well as for the induction of excessive motor activity. In light of these findings, it is discussed how oscillations could be used to guide a more precise targeting of dysfunctional circuits to obtain improved symptomatic treatment of PD.

Personalized transcranial alternating current stimulation (tACS) and physical therapy to treat motor and cognitive symptoms in Parkinson's disease: A randomized cross-over trial.

Abnormal cortical oscillations are markers of Parkinson's Disease (PD). Transcranial alternating current stimulation (tACS) can modulate brain oscillations and possibly impact on behaviour. Mapping of cortical activity (prevalent oscillatory frequency and topographic scalp distribution) may provide a personalized neurotherapeutic target and guide non-invasive brain stimulation. This is a cross-over, double blinded, randomized trial. Electroencephalogram (EEG) from participants with PD referred to Specialist Clinic, University Hospital, were recorded. TACS frequency and electrode position were individually defined based on statistical comparison of EEG power spectra maps with normative data from our laboratory. Stimulation frequency was set according to the EEG band displaying higher power spectra (with beta excess on EEG map, tACS was set at 4 Hz; with theta excess, tACS was set at 30 Hz). Participants were randomized to tACS or random noise stimulation (RNS), 5 days/week for 2-weeks followed by ad hoc physical therapy. EEG, motor (Unified Parkinson's Disease Rating Scale-motor: UPDRS III), neuropsychological (frontal, executive and memory tests) performance and mood were measured before (T0), after (T1) and 4-weeks after treatment (T2). A linear model with random effects and Wilcoxon test were used to detect differences. Main results include a reduction of beta rhythm in theta-tACS vs. RNS group at T1 over right sensorimotor area (p = .014) and left parietal area (p = .010) and at T2 over right sensorimotor area (p = .004) and left frontal area (p = .039). Bradykinesia items improved at T1 (p = .002) and T2 (p = .047) compared to T0 in the tACS group. In the tACS group the Montréal Cognitive Assessment (MoCA) improved at T2 compared with T1 (p = .049). Individualized tACS in PD improves motor and cognitive performance. These changes are associated with a reduction of excessive fast EEG oscillations.

Dietary proteins and amino acids in the control of the muscle mass during immobilization and aging: role of the MPS response.

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

An evaluation of istradefylline treatment on Parkinsonian motor and cognitive deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque models.

Istradefylline (KW-6002), an adenosine A2A receptor antagonist, is used adjunct with optimal doses of L-3,4-dihydroxyphenylalanine (l-DOPA) to extend on-time in Parkinson's disease (PD) patients experiencing motor fluctuations. Clinical application of istradefylline for the management of other l-DOPA-induced complications, both motor and non-motor related (i.e. dyskinesia and cognitive impairments), remains to be determined. In this study, acute effects of istradefylline (60-100 mg/kg) alone, or with optimal and sub-optimal doses of l-DOPA, were evaluated in two monkey models of PD (i) the gold-standard 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of parkinsonian and dyskinetic motor symptoms and (ii) the chronic low dose (CLD) MPTP-treated macaque model of cognitive (working memory and attentional) deficits. Behavioural analyses in l-DOPA-primed MPTP-treated macaques showed that istradefylline alone specifically alleviated postural deficits. When combined with an optimal l-DOPA treatment dose, istradefylline increased on-time, enhanced therapeutic effects on bradykinesia and locomotion, but exacerbated dyskinesia. Istradefylline treatment at specific doses with sub-optimal l-DOPA specifically alleviated bradykinesia. Cognitive assessments in CLD MPTP-treated macaques showed that the attentional and working memory deficits caused by l-DOPA were lowered after istradefylline administration. Taken together, these data support a broader clinical use of istradefylline as an adjunct treatment in PD, where specific treatment combinations can be utilised to manage various l-DOPA-induced complications, which importantly, maintain a desired anti-parkinsonian response.

Performance of repetitive alternating elbow movements in Parkinson's disease.

