Biology subjects

Visser-Vandewalle, V.

Publications and source records attributed to Visser-Vandewalle, V..

12 recordsLinked to original sources

bioRxiv2025

The role of STN beta oscillations on lower extremity muscle activity in Parkinsonian stepping

Freezing of gait (FOG) is a devastating symptom of Parkinsons disease (PD) often resulting in disabling falls and loss of independence. It affects half of patients, yet current therapeutic strategies are insufficient, and the underlying neural mechanisms remain poorly understood. This study investigated beta oscillation dynamics in the STN during different locomotor states, while examining the effects of levodopa. In particular, it aimed to identify pathological activity by analysing the relationship between the STN and lower limb muscles during stepping. Local field potentials (LFP) in the STN and muscle activity (EMG) of the gastrocnemius and peroneus longus were recorded in 14 PD patients during standing and stepping, ON and OFF levodopa. Levodopa reduced stepping variability, implying improved stepping abilities. Distinct STN beta patterns were observed between stepping and standing, with lower high-beta and higher low-beta during stepping compared to standing, suggesting a distinct role of these frequency bands in motor control during postural and movement states. Levodopa reduced low-beta but increased high-beta activity, highlighting a potential physiological function of high-beta in the STN during standing and stepping. In addition, step-phase specific effects of levodopa included reduced broad-beta band activity in the STN and lower limb muscles during the late-stance and pushing-off phase of the contralateral leg when ON medication. Further analyses suggest that pathological STN activity amplifies muscle activation around movement initiation, potentially reducing the ability of the patient to move freely. These findings offer insight for developing phase-specific stimulation strategies targeting STN beta oscillations during gait.

neuroscience↗

bioRxiv2024

Thalamo-frontal connectivity patterns in Tourette Syndrome: Insights from combined intracranial DBS and EEG recordings

Thalamic deep brain stimulation (DBS) has shown clinical improvement for patients with treatment-refractory Tourette Syndrome (TS). Advancing DBS for TS requires identifying reliable electrophysiological markers. Recognising TS as a network disorder, we investigated thalamo-cortical oscillatory connectivity by combining local field potential (LFP) recordings from the DBS thalamic target region using the PerceptTM PC neurostimulator with high-density EEG in eight male TS patients (aged 27 to 38) while stimulation was off. We identified a spatially and spectrally distinct oscillatory network connecting the medial thalamus and frontal regions in the alpha band (8-12 Hz), with connectivity strength negatively correlated with TS symptom severity. Moreover, reduced thalamo-frontal alpha connectivity before tic onset, localised in sensorimotor regions and the inferior parietal cortex, suggests its direct role in tic generation. Importantly, associations with symptoms and pre-tic dynamics were specific to connectivity patterns and not evident in the pure power spectra. These findings underscore the importance of investigating electrophysiological oscillatory connectivity to characterise pathological network connections in TS, potentially guiding stimulation-based interventions and future research on closed-loop DBS for TS.

neuroscience↗

bioRxiv2023

TgF344-AD rat model of Alzheimer's disease: spatial disorientation and asymmetry in hemispheric neurodegeneration

BACKGROUNDThe TgF344-AD ratline represents a transgenic animal model of Alzheimers disease (AD). We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation. Also, we aimed to investigate whether TgF344-AD rats exhibit signs of asymmetry in hemispheric neurodegeneration, similar to what is reported in spatially disoriented AD patients. Finally, we sought to examine how spatial disorientation correlates with working memory performance. METHODSTgF344-AD rats were divided into two groups balanced by sex and genotype. The first group underwent the delayed match-to-sample (DMS) task for the assessment of spatial orientation and working memory, while the second group underwent positron emission tomography (PET) for the assessment of glucose metabolism and microglial activity as in-vivo markers of neurodegeneration. Rats were 13 months old during DMS training and 14-16 months old during DMS testing and PET. RESULTSIn the DMS task, TgF344-AD rats were more likely than their wild-type littermates to display strong preference for one of the two levers, preventing working memory testing. Rats without lever-preference showed similar working memory, regardless of their genotype. PET revealed hemispherically asymmetric clusters of increased microglial activity and altered glucose metabolism in TgF344-AD rats. CONCLUSIONSTgF344-AD rats display spatial disorientation and hemispherically asymmetrical neurodegeneration, suggesting a potential causal relationship consistent with clinical observations. In rats without spatial disorientation, working memory remains intact.

