Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease

The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P = .019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

Emergence of sensory selection mechanisms in Artificial Life simulations

Background The evolutionary advantages of selective attention are unclear. Since the study of selective attention began, it has been suggested that the nervous system only processes the most relevant stimuli because of its limited capacity [1]. An alternative proposal is that action planning requires the inhibition of irrelevant stimuli, which forces the nervous system to limit its processing [2]. An evolutionary approach might provide additional clues to clarify the role of selective attention. Methods We developed Artificial Life simulations wherein animals were repeatedly presented two objects, "left" and "right", each of which could be "food" or "non-food." The animals' neural networks (multilayer perceptrons) had two input nodes, one for each object, and two output nodes to determine if the animal ate each of the objects. The neural networks also had a variable number of hidden nodes, which determined whether or not it had enough capacity to process both stimuli (Table 1). The evolutionary relevance of the left and the right food objects could also vary depending on how much the animal's fitness was increased when ingesting them (Table 1). We compared sensory processing in animals with or without limited capacity, which evolved in simulations in which the objects had the same or different relevances. Table 1. Nine sets of simulations were performed, varying the values of food objects and the number of hidden nodes in the neural networks. The values of left and right food were swapped during the second half of the simulations. Non-food objects were always worth -3. The evolution of neural networks was simulated by a simple genetic algorithm. Fitness was a function of the number of food and non-food objects each animal ate and the chromosomes determined the node biases and synaptic weights. During each simulation, 10 populations of 20 individuals each evolved in parallel for 20,000 generations, then the relevance of food objects was swapped and the simulation was run again for another 20,000 generations. The neural networks were evaluated by their ability to identify the two objects correctly. The detectability (d') for the left and the right objects was calculated using Signal Detection Theory [3]. Results and conclusion When both stimuli were equally relevant, networks with two hidden nodes only processed one stimulus and ignored the other. With four or eight hidden nodes, they could correctly identify both stimuli. When the stimuli had different relevances, the d' for the most relevant stimulus was higher than the d' for the least relevant stimulus, even when the networks had four or eight hidden nodes. We conclude that selection mechanisms arose in our simulations depending not only on the size of the neuron networks but also on the stimuli's relevance for action.

Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network

Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomic responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression.

Sensory phenomena associated with repetitive behaviors in obsessive-compulsive disorder: An exploratory study of 1001 patients

A substantial number of patients with obsessive-compulsive disorder (OCD) report compulsions that are preceded not by obsessions but by subjective experiences known as sensory phenomena. This study aimed to investigate the frequency, severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD patients with and without sensory phenomena in terms of clinical characteristics. We assessed 1,001 consecutive OCD patients, using instruments designed to evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level of insight and presence/severity of sensory phenomena. All together, 651 (65.0%) subjects reported at least one type of sensory phenomena preceding the repetitive behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had musculoskeletal sensations, 519 (79.7%) had externally triggered "just-right" perceptions, 176 (27.0%) presented internally triggered "just right," 144 (22.1%) had an "energy release," and 240 (36.9%) patients had an "urge only" phenomenon. Sensory phenomena were described as being as more severe than were obsessions by 102(15.7%) patients. Logistic regression analysis showed that the following characteristics were associated with the presence of sensory phenomena: higher frequency and greater severity of the symmetry/ordering/arranging and contamination/washing symptom dimensions; comorbid Tourette syndrome, and a family history of tic disorders. These data suggest that sensory phenomena constitute a poorly understood psychopathological aspect of OCD that merits further investigation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway

Aims: Cytokines interfere with signaling pathways and mediators of vascular contraction. Endothelin-1 (ET-1) plays a major role on vascular dysfunction in conditions characterized by increased circulating levels of adipokines. In the present study we tested the hypothesis that the adipokine chemerin increases vascular contractile responses via activation of ET-1/ET-1 receptors-mediated pathways. Main methods: Male, 10-12 week-old Wistar rats were used. Endothelium-intact and endothelium-denuded aortic rings were incubated with chemerin (0.5 ng/mL or 5 ng/mL, for 1 or 24 h), and isometric contraction was recorded. Protein expression was determined by Western blotting. Key findings: Constrictor responses to phenylephrine (PE) and ET-1 were increased in vessels treated for 1 h with chemerin. Chemerin incubation for 24 h decreased PE contractile response whereas it increased the sensitivity to ET-1. Endothelium removal significantly potentiated chemerin effects on vascular contractile responses to PE and ET-1. Incubation with either an ERK1/2 inhibitor (PD98059) or ETA antagonist (BQ123) abolished chemerin effects on PE- and ET-1-induced vasoconstriction. Phosphorylation of MEK1/2 and ERK1/2 was significantly increased in vessels treated with chemerin for 1 and 24 h. Phosphorylation of these proteins was further increased in vessels incubated with ET-1 plus chemerin. ET-1 increased MEK1/2, ERK1/2 and MKP1 protein expression to values observed in vessels treated with chemerin. Significance: Chemerin increases contractile responses to PE and ET-1 via ERK1/2 activation. Our study contributes to a better understanding of the mechanisms by which the adipose tissue affects vascular function and, consequently, the vascular alterations present in obesity and related diseases. (c) 2012 Elsevier Inc. All rights reserved.

