Burst Stimulation Research Articles

Effects of Hyperdirect Pathway Theta Burst Transcranial Magnetic Stimulation on Inhibitory Control, Craving, and Smoking in Adults With Nicotine Dependence: A Double-Blind, Randomized Crossover Trial

BackgroundNicotine dependence is associated with dysregulated hyperdirect pathway (HDP)–mediated inhibitory control (IC). However, there are currently no evidence-based treatments that have been shown to target the HDP to improve IC and reduce cigarette cravings and smoking. MethodsFollowing a baseline nonstimulation control session, this study (N = 37; female: n = 17) used a double-blind, randomized crossover design to examine the behavioral and neural effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) to the right inferior frontal gyrus (rIFG)—a key cortical node of the HDP. Associations between treatment effects were also explored. ResultsAt baseline, HDP IC task-state functional connectivity was positively associated with IC task performance, which confirmed the association between HDP circuit function and IC. Compared with iTBS, rIFG cTBS improved IC task performance. Compared with the baseline nonstimulation control session, both TBS conditions reduced cigarette craving and smoking; however, although craving and smoking were lower for cTBS, no differences were found between the two active conditions. In addition, although HDP IC task-state functional connectivity was greater following cTBS than iTBS, there was no significant difference between conditions. Finally, cTBS-induced improvement in IC task performance was associated with reduced craving, and cTBS-induced reduction in craving was associated with reduced smoking. ConclusionsThese findings warrant further investigation into the effects of rIFG cTBS for increasing IC and reducing craving and smoking among individuals with nicotine dependence. Future sham-controlled cTBS studies may help further elucidate the mechanisms by which rIFG cTBS mediates IC and smoking behavior.

Electric field distribution predicts efficacy of accelerated intermittent theta burst stimulation for late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for late-life depression (LLD) but may have lower rates of response and remission owing to age-related brain changes. In particular, rTMS induced electric field strength may be attenuated by cortical atrophy in the prefrontal cortex. To identify clinical characteristics and treatment parameters associated with response, we undertook a pilot study of accelerated fMRI-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex in 25 adults aged 50 or greater diagnosed with LLD and qualifying to receive clinical rTMS. Participants underwent baseline behavioral assessment, cognitive testing, and structural and functional MRI to generate individualized targets and perform electric field modeling. Forty-five sessions of iTBS were delivered over 9 days (1800 pulses per session, 50-min inter-session interval). Assessments and testing were repeated after 15 sessions (Visit 2) and 45 sessions (Visit 3). Primary outcome measure was the change in depressive symptoms on the Inventory of Depressive Symptomatology-30-Clinician (IDS-C-30) from Visit 1 to Visit 3. Overall there was a significant improvement in IDS score with the treatment (Visit 1: 38.6; Visit 2: 31.0; Visit 3: 21.3; mean improvement 45.5%) with 13/25 (52%) achieving response and 5/25 (20%) achieving remission (IDS-C-30 < 12). Electric field strength and antidepressant effect were positively correlated in a subregion of the ventrolateral prefrontal cortex (VLPFC) (Brodmann area 47) and negatively correlated in the posterior dorsolateral prefrontal cortex (DLPFC). Response and remission rates were lower than in recently published trials of accelerated fMRI-guided iTBS to the left DLPFC. These results suggest that sufficient electric field strength in VLPFC may be a contributor to effective rTMS, and that modeling to optimize electric field strength in this area may improve response and remission rates. Further studies are needed to clarify the relationship of induced electric field strength with antidepressant effects of rTMS for LLD.