BACKGROUND: Bradydiadochokinesia is one main clinical symptom in idiopathic Parkinson's disease (IPD). The pathogenesis of bradydiadochokinesia is not completely clear. METHODS: Fifteen patients with IPD and 15 age-matched healthy volunteers had to perform rhythmic alternating flexion and extension movements in the elbow joint. The rhythm was provided auditorily by a click tone stimulator. Six maneuvers (spatial extents of 48 and 83° at frequencies of 0.45, 0.75 and 1.25 Hz) had to be absolved. The potentiometer converted the horizontal forearm movements into a variable voltage. RESULTS: The duration of single movements varied more significantly in patients than in controls (p < 0.05; Mann-Whitney U test). Patients executed all conditions more slowly than controls, but this difference was only significant at the most difficult condition (83° at 1.25 Hz; p < 0.01). The movement amplitudes or their variability were not significantly different at any condition. No parameter correlated significantly with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) or with the duration of disease. CONCLUSION: An insufficient temporal coordination contributes to bradydiadochokinesia in IPD. This deficit occurs independently of other parkinsonian cardinal motor symptoms.

Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease.

Suppression of excessively synchronous beta-band oscillatory activity in the brain is believed to suppress hypokinetic motor symptoms of Parkinson's disease. Recently, a lot of interest has been devoted to desynchronizing delayed feedback deep brain stimulation (DBS). This type of synchrony control was shown to destabilize the synchronized state in networks of simple model oscillators as well as in networks of coupled model neurons. However, the dynamics of the neural activity in Parkinson's disease exhibits complex intermittent synchronous patterns, far from the idealized synchronous dynamics used to study the delayed feedback stimulation. This study explores the action of delayed feedback stimulation on partially synchronized oscillatory dynamics, similar to what one observes experimentally in parkinsonian patients. We employ a computational model of the basal ganglia networks which reproduces experimentally observed fine temporal structure of the synchronous dynamics. When the parameters of our model are such that the synchrony is unphysiologically strong, the feedback exerts a desynchronizing action. However, when the network is tuned to reproduce the highly variable temporal patterns observed experimentally, the same kind of delayed feedback may actually increase the synchrony. As network parameters are changed from the range which produces complete synchrony to those favoring less synchronous dynamics, desynchronizing delayed feedback may gradually turn into synchronizing stimulation. This suggests that delayed feedback DBS in Parkinson's disease may boost rather than suppress synchronization and is unlikely to be clinically successful. The study also indicates that delayed feedback stimulation may not necessarily exhibit a desynchronization effect when acting on a physiologically realistic partially synchronous dynamics, and provides an example of how to estimate the stimulation effect.

Tratamiento de los trastornos de la marcha en la enfermedad de Parkinson / Treatment of gait disorders in Parkinson's disease

Se observa un interés creciente por el estudio de los síntomas extranígricos de la enfermedad de Parkinson, como las alteraciones de la marcha, que conllevan una importante disminución de la calidad de vida. La marcha es un proceso complejo cuya afectación puede explicarse por la suma de elementos como hipocinesia, asimetría en el movimiento de ambos hemicuerpos, disfunción ejecutiva, alteraciones en la sensibilidad propioceptiva, factores ambientales y emocionales. En la regulación de la marcha y la postura están implicadas diversas estructuras cerebrales y neurotransmisores que en la enfermedad de Parkinson tienen alterada su activación. En las fases iniciales los trastornos de la marcha son controlados aceptablemente con fármacos dopaminérgicos pero la respuesta a estos medicamentos no es satisfactoria en fases avanzadas, lo cual ha llevado a investigar sustancias con otros mecanismos de acción (metilfenidato, dihidroxifenilserina, anticolinesterásicos, memantina, inhibidores selectivos de los receptores de serotonina, entre otros) y tratamientos no farmacológicos como cirugía (estimulación cerebral profunda del núcleo subtalámico y del pedunculopontino), fisioterapia y acupuntura (AU)

