Muthuraman

Gait ataxia in essential tremor is differentially modulated by thalamic stimulation

Patients with advanced stages of essential tremor frequently exhibit tandem gait ataxia with impaired balance control and imprecise foot placement, resembling patients with a cerebellar deficit. Thalamic deep brain stimulation, a surgical therapy for otherwise intractable cases, has been shown to improve tremor, but its impact on cerebellar-like gait difficulties remains to be elucidated. Eleven patients affected by essential tremor (five females; age 69.8 ± 3.9 years; disease duration 24.4 ± 11.2 years; follow-up after surgery 24.7 ± 20.3 months) were evaluated during the following conditions: stimulation off, stimulation on and supra-therapeutic stimulation. Ten age-matched healthy controls served as the comparison group. Locomotion by patients and controls was assessed with (i) overground gait and tandem gait; (ii) balance-assisted treadmill tandem gait and (iii) unassisted treadmill gait. The two treadmill paradigms were kinematically analysed using a 3D opto-electronic motion analysis system. Established clinical and kinesiological measures of ataxia were computed. During stimulation off, the patients exhibited ataxia in all assessment paradigms, which improved during stimulation on and worsened again during supra-therapeutic stimulation. During over ground tandem gait, patients had more missteps and slower gait velocities during stimulation off and supra-therapeutic stimulation than during stimulation on. During balance-assisted tandem gait, stimulation on reduced the temporospatial variability in foot trajectories to nearly normal values, while highly variable (ataxic) foot trajectories were observed during stimulation off and supra-therapeutic stimulation. During unassisted treadmill gait, stimulation on improved gait stability compared with stimulation off and supra-therapeutic stimulation, as demonstrated by increased gait velocity and ankle rotation. These improvements in ataxia were not a function of reduced tremor in the lower limbs or torso. In conclusion, we demonstrate the impact of thalamic stimulation on gait ataxia in patients with essential tremor with improvement by stimulation on and deterioration by supra-therapeutic stimulation, despite continued control of tremor. Thus, cerebellar dysfunction in these patients can be differentially modulated with optimal versus supra-therapeutic stimulation. The cerebellar movement disorder of essential tremor is due to a typical cerebellar deficit, not to trembling extremities. We hypothesize that deep brain stimulation affects two major regulating circuits: the cortico-thalamo-cortical loop for tremor reduction and the cerebello-thalamo-cortical pathway for ataxia reduction (stimulation on) and ataxia induction (supra-therapeutic stimulation).

Oscillating central motor networks in pathological tremors and voluntary movements. What makes the difference

Parkinsonian tremor (PD), essential tremor (ET) and voluntarily mimicked tremor represent fundamentally different motor phenomena, yet, magnetoencephalographic and imaging data suggest their origin in the same motor centers of the brain. Using EEG-EMG coherence and coherent source analysis we found a different pattern of corticomuscular delays, time courses and central representations for the basic and double tremor frequencies typical for PD suggesting a wider range defective oscillatory activity. For the basic tremor frequency similar central representations in primary sensorimotor, prefrontal/premotor and diencephalic (e.g. thalamic) areas were reproduced for all three tremors. But renormalized partial directed coherence of the spatially filtered (source) signals revealed a mainly unidirectional flow of information from the diencephalon to cortex in voluntary tremor, e.g. a thalamocortical relay, as opposed to a bidirectional subcortico-cortical flow in PD and ET promoting uncontrollable, e.g. thalamocortical, loop oscillations. Our results help to understand why pathological tremors although originating from the physiological motor network are not under voluntary control and they may contribute to the solution of the puzzle why high frequency thalamic stimulation has a selective effect on pathological tremor leaving voluntary movement performance almost unaltered.

Representation and propagation of epileptic activity in absences and generalized photoparoxysmal responses.

