Effects of Non-Invasive Neurostimulation on Autism Spectrum Disorder: A Protocol for a Systematic Review

Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by characteristic impairments in social communication and interaction, as well as restricted and repetitive behavior. There is a continued need for exploring effective interventions and evaluating treatment options for ASD. Transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive neurostimulation techniques which have shown clinical benefits in adult psychiatric conditions. While in ASD patients, no guideline has so-far recommended on the application of NIBS due to a lack of high-quality synthetic evidence. Therefore, objective of this study will be to systematically evaluate the evidence on clinical effects of non-invasive neurostimulation in patients with ASD. Methods We designed and registered a study protocol for a systematic review. A comprehensive search from database inception onwards will be conducted in PubMed, EMBASE and Cochrane library. Randomized and non-randomized sham-controlled studies assessing the effects of noninvasive neurostimulation in patients with ASD will be identified. Eligibility of citations retrieved will be independently screened by two reviewers. The risk of bias and quality of included studies will be appraised using appropriate tools. A narrative synthesis around the features of the evidences will provided. There may be a chance for meta-analysis to pool the estimates of studies included if three studies or more meet the requirements for meta-analysis. If so, a random-effects model maybe applied. And we will evaluate heterogeneity between studies using the I² statistic. Discussion This systematic review will provide a broad and comprehensive evaluation of the evidence on clinical effects of TMS and tDCS in patients with ASD. Our findings will be reported according to the PRISMA guidelines and may add more confidence when healthcare professionals are making informed decisions about the choice of this therapy. Results will be published in a peer-reviewed journal. Systematic review registration: Submitted to PROSPERO, 20/11/2021

Brain Stimulation and Identity

This chapter reflects on the impact of brain stimulation on identity. Following substantial advances in our understanding of the brain, surgeons and neuroscientists have been able to develop powerful new medical interventions that aim to treat disease by modifying electrical activity in the brain. At present, Deep Brain Stimulation (DBS) is the most precise tool that we have at our disposal in this regard; it can target a cubic millimeter of brain tissue. In terms of precision, it stands in stark contrast to drugs that influence brain activity by affecting neurotransmitters across the brain. However, despite its precision, in some rare cases, DBS can have unintended side-effects, including behavioural and emotional changes. The possibility of controlling motivational and emotional states has intrigued scientists since the earliest days of invasive neurostimulation. This prospect raises profound ethical questions, regardless of whether such changes are intentional or an unintended side-effect of treatment. To what extent does it make sense to say that a medical intervention like DBS can change the recipient into “a different person”? The chapter then turns to concepts in moral philosophy, considering the nature of identity and the self.

Complex Regional Pain Syndrome. A Comprehensive Review on Neuroplastic Changes Supporting the Use of Non-invasive Neurostimulation in Clinical Settings

Background: Complex regional pain syndrome (CRPS) is a rare debilitating disorder characterized by severe pain affecting one or more limbs. CRPS presents a complex multifactorial physiopathology. The peripheral and sensorimotor abnormalities reflect maladaptive changes of the central nervous system. These changes of volume, connectivity, activation, metabolism, etc., could be the keys to understand chronicization, refractoriness to conventional treatment, and developing more efficient treatments.Objective: This review discusses the use of non-pharmacological, non-invasive neurostimulation techniques in CRPS, with regard to the CRPS physiopathology, brain changes underlying chronicization, conventional approaches to treat CRPS, current evidence, and mechanisms of action of peripheral and brain stimulation.Conclusion: Future work is warranted to foster the evidence of the efficacy of non-invasive neurostimulation in CRPS. It seems that the approach has to be individualized owing to the integrity of the brain and corticospinal function. Non-invasive neurostimulation of the brain or of nerve/muscles/spinal roots, alone or in combination with conventional therapy, represents a fertile ground to develop more efficient approaches for pain management in CRPS.

