Modeling subcortical white matter stimulation

ObjectiveIntracranial electrical stimulation of subcortical axonal tracts is particularly useful during brain surgery, where mapping helps identify and excise dysfunctional tissue while avoiding damage to functional structures. Stimulation parameters are generally set empirically and consequences for the spatial recruitment of axons within subcortical tracts are not well identified.ApproachComputational modeling is employed to study the effects of stimulation parameters on the recruitment of axons: monophasic versus biphasic stimuli induced with monopolar versus bipolar electrodes, oriented orthogonal or parallel to the tract, for isotropic and anisotropic tracts.Main resultsThe area and depth of axonal activation strongly depend on tissue conductivity and electrode parameters. The largest activation area results from biphasic stimulation with bipolar electrodes oriented orthogonal to axonal fasciculi, for anisotropic and especially isotropic tracts. For anisotropic tracts, the maximal activation depth is similar regardless of whether a monopolar or bipolar electrode is employed. For isotropic tracts, bipolar parallel and monopolar stimulation activate axons deeper than orthogonal bipolar stimulation. Attention is warranted during monophasic stimulation: a blockade of action potentials immediately under cathodes and a propagation of action potentials under anodes are found.SignificanceConsidering the spatial patterns of blockade and activation present during monophasic stimulation with both monopolar and bipolar electrodes, biphasic stimulation is recommended to explore subcortical axon responses during intraoperative mapping. Finally, the precise effect of electrical stimulation depends on conductivity profiles of tracts, and as such, should be explicitly considered for each individual subject and tract undergoing intracranial mapping.

Efficacy of Deep Brain Stimulation in a Patient with Genetically Confirmed Chorea-Acanthocytosis

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek, and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after DBS surgery. Here, we present a case of ChAc in a 31-year-old male positive for VPS13A gene mutations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. DBS using monopolar stimulation with placement slightly lateral to the GPi was associated with significant improvement in chorea and dysarthria. This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact and ideal target of DBS in ChAc.

P.012 Bilateral pallidal deep brain stimulation in a patient with chorea-acanthocytosis

Background: Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Methods: Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after deep brain stimulation (DBS) surgery. Results: Here we present a case of ChAc in a 31 year old male positive for VPS13A gene muations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. GPi-DBS using monopolar stimulation was associated with significant improvement in chorea and dysarthria. Conclusions: This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact of DBS in ChAc.

Thalamic short pulse stimulation diminishes adverse effects in essential tremor patients

ObjectiveTo investigate the effect of directional current steering and short pulse stimulation in the ventral intermediate thalamic nucleus (VIM) on stimulation-induced side effects in patients with essential tremor.MethodsWe recruited 8 patients with essential tremor in a stable postoperative condition (>3 months after electrode implantation of deep brain stimulation [DBS] electrodes) with segmented contacts implanted in the VIM. Tremor severity on acute stimulation was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale. Cerebellar impairment was evaluated with the International Cooperative Ataxia Rating Scale. Patients rated paresthesia intensity with a visual analog scale.ResultsIn all patients, tremor was reduced to the same extent by VIM stimulation regardless of pulse width using energy dose–equivalent amplitudes. Short pulse stimulation diminished stimulation-induced ataxia of the upper extremities and paresthesia compared with conventional parameters. Directional steering with monopolar stimulation of single segments successfully suppressed tremor but also induced ataxia. No differences in adverse effects were found between single-segment stimulation conditions.ConclusionThese proof-of-principle findings provide evidence that acute short pulse stimulation is superior to directional steering in the subthalamic area to decrease stimulation-induced side effects while preserving tremor suppression effects in patients with tremor.Classification of evidenceThis study provides Class IV evidence that for patients with tremor with thalamic DBS, acute short pulse stimulation reduces adverse effects, while directional steering does not provide a generalizable benefit regarding adverse effects.

145 Tractography-defined Subregions of Human Nucleus Accumbens Predict Acute Anxiolytic Response to Selective Stimulation

INTRODUCTION The nucleus accumbens (NAc) serves as a key node in reward processing underlying motivated behavior, and its dysfunction is implicated in a host of psychiatric disorders that are amenable to deep brain stimulation (DBS). On the basis of histochemical and structural connectivity data most thoroughly conducted in animals, the NAc is divided into two primary subregions, core (dorsolateral) and shell (ventromedial), which have dissociable afferent and efferent connections and functions. To characterize NAc subregions, the current study used high-resolution diffusion tractography to delineate core and shell and assessed the immediate clinical implications. METHODS Multimodal MRI data from 245 healthy, unrelated subjects was obtained from the Human Connectome Project database. Freesurfer-generated brain regions were used to perform probabilistic tractography using every NAc voxel as seed and every other Freesurfer region as target. NAc voxels with similar connectivity fingerprints were grouped using k-means clustering. This procedure was also performed retrospectively on two other datasets of lesser quality, including that of one patient with obsessive-compulsive disorder who underwent bilateral DBS lead placement targeting the NAc. The final position of the DBS leads relative to tractography-defined subregions was determined, and the effect of monopolar stimulation on self-reported anxiety utilizing subregion-specific contacts was assessed utilizing a Likert scale. RESULTS >Tractography-based segmentation of the NAc produced ventromedial and dorsolateral subregions across subjects and datasets, consistent with prior histochemical evidence from humans. At electrical currents as low as 1.6 mA, monopolar stimulation of dorsolateral but not ventromedial subregions produced an acute reduction in self-reported anxiety. CONCLUSION NAc subregions that resemble histologically defined core and shell with dissociable acute clinical effects can be produced with tractography-based segmentation. These results have implications for DBS targeting of the NAc, and may help to explain variances in clinical outcome among patients receiving NAc DBS to date.