Comprehensive Statistical Analysis of the Gait Parameters in Neurodegenerative Diseases

Neurodegenerative diseases significantly alter the gait dynamics and, hence, various gait parameters. In this paper, we present results of a comprehensive statistical analysis of the gait time parameters, namely swing interval, stance interval, stride interval, and double support interval, in healthy individuals and patients suffering from neurodegenerative diseases (Huntington's, HD, Parkinson's, PD, and amyotrophic lateral sclerosis, ALS). Multivariate analysis of variance (MANOVA) along with other tests, including univariate tests, post-hoc tests, and discriminant analysis, were employed in this study. Results of discriminant analysis demonstrated that the groups differed significantly from each other with respect to the dependent variables (P < 0.05). All the variables had a strong positive relationship with the first variate or factor, and the left swing, right swing, right stride, and left stride had a positive relationship with the second variate; the double support had a negative relationship. Results of our analyses provide a direction for the selection of certain gait parameters for automatic classification of neurodegenerative diseases based on these parameters.

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Anticipatory Inhibition of EMG Activity of the Human M. Soleus at Voluntary Contraction of Its Antagonists

Quantitative changes in background tonic EMG activity of m. soleus within a premotor period of voluntary contraction of its antagonists were examined in healthy humans. The above activity was recorded in the lying position at voluntary moderate tonic tension of this muscle and in the upright position, where the body was supported by both legs. The effect of voluntary flexion of the ipsilateral ankle joint (a simple motor reaction to a light signal) was examined. It was found that the intensity of soleus EMG in both tested positions, began to decrease 30–60 msec before the appearance of EMG activity recorded from the ankle flexor m. tibialis anterior, and such inhibition reached the maximum at the end of the premotor period. The observed dynamics of tonic EMG in the m. soleus show that an anticipatory drop in the activity of soleus motoneurons develops before the beginning of voluntary movements. Possible physiological mechanisms underlying this phenomenon are discussed. We believe that, within the premotor period, impulsation coming via mostly the corticospinal tract to soleus motoneurons decreases due to the action of central motor commands, and this leads to lowering of tonic tension of this muscle.

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Effects of Intrahippocampal Injections of Melipramin on EEG, Brain Self-Stimulation, and Behavioral Indices of Rats under Conditions of Neurogenic Stress

In young (3-month-old) male Wistar rats, we studied the effects of intrahippocampal microinjections of melipramin under conditions of emotional stress induced by sessions of electrical nociceptive stimulation of the limbs. In most cases, seven-day-long stressing resulted in suppression of electrical activity of the hippocampus, exerted ambivalent effects on the frequency of brain self-stimulation (BSS) events, decreased the communicability of animals in the two-chamber test, and increased the latencies of going of the animal from the arena center and grooming episodes in the open field test. Injections of melipramin interfered with the development of stress-induced disorders in the hippocampus, decreased the normalized content of beta oscillations in the neocortex and the theta-index in the hypothalamus, increased the BSS frequency, and decreased the level of negativation of the behavioral manifestations of this phenomenon. The duration of stay of a rat near the partition in the two-chamber test increased, the mobility and number of grooming episodes in the open field enhanced, but the latency of leaving the arena center also increased (similarly to what was observed in the control). On the 8th–9th day of the poststress period, behavioral disorders of rats of the control group in the two-chamber test were smoothed to a significant extent. The stability of the examined indices or the reverse development of stress-induced disorders within the above period in animals injected with melipramin were indicative of a significant role of the hippocampus in the formation of central effects of this antidepressant and also of adaptogenic and stress-protective properties of this drug.

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Pharmacodynamics of Interaction between Propoxazepam and a GABA-Benzodiazepine Receptor-Ionofor Complex

Effects of a propyloxy derivative of 1.4-benzodiazepine, propoxazepam, on GABA-benzodiazepine receptor complexes (GABA RCs) were examined in vitro and in vivo. The parameters of propoxazepam binding to synaptosomes from the rat brain were estimated in vitro. The K_i constant for inhibition of [³H] flumazenil binding by this agent was 3.5 ± 0.3 nM, on average. Considering the value of the GABA shift (1.9), propoxazepam can be considered as GABA-RC full agonist. On the model of picrotoxin-induced seizures in vivo, the propoxazepam average effective dose was estimated as 4.1 ± ± 0.21 mmol/kg. It was found that the parameters of myoclonic components (latent period of the onset of myoclonic seizures and their number), as well as death time of the tested animals, characterize adequately an anticonvulsant action of propoxazepam of picrotoxin-induced seizures in mice. Competitive interaction with picrotoxin is the possible mechanism of these effects at the level of GABA_ARCs. Significant deviations from a competitive model of monomolecular and cooperative binding of the agent at the receptor level have been found.