Melatonin Moderates the Triangle of Chronic Pain, Sleep Architecture and Immunometabolic Traffic

Preclinical as well as human studies indicate that melatonin is essential for a physiological sleep state, promotes analgesia and is involved in immunometabolic signaling by regulating neuroinflammatory pathways. Experimental and clinical neuromodulation studies for chronic pain treatment suggest that neurostimulation therapies such as spinal cord stimulation, vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. Herein, we provide an overview of current literature relevant for the shared pathways of sleep, pain and immunometabolism and elaborate the impact of melatonin on the crossroad of sleep, chronic pain and immunometabolism. Furthermore, we discuss the potential of melatonin as an adjunct to neurostimulation therapies. In this narrative review, we addressed these questions using the following search terms: melatonin, sleep, immunometabolism, obesity, chronic pain, neuromodulation, neurostimulation, neuroinflammation, molecular inflammatory phenotyping. So far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. Thus, the adjunct potential of melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation therapies.

Role of Ayurveda in Managing Tinnitus

Tinnitus is one of the annoying disorders which can significantly impair patient’s quality of life and productivity. Although it is not a life threatening disease, but it results into emotional distress, cognitive distress, intrusiveness, auditory and perceptual difficulties, sleep disturbances, and various somatic complaints. Its incidence and prevalence are enhancing day by day. Various pharmacological agents including anticonvulsants, anxiolytics, antidepressants, muscle relaxants etc. are presently used or trialed for its pacification, but there is little evidence of their benefit over harm. The role of invasive and non-invasive Neurostimulation treatments, supposed to be very effective, are also little known. The introduction of Hearing aids and cochlear implantation are also not very much conclusive. No evidence of a significant change in the subjective loudness of tinnitus has been noticed with Cognitive behavioural treatment. In this way, there is a need for making an availability of uniformly accepted, broadly effective treatments capable of drastically decreasing the loudness and impact of tinnitus and withstanding systematic replication. This article is for serving the very purpose. Here, an effort has been made to present the remedial procedures and regimen for the alleviation of tinnitus described in Ayurveda, an ancient healing science of India. In Ayurveda, tinnitus has been delineated in the name of Karnanada. The article also brings about several case studies and clinical studies on tinnitus carried out at different centres/Institutes of Ayurveda.

Transcutaneous auricular VNS applied to experimental pain: A paired behavioral and EEG study using thermonociceptive CO2 laser

Background Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive neurostimulation technique with potential analgesic effects. Several studies based on subjective behavioral responses suggest that taVNS modulates nociception differently with either pro-nociceptive or anti-nociceptive effects. Objective This study aimed to characterize how taVNS alters pain perception, by investigating its effects on event-related potentials (ERPs) elicited by different types of spinothalamic and lemniscal somatosensory stimuli, combined with quantitative sensory testing (detection threshold and intensity ratings). Methods We performed 3 experiments designed to study the time-dependent effects of taVNS and compare with standard cervical VNS (cVNS). In Experiment 1, we assessed the effects of taVNS after 3 hours of stimulation. In Experiment 2, we focused on the immediate effects of the duty cycle (OFF vs. ON phases). Experiments 1 and 2 included 22 and 15 healthy participants respectively. Both experiments consisted of a 2-day cross-over protocol, in which subjects received taVNS and sham stimulation sequentially. In addition, subjects received a set of nociceptive (thermonociceptive CO2 laser, mechanical pinprick) and non-nociceptive (vibrotactile, cool) stimuli, for which we recorded detection thresholds, intensity of perception and ERPs. Finally, in Experiment 3, we tested 13 epileptic patients with an implanted cVNS by comparing OFF vs. ON cycles, using a similar experimental procedure. Results Neither taVNS nor cVNS appeared to modulate the cerebral and behavioral aspects of somatosensory perception. Conclusion The potential effect of taVNS on nociception requires a cautious interpretation, as we found no objective change in behavioral and cerebral responses to spinothalamic and lemniscal somatosensory stimulations.