Non-Invasive Electric and Magnetic Brain Stimulation for the Treatment of Fibromyalgia.

Although fibromyalgia is defined by its core muscular nociceptive component, it also includes multiple dysfunctions that involve the musculoskeletal, gastrointestinal, immune, endocrine, as well as the central and peripheral nervous systems, amongst others. The pathogenic involvement of the nervous system and the numerous neurological and neuroinflammatory symptoms of this disease may benefit from neuromodulatory stimulation techniques that have been shown to be effective and safe in diverse nervous system pathologies. In this systematic review, we outline current evidence showing the potential of non-invasive brain stimulation techniques, such as therapeutic strategies in fibromyalgia. In addition, we evaluate the contribution of these tools to the exploration of the neurophysiological characteristics of fibromyalgia. Considering that the pathogenesis of this disease is unknown, these approaches do not aim to causally treat this syndrome, but to significantly reduce a range of key symptoms and thus improve the quality of life of the patients.

Emotional health assessment related to COVID-19 in older people: A cross-sectional study.

BACKGROUND: The aim of this study was to assess the presence of anxiety, fear and psychological distress in the population of people over 65 years of age and to study possible differences with a sample of subjects aged between 60 and 65 years. METHODS: A descriptive and psychometric cross-sectional study. The total sample used consisted of 1112 subjects from university training programmes for the old people from all over Spain. Anxiety and fear of COVID-19 were measured using the AMICO scale and psychological distress using the GHQ-12 instrument. RESULTS: Significant differences were found in the AMICO (p = 0.006) and GHQ-12 (p = 0.03) measures between age subgroups, with lower values in older age groups. Contrast statistics showed significant differences on both measures (AMICO and GHQ) in women, single or widowed subjects, and those who had not been infected by the SARS-CoV-2 virus. LIMITATIONS: It would be desirable to increase the sample size, especially in the lower age group (<65). The establishment of the age limit between the two groups could be located at 60 years of age. The use of new technologies to get information should be considered. CONCLUSIONS: Overall, moderate levels of fear and anxiety of COVID-19 were present. Women tended to have higher levels of both general psychological distress and fear and anxiety of COVID-19. Especially in those over 65, higher levels of distress and fear/anxiety of COVID-19 were associated with being widowed or single, and not having been infected before with SARS-CoV-2.

Effects of tDCS applied over the left IFG and pSTG language areas on verb recognition task performance.

Knowledge about the relevance of the left inferior frontal gyrus (lIFG) and the left posterior superior temporal gyrus (lpSTG) in visual recognition of word categories is limited at present. tDCS is a non-invasive brain stimulation method that alters cortical activity and excitability, and thus might be a useful tool for delineating the specific impact of both areas on word recognition. The objective of this study was to explore whether the visual recognition process of verb categories is improved by a single tDCS session. lIFG and lpSTG areas were separately modulated by anodal tDCS to evaluate its effects on verbal recognition. Compared to sham stimulation, motor reaction times (RTs) were reduced after anodal tDCS over the lpSTG, and this effect was independent of the performing hand (right/left). These findings suggest that this region is involved in visual word recognition independently from the performing hand.

Discernible effects of tDCS over the primary motor and posterior parietal cortex on different stages of motor learning.

Implicit motor learning and memory involve complex cortical and subcortical networks. The induction of plasticity in these network components via non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), has shown to improve motor learning. However, studies showing these effects are mostly restricted to stimulation of the primary motor cortex (M1) during the early stage of learning. Because of this, we aimed to explore the efficacy of anodal tDCS applied over the posterior parietal cortex (PPC), which is involved in memory processes, on serial reaction time task (SRTT) performance. Specifically, to evaluate the involvement of both motor learning network components, we compared the effects of tDCS applied over regions corresponding to M1 and PPC during the early and late stages of learning. The results revealed a selective improvement of reaction time (RT) during anodal stimulation over the PPC in the late stage of learning. These findings support the assumption that the PPC is relevant during specific phases of learning, at least for SRTT performance. The results also indicate that not only the target area (i.e., PPC), but also timing is crucial for achieving the effects of stimulation on motor learning.

