Pain management strategies have progressed beyond traditional pharmacologic and physical interventions, integrating advanced neuromodulation techniques such as deep brain stimulation, peripheral nerve stimulation, and high-frequency spinal cord stimulation (hSCS). Despite its clinical efficacy, the supraspinal mechanisms underlying hSCS remain poorly understood. Prior work in sheep demonstrated that hSCS modulates gamma (γ) band (70-150 Hz) activity in the primary somatosensory and association cortices, implicating cortical involvement in pain modulation. Given the interaction between low- and high-oscillations, we hypothesized that hSCS modulates γ activity in a region- and time-dependent manner through specific coupling with theta rhythms (θ, 4-8 Hz). To test this, we quantified θ-γ phase-amplitude coupling (PAC) during tibial nerve stimulation (TNS) before (TNS0) and after (TNS1) hSCS to assess cortical processing of TNS-evoked activity, while recording cortical (association and somatosensory cortices) neural activity using 96-channel subdural electrocorticography (ECoG). We then computed the corresponding modulation index (MI) to quantify PAC strength. While the preferred θ phase of γ activity remained consistent across conditions in both cortical areas, θ-γ coupling was more robust and stable in the association than the somatosensory cortex. However, MI increased significantly post-hSCS in both cortices, indicating enhanced θ-γ coupling during TNS1. Temporally, both cortices showed distinct response patterns: the somatosensory cortex exhibited strongest coupling increase early post-hSCS, followed by a progressive decline, whereas the association cortex showed a more delayed and temporally distributed enhancement. These findings indicate that hSCS modulates cortical cross-frequency interactions during TNS-evoked sensory processing, wherein somatosensory and association cortices show distinct temporal coupling dynamics that may contribute to supraspinal mechanisms of pain modulation.

Background:With the commercial availability of deep brain stimulation neurostimulators and sensing leads capable of recording deep brain Local Field Potentials, researchers now commonly study the spectral characteristics of Local Field Potentials recorded from the subthalamic nucleus of patients with Parkinson's disease. Correlating subthalamic synchronized oscillatory activity with motor impairment in Parkinson's disease patients has recently gained attention in the literature. Objective:Based on the deep brain recordings of a Parkinson's disease patient our objective is to (i) Use actual measurements of the patient's tremor to support a hypothesis that connects the features of the Local Field Potential's beta-band spectrum (13-31 Hz), with the lower frequency (4-8 Hz) features of the patient's tremor, such as tremor frequency and tremor fluctuation time and (ii) Justify the hypothesis through theoretical reasoning based on communication theory in Electrical Engineering. Methods:Tremor characteristics (i.e., tremor frequency and tremor fluctuation time) derived from limb coordinate time-series were obtained from a video of the patient by using Google's MediaPipe Artificial Intelligence Framework. Spectra of the deep brain recordings and measured tremor time-series were analyzed using the Fast Fourier Transform. Burst trains in the deep brain signals and tremor bursts in the measured tremor signal were investigated by using Continuous Wave Transform scalograms. Results:Support for the hypothesis is provided by a close agreement between the measured results of the tremor (from a patient's video) and the predictions of the hypothesis based on the Local Filed Potential deep brain spectrum. We show that the defining features in the scalogram obtained from the deep brain signal are directly related to the features in the scalogram of the measured tremor. We provide a theoretical justification of the hypothesis by relating features of the deep brain beta-bursts, seen in the Local Field Potential scalogram, to a pair of beta-band dominant peaks found in the spectrum of the deep brain signal by leveraging the phenomena of "beating" (amplitude modulation) from communications theory. Conclusion:We conclude that tremor properties of a Parkinson's disease patient, like tremor frequency and tremor fluctuation duration, can be obtained from the patient's subthalamic nucleus beta-band spectrum.

Functional radiosurgery is a minimally invasive and highly precise approach to managing refractory cancer pain, offering targeted interventions for both nociceptive and neuropathic pain mechanisms. By focusing on key neuroanatomical targets, such as the thalamus, cingulate cortex, pituitary gland, celiac plexus, and dorsal root ganglia, functional radiosurgery provides effective relief for complex pain syndromes that are often unresponsive to conventional therapies. Advances in imaging and treatment delivery have enhanced the safety and efficacy of these techniques, allowing clinicians to tailor interventions to individual patients.