Prolonged continuous theta burst stimulation increases motor corticospinal excitability and intracortical inhibition in patients with neuropathic pain: An exploratory, single-blinded, randomized controlled trial

ObjectivesA new paradigm for Transcranial Magnetic Stimulation (TMS), referred to as prolonged continuous theta burst stimulation (pcTBS), has recently received attention in the literature because of its advantages over high frequency repetitive TMS (HF-rTMS). Clinical advantages include less time per intervention session and the effects appear to be more robust and reproducible than HF-rTMS to modulate cortical excitability. HF-rTMS targeted at the primary motor cortex (M1) has demonstrated analgesic effects in patients with neuropathic pain but their mechanisms of action are unclear and pcTBS has been studied in healthy subjects only. This study examined the neural mechanisms that have been proposed to play a role in explaining the effects of pcTBS targeted at the M1 and DLPFC brain regions in neuropathic pain (NP) patients with Type 2 diabetes. MethodsForty-two patients with painful diabetic neuropathy were randomized to receive a single session of pcTBS targeted at the left M1 or left DLPFC. pcTBS stimulation consisted of 1,200 pulses delivered in 1 min and 44 s with a 35–45 min gap between sham and active pcTBS stimulation. Both the activity of the descending pain system which was examined using conditioned pain modulation and the activity of the ascending pain system which was assessed using temporal summation of pain were recorded using a handheld pressure algometer by measuring pressure pain thresholds. The amplitude of the motor evoked potential (MEP) was used to measure motor corticospinal excitability and GABA activity was assessed using short (SICI) and long intracortical inhibition (LICI). All these measurements were performed at baseline and post-pcTBS stimulation. ResultsFollowing a single session of pcTBS targeted at M1 and DLPFC, there was no change in BPI-DN scores and on the activity of the descending (measured using conditioned pain modulation) and ascending pain systems (measured using temporal summation of pain) compared to baseline but there was a significant improvement of >13% in perception of acute pain intensity, increased motor corticospinal excitability (measured using MEP amplitude) and intracortical inhibition (measured using SICI and LICI). ConclusionIn patients with NP, a single session of pcTBS targeted at the M1 and DLPFC modulated the neurophysiological mechanisms related to motor corticospinal excitability and neurochemical mechanisms linked to GABA activity, but it did not modulate the activity of the ascending and descending endogenous modulatory systems. In addition, although BPI-DN scores did not change, there was a 13% improvement in self-reported perception of acute pain intensity.

The changes in metabolomics profile induced by intermittent theta burst stimulation in major depressive disorder: an exploratory study

BackgroundRecently, there has been an ongoing interest in the mechanism of intermittent theta burst stimulation (iTBS) in major depressive disorder. Studying the metabolite changes induced by iTBS may help to understand the mechanism.MethodsEleven participants with major depressive disorder received 10 days iTBS treatment. Magnetic resonance imaging (MRI) was used to target the region of the left dorsolateral prefrontal cortex (DLPFC) in each participant. We analyzed the effects of iTBS on metabolites using high-throughput profiling and assessed its impact on depressive symptoms. These analyses were considered exploratory, and no correction for multiple comparisons was applied.ResultsAmong the 318 measured metabolites, a significant increase in cystine, asymmetric dimethylarginine (ADMA), 1-methylhistidine, indoleacetic acid (IAA), diethanolamine (DEA), dopa, riboflavin-5′-monophosphate (FMN), and a significant decrease in alphalinolenic acid (ALA), gamma-linolenic acid (GLA), serotonin, linoleic acid (LA) (p < 0.05) were detected in the patients after iTBS treatment. In Pearson correlation analysis, the plasma levels of LA, FMN and ADMA at baseline were significantly related to the reduction rate of the 17‐item Hamilton Depression Rating Scale and the Patient Health Questionnaire-9 scores (p < 0.05).ConclusionsOur study highlights that LA, FMN, ADMA and their relationship with oxidative stress, may be key factors in the antidepressant efficacy of iTBS.

Efficacy of Continuous Theta Burst Stimulation to the Pre-supplementary Motor Area in Gambling Disorder: a Randomized Double-Blind Controlled Trial

Efficacy of Continuous Theta Burst Stimulation to the Pre-supplementary Motor Area in Gambling Disorder: a Randomized Double-Blind Controlled Trial

The Efficacy and Safety of Different Noninvasive Therapies in the Treatment of Central Poststroke Pain (CPSP): A Network Meta-Analysis and Systematic Review.

