Development and characterization of an intracortical closed-loop brain-computer interface

Intracortical brain-computer interfaces (BCI) have the potential to restore motor function to people with paralysis by extracting movement intent signals directly from motor cortex. While current technology has allowed individuals to perform simple object interactions with robotic arms, such demonstrations have depended exclusively on visual feedback. Additional forms of sensory feedback may lessen the dependence on vision and allow for more dexterous control. Intracortical microstimulation (ICMS) has been proposed as a method of adding somatosensory feedback to BCI by directly stimulating somatosensory cortex to evoke tactile sensations referred to the hand. Our lab recently demonstrated that ICMS can elicit graded and focal tactile sensations in an individual with spinal cord injury (SCI). However, several challenges must be resolved to demonstrate the viability of ICMS as a technique for incorporating sensory feedback in a closed-loop BCI. First, microstimulation generates large voltage transients that appear as artifacts in the neural recordings used for BCI control. These artifacts can corrupt the recorded signal throughout the entire stimulus train, and must be eliminated to allow for continuous BCI decoding. Second, it is unknown whether the sensations elicited by ICMS can be perceived quickly enough for use as a feedback signal. Here, I present several aspects of the development of a closed-loop BCI system, including a method for artifact rejection and the characterization of simple reaction times to ICMS of human somatosensory cortex. A human participant with tetraplegia due to SCI was implanted with four microelectrode arrays in primary motor and somatosensory cortices. I implemented a robust method of artifact rejection that preserves neural data as soon as 750 microseconds after each stimulus pulse by applying signal blanking and an appropriate digital filter. I validated this method by comparing BCI performance with and without ICMS and found that performance was maintained with ICMS and artifact rejection. Next, I characterized simple reaction times to single-channel ICMS, and found that responses to ICMS were comparable, and often faster, than responses to electrical stimulation on the hand. These findings suggest that ICMS is a viable method to provide feedback in a closed-loop BCI

Objective Assessment of Fall Risk in Parkinson's Disease Using a Body-Fixed Sensor Worn for 3 Days

Background: Patients with Parkinson's disease (PD) suffer from a high fall risk. Previous approaches for evaluating fall risk are based on self-report or testing at a given time point and may, therefore, be insufficient to optimally capture fall risk. We tested, for the first time, whether metrics derived from 3 day continuous recordings are associated with fall risk in PD. Methods and Materials 107 patients (Hoehn & Yahr Stage: 2.6±0.7) wore a small, body-fixed sensor (3D accelerometer) on lower back for 3 days. Walking quantity (e.g., steps per 3-days) and quality (e.g., frequency-derived measures of gait variability) were determined. Subjects were classified as fallers or non-fallers based on fall history. Subjects were also followed for one year to evaluate predictors of the transition from non-faller to faller. Results: The 3 day acceleration derived measures were significantly different in fallers and non-fallers and were significantly correlated with previously validated measures of fall risk. Walking quantity was similar in the two groups. In contrast, the fallers walked with higher step-to-step variability, e.g., anterior-posterior width of the dominant frequency was larger (p = 0.012) in the fallers (0.78±0.17 Hz) compared to the non-fallers (0.71±0.07 Hz). Among subjects who reported no falls in the year prior to testing, sensor-derived measures predicted the time to first fall (p = 0.0034), whereas many traditional measures did not. Cox regression analysis showed that anterior-posterior width was significantly (p = 0.0039) associated with time to fall during the follow-up period, even after adjusting for traditional measures. Conclusions/Significance: These findings indicate that a body-fixed sensor worn continuously can evaluate fall risk in PD. This sensor-based approach was able to identify transition from non-faller to faller, whereas many traditional metrics were not successful. This approach may facilitate earlier detection of fall risk and may in the future, help reduce high costs associated with falls

