Adherence is a complex concept, with multiple definitions, over 200 possible predictors, and inconsistent measurement. This has had a detrimental impact on producing interventions to promote treatment adherence. Promoting and maintaining treatment adherence can decrease the likelihood of poor health outcomes and decrease healthcare costs for patients. This study created a conceptual model that was utilized in a secondary analysis to determine if patient factors (Income, Depression, Perceived Threat of Illness Severity, Social Support, and Treatment Beliefs) in the model predict adherence to Transcutaneous Electrical Nerve Stimulation (TENS) when used for pain control post-Total Knee Replacement (TKR). The sample included 97 patients who were randomized to TENS treatment. A higher level of Perceived Threat of Illness Severity, measured with the Pain Catastrophizing Scale, was significantly related to a Moderate level of Adherence (60-79%) versus Non-Adherence (0-59%) (OR= .260, 95% CI= .073-.992, p= .037). The other patient factors of income, depression, social support and treatment beliefs did not significantly predict adherence. This finding is clinically important, as clinicians can assess how patients are interpreting or perceiving actual (or potential) threats of illness severity, then provide education and support to help patients adhere to treatment. The effect of Daily Pain [measured with an 11-point Numeric Rating Scale (0-10)] on Daily Adherence was also investigated in this study. Daily Pain and Daily Adherence did not show a significant association in this sample. This could be attributed to the fact that Daily Adherence was maintained consistently around 70% throughout the 2-week period.

Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. Stimulation of the vagus nerve, which innervates the heart and abdominal organs, is proving to be an effective therapeutic in heart failure. We hypothesized that cervical vagus nerve stimulation (VNS) could alter fecal flora and prevent aberrations observed in fecal samples from heart failure animals. To determine whether microbial abundances were altered by pressure overload (PO), leading to heart failure and VNS therapy, a VNS pulse generator was implanted with a stimulus lead on either the left or right vagus nerve before creation of PO by aortic constriction. Animals received intermittent, open-loop stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end-systolic and diastolic volumes, as well as cardiac output, were impaired in PO animals compared with baseline. VNS mitigated these effects. Metagenetic analysis was then performed using 16S rRNA sequencing to identify bacterial genera present in fecal samples. The abundance of 10 genera was significantly altered by PO, 8 of which were mitigated in animals receiving either left- or right-sided VNS. Metatranscriptomics analyses indicate that the abundance of genera that express genes associated with ATP-binding cassette transport and amino sugar/nitrogen metabolism was significantly changed following PO. These gut flora changes were not observed in PO animals subjected to VNS. These data suggest that VNS prevents aberrant gut flora following PO, which could contribute to its beneficial effects in heart failure patients.

Chronic heart failure (HF) is estimated to affect 23 million people worldwide, and many patients show minimal improvement after treatment with high-potency medications. HF with reduced left ventricular ejection fraction makes up approximately half of cases and is associated with high mortality: a 5-year survival rate of only 25% after hospitalization. This disease is marked by autonomic and cardiac dysfunction, as well as increased inflammatory markers both in the brain and microbiota of the gastrointestinal tract. As a main component of the autonomic nervous system, the vagus nerve has been identified as a potential treatment target for HF. Vagus nerve stimulation (VNS) is thought to help re-balance the autonomic system and has shown promising results in clinical trials for treatment of HF. Although the mechanism of action for VNS remains partially understood, anti-inflammatory pathways have been shown to play a significant role, and these pathways may be enhanced by microbiota signaling via the vagus nerve. The goal of the current study is to provide insight into VNS treatment for HF with reduced ejection fraction via a pressure overload (PO) model. Male Sprague-Dawley rats were randomly divided into age-matched control (n=7), PO (n=6), and PO+VNS (n=11). PO rats underwent aortic constriction (~40%) to induce HF, and a subset of these had VNS leads implanted around the left cervical vagus nerve. Treatment was initiated for PO+VNS rats after reaching a 20% drop in left ventricular relative ejection fraction (EF, p<0.001). VNS was delivered using 1.0 mA pulses at 20 Hz, with 14 sec on-time followed by 66 sec off-time for 2 months to model settings used in successful clinical studies. Echocardiography to image the heart and fecal samples to assess microbiota were collected at regular intervals for all rats. Hearts were weighed at termination for a final heart to body weight ratio, and brains were processed to assess neuroinflammation. Findings indicate that while PO reduced EF ~40% at termination (p<0.05), VNS treatment restored EF back to control levels (p<0.0001 compared to study midpoint). Further, the heart/body weight ratio was increased for PO rats (p<0.05) compared to controls and PO+VNS rats. These data demonstrate that physiological markers of heart failure can be mitigated using these VNS settings. Notably, 66% of microbiota populations altered by PO were prevented with VNS treatment. Further, prolonged VNS significantly affected microbiota populations involved in inflammatory processes. Neuroinflammation was assessed in two key autonomic nuclei: paraventricular nucleus of the hypothalamus and locus coeruleus. PO displayed increased neuroinflammation as measured by microglial density in both regions, and VNS attenuated this effect (p<0.001). These findings indicate relevant contributions of inflammatory mechanisms and microbiome alterations for beneficial VNS effects leading to improved cardiac function in HF.