Although functional imaging studies described networks associated with generalized epileptic activity, propagation patterns within these networks are not clear. In this study, electroencephalogram (EEG)‐based coherent source imaging dynamic imaging of coherent sources (DICS) was applied to different types of generalized epileptiform discharges, namely absence seizures (10 patients) and photoparoxysmal responses (PPR) (eight patients) to describe the representation and propagation of these discharges in the brain. The results of electrical source imaging were compared to EEG‐functional magnetic resonance imaging (fMRI) which had been obtained from the same data sets of simultaneous EEG and fMRI recordings. Similar networks were described by DICS and fMRI: (1) absence seizures were associated with thalamic involvement in all patients. Concordant results were also found for brain areas of the default mode network and the occipital cortex. (2) Both DICS and fMRI identified the occipital, parietal, and the frontal cortex in a network associated with PPR. (3) However, only when PPR preceded a generalized tonic‐clonic seizure, the thalamus was involved in the generation of PPR as shown by both imaging techniques. Partial directed coherence suggested that during absences, the thalamus acts as a pacemaker while PPR could be explained by a cortical propagation from the occipital cortex via the parietal cortex to the frontal cortex. In conclusion, the electrical source imaging is not only able to describe similar neuronal networks as revealed by fMRI, including deep sources of neuronal activity such as the thalamus, but also demonstrates interactions interactions within these networks and sheds light on pathogenetic mechanisms of absence seizures and PPR. Hum Brain Mapp, 2013.

Cortical correlates of the basic and first harmonic frequency of Parkinsonian tremor

OBJECTIVE It has been hypothesized that the basic and first harmonic frequency of Parkinsonian tremor are somewhat independent oscillations the biological basis of which remains unclear. METHODS We recorded 64-channel EEG in parallel with EMG of the forearm muscles most affected by rest tremor in 21 PD patients. EMG power spectrum, corticomuscular coherence spectra and EEG power spectra for each EEG electrode were calculated. The dynamics of the coherence and relative EMG and EEG power at the basic (tremor) frequency were calculated by a sliding, overlapping window analysis. Corticomuscular delays and direction of interaction were analysed by the maximizing coherence method for narrow band signals. RESULTS The contralateral EEG electrodes with maximal coherence were different for the basic and first harmonic frequency. The dynamical coherence curves showed non-parallel time courses for the two frequencies. The mean EEG-EMG and EMG-EEG delays were all around 15-20ms but significantly longer for the first harmonic than for the basic frequency. CONCLUSIONS Our data indicate different cortical representations and corticomuscular interaction of the basic and first harmonic frequencies of Parkinsonian tremor. SIGNIFICANCE Separate central generators seem to contribute to the tremor via different pathways. Further studies on this complex tremor network are warranted.

The central oscillatory network of orthostatic tremor

Orthostatic tremor (OT) is a movement disorder of the legs and trunk that is present in the standing position but typically absent when sitting. The pathological central network involved in orthostatic tremor is still unknown. In this study we analyzed 15 patients with simultaneous high‐resolution electroencephalography and electromyography recording to assess corticomuscular coherence. In 1 patient we were able to simultaneously record the local field potential in the ventrolateral thalamus and electroencephalography. Dynamic imaging of coherent source analysis was used to find the sources in the brain that are coherent with the peripheral tremor signal. When standing, the network for the tremor frequency consisted of unilateral activation in the primary motor leg area, supplementary motor area, primary sensory cortex, two prefrontal/premotor sources, thalamus, and cerebellum for the whole 30‐second segment recorded. The source coherence dynamics for the primary leg area and the thalamic source signals with the tibialis anterior muscle showed that they were highly coherent for the whole 30 seconds for the contralateral side but markedly decreased after 15 seconds for the ipsilateral side. The source signal and the recorded thalamus signal followed the same time frequency dynamics of coherence in 1 patient. The corticomuscular interaction in OT follows a consistent pattern with an initially bilateral pattern and then a segregated unilateral pattern after 15 seconds. This may add to the feeling of unsteadiness. It also makes the thalamus unlikely as the main source of orthostatic tremor.

A new diagnostic test to distinguish tremulous Parkinson's disease from advanced essential tremor

Clinical distinction between advanced essential tremor and tremulous Parkinsons disease can be difficult.

Developmental changes of functional and directed resting-state connectivities associated with neuronal oscillations in EEG.

