Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol.

Stimulation of the vagus nerve, a parasympathetic nerve that controls the neuro-digestive, vascular, and immune systems, induces pain relief, particularly in clinical conditions such as headache and rheumatoid arthritis. Transmission through vagal afferents towards the nucleus of the solitary tract (NST), the central relay nucleus of the vagus nerve, has been proposed as the main physiological mechanism that reduces pain intensity after vagal stimulation. Chronic pain symptoms of fibromyalgia patients might benefit from stimulation of the vagus nerve via normalization of altered autonomic and immune systems causing their respective symptoms. However, multi-session non-invasive vagal stimulation effects on fibromyalgia have not been evaluated in randomized clinical trials. We propose a parallel group, sham-controlled, randomized study to modulate the sympathetic-vagal balance and pain intensity in fibromyalgia patients by application of non-invasive transcutaneous vagus nerve stimulation (tVNS) over the vagal auricular and cervical branches. We will recruit 136 fibromyalgia patients with chronic moderate to high pain intensity. The primary outcome measure will be pain intensity, and secondary measures will be fatigue, health-related quality of life, sleep disorders, and depression. Heart rate variability and pro-inflammatory cytokine levels will be obtained as secondary physiological measures. We hypothesize that multiple tVNS sessions (five per week, for 4 weeks) will reduce pain intensity and improve quality of life as a result of normalization of the vagal control of nociception and immune-autonomic functions. Since both vagal branches project to the NST, we do not predict significantly different results between the two stimulation protocols.

Bilateral Motor Cortex tDCS Effects on Post-Stroke Pain and Spasticity: A Three Cases Study.

Stroke patients frequently suffer from chronic limb pain, but well-suited treatment approaches have been not established so far. Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation technique that alters cortical excitability, and it has been shown that motor cortex tDCS can reduce pain. Some data also suggest that spasticity may be improved by tDCS in post-stroke patients. Moreover, multiple sessions of tDCS have shown to induce neuroplastic changes with lasting beneficial effects in different neurological conditions. The aim of this pilot study was to explore the effect of multiple anodal tDCS (atDCS) sessions on upper limb pain and spasticity of stroke patients, using a within-subject, crossover, sham-controlled design. Brain damage was of similar extent in the three patients evaluated, although located in different hemispheres. The results showed a significant effect of 5 consecutive sessions of atDCS, compared to sham stimulation, on pain evaluated by the Adaptive Visual Analog Scales -AVAS-, and spasticity evaluated by the Fugl-Meyer scale. In two of the patients, pain was completely relieved and markedly reduced, respectively, only after verum tDCS. The pain improvement effect of atDCS in the third patient was considerably lower compared to the other two patients. Spasticity was significantly improved in one of the patients. The treatment was well-tolerated, and no serious adverse effects were reported. These findings suggest that multiple sessions of atDCS are a safe intervention for improving upper limb pain and spasticity in stroke patients, although the inter-individual variability is a limitation of the results. Further studies including longer follow-up periods, more representative patient samples and individualized stimulation protocols are required to demonstrate the efficacy and safety of tDCS for improving limb symptoms in these patients.

Decision Making Profile of Positive and Negative Anticipatory Skin Conductance Responders in an Unlimited-Time Version of the IGT.

Based on the somatic marker hypothesis (Damasio, 1994), many studies have examined whether or not physiological responses are "somatic markers" that implicitly guide the decision making process. Vegetative or motor reactions that are produced by negative or positive stimuli generate a series of somatic markers. So, when a similar stimuli is encountered in the future, these somatic marks will facilitate favorable decisions and inhibit the disadvantageous ones (Martínez-Selva et al., 2006). The most widely studied physiological responses, as indicators of these markers, are heart rate and the skin conductance response (Damasio, 1994; Bechara et al., 1996). The Iowa Gambling Task (IGT) has been the most widely used tool in this research. The common IGT protocol for psychophysiological studies comprises limited inter-trial intervals, and does not distinguish participants as a function of relevant physiological traits, such as the anticipatory skin conductance response (aSCR). The objectives of this work were to determine whether "somatic markers" guide the decision making process without time restrictions and to examine the effects of opposite aSCR profiles on this process. Participants were 29 healthy subjects, divided into two groups according to positive (+) and negative (-) aSCR. Two different data analysis strategies were applied: firstly, gambling indices were computed and, secondly, we examined the parameters of the probabilistic Prospect Valence Learning (PVL) model in three versions: maximum likelihood estimation (MLE), PVL-Delta and PVL-Decay simulations with Hierarchical Bayesian analysis (HBA) for parameter estimation. The results show a significant group effect in gambling indices, with the aSCR+ group presenting lower risk in the decision making process than the aSCR- group. Significant differences were also observed in the Utility parameter of MLE-PVL, with the aSCR- group have low sensitivity to feedback outcomes, than aSRC+ group. However, data from the PVL simulations do not show significant group differences and, in both cases, the utility value denotes low sensitivity to feedback outcomes.

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance.

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS-namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.