Automated detection of near falls: algorithm development and preliminary results

<p>Abstract</p> <p>Background</p> <p>Falls are a major source of morbidity and mortality among older adults. Unfortunately, self-report is, to a large degree, the gold-standard method for characterizing and quantifying fall frequency. A number of studies have demonstrated that near falls predict falls and that near falls may occur more frequently than falls. These studies suggest that near falls might be an appropriate fall risk measure. However, to date, such investigations have also relied on self-report. The purpose of the present study was to develop a method for automatic detection of near falls, potentially a sensitive, objectivemarker of fall risk and to demonstrate the ability to detect near falls using this approach.</p> <p>Findings</p> <p>15 healthy subjects wore a tri-axial accelerometer on the pelvis as they walked on a treadmill under different conditions. Near falls were induced by placing obstacles on the treadmill and were defined using observational analysis. Acceleration-derived parameters were examined as potential indicators of near falls, alone and in various combinations. 21 near falls were observed and compared to 668 "non-near falls" segments, consisting of normal and abnormal (but not near falls) gait. The best single method was based on the maximum peak-to-peak vertical acceleration derivative, with detection rates better than 85% sensitivity and specificity.</p> <p>Conclusions</p> <p>These findings suggest that tri-axial accelerometers may be used to successfully distinguish near falls from other gait patterns observed in the gait laboratory and may have the potential for improving the objective evaluation of fall risk, perhaps both in the lab and in at home-settings.</p

Impact of sub-thalamic nucleus deep brain stimulation on dual tasking gait in Parkinson’s disease

Background: The beneficial effects of bilateral sub-thalamic nucleus deep brain stimulation on motor function and gait in advanced Parkinson’s disease are established. Less is known about the effect of stimulation on cognitive function and the capacity to walk while dual tasking, an ability that has been related to fall risk. Everyday walking takes place in complex environments that often require multi-tasking. Hence, dual tasking gait performance reflects everyday ambulation as well as gait automaticity. The purpose of this study was to examine the impact of sub-thalamic nucleus deep brain stimulation on dual task walking in patients with advanced Parkinson’s disease. Methods: Gait was assessed using a performance-based test and by quantifying single-task and dual task walking conditions in 28 patients with advanced Parkinson’s disease. These tests were conducted in 4 conditions: “OFF” medication, with the stimulator turned on and off, and “ON” medication, with the stimulator turned on and off. A previously validated, computerized neuro-psychological battery assessed executive function, attention and memory “OFF” and “ON” deep brain stimulation, after subjects took their anti-Parkinsonian medications. Results: Stimulation improved motor function and the spatiotemporal parameters of gait (e.g., gait speed) during both single-task and dual task walking conditions. Attention improved, but executive function did not. The dual task effect on gait did not change in response to stimulation. For example, during serial 3 subtractions, gait speed was reduced by -0.20 ± 0.14 m/sec while OFF DBS and OFF meds and by -0.22 ± 0.14 m/sec when the DBS was turned on (p = 0.648). Similarly, ON medication, serial 3 subtractions reduced gait speed by -0.20 ± 0.16 m/sec OFF DBS and by -0.22 ± 0.09 m/sec ON DBS (p = 0.543). Conclusions: Bilateral sub-thalamic nucleus deep brain stimulation improves motor symptoms, certain features of gait and even some aspects of cognitive function. However, stimulation apparently fails to reduce the negative impact of a dual task on walking abilities. These findings provide new insight into the effects of deep brain stimulation on gait during cognitively challenging conditions and everyday walking

Using a Body-Fixed Sensor to Identify Subclinical Gait Difficulties in Older Adults with IADL Disability: Maximizing the Output of the Timed Up and Go