To evaluate the efficacy and safety of noninvasive therapies in the treatment of central poststroke pain (CPSP) by network meta-analysis and to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMBASE, CNKI, Wanfang, and VIP were searched for clinical randomized controlled studies on noninvasive therapy for CPSP. The retrieval time limit was from the establishment of each database to July 2022. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included randomized controlled trials (RCTs). Stata 14.0 was used for network meta-analysis, and Review Manager 5.3 software was used for traditional meta-analysis. Twelve RCTs involving 8 treatment schemes and 641 patients were finally included. The results of the network meta-analysis showed the following rankings in visual analysis scale (VAS): super laser injury on stellate ganglia (SLI) > transcranial direct current stimulation (tDCS) > music therapy (MT) > repetitive transcranial magnetic stimulation (rTMS) > continuous theta burst stimulation (cTBS) > transcutaneous acupoint electrical stimulation (TAES) > common therapy (CT). The total clinical efficiency ranked as follows: psychological training of mindfulness (PT) > rTMS > CT. Clinical adverse reactions ranked as follows: rTMS > MT > CT > SLI. Noninvasive complementary therapy can effectively alleviate the pain of CPSP patients, and the efficacy and safety of SLI are relatively significant. However, due to the limitations of this study, the efficacy ranking cannot fully explain the advantages and disadvantages of clinical efficacy. In the future, more multicentre, large sample, double-blind clinical randomized controlled trials are needed to supplement and demonstrate the results of this study.

Right, but not left, posterior superior temporal gyrus is causally involved in vocal feedback control

The posterior superior temporal gyrus (pSTG) has been implicated in the integration of auditory feedback and motor system for controlling vocal production. However, the question as to whether and how the pSTG is causally involved in vocal feedback control is currently unclear. To this end, the present study selectively stimulated the left or right pSTG with continuous theta burst stimulation (c-TBS) in healthy participants, then used event-related potentials to investigate neurobehavioral changes in response to altered auditory feedback during vocal pitch regulation. The results showed that, compared to control (vertex) stimulation, c-TBS over the right pSTG led to smaller vocal compensations for pitch perturbations accompanied by smaller cortical N1 and larger P2 responses. Enhanced P2 responses received contributions from the right-lateralized temporal and parietal regions as well as the insula, and were significantly correlated with suppressed vocal compensations. Surprisingly, these effects were not found when comparing c-TBS over the left pSTG with control stimulation. Our findings provide evidence, for the first time, that supports a causal relationship between right, but not left, pSTG and auditory-motor integration for vocal pitch regulation. This lends support to a right-lateralized contribution of the pSTG in not only the bottom-up detection of vocal feedback errors but also the involvement of driving motor commands for error correction in a top-down manner.

Efficacy of cerebellar transcranial magnetic stimulation in spinocerebellar ataxia type 3: a randomized, single-blinded, controlled trial.

Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA without effective treatment. This study aimed to evaluate the comparative efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) in a larger cohort of SCA3 patients. One hundred and twenty patients with SCA3 were randomly assigned to the 3 groups: 40 patients in the 1Hz rTMS, 40 in the iTBS and 40 in the sham group. Patients underwent 10 sessions of rTMS targeting the cerebellum delivering for 5 consecutive days per week for 2weeks (a total of 1200 pulses per session). Primary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Secondary outcomes included 10-m walking test (10MWT), nine-hole peg test (9-HPT), and PATA Rate Test (PRT). Outcome assessments were performed at baseline and on the last day of rTMS intervention. This study revealed that active rTMS outperformed sham in reducing the SARA and ICARS scores in SCA3 patients, but with no difference between the 1Hz rTMS and iTBS protocol. Moreover, no significant differences were observed in SARA and ICARS scores between the mild and moderate to severe groups after the 1Hz rTMS/iTBS therapy. Additionally, no severe adverse events were recorded in this study. The study concluded that both 1Hz rTMS and iTBS interventions targeting the cerebellum are effective to improve the symptoms of ataxia in patients with SCA3.

