Model-Based Analyses for the Causal Relationship Between Post-stroke Impairments and Functional Brain Connectivity Regarding the Effects of Kinesthetic Illusion Therapy Combined With Conventional Exercise

Aims: Therapy with kinesthetic illusion of segmental body part induced by visual stimulation (KINVIS) may allow the treatment of severe upper limb motor deficits in post-stroke patients. Herein, we investigated: (1) whether the effects of KINVIS therapy with therapeutic exercise (TherEx) on motor functions were induced through improved spasticity, (2) the relationship between resting-state functional connectivity (rs-FC) and motor functions before therapy, and (3) the baseline characteristics of rs-FC in patients with the possibility of improving their motor functions.Methods: Using data from a previous clinical trial, three path analyses in structural equation modeling were performed: (1) a mediation model in which the indirect effects of the KINVIS therapy with TherEx on motor functions through spasticity were drawn, (2) a multiple regression model with pre-test data in which spurious correlations between rs-FC and motor functions were controlled, and (3) a multiple regression model with motor function score improvements between pre- and post-test in which the pre-test rs-FC associated with motor function improvements was explored.Results: The mediation model illustrated that although KINVIS therapy with TherEx did not directly improve motor function, it improved spasticity, which led to ameliorated motor functions. The multiple regression model with pre-test data suggested that rs-FC of bilateral parietal regions is associated with finger motor functions, and that rs-FC of unaffected parietal and premotor areas is involved in shoulder/elbow motor functions. Moreover, the multiple regression model with motor function score improvements suggested that the weaker the rs-FC of bilateral parietal regions or that of the supramarginal gyrus in an affected hemisphere and the cerebellar vermis, the greater the improvement in finger motor function.Conclusion: The effects of KINVIS therapy with TherEx on upper limb motor function may be mediated by spasticity. The rs-FC, especially that of bilateral parietal regions, might reflect potentials to improve post-stroke impairments in using KINVIS therapy with TherEx.

Acute onset of chronic infl ammatory demyelinating polyneuropathy in combination with COVID-19

Acute onset of chronic infl ammatory demyelinating polyneuropathy (A-CIDP) presents signifi cant diffi culties in differential diagnosis with acute infl ammatory demyelinating polyneuropathy (AIDP). The article presents review of literature about diff erential diagnosis between A-CIDP and AIDP and a clinical case of A-CIDP at 26-year-old man. The disease started after vaccination against infl uenza and an episode of enteritis, the clinical picture matched Guillain–Barré syndrome criteria, according to electromyography data: demyelinating lesion of the left facial nerve, motor and sensory fi bers of the median and ulnar nerves on both sides, demyelinating lesions of motor fi bers of the tibial nerve and peroneal nerve on both sides. Chronic infl ammatory demyelinating polyneuropathy was diagnosed. Lack of eff ect from plasma exchange was the reason for changing the treatment to pulse therapy with prednisolone (with a subsequent transition to a 1 mg/kg dose and further reduction until canceled within 16 weeks). Response to prednisolone — rapid recovery of motor functions, which worsened signifi cantly due to a new coronavirus infection during treatment in the neurology department. Further continuation of prednisolone therapy made it possible to restore motor functions completely, except mild prosopoparesis. At the same time, deep refl exes were absent; no signifi cant EMG dynamics was observed. Considering the eff ect of glucocorticosteroids and lack of positive dynamics on the second electromyography, the patient was diagnosed as A-CIDP.

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats

Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson’s disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.

The Role of Autophagy and Mitophagy in Huntington’s Disease

Huntington’s disease (HD) is an inherited autosomal-dominant neurodegenerative disorder that occurs due to mutations in the polyglutamine expansions of the Huntingtin protein (Htt). HD is characterised by the loss of cognitive and motor functions, as well as the development of emotional and psychiatric disturbances. The HD pathology is manifested through the cellular changes that arise due to the toxic functions of mutant Htt (mHtt). Autophagy is a lysosomal pathway that functions to remove damaged intracellular components while mitophagy is a selective form of autophagy involving mitochondria; and PINK1/Parkin-mediated mitophagy is the most well-understood pathway. Mitochondrial dysfunction and defects in mitophagy can be linked to the pathogenesis of HD. Previous research has shown that the presence of mHtt hinders mitophagy; while PINK1/Parkin-mediated mitophagy provides neuroprotection in HD. Hence, this review discusses the roles and regulations of mitophagy, along with an overview of mitophagy in HD.

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.