neuroscience↗

bioRxiv2023

Phonic Tics in a Rat Model of Tourette Syndrome Enable Research on Symptom-Based DBS

The lack of a rodent model for both motor and phonic tics hinders research on deep brain stimulation (DBS) for refractory Tourette syndrome (TS). Striatal disinhibition with a GABA-A antagonist (bicuculline) was previously shown to induce tic-like hyperkinesia in rats and monkeys, while tic-like vocalizations were studied and confirmed only in the latter. We, therefore, assessed whether vocalizations accompany hyperkinesia also in rats and whether they respond to thalamic DBS. Rats underwent surgical implantation of a unilateral guide cannula targeting the caudate putamen (CPu) or nucleus accumbens (NAc). Additionally, they were implanted with an ipsilateral stimulation electrode targeting the border between the central medial (CM) and ventrolateral (VL) thalamic nuclei. Motor changes and ultrasound vocalizations were recorded and characterized offline. Bicuculline in CPu led to the development of hyperkinesia in the form of arrhythmic, myocloniform shoulder jerks sporadically alternating with episodes of dystonic lordosis. Likewise, bicuculline in NAc resulted in hyperkinesia, but at a much smaller dose and in conjunction with nonsensical vocalizations. DBS of CM/VL, but not adjacent regions, attenuated hyperkinesia. Also, early results indicate that thalamic DBS attenuates vocalizations, yet the hotspot for stimulation remains to be determined. In conclusion, striatal disinhibition leads not only to the development of hyperkinesia but also vocalizations in rats. The resemblance of hyperkinesia to motor tics and vocalizations to phonic tics is evident in their appearance and susceptibility to DBS. Rats can, therefore, be used to study DBS for symptom-based TS therapy.

animal behavior and cognition↗

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↗

bioRxiv2020

Chronic deep brain stimulation of the human nucleus accumbens region disrupts the stability of inter-temporal preferences.

When choosing between rewards that differ in temporal proximity (inter-temporal choice), human preferences are typically stable, constituting a clinically-relevant transdiagnostic trait. Here we show in patients undergoing deep brain stimulation (DBS) of the anterior limb of the internal capsule / nucleus accumbens region for treatment-resistant obsessivecompulsive disorder (OCD), that long-term chronic (but not phasic) DBS disrupts inter-temporal preferences. Hierarchical Bayesian modeling accounting for temporal discounting behavior across multiple time points allowed us to assess both short-term and long-term reliability of inter-temporal choice. In controls, temporal discounting was highly reliable, both long-term (6 months) and short-term (1 week). In contrast, in patients undergoing DBS, short-term reliability was high, but long-term reliability (6 months) was severely disrupted. Control analyses confirmed that this effect was not due to range restriction, the presence of OCD symptoms or group differences in choice stochasticity. Model-agnostic between- and within-subject analyses confirmed this effect. These findings provide initial evidence for long-term modulation of cognitive function via DBS and highlight a potential contribution of the human nucleus accumbens region to inter-temporal preference stability over time. Significance StatementChoosing between rewards that differ in temporal proximity is in part a stable trait with relevance for many mental disorders, and depends on prefrontal regions and regions of the dopamine system. Here we show that chronic deep brain stimulation (DBS) of the human anterior limb of the internal capsule / nucleus accumbens region for treatment-resistant obsessive compulsive disorder disrupts the stability of inter-temporal preferences. These findings show that chronic stimulation of one of the brains central motivational hubs can disrupt preferences thought to depend on this circuit.

neuroscience↗

bioRxiv2020

Cortical network fingerprint and prediction of stimulation induced speech impairment in essential tremor

ObjectiveTo gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). MethodsMonopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was than validated in a leave-one-out design. ResultsFibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brainstem. In the thalamic area, they ran laterally to the thalamus and postero-medially to the subthalamic nucleus, in close proximity, mainly antero-laterally, to fibers beneficial for tremor control as published by Al-Fatly et al. (2019). The overlap of the respective clinical stimulation settings VTAs with these fibers explained 62.4% (p<0.001) of the variance of stimulation-induced change in intelligibility in a leave-one out analysis. InterpretationThis study demonstrates that SID in essential tremor patients is associated with both, motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in ET patients with thalamic DBS.