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.

Standard Non-Personalized Electric Field Modeling of Twenty Typical tDCS Electrode Configurations via the Computational Finite Element Method: Contributions and Limitations of Two Different Approaches.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation procedure to modulate cortical excitability and related brain functions. tDCS can effectively alter multiple brain functions in healthy humans and is suggested as a therapeutic tool in several neurological and psychiatric diseases. However, variability of results is an important limitation of this method. This variability may be due to multiple factors, including age, head and brain anatomy (including skull, skin, CSF and meninges), cognitive reserve and baseline performance level, specific task demands, as well as comorbidities in clinical settings. Different electrode montages are a further source of variability between tDCS studies. A procedure to estimate the electric field generated by specific tDCS electrode configurations, which can be helpful to adapt stimulation protocols, is the computational finite element method. This approach is useful to provide a priori modeling of the current spread and electric field intensity that will be generated according to the implemented electrode montage. Here, we present standard, non-personalized model-based electric field simulations for motor, dorsolateral prefrontal, and posterior parietal cortex stimulation according to twenty typical tDCS electrode configurations using two different current flow modeling software packages. The resulting simulated maximum intensity of the electric field, focality, and current spread were similar, but not identical, between models. The advantages and limitations of both mathematical simulations of the electric field are presented and discussed systematically, including aspects that, at present, prevent more widespread application of respective simulation approaches in the field of non-invasive brain stimulation.

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.

Taste Processing: Insights from Animal Models.

Taste processing is an adaptive mechanism involving complex physiological, motivational and cognitive processes. Animal models have provided relevant data about the neuroanatomical and neurobiological components of taste processing. From these models, two important domains of taste responses are described in this review. The first part focuses on the neuroanatomical and neurophysiological bases of olfactory and taste processing. The second part describes the biological and behavioral characteristics of taste learning, with an emphasis on conditioned taste aversion as a key process for the survival and health of many species, including humans.

Temporal specificity of latent inhibition in rats with daily water restriction prior to taste conditioning.

Temporal specificity of latent inhibition of conditioned taste aversion (CTA) has been demonstrated after prolonged habituation to temporal contexts in the stages preceding conditioning, and it has been eliminated by restricting consumption during conditioning. However, it is not known if latent inhibition of CTA is still dependent on the temporal context when fluid consumption is limited in the stages prior to conditioning. We tested temporal specificity of latent inhibition in rats with (different time of day for the conditioning stage) and without (same time of day for pre-exposure and conditioning stages) temporal changes on the conditioning day. All animals had limited access to water in the morning sessions of the stages prior to the conditioning day and 15 min of free access to fluid in the evening sessions of these stages. Compared to animals without temporal changes between stages, animals with a different temporal context during conditioning did not show evidence of latent inhibition. Unlike the effects observed after taste stimulus restrictions during conditioning, these results suggest that the temporal specificity of latent inhibition of CTA is not abolished when access to water is limited in the stages preceding conditioning.

Anodal tDCS over Wernicke's area improves verbal memory and prevents the interference effect during words learning.

BACKGROUND: Wernicke's area is a key component of the cortical language network, and it is functionally related to the comprehension of oral and written language. In addition to its main role in the perception of language, some other functions related to verbal learning also seem to involve the activity of this cortical region. It is unknown whether different degrees of neuromodulation on this area determine its effect on word learning. OBJECTIVE: We aimed to analyze the influence of the application of anodal transcranial DC stimulation (tDCS) over Wernicke's area at two different intensities on word learning. METHOD: We compared the effect of anodal tDCS at an intensity of 0.5 mA and 1.5 mA with sham tDCS, separately in different groups, on performance in a word learning and recall task. RESULTS: The results show that 1.5 mA anodal tDCS improved performance. The number of words learned in this condition was higher compared with stimulation at 0.5 mA current strength and sham stimulation. Furthermore, stimulation with 1.5 mA specifically prevented the interference effect over word learning, compared to the other two tDCS conditions. CONCLUSIONS: These results show an intensity-dependent effect of anodal tDCS on verbal memory formation. These findings are discussed in the context of the various functions of Wernicke's area and the ability of tDCS to modulate the activity and functionality of this cortical area at different intensities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Bilateral Prefrontal Cortex Anodal tDCS Effects on Self-reported Aggressiveness in Imprisoned Violent Offenders.

