Effect of Propranolol on Motor Cortex Excitability in Essential Tremor: An Exploratory Study.

Background: Essential tremor, the world's most prevalent movement disorder, lacks a clear understanding of its pathophysiology. Propranolol, a non-specific beta-blocker capable of crossing the blood-brain barrier, is a primary choice for essential tremor treatment. While its tremor-reducing effects are generally attributed to peripheral actions, various uses hint at central adrenergic effects. Nevertheless, propranolol's precise impact on the central nervous system in essential tremor subjects remains unexplored. Methods: In this study, we employed transcranial magnetic stimulation to assess the influence of propranolol on the excitability of the primary motor cortex (M1) in patients with essential tremor, compared to an age- and sex-matched control group. Cortical excitability parameters were measured following placebo and propranolol administration, encompassing resting and active motor thresholds, motor evoked potential characteristics, cortical silent period, and the input/output curve. Results: Distinct effects were observed across the two cortical hemispheres. Essential tremor patients displayed inhibition of the left M1 cortex and heightened excitability in the right M1 cortex four hours after propranolol administration, but not following placebo. Conclusions: These findings suggest potential differential noradrenergic excitatory and inhibitory modulation. However, comprehensive understanding necessitates further investigations, including left-handed participants and more diverse essential tremor subpopulations. This study underscores the need for continued exploration to unravel propranolol's complex effects on motor cortex excitability in essential tremor.

High Frequency and Low Intensity Transcranial Magnetic Stimulation for Smoking Cessation.

INTRODUCTION: Tobacco consumption is one of the main causes of mortality in the world. Because of its effect on health, smoking cessation should be prioritized as an important health intervention; however, current interventions have shown low success rates as only 31% of the cases can stop smoking. In this paper, an intervention with high frequency and low intensity transcranial magnetic stimulation (HFLI TMS) was applied to determine if this type of neuromodulation could have an effect in decreasing tobacco addiction. METHODS: Retrospective data from ten ambulatory smoker patients that underwent 24 sessions of HFLI TMS over 8 weeks were retrieved and are here presented. RESULTS: Exhaled CO concentrations were statistically significantly different from baseline at the weeks 3, 5, 6, and 8. After the 24 sessions, all patients stopped smoking; this was confirmed directly by exhaled carbon monoxide and the smoking diary. Three months after intervention, eight out of ten subjects continued without smoking. No severe adverse effects were reported by participants. CONCLUSIONS: Overall, employing HFLI TMS appears to have acceptable result; however, further evidence is needed to determine with more certainty its therapeutic effect and adverse effects for addiction intervention.

Use of Fast Gamma Magnetic Stimulation Over the Left Prefrontal Dorsolateral Cortex for the Treatment of MCI and Mild Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled, Pilot Study.

Background: Alzheimer's disease (AD) animal models have shown a reduced gamma power in several brain areas, and induction of these oscillations by non-invasive methods has been shown to modify several pathogenic mechanisms of AD. In humans, the application of low-intensity magnetic fields has shown to be able to produce neural entrainment at the magnetic pulse frequency, making it useful to induce gamma frequencies. Objective: The aim of this study was to assess if the application of fast gamma magnetic stimulation (FGMS) over the left prefrontal dorsolateral cortex would be a safe and well-tolerated intervention that could potentially improve cognitive scores in subjects with mild cognitive impairment and mild AD. Methods: In these randomized, double-blind, sham-controlled study, participants were assigned to either receive daily sessions two times a day of active or sham FGMS for 6 months. Afterward, measurements of adverse effects, cognition, functionality, and depression were taken. Results: Thirty-four patients, 17 in each group, were analyzed for the primary outcome. FGMS was adequately tolerated by most of the subjects. Only four patients from the active FGMS group (23.52%) and one patient from the sham FGMS group (5.88%) presented any kind of adverse effects, showing no significant difference between groups. Nevertheless, FGMS did not significantly change cognitive, functionality, or depressive evaluations. Conclusion: FGMS over the left prefrontal dorsolateral cortex applied twice a day for 6 months resulted to be a viable intervention that can be applied safely directly from home without supervision of a healthcare provider. However, no statistically significant changes in cognitive, functionality, or depression scores compared to sham stimulation were observed. Clinical Trial Registration:www.ClinicalTrials.gov, Identifier: NCT03983655, URL: https://clinicaltrials.gov/ct2/show/NCT03983655.

High-Frequency and Low-Intensity Patterned Transcranial Magnetic Stimulation over Left Dorsolateral Prefrontal Cortex as Treatment for Major Depressive Disorder: A Report of 3 Cases.

Current transcranial magnetic stimulation devices apply intense (near 1 tesla) repetitive magnetic pulses over a specific area of the skull at relatively lower frequencies (1-50 Hz). Nevertheless, different studies have shown that very small magnetic fields, at higher frequencies (50-1000 Hz.), produce therapeutic effects in major depressive disorder. We report the application of high-frequency and low-intensity patterned magnetic pulses over the left prefrontal dorsolateral cortex in three subjects diagnosed with clinical major depressive disorder. All three patients showed sharp changes in their self-reports as well as in the standardized clinical assessment. Hypothesized mechanisms of action of this new variant of magnetic stimulation are discussed.