Several studies demonstrated that resting-state EEG power differs tremendously between school-aged children and adults. Low-frequency oscillations (delta and theta, <7 Hz) are dominant in children but become less prominent in the adult brain, where higher-frequency alpha oscillations (8-12 Hz) dominate the mature brain rhythm. However, this assessment of developmental effects with EEG power mapping is restricted to the scalp level and blind to the information flow between brain regions, thus limiting insights about brain development. In contrast dynamic source synchronization provides a tool to study inter-regional directionality on the cortical and sub-cortical source level. In this study we investigated functional and directed connectivities (information flow) with renormalized partial directed coherence during resting state EEG (eyes open and eyes closed) recordings in 17 school-aged children and 17 young adults. First, we found higher spectral mean source power in children relative to adults, irrespective of the examined frequency band and resting state. We further found that coherence values were stronger in adults compared to children in all frequency bands. The directed within-group coherence analysis indicated information flow from frontal to parietal sources in children, while information flow from parietal to frontal was observed in adults. In addition, significant thalamocortical connectivity was unidirectional (i.e., outflow to cortical regions) in adults, but bidirectional in children. Group comparison confirmed the results of the single subject analyses for both functional and directed connectivities. Our results suggest that both functional and directed connectivities are sensitive to brain maturation as the distribution and directionality of functional connections differ between the developing and adult brains.

Postural control and freezing of gait in Parkinson's disease

INTRODUCTION The relationship between freezing of gait (FOG) and postural instability in Parkinsons disease (PD) is unclear. We analyzed the impact of FOG on postural control. METHODS 31 PD patients with FOG (PD+FOG), 27 PD patients without FOG (PD-FOG) and 22 healthy control (HC) were assessed in the ON state. Postural control was measured with the Fullerton Advanced Balance (FAB) scale and with center of pressure (COP) analysis during quiet stance and maximal voluntary forward/backward leaning. RESULTS The groups were balanced concerning age, disease duration and disease severity. PD+FOG performed significantly worse in the FAB scale (21.8 ± 5.8) compared to PD-FOG (25.6 ± 5.0) and HC (34.9 ± 2.4) (mean ± SD, p < 0.01). PD+FOG had impaired ability to voluntary lean forward, difficulties to stand on foam with eyes closed and reduced limits of stability compared to PD-FOG (p < 0.05). During quiet stance the average anterior-posterior COP position was significantly displaced towards posterior in PD+FOG in comparison to PD-FOG and HC (p < 0.05). The COP position correlated with severity of FOG (p < 0.01). PD+FOG and PD-FOG did not differ in average COP sway excursion, sway velocity, sway regularity and postural control asymmetry. CONCLUSIONS PD+FOG have reduced postural control compared to PD-FOG and HC. Our results show a relationship between the anterior-posterior COP position during quiet stance and FOG. The COP shift towards posterior in PD+FOG leads to a restricted precondition to generate forward progression during gait initiation. This may contribute to the occurrence of FOG or might be a compensatory strategy to avoid forward falls.

Imaging coherent sources of tremor related EEG activity in patients with Parkinson's disease

The cortical sources of both the basic and first “harmonic” frequency of Parkinsonian tremor are addressed in this paper. The power and coherence was estimated using the multitaper method for EEG and EMG data from 6 Parkinsonian patients with a classical rest tremor. The Dynamic Imaging of Coherent Sources (DICS) was used to find the coherent sources in the brain. Before hand this method was validated for the application to the EEG by showing in 3 normal subjects that rhythmic stimuli (1–5Hz) to the median nerve leads to almost identical coherent sources for the basic and first harmonic frequency in the contralateral sensorimotor cortex which is the biologically plausible result. In all the Parkinson patients the corticomuscular coherence was also present in the basic and the first harmonic frequency of the tremor. However, the source for the basic frequency was close to the frontal midline and the first harmonic frequency was in the region of premotor and sensory motor cortex on the contralateral side for all the patients. Thus the generation of these two oscillations involves different cortical areas and possibly follows different pathways to the periphery.

The central oscillatory network of essential tremor

The responsible pathological mechanisms of essential tremor are not yet clear. In order to understand the mechanisms of the central network its sources need to be found. The cortical sources of both the basic and first “harmonic” frequency of essential tremor are addressed in this paper. The power and coherence were estimated using the multitaper method for EEG and EMG data from 6 essential tremor patients. The Dynamic Imaging of Coherent Sources (DICS) was used to find the coherent sources in the brain. Before hand this method was validated for the application of finding multiple sources for the same oscillation in the brain by using two model simulations which indicated the accuracy of the method. In all the essential tremor patients the corticomuscular coherence was also present in the basic and the first harmonic frequency of the tremor. The source for the basic frequency and the first harmonic frequency was in the region of primary sensory motor cortex, prefrontal and in the diencephalon on the contralateral side for all the patients. Thus the generation of these two oscillations involves the same cortical areas and indicates the oscillation at double the tremor frequency is a harmonic of the basic tremor frequency.