Reduced activity of the frontal lobes, and particularly of the prefrontal cortex, has been related with violent behavior, aggression and crime. The causal importance of prefrontal cortex activity for aggressive behaviors and the self-perception of aggressiveness needs however to be clarified. The aim of this study was to explore the effect of an anodal transcranial direct current stimulation protocol (tDCS, 1.5 mA, 15 min), which, according to previous studies, enhances cortical excitability, applied bilaterally over the prefrontal cortex on self-reported aggressiveness. Two imprisoned violent offender cohorts, discerned by the degree of aggressiveness (murderers vs. non-murderers), were included in this single-blind sham-controlled study. Self-reported aggressiveness was recorded before and after 3 tDCS sessions (one session per day). Four dimensions of aggression were evaluated by means of the standardized Buss-Perry Aggression Questionnaire (BAQ). In both inmate groups the results revealed an aggression-reducing effect of tDCS on the Physical aggression, Anger, and Verbal aggression dimensions of the BAQ. In the Hostility dimension, tDCS significantly reduced aggression only in the group of murderers. These results suggest that modulation of prefrontal cortex excitability by 3 consecutive sessions of tDCS reduces self-reported aggressiveness similarly in murderer and non-murderer samples.

Effects of extensive amygdaloid lesions on conditioned taste aversion in rats.

The role of the amygdala in the acquisition of conditioned taste aversion (CTA) is unclear. The lesion studies that have explored specific nuclei of the amygdala point to a probable involvement of the basolateral amygdala, but it remains unclear whether the function of the amygdala in CTA is limited to the activity of the basolateral amygdala. In the current study, extensive bilateral lesions of the amygdala were performed in Wistar rats to explore if the destruction of the amygdala affects the acquisition of CTA, as has been reported with selective lesions of the basolateral amygdala. The magnitude of the taste aversion of animals with extensive lesions of the amygdala was compared with those of animals with similar lesions of the striatum (a structure apparently unrelated to CTA) and animals without lesions. Taste aversion was analyzed by the one­bottle test and two­bottle choice test. The results of the one­bottle test indicated that amygdaloid lesions significantly reduced the magnitude of taste aversion compared with that of animals without lesions. Animals with lesions of the amygdala also showed a greater preference for the conditioned taste stimulus, but this preference did not reach statistical significance. Besides the effect on CTA, animals with amygdaloid lesions showed no evidence of taste neophobia on the day of conditioning. These findings suggest that amygdaloid lesions may affect CTA by disrupting the perception of novelty during conditioning in a manner similar to the effect reported with basolateral lesions.

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.

Changes in the time of day of conditioning with respect to the pre-exposure interfere with the latent inhibition of conditioned taste aversion in rats.

In rats, the reduction of the magnitude of a conditioned taste aversion (CTA) that occurs after taste pre-exposures (that is, the latent inhibition of CTA) can be attenuated by contextual changes of the external cues in the conditioning stage. Similarly, circadian internal cues such as those induced by the time of day may also modulate the magnitude of the taste aversion. Under a long period of temporal-contextual habituation, the latent inhibition of CTA is reduced if the pre-exposure and conditioning stages occur at different times of day. However, it is unknown if this effect is consistent when different changes in the time of day of conditioning with respect to the pre-exposure are compared. In this study, the effect of two different changes in the time of day of conditioning (one from morning to evening, and one from evening to morning) on the latent inhibition of CTA was compared with the response of a typical latent inhibition group without temporal change between stages, and with control groups without pre-exposures. The results indicate that the latent inhibition of CTA of both groups with temporal change between pre-exposure and conditioning is significantly reduced when compared with the latent inhibition of the group without temporal change. These findings suggest that the temporal context may be a critical cue for the latent inhibition of CTA, and they show that different changes in the time of day of conditioning interfere similarly with this learning.