Retreatment with theta burst stimulation (TBS) for late life depression (LLD): A retrospective chart review

Retreatment with theta burst stimulation (TBS) for late life depression (LLD): A retrospective chart review

Longstanding effects of continuous theta burst stimulation in adult amblyopes

ABSTRACT Clinical Relevance Continuous theta burst stimulation may be an important tool in the therapeutic management of amblyopia, when trying to correct the established neuronal imbalance. It is important to understand whether two sessions of continuous theta burst stimulation produce greater and longstanding changes in visual acuity and suppressive imbalance than one session of continuous theta burst stimulation Background We hypothesise that through the usage of continuous theta burst stimulation (cTBS) it is possible to change cortical excitability in a situation where visual impairment is present. Methods We selected 22 adult amblyopes, 18 females and 4 males, with an age range of 20–59 years. They were randomised into two groups: group A with 10 amblyopes was submitted to one session of cTBS and group B with 12 amblyopes submitted to two sessions of cTBS. Visual acuity (VA) and suppressive imbalance (SI) were evaluated immediately before and after stimulation in both groups A and B. A follow-up was done in both groups. Results For both group A and B, the VA improvements were significant after cTBS (p = 0.005 and p = 0.003, respectively). Regarding SI, both group A and B had significant improvements after cTBS (p = 0.03 and p = 0.005, respectively). Comparing groups, A and B no significant differences were found with regard to the results obtained both for VA (p = 0.72) and SI (p = 0.24). However, significant differences were found between group A and B with regard to the duration of stimulation effect for VA (p = 0.049) and SI (p = 0.03). Conclusion We conclude that two sessions of cTBS do not produce better results than one session of stimulation. However, it seems that two sessions of cTBS produce longstanding effects in VA and SI.

Network effects of Stanford Neuromodulation Therapy (SNT) in treatment-resistant major depressive disorder: a randomized, controlled trial

Here, we investigated the brain functional connectivity (FC) changes following a novel accelerated theta burst stimulation protocol known as Stanford Neuromodulation Therapy (SNT) which demonstrated significant antidepressant efficacy in treatment-resistant depression (TRD). In a sample of 24 patients (12 active and 12 sham), active stimulation was associated with significant pre- and post-treatment modulation of three FC pairs, involving the default mode network (DMN), amygdala, salience network (SN) and striatum. The most robust finding was the SNT effect on amygdala-DMN FC (group*time interaction F(1,22) = 14.89, p < 0.001). This FC change correlated with improvement in depressive symptoms (rho (Spearman) = −0.45, df = 22, p = 0.026). The post-treatment FC pattern showed a change in the direction of the healthy control group and was sustained at the one-month follow-up. These results are consistent with amygdala-DMN connectivity dysfunction as an underlying mechanism of TRD and bring us closer to the goal of developing imaging biomarkers for TMS treatment optimization.Trial registration: ClinicalTrials.gov NCT03068715

Accelerated intermittent theta burst stimulation for major depressive disorder or bipolar depression: A systematic review and meta-analysis.

We aimed to systematically evaluate the clinical efficacy and safety of accelerated intermittent theta burst stimulation (aiTBS) for patients with major depressive disorder (MDD) or bipolar depression (BD). A random-effects model was adopted to analyze the primary and secondary outcomes using the Review Manager, Version 5.3 software. This meta-analysis (MA) identified five double-blind randomized controlled trials (RCTs) comprising 239 MDD or BD patients with a major depressive episode. Active aiTBS overperformed sham stimulation in the study-defined response. This MA found preliminary evidence that active aiTBS resulted in a greater response in treating major depressive episodes in MDD or BD patients than sham stimulation.

Neuromodulatory effects and reproducibility of the most widely used repetitive transcranial magnetic stimulation protocols.

