Activity In Dystonia Research Articles

Multifractal characteristics of neuronal activity of the <i> globus pallidus </i> in patients with dystonia

Dystonia is a movement disorder characterized by involuntary muscle contractions resulting in anomalous postures, often accompanied by dystonic tremors. Among the indicative dystonic postures is an involuntary tonic tilt or rotation of the head. Currently, the etiology and pathogenesis of the disease remain theories. Currently, only low-frequency (theta-alpha) oscillations in the globus pallidus are regarded as the possible biomarker of pathological activity in dystonia. In many patients with dystonia, the absence of rhythmic neuronal activity in the basal ganglia renders this biomarker unusable for surgical treatment of the disease. Additionally, the mechanisms underlying the rearrangement of temporary patterns of neural activity that result in pathological symptoms remain unclear. We propose that the appearance of these pathological rhythms is associated with the reduction of dynamic complexity in the pattern of neural activity within the globus pallidus. We aim to use multifractal analysis in this study to evaluate changes in the globus pallidus neural activity pattern’s dynamic complexity and their correlation with the clinical manifestations of dystonia. The study examined the electrical activity of the globus pallidus in 23 patients receiving deep brain stimulation (DBS) treatment. We used the microelectrode registration technique and local field potential (LFP) registration during intraoperative neuron monitoring to precisely identify the specific locations of the external and internal segments of the globus pallidus (GPe and GPi). In four patients, an additional postoperative recording of local field potentials (LFP) was conducted while performing DBS and vibrational impact on the neck muscles. A neurologist evaluated the patients to determine the severity of the disease using the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS). The LEAD DBS software package was employed for postoperative reconstruction of the DBS stimulating electrode positions and for simulating the optimal stimulation zone, selected by the neurologist (i.e., volume of tissue activated, VTA). Subsequently, we identified the region that presented the most significant variation in multifractal spectrum parameters following DBS to understand its correlation with the optimal VTA. A total of 745 local potential records were analyzed, with 433 in GPe and 312 in GPi. The severity of dystonia was found to be correlated with the parameters of the multifractal spectrum (rho: –0.5630882, p=0.005149 for GPe and rho: –0.5180609, p=0.01133 for GPi). Moreover, as the dystonia severity increased along the BFMDRS scale, the multifractal spectrum became narrower and more asymmetric. In post-surgery recordings, we observed changes in the shape of the multifractal spectrum during DBS stimulation or vibration. In particular, when exposed, the multifractal spectrum significantly widened, and its symmetry was restored. We identified the region with the greatest alteration in the width of the multifractal spectrum following DBS and discovered that this region considerably intersected or fully matched the neurologist’s chosen zone for optimal DBS stimulation. We demonstrated that multifractal analysis can serve as an ancillary approach to evaluate the extent of proprioceptive feedback impairment and as a biomarker of dystonia. The noteworthy and substantial correlation with dystonia severity underscores the considerable potential of multifractal spectrum features as a biomarker of dystonia. Additionally, the overlapping areas with the most significant DBS impact and the widest variation in the multifractal spectrum in DBS can be used as a tool for identifying the most favorable region for DBS stimulation.

Globus pallidus internus activity increases during voluntary movement in children with dystonia

The rate model of basal ganglia function predicts that muscle activity in dystonia is due to disinhibition of thalamus resulting from decreased inhibitory input from pallidum. We seek to test this hypothesis in children with dyskinetic cerebral palsy undergoing evaluation for deep brain stimulation (DBS) to analyze movement-related activity in different brain regions. The results revealed prominent beta-band frequency peaks in the globus pallidus interna (GPi), ventral oralis anterior/posterior (VoaVop) subnuclei of the thalamus, and subthalamic nucleus (STN) during movement but not at rest. Connectivity analysis indicated stronger coupling between STN-VoaVop and STN-GPi compared to GPi-STN. These findings contradict the hypothesis of decreased thalamic inhibition in dystonia, suggesting that abnormal patterns of inhibition and disinhibition, rather than reduced GPi activity, contribute to the disorder. Additionally, the study implies that correcting abnormalities in GPi function may explain the effectiveness of DBS targeting the STN and GPi in treating dystonia.

