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The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson’s disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward.

Several studies have illustrated that transcutaneous vagus nerve stimulation (tVNS) can elicit therapeutic effects that are similar to those produced by its invasive counterpart, vagus nerve stimulation (VNS). VNS is an FDA-approved therapy for the treatment of both depression and epilepsy, but it is limited to the management of more severe, intervention-resistant cases as a second or third-line treatment option due to perioperative risks involved with device implantation. In contrast, tVNS is a non-invasive technique that involves the application of electrical currents through surface electrodes at select locations, most commonly targeting the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck. Although it has been shown that tVNS elicits hypo- and hyperactivation in various regions of the brain associated with anxiety and mood regulation, the mechanism of action and influence of stimulation parameters on clinical outcomes remains predominantly hypothetical. Suppositions are largely based on correlations between the neurobiology of the vagus nerve and its effects on neural activity. However, tVNS has also been investigated for several other disorders, including tinnitus, migraine and pain, by targeting the vagus nerve at sites in both the ear and the neck. As most of the described methods differ in the parameters and protocols applied, there is currently no firm evidence on the optimal location for tVNS or the stimulation parameters that provide the greatest therapeutic effects for a specific condition. This review presents the current status of tVNS with a focus on stimulation parameters, stimulation sites, and available devices. For tVNS to reach its full potential as a non-invasive and clinically relevant therapy, it is imperative that systematic studies be undertaken to reveal the mechanism of action and optimal stimulation modalities.

Introduction: The axillary plexus block is one of the most used regional anesthesia techniques in upper limb surgery. In this study, we retrospectively evaluated the advantages of using the technique with a single injection in the axillary block, a technique that was used in the Orthopedic Clinic of SCJU between 1.01.2016 and 31.05.2016.Methods: The patients admitted to the study were those with ASA I-III in the number of 50 of which 35 were men and 15 women who underwent axillary brachial plexus block using the single injection technique with the help of the neurostimulator. All patients had surgical interventions in the region of the distal arm, elbow, forearm and hand.The axillary block was performed with the nerve stimulator, using a 22g and 50mm needle, the puncture site used was above the artery where, after obtaining the motor response to the 0.5 mA impulse, Ropivacaine 0.5% 20 ml was injected. Later we analyzed the installation time of the motor and sensory block, what success rate it had and the possible complications.Results: The average motor block installation time was 21+/-1.3 min in the 35 patients. The motor block installation time was 19.2+/-1.5 min and the sensory block a was 16.19+/-1.1 min. block success rate was 91.5 percent. There were no recent or late complications.Conclusions: Axillary plexus block using the single injection technique can be used with great benefits, few complications and low failure rate of the technique.