There is currently a growing interest in the study of the extra-nigral symptoms of Parkinson's disease, such as gait disorders, which result in an important reduction in quality of life. Walking is a complex process and the problems affecting it can be explained by the sum of elements like hypokinesia, asymmetry in the movement of the two halves of the body, executive dysfunction, alterations affecting proprioceptive sensitivity, and environmental and emotional factors. The activation of a number of different brain structures and neurotransmitters involved in the regulation of gait and posture is altered in Parkinson's disease. In the early phases gait disorders are controlled to an acceptable extent with dopaminergic drugs, but the response to these agents is not satisfactory in advanced phases. This has led researchers to look for substances with other mechanisms of action (methylphenidate, dihydroxyphenylserine, anticholinesterases, memantine and selective serotonin receptor inhibitors, among others) and non-pharmacological treatments such as surgery (deep brain stimulation of the subthalamic nucleus and of the pedunculopontine), physiotherapy and acupuncture (AU)

External cueing improves motor imagery quality in patients with Parkinson disease.

BACKGROUND: Patients with Parkinson disease (PD) are often profoundly slow in their performance of physical tasks, as well as in motor imagery (MI). This may limit the implementation and potential benefits of MI practice during rehabilitation. OBJECTIVE: The authors investigated whether the quality of MI could be improved by external cueing. METHODS: Fourteen patients with PD and 14 healthy controls physically executed and visually imagined a goal-directed aiming task and a box-and-block task, both in the presence and absence of visual and auditory cues. Mental chronometry and eye movement recording allowed objective evaluation of the temporal and spatial characteristics of MI when compared with physical execution. Visual analogue scales were used to assess imagery vividness. RESULTS: The presence of visual cues significantly reduced the patients' bradykinesia during MI and increased their imagery vividness. CONCLUSIONS: Visual cueing optimizes MI quality for PD patients and is a potential tool to increase the efficacy of MI practice in PD rehabilitation.

Motor imagery ability in patients with early- and mid-stage Parkinson disease.

BACKGROUND: Motor imagery has recently gained attention as a promising new rehabilitation method for patients with neurological disorders. Up to now, however, it has been unclear whether this practice method can also be successfully applied in the rehabilitation of patients with Parkinson disease (PD). OBJECTIVE: This study aimed to investigate whether the motor imagery ability of patients with PD is still intact despite basal ganglia dysfunctioning. METHODS: A total of 14 patients with early- and mid-stage PD (Hoehn and Yahr 1-3) and 14 healthy controls were evaluated by means of an extensive imagery ability assessment battery, consisting of 2 questionnaires, the Chaotic Motor Imagery Assessment battery, and a test based on mental chronometry. RESULTS: PD patients performed the imagery tasks more slowly than controls, but the motor imagery vividness and accuracy of most patients were well preserved. CONCLUSIONS: These results are promising regarding the potential use of motor imagery practice in the rehabilitation of patients with PD.

[A new look at the corticostriatal-thalamocortical circuit in sporadic Parkinson's disease]. / Neue Sicht des kortiko-striato-thalamo-kortikalen Regelkreises bei M. Parkinson.

The traditional model of corticostriatal-thalamocortical projections, with indirect and direct pathways, provides a simplified and useful explanation for the motor deficits (hypokinesia, bradykinesia) that develop in the course of sporadic Parkinson's disease. In the classic model, major emphasis is placed on the dopamine deficiency in the dorsal striatum that occurs as a result of neuronal loss in the substantia nigra of the midbrain. Nevertheless, because the pathological process that underlies Parkinson's disease also involves many key nondopaminergic connectivities, a revised model is needed that incorporates these projections. The focus on damage to nondopaminergic and extranigral sites is becoming increasingly important for clinical practice.

Inadequacy of calcium supplements to normalize muscle calcium deficiency in healthy subjects during prolonged hypokinesia.