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↗

bioRxiv2019

Directional DBS Leads Show Large Deviations from their Intended Implantation Orientation

ObjectiveLead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort.\n\nMethodsThe Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analysed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared.\n\nResultsDeviations of up to 90{degrees} from the intended implantation direction were observed. Deviations of more than 30{degrees} were seen in 42 % of the leads and deviations of more than 60{degrees} in about 11 % of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used.\n\nDiscussionOur results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.\n\nFull DisclosuresTill A. Dembek reports speaker honoraria from Medtronic and Boston Scientific.\n\nMauritius Hoevels has nothing to disclose.\n\nAlexandra Hellerbach has nothing to disclose.\n\nAndreas Horn reports speaker honoraria from Medtronic.\n\nJan Niklas Petry-Schmelzer reports travel grants from Boston Scientific.\n\nJan Borggrefe has nothing to disclose.\n\nJochen Wirths reports travel grants from Boston Scientific.\n\nHaidar Salimi-Dafsari reports honoraria from Medtronic and Boston Scientific.\n\nMichael T. Barbe reports grants from Medtronic and Boston Scientific.\n\nVeerle Visser-Vandewalle is a member of the advisory boards and reports consultancies for Medtronic, Boston Scientific and St Jude Medical. She received a grant from SAPIENS Steering Brain Stimulation. Harald Treuer has nothing to disclose.

neuroscience↗

bioRxiv2019

Toward a unified connectomic target for deep brain stimulation in obsessive-compulsive disorder

Multiple surgical targets have been proposed for treating obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS). However, different targets may modulate the same neural network responsible for clinical improvement. Here we analyzed data from four cohorts of OCD patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens (NAcc) or the subthalamic nucleus (STN). Fiber tracts that were predominantly connected to electrodes in good or poor DBS responders were isolated from a normative structural connectome and assigned a predictive value. Strikingly, the same fiber bundle was related to treatment response when independently analyzing two large training cohorts that targeted either ALIC or STN. This discriminative tract is a subsection of the ALIC and connects frontal regions (such as the dorsal anterior cingulate, dACC, and ventral prefrontal, vlPFC, cortices to the STN). When informing the tract solely based on one cohort (e.g. ALIC), clinical improvements in the other (e.g. STN) could be significantly predicted, and vice versa. Finally, clinical improvements of eight patients from a third center with electrodes in the NAcc and six patients from a fourth center in which electrodes had been implanted in both STN and ALIC were significantly predicted based on this novel tract-based DBS target. Results suggest a functional role of a limbic hyperdirect pathway that projects from dACC and vlPFC to anteriomedial STN. Obsessive-compulsive symptoms seem to be tractable by modulating the specific bundle isolated here. Our results show that connectivity-derived improvement models can inform clinical improvement across DBS targets, surgeons and centers. The identified tract is now three-dimensionally defined in stereotactic standard space and will be made openly available.

neuroscience↗

bioRxiv2019

Cognitive Improvements after Intermittent Deep Brain Stimulation of the Nucleus Basalis of Meynert in a Transgenic Rat Model for Alzheimer’s disease; a Preliminary Approach

BackgroundDeep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has shown to have promising results in a pilot study with patients suffering from Alzheimers disease (AD). A recent study in aged monkeys shows a novel intermittent stimulation pattern to have superior cognitive benefits over continuous paradigms.\n\nObjective/HypothesisWe aimed at comparing the cognitive effects elicited by intermittent and continuous NBM stimulation paradigms in an animal model for AD (TgF344-AD rat line; TG), i.e. rats expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1{Delta}E9) genes, each independent causes of early-onset familial AD.\n\nMethodsIn this exploratory study, aged APP/PS1 rats were tested pre-, and post implantation with several stimulation parameters, i.e. unilateral- or bilateral-intermittent, and bilateral-continuous, while performing various behavioral tasks (open field, novel object recognition, and modified Barnes maze).\n\nResults and ConclusionBilateral-intermittent NBM DBS allowed aged TG rats to perform better and maintain their performance longer in a spatial memory task, as compared to other conditions. These data support the notion that NBM DBS could be further refined in the clinic, thereby improving patient care.

neuroscience↗

bioRxiv2018

Decoding voluntary movements and postural tremor based on thalamic LFPs for closed-loop stimulation for essential tremor

High frequency deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET. We recorded LFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements in seven ET patients during temporary lead externalization after the first surgery for DBS when they performed different voluntary upper limb movements and in nine more patients during the surgery, when they were asked to lift their arms to trigger postural tremor. We show that both voluntary movements and postural tremor can be decoded based on features extracted from thalamic LFPs using a machine learning based binary classifier. This information can be used to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes.

neuroscience↗