Effects of lesions in different nuclei of the amygdala on conditioned taste aversion.

Conditioned taste aversion (CTA) is an adaptive learning that depends on brain mechanisms not completely identified. The amygdala is one of the structures that make up these mechanisms, but the involvement of its nuclei in the acquisition of CTA is unclear. Lesion studies suggest that the basolateral complex of the amygdala, including the basolateral and lateral amygdala, could be involved in CTA. The central amygdala has also been considered as an important nucleus for the acquisition of CTA in some studies. However, to the best of our knowledge, the effect of lesions of the basolateral complex of the amygdala on the acquisition of CTA has not been directly compared with the effect of lesions of the central and medial nuclei of the amygdala. The aim of this study is to compare the effect of lesions of different nuclei of the amygdala (the central and medial amygdala and the basolateral complex) on the acquisition of taste aversion in male Wistar rats. The results indicate that lesions of the basolateral complex of the amygdala reduce the magnitude of the CTA when compared with lesions of the other nuclei and with animals without lesions. These findings suggest that the involvement of the amygdala in the acquisition of CTA seems to depend particularly on the integrity of the basolateral complex of the amygdala.

Effects of temporal contexts and contextual habituation on latent inhibition / Efectos de contextos temporales y habituación contextual sobre inhibición latente

Background: Latent inhibition of conditioned taste aversion (CTA) is sensitive to external and internal cues. Time of day can serve as an internal cue, and latent inhibition may be reduced if the pre-exposure and conditioning stages occur at different times of day. This contextual cue attributed to a change in the time of day may reveal a temporal specificity of latent inhibition. Although the habituation period to spatial contexts is a determinant variable for the spatial specificity of latent inhibition of CTA, the influence of contextual-temporal familiarity (time of day) on latent inhibition of CTA has not been explored through direct comparisons between different periods of habituation to the temporal context. Method: Two different periods of contextual habituation (short vs. long) previous to taste pre-exposures were compared in Wistar rats to analyze the influence of these periods on the temporal specificity of latent inhibition of CTA. Results: A long period of habituation, in relation to a short period, facilitated the effect of a change of the time of day between pre-exposure and conditioning on the magnitude of taste aversion. Conclusions: A long habituation to temporal contexts facilitates the temporal specificity of latent inhibition of CTA (AU)

Antecedentes: la inhibición latente del aprendizaje aversivo gustativo (AAG) es sensible a claves externas e internas. La hora del día puede actuar como una clave interna, y la inhibición latente puede ser reducida si pre-exposición y condicionamiento ocurren a diferentes horas del día. Esta clave contextual atribuida a un cambio en la hora del día puede revelar una especificidad temporal de la inhibición latente. Aunque el período de habituación a contextos espaciales es determinante para la especificidad espacial de la inhibición latente del AAG, la influencia de la familiaridad contextual-temporal (hora del día) sobre la inhibición latente del AAG no ha sido explorada mediante comparaciones directas entre diferentes períodos de habituación al contexto temporal. Método: en ratas Wistar se compararon dos diferentes períodos de habituación contextual (corto versus largo) previos a pre-exposiciones gustativas para analizar la influencia de éstos sobre la especificidad temporal de la inhibición latente del AAG. Resultados: un largo período de habituación, en relación con uno corto, facilitó el efecto de un cambio de la hora del día entre pre-exposición y condicionamiento sobre la magnitud de la aversión gustativa. Conclusiones: una larga habituación a contextos temporales facilita la especificidad temporal de la inhibición latente del AAG (AU)

Effects of temporal contexts and contextual habituation on latent inhibition.

BACKGROUND: Latent inhibition of conditioned taste aversion (CTA) is sensitive to external and internal cues. Time of day can serve as an internal cue, and latent inhibition may be reduced if the pre-exposure and conditioning stages occur at different times of day. This contextual cue attributed to a change in the time of day may reveal a temporal specificity of latent inhibition. Although the habituation period to spatial contexts is a determinant variable for the spatial specificity of latent inhibition of CTA, the influence of contextual-temporal familiarity (time of day) on latent inhibition of CTA has not been explored through direct comparisons between different periods of habituation to the temporal context. METHOD: Two different periods of contextual habituation (short vs. long) previous to taste pre-exposures were compared in Wistar rats to analyze the influence of these periods on the temporal specificity of latent inhibition of CTA. RESULTS: A long period of habituation, in relation to a short period, facilitated the effect of a change of the time of day between pre-exposure and conditioning on the magnitude of taste aversion. CONCLUSIONS: A long habituation to temporal contexts facilitates the temporal specificity of latent inhibition of CTA.