Imperceptible electrical noise attenuates isometric plantar flexion force fluctuations with correlated reductions in postural sway

Optimal levels of noise stimulation have been shown to enhance the detection and transmission of neural signals thereby improving the performance of sensory and motor systems. The first series of experiments in the present study aimed to investigate whether subsensory electrical noise stimulation applied over the triceps surae (TS) in seated subjects decreases torque variability during a force-matching task of isometric plantar flexion and whether the same electrical noise stimulation decreases postural sway during quiet stance. Correlation tests were applied to investigate whether the noise-induced postural sway decrease is linearly predicted by the noise-induced torque variability decrease. A second series of experiments was conducted to investigate whether there are differences in torque variability between conditions in which the subsensory electrical noise is applied only to the TS, only to the tibialis anterior (TA) and to both TS and TA, during the force-matching task with seated subjects. Noise stimulation applied over the TS muscles caused a significant reduction in force variability during the maintained isometric force paradigm and also decreased postural oscillations during quiet stance. Moreover, there was a significant correlation between the reduction in force fluctuation and the decrease in postural sway with the electrical noise stimulation. This last result indicates that changes in plantar flexion force variability in response to a given subsensory random stimulation of the TS may provide an estimate of the variations in postural sway caused by the same subsensory stimulation of the TS. We suggest that the decreases in force variability and postural sway found here are due to stochastic resonance that causes an improved transmission of proprioceptive information. In the second series of experiments, the reduction in force variability found when noise was applied to the TA muscle alone did not reach statistical significance, suggesting that TS proprioception gives a better feedback to reduce force fluctuation in isometric plantar flexion conditions.

Changes in FDB and soleus muscle activity after a train of stimuli during upright stance

Background: Evidence of self-sustained muscle activation following a brief electrical stimulation has been reported in the literature for certain muscles. Objectives: This report shows that the foot muscle (Flexor Digitorum Brevis - FDB) shows a self-sustained increase in muscle activity during upright stance in some subjects following a train of stimuli to the tibial nerve. Methods: Healthy subjects were requested to stand upright and surface EMG electrodes were placed on the FDB, Soleus and Tibialis Anterior muscles. After background muscle activity (BGA) acquisition, a 50 Hz train of stimuli was applied to the tibial nerve at the popliteal fossa. The root mean square values (RMS) of the BGA and the post-stimulus muscle activation were computed. Results: There was a 13.8% average increase in the FDB muscle EMG amplitude with respect to BGA after the stimulation was turned off. The corresponding post-stimulus Soleus EMG activity decreased by an average of 9.2%. We hypothesize that the sustained contraction observed in the FDB following stimulus may be evidence of persistent inward currents (PIC) generated in FDB spinal motoneurons. The post-stimulus decrease in soleus activity may have occurred due to the action of inhibitory interneurons caused by the PICs, which were triggered by the stimulus train. Conclusions: These sustained post-stimulation changes in postural muscle activity, found in different levels in different subjects, may be part of a set of possible responses that contribute to overall postural control.

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. The cytokines present at highest concentrations in the rat NP were TNF-alpha, IL-1 beta and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-alpha, IL-1 beta and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

Characterization of red wines from South America based on sensory properties and antioxidant activity

BACKGROUND: It is widely accepted that red wines constitute one of the most important sources of dietary polyphenolic antioxidants. However, it is still not known how some variables such as variety, vintage, country of origin, and retail price are associated with the antioxidant activity and sensory profile of South American red wines. In this regard, 80 samples produced in Brazil, Chile and Argentina were assessed in relation to their sensory properties, color and in vitro antioxidant activity, and results were subjected to multivariate statistical techniques. RESULTS: Samples were grouped in clusters, characterized by high, intermediate and low in vitro antioxidant activity, sensory properties and prices. It was possible to observe that wines with high antioxidant activity were associated to high retail prices and overall perception of sensory quality. CONCLUSION: South American wines produced from Vitis vinifera such as Syrah, Malbec and Cabernet Sauvignon had higher in vitro antioxidant activity and also higher sensory quality than wines produced from Vitis labrusca. This result was independent of vintage (2002-2010), corroborating the idea that the same grape varietal, even when produced in different years, displays similar sensory characteristics and antioxidant activity. (C) 2011 Society of Chemical Industry

Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: Possible pathways for antinociception

Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, delta-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Cough and dyspnea during bronchoconstriction: comparison of different stimuli

Abstract Background Bronchial challenge tests are used to evaluate bronchial responsiveness in diagnosis and follow-up of asthmatic patients. Challenge induced cough has increasingly been recognized as a valuable diagnostic tool. Various stimuli and protocols have been employed. The aim of this study was to compare cough and dyspnea intensity induced by different stimuli. Methods Twenty asthmatic patients underwent challenge tests with methacholine, bradykinin and exercise. Cough was counted during challenge tests. Dyspnea was assessed by modified Borg scale and visual analogue scale. Statistical comparisons were performed by linear mixed-effects model. Results For cough evaluation, bradykinin was the most potent trigger (p < 0.01). In terms of dyspnea measured by Borg scale, there were no differences among stimuli (p > 0.05). By visual analogue scale, bradykinin induced more dyspnea than other stimuli (p ≤ 0.04). Conclusion Bradykinin seems to be the most suitable stimulus for bronchial challenge tests intended for measuring cough in association with bronchoconstriction.