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique used to activate vagal afferent fibers located in the concha of the outer ear. Vagal afferents project to the nucleus of the solitary tract (NTS) where information is processed and propagated to higher brain regions. Widespread NTS connections provide a mechanism through which taVNS can be used to influence multiple systems and be a potential treatment for many disorders including heart failure, gastric motility disorders, and migraines. Recent studies are now investigating taVNS as an alternative treatment option to invasive cervical vagus nerve stimulation (cVNS) which is FDA approved to treat drug-resistant epilepsy and depression but has limited patient availability due to the invasiveness of the procedure. Migraine and epilepsy clinical studies have shown therapeutic taVNS benefits and human fMRI studies have demonstrated comparable brain activation between cVNS and taVNS. However, questions remain regarding optimal taVNS parameters, and no study has compared the direct mechanisms responsible for cVNS and taVNS effects. In this study, a high-impedance tungsten electrode was stereotaxically placed into NTS in 10 chloralose-anesthetized rats, and 40-70 neurons were interrogated using electrophysiological methods. Firing rate changes during stimulation on-times were compared to activity levels during stimulation off-times. Neurons were classified as positive responders if they displayed consistent firing rate increases during stimulation, negative responders if they displayed consistent decreases, and non-responders if there was no consistency using a mathematical cosine similarity score. Six taVNS stimulation parameters were investigated using three frequencies (20, 100, 250Hz) at two intensities (0.5, 1.0mA) to identify parameter-specific effects on NTS neurons. Additionally, neuronal activity was evaluated following cVNS at 20 and 250Hz at the bradycardic intensity (lowest intensity to generate a transient 5% decrease in heart rate, BI) and compared to taVNS effects at the corresponding frequencies. Our data shows that taVNS at 20Hz, 1.0mA yields the greatest number of positive responders and 100Hz, 1.0mA yields the greatest number of negative responders (p<0.05) suggesting different taVNS parameters can differentially influence NTS activity. Comparisons between the number of responders generated with cVNS and taVNS revealed significantly fewer negative responders with cVNS at 20Hz compared to taVNS at 20Hz regardless of intensity (p<0.01) but yielded comparable positive responders between cVNS at 20Hz, BI and taVNS at 20Hz, 1.0mA. No significant differences were observed between the number of cVNS and taVNS responders at 250Hz. Interestingly, individual neuronal responses were different between both methods of stimulation, suggesting that they could work through different neuronal pathways.

