Central Stimulation Research Articles

Stimulant Use for ADHD in a Cardiac Transplant Recipient: A Case Report

AbstractIntroductionMethylphenidate is a central nervous system stimulant used as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). CNS stimulant use is associated with increased risk of cardiovascular events such as increased resting heart rate and blood pressure, sudden cardiac death, arrhythmia, and stroke. Its safety profile in recipients of cardiovascular transplants is unknown, and more research is warranted to determine the risk of adverse cardiac events due to stimulant medication in this population.MethodsClinical case report, n=1Results/Clinical CaseA 19-year-old female with a history of restrictive cardiomyopathy, cardiac arrest, and orthotopic cardiac transplant has been treated with methylphenidate for ADHD for approximately 2 years without incident. The patient was diagnosed with ADHD between the ages of 8 and 10 and historically was treated with stimulant medication. At age 13, she experienced a cardiac arrest after a volleyball game with 4–6 minutes of pulselessness. She was successfully resuscitated and underwent defibrillator placement. It was concluded that the patient had restrictive cardiomyopathy undetected at birth, leading to the need for orthotopic cardiac transplantation at age 16. After her cardiac arrest, the patient’s memory and cognition worsened, and approximately 1 year after her transplant, she was prescribed amantadine. The patient remained untreated for her ADHD until approximately 1.5 years after her cardiac transplant, at which time she underwent neuropsychological testing that showed findings consistent with attention deficit disorder, and was restarted on stimulant medication. Her transplant cardiologist and psychiatrist have collaborated in her ongoing treatment with methylphenidate 40 mg daily and monitoring symptom response and cardiac stability. Because the patient had previously been stable on stimulant medication for many years, it is reasonable to conclude that stimulant medication did not lead to her cardiac arrest. The patient reports that methylphenidate has been helpful in improving her functioning as a college student, through reduction of her ADHD symptoms. The patient’s blood pressure and heart rate remain within an acceptable range and she has not experienced any adverse cardiac events to date while taking methylphenidate.ConclusionThis case sheds light on the potential to treat cardiac transplant recipients with stimulant medication for ADHD. Although a careful evaluation of risk factors must be undertaken in cooperation with cardiology and other specialists, a role exists for the safe use of stimulant medications in the cardiac transplant population.FundingNo Funding

Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis

ObjectiveExamine patterns of adult medical use of amphetamine and methylphenidate stimulant drugs, classified in the USA as Schedule II controlled substances with a high potential for psychological or physical dependence.DesignCross-sectional...

Applications and Physiological Mechanisms of Music Therapy in Insomnia Patients

Music has long been an inherent aspect of culture and self-expression. Recently, music has also been used as a form of therapy because of its distinctive ability to relieve stress and promote relaxation in the human body. This has been found to be especially useful as a treatment for stress-linked disorders such as primary insomnia, which is characterized by increased sympathetic nervous system activity (Jerath, R., Beveridge, C., & Barnes, V. A., 2021). Secondary research conducted through a literature review showed that music processing is a “whole-brain activity” (Warren, J., 2008). Stimulation of pleasure centers and regions of the brain which control biorhythms, such as the brain stem, improves mood and promotes relaxation, and therefore better sleep, by releasing hormones such as dopamine and serotonin (Harvard Health, 2021).
 Music therapy’s unique potential as a widely accessible form of therapy inspired me to write this article on the mechanisms in which this form of therapy fosters the well-being of insomnia patients. As the fast-paced lifestyles of many individuals has led to a rapid increase in stress-linked insomnia patients, an effective method of treatment should be available to all.

