Kinematic analysis of thalamic versus subthalamic neurostimulation in postural and intention tremor.

Deep brain stimulation of the thalamus (thalamic DBS) is an established therapy for medically intractable essential tremor and tremor caused by multiple sclerosis. In both disorders, motor disability results from complex interaction between kinetic tremor and accompanying ataxia with voluntary movements. In clinical studies, the efficacy of thalamic DBS has been thoroughly assessed. However, the optimal anatomical target structure for neurostimulation is still debated and has never been analysed in conjunction with objective measurements of the different aspects of motor impairment. In 10 essential tremor and 11 multiple sclerosis patients, we analysed the effect of thalamic DBS through each contact of the quadripolar electrode on the contralateral tremor rating scale, accelerometry and kinematic measures of reach-to-grasp-movements. These measures were correlated with the anatomical position of the stimulating electrode in stereotactic space and in relation to nuclear boundaries derived from intraoperative microrecording. We found a significant impact of the stereotactic z-coordinate of stimulation contacts on the TRS, accelerometry total power and spatial deviation in the deceleration and target period of reach-to-grasp-movements. Most effective contacts clustered within the subthalamic area (STA) covering the posterior Zona incerta and prelemniscal radiation. Stimulation within this region led to a mean reduction of the lateralized tremor rating scale by 15.8 points which was significantly superior to stimulation within the thalamus (P < 0.05, student's t-test). STA stimulation resulted in reduction of the accelerometry total power by 99%, whereas stimulation at the ventral thalamic border (68%) or within the thalamus proper (2.5%) was significantly less effective (P < 0.01). Concomitantly, STA stimulation led to a significantly higher increase of tremor frequency and decrease in EMG synchronization compared to stimulation within the thalamus proper (P < 0.001). In reach-to-grasp movements, STA stimulation reduced the spatial variability of the movement path in the deceleration period by 28.9% and in the target period by 58.4%, whereas stimulation within the thalamus was again significantly less effective (P < 0.05), with a reduction in the deceleration period between 6.5 and 21.8% and in the target period between 1.2 and 11.3%. An analysis of the nuclear boundaries from intraoperative microrecording confirmed the anatomical impression that most effective electrodes were located within the STA. Our data demonstrate a profound effect of deep brain stimulation of the thalamic region on tremor and ataxia in essential tremor and tremor caused by multiple sclerosis. The better efficacy of stimulation within the STA compared to thalamus proper favours the concept of a modulation of cerebello-thalamic projections underlying the improvement of these symptoms.

Hand coordination following capsular stroke.

Motor outcome following stroke of the internal capsule is variable and its determinants are poorly understood. While many patients fully regain their abilities, recovery of motor functions remains incomplete in others. We analysed functional motor tasks of the upper limb to determine the pattern of focal disability after a small infarct of the internal capsule ('pure motor stroke') in the chronic stage (mean 2.4 years after stroke) with kinematic recordings of a reaching-to-grasp movement, with a quantitative analysis of the precision grip, and with clinical rating scales. The location of the lesions within the posterior limb of the internal capsule (PLIC) in 18 patients was determined from neuroimages obtained in the acute stage (5-20 days after the insult). Involvement of the PLIC was assessed at the level of the basal ganglia, approximately 8 mm above the anterior commissure-posterior commissure level. The distance between the posterior edge of the internal capsule and the centre of gravity of the lesion was determined. Chronic disabilities affected dextrous movements, while paresis was mild and sensitivity for light touch or passive finger flexion was almost normal. For both the reaching-to-grasp movement and the precision grip paradigm, the slowness of movement or force development was confined to the phases when grip formation and stabilization occur, while the onset of hand transport and of the vertical lifting force were not delayed. Grip forces were increased. We observed a close correlation between posterior location within the PLIC and the altered measures of timing and precision grip force. The more posterior the acute lesion was located within the PLIC, the more pronounced were the chronic motor deficits, as seen both in the quantitative measures and in the rating scales. The present study demonstrates for the first time that the amount and quality of chronic motor deficits of dextrous movements are related to a simple measure drawn from routine neuroimaging in the acute stage in patients with capsular stroke. The poor motor outcome in lesions involving the most posterior parts of the PLIC could be due to the condensed organization of corticofugal projections and the density of pyramidal fibres from the primary motor cortex in this subsector. Even small infarcts of this strategic area can disrupt many of the projections from the motor cortices and could thereby limit recovery strategies between homolateral motor representations.

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.

Recovery of the precision grip in children after traumatic brain injury.

OBJECTIVE: To identify quantitative parameters that are sensitive enough to detect impairments and improvements of grasping in children after traumatic brain injury (TBI) by analyzing the isometric fingertip forces of a precision grip-lift task. DESIGN: Follow-up and case-control study. SETTING: Tertiary pediatric trauma rehabilitation center in Germany. PARTICIPANTS: Thirteen children (age range, 5-14 y) with moderate or severe TBI. Trauma severity was assessed with the Glasgow Coma Scale (score range, 3-9) and the Injury Severity Score (range, 16-66 points). Control data were obtained from 13 age- and gender-matched healthy children. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Children were examined 3 times (t0, t1, t2). The first date of examination (t0) was defined by the Barthel Index (part B, >20 points). Reexaminations followed after 1 (t1) and 5 (t2) months of inpatient rehabilitation. Quantitative measures included 3 grip-force parameters, 2 load force parameters, 1 parameter of the coordination between grip force and load force, and 3 timing parameters in a precision grip-lift task. Clinical improvements and recovery of activities of daily living were described with the Barthel Index (qualitative measure). RESULTS: Peak grip force, maximum negative load force, grip force in the static phase and its standard deviation, and grip-force/load-force ratio at maximum grip force showed significant improvements during the observation period (5 mo). Also, the preparation phase and preload duration, but not the load duration, changed significantly. CONCLUSIONS: Impairments and the recovery of grasping in children after TBI can be objectified with quantitative analyses of the precision grip. Several grip-force and timing parameters were sensitive for the description of restitution processes.