Applications of transcranial direct current stimulation in children and pediatrics.

Transcranial direct current stimulation (tDCS) is a neuromodulatory noninvasive brain stimulation tool with potential to increase or reduce regional and remote cortical excitability. Numerous studies have shown the ability of this technique to induce neuroplasticity and to modulate cognition and behavior in adults. Clinical studies have also demonstrated the ability of tDCS to induce therapeutic effects in several central nervous system disorders. However, knowledge about its ability to modulate brain functions in children or induce clinical improvements in pediatrics is limited. The objective of this review is to describe relevant data of some recent studies that may help to understand the potential of this technique in children with specific regard to effective and safe treatment of different developmental disorders in pediatrics. Overall, the results show that standard protocols of tDCS are well tolerated by children and have promising clinical effects. Nevertheless, treatment effects seem to be partially heterogeneous, and a case of a seizure in a child with previous history of infantile spasms and diagnosed epilepsy treated with tDCS for spasticity was reported. Further research is needed to determine safety criteria for tDCS use in children and to elucidate the particular neurophysiological changes induced by this neuromodulatory technique when it is applied in the developing brain.

Modulation of the magnitude of conditioned taste aversion in rats with excitotoxic lesions of the basolateral amygdala.

The amygdala is one of the structures involved in the acquisition of conditioned taste aversion (CTA). Nevertheless, the specific roles that the nuclei of this structure play in CTA learning are controversial. Electrolytic lesions applied to the basolateral nucleus of the amygdala can eliminate or reduce the acquisition of this learning. This effect has been attributed to the involvement of fibers that pass through this nucleus and connect with other structures that are critical for CTA. Excitotoxic lesions may allow a clearer insight as to the potential involvement of this nucleus in the acquisition of CTA. The few studies to date that have used this paradigm have shown effects on taste aversion learning after applying extensive lesions to the amygdala. Thus, the aim of the present study was to determine the effect of selective excitotoxic lesions of the basolateral amygdala on the acquisition of CTA. The effects of these lesions on learning were compared with the effects observed in animals with sham lesions and animals with lesions of the hippocampus, which is a structure apparently not involved in CTA. The results revealed a decreased aversion in animals with basolateral lesions compared with both the sham and hippocampus-lesioned groups. Based on these findings, the role of this specific nucleus of the amygdala in the acquisition of taste aversion is briefly discussed.

Circadian-temporal context and latent inhibition of conditioned taste aversion: Effect of restriction in the intake of the conditioned taste stimulus.

Latent inhibition of conditioned taste aversion (CTA) is sensitive to changes in the temporal context. A change in the time of day of conditioning with respect to the time of day of the preexposure can disrupt the latent inhibition. This contextual change in the time of day may reveal a temporal specificity of latent inhibition. The optimum procedure to induce this temporal specificity is not well established. For example, it has been shown that a long period of habituation to temporal contexts is one factor that can determine the effect. However, the experimental conditions on the conditioning day that facilitate this phenomenon are unknown. The aim of this study is to elucidate whether a restriction in the intake of the conditioned taste stimulus affects the temporal specificity of latent inhibition. Two main groups of Wistar rats were tested in a latent inhibition of CTA paradigm, in which the temporal specificity of this phenomenon was analyzed by a change in the time of day of conditioning. The intake of the taste stimulus was restricted in the conditioning day in one of the groups, but this restriction was not applied in the other group. The results indicated temporal specificity of latent inhibition only in the group without restriction, but not in the group with limitation in the intake of the taste stimulus during conditioning. These findings can help to elucidate the characteristics of the procedure to induce temporal specificity of latent inhibition.