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

Abstract

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.