The influence of speech stimuli contrast in cortical auditory evoked potentials

Studies about cortical auditory evoked potentials using the speech stimuli in normal hearing individuals are important for understanding how the complexity of the stimulus influences the characteristics of the cortical potential generated. OBJECTIVE: To characterize the cortical auditory evoked potential and the P3 auditory cognitive potential with the vocalic and consonantal contrast stimuli in normally hearing individuals. METHOD: 31 individuals with no risk for hearing, neurologic and language alterations, in the age range between 7 and 30 years, participated in this study. The cortical auditory evoked potentials and the P3 auditory cognitive one were recorded in the Fz and Cz active channels using consonantal (/ba/-/da/) and vocalic (/i/-/a/) speech contrasts. Design: A crosssectional prospective cohort study. RESULTS: We found a statistically significant difference between the speech contrast used and the latencies of the N2 (p = 0.00) and P3 (p = 0.00) components, as well as between the active channel considered (Fz/Cz) and the P3 latency and amplitude values. These correlations did not occur for the exogenous components N1 and P2. CONCLUSION: The speech stimulus contrast, vocalic or consonantal, must be taken into account in the analysis of the cortical auditory evoked potential, N2 component, and auditory cognitive P3 potential.

Estudo prospectivo da sensibilidade tátil em mãos de uma população brasileira usando pressure-specified sensory device

OBJETIVO: Avaliar os limiares de percepção da pressão em polpas de dois dedos (indicador e mínimo), em uma população brasileira, sem lesão nervosa ou neuropatia. MÉTODOS: Usamos Pressure-Specified Sensory Device, um equipamento computadorizado para obter limiares de percepção da pressão normal, tanto estáticos quanto dinâmicos, e discriminação de dois pontos. RESULTADOS: Testamos a sensibilidade nos dedos, em 30 voluntários. Os testes de significância foram realizados utilizando o teste t de Student. Os valores médios (g/mm²) para os limiares de pressão estática de um e dois pontos (s1PD, s2PD) e discriminação dinâmica de um e dois pontos (m1PD, m2PD) no dedo indicador dominante foram: s1PD = 0,4, m1PD = 0,4, s2PD = 0,48, m2PD = 0,51. CONCLUSÃO: Não há diferença significativa na sensibilidade entre as mãos dominante e não dominante.

Componentes sensoriais e atencionais do tempo de reação: efeitos do tamanho, excentricidade e previsibilidade de estímulos visuais

A percepção visual depende do arcabouço sensorial e do processamento atencional. Este trabalho estudou o efeito, sobre o tempo de reação manual (TR), do tamanho, excentricidade e previsibilidade de estímulos visuais. No experimento 1 (n=8), um alvo foi apresentado aleatoriamente em uma de quatro excentricidades diferentes, possuindo três possíveis tamanhos. O experimento 2 (n=12) apresentava configuração similar, porém uma pista indicava o quadrante de maior probabilidade (70%) de apresentação do alvo. Os resultados mostraram um aumento do TR em função da excentricidade do alvo, além de uma diminuição do TR com o aumento do tamanho do alvo e indicação correta da pista. Uma análise das interações sugere uma superposição de mecanismos atencionais e puramente sensoriais compartilhando um estágio comum do processamento visual.

Effects of visual and auditory stimuli in a choice reaction time task

The effect produced by a warning stimulus(i) (WS) in reaction time (RT) tasks is commonly attributed to a facilitation of sensorimotor mechanisms by alertness. Recently, evidence was presented that this effect is also related to a proactive inhibition of motor control mechanisms. This inhibition would hinder responding to the WS instead of the target stimulus (TS). Some studies have shown that auditory WS produce a stronger facilitatory effect than visual WS. The present study investigated whether the former WS also produces a stronger inhibitory effect than the latter WS. In one session, the RTs to a visual target in two groups of volunteers were evaluated. In a second session, subjects reacted to the visual target both with (50% of the trials) and without (50% of the trials) a WS. During trials, when subjects received a WS, one group received a visual WS and the other group was presented with an auditory WS. In the first session, the mean RTs of the two groups did not differ significantly. In the second session, the mean RT of the two groups in the presence of the WS was shorter than in their absence. The mean RT in the absence of the auditory WS was significantly longer than the mean RT in the absence of the visual WS. Mean RTs did not differ significantly between the present conditions of the visual and auditory WS. The longer RTs of the auditory WS group as opposed to the visual WS group in the WS-absent trials suggest that auditory WS exert a stronger inhibitory influence on responsivity than visual WS.