Pain management strategies have progressed beyond traditional pharmacologic and physical interventions, integrating advanced neuromodulation techniques such as deep brain stimulation, peripheral nerve stimulation, and high-frequency spinal cord stimulation (hSCS). Despite its clinical efficacy, the supraspinal mechanisms underlying hSCS remain poorly understood. Prior work in sheep demonstrated that hSCS modulates gamma (γ) band (70–150 Hz) activity in the primary somatosensory and association cortices, implicating cortical involvement in pain modulation. Given, the interaction between low and high oscillations, we hypothesized that hSCS modulates γ activity in a region- and time-dependent manner through specific coupling with theta (□) rhythms (4–8 Hz). Using 96-channel subdural electrocorticography (ECoG), we computed □-γ phase–amplitude coupling (PAC) and the corresponding modulation index (MI) to quantify the effects of hSCS. While the preferred □phase of γ activity remained consistent across conditions and regions, MI increased significantly post-stimulation—most prominently in the association cortex, where robust -γ phase locking was observed. In contrast, the somatosensory cortex exhibited weaker and more variable locking. Temporally, both cortices demonstrated an early, rapid increase in MI post-hSCS, accompanied by a shift (association) and attenuation (somatosensory) of the secondary peak. These findings reveal distinct regional and temporal dynamics in PAC following hSCS and suggest complementary roles of somatosensory and association cortices in processing neuromodulatory input. hSCS appears to reorganize cortical cross-frequency interactions, supporting its role in reorganizing functional network dynamics relevant to sensory processing and the subjective pain experience. ### Competing Interest Statement The authors have declared no competing interest.

Spinal Cord Stimulation (SCS) has been a cornerstone in managing chronic pain since the late 1960s. However, traditional SCS is often associated with variable efficacy and side effects, driving the development of advanced techniques like high-frequency SCS (hSCS). Previous studies have demonstrated that the power of high-frequency cerebral oscillations increases as a function of stimulus intensity and plays a critical role in local neural processing of peripheral sensory stimuli. Extending from the current body of literature, we hypothesized that hSCS could selectively influence stimulus-triggered neural oscillations involved in sensory processing and perception. Using electrocorticography (ECoG) in sheep (n = 4), we investigated the effects of 8.2 KHz hSCS on low-frequency (4-30 Hz) and high-frequency (70-150 Hz) oscillations in ovine somatosensory and association cortices. Neural signals were recorded before, and after hSCS application to assess frequency-specific modulation of cortical activity. Our findings reveal that hSCS induces broad suppression of high-frequency oscillations across both cortical regions. In contrast, low-frequency oscillations were selectively suppressed or enhanced in both cortices. Furthermore, a linear mixed model analysis revealed that low-frequency oscillations better predict high-frequency modulation in the association than the somatosensory cortex, highlighting a reciprocal low-/high-frequency relationship between cortices. These distinct effects on cortical oscillations suggest potential supraspinal mechanisms through which hSCS may exert its analgesic effects. Our findings provide new insights for optimizing neuromodulation strategies in pain management, emphasizing the role of frequency-specific modulation in sensory and cognitive pain processing. PERSPECTIVE: This study demonstrates that high-frequency spinal cord stimulation modulates cortical oscillations in a frequency- and region-specific manner, suggesting a supraspinal mechanism of pain. These findings advance our understanding of how neuromodulation influences sensory components of pain, with implications for optimizing stimulation protocols in chronic pain management.

