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Background Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson’s Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. Objective We explored whether recovery of the H-reflex—an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD—could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation. Methods Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. Results Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. Conclusion H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

We describe diffusion tensor imaging metrics of brain microstructure changes following magnetic resonance guided focused ultrasound (MRgFUS) ablation of the ventral intermediate nucleus of the thalamus for the treatment of tremor in order to explore the mechanisms of tremor reduction post-MRgFUS. Tractography was performed on pre-treatment images to identify the portion of the dentato-rubro-thalamo-cortical tract (DRTT) intersecting the MRgFUS thalamotomy lesions in 17 essential tremor patients. The resulting tract was divided into regions of interest (ROI), which were then analyzed on pre-, one day post-, and three months post-treatment scans. Fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, AD, and RD) were computed in each ROI at each time point. At both one day and three months post-treatment, we observed decreased FA and increased MD and RD in the section of the treated tract between the lesion and cortex. At three months post-treatment, we additionally observed increased AD in the section between the lesion and cortex, and decreased FA in the section between the dentate nucleus and the decussation of the superior cerebellar peduncles. Diffusion changes at one day post-treatment may reflect local, acute effects such as inflammation and edema, as opposed to chronic degenerative processes such as axonal degeneration and myelin loss that would be expected at later time points. No significant correlations were detected between diffusion measures and clinical effects, suggesting that microstructural changes in the treated portion of the DRTT alone do not fully explain tremor reduction and motivating additional research using higher spatial resolution diffusion imaging and multimodal approaches such as integrating diffusion and functional magnetic resonance imaging data. Our individualized approach, in which patient-specific lesions are incorporated into the tractography analysis, provided novel insight into both immediate and longer term MRgFUS-related microstructural brain changes.

This chapter explores the complex neuroethical aspects of neurosurgery and neuromodulation in the context of Canadian healthcare and innovation, as seen through the lens of the Pan Canadian Neurotechnology Ethics Consortium (PCNEC). Highlighted are key areas of ethical focus, each with its own unique challenges: technical advances, readiness and risk, vulnerable populations, medico-legal issues, training, and research. Through an exploration of Canadian neurotechnological practice from these various clusters, we provide a critical review of progress, describe opportunities to address areas of debate, and seek to foster ethical innovation. Underpinning this comprehensive review are the fundamental principles of solution-oriented, practical neuroethics, with beneficence and justice at the core. In our view, it is a moral imperative that neurotechnological advancements include a delineation of ethical priorities for future guidelines, oversight, and interactions.

Background Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. Objective/Hypothesis We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. Methods In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients ( n = 25) not receiving DBS. Results We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. Conclusion We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.

Functional surgery is the branch of neurosurgery concerned with surgically altering the nervous system and modulating activity in neural circuits to treat neurological illness. Safe and effective functional surgery depends on accurate brain mapping and selecting appropriate brain targets in various disease states. We briefly review the history of functional surgery, from early lesioning procedures to the development of stereotaxis. We then review the principles and applications of deep brain stimulation, a key technique at the functional neurosurgeon's disposal. We conclude by highlighting emerging technologies that have the potential to increase the scope and efficacy of functional surgery.

There are a number of emerging surgical indications for deep brain stimulation. We have shown that modulation of activity within motor, mood, and cognitive circuits has beneficial effects in patients with Parkinson's disease, treatment-resistant depression, and perhaps Alzheimer's type dementia. We review the rationale, safety, and efficacy for each of these indications, focusing on disease mechanisms and relevant data that are necessary to document therapeutic value in each case. The review closes with some thoughts on possible future directions for deep brain stimulation. It is likely that applications for deep brain stimulation will continue to expand as accumulating data establish its safety and efficacy profile in these and other conditions.