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Learning motor skills commonly requires repeated execution to achieve gains in performance. Motivated by memory reactivation frameworks predominantly originating from fear-conditioning studies in rodents, which have extended to humans, we asked the following: Could motor skill learning be achieved by brief memory reactivations? To address this question, we had participants encode a motor sequence task in an initial test session, followed by brief task reactivations of only 30 s each, conducted on separate days. Learning was evaluated in a final retest session. The results showed that these brief reactivations induced significant motor skill learning gains. Nevertheless, the efficacy of reactivations was not consistent but determined by the number of consecutive correct sequences tapped during memory reactivations. Highly continuous reactivations resulted in higher learning gains, similar to those induced by full extensive practice, while lower continuity reactivations resulted in minimal learning gains. These results were replicated in a new independent sample of subjects, suggesting that the quality of memory reactivation, reflected by its continuity, regulates the magnitude of learning gains. In addition, the change in noninvasive brain stimulation measurements of corticospinal excitability evoked by transcranial magnetic stimulation over primary motor cortex between pre- and postlearning correlated with retest and transfer performance. These results demonstrate a unique form of rapid motor skill learning and may have far-reaching implications, for example, in accelerating motor rehabilitation following neurological injuries.

Sexual health is a critical component of quality of life. Chronic pain can significantly impair sexual functioning through complex and multimodal effects spanning physical, psychological, and social domains. Nevertheless, when properly managed, many people with chronic pain can still enjoy fulfilling sexual relationships. Therefore, addressing sexual health concerns is an important aspect of holistic modern chronic pain management. This study is the first to investigate attitudes and perspectives of pain specialists regarding sexual health issues, including barriers to diagnosis and management. A Nationwide web-based survey of all registered and active board-certified pain specialists in Israel held in August–September 2024. Out of 133 physician members of the Israeli Pain Association, 75 (56.4%) completed the survey, 62.7% of them males, and most (73.3%) worked in public facilities, and the primary specialty of 41.3% was anesthesiology. While 81.3% of physicians acknowledged the high prevalence of sexual dysfunction in chronic pain patients, only 14.7% proactively discuss it with patients. Similarly, 89.3% reported little to no training on sexual health, and 60% felt underprepared to address these issues. Most felt more comfortable discussing sexual health with same-gender patients, time constraints, low priority, and lack of knowledge were noted as key barriers. This study reveals a gap between physicians’ awareness of sexual health issues and their translation of this into clinical practice. Time constraints, discomfort, and insufficient training hinder discussions. Improving referral pathways and fostering system-level support are essential to integrating sexual health into routine pain management. In particular, the results underscore an urgent need to integrate sexual health training into pain medicine, which could improve patient outcomes and quality of life among chronic pain patients.

According to the Israeli Ministry of Health, more than 10 000 patients with cancer receive permits annually, making it the most commonly prescribed medication by the Israeli oncologists. [...]Israeli oncologists are unique in terms of their vast expertise in the use of cannabis for cancer-associated symptoms.3,4 To examine the experience, perceptions, and attitudes of Israeli oncologists towards the use of cannabis, we did a national web-based survey among all those oncologists who are registered with the Israeli Society of Clinical Oncology and Radiation Therapy. 126 (53%) of 238 registered oncologists responded to the survey. Importantly, pattern of use was affected by personal views. [...]although physicians favouring legalisation (n=46) and opposing legalisation (n=78) had similar views regarding indications, contraindications, activity, safety, and knowledge, those favouring legalisation reported recommending more permits per year than those opposing it (p=0·045; table). Because the use of cannabis for such purpose is not allowed, according to the Israeli Ministry of Health guidelines, and is not reported to oncologists, the magnitude of the phenomenon could not be assessed in this survey. Since no prospective clinical data regarding the efficacy of cannabis for cancer-related symptoms are available, the knowledge of oncologists who are experienced in its use is highly valuable.

Ketamine has been demonstrated to improve depressive symptoms.AimsEvaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD). In a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery-Åsberg Depression Rating Scale (MADRS). Twenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient. Repeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.Declaration of interestNone.