Concussed patients with visually induced dizziness exhibit increased ocular torsion and vertical vergence during optokinetic gaze-stabilization

Visually Induced Dizziness (VID) is a common post-concussion sequalae that remains poorly understood and difficult to quantify. The present study aims to identify biomarkers for VID in the form of gaze-stabilizing eye movements. Nine patients with post-commotio VID and nine age-matched healthy controls were recruited by physiotherapists at a local neurorehabilitation centre. Torsional and vergence eye movements were recorded while participants viewed a series of optokinetic rotations where the central- and peripheral regions moved coherently, incoherently, or semi-randomly. Results showed that vergence and torsional velocities were increased in VID patients, reflecting increased oculomotor gain to visual motion, and that responses correlated with symptom severity. Coherent stimulation produced fastest torsional slow-phases across all participants; when faced with confliction directional information, eye movements tended to follow the direction of the central visual field, albeit at slower velocities than during coherent motion, meaning that while torsion was sensitive to visual content of the entire visual field it expressed directional preference to the central stimulation. In conclusion, post-commotio VID was associated with faster slow-phases during optokinetic gaze-stabilization, with both vergence and torsion being correlated to symptom intensity. As torsional tracking remains inaccessible using commercial eye-trackers, vertical vergence may prove particularly accessible for clinical utility.

Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis

Background: Non-stimulant guanfacine is a common second-line medication for attention-deficit hyperactivity disorder (ADHD). Numerous randomized controlled trials (RCTs) have explored the efficacy of guanfacine in ADHD treatment. This meta-analysis combined data from selected RCTs to analyze the efficacy and safety of guanfacine in treating ADHD. Methods: RCTs were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase (up to February 2022), defining the Clinical Global Impression of Improvement (CGI-I) treatment response score of ≤2 as the primary outcome. Subgroup analysis was performed with a bound treatment duration of 10 weeks. Safety was defined by treatment-emergent adverse events (TEAEs). Results: Twelve out of 332 studies with 2653 participants were included. All studies compared guanfacine with placebos. Guanfacine was significantly more effective in treating ADHD (Risk Ratio [RR] 1.78, 95% CI: 1.59-2.01). In the <10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 58.5% versus 29.4%, respectively (RR 1.97, 95% CI: 1.71-2.26). In the >10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 63.6% versus 39.7%, respectively (RR 1.57, 95% CI: 1.37-1.79). Both subgroups lacked heterogeneity (I2 = 0), and a funnel plot showed a low publication bias risk. Around 80% of participants in the guanfacine group experienced at least one TEAE, compared with 66.5% in the placebo group (RR 1.23, 95% CI: 1.14-1.32), with low heterogeneity (I2 = 46, p = 0.05). The most common TEAEs in the guanfacine group were somnolence (38.6%), headaches (20.5%), and fatigue (15.2%). Conclusions: Guanfacine is safe and effective for treating ADHD, with no serious adverse events. Guanfacine should be considered as an effective treatment option where effectiveness or tolerability of the central nervous system stimulant is of concern. There is stronger evidence of efficacy for children; more clinical studies are needed for adults.

Central Nervous Stimulation for Neurogenic Lower Urinary Tract Dysfunction: Current Application and Emergent Therapies

Central Nervous Stimulation for Neurogenic Lower Urinary Tract Dysfunction: Current Application and Emergent Therapies

Pay attention to the clinical application of radiofrequency ablation in the treatment of neuropathic pain

Neuropathic pain is the pain triggered or caused by primary damage and dysfunction of the nervous system. Its pathogenesis is complex, involving changes in ion channel function, abnormal action potential generation and expansion, and central and peripheral sensitization. Therefore, it has always been the most intractable problem in clinical pain diagnosis and treatment, and there are many kinds of treatment methods. In addition to various oral drugs, nerve block, pulsed radiofrequency, radiofrequency ablation, central nerve electrical stimulation, peripheral nerve electrical stimulation, intra-thecal infusion system, craniotomy nerve decompression or carding, the dorsal root entry zone disfigurement, etc. various methods have mixed efficacy. So far, radiofrequency ablation of peripheral nerves is still the most simple and effective means for the treatment of neuropathic pain. In this paper, the definition, clinical manifestations, pathological mechanism and the treatment methods of radiofrequency ablation of neuropathic pain were expounded, in order to provide reference for related clinicians in radiofrequency ablation.

Tryptophan and Substance Abuse: Mechanisms and Impact.

Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads to severe health issues, including cardiovascular diseases, serious infections, and pulmonary/dental diseases. Drug dependence may result in unfavorable cognitive impairments that can continue during abstinence and negatively influence recovery performance. Although addiction is a critical global health challenge with numerous consequences and complications, currently, there are no efficient options for treating drug addiction, particularly METH. Currently, novel treatment approaches such as psychological contingency management, cognitive behavioral therapy, and motivational enhancement strategies are of great interest. Herein, we evaluate the devastating impacts of different addictive substances/drugs on users' mental health and the role of tryptophan in alleviating unfavorable side effects. The tryptophan metabolites in the mammalian brain and their potential to treat compulsive abuse of addictive substances are investigated by assessing the functional effects of addictive substances on tryptophan. Future perspectives on developing promising modalities to treat addiction and the role of tryptophan and its metabolites to alleviate drug dependency are discussed.

Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson's disease.

The globus pallidus internus (GPI) has been demonstrated to be an effective surgical target for deep brain stimulation (DBS) treatment in patients with medication-refractory Parkinson's disease (PD). The ability of neurosurgeons to define the area of greatest therapeutic benefit within the globus pallidus (GP) may improve clinical outcomes in these patients. The objective of this study was to determine the best DBS therapeutic implantation site within the GP for effective treatment in PD patients. The authors performed a retrospective review of 56 patients who underwent bilateral GP DBS implantation at their institution during the period from January 2015 to January 2020. Each implanted contact was anatomically localized. Patients were followed for stimulation programming for at least 6 months. The authors reviewed preoperative and 6-month postsurgery clinical outcomes based on data from the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), dyskinesia scores, and levodopa equivalent daily dose (LEDD). Of the 112 leads implanted, the therapeutic cathode was most frequently located in the lamina between the GPI external segment (GPIe) and the GP externus (GPE) (n = 40). Other common locations included the GPE (n = 24), the GPIe (n = 15), and the lamina between the GPI internal segment (GPIi) and the GPIe (n = 14). In the majority of patients (73%) a monopolar programming configuration was used. At 6 months postsurgery, UPDRS III off medications (OFF) and on stimulation (ON) scores significantly improved (z = -4.02, p < 0.001), as did postsurgery dyskinesia ON scores (z = -4.08, p < 0.001) and postsurgery LEDD (z = -4.7, p < 0.001). Though the ventral GP (pallidotomy target) has been a commonly used target for GP DBS, a more dorsolateral target may be more effective for neuromodulation strategies. The assessment of therapeutic contact locations performed in this study showed that the lamina between GPI and GPE used in most patients is the optimal central stimulation target. This information should improve preoperative GP targeting.

Central retina plays a decisive role in the suppression of pupillary escape

PurposeTo explore the pupil redilation during persistent light exposure (pupillary escape phenomenon) at the macula and periphery with monochromatic light stimuli.MethodsForty healthy subjects aged 18–64 years (24 females) were examined by chromatic pupil campimetry (CPC) using red and blue 4-s stimuli of 10° radius at the center and 20°-peripheral locations one per quadrant. One glaucoma patient and one achromatopsia patient served as disease models. For statistical analyses, linear mixed-effects models were performed followed by post hoc t-tests.ResultsA distinct pupillary escape could be demonstrated peripherally (blue 0.099%*s, red 0.153%*s); at the central healthy retina, there was no relevant escape, neither for blue nor red stimulation. Comparing central versus peripheral stimulation revealed highly significant differences in the escape (difference blue 0.100 ± 0.013, red 0.144 ± 0.013, < 0.0001, respectively). In the periphery, the escape was significantly more pronounced for red compared with blue stimulation (difference 0.054 ± 0.013; p = 0.0001). Enhanced pupillary escape outside of the 95% confidence interval of the linear mixed-effects model of the healthy population could be exemplarily shown in a patient with glaucomatous ganglion cell damage. In the achromatopsia example, no relevant escape was found for blue stimulation, but for red stimulation in the periphery in a comparable range to healthy controls.ConclusionThe results emphasize that an intact inner retinal network of nerve fibers arising from the central macular region is necessary for maintaining pupillary constriction during a bright 4-s light stimulus and preventing increase of pupillary escape. Increasing receptive field sizes towards the periphery on the level of retinal ganglion cells and less input from central 1:1 connections could be one of the driving mechanisms for pupillary escape.

Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multi ational Study.

Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure.Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors.Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16).Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.

The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC-A Preclinical Study in Mice.

Several new psychoactive substances (NPS) are responsible for intoxication involving the cardiovascular and respiratory systems. Among NPS, synthetic cannabinoids (SCs) provoked side effects in humans characterized by tachycardia, arrhythmias, hypertension, breathing difficulty, apnoea, myocardial infarction, and cardiac arrest. Therefore, the present study investigated the cardio-respiratory (MouseOx Plus; EMKA electrocardiogram (ECG) and plethysmography TUNNEL systems) and vascular (BP-2000 systems) effects induced by 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018; 0.3-3-6 mg/kg) and Δ9-tetrahydrocannabinol (Δ9-THC; 0.3-3-6 mg/kg), administered in awake CD-1 male mice. The results showed that higher doses of JWH-018 (3-6 mg/kg) induced deep and long-lasting bradycardia, alternated with bradyarrhythmia, spaced out by sudden episodes of tachyarrhythmias (6 mg/kg), and characterized by ECG electrical parameters changes, sustained bradypnea, and systolic and transient diastolic hypertension. Otherwise, Δ9-THC provoked delayed bradycardia (minor intensity tachyarrhythmias episodes) and bradypnea, also causing a transient and mild hypertensive effect at the tested dose range. These effects were prevented by both treatment with selective CB1 (AM 251, 6 mg/kg) and CB2 (AM 630, 6 mg/kg) receptor antagonists and with the mixture of the antagonists AM 251 and AM 630, even if in a different manner. Cardio-respiratory and vascular symptoms could be induced by peripheral and central CB1 and CB2 receptors stimulation, which could lead to both sympathetic and parasympathetic systems activation. These findings may represent a starting point for necessary future studies aimed at exploring the proper antidotal therapy to be used in SCs-intoxicated patient management.

Characteristics and outcomes of cases with methylphenidate abuse, dependence or withdrawal: an analysis of spontaneous reports in EudraVigilance.

Methylphenidate (MPH) is a central nervous stimulant, which is mainly used in attention deficit hyperactivity disorder (ADHD) and narcolepsy. In recent years, rising MPH prescription volumes have drawn attention to possible misuse. We analyzed data on suspected MPH abuse, dependence or withdrawal reported to the EudraVigilance database (1996-2019), comparing case characteristics (e.g. age, indications and outcome). In 1531 cases from 35 countries (median: 29 years, 57.6% male), 42.3% had been diagnosed with ADHD and 8.0% with narcolepsy. Narcolepsy cases were older than ADHD cases (mean age: 47 vs. 22 years), and used co-medications more frequently (79.4 vs. 47.8%). Intravenous MPH administration was most common among individuals not diagnosed with ADHD or narcolepsy. A history of abuse, dependence or withdrawal of any substance was more often documented in fatal than in nonfatal cases (49.0 vs. 22.5%), whereas differences regarding the route of administration were less pronounced. Minors, who presumably received MPH for ADHD treatment, presented less frequently with serious outcomes than older cases or those without an approved indication. Prescribers should exercise caution in adult MPH users and should make a thorough co-medication assessment. Finally, more research on substance abuse in narcolepsy patients is required, which should include comorbidities and co-medication.

Microscale multicircuit brain stimulation: Achieving real-time brain state control for novel applications.

Neurological and psychiatric disorders typically result from dysfunction across multiple neural circuits. Most of these disorders lack a satisfactory neuromodulation treatment. However, deep brain stimulation (DBS) has been successful in a limited number of disorders; DBS typically targets one or two brain areas with single contacts on relatively large electrodes, allowing for only coarse modulation of circuit function. Because of the dysfunction in distributed neural circuits - each requiring fine, tailored modulation - that characterizes most neuropsychiatric disorders, this approach holds limited promise. To develop the next generation of neuromodulation therapies, we will have to achieve fine-grained, closed-loop control over multiple neural circuits. Recent work has demonstrated spatial and frequency selectivity using microstimulation with many small, closely-spaced contacts, mimicking endogenous neural dynamics. Using custom electrode design and stimulation parameters, it should be possible to achieve bidirectional control over behavioral outcomes, such as increasing or decreasing arousal during central thalamic stimulation. Here, we discuss one possible approach, which we term microscale multicircuit brain stimulation (MMBS). We discuss how machine learning leverages behavioral and neural data to find optimal stimulation parameters across multiple contacts, to drive the brain towards desired states associated with behavioral goals. We expound a mathematical framework for MMBS, where behavioral and neural responses adjust the model in real-time, allowing us to adjust stimulation in real-time. These technologies will be critical to the development of the next generation of neurostimulation therapies, which will allow us to treat problems like disorders of consciousness and cognition.

