Estimation of fiber diameters in the spinal dorsal columns from clinical data

Lack of human morphometric data regarding the largest nerve fibers in the dorsal columns (DCs) of the spinal cord has lead to the estimation of the diameters of these fibers from clinical data retrieved from patients with a new spinal cord stimulation (SCS) system. These patients indicated the perception threshold of stimulation induced paresthesia in various body segments, while the stimulation amplitude was increased. The fiber diameters were calculated with a computer model, developed to calculate the effects of SCS on spinal nerve fibers. This computer model consists of two parts: (1) a three-dimensional (3-D) volume conductor model of a spinal cord segment in which the potential distribution due to electrical stimulation is calculated and (2) an electrical equivalent cable model of myelinated nerve fiber, which uses the calculated potential field to determine the threshold stimulus needed for activation. It is shown that the largest fibers in the medial DCs are significantly smaller than the largest fibers in the lateral parts. This finding is in accordance with the fiber distribution in cat, derived from the corresponding propagation velocities. Moreover, it is shown that the mediolateral increase in fiber diameter is mainly confined to the lateral parts of the DCs. Implementation of this mediolateral fiber diameter distribution of the DCs in the computer model enables the prediction of the recruitment order of dermatomal paresthesias following increasing electrical stimulation amplitud

Deep brain stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis

BackgroundOne of the experimental neuromodulation techniques being researched for the treatment of Alzheimer's disease (AD) is deep brain stimulation (DBS). To evaluate the effectiveness of DBS in AD, we performed a systematic review and meta-analysis of the available evidence.MethodsFrom the inception through December 2021, the following databases were searched: Medline via PubMed, Scopus, Embase, Cochrane Library, and Web of Science. The search phrases used were “Alzheimer's disease,” “AD,” “deep brain stimulation,” and “DBS.” The information from the included articles was gathered using a standardized data-collecting form. In the included papers, the Cochrane Collaboration methodology was used to evaluate the risk of bias. A fixed-effects model was used to conduct the meta-analysis.ResultsOnly five distinct publications and 6 different comparisons (one study consisted of two phases) were included out of the initial 524 papers that were recruited. DBS had no impact on the cognitive ability in patients with AD [0.116 SMD, 95% confidence interval (CI), −0.236 to 0.469, p = 0.518]. The studies' overall heterogeneity was not significant (κ2 = 6.23, T2 = 0.053, df = 5, I2 = 19.76%, p = 0.284). According to subgroup analysis, the fornix-DBS did not improve cognitive function in patients with AD (0.145 SMD, 95%CI, −0.246 to 0.537, p = 0.467). Unfavorable neurological and non-neurological outcomes were also reported.ConclusionThe inconsistencies and heterogeneity of the included publications in various target and age groups of a small number of AD patients were brought to light by this meta-analysis. To determine if DBS is useful in the treatment of AD, further studies with larger sample sizes and randomized, double-blinded, sham-controlled designs are required

Habenular Stimulation for Neurosurgery Resistant Obsessive-Compulsive Disorder: A Case Report.

BACKGROUND: Some patients suffer from persistent and severely disabling Obsessive-Compulsive Disorder (OCD) symptoms that cannot be alleviated by conventional treatments or neuroablative interventions targeting cortico-striatal loop circuits. Currently, it is unclear how to manage the clinical symptoms of these unique patients. We reasoned that deep brain stimulation (DBS) of the habenula (HB) could be a valuable subsequent treatment option for these otherwise medically intractable cases of severe OCD. The HB is an epithalamic structure critically involved in the encoding and responding to aversive stimulus events, cognitive and brain processes known to be impaired in many patients with OCD. Similarly, HB DBS can alleviate depression and anxiety, which often co-occur with OCD. Here, we explore the clinical benefits and risks of HB DBS treatment in a patient with severe and refractory OCD. CASE PRESENTATION: A 30-year-old male patient presented with persistent and severely disabling OCD symptoms that were refractory to previous psychological and pharmacological treatments as well as to neuroablative surgical interventions involving both capsulotomy and cingulotomy. After HB DBS, however, the severity of the patient's OCD symptoms was markedly reduced at 1-month follow-up, which was sustained until the final (at 12-month) follow-up. The patient also reported enduring improvements in depression, anxiety, and health-related quality of life after several months of HB DBS treatment. CONCLUSIONS: This case report provides the first clinical evidence suggesting that HB DBS could serve as a safe and effective alternative neurosurgical intervention for severe and refractory OCD. The present findings are promising and warrant further research into the role of the HB in pathophysiology and treatment of OCD