Fresh Water Aquatic Training in Patients with Upright Posture Maintaining Disorders

The use of the fresh water aquatic training course, as a more gentle training method, may allow patients to ensure effective restoration of muscle functions responsible for maintaining an upright body position. A more accurate control of the course results can be performed using a virtual analysis carried out using the «Habilect» system that allows to determine the body parts attitude. Aim. To study the effect of training in fresh water using the Habilect system based on the Microsoft Kinect infrared sensor (video stabilometry) on motor functions that contribute to maintaining an upright body posture in patients with mild gait disturbances. Material and methods. An open descriptive study was conducted including 12 patients (7 men, 5 women), aged 40 to 62 years, with upright posture maintaining disorders, which correspond to the functional diagnosis encoded by the ICF «Gait Stereotype Functions» B770.1 – mild violations (5–24%). A group of subjects (n = 12), in addition to basic therapy and training with an exercise therapy instructor, underwent aquatic training in fresh water for two weeks (30 minutes, 6 days a week). Assessment methods: the research was carried out using the Habilect gait video analysis system before and after the rehabilitation course. The χ2 test was used to assess the significance of differences between groups of qualitative variables. When analyzing quantitative variables, the Shapiro-Wilk’s (W) test was performed. For abnormal distribution, the data is in Me format [Q25-Q75]. The Wilcoxon T-test was used to assess the significance of differences in quantitative variables of the two studied groups. The processing of the obtained research results was carried out using the Statistica for Windows, v. 8.0 (StatSoft Inc., USA) and Microsoft Excel (Microsoft, USA). The significance of the differences was considered established at p <0.05. Result and discussion. When examining the amplitude of body deflection along the X-axis before training, they were 3.25 cm [-98 cm; 93.9 cm], after – -9.96 cm [-100.92 cm; -81.96 cm], on the Y-axis before training – -29.01 cm [-29.01 cm; 13.76 cm], after –-30.59 cm [-30.59 cm; 31.09 cm], on the Z-axis before training – 388.1 cm [369.22 cm; 393.39 cm], after training – 380.96 cm [377.98cm, 400.05 cm], deviation of the body movement vector before training 16.45 cm [7.46 cm; 338.67 cm], after training – 324.7 cm [324.7 cm; 342.56 cm]. When examining the amplitude of head deflection along the X-axis before training, they were -0.92 cm [-1.24 cm; -0.92 cm], after – 1.5 cm [-10.19 cm; 2.38 cm], Y-axis before training – 125.33 cm [61.13 cm; 128.94 cm], after – 107.42 cm [52.49 cm; 107.42 cm], along the Z-axis before training – -8.59 cm [-8.97 cm; -5.33 cm], after training – -14.89 cm [-14.89 cm, -3.45cm]. When calculating the increase in deviation (deviations of the main body axes from the initial value) using the Wilcoxon T-test revealed statistically significant deviations in the X-axis (an increase of 306.5%, p = 0.0504), the Z-axis (an increase of 112.68%, p =0.0225) and the Body Angle parameter (an increase of 1973.86% p = 0.0323). When calculating the increase in the deviation of the head axes from the initial value using the Wilcoxon T-test, statistically significant deviations were revealed along the X axis (increase of 163.04%, p = 0.0280), the Y axis (increase of 85.71%, p = 0.0199) and the parameter Z (an increase of 173.34% p = 0.0292). The study revealed a decrease in the body axes deviations amplitude in all 3 planes, which indicates an improvement in the work of all brain parts that are responsible for the coordination of motor functions and their vegetative support, an improvement in functional interaction within individual muscle chains. The reduction in the head and neck muscles in compensatory balancing participation during walking and maintaining a vertical body posture mainly due to the muscles of the lower extremities and pelvis contributes to the prevention of arterial and venous circulation disorders in the head and neck and makes training not only more effective, but also safer. Conclusion. Due to the decrease in the amplitude of deviations along all three axes (Z, Y, X), the course of aquatic training contributes to the correction of upright posture maintaining disorders, a statistically significant decrease in the amplitude of head and neck movements.

Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

The cerebellum has a long history in terms of research on its network structures and motor functions, yet our understanding of them has further advanced in recent years owing to technical developments, such as viral tracers, optogenetic and chemogenetic manipulation, and single cell gene expression analyses. Specifically, it is now widely accepted that the cerebellum is also involved in non-motor functions, such as cognitive and psychological functions, mainly from studies that have clarified neuronal pathways from the cerebellum to other brain regions that are relevant to these functions. The techniques to manipulate specific neuronal pathways were effectively utilized to demonstrate the involvement of the cerebellum and its pathways in specific brain functions, without altering motor activity. In particular, the cerebellar efferent pathways that have recently gained attention are not only monosynaptic connections to other brain regions, including the periaqueductal gray and ventral tegmental area, but also polysynaptic connections to other brain regions, including the non-primary motor cortex and hippocampus. Besides these efferent pathways associated with non-motor functions, recent studies using sophisticated experimental techniques further characterized the historically studied efferent pathways that are primarily associated with motor functions. Nevertheless, to our knowledge, there are no articles that comprehensively describe various cerebellar efferent pathways, although there are many interesting review articles focusing on specific functions or pathways. Here, we summarize the recent findings on neuronal networks projecting from the cerebellum to several brain regions. We also introduce various techniques that have enabled us to advance our understanding of the cerebellar efferent pathways, and further discuss possible directions for future research regarding these efferent pathways and their functions.