Background:Intrathecal baclofen (ITB) delivery is an FDA-approved indication for patients with intractable spasticity. Often, implantation in these patients can be considerably challenging, especially if previous surgical fusion involves the procedure access location. Case report:We present the case of a 27-year-old female with T2 American Spinal Injury Association (ASIA) A spinal cord injury (SCI) and chronic spastic dystonia. She was maximized on oral medications without satisfactory control of her painful muscle spasms and was a candidate for ITB trial, which ultimately failed due to the difficulty of accessing the spinal canal due to extensive pseudoarthrosis secondary to thoracic to lumbar fusion. A decision was made to directly implant the pump in the operative room using O-arm-aided neuronavigation to guide catheter access at L5-S1. Currently, at 22 months of follow-up post-pump implant, ITB delivery has led to persistent improvements in her spastic dystonia and many aspects of quality of life. Discussion:The current case indicates that a multidisciplinary approach when considering surgical treatments for medication-refractory spasticity may help expand the indications to large numbers of patients with postsurgical spine abnormalities.

BACKGROUND:Cancer is commonly associated with pain. For patients with advanced cancer and intractable pain, ablative neurosurgical procedures can significantly improve pain and transition patients out of inpatient settings. These procedures are normally invasive, and this poses an important risk in this population. Cingulotomy has been reported to improve pain perception and contribute substantially to the quality of life of cancer patients with refractory pain. OBSERVATIONS:One fresh human cadaver specimen was used for the setup. The cingulate gyrus was targeted using intraoperative magnetic resonance images, and osseous aberrations were corrected after coregistration with the preoperative head computed tomography. After accounting for sinuses, membrane folds, and calcifications, a total of 737 elements were available for thermal ultrasound ablation. On high-power sonications, the total energy delivered reached a peak temperature of 57°C (15,050 J, 350 W, 45 seconds) in the right cingulate and 52°C (13,000 J, 405 W, 46 seconds) in the left cingulate. LESSONS:Despite the limitations of using a cadaver model (temperature, vascularization), cingulotomy appears to be feasible using high-intensity focused ultrasound. https://thejns.org/doi/10.3171/CASE2459.

Background Patients’ hand-drawn Archimedes spirals are widely used in the neurological community to grade tremors. These spirals are either drawn on paper and Xeroxed/scanned into digital images or digitizing tablets are used for the drawings. This process introduces artifacts such as variable widths of the drawn lines with varying pixel grey scale values. Xeroxing introduces additional artifacts resulting from paper misalignments. These artifacts and the presence of the reference spiral in the image complicate an automatic extraction of a mathematical spiral signal from the image. New Methods We introduce a mathematical mapping that transforms the image pixels of the patient’s hand-drawn spiral into a one-dimensional discrete signal that can be used for mathematical analysis. Results A cohort of 18 hand-drawn spirals with various artifacts is used to validate our method.We extract the parameters of the discrete signals and show that the signals can be represented by truncating to as few as 150 parameters with a truncation RMS error of 6.26% across the cohort. Using only 150 features makes machine learning a viable option for future applications. Furthermore, our method can be used to evaluate the frequency and the amplitude of the tremor. Comparison with Existing Methods In existing methods, the patient draws the spiral on a digitizing tablet, and features are extracted from this data for machine learning. We recognize that a vast majority of hospitals are still using the pencil-and-paper approach, and there is an abundance of ready-to-be-mined tremor-related data already stored as paper or digitized drawings. Our procedure is equally applicable to Xeroxed documents as well as files generated from digital tablets. Conclusions We have validated a new procedure requiring minimal user intervention to automatically extract a patient’s hand-drawn spiral as a discrete mathematical one-dimensional signal from a scanned image or a file from a digital tablet.