Background. Chronic pain (CP) prevalence in different studies has been inconsistent, ranging from 12% in Spain to 42% in the UK. Purpose. We conducted an internet-based survey in a representative cohort of Israeli adults assembled by a large professional survey company in order to probe the prevalence of CP in Israel. Methods. 8,300 Israeli adults comprising a representative cohort of the Israeli population were asked whether they were suffering from pain lasting over 3 months. 1647 participants responded (19.8% response rate). Of these, 515 (31.3%) had CP. Participants with CP were then asked a series of follow-up questions regarding their chronic pain. Statistical weights were used to correct for the distribution of the Israeli population based on sociodemographic characteristics. Results. CP patients were significantly older than respondents without pain. The average daily pain was 5.8/10 on a numerical rating scale. Common pain locations were axial skeleton and headaches. However, over half of patients reported pain in multiple body areas, and around a fifth had an undiagnosed chronic pain syndrome. Around 40% of pain patients reported to have visited a specialized pain clinic, and the same proportion has consulted several specialists. Despite this, a sizable proportion of high pain intensity patients were still left with no or inefficient treatment to alleviate their pain. Conclusions. This is the first internet survey conducted in Israel to estimate the incidence of CP, and the high CP prevalence documented is in agreement with previous reports from Europe and the USA. It also reaffirms the widespread existence of multifocal or widespread pain in clinical chronic pain and the correlation between pain intensity, impact on patients’ quality of life and disability, and pain intractability. These data reaffirm the similarly major health burden CP presents across different countries and cultures.

Background and objectivesCancer-related pain management in advanced stages presents a significant challenge that often requires a multidisciplinary approach. Although advancements in pharmacological and interventional therapies, a considerable number of patients still suffer from refractory pain, leading to unmet clinical needs. This study shares our experience with medical cannabis (MC) as a potential therapy for this specific population of patients with cancer-related refractory pain.MethodsIn a cross-sectional study, 252 consecutive refractory cancer-related pain patients (mean age=61.71, SD=14.02, 47.6% males) filled out detailed self-report questionnaires. Of these, 126 patients (55%) were treated with MC and 105 patients (45%) were not.ResultsMost patients received pain management from their oncologist, not a pain specialist. MC was mainly started for pain relief, sleep difficulties and anorexia. About 70% of patients reported subjective improvement from MC, with almost 40% reporting a significant improvement in coping with their illness. Side effects were generally mild, with fatigue and dizziness being the most common (21.78% and 23.46%, respectively). No patient required dedicated medical care for side effects. Of non-users, 65% had tried MC before and stopped due to lack of effectiveness or side effects (39.7% and 34.6%, respectively).ConclusionRefractory cancer pain necessitates innovative approaches. This registry highlights that MC can effectively improve symptoms in non-responsive patients, with favourable safety profiles for this vulnerable population.

Contemporary symptom-based diagnosis of post-traumatic stress disorder (PTSD) largely overlooks related neurobehavioral mechanisms and relies entirely on subjective interpersonal reporting. Previous studies associating biomarkers with PTSD have mostly used symptom-based diagnosis as the main outcome measure, disregarding the wide variability and richness of PTSD phenotypical features. Here, we aimed to computationally derive potential biomarkers that could efficiently differentiate PTSD subtypes among recent trauma survivors. A three-staged semi-unsupervised method (“3C”) was used to firstly categorize individuals by current PTSD symptom severity, then derive clusters based on clinical features related to PTSD (e.g. anxiety and depression), and finally to classify participants’ cluster membership using objective multi-domain features. A total of 256 features were extracted from psychometrics, cognitive functioning, and both structural and functional MRI data, obtained from 101 adult civilians (age = 34.80 ± 11.95; 51 females) evaluated within 1 month of trauma exposure. The features that best differentiated cluster membership were assessed by importance analysis, classification tree, and ANOVA. Results revealed that entorhinal and rostral anterior cingulate cortices volumes (structural MRI domain), in-task amygdala’s functional connectivity with the insula and thalamus (functional MRI domain), executive function and cognitive flexibility (cognitive testing domain) best differentiated between two clusters associated with PTSD severity. Cross-validation established the results’ robustness and consistency within this sample. The neural and cognitive potential biomarkers revealed by the 3C analytics offer objective classifiers of post-traumatic morbidity shortly following trauma. They also map onto previously documented neurobehavioral mechanisms associated with PTSD and demonstrate the usefulness of standardized and objective measurements as differentiating clinical sub-classes shortly after trauma.

