Biology subjects

Barbe, M.

Publications and source records attributed to Barbe, M..

4 recordsLinked to original sources

bioRxiv2024

Control of spatiotemporal activation of organ-specific fibers in the vagus nerve by intermittent interferential current stimulation

Vagus nerve stimulation (VNS) is emerging as potential treatment for several chronic diseases, however, limited control of fiber activation to promote desired effects over side effects restricts clinical translation. Here we describe a new VNS method that relies on intermittent, interferential sinusoidal current stimulation (i2CS) through implanted, multi-contact epineural cuffs. In swine, i2CS elicits specific nerve potentials and end organ responses, distinct from equivalent non-interferential sinusoidal stimulation. Comparing experimental results with anatomical trajectories of nerve fascicles from end organs to the stimulation electrode indicates that i2CS activates organ-specific fascicles rather than the entire nerve. Experimental results and anatomically realistic, physiologically validated biophysical models of the vagus nerve demonstrate that i2CS reduces fiber activation at the focus of interference. Current steering and repetition frequency determine spatiotemporal pattern of vagal fiber activation, allowing tunable and precise control of neural and organ responses. In experiments in a cohort of anesthetized swine, i2CS has improved selectivity for a desired effect, mediated by smaller bronchopulmonary fibers, over a side effect, mediated by larger laryngeal fibers, compared to non-interferential sinusoidal or square pulse VNS.

neuroscience↗

bioRxiv2022

Organ- and function-specific organization and bioelectronic modulation of vagus fascicles and fibers

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Vagus nerve stimulation (VNS) therapies activate fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. Transverse and longitudinal arrangement of fibers according to functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using microcomputed tomography, we found that, in swine, fascicles are arranged in 2 overlapping axes, with sensory and motor fascicles separated cephalad and merging caudad, and larynx-, heart- and lung-specific fascicles separated caudad and progressively merging cephalad. Using immunohistochemistry, we found that the distribution of single fibers is highly nonuniform: myelinated afferents and efferents occupy separate fascicles, unmyelinated efferents co-localize with myelinated afferents, and small unmyelinated afferents are widely distributed. Using a multi-contact cuff electrode, we delivered fascicular cervical VNS in anesthetized and awake swine. Compound action potentials, from distinct fiber types, and organ responses, including laryngeal muscle, cough, breathing, heart rate and blood pressure responses are elicited in a radially asymmetric manner, with consistent angular separations. These results indicate that vagal fibers are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.

neuroscience↗

bioRxiv2021

A functional network target for tic reduction during thalamic stimulation for Tourette Syndrome

BackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results. MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction. ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofrontal cortex was negatively associated. The overall connectivity pattern was robust to leave-one-out cross-validation, explaining 25 % of outcome variance (R = 0.500; p = 0.005). ConclusionsWe delineated a functional connectivity profile seeding from stimulation sites associated with TS-DBS outcome. This pattern comprised areas linked to the processing of premonitory urges and tic execution, thereby extending our current understanding of effective neuromodulation for TS.

neuroscience↗

bioRxiv2019

Left prefrontal connectivity links subthalamic stimulation with depressive symptoms in Parkinson’s disease

ObjectiveSubthalamic nucleus deep brain stimulation (STN-DBS) in Parkinsons Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS which have been reported to improve, worsen or remain unchanged. MethodsDepressive symptoms before and after STN-DBS surgery were documented in 116 PD patients from three DBS centers (Berlin, Queensland, Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTA) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as test-set for which depressive symptom change was predicted. ResultsStructural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity. InterpretationFibers linking the STN electrode with left prefrontal areas predicted worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

neuroscience↗