Reflex inhibition of the quadriceps muscle group is a frequent and significant consequence of knee trauma, disease and surgical insult. The resultant quadriceps atrophy can be expected to delay rehabilitation and render the joint vulnerable to repeated injury resulting in capsular and synovial thickening, effusion and pain. A major purpose of this study was to examine the degree of quadriceps inhibition experienced by patients who undergo arthroscopic menisectomy. A secondary goal of this study was to investigate the efficacy of transcutaneous electrical nerve stimulation on the relief of reflex inhibition. Tests were performed on 12 patients prior to, and on day 1 and day 2 post surgery. True and placebo treatments of transcutaneous electrical nerve stimulation were administered on day 1 and day 2 post surgery. Measurements were made on the injured and normal limb with the knee fixed at 38G of flexion. Motor unit activation was determined by the twitch interpolation technique. Reduced motor unit activation was considered indicative of quadriceps reflex inhibition. Testing demonstrated that at all times the injured leg was weaker than the normal leg (p=.OOl). Following surgery, strength of the injured limb was significantly less than its pre operative score (p=.Ol). No significant recovery of strength was observed during the first two days following surgery. Injured legs were characterized by significantly lower motor unit activation at all times of testing Cp=.003). Following surgery, motor unit activation for the injured leg was significantly lower than its pre operative value (p=.Ol). By day 2 post surgery, motor unit activation had recovered Cp=.05) and was similar to the pre operative values for that leg. Transcutaneous electrical nerve stimulation had no effect on strength or motor unit activation. Recovery following arthroscopic surgery is characterized by an initial loss of strength and motor unit activation. By day 2, isometric strength remains depressed, however motor unit activation returns to pre surgery levels. / Thesis / Master of Science (MSc)

No description available.

Evidence indicates attention can alter afferent inhibition, a Transcranial Magnetic Stimulation (TMS) evoked measure of cortical inhibition following somatosensory input. This measure is emerging as a valuable tool for clinical assessment of sensorimotor function. However, the reliability of the measure remains relatively low. Further, attention is capable of modifying the magnitude of afferent inhibition. Therefore, for afferent inhibition to become an assessment with translation within and beyond the research lab, the reliability of the measure must be improved. Controlling the focus of attention may be one method to improve the reliability of afferent inhibition. In the present study, two experiments were conducted. One to assess the biological effects of attention on SAI and LAI, and the other to address whether the reliability of SAI and LAI are altered in the presence of varying attentional demands. The magnitude of short- and long-latency afferent inhibition (SAI and LAI, respectively) was assessed under four conditions with varying attentional demands focused on the somatosensory input that mediates SAI and LAI circuits. Further, the reliability of SAI and LAI was assessed with and without directed attention to the relevant somatosensory input to explore whether attention to the tactile stimulation can improve intrasession and intersession reliability of these measures. Thirty individuals participated in four conditions; three conditions were identical in their physical parameters and varied only in the focus of directed attention (visual attend, tactile attend, non- directed attend) and one condition consisted of no external physical parameters (no stimulation). Reliability was measured by repeating conditions at three time points to assess intrasession and intersession reliability. Results indicate the magnitude of SAI and LAI were not modulated by varied attention. Reliability assessments demonstrated that the attention manipulations increased intrasession and intersession reliability of SAI and LAI compared to the no stimulation condition. This research exposes the influence of attention, and its impact on the reliability of afferent inhibition. By quantifying these influences, this research has identified new information to inform the design of TMS research in sensorimotor integration. / Thesis / Master of Science in Kinesiology / Attention can alter transcranial magnetic stimulation (TMS) evoked afferent inhibition. Measures of afferent inhibition are emerging as valuable tools for clinical assessments of sensorimotor function. However, the reliability of afferent inhibition remains relatively low, limiting its value in the clinic. Afferent inhibition is increased when the one’s attention is focused on the peripheral nerve stimulation used to elicit afferent inhibition. However, it is unknown whether afferent inhibition, with attention directed to somatosensory input, will improve the reliability of these measures. This is important as it suggests that changes to the methodology used to acquire afferent inhibition can improve the reliability of this measure, thereby increasing the opportunity for translation to the clinic. The goal of this study was to assess the influence of attention on afferent inhibition circuits, short afferent inhibition (SAI) and long afferent inhibition (LAI) and determine whether attention modulation would increase the reliability of afferent inhibition.