Differences between oral and written calculation: evidence from cognitive neuropsychology from six brain-damaged patients / Diferencias entre cálculo oral y escrito: evidencias desde la neuropsicología cognitiva a partir de seis casos de daño cerebral

Introduction: The study of patients with acquired brain injury shows the existence of several double dissociations in the calculation sys-tem. In this paper, we focus on the double dissociation observed between oral and written calculation. Method: Instrument: Battery of Evaluation and Numerical Processing and Calculation. Participants: Six patients with acquired brain injury who have different alterations in the processing of numbers and calculations. Data analysis: Difference of proportions. Results: MC and BET have impaired the written calculation but they preserve oral calculation (addition, subtraction and multiplication). The same is ob-served in MNL for addition and multiplication and in PP for subtraction. The reverse pattern is observed in IRS and ACH who have alterations in written calculation but preserve oral calculation (in multiplication and sub-traction, respectively). Conclusions: The results demonstrate the functional independence of oral and written calculation. This could indicate that the calculation system is not unitary and responsible for any calculation task, but a multi-componential system involving different processes and of a different nature

Introducción: El estudio de pacientes con daño cerebral adquirido pone de manifiesto la existencia de varias dobles disociaciones en el sistema de cálculo. En este trabajo nos centramos en la doble disociación observada entre cálculo oral y cálculo escrito. Método: Instrumento: Batería de Evaluación del Procesamiento Numérico y Cálculo. Participantes: Seis pacientes con daño cerebral adquirido que presentan distintas alteraciones en el procesamiento de los números y el cálculo. Análisis de los datos: Diferencia de proporciones. Resultados: MC y BET presentan alterado el cálculo escrito pero conservan el cálculo oral (suma, resta y multiplicación). Lo mismo sucede a MNL en suma y multiplicación y a PP en la resta. El patrón inverso, se observa en IRS y ACH con alteraciones en cálculo escrito y preservación del oral (en multiplicación y resta, respectivamente). Conclusiones: Los resultados ponen de manifiesto la independencia funcional entre cálculo oral y escrito. Esto podría indicar que el sistema de cálculo no es un todo unitario responsable de cualquier tarea de cálculo, sino que posiblemente sea un sistema multicomponencial en el que intervendrían distintos procesos y de diferente naturaleza

Independence of basic arithmetic operations: Evidence from cognitive neuropsychology / Independencia entre operaciones aritméticas básicas: evidencia desde la neuropsicología cognitiva

Los casos descritos en la literatura ponen de manifiesto que las operaciones aritméticas pueden funcionar independientemente, lo que permite inferir que los procesos cognitivos implicados en las distintas operaciones podrían ser distintos. El objetivo de este trabajo es determinar los distintos procesos implicados en la resolución de operaciones aritméticas: suma, resta y multiplicación. Método. Instrumento: Batería de evaluación del procesamiento numérico y el cálculo (Salguero y Alameda, 2007, 2011). Sujetos: pacientes con daño cerebral adquirido. Resultados y conclusiones: El paciente MNL conserva la suma y la multiplicación pero presenta alterada la resta. Por el contrario, el paciente PP manifiesta alteraciones en la suma y multiplicación pero conserva intacta la resta. ISR presenta un déficit selectivo para la multiplicación estando intactas la suma y la resta. Por último, ACH, conserva la suma pero tiene alteradas la resta y la multiplicación. Esta doble disociación confirma los postulados del modelo anatómico funcional de Dehaene y Cohen (1995, 1997), que plantea la existencia de una doble vía para la resolución de operaciones aritméticas simples: la ruta lingüística, para datos numéricos aprendidos memorísticamente, que se utilizaría para sumar y multiplicar, y por otro lado, la elaboración semántica, para la resta (AU)

The cases described in literature evidence that arithmetical operations can function independently, which allows to infer that the cognitive processes involved in the different operations might be different. Objective of that work is to determine the different processes involved in the resolution of arithmetical operations: addition, subtraction and multiplication. Method. Instrument: Assesment of Numeric Processing and Calculation Battery (Salguero & Alameda, 2007, 2011). Subjects. Patients of acquired cerebral injury. Results and conclusions. The patient MNL preserves the addition and the multiplication but he presents altered the subtraction. On the contrary, the patient PP shows alterations in addition and multiplication but he conserves the skills for the subtraction. ISR presents a selective deficit for multiplication with intact addition and substraction. Finally, ACH preserves the addition but presents deficit for substraction and multiplication. This double dissociation confirms the postulates of the anatomical functional model of Dehaene and Cohen (1995, 1997) that consider a double route for the resolution of arithmetical simple operations: linguistic route, for numerical information learned automatically (of memory) and would be used for the operations of addition and multiplication, on the other hand the semantic elaboration would be for substraction (AU)

[Quantitative numerical and lexical knowledge: evidence of double dissociation]. / Conocimiento numérico cuantitativo y léxico: evidencia de doble disociación.

The aim of this work was to explain the involvement of a specific brain injury in the numerical processing and calculation system. The method employed was > analysis and the administration of various cognitive neuropsychology tests. The results of this study revealed a double dissociation between quantitative numerical knowledge and qualitative or lexical numerical knowledge. Patient M.C. preserved quantitative numerical knowledge, as indicated by the results obtained in the numerical comprehension and calculation tasks. However, she showed a drastic deficit in qualitative numerical knowledge. On the other hand, patient M.L. preserved qualitative numerical knowledge, but she had serious problems in all the abilities that require internal manipulation of magnitude; that is, quantitative numerical knowledge. These results have two important implications, as conclusions: firstly, quantitative numerical knowledge may be made up of different elements susceptible to damage independently. And secondly, quantitative and qualitative numerical knowledge were functionally independent.