Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Short-term resistance training with instability reduces impairment in V wave and H reflex in individuals with Parkinson's disease.

This study had two objectives: 1) to compare the effects of 3 wk of resistance training (RT) and resistance training with instability (RTI) on evoked reflex responses at rest and during maximal voluntary isometric contraction (MVIC) of individuals with Parkinson's disease (PD) and 2) to determine the effectiveness of RT and RTI in moving values of evoked reflex responses of individuals with PD toward values of age-matched healthy control subjects (HCs) (z-score analysis). Ten individuals in the RT group and 10 in the RTI group performed resistance exercises twice a week for 3 wk, but only the RTI group included unstable devices. The HC group (n = 10) were assessed at pretest only. Evoked reflex responses at rest (H reflex and M wave) and during MVIC [supramaximal M-wave amplitude (Msup) and supramaximal V-wave amplitude (Vsup)] of the plantar flexors were assessed before and after the experimental protocol. From pretraining to posttraining, only RTI increased ratio of maximal H-reflex amplitude to maximal M-wave amplitude at rest (Hmax/Mmax), Msup, Vsup/Msup, and peak torque of the plantar flexors (P < 0.05). At posttraining, RTI was more effective than RT in increasing resting Hmax and Vsup and in moving these values to those observed in HCs (P < 0.05). We conclude that short-term RTI is more effective than short-term RT in modulating H-reflex excitability and in increasing efferent neural drive, approaching average values of HCs. Thus short-term RTI may cause positive changes at the spinal and supraspinal levels in individuals with PD. NEW & NOTEWORTHY Maximal H-reflex amplitude (Hmax) at rest and efferent neural drive [i.e., supramaximal V-wave amplitude (Vsup)] to skeletal muscles during maximal contraction are impaired in individuals with Parkinson's disease. Short-term resistance training with instability was more effective than short-term resistance training alone in increasing Hmax and Vsup of individuals with Parkinson's disease, reaching the average values of healthy control subjects.

Resistance training with instability is more effective than resistance training in improving spinal inhibitory mechanisms in Parkinson's disease.

This study assessed 1) the effects of 12 wk of resistance training (RT) and resistance training with instability (RTI) on presynaptic inhibition (PSI) and disynaptic reciprocal inhibition (DRI) of patients with Parkinson's disease (PD); 2) the effectiveness of RT and RTI in moving PSI and DRI values of patients toward values of age-matched healthy controls (HC; Z-score analysis); and 3) associations between PSI and DRI changes and clinical outcomes changes previously published. Thirteen patients in RT group, 13 in RTI group, and 11 in a nonexercising control group completed the trial. While RT and RTI groups performed resistance exercises twice a week for 12 wk, only the RTI group used unstable devices. The soleus H reflex was used to evaluate resting PSI and DRI before and after the experimental protocol. The HC (n = 31) was assessed at pretest only. There were significant group × time interactions for PSI (P < 0.0001) and DRI (P < 0.0001). RTI was more effective than RT in increasing the levels of PSI (P = 0.0154) and DRI (P < 0.0001) at posttraining and in moving PSI [confidence interval (CI) 0.1-0.5] and DRI (CI 0.6-1.1) levels to those observed in HC. There was association between DRI and quality of life changes (r = -0.69, P = 0.008) and a strong trend toward association between PSI and postural instability changes (r = 0.60, P = 0.051) after RTI. RTI increased PSI and DRI levels more than RT, reaching the average values of the HC. Thus RTI may cause plastic changes in PSI and DRI pathways that are associated with some PD clinical outcomes. NEW & NOTEWORTHY: Patients with Parkinson's disease (PD) have motor dysfunction. Spinal inhibitory mechanisms are important for modulating both supraspinal motor commands and sensory feedback at the spinal level. Resistance training with instability was more effective than resistance training in increasing the levels of presynaptic inhibition and disynaptic reciprocal inhibition of lower limb at rest of the patients with PD, reaching the average values of the healthy controls.

Resistance Training with Instability for Patients with Parkinson's Disease.