Continuous Theta Burst Stimulation Over the Right Orbitofrontal Cortex Impairs Conscious Olfactory Perception.

The right orbitofrontal cortex (rOFC) has been proposed as the region where conscious olfactory perception arises; however, evidence supporting this hypothesis has all been collected from neuroimaging and lesion studies in which only correlation and not a temporal pattern can be established. Continuous theta burst stimulation (cTBS) causes a reversible disruption of cortical activity and has been used successfully to disrupt orbitofrontal activity. To overcome intrinsic limitations of current experimental research, a crossover, double-blind, prospective and longitudinal study was carried out in which cTBS was applied over the rOFC to evaluate its effect on odorant stimuli detection. All subjects received real and sham cTBS. Experimental procedures were done in two different sessions with a separation of at least one week between them to avoid carryover and learning effects. A total of 15 subjects completed the experiment, and their data were included in the final analysis (10 women, 5 men, mean age 22.40 ± 3.41). Every session consisted of two different measures of the conscious olfactory perception task: A baseline measure and one 5 min after cTBS/sham. Compared to baseline, marks in the olfactory task during the sham cTBS session increased (p = 0.010), while marks during the real cTBS session decreased (p = 0.017). Our results support the hypothesis that rOFC is an important node of a complex network required for conscious olfactory perception to arise. However, the exact mechanism that explains our results is unclear and could be explained by the disruption of other cognitive functions related to the rOFC.

Therapeutic Interventions for Vascular Parkinsonism: A Systematic Review and Meta-analysis.

BACKGROUND: Vascular parkinsonism (VP) is defined as the presence of parkinsonian syndrome, evidence of cerebrovascular disease, and an established relationship between the two disorders. However, the diagnosis of VP is problematic, particularly for the clinician confronted with moving from diagnosis to treatment. Given the different criteria used in the diagnosis of VP, the effectiveness of available therapeutic interventions for this disease are currently unknown. METHODS: To assess the clinical response of all published therapeutic interventions for VP that have been reported in the literature, we conducted a systematic review looking for VP subjects treated with any therapeutic intervention. To clarify the prevalence of responsiveness to levodopa among VP subjects, we conducted a meta-analysis of 17 observational studies retrieved with the search criteria of our review. Also, four studies were included in a second analysis to explore if nigrostriatal lesion affected the prevalence of levodopa response in VP subjects. Relevant articles were identified from MEDLINE, Scopus, and Web of Science published until June 2017. RESULTS: 436 non-duplicate citations were identified for screening, 107 articles were assessed for eligibility, and only 23 observational studies were included in this review. No randomized clinical trials were found. Four different therapies were found in the literature; among them, levodopa was the only one repetitively reported. The calculated event rate of levodopa response in VP subjects was of 0.304 [95% confidence interval (CI) of 0.230-0.388]. The overall odds ratio for good response to levodopa in VP with lesion in the nigrostriatal pathway vs. no lesion in the nigrostriatal pathway was 15.15 (95% CI: 5.2-44.17). CONCLUSION: Despite the lack of randomized controlled trials, results of this systematic review and meta-analysis show that VP subjects, as operationally defined here, have a low response rate to levodopa; nigrostriatal lesion could be used as a proxy predictor of levodopa response in VP subjects. Other therapies seem to be co-adjuvant. Randomized controlled trials with a clear definition of VP are necessary to be able to assign positive or negative predictive values to available treatments and to recommend any of the therapeutic interventions for these subjects.

Psychiatric comorbidities in movement disorders.

Psychiatric comorbidities are common in movement disorders. This review provides a practical approach to help clinicians to recognize psychiatric disorders in the most frequent movement disorders. However, the extent of neurodegeneration, as well as the impact of medications with considerable CNS effects, influences the diverse psychiatric presentations that, in turn, are influenced by the stress of living with a movement disorder. Depression, anxiety, and psychosis are the most common psychiatric comorbidities in movement disorders and of the medications used to treat the motor disturbances. These psychiatric problems impair patients' functioning throughout the course of the chronic neurodegenerative diseases. Due to the direct connection between brain dysfunction and psychiatric symptoms, there is hope that understanding the psychiatric comorbidities in movement disorders will lead to a better quality-of-life.

Sleep deprivation and oxidative stress in animal models: a systematic review.

Because the function and mechanisms of sleep are partially clear, here we applied a meta-analysis to address the issue whether sleep function includes antioxidative properties in mice and rats. Given the expansion of the knowledge in the sleep field, it is indeed ambitious to describe all mammals, or other animals, in which sleep shows an antioxidant function. However, in this paper we reviewed the current understanding from basic studies in two species to drive the hypothesis that sleep is a dynamic-resting state with antioxidative properties. We performed a systematic review of articles cited in Medline, Scopus, and Web of Science until March 2015 using the following search terms: Sleep or sleep deprivation and oxidative stress, lipid peroxidation, glutathione, nitric oxide, catalase or superoxide dismutase. We found a total of 266 studies. After inclusion and exclusion criteria, 44 articles were included, which are presented and discussed in this study. The complex relationship between sleep duration and oxidative stress is discussed. Further studies should consider molecular and genetic approaches to determine whether disrupted sleep promotes oxidative stress.