Repetitive transcranial magnetic stimulation (rTMS) is widely used in both research and clinical settings to modulate human brain function and behavior through the engagement of the mechanisms of plasticity. Based upon experiments using single-pulse TMS as a probe, the physiologic mechanism of these effects is often assumed to be via changes in cortical excitability, with 10 Hz rTMS increasing and 1 Hz rTMS decreasing the excitability of the stimulated region. However, the reliability and reproducibility of these rTMS protocols on cortical excitability across and within individual subjects, particularly in comparison to robust sham stimulation, have not been systematically examined. In a cohort of 28 subjects (39 ± 16 years), we report the first comprehensive study to (1) assess the neuromodulatory effects of traditional 1 Hz and 10 Hz rTMS on corticospinal excitability against both a robust sham control, and two other widely used patterned rTMS protocols (intermittent theta burst stimulation, iTBS; and continuous theta burst stimulation, cTBS), and (2) determine the reproducibility of all rTMS protocols across identical repeat sessions. At the group level, neither 1 Hz nor 10 Hz rTMS significantly modulated corticospinal excitability. 1 Hz and 10 Hz rTMS were also not significantly different from sham and both TBS protocols. Reproducibility was poor for all rTMS protocols except for sham. Importantly, none of the real rTMS and TBS protocols demonstrated greater neuromodulatory effects or reproducibility after controlling for potential experimental factors including baseline corticospinal excitability, TMS coil deviation and the number of individual MEP trials. These results call into question the effectiveness and reproducibility of widely used rTMS techniques for modulating corticospinal excitability, and suggest the need for a fundamental rethinking regarding the potential mechanisms by which rTMS affects brain function and behavior in humans.

Modulation of the thalamus by microburst vagus nerve stimulation: a feasibility study protocol.

Vagus nerve stimulation (VNS) was the first device-based therapy for epilepsy, having launched in 1994 in Europe and 1997 in the United States. Since then, significant advances in the understanding of the mechanism of action of VNS and the central neurocircuitry that VNS modulates have impacted how the therapy is practically implemented. However, there has been little change to VNS stimulation parameters since the late 1990s. Short bursts of high frequency stimulation have been of increasing interest to other neuromodulation targets e.g., the spine, and these high frequency bursts elicit unique effects in the central nervous system, especially when applied to the vagus nerve. In the current study, we describe a protocol design that is aimed to assess the impact of high frequency bursts of stimulation, called "Microburst VNS", in subjects with refractory focal and generalized epilepsies treated with this novel stimulation pattern in addition to standard anti-seizure medications. This protocol also employed an investigational, fMRI-guided titration protocol that permits personalized dosing of Microburst VNS among the treated population depending on the thalamic blood-oxygen-level-dependent signal. The study was registered on clinicaltrials.gov (NCT03446664). The first subject was enrolled in 2018 and the final results are expected in 2023.

Six-Month Follow-up of a Trial of Spinal Cord Burst Stimulation vs Placebo Stimulation and Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery

This follow-up study examines back pain–related disability at 6 months following a randomized trial of spinal cord burst stimulation for chronic radicular pain after lumbar spine surgery.

Evaluation of a three-axial acceleromyography monitor in dogs compared with mechanomyography

ObjectiveTo compare the ratio of the train-of-four (TOF) and double burst stimulation (DBS) obtained with three-axial acceleromyography (AMG) and mechanomyography (MMG) in dogs during recovery from a rocuronium-induced neuromuscular block. Study designProspective, randomized, experimental study. AnimalsA total of six intact healthy adult male Beagle dogs, weighing 9.1 ± 1.9 kg and aged 3–5 years. MethodsDogs were anesthetized with intravenous (IV) dexmedetomidine and propofol, and isoflurane in oxygen. Neuromuscular function was measured with AMG and MMG in the contralateral thoracic limbs. Rocuronium (0.5 mg kg–1) was administered IV, and the TOF and DBS ratios measured. During neuromuscular block offset, MMG values were recorded when AMG first reached ratios of 0.9 and 1.0. True recovery from neuromuscular block was determined as MMG ratio ≥ 0.9. The false-positive (AMG ≥ 0.9 or 1.0, and MMG ratio < 0.9) rate was determined. Paired values were compared, and bias and limits of agreement were calculated. Receiver operating characteristic (ROC) curves were created. ResultsWhen AMG first reached 0.9 and 1.0 during recovery, MMG values were lower (p < 0.040). When AMG reached 0.9, the false-positive rate was 29% with TOF and 27% with DBS. It decreased to 12% (TOF) and 11% (DBS) when a ratio of 1.0 was used. AMG values were higher than paired MMG values (p < 0.001). The AMG overestimated MMG by 24% and 22% for TOF and DBS, respectively. Areas under the ROC curves (95% confidence interval) were 0.91 (0.89, 0.94) and 0.86 (0.81, 0.94) for TOF and DBS, respectively. Conclusionsand clinical relevance The three-axial AMG monitor overestimated neuromuscular function and, in some cases, indicated adequate recovery despite the MMG ratio being < 0.9. A TOF or DBS ratio of at least 1.0 should be considered when monitoring recovery of neuromuscular block with this AMG device.

