Aim The purpose of this study was to compare resistance-trained (RT) and non-trained (NT) males regarding mechanisms for neural activation during isometric muscle contractions of the soleus muscle. Further the plantar flexor strength of the two groups were compared. Method Ten males that had been resistance training for at least 3 years (RT) and 10 who did not train regularly (NT) participated in the study. The participants performed isometric contractions of their right plantar flexors against an isokinetic dynamometer at 15, 25, 50, 80 and 100% of maximal voluntary contraction. Five contractions were performed for each level in two different conditions; one where the participants were stimulated using transcranial magnetic stimulation over the left motor cortex and one in which they were stimulated electrically over the tibial nerve. Stimulations were also delivered at rest. The resulting soleus muscle motor evoked potentials (MEPs) and V-waves were normalized to a maximal M-wave (Mmax). Plantar flexor strength was measured and voluntary activation estimated using the twitch interpolation technique. Results No significant difference was found between the RT and the NT group for voluntary activation, V/Mmax ratio or MEP/Mmax at any level of maximal voluntary contraction (MVC). The RT group was significantly stronger than the NT group. Conclusions The study showed that the RT group was stronger than the NT group. Despite the difference in strength there was no significant group difference between the two groups in MEPs, V/Mmax or voluntary activation. This indicates that there is no, or a very small difference in corticospinal excitability of the soleus muscle between the chronic RT males and the NT males.

Transcranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. TMS is now being used in the investigation of fatigue to help partition the effects of central fatigue. Few studies have utilized this technique to evaluate the effects of locomotor exercise and none in conditions of extreme exercise. Therefore, the purpose of this thesis was twofold; first, to answer methodological questions pertaining to the use of TMS in fatigue evaluation, particularly of the quadriceps, and second, to investigate the effects of extreme exercise conditions on the development of central and supraspinal fatigue and corticospinal excitability and inhibition. In Studies 1 and 2, the effect of approaching a target force in different ways before the delivery a TMS pulse and the difference between commonly-employed methods of determining TMS intensity on the selection of optimal TMS intensity were investigated. In Study 3, the effect of one night sleep deprivation on cognitive and exercise performance and central parameters was investigated. The effect of a 110-km ultra-trail on the supraspinal component of central fatigue was evaluated in Study 4. The principal findings from this thesis are that during TMS evaluation during brief voluntary contractions, it is essential to deliver the TMS pulse once the force has stabilized at the target and that a stimulus-response curve at 20% MVC is appropriate for determining optimal TMS intensity in exercise and fatigue studies. Furthermore, while sleep deprivation negatively-impacted cognitive and exercise performance, it did not influence neuromuscular parameters nor result in greater central fatigue. Supraspinal fatigue develops and corticospinal excitability increases during endurance/ultra-endurance running and cycling, while the effects on inhibitory corticospinal mechanisms are equivocal and probably depend on exercise characteristics and TMS intensity

Conventional functional electrical stimulation (FES) therapy, if provided shortly after an incomplete spinal cord injury, is able to help an individual to restore voluntary hand function. This is thought to occur through the induction of neuroplasticity. However, conventional FES therapy employs a push-button-based control scheme, which does not fully require the recipient to generate volitional movements. The first study in this thesis therefore sought to determine, in an early proof-of-concept test with able-bodied participants, whether control strategies which are triggered by volitional activity (including an electroencephalography-based brain-machine interface (BMI-FES) and an electromyogram-based control scheme (EMG-FES)) might provide greater benefits to hand function. The results offer relatively weak evidence to suggest that BMI-FES, and especially EMG-FES, were able to induce greater neuroplasticity than conventional treatments in the corticospinal tract leading to the hands, but that this did not immediately translate to more functional improvements such as maximum grip force. ii The second study in this thesis focussed on spinal associative stimulation (SAS), which involves paired stimulation pulses at both the head (via transcranial magnetic stimulation), and the wrist (via peripheral nerve stimulation). The purpose of this, as with the first study, was to induce neuroplasticity and upregulate the corticospinal tract leading to the hands. While limited research has suggested that it is possible to produce neuroplasticity through SAS, all such studies have provided stimulation at a fixed frequency of 0.1 or 0.2 Hz. The present study therefore sought to compare the effectiveness of a typical 0.1 Hz paradigm with a 1 Hz paradigm, and a paradigm which provided stimulation in 5 Hz “bursts”. None of the paradigms were able to successfully induce neuroplasticity in a consistent manner. The increased variability in this study as compared to the previous one, despite the nearly identical assessment methodology, suggests that responses to the SAS treatment may have been highly individual. This serves to highlight a potential limitation of the treatment, which is that its effectiveness may not be universal, but rather dependent on each specific recipient. This may be a challenge faced by SAS should it continue to be tested as a novel therapy.