Objective:The aim of the present study was to analyse the effects of the transcranial random noise stimulation (tRNS) technique when placed on the left dorsolateral prefrontal cortex (L-DPFC) and left inferior frontal gyrus (L-IFG), for the improvement of verbal fluency performance and creativity skills in a group of multilingual healthy adults.Participants and Methods:Fifty healthy adults, aged 18-47 years, participated in the study. All of them were native Spanish speakers of which three were bilingual (Spanish and English) and 47 were multilingual (Spanish, Basque and English). The study had a randomized, counterbalanced, double-blind, sham-controlled design. The participants were randomly allocated to either a tRNS active group or a placebo-control group. All participants were tested individually in one session divided into three parts: (1) baseline, (2) online, and (3) offline assessment. In the active condition, a 1.5mA current (100-500 Hz) was delivered for 20 minutes (online phase). Participants’ verbal fluency was assessed through semantic and phonemic verbal fluency tasks in three different languages (Spanish, Basque and English), while creativity was assessed in their native language with the Remote Associations Test (RAT, pre and post forms) for convergent thinking, and with the Unusual Uses subtest (UU, pre and post forms) for divergent thinking. In addition, the linguistic profile of the participants was evaluated with the Language Experience and Proficiency Questionnaire (LEAP-Q), and their processing speed and cognitive flexibility were assessed with the Stroop Color and Word Test (SCWT).Results:The results showed significant differences in phonemic fluency between the groups during the online assessment in Spanish (F= 5.31, p = 0.026), and in the offline assessments in Spanish (F=6.44, p = 0.015) and English (F=10.80, p = 0.002), with participants in the active condition performing better. While no differences were observed in the performance of the groups in verbal fluency in Basque, neither in the online (F=1.06, p = 0.31), nor in the offline assessment (F=2.62, p = 0.11). Furthermore, no significant differences were observed between groups in semantic verbal fluency tasks in any of the languages, neither during stimulation nor offline. However, there were no differences between conditions in the online (Spanish, F=0.86, p = 0.35; English, F=2.95, p = 0.09; and Basque, F=0.01 p = 0.94) and offline (Spanish, F=2.53, p = 0.11; English, F=0.74, p = 0.39; and Basque, F=1.39, p = 0.24) semantic tasks. In creativity, significant differences were observed between groups on the RAT (F=9.58, p = 0.003), while no differences were observed in the performance of any of the three dimensions of the UU (Originality, F=0.44, p = 0.51; Flexibility, F=0.42, p = 0.51; Fluency, F=0.69, p = 0.41). In the SCWT, statistically significant differences were only observed in the colour-word part (F=7.60, p = 0.008) during the online assessment, showing a better performance of the participants under the tRNS condition compare to the sham condition.Conclusions:The results obtained in this study suggest that the excitatory effects of tRNS over the L-DLPFC L-IFG could contribute to the improvement of phonemic verbal fluency and verbal convergent thinking, in healthy individuals.

Objective:High-definition transcranial direct current stimulation (HD-tDCS) is a non-invasive brain stimulation technique shown to modulate neuronal networks. In order for HD-tDCS to be used in randomized, placebo-controlled clinical trials, it is critical to have methods that enable blinding. Some research has shown that sham stimulation is an effective blind in tDCS. However, few studies have investigated the double-blinding of HD-tDCS, especially at intensities greater than 2mA. We address this knowledge gap by examining the blinding and double-blinding of HD-tDCS among a mixed neurologic sample of older adults.Participants and Methods:A sample of 240 older adults (Mage = 72.21±8.94) with various clinical diagnoses (Normal Cognition = 34, Amnestic MCI [aMCI] = 172, Dementia-Alzheimer’s Type [DAT] = 27, Other = 7) were recruited through five double-blind, randomized controlled trials. All participants were stimulation naive at their first session and received one to thirty sessions of 20- or 30-minutes of active (n=1472) or sham (n=681) stimulation at total amplitudes of 2mA, 4mA, or 6mA. At the start of each stimulation session, a study team member entered a code into the tDCS unit, and the electrical current was gradually ramped up to the specified (blinded) amplitude over a period of 30 seconds. The current remained at this level for the specified amount of time in the active condition (e.g., 20-minutes) but was ramped down over the next 30 seconds for those in the sham condition. This ramp up/down process was repeated in the final minute (e.g., 20th minute) in the sham session to provide both primacy and recency effects. After each active or sham session, participants were asked whether they received 'real’ or sham stimulation. One study also asked a study team member if they believed the participant received real or sham stimulation at two primary outcome endpoints.Results:We used Fisher’s Exact tests to evaluate the efficacy of our blinding and double-blinding procedures. In stimulation naive participants receiving their first session, there were no differences in accuracy, suggesting adequate blinding. We also examined participant blinding across all sessions to determine whether repeated HD-tDCS exposure might impact blinding. Across all sessions, participants in the sham condition were more likely to endorse being in the 'real’ (active) condition, again suggesting adequate blinding. There were no significant group differences for active versus sham in the frequency of the study team correctly stating the participant’s condition, suggesting sufficient double-blinding. No significant differences were found in study team blinding when data from the 2mA versus 4mA to 6mA were analyzed separately.Conclusions:These results suggest that the HD-tDCS sham method is an effective blind and double-blind for HD-tDCS in clinical trials, even at total amplitudes as high as 6mA.