GABA promotes interstitial fluid clearance in an AQP4-dependent manner by activating the GABAA R.

The glymphatic system is a newly discovered perivascular network where cerebrospinal fluid mixes with interstitial fluid, facilitating clearance of protein solutes and metabolic waste from the parenchyma. The process is strictly dependent on water channel aquaporin-4 (AQP4) expressed on the perivascular astrocytic end-feet. Various factors, such as noradrenaline levels related to the arousal state, influence clearance efficiency, highlighting the possibility that other neurotransmitters additionally modulate this process. To date, the specific role of γ-aminobutyric acid (GABA) in the glymphatic system remains unknown. We used C57BL/6J mice to observe the regulatory effect of GABA on glymphatic pathway by administering a cerebrospinal fluid tracer containing GABA or its GABAA receptor (GABAA R) antagonist through cisterna magna injection. Then, we employed an AQP4 knockout mouse model to explore the regulatory effects of GABA on glymphatic drainage and further study whether transcranial magnetic stimulation-continuous theta burst stimulation (cTBS) could regulate the glymphatic pathway through the GABA system. Our data showed that GABA promotes glymphatic clearance in an AQP4-dependent manner by activating the GABAA R. Furthermore, cTBS was found to modulate the glymphatic pathway by activating the GABA system. Accordingly, we propose that regulating the GABA system by cTBS could modulate glymphatic clearance and provide new insight for clinical prevention and treatment of abnormal protein deposition-related diseases.

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

BackgroundCognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies.MethodsWithin this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV).DiscussionThe study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition.Trial registrationThe clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).

ID: 213578 Sensing Capability of BurstDR as a Sub-Paresthesia Therapeutic Waveform

The BurstDRTM waveform (burst) for spinal cord stimulation to relieve chronic pain demonstrated superior to classical tonic stimulation efficacy. Burst stimulation allows effective stimulation at sub-paresthesia level, improving patient’s experience. Regarding sensing and closed-loop approach, burst waveform raises a question if a spinal cord stimulation evoked compound action potential (ECAP) can be recorded and analyzed using this complicated waveform.

Dynamic modulation of subthalamic nucleus activity facilitates adaptive behavior.

Adapting actions to changing goals and environments is central to intelligent behavior. There is evidence that the basal ganglia play a crucial role in reinforcing or adapting actions depending on their outcome. However, the corresponding electrophysiological correlates in the basal ganglia and the extent to which these causally contribute to action adaptation in humans is unclear. Here, we recorded electrophysiological activity and applied bursts of electrical stimulation to the subthalamic nucleus, a core area of the basal ganglia, in 16 patients with Parkinson's disease (PD) on medication using temporarily externalized deep brain stimulation (DBS) electrodes. Patients as well as 16 age- and gender-matched healthy participants attempted to produce forces as close as possible to a target force to collect a maximum number of points. The target force changed over trials without being explicitly shown on the screen so that participants had to infer target force based on the feedback they received after each movement. Patients and healthy participants were able to adapt their force according to the feedback they received (P < 0.001). At the neural level, decreases in subthalamic beta (13 to 30 Hz) activity reflected poorer outcomes and stronger action adaptation in 2 distinct time windows (Pcluster-corrected < 0.05). Stimulation of the subthalamic nucleus reduced beta activity and led to stronger action adaptation if applied within the time windows when subthalamic activity reflected action outcomes and adaptation (Pcluster-corrected < 0.05). The more the stimulation volume was connected to motor cortex, the stronger was this behavioral effect (Pcorrected = 0.037). These results suggest that dynamic modulation of the subthalamic nucleus and interconnected cortical areas facilitates adaptive behavior.