Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves.

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We explored the impact of pulse durations <60 μsec on the therapeutic window of subthalamic neurostimulation in Parkinson's disease. Current thresholds for full rigidity control and first muscle contractions were evaluated at pulse durations between 20 and 120 μsec during a monopolar review session in four patients. The average therapeutic window was 2.16 mA at 60 μsec, which proportionally increased by 182% at 30 μsec, while decreasing by 46% at 120 μsec. Measured chronaxies and model data suggest, that pulse durations <60 μsec lead to a focusing of the neurostimulation effect on smaller diameter axons close to the electrode while avoiding stimulation of distant pyramidal tract fibers.

Objective-Therapeutic hypothermia after cardiac arrest improves survival and functional outcomes, whereas hyperthermia is harmful. The optimal method of tracking the effect of temperature on neurologic recovery after cardiac arrest has not been elucidated. We studied the recovery of cortical electrical function by quantitative electroencephalography after 7-min asphyxial cardiac arrest, using information quantity (IQ). Design-Laboratory investigation.Setting-University medical school and animal research facility. Subjects-A total of 28 male Wistar rats.Interventions-Using an asphyxial cardiac arrest rodent model, we tracked quantitative electroencephalography of 6-hr immediate postresuscitation hypothermia (at 33°C), normothermia (37°C), or hyperthermia (39°C) (N=8 per group). Neurological recovery was evaluated using the Neurological Deficit Score. Four rats were included as a sham control group. Measurements and MainResults-Greater recovery of IQ was found in rats treated with hypothermia (IQ=0.74), compared to normothermia (IQ=0.60) and hyperthermia (IQ=0.56) (p<. 001). Analysis at different intervals demonstrated a significant separation of IQ scores among the temperature groups within the first 2 hrs postresuscitation (p<.01). IQ values of >0.523 at 60 mins postresuscitation predicted good neurological outcome (72-hr Neurological Deficit Score of≥60) with a specificity of 100% and sensitivity of 81.8%. IQ was also significantly lower in rats that died prematurely compared to survivors (p<.001). IQ values correlated strongly with 72-hr Neurological Deficit Score as early as 30 mins post-cardiac arrest (Pearson correlation 0.735, p<.01) and maintained a significant association throughout the 72-hr experiment. No IQ difference was noted in sham rats with temperature manipulation. Approximately 164,600 cardiac arrests (CAs) occur in the United States each year (1). Among initial survivors, 80% remain comatose after resuscitation (2) and neurological complications represent the leading cause of disability (3,4). The ischemic brain is sensitive to temperature, such that small differences can critically influence neuropathological outcomes (5). Hyperthermia has been demonstrated to worsen ischemic outcome and is associated with increased brain injury in animal models (5,6) and clinical studies (7-9). On the other hand, induced hypothermia to 32-34°C is recommended for comatose survivors of CA (10,11) and was recently shown to significantly mitigate brain injury in animal models (12)(13)(14) and clinical trials (15-18). NIH Public AccessNeurological monitoring of comatose CA survivors is complicated by the requirement for sedative and paralytic agents, particularly in patients who are treated with hypothermia. Comatose CA survivors are typically cared for by nurses and physicians in general or cardiac intensive care units with little specialized training in neurological examination. In addition, the ability to detect even major changes in brain function in comatose patients is limited. Electroencephalograp...

Significance We studied deep brain stimulation effects in two types of dystonia and conclude that different specific connections between the pallidum and thalamus are responsible for optimal treatment effects. Since alternative treatment options for dystonia beyond deep brain stimulation are scarce, our results will be crucial to maximize treatment outcome in this population of patients.

Background and Objectives:The restoration of touch to fingers and fingertips is critical to achieving dexterous neuroprosthetic control for individuals with sensorimotor dysfunction. However, localized fingertip sensations have not been evoked via intracortical microstimulation (ICMS).Methods:Using a novel intraoperative mapping approach, we implanted electrode arrays in the finger areas of left and right somatosensory cortex and delivered ICMS over a 2-year period in a human participant with spinal cord injury.Results:Stimulation evoked tactile sensations in 8 fingers, including fingertips, spanning both hands. Evoked percepts followed expected somatotopic arrangements. The subject was able to reliably identify up to 7 finger-specific sites spanning both hands in a finger discrimination task. The size of the evoked percepts was on average 33% larger than a fingerpad, as assessed via manual markings of a hand image. The size of the evoked percepts increased modestly with increased stimulation intensity, growing 21% as pulse amplitude increased from 20µA to 80µA. Detection thresholds were estimated on a subset of electrodes, with estimates of 9.2-35µA observed, roughly consistent with prior studies.Discussion:These results suggest that ICMS can enable the delivery of consistent and localized fingertip sensations during object manipulation by neuroprostheses for individuals with somatosensory deficits.Clinical Trial Information:This study is registered on ClinicalTrials.gov with identifier NCT03161067.

The restoration of cutaneous sensation to fingers and fingertips is critical to achieving dexterous prosthesis control for individuals with sensorimotor dysfunction. However, localized and reproducible fingertip sensations in humans have not been reported via intracortical microstimulation (ICMS) in humans. Here, we show that ICMS in a human participant was capable of eliciting percepts in 7 fingers spanning both hands, including 6 fingertip regions (i.e., 3 on each hand). Median percept size was estimated to include 1.40 finger or palmar segments (e.g., one segment being a fingertip or the section of upper palm below a finger). This was corroborated with a more sensitive manual marking technique where median percept size corresponded to roughly 120% of a fingertip segment. Percepts showed high intra-day consistency, including high performance (99%) on a blinded finger discrimination task. Across days, there was more variability in percepts, with 75.8% of trials containing the modal finger or palm region for the stimulated electrode. These results suggest that ICMS can enable the delivery of localized fingertip sensations during object manipulation by neuroprostheses.

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