Pallidal and Cortical Oscillations in Freely Moving Patients With Dystonia

ObjectivesTo evaluate the correlation between the pallidal local field potentials (LFPs) activity and the cortical oscillations (at rest and during several motor tasks) in two freely moving patients with generalized dystonia and pallidal deep brain stimulation (DBS). Materials and MethodsTwo women with isolated generalized dystonia were selected for bilateral globus pallidus internus (GPi) DBS. After the electrodes' implantation, cortical activity was recorded by a portable electroencephalography (EEG) system simultaneously with GPi LFPs activity, during several motor tasks, gait, and rest condition. Recordings were not performed during stimulation. EEG and LFPs signals relative to each specific movement were coupled together and grouped in neck/upper limbs movements and gait. Power spectral density (PSD), EEG-LFP coherence (through envelope of imaginary coherence operator), and 1/f exponent of LFP-PSD background were calculated. ResultsIn both patients, the pallidal LFPs PSD at rest was characterized by prominent 4–12 Hz activity. Voluntary movements increased activity in the theta (θ) band (4–7 Hz) compared to rest, in both LFPs and EEG signals. Gait induced a drastic raise of θ activity in both patients' pallidal activity, less marked for the EEG signal. A coherence peak within the 8–13 Hz range was found between pallidal LFPs and EEG recorded at rest. ConclusionsNeck/upper limbs voluntary movements and gait suppressed the GPi-LFPs—cortical-EEG coherence and differently impacted both EEG and LFPs low frequency activity. These findings suggest a selective modulation of the cortico-basal ganglia network activity in dystonia.

Motor Cortex Activation During Writing in Focal Upper-Limb Dystonia: An fNIRS Study

Background Functional imaging studies have associated dystonia with abnormal activation in motor and sensory brain regions. Commonly used techniques such as functional magnetic resonance imaging impose physical constraints, limiting the experimental paradigms. Functional near-infrared spectroscopy (fNIRS) offers a new noninvasive possibility for investigating cortical areas and the neural correlates of complex motor behaviors in unconstrained settings. Methods We compared the cortical brain activation of patients with focal upper-limb dystonia and controls during the writing task under naturalistic conditions using fNIRS. The primary motor cortex (M1), the primary somatosensory cortex (S1), and the supplementary motor area were chosen as regions of interest (ROIs) to assess differences in changes in both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) between groups. Results Group average activation maps revealed an expected pattern of contralateral recruitment of motor and somatosensory cortices in the control group and a more bilateral pattern of activation in the dystonia group. Between-group comparisons focused on specific ROIs revealed an increased activation of the contralateral M1 and S1 cortices and also of the ipsilateral M1 cortex in patients. Conclusions Overactivity of contralateral M1 and S1 in dystonia suggest a reduced specificity of the task-related cortical areas, whereas ipsilateral activation possibly indicates a primary disorder of the motor cortex or an endophenotypic pattern. To our knowledge, this is the first study using fNIRS to assess cortical activity in dystonia during the writing task under natural settings, outlining the potential of this technique for monitoring sensory and motor retraining in dystonia rehabilitation.

Task-related brain activity and functional connectivity in upper limb dystonia: a functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) study.

.Significance: Dystonia is a dynamic and complex disorder. Real-time analysis of brain activity during motor tasks may increase our knowledge on its pathophysiology. Functional near-infrared spectroscopy (fNIRS) is a noninvasive method that enables the measurement of cortical hemodynamic activity in unconstrained environments.Aim: We aimed to explore the feasibility of using fNIRS for the study of task-related brain activity in dystonia. Task-related functional magnetic resonance imaging (fMRI) and resting-state functional connectivity were also analyzed.Approach: Patients with idiopathic right-upper limb dystonia and controls were assessed through nonsimultaneous fMRI and fNIRS during a finger-tapping task. Seed-based connectivity analysis of resting-state fMRI was performed in both groups.Results: The fMRI results suggest nonspecific activation of the cerebellum and occipital lobe in dystonia patients during the finger-tapping task with the affected hand. Moreover, fNIRS data show lower activation in terms of oxyhemoglobin and total hemoglobin in the frontal, ipsilateral cortex, and somatosensory areas during this task. In dystonia, both fMRI and fNIRS data resulted in hypoactivation of the frontal cortex during finger tapping with both hands simultaneously. Resting-state functional connectivity analysis suggests that the cerebellar somatomotor network in dystonia has an increased correlation with the medial prefrontal cortex and the paracingulate gyrus.Conclusions: These data suggest that unbalanced activation of the cerebellum, somatosensory, and frontal cortical areas are associated with dystonia. To our knowledge, this is the first study using fNIRS to explore the pathophysiology of dystonia. We show that fNIRS and fMRI are complementary methods and highlight the potential of fNIRS for the study of dystonia and other movement disorders as it can overcome movement restrictions, enabling experiments in more naturalistic conditions.