OBJECTIVE: We investigated the effect of hypokinesia (diminished movement) on muscle calcium (Ca(2+)) content with and without Ca(2+) supplementation and Ca(2+) loss with different muscle Ca(2+) deficiency; muscle Ca(2+) content, plasma Ca(2+) level, and Ca(2+) loss were measured. METHODS: Studies were performed in 40 physically healthy male volunteers during a pre-experimental period of 30 d and an experimental period of 364 d. Subjects in equal numbers were assigned to one of four groups: unsupplemented active control subjects (UACSs), unsupplemented hypokinetic subjects (UHKSs), supplemented active control subjects (SACSs), and supplemented hypokinetic subjects (SHKSs). A daily supplementation of 0.7 mmol of calcium lactate per kilogram of body weight was given to SACSs and SHKSs. RESULTS: Muscle Ca(2+) content decreased, and plasma Ca(2+) concentration and Ca(2+) loss in urine and feces increased (P < 0.05) in the SHKS and UHKS groups compared with their pre-experimental values and the values in their respective active control groups (SACS and UACS). However, muscle Ca(2+) content decreased more, and plasma Ca(2+) concentration and Ca(2+) loss increased more (P < 0.05) in the SHKS group than in the UHKS group. CONCLUSION: Muscle Ca(2+) deficiency is more evident when Ca(2+) intake is higher and Ca(2+) loss is more exacerbated with higher than with lower muscle Ca(2+) deficiency, indicating that muscle Ca(2+) deficiency during prolonged hypokinesia is due to an inability of the body to use Ca(2+) but not to a Ca(2+) shortage in the diet.

The time course of the return of upper limb bradykinesia after cessation of subthalamic stimulation in Parkinson's disease.

To investigate the time span within which bradykinesia re-occurs, we registered movement parameters immediately after the termination of deep brain stimulation of the subthalamic nucleus (STN) in nine Parkinson patients with chronically implanted bilateral STN electrodes. Two repetitive movements were investigated: finger-tapping and forearm pronation-supination. When stimulation was switched off, the amplitude and velocity of the investigated movements significantly declined, but the frequency did not. The time course of this decline was modeled by an exponential function that yielded time constants between 15 and 30s. The effect of stimulation had completely disappeared within 1 min. These results suggest that it is necessary to wait at least for 1 min after the end of stimulation before performing further assessments.

Sudden infant death syndrome: selenium administered above dietary needs stabilizes the electrocardiograms of subjects deprived of exercise stimuli to the brain.

The human foetus begins preparation for extrauterine life in the 26th week of gestation. Victims of sudden infant death syndrome (SIDS) were described as having less-intensive reactions to environmental stimuli than their siblings. They were described as less-active physically and more breathless and exhausted during feeding. These foetal-like qualities are similar to the microgravity deconditioning of the space traveller and the autonomic dysfunction of hypokinetic humans. During quiet sleep, a group of near-miss SIDS victims displayed a faster heart-rate and a decreased movement-time, compared to controls. Another group of SIDS victims linked delayed repolarisation and sympathetic overactivity of the nervous system. The excessive Q-T wave intervals, cardiac instability and autonomic dysfunction tended to coincide with the peak incidence of SIDS which is the normal period of autonomic transformation at 2-3 months of age. Sympathetic hyperactivity transforms the subject into an energy-intensive species with an accelerated heartbeat, intensive vasoconstriction and general reactions to a hostile environment. Energy-intensive species (flight-oriented species) were sensitive to selenium (Se) deficiency. Altered mitochondrial structure and defective electron transport of heart mitochondria were features of this syndrome. Runaway excessive sympathetic autonomic activity transforms the subject into an energy-intensive species responsive to selenium. Groups of Se-deficient lambs confined for eight weeks developed abnormal electrocardiograms (ECGs). Groups exercised daily on a treadmill or Se-supplemented groups retained virtually normal ECGs. Foetuses and subjects unreactive to the environment are space travellers lacking parasympathetic stimuli to the brain. Decreased movement-time deprives the brain receptors of the stimulus induced by gravity.