Vagus nerve stimulation (VNS) is a promising neuromodulatory therapy under investigation for a range of disorders, including heart failure, gastric dysmotility, and migraine. Two primary forms of VNS are currently investigated: cervical VNS (cVNS), involving surgically implantation to activate vagal afferents in the cervical branch in the neck and transcutaneous auricular VNS (taVNS) which subcutaneously stimulates the auricular branch in the outer ear. The nucleus of the solitary tract (NTS) serves as a relay-station receiving 90% of vagal afferents, enabling connections with higher-order brain regions and other brainstem nuclei like the spinal trigeminal nucleus (Sp5) and locus coeruleus (LC), facilitating neuromodulation through VNS. Research has established the efficacy of VNS at 20–30 Hz for disorders like depression, but the impact of alternative stimulation parameters on medullary nuclei neuromodulation remains unclear. These studies used anesthetized rats to extracellularly record neuronal activity across varying VNS parameters within NTS, Sp5, and LC. Neuronal responses were classified as positive (increased activity), negative (decreased activity), or non-responders (no response). In LC, cVNS at standard paradigms (≥ 10 Hz) and bursting paradigms with shorter interburst intervals or increased pulses induced more positive responders, while standard 5 Hz generated more negative responders. Additionally, a build-up effect was observed in LC, with increased responders over consecutive VNS cycles. In NTS and Sp5, taVNS evoked comparable activation, with more positive responders at 20 Hz and 100 Hz and stronger responses at higher intensities. However, Sp5 responses were twice as strong compared to NTS. Furthermore, comparative analysis between taVNS and cVNS revealed similar overall activation in NTS, but distinct activation profiles in individual neurons indicate different pathways. Finally, the therapeutic efficacy of VNS therapy was evaluated in heart failure using a pressure-overload rat model. A 60-day cVNS treatment restored adverse cardiac remodeling and dysfunction, mitigated cardiac molecular changes, and prevented neuroinflammatory responses within brainstem nuclei. The findings presented herein demonstrated differential parameter-specific and nuclei-specific responses to taVNS and cVNS, investigated the mechanisms responsible for taVNS modulation, and confirmed that VNS therapy, when initiated early, can mitigate heart failure development and restore multiorgan homeostasis in a PO model.

Peripheral nerve stimulation (PNS) is commonly used to promote use-dependent cortical plasticity for rehabilitation of motor function in spinal cord injury. Pairing transcranial magnetic stimulation (TMS) with PNS has been shown to increase motor evoked potentials most when the two stimuli are timed to arrive in the cortex simultaneously. This suggests that a mechanism of timing-dependent plasticity (TDP) may be a more effective method of promoting motor rehabilitation. The following thesis is the result of applying a brain-computer interface to apply PNS in closed-loop simultaneously to movement intention onset as measured by EEG of the sensorimotor cortex to test whether TDP can be induced in incomplete spinal cord injured individuals with upper limb motor impairment. 4 motor incomplete SCI subjects have completed 12 sessions of closed-loop PNS delivered over 4-6 weeks. Benefit was observed for every subject although not consistently across metrics. 3 out of 4 subjects exhibited increased maximum voluntary contraction force (MVCF) between first and last interventions for one or both hands. TMS-measured motor map volume increased for both hemispheres in one subject, and TMS center of gravity shifted in 3 subjects consistent with studies in which motor function improved or was restored. These observations suggest that rehabilitation using similar designs for responsive stimulation could improve motor impairment in SCI.

