Multifractal Characteristics of Pallidal Single Unit Activity in Patients with Dystonia

Statistically, dystonia is the third most common movement disorder. This disease is characterized by involuntary muscle contractions, dystonic tremors, and abnormal postures. To date, the most effective treatment for dystonia is neurosurgical implantation of electrodes for chronic stimulation of deep brain structures (DBS) in the internal segment of the globus pallidus (GPi). To improve the clinical effect, it is necessary to implant a DBS electrode into the zone of pathological activity, the patterns and parameters of which remain unknown. Currently, low-frequency (θ-α) oscillations in the globus pallidus are considered the only potential biomarker of pathological activity in dystonia. It also remains unclear what causes rearrangements in the temporal organization of patterns of neuronal activity, leading to the emergence of pathological symptoms. It's believed that the emergence of such pathological rhythms is associated with the loss of the dynamic complexity of the pattern of neuronal activity in the globus pallidus. This study proposes to use multifractal analysis to assess the relationship between changes in dynamic complexity of single-unit pallidal neural activity and clinical manifestations of dystonia. Microelectrode recordings of single-unit activity were performed from the internal (GPi) and external (GPe) segments of the globus pallidus in 39 patients with dystonia. The multifractal spectra of single-unit activity was calculated using the detrended fluctuation analysis method. The relationship between the parameters of this spectrum and the clinical manifestations of dystonia were assessed. It was shown that a correlation between the multifractal characteristics of pallidal activity and the severity of dystonia is significant only for the pause pattern of the activity of neurons in the internal segment of the globus pallidus. As the severity of dystonia increased, there was a decrease in the width of the multifractal spectrum and an increase in its asymmetry. In addition, it has been revealed that as the microelectrode is immersed deep into the globus pallidus and approaches the intended target point for implantation of the stimulating DBS electrode, the tendency towards asymmetry increases. The clinical effect of DBS on the BFMDRS (The Burke-Fahn-Marsden Dystonia Rating Scale) severity was correlated with the asymmetry of the multifractal spectrum of activity of pallidal neurons located in the stimulation area. It was also demonstrated that clinical effect on dystonic tremor was significantly correlated with multifractal spectral parameters, which reflect degree of anti-correlation in the signal. These parameters of the multifractal spectrum were also correlated with the intensity of low-frequency (3-8 Hz) oscillations. These results imply that a decrease in the degree of anticorrelation of the neural activity pattern and the appearance of pathological θ-oscillations, as a consequence of these changes in the temporal organization of neural patterns, may be associated with phasic symptoms of dystonia, such as dystonic tremor. At the same time, the asymmetry of the multifractal spectrum, expressed in its shift towards insensitivity to large «corrective» fluctuations in head position and to the full influence of «fixing» fluctuations of small amplitudes, probably determines the tonic component of dystonia symptoms and its generalization. In general, the findings of this study suggest the potential use of multifractal features of neural activity in the globus pallidus as biomarkers for pathological activity in dystonia and for assessing and predicting the clinical response to deep brain stimulation (DBS).