Pathophysiology of motor fluctuations in Parkinson's disease.

Loss of dopamine neurons in Parkinson's disease (PD) initiates a complex stream of effects that results in the development of tremor, bradykinesia, and rigidity. While levodopa remains the most effective drug for the symptomatic treatment of PD, its chronic administration is associated with the development of motor fluctuations and dyskinesias. The risk of developing motor fluctuations has been linked to disease severity, dosage of levodopa, and the age of the patient. A recent body of preclinical data has demonstrated that alterations in dopaminergic tone as well as in treatment patterns results in cellular adaptations, including alterations in gene expression. This body of preclinical data suggests that nonphysiological, pulsatile stimulation of dopamine receptors induces the development of motor fluctuations and dyskinesias and raises the possibility that nonpulsatile stimulation of dopamine receptors (continuous dopaminergic stimulation) might induce fewer fluctuations. We discuss the theory of continuous dopaminergic stimulation and its implications for the management of motor fluctuations in patients with advanced and early PD.

Progression of Parkinson's disease following thalamic deep brain stimulation for tremor.

We assessed the long-term effect of thalamic deep brain stimulation (DBS) on motor symptoms and progression of Parkinson's disease (PD) in PD patients treated for resting and postural/action tremor. Thalamic DBS was performed in 17 patients with treatment-resistant resting and postural/action tremor. Nine patients were available for follow-up examination a mean of 5.5 years after surgery. Three had tremor-dominant PD. DBS produced marked improvement in resting and postural/action tremor in target upper extremity in all 9 patients, which persisted unchanged at the time of the last follow-up visit 5.5 years after surgery. PD severity with DBS 'on' and 'off' 1 year after surgery was compared to PD severity at the last follow-up visit using UPDRS (Unified Parkinson's Disease Rating Scale) III motor scores and individual motor item subscores. Patients were tested while on medication. There was no significant worsening of tremor, rigidity, speech, postural stability, gait, or axial bradykinesia with DBS either on or off at the last follow-up visit compared to the 12-month visit. UPDRS III motor scores were unchanged. However, global assessment of PD progression and increased mean L-dopa dose and L-dopa equivalent daily dose at the time of last follow-up visit indicated that a progression of PD had occurred.

Phosphate deposition during and after hypokinesia in phosphate supplemented and unsupplemented rats.

The objective of this study was to show that prolonged restriction of motor activity (hypokinesia) could reduce phosphate (P) deposition and contribute to P loss with tissue P depletion. To this end, measurements were made of tissue P content, P absorption, plasma P levels, urinary and fecal P excretion of rats during and after hypokinesia (HK) and daily phosphate supplementation. Studies were conducted on male Wistar rats during a pre-hypokinetic period, a hypokinetic period and a post-hypokinetic period. All rats were equally divided into four groups: unsupplemented vivarium control rats (UVCR), unsupplemented hypokinetic rats (UHKR), supplemented vivarium control rats (SVCR) and supplemented hypokinetic rats (SHKR). Bone and muscle P content, plasma intact parathyroid hormone (iPTH) levels, P absorption, plasma P levels and urinary and fecal P excretion did not change in SVCR and UVCR compared with their pre-HK values. During HK, plasma P levels, urinary and fecal P excretion increased significantly (p<0.05) while muscle and bone P content, P absorption and plasma iPTH levels decreased significantly (p<0.05) in SHKR and UHKR compared with their pre-HK values and the values in their respective vivarium controls (SVCR and UVCR). During the initial 9-days of post-HK, plasma, urinary and fecal P levels decreased significantly (p<0.05), and plasma iPTH levels, muscle and bone P levels remained significantly (p<0.05) depressed in hypokinetic rats compared with their pre-HK values and the values in their respective vivarium control rats. By the 15th day, these values approached the control values. During HK and post-HK, changes in P absorption, plasma iPTH levels, and P levels in muscle, bone, plasma, urine and feces were significantly (p<0.05) greater in SHKR than in UHKR. Decreased tissue P content with increased P loss in animals receiving and not receiving P supplementation demonstrates decreased P deposition during HK. Higher P excretion with lower tissue content in SHKR and UHKR demonstrates that P deposition is decreased more with P supplementation than without. Because SHKR with a lower tissue P content showed higher P excretion than UHKR it was concluded that the risk of decreased P deposition with greater tissue P depletion is inversely related to P intake, that is, the higher the P intake the greater the risk for decreased P deposition and the greater tissue P depletion. It was shown that P (regardless of the intensity of its tissue depletion) is lost during HK unless factors contributing to the decreased P deposition are partially or totally reversed. It was concluded that dissociation between (decreased) tissue P content and (increased) P uptake indicates decreased P (absorption and) deposition as the main mechanisms of tissue P depletion during prolonged HK.