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by reducing sleep disorder improving emotion regulation. We further expected that improved clinical status would correspond with successful training as indicated by improved down modulation of the Amygdala-EFP signal. Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions or sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion. REM latency and objective sleep quality index were robustly improved following the treatment course only in the real-neurofeedback group (time × group p < 0.05) and to a greater extent among good modulators (time × sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the neurofeedback training. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the real-neurofeedback group (time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures. Our findings suggest that Amyg-EFP-neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation treatment in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the substantial link between somatic and affective dysregulation that can be successfully targeted using neurofeedback. [Display omitted] •Fibromyalgia patients were trained in limbic neuromodulation.•After training, only real NF group showed improvement in objective sleep measures.•Follow-up revealed group specific improvement in pain and subjective sleep.•Pain alleviation was moderated by initial improvement in objective sleep and affect.•fMRI driven EEG-NF can serve as a novel approach to treat Fibromyalgia.

Motor performance varies substantially between individuals. This variance is rooted in individuals' innate motor abilities, and should thus have a neural signature underlying these differences in behavior. Could these individual differences be detectable with neural measurements acquired at rest? Here, we tested the hypothesis that motor performance can be predicted by resting motor-system functional connectivity and motor-evoked-potentials (MEPs) induced by non-invasive brain stimulation. Twenty healthy right handed subjects performed structural and resting-state fMRI scans. On a separate day, MEPs were measured using transcranial magnetic stimulation (TMS) over the contrateral primary motor cortex (M1). At the end of the session, participants performed a finger-tapping task using their left non-dominant hand. Resting-state functional connectivity between the contralateral M1 and the supplementary motor area (SMA) predicted motor task performance, indicating that individuals with stronger resting M1-SMA functional connectivity exhibit better motor performance. This prediction was neither improved nor reduced by the addition of corticospinal excitability to the model. These results confirm that motor behavior can be predicted from neural measurements acquired prior to task performance, primarily relying on resting functional connectivity rather than corticospinal excitability. The ability to predict motor performance from resting neural markers, provides an opportunity to identify the extent of successful rehabilitation following neurological damage.

Background Fibromyalgia (FM), involving somatic, cognitive, and affective domains is often regarded as a hallmark central sensitization syndrome. Despite limited current therapeutic options, emerging understanding of its neural underpinnings offers the potential of applying novel neuromodulation strategies. Specifically, limbic dysregulation underlying abnormalities in pain modulation and somatic-affective processing, has been shown to play a key role in FM. Here, we assessed the long-term efficacy of targeted limbic self-neuromodulation for improving clinical disease burden in FM. Methods Forty-seven patients with FM participated in a double-blind, randomized, dual-control study employing a novel specialized neurofeedback probe representing amygdala activity. Patients underwent 10 sessions of either genuine neurofeedback training (NFT = 21), or sham neurofeedback training (NFS = 13), or treatment as usual (TAU = 13). Disease severity and symptom burden were assessed using the Symptom Severity Score (SSS), along with other questionnaires administered before and after treatment. A clinical follow-up was performed 10–12 months post-intervention. Results NFT led to a significant immediate and long-term reduction in the SSS (F (2,40)  = 7.32, p  = 0.00, ηp2 = 0.27) and the Fibromyalgia Impact Questionnaire (FIQ) (F (2,40)  = 9.85, p  = 0.00, ηp2 = 0.33), alongside multidomain short- and long-term clinical benefits. NFS resulted in a long-term reduction in pain but did not affect other disease measures or overall disease burden. The TAU group showed no clinical improvements. Conclusions Our findings support the intimate involvement of limbic brain areas in the pathophysiology of FM and suggest that targeted neuromodulation offers a novel, mechanism-based approach for managing multidomain symptoms in FM. Trial registration This study was preregistered with the National Institutes of Health (NIH). Registration number: NCT02146495. Name of trial registry: Targeted Limbic Self-modulation as a Potential Treatment for Patients Suffering From Fibromyalgia  https://clinicaltrials.gov/study/NCT02146495 .