Outcomes1. Using a think-pair-share approach, participants will compare and contast non-pharmacological and pharmacological approaches for various difficult to treat symptoms in both hospice and palliative care patients.2. Upon completion of this activity, partcipants will be able to analyze difficult to treat symptoms in hospice and palliative care for the possible use of interventional approaches.This half-day workshop is designed for intermittent to advanced palliative and hospice providers looking to develop individualized treatment plans for difficult to manage symptoms within hospice and palliative care. Interdisciplinary faculty will present both non-pharmacological and pharmacological approaches to common and uncommon symptoms.The expert panel will prepare five patient cases to discuss with the audience. Possible topics include, but are not limited to, pain, nausea, dyspnea, delirium, cough, hiccoughs, secretions, anxiety, and depression. A pre-conference survey will be sent to “crowd-source” the audience to guide development of focused cases and discussion that are of most interest. Each symptom will be discussed in the context of prognosis, differentiating treatment for patients with months to years remaining versus days to weeks.A key point of emphasis is to provide participants with ample opportunity to actively engage with the expert panel and each other. Participants will be broken down into smaller groups to facilitate active discussion. A case will be presented, groups will think-pair-share, and then the conference faculty will provide concluding thoughts including available evidence/data. After these five cases have concluded, the audience will be given an opportunity to bring cases to discuss following a similar format described above albeit a shorter timeframe to maximize participant cases. Faculty will have additional cases prepared as for continued discussion as needed.

Importance:Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. Objective:To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. Design, Setting, and Participants:This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). Intervention:A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Main Outcomes and Measures:Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. Results:The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Conclusions and Relevance:Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. Trial Registration:ClinicalTrials.gov Identifier NCT04112381.

- BACKGROUND: Trigeminal neuralgia (TN) is characterized by paroxysmal episodes of severe shocklike orofacial pain typically resulting from arterial compression on the trigeminal root entry zone. However, neurovascular conflict in more proximal parts of the trigeminal pathway within the pons is extremely rare. - METHODS: The authors present a case of microvascular decompression for TN caused by dual arterial compression on the dorsolateral pons, along with a brief literature review. - RESULTS: Our patient was a 74-year-old man with episodic left-sided facial stabbing pain. Brain magnetic resonance imaging revealed a dual arterial compression on dorsolateral pons, the known site of the trigeminal sensory - ucleus and descending trigeminal tract. Microvascular decompression was performed via a retrosigmoid approach. Complete pain relief and partial improvement of the facial hypesthesia were achieved immediately after surgery and the Barrow Neurological Institute (BNI) pain intensity score improved from V to I, and the BNI hypesthesia score decreased from III to II within a month following surgery. The literature review identified 1 case of TN secondary to an arteriovenous malformation in root entry zone with lateral pontine extension. One month following partial coagulation of the draining vein, the patient was reportedly able to reduce medication dosage by half to achieve an improvement of BNI pain intensity score from V to IIIa. - CONCLUSIONS: Neurovascular compression in the trigeminal tract and nucleus is a rare but potential cause of TN. A thorough investigation of the trigeminal pathway should be considered during preoperative evaluation and intraoperative inspection, particularly if no clear offending vessel is identified.

Introduction: We sought to explore whether electrode visualization tools (EVT) can accurately predict the selection of optimal Deep Brain Stimulation (DBS) electrode contacts. Methods: Twelve patients with Parkinson's disease (PD) undergoing STN-DBS at The Ohio State University were enrolled in a prospective analysis to evaluate the accuracy of EVT-based vs. standard DBS programming. EVTs were generated by the Surgical Information Sciences (SIS) system to develop a 3D model showing the implanted lead location relative to the STN. Then, imaging-based data were compared to the results of a standard monopolar review to evaluate concordance with clinical data and time spent selecting useable, non-useable, and borderline electrode contacts. Results: A total of 18 DBS leads (n = 68 electrode contacts) were analyzed. The concordance between EVT and standard clinical programming expressed as the kappa coefficient was 0.65 (82.35% raw agreement) for nonuseable, 0.52 for useable (64.71% raw agreement), and 0.52 for borderline (58.82% raw agreement). The average time spent determining whether an electrode contact was useable, non-useable, or borderline was 1.46 +/- 0.76 min with EVT vs. 61.25 +/- 17.47 with standard monopolar review. Eight different categories of side effects were identified, with facial pulling and speech difficulties being observed with the most frequency. The type of side effect observed was accurately predicted using EVT 90% of the time. Conclusions: This study demonstrates that next-generation EVT-based programming can be implemented into STN-DBS programming workflows with a considerable saving of time and effort spent in testing combinations of stimulation settings, particularly for the identification of non-useable electrode contacts.