We prospectively evaluated 30 consecutive patients with echo-enhanced transcranial color-coded duplexsonography (TCCD) and correlative transfemoral digital subtraction angiography to assess the diagnostic efficacy of echo-enhanced TCCD for evaluation of collateral pathways through the circle of Willis in patients with limited acoustic bone windows and critical symptomatic carotid disease. Echo-enhanced TCCD detected collateral blood flow through the anterior communicating artery in 16 of 18 patients (sensitivity 89%, 95% CI 65–99%) and was false positive in one out of 12 patients without collateral flow (specificity 92%, 95% CI 59–100%). For the posterior communicating artery, sensitivity was 11/14 (79%, 95% CI 49–95%) and specificity was 15/16 (94%, 95% CI 70–100%). Echo-enhanced TCCD enables to study collateral blood flow through the communicating arteries of the circle of Willis with high sensitivity and specificity in patients with obstructions of the internal carotid artery and limited acoustic bone windows. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Thirty-four patients with acute hemispheric ischemic strokes underwent both CT angiography and contrast-enhanced transcranial color-coded duplexsonography (TCCD) to study the effectiveness of the combined noninvasive techniques for evaluation of the circle of Willis. In 3/34 patients, CT angiography and contrast-enhanced TCCD demonstrated middle cerebral artery (MCA) occlusion, in 5 others MCA stenosis. A severe posterior cerebral artery stenosis was missed by CT angiography. In 8 patients, contrast-enhanced TCCD failed because of poor bone windows. In these patients, CT angiography was normal. CT angiography and contrast-enhanced TCCD are complementary noninvasive diagnostic tools. Disagreements between the diagnostic findings of these methods still need further evaluation by digital subtraction angiography. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

[Truncated abstract] A reduction in the force-generating capacity of a muscle is the primary indicator of fatigue and the majority of this force loss is the result of peripheral fatigue. However, there is also evidence that the central nervous system (CNS) does not drive muscles maximally during fatiguing exercise, which has led to the concept of central fatigue. The strongest evidence for this comes from interpolated twitch studies showing that transcranial magnetic stimulation (TMS) during a maximal voluntary contraction can produce an increment in force which becomes greater as fatigue develops. In addition, the silent period (SP) duration increases during a fatiguing exercise, suggesting that there is a buildup of intracortical inhibition that might limit central motor drive. In contrast, motor evoked potential (MEP) amplitude increases during fatigue suggesting an increase in corticomotor excitability during exercise . . . The primary finding was a progressive increase in the fMRI signal during exercise, with a reduction following exercise, and signal changes were observed in all regions. These studies provide evidence that central adaptive processes occur during muscle fatigue and highlight the potential to facilitate these processes with interventional paradigms. The findings indicate the extent of cortical changes during fatigue and suggest that there may also be neurohaemodynamic and/or metabolic components to central adaptive processes. Understanding the central response to muscle fatigue should incorporate mechanisms both of central adaptation and central fatigue.