Objective:This study builds on the work by Rehman et al (2022) who argued that transcranial magnetic stimulation (TMS) treatment not only helps treat depression but also decreases sleep problems such as difficulty falling asleep,staying asleep, and waking too early. The present study further explores differences in sleep onset latency, meaning the time it takes to fall asleep, and duration of sleep per night in the pre and post treatment phases of rTMS. The information regarding major attributes of sleep is critical because recent research shows that about 90% of patients with major depressive disorder (MDD) also struggle with sleep disorders (Li et al., 2022), and sleeping for less than seven hours may eventually lead to sleep deprivation (Hirshkowitz et al., 2015), with increased risk of physical and mental health problems (Sheehan et al, 2019). Sleep onset latency estimates vary from individual to individual but typical sleep latency is considered between 10 to 20 minutes (Jung et al, 2013). As it has been shown that overall sleep problems improve with rTMS, we hypothesized that self-reported sleep onset latency will decrease, and sleep duration will increase.Participants and Methods:All participants met inclusion criteria for MDD diagnosis and completed a full course of TMS treatment (N=470; Mean age=53.45, SD=13.73). The sample was mostly male (81%) and ethnically diverse: 77.7% non-Hispanic White, 13.3% Black Americans, 1.9% Asian, 0.2 % Asian Indian, and 1.9% other ethnicities. Sleep problems were assessed using the following questions at the pre and post treatment stages: the number of minutes it takes to fall asleep and duration of sleep each night.Results:A Wilcoxon matched-pairs signed-rank test was conducted to determine whether there was a difference in sleep onset latency and hours of sleep per night between pre and post intervention. The results indicated a significant difference in time to fall asleep between pre and post treatment (pre-treatment M = 1.19, SD = 0.99, post-treatment M = 0.93, SD = 0.91; z = -5.01, p < .001. In addition, there was a significant increase in the minutes of sleep per night in pre (M = 6.11, SD = 2.07) compared to the post treatment (M = 6.32, SD = 1.77), z = -2.56, p = .010.Conclusions:Reduced sleep is known to negatively impact mood, cognitive ability, work performance, and immune function (Besedovsky et al., 2012; Killgore, 2010; Massar et al, 2019; Vandekerckhove & Wang, 2018). Similarly, longer sleep onset latency can cause an individual to enter the first sleep stage later than expected and complete fewer sleep cycles. The results of the present study show the effectiveness of rTMS in decreasing sleep onset latency and increasing the duration of sleep. Given the comorbidity and bidirectionality between sleep disturbances and mood disorders (Fang et al., 2019; Palagini et al., 2019), further researching treatments such as rTMS to improve sleep as a means to also improve mood is crucial. We propose acquiring knowledge about sleep attributes as an essential part of clinicians’ work early on in the rTMS treatment in order to monitor an individual’s global functioning level in light of improved sleep.

Objective:Repetitive transcranial magnetic stimulation (TMS) is an evidenced based treatment for adults with treatment resistant depression (TRD). The standard clinical protocol for TMS is to stimulate the left dorsolateral prefrontal cortex (DLPFC). Although the DLPFC is a defining region in the cognitive control network of the brain and implicated in executive functions such as attention and working memory, we lack knowledge about whether TMS improves cognitive function independent of depression symptoms. This exploratory analysis sought to address this gap in knowledge by assessing changes in attention before and after completion of a standard treatment with TMS in Veterans with TRD.Participants and Methods:Participants consisted of 7 Veterans (14.3% female; age M = 46.14, SD = 7.15; years education M = 16.86, SD = 3.02) who completed a full 30-session course of TMS treatment and had significant depressive symptoms at baseline (Patient Health Questionnaire-9; PHQ-9 score >5). Participants were given neurocognitive assessments measuring aspects of attention [Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) subtests: Digits Forward, Digits Backward, and Number Sequencing) at baseline and again after completion of TMS treatment. The relationship between pre and post scores were examined using paired-samples t-test for continuous variables and a linear regression to covary for depression and posttraumatic stress disorder (PTSD), which is often comorbid with depression in Veteran populations.Results:There was a significant improvement in Digit Span Forward (p=.01, d=-.53), but not Digit Span Backward (p=.06) and Number Sequencing (p=.54) post-TMS treatment. Depression severity was not a significant predictor of performance on Digit Span Forward (f(1,5)=.29, p=.61) after TMS treatment. PTSD severity was also not a significant predictor of performance on Digit Span Forward (f(1,5)=1.31, p=.32).Conclusions:Findings suggested that a standard course of TMS improves less demanding measures of working memory after a full course of TMS, but possibly not the more demanding aspects of working memory. This improvement in cognitive function was independent of improvements in depression and PTSD symptoms. Further investigation in a larger sample and with direct neuroimaging measures of cognitive function is warranted.