Force overflow and levodopa-induced dyskinesias in Parkinson's disease.

We assessed force coordination of the hand in Parkinson's disease and its relationship to motor complications of levodopa therapy, particularly to levodopa-induced dyskinesias (LID). We studied two groups of Parkinson's disease patients with (Parkinson's disease + LID, n = 23) and without levodopa-induced dyskinesias (Parkinson's disease - LID, n = 10), and age-matched healthy controls. The motor score of the Unified Parkinson's Disease Rating Scale, a dyskinesia score and force in a grip-lift paradigm were assessed ON and OFF levodopa. A pathological increase of forces was seen in ON-state in Parkinson's disease + LID only. In Parkinson's disease + LID, the force involved in pressing down the object before lifting was significantly increased by levodopa (by 61%, P < 0.05). An overshooting of peak grip force by 51% (P < 0.05) and of static grip force by 45% (P < 0.01) was observed in the ON- compared with the OFF-drug condition. In contrast, no excessive force was found in Parkinson's disease - LID. Peak grip force in ON-state was 140% (P < 0.05) higher in Parkinson's disease + LID than in Parkinson's disease - LID, while static grip force was increased by 138% (P < 0.01) between groups. Severity of peak-dose dyskinesias was strongly correlated with grip force in ON-state (r = 0.79 with peak force, P < 0.01). No correlation was observed between forces and the motor score as well as with the daily dose of dopaminergic medication. Force excess was only observed in patients with LID and motor fluctuations. A close relationship was seen between the overshooting of forces and dyskinesias in the ON-drug condition. We postulate that both LID and grip force excess share common pathophysiological mechanisms related to motor fluctuations.

Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces akinesia in Parkinson's disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L-dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS-items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L-dopa test than in the pure STN-DBS condition. Other akinesia items and the time for build-up of lifting force were equally improved in both conditions. This suggests that routine STN-DBS might not be equally effective on all aspects of fine motor functions.

Is the rhythm of physiological tremor involved in cortico-cortical interactions?

The function of low-frequency oscillations as correlates of physiological tremor in supplementary motor area (SMA) and M1 remains unclear. In epicortical recordings from M1 and SMA and surface electromyographic (EMG) recordings in an epileptic patient we found reproducibly significant coherence between all three recording sites in the 6- to 15-Hz band. The partial coherence between SMA and muscle, however, was not significant. There was a constant phase shift between SMA and M1 indicating synchronized activity. We conclude that the cortical correlates of physiological tremor may be involved in linking different cortical motor centers and might therefore play a role in cortical motor planning.

Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus.

Deep-brain stimulation of the subthalamic nucleus appears to reduce levodopa-induced dyskinesias, but whether this effect is caused by the reduction of the total levodopa ingestion or represents a direct effect on the motor system is unknown. Precision grip force of grasping movements and levodopa-induced dyskinesias was analyzed in 10 parkinsonian patients before and after 3 months of deep-brain stimulation of the subthalamic nucleus. Peak grip force was abnormally increased before surgery in the off-drug state and, particularly, in the on-drug state (sensitization). This grip force upregulation normalized with chronic deep-brain stimulation in both conditions (desensitization). Peak-dose dyskinesias also improved, and off-dystonia was completely abolished. Mean dosage of dopaminergic drugs was reduced, but force overflow and dyskinesias were equally improved in 2 patients without a reduction. Despite the same single levodopa test dose, force excess and levodopa-induced dyskinesias were drastically reduced after 3 months of deep-brain stimulation of the subthalamic nucleus. This indicates that direct effects of deep-brain stimulation of the subthalamic nucleus on levodopa-induced dyskinesias are likely to occur. Grip force overflow is a promising parameter to study the desensitizing effect of chronic deep-brain stimulation on levodopa-induced dyskinesias.

Corticomuscular coherence in the 6-15 Hz band: is the cortex involved in the generation of physiologic tremor?

Physiologic tremor (PT) consists of a peripheral mechanical oscillation at the limbs' resonance frequency and an independent central component in the 6-15 Hz band. This central component has mainly been attributed to spinal interneuronal systems or subcortical oscillators but more recently also to cortical rhythms. We recorded PT electromyographically and accelerometrically from different parts of the arm in parallel to epicortical recordings from grid electrodes covering the primary sensorimotor areas of the contralateral cortex in six epileptic patients. Previous bipolar electrical stimulation of the cortical electrodes resulted in a somatotopic map of the primary cortex underlying the grid. Spectral and cross-spectral analysis including coherence spectra between epicortical electrodes and EMG and the corresponding phase spectra were performed off-line. We found significant corticomuscular coherence in the 6-15 Hz range in four out of the six patients. This coherence was focal on the cortex and it was distributed somatotopically mainly within the primary motor area. The frequency band of the coherence mostly corresponding to the EMG frequency remained stable with added inertia, while the main accelerometric frequency was clearly reduced following the resonance frequency. The phase spectra between electrocorticogram (ECoG) and EMG showed a clear delay between cortex and muscle in two of the patients, which was compatible with conduction in fast pyramidal pathways. These findings indicate that the 6-15 Hz coherence between cortex and EMG reflects a corticomuscular transmission of the oscillation rather than peripheral feedback to the cortex. We conclude that cortical networks are involved in the generation of physiologic tremor.