Le but de cette thèse était la recherche de biomarqueurs des troubles de l'humeur (dépression unipolaire et troubles bipolaires). Compte tenu de l'étiologie de ces troubles (hypométabolisme du cortex préfrontal dorso-latéral et déficit de la neurotransmission GABA/glutamatergique), nous avons choisi d'étudier deux biomarqueurs : la performance saccadique et l'excitabilité corticale. Nos résultats montrent que les performances saccadiques (antisaccades) permettent (i) de discriminer les patients présentant des troubles de l'humeur de sujets sains, (ii) d'objectiver l'amélioration thymique des patients suite à un traitement, et (iii) d'évaluer l'effet neuromodulateur à court-terme d'une séance de stimulation magnétique transcrânienne répétée. Concernant les mesures d'excitabilité corticale, aucune différence liée à l'amélioration thymique des patients, ni de différences entre patients et contrôles ne ressortent significativement. Nous avons suggéré que le non-contrôle du « State-Dependency » (i.e., de l'« état neurocognitif » des sujets pendant les stimulations) puisse être l'une des causes de l'absence de résultats, et validé cette hypothèse en manipulant les registres cognitifs et émotionnels des sujets.Le second aspect de notre travail de thèse avait trait à l'étude de l'efficacité de la stimulation magnétique transcrânienne répétée (rTMS) comme alternative thérapeutique non médicamenteuse des troubles de l'humeur. Si la littérature s'accorde sur une efficacité significative mais modérée de la rTMS comme traitement, nos données n'ont pas mis en évidence de supériorité du traitement actif par rapport au traitement placebo dans le cas de la neurostimulation iTBS. Une des raisons de ce manque d'efficacité du traitement actif pourrait être liée à des questions d'ordre méthodologique, comme le choix des paramètres de stimulation. Plus généralement, cette absence de résultats incite à questionner le postulat théorique basant l'étude de la réactivité du CPFDL ou sa neuromodulation sur les propriétés du cortex moteur. Notre expérience, étudiant la réactivité de différentes zones corticales par couplage TMS-EEG, va dans ce sens en montrant que la réactivité du cortex moteur diffère de celle des autres cortex. Le couplage TMS-EEG devrait permettre de mieux comprendre l'impact de la neuromodulation rTMS sur la cible corticale visée, et donc d'adapter les paramètres de stimulations aux aires cérébrales stimulées, permettant à terme de traiter plus efficacement les troubles de l'humeur. / The aim of this doctoral thesis was to develop biomarkers for mood disorders (unipolar major depression and bipolar disorders). Considering mood disorders' etiology (Dorso lateral prefrontal cortex hypometabolism and GABA/glutamate neurotransmission deficits), we decided to study two biomarkers: saccadic performance and cortical excitability. Our results showed that saccadic performance (notably Antisaccades) allows (i) discriminating bipolar patients from healthy subjects, (ii) ascertaining patients' mood improvement, and (iii) evaluating the short-term neuromodulation induced by repetitive transcranial magnetic stimulation.Regarding cortical excitability measurements, our results did not reveal any differences neither between patients and healthy subjects, nor between Responders and non Responders to a treatment (Ketamine injection or rTMS). We suggested that the null results could be explained by the lack of control of State-Dependency. This assumption was tested and validated through the manipulation of the subjects' cognitive and emotional states.A second aim of this doctoral thesis was to study the efficacy of rTMS, a non pharmacological therapeutic alternative, as a treatment for mood disorders. Meta-analyses showed that anti depressant effect of rTMS seems to be significant but still moderate. In our experiment, mood improvement did not differ between active and sham rTMS. Basic methodological reasons such as stimulation parameters could explain this lack of efficacy. Overall, one could wonder about the validity of the theoretical postulate of rTMS, drawn upon motor cortex reactivity. This postulate inferred that both cortical reactivity of motor cortex and DLPFC are similar. Using TMS-EEG coupling, we studied the reactivity of these cortices, to TMS pulses, which revealed that motor cortex and DLPFC reactivities should not be assimilated. This result calls into question the relevance of the rTMS theoretical postulate. Coupling TMS and EEG should allow a better understanding of the impact of rTMS neuromodulatory effect over the targeted area, and thus to a better adaption of the stimulation parameters, which could lead to an improvement of rTMS efficacy as a treatment for mood disorders.