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Effects of Vitamin/Sorbent Complexes on Behavioral Activity of Gamma-Irradiated Rats in the Open Field

The dynamics of behavioral indices of male albino rats were examined in the open field test. Total gamma irradiation (absorbed dose 5 Gy) resulted in decreases in the indices of all types of motor and orientational/research activity and increased emotional tension. The treatment of animals with the chitin/protein and carotene-tocopherol complexes (0.35 and .6.67 g/kg, respectively) before and after irradiation, due to the antioxidant and enterosorbent properties of these complexes, significantly moderated the negative effects of irradiation and provided a clear trend toward normalization of the measured behavioral indices (period of observation 30 days).

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Effects of Melatonin on the Behavioral Indices and Structural Characteristics of Cerebral and Spinal Neurons of Rats with Experimental Hemiparkinsonism

In adult Wistar rats, a model of experimental hemiparkinsonism (EHP) was induced by stereotaxic microinjection of 8.0 μg 6-hydroxydopamine (6-HODA) into the left forebrain lateral ascending bundle. In such animals, we studied behavioral indices in the open field and elevated plus maze tests and also structural changes in the cerebral substantia nigra and spinal L5 ventral horn neurons. Six groups of animals were formed (in each group, n = 8): intact rats (I), animals that obtained microinjections of saline into the above lateral bundle (sham-injected, ShI), two groups with weak and intense motor EHP manifestations (frequency of circulatory movements in the apomorphine test less than one and six and more per 1 min, groups HP_<1 and HP_≥6, respectively), and two groups of rats with weak and intense EHP manifestations, which obtained daily i.p. injections of 10 mg/kg melatonin during 18 days (groups HP_<1+M and HP_≥6+M). In the open-field test, we observed in groups HP_<1 and HP_≥6 significant suppression of horizontal motor activity (very intense in the latter of the above-mentioned groups) and also significant weakening of vertical activity (number of rearings). Changes in the number of defecation acts were less expressed. In the elevated plus maze, manifestations of a significantly increased anxiety level were observed in rats of the above two groups. In the substantia nigra of animals with EHP, a considerable part of the neurons demonstrated clear signs of negative structural modifications; the number of neurons with the normal structure was considerably smaller than in the control. Analogous negative morphological changes were found in the lumbar segment of the spinal cord. Course injections of melatonin into rats with EHP noticeable weakened negative shifts in both open-field behavioral indices and level of anxiety (according to estimates in the elevated plus maze). Under the action of melatonin, morphological characteristics of neurons and gliocytes in the substantia nigra and spinal cord of rats with EHP demonstrated appreciable normalization. The mechanisms underlying functionaland structural disorders in the CNS of animals after central microinjections of the 6-HODA neurotoxin and also neuroprotective effects of melatonin, which provide weakening of such disorders, are discussed.

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Extraction of Parkinson’s Disease-Related Features from Local Field Potentials for Adaptive Deep Brain Stimulation

Despite the efficiency of deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD), the respective systems need to be further optimized. The lack of accurate PD-related quantitative biomarkers limits the improvement of adaptive DBS (aDBS) systems. Now, most DBS devices are open-loop sets with fixed stimulation parameters, which prevents them from coping with movement fluctuations and rapid changes of the symptoms. At the same time, ample evidence has shown that abnormal oscillations in the composition of local field potential (LFP) signals recorded in PD patients can reflect, to a certain extent, the crucial symptoms of the desease. Therefore, acquisition of LFP signals, extraction of abnormal oscillations, and acquisition of indicative biomarkers is the core technical issue with respective to the aDBS systems. Here, we review the current feature extraction methods in PD, summarize results of the latest research, analyze the difficulties of extracting the quantitative biomarkers, and discuss the developmental trend of feature extraction for aDBS.

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