How do parkinsonian signs return after discontinuation of subthalamic DBS?

OBJECTIVE: To study the reappearance of the clinical signs of PD when subthalamic nucleus (STN) deep brain stimulation (DBS) was turned off. METHOD: The authors studied 35 patients treated with STN DBS 6.7 +/- 3.3 months (mean +/- SD) after implantation. All were clinically improved. Twenty-four had not required any antiparkinsonian medication for many months and 11 were in "practically defined off" conditions when studied. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were assessed at baseline and 5, 15, 30, 60, 90, 120, 150, 180, and 240 minutes after switching off STN DBS. RESULTS: A sequential pattern of return of parkinsonian signs was observed, with a fast worsening of tremor within minutes, followed by a smoother, slower worsening of bradykinesia and rigidity over half an hour to an hour, and finally a slow and steady worsening of axial signs over 3 to 4 hours. Ninety percent of the UPDRS motor score worsening was reached after 2 hours. When switching STN DBS "on" again, all motor UPDRS subscores improved with a similar pattern, but faster than their rate of worsening, especially for axial signs. CONCLUSIONS: STN DBS may act by different mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is needed to estimate the clinical effect of stimulation.

[Comparative efficiency of correction of unfavorable effects of hypokinesia by compression of veins of lower extremities and local thermovasodilatation]. / Sravnitel'naia otsenka éffektivnosti korrektsii neblagopriiatnykh éffektov gipokinezii metodami kompressii ven nizhnikh konechnostei i lokal'noi termovazodilatatsii.

As a result of the trials it was established that occlusion of the veins in the lower limbs made by means of "Pneumatic" suit under the pressure 60 mmHg in the cuffs is as effective as local thermovasodilation in the area of feet, crura and thighs with submaximal intensity in terms of protective redistribution of blood in experimental hypokinesia. These methods can be used for correction of negative symptoms of hypokinesia. Occlusion of the veins is less effective than local thermotherapy in normalization of subjective assessment of general condition, activity, mood and reactive-situational anxiety.

Intermuscular coherence in Parkinson's disease: relationship to bradykinesia.

We hypothesised that bradykinesia may be partly due to the failure of the corticomuscular system to engage in high frequency oscillatory activity in Parkinson's disease (PD). In healthy subjects such oscillations are evident in coherence between active muscles at 15--30 Hz. We therefore investigated the effects of therapeutic stimulation of the basal ganglia on this coherence and related it to changes in bradykinesia in the contralateral arm. Increases in coherence at 15--30 Hz and improvements in bradykinesia upon stimulation were correlated (r = 0.564, p < 0.001). This suggests that the basal ganglia modulate oscillatory activity in the corticomuscular system and that impairment of the motor system's ability to engage in synchronised oscillations at high frequency may contribute to bradykinesia in PD.