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We read with great interest the article by Fargen et al (1), which reports the Journal of Neurointerventional Surgery (JNIS) experience in social media. The journal recently implemented a three-pronged social media strategy, along with the hiring of dedicated social media staffing, to enhance their online viewership. Since implementing this marketing approach, JNIS has had significantly more website accessions to their peer reviewed articles, and gained more insight into their Twitter analytics. The information presented provide a road-map to guide social media marketing strategies for journals in neurosurgery, neurology, and radiology.While not studied in this manuscript directly, the authors discuss the potential for social media metrics to predict subsequent article citations. In Toronto, our group studied the association between social media metrics and traditional indices of scientific impact among neurosurgical …

We thank Dr. Venketasubramanian for the interest in our article,[1] and for highlighting the safety concerns of focused ultrasound (FUS) as well as the need for more studies, which we agree on. Temporal bone window applies to standard brain diagnostic ultrasound whereas FUS uses over a thousand ultrasound beams directed towards a deep target from all directions surrounding the patient's head.[2] Therefore, the problem of temporal bone window doesn't apply to FUS. However, it is estimated that roughly 20% of FUS candidates cannot receive the treatment due to the high bone density of their skull.[3]

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as treatment for refractory aggressive behaviour, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. 91% of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral posterior hypothalamic area and normative connectomic analyses identified fiber tracts and interconnected brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and the amygdala – together with patient age – was highly predictive of treatment outcome. Finally, transcriptomic analysis showed that genes involved in mechanisms of aggressive behaviour, neuronal communication, plasticity and neuroinflammation may underlie this functional network.SIGNIFICANCE STATEMENTThis study investigated the brain mechanisms associated with symptom improvement following deep brain stimulation of the posterior hypothalamus for severe and refractory aggressive behavior. Conducting an integrated imaging analysis of a large international multi-center dataset of patients treated with hypothalamic deep brain stimulation, we were able to show for the first time that treatment is highly efficacious across various patients with an …

A wide range of disorders are thought to arise from dysfunction in brain circuitry (Bonelli and Cummings, 2007). These pathological circuits are not directly appreciated on routinely acquired structural MRI sequences. In contrast, functional sequences, such as resting state functional magnetic resonance imaging (rs-fMRI), allow us to probe networks and generate a “connectome” that facilitates a global assessment of brain circuitry and function (Yeo et al., 2011). The dearth of patient-specific, or “native”, functional imaging in the majority of clinical protocols and the limited reliability of individual acquisitions has led investigators to instead use large, publicly available aggregates of rs-fMRI (ie, normative connectomes) to examine brain connectivity and study relationships between connectivity and clinical outcome (Supplementary Table 1)(Fox, 2018). However, a common limitation is that these datasets are often derived from healthy subjects. Differences between the inherent connectivity of the healthy and diseased brain mean that these normative connectomes may not be optimal to study brain circuits in diseased populations (Sala et al., 2017). Even while initial studies made cursory efforts at using disease-matched connectomes (Horn et al., 2017), it may be crucial to match disease-severity and patient age as closely as possible to the patient collective of study. For instance, if the connectomes would be used in the context of Parkinson’s Disease (PD) patients undergoing deep brain stimulation (DBS), it would be most optimal to acquire the connectome within exactly such a sample of patients. This was the motivation for constructing the present …

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized.Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr).Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for PD. Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode.Results: Excitatory and inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal …

Deep brain stimulation (DBS) to the fornix is an investigational treatment option for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. One reason could be variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we analyzed a multi-center cohort of 46 patients with DBS to the fornix. Using normative structural and functional connectivity data, we demonstrate that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.45, p = 0.031). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.33, p = 0.016). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.38, p = 0.006). Findings were robust to multiple cross-validation designs and may now define an optimal network target which could subsequently guide refinement of DBS surgery and programming.

MethodsMicroelectrode recordings were acquired from 134 STN neurons across 17 patients. Local field potentials (LFP) were derived by low-pass filtering (< 50Hz) while high-pass filtering (> 300Hz) was applied to isolate single-neuron activity; effectively decoupling these signals. Spiking activity was thresholded as “bursting” or “non-bursting” based on measures of interspike intervals then enveloped using the Hilbert transform. Relationships between LFP and spiking were assessed using frequency, time-frequency, and phase amplitude analyses, and statistics were performed using generalized linear mixed models.ResultsTime, frequency, time-frequency (Fig. A, B), and phase-amplitude (Fig. C) analyses revealed that LFP beta activity was strongly coupled, temporally and spectrally, to bursting activity of STN neurons only. Spectral power in the beta range was significantly increased during bursting (Fig. Di), as …

A system and method for identifying a patient-specific neurosurgery target location is provided. The system receives brain imaging data for a patient that includes tracts and networks in the patient brain, accesses a quantitative connectome atlas comprising population-based, disease-specific structural and functional connectivity maps comprising a pattern of tracts and networks associated with an optimal target area (OTA) identified from a population of patients, and defines the patient-specific neurosurgery target location based on a comparison between a pattern of the tracts and networks from the brain imaging data for the patient and the pattern of tracts and networks associated with the OTA identified from the population of patients in the quantitative connectome atlas. The quantitative connectome atlas comprises a disease-specific, population-based quantitative connectome atlas that identifies an optimal target …