BackgroundDeep brain stimulation (DBS) has shown promise in effectively treating chronic pain. This study aimed to assess the efficacy of DBS in this context.MethodsWe conducted a systematic literature search using PubMed, Scopus, and Web of Science, following the PRISMA guidelines. A well-constructed search strategy was utilized. Our literature search identified two groups of subjects: one group underwent DBS specifically for chronic pain treatment (DBS-P), while the second group received DBS for other indications (DBS-O), such as Parkinson’s disease or dystonia, with pain perception investigated as a secondary outcome in this population. Meta-analysis was performed using R version 4.2.3 software. Heterogeneity was assessed using the tau^2 and I^2 indices, and Cochran’s Q-test was conducted.ResultsThe analysis included 966 patients in 43 original research studies with chronic pain who underwent DBS (340 for DBS-P and 625 for DBS-O). Subgroup analysis revealed that DBS-P exhibited a significant effect on chronic pain relief, with a standardized mean difference (SMD) of 1.65 and a 95% confidence interval (CI) of [1.31; 2.00]. Significant heterogeneity was observed among the studies, with an I^2 value of 85.8%. However, no significant difference was found between DBS-P and DBS-O subgroups. Subgroup analyses based on study design, age, pain diseases, and brain targets demonstrated varying levels of evidence for the effectiveness of DBS across different subgroups. Additionally, meta-regression analyses showed no significant relationship between age or pain duration and DBS effectiveness for chronic pain.ConclusionThese findings significantly contribute to the expanding body of knowledge regarding the utility of DBS in the management of chronic pain. The study underscores the importance of conducting further research to enhance treatment outcomes and elucidate patient-specific factors that are associated with treatment response.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=428442, identifier CRD42023428442.

Analysis of patient’s hand drawn Archimedes spirals is commonly used in the medical community to grade various forms of tremors. These spirals are often drawn on paper using a pen or a pencil and then Xeroxed/scanned to turn the drawings into computer images. This process introduces artifacts such as misalignment of the paper, finite/variable width of the drawn line, light grey marks left by the toner, and greyscale background pixels introduced by the Xeroxing/scanning steps. Even a spiral drawn directly on the screen of a tablet produces lines with multi-pixel widths and varying greyscale values. These artifacts make it difficult to use image processing techniques to automatically extract the patient’s spiral as a clean single-valued discrete signal which could be treated mathematically for further analysis. We present a procedure in this paper to extract the patient’s hand-drawn spiral automatically as a mathematical discrete signal even in the presence of artifacts, with minimal user intervention. We also note that the spirals used by some hospitals and clinics are distorted and not perfect Archimedes spirals; nevertheless, our procedure can still be used for these cases. The extracted discrete signal is composed of a couple of thousand samples (features). The largeness of this feature space compared with the typical number of spiral samples at our disposal (of the order of only hundreds) makes it infeasible to apply Machine Learning techniques for predictions which generalize well in the real world without overfitting. We analyze the extracted discrete signal using FFT (Fast Fourier Transforms) and show that in FFT space the signal can be represented by as few as 300 parameters. The paper concludes that if these 300 parameters (or even 150 parameters for some problems) are used as a feature set for Machine Learning then it could very well be possible to make predictions which generalize well to the real world without overfitting. As a note, applications to actual Machine Learning problems are not covered in this paper.

Objective:Substance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates. Methods:We performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version 4.2.3 software was utilized to calculate the mean effect size. We estimated study heterogeneity by employing tau2 and I2 indices and conducting Cochran's Q test. Results:The results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%. The observed relapse rate was 8%. The meta-analysis estimated a mean effect size of 55.9 [40.4; 71.4]. Heterogeneity analysis showed a large degree of heterogeneity among the included studies. Subgroup and meta-regression analysis based on age and SUD type suggested that DBS may be more effective for patients above 45 years of age, and for alcohol and opioid addiction compared to nicotine addiction. Conclusion:The current literature suggests that DBS has a moderate effect on SUD symptoms. However, the limited number of studies and small sample size indicate that more research is needed to better understand the factors that influence its effectiveness.