Estimulação transcraniana por corrente contínua (ETCC) sobre o córtex motor na modulação autonômica em pessoas com lesão medular com diferentes graus e níveis de lesão

Introduction: Transcranial Direct Current Stimulation (tDCS) has been used in studies for the treatment of chronic pain, but their effects on the autonomic nervous system (ANS) are non-existent. Therefore, the need for studies is of fundamental importance, as these individuals have autonomic imbalance and the intensity of this is dependent on the degree and level of injury. Objective: We investigated the effect of tDCS on the ANS in people with spinal cord injury (SCI) with different degrees and levels of injury. Methods: Randomized, placebo-controlled, double-blind, applied anodal tDCS or sham on the primary motor cortex (M1), bilaterally. The subjects (lower incomplete injury, n = 7; lower complete injury, n = 9; and high complete thoracic injury, n = 3) visited the laboratory three times and received active or sham tDCS for 13min. The heart rate variability (HRV) was measured before, during and after stimulation and analyzed the variables LF, HF and LF / HF. Results: The tDCS modulated the ANS in different ways among the groups. In individuals with SCI high complete thoracic the tDCS did not change the HRV. However, for individuals with SCI low incomplete, tDCS changed the HRV in order to increase sympathetic (LF, p = 0.046) and reduced parasympathetic (HF, p = 0.046). For individuals SCI low complete to tDCS changed the HRV reduction sympathetic (LF, p = 0.017) and increased parasympathetic (HF, p = 0.017). Conclusions: The present study suggests that anodal tDCS applied on the motor cortex bilaterally could modulate the ANS balance in people with spinal cord injury and that this effect is dependent on the degree and level of injury.

Avaliação por ressonância magnética funcional e estimulação magnética transcraniana da intervenção única da terapia espelho em pacientes após acidente vascular cerebral isquêmico

Mirror therapy (MT) is being used as a rehabilitation tool in various diseases, including stroke. Although some studies have shown its effectiveness, little is known about neural mechanisms that underlie the rehabilitation process. Therefore, this study aimed at assessing cortical neuromodulation after a single MT intervention in ischemic stroke survivors, by means of by functional Magnetic Resonance Imaging (fMRI) and Transcranial Magnetic Stimulation (TMS). Fifteen patients participated in a single thirty minutes MT session. fMRI data was analyzed bilaterally in the following Regions of Interest (ROI): Supplementary Motor Area (SMA), Premotor cortex (PMC), Primary Motor cortex (M1), Primary Sensory cortex (S1) and Cerebellum. In each ROI, changes in the percentage of occupation and beta values were computed. Group fMRI data showed a significant decreased in the percentage of occupation in PMC and cerebellum, contralateral to the affected hand (p <0.05). Significant increase in beta values was observed in the following contralateral motor areas: SMA, Cerebellum, PMC and M1 (p<0,005). Moreover, a significant decrease was observed in the following ipsilateral motor areas: PMC and M1 (p <0,001). In S1 a bilateral significant decrease (p<0.0005) was observed.TMS consisted of the analysis of Motor Evoked Potential (MEP) of M1 hotspot. A significant increase in the amplitude of the MEP was observed after therapy in the group (p<0,0001) and individually in 4 patients (p <0.05). Altogether, our results imply that single MT intervention is already capable of promoting changes in neurobiological markers toward patterns observed in healthy subjects. Furthermore, the contralateral hemisphere motor areas changes are opposite to the ones in the ipsilateral side, suggesting an increase system homeostasis.

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Experience-dependent upregulation of multiple plasticity factors in the hippocampus during early REM sleep

Sleep is beneficial to learning, but the underlying mechanisms remain controversial. The synaptic homeostasis hypothesis (SHY) proposes that the cognitive function of sleep is related to a generalized rescaling of synaptic weights to intermediate levels, due to a passive downregulation of plasticity mechanisms. A competing hypothesis proposes that the active upscaling and downscaling of synaptic weights during sleep embosses memories in circuits respectively activated or deactivated during prior waking experience, leading to memory changes beyond rescaling. Both theories have empirical support but the experimental designs underlying the conflicting studies are not congruent, therefore a consensus is yet to be reached. To advance this issue, we used real-time PCR and electrophysiological recordings to assess gene expression related to synaptic plasticity in the hippocampus and primary somatosensory cortex of rats exposed to novel objects, then kept awake (WK) for 60 min and finally killed after a 30 min period rich in WK, slow-wave sleep (SWS) or rapid-eye-movement sleep (REM). Animals similarly treated but not exposed to novel objects were used as controls. We found that the mRNA levels of Arc, Egr1, Fos, Ppp2ca and Ppp2r2d were significantly increased in the hippocampus of exposed animals allowed to enter REM, in comparison with control animals. Experience-dependent changes during sleep were not significant in the hippocampus for Bdnf, Camk4, Creb1, and Nr4a1, and no differences were detected between exposed and control SWS groups for any of the genes tested. No significant changes in gene expression were detected in the primary somatosensory cortex during sleep, in contrast with previous studies using longer post-stimulation intervals (>180 min). The experience-dependent induction of multiple plasticity-related genes in the hippocampus during early REM adds experimental support to the synaptic embossing theory.