Objective: The identification and documentation of subclinical gait impairments in older adults may facilitate the appropriate use of interventions for preventing or delaying mobility disability. We tested whether measures derived from a single body-fixed sensor worn during traditional Timed Up and Go (TUG) testing could identify subclinical gait impairments in community dwelling older adults without mobility disability. Methods: We used data from 432 older adults without dementia (mean age 83.30±7.04 yrs, 76.62% female) participating in the Rush Memory and Aging Project. The traditional TUG was conducted while subjects wore a body-fixed sensor. We derived measures of overall TUG performance and different subtasks including transitions (sit-to-stand, stand-to-sit), walking, and turning. Multivariate analysis was used to compare persons with and without mobility disability and to compare individuals with and without Instrumental Activities of Daily Living disability (IADL-disability), all of whom did not have mobility disability. Results: As expected, individuals with mobility disability performed worse on all TUG subtasks (p<0.03), compared to those who had no mobility disability. Individuals without mobility disability but with IADL disability had difficulties with turns, had lower yaw amplitude (p<0.004) during turns, were slower (p<0.001), and had less consistent gait (p<0.02). Conclusions: A single body-worn sensor can be employed in the community-setting to complement conventional gait testing. It provides a wide range of quantitative gait measures that appear to help to identify subclinical gait impairments in older adults

Nocturia as an Unrecognized Symptom of Uncontrolled Hypertension in Black Men Aged 35 to 49&nbsp;Years.

Background Hypertension is assumed to be asymptomatic. Yet, clinically significant nocturia (≥2 nightly voids) constitutes a putative symptom of uncontrolled hypertension. Black men with hypertension may be prone to nocturia because of blunted nocturnal blood pressure ( BP ) dipping, diuretic drug use for hypertension, and comorbidity that predisposes to nocturia. Here, we test the hypothesis that nocturia is a common and potentially reversible symptom of uncontrolled hypertension in black men. Methods and Results We determined the strength of association between nocturia (≥2 nightly voids) and high BP (≥135/85&nbsp;mm&nbsp;Hg) by conducting in-person health interviews and measuring BP with an automated monitor in a large community-based sample of black men in their barbershops. Because nocturia is prevalent and steeply age-dependent after age 50&nbsp;years, we studied men aged 35 to 49&nbsp;years. Among 1673 black men (mean age, 43±4&nbsp;years [ SD ]), those with hypertension were 56% more likely than men with normotension to have nocturia after adjustment for diabetes mellitus and sleep apnea (adjusted odds ratio, 1.56; 95% CI , 1.25-1.94 [ P&lt;0.0001]). Nocturia prevalence varied by hypertension status, ranging from 24% in men with normotension to 49% in men whose hypertension was medically treated but uncontrolled. Men with untreated hypertension were 39% more likely than men with normotension to report nocturia ( P=0.02), whereas men whose hypertension was treated and controlled were no more likely than men with normotension to report nocturia ( P=0.69). Conclusions Uncontrolled hypertension was an independent determinant of clinically important nocturia in a large cross-sectional community-based study of non-Hispanic black men aged 35 to 49&nbsp;years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unqiue identifier: NCT 02321618

Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways

<p>Abstract</p> <p>Background</p> <p>Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways.</p> <p>Methods</p> <p>To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot.</p> <p>Results</p> <p>OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21.</p> <p>Conclusion</p> <p>The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways.</p

Fluctuation Properties of Steady-State Langevin Systems

Motivated by stochastic models of climate phenomena, the steady-state of a linear stochastic model with additive Gaussian white noise is studied. Fluctuation theorems for nonequilibrium steady-states provide a constraint on the character of these fluctuations. The properties of the fluctuations which are unconstrained by the fluctuation theorem are investigated and related to the model parameters. The irreversibility of trajectory segments, which satisfies a fluctuation theorem, is used as a measure of nonequilibrium fluctuations. The moments of the irreversibility probability density function (pdf) are found and the pdf is seen to be non-Gaussian. The average irreversibility goes to zero for short and long trajectory segments and has a maximum for some finite segment length, which defines a characteristic timescale of the fluctuations. The initial average irreversibility growth rate is equal to the average entropy production and is related to noise-amplification. For systems with a separation of deterministic timescales, modes with timescales much shorter than the trajectory timespan and whose noise amplitudes are not asymptotically large, do not, to first order, contribute to the irreversibility statistics, providing a potential basis for dimensional reduction.Comment: 8 pages, to be published in Physical Review