PURPOSE: This randomized controlled trial compared the effects of resistance training (RT) and RT with instability (RTI) on the timed up and go test (TUG), on-medication Unified Parkinson's Disease Rating Scale part III motor subscale score (UPDRS-III), Montreal Cognitive Assessment (MoCA) score, Parkinson's Disease Questionnaire (PDQ-39) score, and muscle strength in the leg press exercise (one-repetition maximum) of patients with Parkinson's disease (PD). METHODS: Thirty-nine patients with moderate to severe PD were randomly assigned to a nonexercising control group (C), RT group, and RTI group. The RT and RTI groups performed progressive RT twice a week for 12 wk. However, only the RTI group used high motor complexity exercises (i.e., progressive RT with unstable devices), for example, half squat exercise on the BOSU® device. The primary outcome was mobility (TUG). The secondary outcomes were on-medication motor signs (UPDRS-III), cognitive impairment (MoCA), quality of life (PDQ-39), and muscle strength (one-repetition maximum). RESULTS: There were no differences between RTI and RT groups for any of the outcomes at posttraining (P > 0.05). However, there were differences between RTI and C groups in the TUG, MoCA, and muscle strength values at posttraining (P < 0.05). Only the RTI group improved the TUG (-1.9 s), UPDRS-III score (-4.5 score), MoCA score (6.0 score), and PDQ-39 score (-5.2 score) from pre- to posttraining (P < 0.001). Muscle strength improved for both training groups (P < 0.001). No adverse events were reported during the trial. CONCLUSIONS: Both training protocols improved muscle strength, but only RTI improved the mobility, motor signs, cognitive impairment, and quality of life, likely because of the usage of high motor complexity exercises. Thus, RTI may be recommended as an innovative adjunct therapeutic intervention for patients with PD.

Comparação de inibições medulares entre indivíduos com doença de Parkinson e saudáveis / Comparison of spinal inhibitions between parkisonian and helathy individuals

O objetivo do presente estudo foi comparar os níveis de inibição pré-sináptica (IPS) e inibição recíproca (IR) entre indivíduos com Doença de Parkinson e saudáveis e, a correlação entre essas inibições e a rigidez muscular e a severidade clínica de indivíduos com Doença de Parkinson (avaliadas através da Escala Unificada de Avaliação da Doença de Parkinson). Foram avaliados 11 indivíduos nos estágios 2 e 3 da doença e 13 indivíduos saudáveis pareados pela idade. A IPS foi menor em indivíduos com Doença de Parkinson (31,6%) do que em saudáveis (67,1%) (p = 0,02). A IR não diferiu entre indivíduos com Doença de Parkinson (26,9%) e saudáveis (27,6%) (p = 0,91). Adicionalmente, não foram detectadas correlações entre os níveis de IPS com a rigidez e a severidade clínica (p > 0,05). Portanto, mecanismos inibitórios não explicam totalmente a rigidez muscular e a severidade clinica da doença. Alterações entre ativação de músculos agonistas e antagonistas parecem estar relacionadas a influências supraespinhais anormais nos mecanismos espinhais decorrentes da doença...

The purposes of the present study were to compare presynaptic inhibition (PI) and disynaptic reciprocal inhibition (DRI) levels between parkinsonians and healthy individuals and to verify the correlation of such inhibitions with muscle rigidity and clinical severity (assessed by the Unified Parkinson Disease Rating Scale). We evaluated 11 parkinsonians in stages 2 and 3 of the disease and 13 healthy individuals matched for age. The PI was significant lower in parkinsonians (31.6%) than in healthy individuals (67.1%) (p = 0.02). The DRI did not differ between parkinsonians (26.9%) and healthy individuals (27.6%) (p = 0.91). Furthermore, no significant correlation was observed between PI with muscle rigidity and clinical severity (p > 0.05). Therefore, inhibitory mechanisms do not fully explain the cause of muscle rigidity and clinical severity of parkinsonians. Changes between the activation of agonist and antagonist muscles seem to be caused by abnormal supraspinal influence on spinal mechanisms...

Avaliação da inibição recíproca em humanos durante contrações isométricas dos músculos tibial anterior e sóleo / Assessment of reciprocal inhibition in humans during isometric contractions of the tibialis anterior and soleus muscles