Objective:Poor mood and quality of life is common among patients with medically intractable seizures. Many of these patients are not candidates for seizure focus resection and continue to receive standard medical care. Responsive neurostimulation (RNS) has been an effective approach to reduce seizure frequency for nonsurgical candidates. Previous research using RNS clinical trial participants has demonstrated improved mood and quality of life when patients received RNS-implantation earlier in their medically resistant epilepsy work-up (Loring et al., 2021). We aimed to describe the level of depression and quality of life in adults with medical resistant epilepsy, treated with RNS, presenting to an outpatient clinic.Participants and Methods:This pilot study was conducted among 11 adult epilepsy patients treated with RNS at the epilepsy specialty clinic at Baylor College of Medicine. Ages of participants ranged from 18-56 (M=32.01, SD=12.37) with a mean education of 12.43 (SD=0.85). The majority of the participants identified as White (White=72.2%; Hispanic/Latino/a=14.3%, Other=7.1%). We also present pre- and post-RNS preliminary results of a subset of 4 patients for whom pre and post implantation data was available. Depression symptoms were assessed through the Beck Depression Inventory, 2nd Edition (BDI-II) and quality of life was determined using the Quality of Life in Epilepsy (QoLiE-31).Results:Patients reported minimal symptoms of depression (M=5.45, SD=4.03) and good overall quality of life (M=71.18, SD=14.83) after RNS. Participants’ scores on their overall quality of life ranged from 50 to 95 (100=better quality of life). The QoLiE-31 showed high scores on emotional wellbeing (M=69.45, SD=14.56) and cognitive functioning (M=65.36, SD=16.66) domains. Post-hoc analysis revealed a significant difference in the cognitive functioning domain of QoLiE-31 before (M=44.75, SD=12.58) and after (M=51.0, SD=11.58) RNS implantation(t(3)=-3.78, p=0.016. Additionally, overall QoLiE score approached statistical significance when comparing pre-RNS (M=44.75 SD=9.29) to post-RNS (M=49.75 SD=11.62; t(3)=-2.01, p = 0.069). No significant differences were evident on seizure worry, energy/fatigue, medication effects, and social functioning domains of QoLiE-31 before and after RNS treatment.Conclusions:These pilot study results suggest low levels of depression with this population post-RNS implantation. Additionally, there is preliminary evidence to suggest improved patient-rated cognitive functioning and overall quality of life. While this is a small study population, the results have important implications for patients with intractable epilepsy, even with those form who surgical resection may not be possible. Future studies with large enough samples to examine moderating and mediating factors to mood and quality of life changes post-RNS will be important.

Post-stroke dysphagia (PSD) is present in more than 50% of acute stroke patients, increases the risk of complications, in particular aspiration pneumonia, malnutrition and dehydration, and is linked to poor outcome and mortality. The aim of this guideline is to assist all members of the multidisciplinary team in their management of patients with PSD. These guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. An interdisciplinary working group identified 20 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found moderate quality of evidence to recommend dysphagia screening in all stroke patients to prevent post-stroke pneumonia and to early mortality and low quality of evidence to suggest dysphagia assessment in stroke patients having been identified at being at risk of PSD. We found low to moderate quality of evidence for a variety of treatment options to improve swallowing physiology and swallowing safety. These options include dietary interventions, behavioural swallowing treatment including acupuncture, nutritional interventions, oral health care, different pharmacological agents and different types of neurostimulation treatment. Some of the studied interventions also had an impact on other clinical endpoints such as feedings status or pneumonia. Overall, further randomized trials are needed to improve the quality of evidence for the treatment of PSD.