EEG-based biomarkers for optimizing deep brain stimulation contact configuration in Parkinson’s disease

ObjectiveSubthalamic deep brain stimulation (STN-DBS) is a neurosurgical therapy to treat Parkinson’s disease (PD). Optimal therapeutic outcomes are not achieved in all patients due to increased DBS technological complexity; programming time constraints; and delayed clinical response of some symptoms. To streamline the programming process, biomarkers could be used to accurately predict the most effective stimulation configuration. Therefore, we investigated if DBS-evoked potentials (EPs) combined with imaging to perform prediction analyses could predict the best contact configuration.MethodsIn 10 patients, EPs were recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. In two patients, we recorded from both hemispheres, resulting in recordings from a total of 12 hemispheres. A monopolar review was performed by stimulating on each contact and measuring the therapeutic window. CT and MRI data were collected. Prediction models were created to assess how well the EPs and imaging could predict the best contact configuration.ResultsEPs at 3 ms and at 10 ms were recorded. The prediction models showed that EPs can be combined with imaging data to predict the best contact configuration and hence, significantly outperformed random contact selection during a monopolar review.ConclusionEPs can predict the best contact configuration. Ultimately, these prediction tools could be implemented into daily practice to ease the DBS programming of PD patients

Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response

Background Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. Methods We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. Findings Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate 27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. Conclusions Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS

Automated Assessment of Endpoint and Kinematic Features of Skilled Reaching in Rats

Background: Neural injury to the motor cortex may result in long-term impairments. As a model for human impairments, rodents are often used to study deficits related to reaching and grasping, using the single-pellet reach-to-grasp task. Current assessments of this test capture mostly endpoint outcome. While qualitative features have been proposed, they usually involve manual scoring.Objective: To detect three phases of movement during the single-pellet reach-to-grasp test and assess completion of each phase. To automatically monitor rat forelimb trajectory so as to extract kinematics and classify phase outcome.Methods: A top-view camera is used to monitor three rats during training, healthy and impaired testing, over 33 days. By monitoring the coordinates of the forelimb tip along with the position of the pellet, the algorithm divides a trial into reaching, grasping and retraction. Unfulfilling any of the phases results in one of three possible errors: miss, slip or drop. If all phases are complete, the outcome label is success. Along with endpoints, movement kinematics are assessed: variability, convex hull, mean and maximum reaching speed, length of trajectory and peak forelimb extension.Results: The set of behavior endpoints was extended to include miss, slip, drop and success rate. The labeling algorithm was tested on pre- and post-lesion datasets, with overall accuracy rates of 86% and 92%, respectively. These endpoint features capture a drop in skill after motor cortical lesion as the success rate of 59.6 ± 11.8% pre-lesion decreases to 13.9 ± 8.2% post-lesion, along with a significant increase in miss rate from 7.2 ± 6.7% pre-lesion to 50.2 ± 18.7% post-lesion. Kinematics reveals individual-specific strategies of improvement during training, with a common trend of trajectory variability decreasing with success. Correlations between kinematics and endpoints reveal a more complex pattern of relationships during rehabilitation (18 significant pairs of features) than during training (nine correlated pairs).Conclusion: Extended endpoint outcomes and kinematics of reaching and grasping are captured automatically with a robust computer program. Both endpoints and kinematics capture intra-animal drop in skill after a motor cortical lesion. Correlations between kinematics and endpoints change from training to rehabilitation, suggesting different mechanisms that underlie motor improvement

Electrical stimulation in the bed nucleus of the stria terminalis exerts anxiolytic effects in a rat model of contextual anxiety (poster)

status: publishe