Os objetivos do presente trabalho foram: (1) desenvolver um método para estimar o grau de inibição recíproca (IR) entre músculos antagonistas em humanos (sóleo e tibial anterior) e (2) comparar os níveis de IR no repouso, na dorsiflexão (DF) e na flexão plantar (FP). Participaram nove sujeitos saudáveis com idade entre 20 e 30 anos, quatro homens e cinco mulheres. Os sujeitos permaneceram sentados numa cadeira com o pé direito apoiado e fixo num pedal acoplado a um torquímetro. Foi aplicado um pulso elétrico na fossa poplítea, denominado estímulo “teste”, para se obter o reflexo H (RH) do músculo sóleo. Num segundo momento, foi aplicado um estímulo “condicionante” ao redor da cabeça da fíbula, que precedia o “teste” em 1 a 3ms. A onda H do músculo sóleo foi captada por eletrodos de superfície. O estudo foi realizado com o sujeito em repouso e realizando contração isométrica dos músculos dorsiflexores e flexores plantares do tornozelo. As amplitudes pico-a-pico dos RH controle e condicionado foram utilizadas para o cálculo da IR. Os valores de IR foram: 16,41% - 8,68 no repouso; 21,94% - 5,39 na DF e 3,12% - 11,84 na FP. Foi constatada menor inibição recíproca na FP quando comparada às demais condições (p<0,05), mas não houve aumento da IR detectável, pela metodologia aplicada...

The purposes of the present study were (1) to develop a method to estimate the level of reciprocal inhibition (RI) between antagonist muscles (soleus and anterior tibial) in humans, and (2) to compare RI levels during rest, dorsiflexion (DF) and plantarflexion (PF). Nine healthy subjects (four men, five women) aged between 20 and 30 years were assessed. Each subject remained seated with his/her right foot straped to a rigid foot plate coupled to a torquemeter. An electrical pulse (“test stimulus”) was applied to the popliteal fossa (tibial nerve) to generate an H reflex from the soleus muscle. After this control situation was tested, a “conditioning stimulus” was applied near the head of the peroneal bone, preceding by 1-3 ms the test stimulus to the tibial nerve. Each subject was tested in the three conditions RE, DF and PF. In the last two cases the subject pressed or pulled on the foot plate with a constant effort. The H reflex amplitudes were measured peak-to-peak and expressed in terms of the maximum M response. The values obtained for RI were 16,41% - 8,68 at RE; 21,94% - 5,39 in DF and 3,12% - 11,84 in PF. There was a statistically significant decrease of RI during PF when compared with the other conditions (Tukey, p<0.05) but no difference between DF compared to RE...

Adaptações neurais na medula espinhal de humanos para diferentes tipos de treinamento físico / Neural changes in the spinal cord rights for different types of physical training

Introdução: As adaptações neurais ao treinamento físico vêm sendo amplamente estudadas e a medula espinhal é um dos locais de possível adaptação. No entanto nenhuma avaliação longitudinal havia sido feita diretamente sobre as circuitarias inibitórias medulares. Até o presente momento as alterações eram somente suposições. O presente trabalho verificou as circuitarias medulares responsáveis pela inibição recíproca (IR) e inibição pré-sináptica (IPS) em sujeitos submetidos a diferentes treinamentos. Materiais e Métodos: Para o treino aeróbico (resistência) foram avaliados 25 soldados submetidos ao treinamento militar do Exército Militar Brasileiro. Foram feitas 3 avaliações uma pré-treino e outras duas com 3 e 9 meses após o inicio das atividades no ano de 2006. Outros 29 sujeitos foram divididos em 3 grupos: controle (permaneceram 8 semanas sem atividades de treinamento), grupo de treino de força máxima e treino de potência. Eles foram submetidos a 8 semanas de treino, realizado com séries de agachamento livre com peso. Para avaliação das circuitarias medulares foi utilizado o reflexo H do sóleus condicionado com estímulos no nervo fibular comum (NFC) - que inerva o músculo tibial anterior (TA). O intervalo entre o estímulo condicionante e o estímulo teste determinou a avaliação da IR, da inibição D1 e da inibição D2 (IPS). Outras variáveis também foram calculadas como: contração voluntária máxima isométrica (CVM) do sóleus e TA e seus respectivos eletromiogramas (EMG), relação elétrica e mecânica entre Hmax/Mmax e condicionamento do EMG do sóleus por estímulos no NFC. Foram feitas análises pareadas com teste t-student para o grupo militar e ANOVA two-way para comparação dos grupos de força máxima e potência com o grupo controle. (...)