O transtorno do déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento e sua prevalência na vida adulta é em torno de 2,5%. O tratamento farmacológico, apesar de efetivo, possui importantes limitações, justificando a busca por outras estratégias terapêuticas. A estimulação elétrica transcraniana (EETC) é uma técnica não invasiva de neuroestimulação que tem apresentado resultados promissores em melhorar o desempenho cognitivo em vários distúrbios neuropsiquiátricos, no entanto, poucos estudos avaliaram a sua eficácia e tolerabilidade no TDAH. Foi realizado um ensaio clínico randomizado, duplo-cego e controlado, com estimulação falsa para avaliar a eficácia da EETC nos sintomas de TDAH. Dezessete adultos com TDAH foram randomizados em dois grupos, nove receberam EETC verdadeira e oito, falsa. No grupo da EETC verdadeira foi aplicada estimulação com intensidade de corrente de 2 mA, durante 20 minutos, em cinco dias consecutivos. O ânodo foi posicionado sobre o córtex pré-frontal dorsolateral (CPFDL) direito e o cátodo sobre o CPFDL esquerdo. O grupo controle recebeu estimulação falsa durante o mesmo período. Os sintomas do TDAH foram mensurados por meio da escala Adult ADHD Self-Report Scale (ASRS) e a incapacidade com a escala Sheehan Disability Scale (SDS). As duas escalas foram aplicadas nos seguintes momentos: antes de iniciar (t0) as estimulações, ao final do protocolo (t1) e uma (t2), duas (t3) e quatro semanas (t4) após a intervenção. Observamos redução, estatisticamente significativa, na pontuação das escalas ASRS desatenção (p = 0,02) e SDS (p = 0,04) entre t0 e t1 após a intervenção em comparação ao grupo controle. Na ASRS total também observamos essa tendência, mas não se mostrou estatisticamente significativa (p = 0,07). Ampliando a análise dos dados observamos interação positiva entre tempo e tratamento na pontuação da ASRS total (p = 0,003), ASRS desatenção (p = 0,0001) e SDS (p = 0,001). Os dados deste estudo apontam que a EETC é eficaz para melhorar a atenção em adultos com TDAH. Contudo, mais pesquisas são necessárias para avaliar a eficácia clínica da ETCC nessa população. / Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with 2,5% prevalence in adulthood. Pharmacological treatment, although effective, has important limitations, justifying the search for other therapeutic strategies. Transcranial direct-current stimulation (tDCS) is a non-invasive neurostimulation technique which has show promising results to improve cognitive performance in several neuropsychiatric disorders, nonetheless few studies have evaluated their efficacy and tolerability in ADHD. A randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on ADHD symptoms. in adults with ADHD. Seventeen adults with ADHD were randomized into two groups, nine received active EETC eight, false. In the active group was applied EETC with 2mA current intensity, for 20 minutes, in five consecutive days. Anode was positioned on the right dorsolateral prefrontal cortex (DLPFC) and cathode over the left DLPFC. Control group received false stimulation during the same period. ADHD symptoms were measured using the scale Adult ADHD Self-Report Scale (ASRS) and the disability with Sheehan Disability Scale Scale (SDS). Both scales were applied at the following times: before starting the stimulation, the end of the protocol, and one, two and four weeks after the intervention. Subjects in the active group achieved significant reduction in ASRS inattention (p = 0,02) and SDS (p = 0,04) scores after intervention compared to control group. At ASRS total score was also observed this trend, without statistical significance (p = 0.07). Extending data analysis shows there are positive interaction between time and treatment on ASRS total score (p = 0,003), ASRS inattention (p = 0,0001) and SDS (p = 0,001). These data indicate that tDCS is effective to improving attention in adults with ADHD. However, further research is needed to assess the clinical efficacy of tDCS in this population.

