Coupled Activation of the Hyperdirect and Cerebellothalamic Pathways with Zona Incerta Deep Brain Stimulation

Bingham, Clayton S.; McIntyre, Cameron C.

doi:10.1002/mds.29717

Cited by 3 publications

References 42 publications

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Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor

Scerrati,

Gozzi,

Cavallo

et al. 2024

J Neurol

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Background Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies. Objective To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor. Methods Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported. Results Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients. All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred. Conclusion In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.

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Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor

Scerrati,

Gozzi,

Cavallo

et al. 2024

J Neurol

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Neural pathway activation in the subthalamic region depends on stimulation polarity

Borgheai,

Opri,

Isbaine

et al. 2024

Preprint

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Deep brain stimulation (DBS) is an effective treatment for Parkinsońs disease (PD); however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic vs. anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioral responses, but anodic DBS broadens the therapeutic window. This suggests that neural pathways involved respond preferentially depending on stimulus polarity. To experimentally compare the activation of therapeutically relevant pathways during cathodic and anodic subthalamic nucleus (STN) DBS, pathway activation was quantified by measuring evoked potentials resulting from antidromic or orthodromic activation in 15 PD patients undergoing DBS implantation. Cortical evoked potentials (cEP) were recorded using subdural electrocorticography, DBS local evoked potentials (DLEP) were recorded from non-stimulating contacts and EMG activity was recorded from arm and face muscles. We measured: 1) the amplitude of short-latency cEP, previously demonstrated to reflect activation of the cortico-STN hyperdirect pathway, 2) DLEP amplitude thought to reflect activation of STN-globus pallidus (GP) pathway, and 3) amplitudes of very short-latency cEP and motor evoked potentials (mEP) for activation of cortico-spinal/bulbar tract (CSBT). We constructed recruitment and strength-duration curves for each EP/pathway to compare the excitability for different stimulation polarities. We compared experimental data with the most advanced DBS computational models. Our results provide experimental evidence that subcortical cathodic and anodic stimulation activate the same pathways in the STN region and that cathodic stimulation is in general more efficient. However, relative efficiency varies for different pathways so that anodic stimulation is the least efficient in activating CSBT, more efficient in activating the HDP and as efficient as cathodic in activating STN-GP pathway. Our experiments confirm biophysical model predictions regarding neural activations in the central nervous system and provide evidence that stimulus polarity has differential effects on passing axons, terminal synapses, and local neurons. Comparison of experimental results with clinical DBS studies provides further evidence that the hyperdirect pathway may be involved in the therapeutic mechanisms of DBS.

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Mapping the topographic organization of the human zona incerta using diffusion MRI

Haast,

Kai,

Taha

et al. 2024

Preprint

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The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an “immensely confusing area about which nothing can be said.” Despite the elusive nature of this structure, mounting evidence supports the role of the ZI and surrounding regions across a diverse range of brain functions and as a candidate target for neuromodulatory therapies. Usingin vivodiffusion MRI and data-driven connectivity, we identify a topographic organization between the ZI and neocortex. Specifically, our methods identify a rostral-caudal gradient predominantly connecting the frontopolar and ventral prefrontal cortices with the rostral ZI, and the primary sensorimotor cortices with the caudal ZI. Moreover, we demonstrate how clustering and gradient approaches build complementary evidence including facilitating the mapping of a central region of the ZI, connected with the dorsal prefrontal cortex. These results were shown to be replicable across multiple datasets and at the individual subject level, building evidence for the important role of the ZI in mediating frontal lobe-associated tasks, ranging from motor to cognitive to emotional control. Finally, we consider the impact of this topographic organization on the refinement of neuromodulatory targets. These results pave the way for an increasingly detailed understanding of ZI substructures, and considerations forin vivotargeting of the ZI for neuromodulation.

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Coupled Activation of the Hyperdirect and Cerebellothalamic Pathways with Zona Incerta Deep Brain Stimulation

Cited by 3 publications

References 42 publications

Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor

Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor

Neural pathway activation in the subthalamic region depends on stimulation polarity

Mapping the topographic organization of the human zona incerta using diffusion MRI

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