Pallidal low-frequency activity in dystonia after cessation of long-term deep brain stimulation.

This study investigates the association between pallidal low-frequency activity and motor sign severity in dystonia after chronic deep brain stimulation for several months. Local field potentials were recorded in 9 dystonia patients at 5 timepoints (T1-T5) during an OFF-stimulation period of 5 to 7 hours in parallel with clinical assessment using Burke-Fahn-Marsden Dystonia Rating Scale. A linear mixed effects model was used to investigate the potential association of motor signs with local field potential activity in the low frequency (3-12 Hz) and beta range (13-30 Hz). A significant association of Burke-Fahn-Marsden Dystonia Rating Scale scores with low-frequency activity (3-12 Hz; b = 4.4; standard error = 1.5, degrees of freedom = 43, P = 0.006, 95% confidence interval, 1.3-7.5), but not beta activity (13-30 Hz) was revealed within participants across timepoints. Low-frequency activity is associated with dystonic motor sign severity, even months after chronic deep brain stimulation. Our findings corroborate the pathophysiological role of low-frequency activity in dystonia and highlight the potential utility as a biomarker for adaptive neuromodulation. © 2019 International Parkinson and Movement Disorder Society.

Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson’s disease

Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies.

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task‐related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta‐analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia‐related alterations in task‐related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task‐related increases or decreases in dystonia patients compared to healthy controls. The meta‐analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task‐related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task‐related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between‐group differences in task‐related activity were retrieved in a sub‐analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547–557, 2016. © 2015 Wiley Periodicals, Inc.

Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia—An fMRI‐TMS study

Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for noninvasive stimulation of the human cortex and can alter cortical excitability and associated behavior. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls. We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients with right-sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS-induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI). Before rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task-related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG. Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG-S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task.

Childhood onset generalised dystonia can be modelled by increased gain in the indirect basal ganglia pathway

Clinical experience suggests an important role of the indirect basal ganglia pathway in the genesis of childhood onset generalised dystonia, but it has been difficult to reconcile the increased muscle...

Abnormal cortical sensory activation in dystonia: an fMRI study.

Despite the obvious motor manifestations of focal dystonia, it is recognised that the sensory system plays an important role in this condition. This functional magnetic resonance imaging study examines the sensory representations of individual digits both within the subregions of the primary sensory cortex (SI) and in other nonprimary sensory areas. Patients with focal dystonia and controls were scanned during vibrotactile stimulation of both the index (digit 2) and little (digit 5) fingers of their dominant hand (which was the affected hand in all the dystonic subjects). The activation maps obtained were analysed for location, size, and magnitude of activation and three-dimensional (3-D) orientation of digit representations. Data from both groups were compared. There were significant differences in the average 3-D separation between the two digit representations in area 1 of SI between subject groups (9.6 +/- 1.2 mm for controls and 4.1 +/- 0.2 mm for dystonic subjects). There were also strong trends for reversed ordering of the representation of the two digits in both the secondary sensory cortex and posterior parietal area between the two groups. In addition, in dystonic subjects, there was significant under activation in the secondary somatosensory cortex (SII/area 40) for both digits and in the posterior parietal area for digit 5. These results indicate the presence of widespread activation abnormalities in the cortical sensory system in dystonia.

Bradykinesia in Parkinson's disease and cocontraction activity in dystonia are unlikely to be due to adaptive changes in the CNS

AbstractLatash & Anson's explanation of bradykinesia in patients with Parkinson's disease and cocontraction in dystonic patients is intriguing. However, the proposed adaptive changes in the central nervous system do not fit well with both clinical and experimental evidence of motor impairment in these patients. In particular, we question the explanation of: (1) the role of postural reactions and spatial accuracy in bradykinesia, (2) certain abnormalities during the execution of sequential and simultaneous movements, (3) the sudden changes in mobility (ON and OFF) of Parkinsonian patients, and (4) the meaning of reflex circuitry changes in dystonia.