No description available.

O transtorno do déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento e sua prevalência na vida adulta é em torno de 2,5%. O tratamento farmacológico, apesar de efetivo, possui importantes limitações, justificando a busca por outras estratégias terapêuticas. A estimulação elétrica transcraniana (EETC) é uma técnica não invasiva de neuroestimulação que tem apresentado resultados promissores em melhorar o desempenho cognitivo em vários distúrbios neuropsiquiátricos, no entanto, poucos estudos avaliaram a sua eficácia e tolerabilidade no TDAH. Foi realizado um ensaio clínico randomizado, duplo-cego e controlado, com estimulação falsa para avaliar a eficácia da EETC nos sintomas de TDAH. Dezessete adultos com TDAH foram randomizados em dois grupos, nove receberam EETC verdadeira e oito, falsa. No grupo da EETC verdadeira foi aplicada estimulação com intensidade de corrente de 2 mA, durante 20 minutos, em cinco dias consecutivos. O ânodo foi posicionado sobre o córtex pré-frontal dorsolateral (CPFDL) direito e o cátodo sobre o CPFDL esquerdo. O grupo controle recebeu estimulação falsa durante o mesmo período. Os sintomas do TDAH foram mensurados por meio da escala Adult ADHD Self-Report Scale (ASRS) e a incapacidade com a escala Sheehan Disability Scale (SDS). As duas escalas foram aplicadas nos seguintes momentos: antes de iniciar (t0) as estimulações, ao final do protocolo (t1) e uma (t2), duas (t3) e quatro semanas (t4) após a intervenção. Observamos redução, estatisticamente significativa, na pontuação das escalas ASRS desatenção (p = 0,02) e SDS (p = 0,04) entre t0 e t1 após a intervenção em comparação ao grupo controle. Na ASRS total também observamos essa tendência, mas não se mostrou estatisticamente significativa (p = 0,07). Ampliando a análise dos dados observamos interação positiva entre tempo e tratamento na pontuação da ASRS total (p = 0,003), ASRS desatenção (p = 0,0001) e SDS (p = 0,001). Os dados deste estudo apontam que a EETC é eficaz para melhorar a atenção em adultos com TDAH. Contudo, mais pesquisas são necessárias para avaliar a eficácia clínica da ETCC nessa população. / Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with 2,5% prevalence in adulthood. Pharmacological treatment, although effective, has important limitations, justifying the search for other therapeutic strategies. Transcranial direct-current stimulation (tDCS) is a non-invasive neurostimulation technique which has show promising results to improve cognitive performance in several neuropsychiatric disorders, nonetheless few studies have evaluated their efficacy and tolerability in ADHD. A randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on ADHD symptoms. in adults with ADHD. Seventeen adults with ADHD were randomized into two groups, nine received active EETC eight, false. In the active group was applied EETC with 2mA current intensity, for 20 minutes, in five consecutive days. Anode was positioned on the right dorsolateral prefrontal cortex (DLPFC) and cathode over the left DLPFC. Control group received false stimulation during the same period. ADHD symptoms were measured using the scale Adult ADHD Self-Report Scale (ASRS) and the disability with Sheehan Disability Scale Scale (SDS). Both scales were applied at the following times: before starting the stimulation, the end of the protocol, and one, two and four weeks after the intervention. Subjects in the active group achieved significant reduction in ASRS inattention (p = 0,02) and SDS (p = 0,04) scores after intervention compared to control group. At ASRS total score was also observed this trend, without statistical significance (p = 0.07). Extending data analysis shows there are positive interaction between time and treatment on ASRS total score (p = 0,003), ASRS inattention (p = 0,0001) and SDS (p = 0,001). These data indicate that tDCS is effective to improving attention in adults with ADHD. However, further research is needed to assess the clinical efficacy of tDCS in this population.