O uso da Estimulação Elétrica Transcutânea do Nervo (TENS) vem sendo muito pesquisado em pós-operatórios, todavia os estudos não analisam se a TENS de baixa freqüência -- que estimula a liberação de opióides endógenos -- seria eficiente em promover analgesia preemptiva. Objetivo. Analisar se essa modalidade de TENS, aplicada antes de colecistectomias por laparotomia, poderia proporcionar analgesia preemptiva. Casuística e método. A pesquisa -- clínica, controlada, randomizada e duplamente encoberta -- foi realizada no Hospital São Domingos Sávio, e teve uma amostra de 50 pacientes, todas do sexo feminino: grupo preemptivo (n = 25) e placebo (n = 25). As pacientes do primeiro grupo foram submetidas à aplicação da TENS de baixa freqüência antes da cirurgia: e as do grupo placebo, a uma falsa estimulação. Houve a padronização do cloridrato de bupivacaína (0,5%) como droga anestésica, associado ao fentanil (2 ml) para a realização das colecistectomias; e da medicação analgésica utilizada no pós-operatório: dipirona, prescrita de 6 em 6 horas, e diclofenaco de sódio, como medicação de resgate. A intensidade de dor pós-operatória foi mensurada pela Escala Numérica de Mensuração da Dor (END), em 8 momentos (2½, 3½, 4½, 5½, 7, 8 e 16 horas após a indução do bloqueio anestésico, além de uma última verificação no momento da alta hospitalar), e pelo Questionário de Dor McGill (MPQ), aplicado 16 horas após a indução do bloqueio anestésico. Outrossim, o grau de satisfação das pacientes com o tratamento foi mensurado pela Escala de Satisfação do Paciente (ESP). Os dados foram analisados por meio de testes estatísticos descritivos, Teste de Mann-Whitney, Teste-t de Student para amostras não-pareadas e qui-quadrado, sendo o nível de significância de 5%. Resultados. A intensidade de dor, mensurada pela END, foi significantemente menor no grupo preemptivo nas terceira e quarta coletas. Não houve diferença significante quanto aos índices obtidos pelo MPQ, e nem quanto à satisfação das pacientes, o consumo de drogas analgésicas no pós-operatório e o tempo para o primeiro requerimento de diclofenaco de sódio. Conclusão. A TENS de baixa freqüência proporcionou analgesia preemptiva após colecistectomia por laparotomia. / Introduction. Transcutaneous Electrical Nerve Stimulation (TENS) has been searched in the postoperative period, however these studies don\'t analyze whether low frequency TENS -- that stimulates the release of endogenous opioids -- could be efficient to provide preemptive analgesia. Objective. The aim of this study was to verify whether low frequency TENS, applied before open cholecystectomies, could provide it. Cases and method. It was a controlled, randomized and double-blinded trial, carried out at the Hospital São Domingos Sávio (Aracaju city, Brazil), and had a sample of 50 patients: preemptive group (n = 25) and placebo (n = 25). The patients from the first group were submitted to the application of TENS before the surgery; and the placebo group to a false stimulation. There was the standardization of the bupivacaine (0,5 %) as anesthetic drug plus fentanyl (2 ml) for the accomplishment of the cholecystectomies; and of the analgesic medication used in the postoperative period: dipyrone, prescribed for every 6 hours, and diclofenac, only if the patients complained about pain. Pain intensity was measured by the Numerical Rating Scale (NRS), in 8 moments (2½, 3½, 4½, 5½, 7, 8 e 16 hours after inducing the anesthesia besides one last verification at the hospital discharge), and by the Brazilian version of the McGill Pain Questionnaire (Br-MPQ), applied 16 hours after inducing the anesthesia. Patient satisfaction level in relation to the treatment was measured by the Patient Satisfaction Scale (PSS). The data were analyzed by Mann-Whitney Test, unpaired t-test and qui-square, being significant, those data with p < 0,05. Results. Pain intensity, measured by the NRS, was lower in the preemptive group in the third and fourth verifications. There was no difference neither in relation to the indexes obtained with the Br-MPQ, nor the PSS, consume of analgesics in the postoperative and time for the first request of diclofenac. Conclusion. Low frequency TENS provided preemptive analgesia after open cholecystectomy.