... Resultados: O grupo do exército apresentou aumento na força do sóleus e do TA, juntamente com aumento no RMS do EMG do sóleus e do torque gerado pela onda Mmax, sem alterações nos relações Hmax/Mmax. O treinamento militar reduziu significativamente a inibição D1 e mostrou tendências a aumento da IPS. O grupo de força máxima não mostrou aumento de força isométrica, no entanto apresentou aumento na relação elétrica Hmax/Mmax, com concomitante redução da IR e aumento da IPS. O grupo de potência mostrou ganho na força máxima isométrica somente do sóleus. A capacidade de gerar torque reflexamente também aumentou neste grupo, com aumento significativo na relação mecânica Hmax/Mmax. Esta melhora na utilização do arco reflexo também foi verificada com redução da IPS e aumento da IR neste grupo. Conclusões: Estes resultados mostraram que a medula espinal sofre plasticidade nas vias inibitórias IR, inibição D1 e D2, e que esta plasticidade é dependente do tipo de tarefa realizada

Introduction: Neural adaptations with physical training have been widely studied. The spinal cord is a possible locus of adaptation. However, longitudinal studies that evaluate directly the spinal cord pathways have not been found in the literature. Therefore, all reports from the literature justify changes found in measured responses to exercise by hypotheses on spinal cord mechanisms. This study had the objective of measuring features of specific spinal cord pathways to check if they change according to the type of physical training. The pathways related to reciprocal inhibition (RI) and pre-synaptic inhibition (PSI) were investigated in subjects undergoing different trainings. Materials and Methods: For endurance training 25 soldiers were subjected to military training of the Brazilian Army. Evaluations were made three times, one previous to the beginning of the activity and twice post-training (within 3 and 9 months). Other 29 subjects were divided into: control group (with no training), maximal strength group and power group. They were subjected to 8 weeks of training with series of squat movements. The soleus H reflex conditioning with stimuli in the common peroneal nerve (CPN) was used to evaluate the spinal cord pathways. The interval between the conditioning and the test stimulus determine the assessment of RI, D1 inhibition and D2 inhibition (PSI). Other variables were also calculated: maximum voluntary isometric contraction from soleus and tibialis anterior and their electromyograms (EMG), electrical and mechanical Hmax/Mmax ratio and 3 inhibitions over the soleus EMG conditioned by stimuli to the CPN. (...)

... The results were analyzed with paired t-student test for the military group and with two-way ANOVA to compare the maximal strength and power groups with the control group. Main Results: The military group had increased strength of the soleus and the TA muscles, with an increase in the RMS of the soleus EMG. This group also increased the torque generated by the Mmax-wave, without changes in Hmax/Mmax ratio. The military training significantly reduced D1 inhibition and showed tendencies to increase the PSI. The maximal strength group showed no differences in isometric strength, but had increased Hmax/Mmax ratio with concomitant reduction of RI and increased PSI. The power group increased isometric strength only for the soleus muscle. This group also improved the ability to generate torque by reflex pathways, with significant increase in the mechanical Hmax/Mmax ratio, with a reduction of PSI and increase of RI. Conclusions: These results show that spinal cord plasticity occurs in the inhibitory pathways of reciprocal inhibition, D1 inhibition and D2 inhibition (pre-synaptic inhibition), and that plasticity is dependent on the type of trained movement

Metodologia para a quantificação da inibição pré-sináptica no músculo sóleus em humanos em repouso e durante contração / Methodology for pre-synaptic inhibition quantification in humans soleus muscle, at rest and during contraction

O presente trabalho teve como objetivos: o desenvolvimento de uma metodologia para a verificação do grau de inibição pré-sináptica (IPS) em humanos, e comparar o grau de inibição no repouso e durante a dorsiflexão e a flexão plantar. Além disto, este trabalho também analisou a inibição recíproca de média latência (IRML) em condições experimentais semelhantes. A análise da IPS foi realizada com o condicionamento do reflexo H com um estímulo no nervo fibular comum, aplicado 100ms antes do estímulo teste. A IRML foi analisada utilizando-se o mesmo paradigma, porém com intervalos entre os estímulos condicionante e teste de 20 a 25ms. A IRML e a IPS apresentaram-se menores durante a flexão plantar (p < 0,05) em comparação com o repouso. Durante a dorsiflexão a IRML não apresentou nenhuma diferença estatística (p > 0,05) quando comparada ao repouso. Já a IPS apresentou-se menor durante a dorsiflexão do que no repouso. Este resultado pode refletir uma oclusão dos interneurônios da medula espinhal responsáveis pela IPS (AU)