ADHD and central nervous system stimulant prescribing has increased by almost 70% in five years

ADHD and central nervous system stimulant prescribing has increased by almost 70% in five years

ADHD and central nervous system stimulant prescribing nearly doubles in adults in three years

ADHD and central nervous system stimulant prescribing nearly doubles in adults in three years

Caffeine Consumption among Indonesian Population

Background: Caffeine is the most commonly used central nervous system stimulant in all age groups. High daily caffeine consumption can affect health. Most caffeine users are unaware of the amount of daily caffeine consumption or the effect of caffeine on the physical and psychological health of its users. This study aimed to determine the prevalence of caffeine addiction in Indonesian society. Materials and Methods: This study used a Cross-Sectional Study design using an online questionnaire of 345 Indonesians. Data were collected using caffeine consumption questionnaires. The data is analyzed descriptively. Results: More than half of the study’s respondents were female (53%), had a higher level of higher education (71%), and were employed (71%). The average total caffeine consumption in the community is 234 ±191 mg daily. Conclusion: Caffeine use in adults is quite high compared to that reported in other countries. The public should be better informed regarding the possible side effects that arise from the use of caffeine

Salience and hedonic experience as predictors of central stimulant treatment response in ADHD

Salience and hedonic experience as predictors of central stimulant treatment response in ADHD

Coordinated neurostimulation promotes circuit rewiring and unlocks recovery after spinal cord injury.

Functional recovery after incomplete spinal cord injury depends on the effective rewiring of neuronal circuits. Here, we show that selective chemogenetic activation of either corticospinal projection neurons or intraspinal relay neurons alone led to anatomically restricted plasticity and little functional recovery. In contrast, coordinated stimulation of both supraspinal centers and spinal relay stations resulted in marked and circuit-specific enhancement of neuronal rewiring, shortened EMG latencies, and improved locomotor recovery.

Assessment of caffeine consumption behavior among Jazan University students in the south of Saudi Arabia: A cross-sectional study

Caffeine is a central nervous system stimulant. High consumption levels of caffeine can lead to intoxication and serious side effects. Saudi Arabia is witnessing a rise in the commercialization and consumption of caffeine. Young adults such as university students may exhibit high levels of caffeine consumption. This investigation aims to assess caffeine consumption habits among a sample of Jazan University students in the south of Saudi Arabia. This study was a cross-sectional investigation that utilized multistage sampling to recruit the students. Data was collected via a self-administered questionnaire that measured student demographics, their frequency of consuming caffeine-containing food, portion sizes, and patterns of consumption during different times of the day. Caffeine consumption levels were estimated based on a cutoff point of 400 mg per day. A chi-squared test was used to investigate the association between levels of caffeine consumption and measured study characteristics. A sample of 964 students was recruited with a mean age of 21.8 years. The most frequently consumed product among the recruited students was coffee (32%), followed by chocolate bars (16%) and soft drinks (12%). The median total consumed caffeine amount was 185 mg per day. 194 (20%) students of the sample exceeded the recommended level of daily caffeine consumption (>400 mg/day). Among the measured demographics, only the year of study was associated with caffeine consumption (P value of .003), suggesting that students in their earlier years of university are likely to exceed the recommended daily consumption of caffeine in comparison with those who are in their later years of study. Our investigation identified high levels of caffeine consumption among some students. The findings imply the need to enhance the awareness of students who exceed the recommended daily intake of caffeine regarding the harmful impacts of caffeine toxicity.