Publications by authors named "Zachary Irwin"

19 Publications

  • Page 1 of 1

Subcortical short-term plasticity elicited by deep brain stimulation.

Ann Clin Transl Neurol 2021 Apr 7. Epub 2021 Apr 7.

Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Objective: To investigate local short-term neuroplasticity elicited by subthalamic, thalamic, and pallidal deep brain stimulation (DBS) for movement disorders.

Methods: During DBS surgery, we delivered pairs of stimulus pulses with both circular and directional leads across 90 interstimulus intervals in 17 participants and recorded local field potentials from unused contacts on the implanted electrode array. We removed the stimulus artifact, validated the neural origin of the underlying signals, and examined short-term plasticity as a function of interstimulus interval and DBS target, using linear mixed effects models.

Results: DBS evokes short latency local field potentials that are readily detected with both circular and directional leads at all stimulation targets (0.31 ± 0.10 msec peak latency, mean ± SD). Peak amplitude, area, and latency are modified strongly by interstimulus interval (P < 0.001) and display absolute and relative refractory periods (0.56 ± 0.08 and 2.94 ± 1.05 msec, respectively). We also identified later oscillatory activity in the subthalamic-pallidal circuit (4.50 ± 1.11 msec peak latency) that displays paired pulse facilitation (present in 5/8 subthalamic, 4/5 pallidal, and 0/6 thalamic trajectories, P = 0.018, Fisher's exact test), and correlates with resting beta frequency power (P < 0.001), therapeutic DBS frequencies, and stimulation sites chosen later for therapy in the ambulatory setting (P = 0.031).

Interpretation: Paired DBS pulses synchronize local circuit electrophysiology and elicit short-term neuroplasticity in the subthalamic-pallidal circuit. Collectively, these responses likely represent the earliest detectable interaction between the DBS pulse and local neuronal tissue in humans. Evoked subcortical field potentials could serve as a predictive biomarker to guide the implementation of next-generation directional and adaptive stimulation devices.
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http://dx.doi.org/10.1002/acn3.51275DOI Listing
April 2021

Latency of subthalamic nucleus deep brain stimulation-evoked cortical activity as a potential biomarker for postoperative motor side effects.

Clin Neurophysiol 2020 06 12;131(6):1221-1229. Epub 2020 Mar 12.

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.

Objective: Here, we investigate whether cortical activation predicts motor side effects of deep brain stimulation (DBS) and whether these potential biomarkers have utility under general anesthesia.

Methods: We recorded scalp potentials elicited by DBS during surgery (n = 11), both awake and under general anesthesia, and in an independent ambulatory cohort (n = 8). Across a range of stimulus configurations, we measured the amplitude and timing of short- and long-latency response components and linked them to motor side effects.

Results: Regardless of anesthesia state, in both cohorts, DBS settings with capsular side effects elicited early responses with peak latencies clustering at <1 ms. This early response was preserved under anesthesia in all participants (11/11). In contrast, the long-latency components were suppressed completely in 6/11 participants. Finally, the latency of the earliest response could predict the presence of postoperative motor side effects both awake and under general anesthesia (84.8% and 75.8% accuracy, awake and under anesthesia, respectively).

Conclusion: DBS elicits short-latency cortical activation, both awake and under general anesthesia, which appears to reveal interactions between the stimulus and the corticospinal tract.

Significance: Short-latency evoked cortical activity can potentially be used to aid both DBS lead placement and post-operative programming.
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http://dx.doi.org/10.1016/j.clinph.2020.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214089PMC
June 2020

A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees.

Sci Transl Med 2020 03;12(533)

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

Peripheral nerves provide a promising source of motor control signals for neuroprosthetic devices. Unfortunately, the clinical utility of current peripheral nerve interfaces is limited by signal amplitude and stability. Here, we showed that the regenerative peripheral nerve interface (RPNI) serves as a biologically stable bioamplifier of efferent motor action potentials with long-term stability in upper limb amputees. Ultrasound assessments of RPNIs revealed prominent contractions during phantom finger flexion, confirming functional reinnervation of the RPNIs in two patients. The RPNIs in two additional patients produced electromyography signals with large signal-to-noise ratios. Using these RPNI signals, subjects successfully controlled a hand prosthesis in real-time up to 300 days without control algorithm recalibration. RPNIs show potential in enhancing prosthesis control for people with upper limb loss.
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http://dx.doi.org/10.1126/scitranslmed.aay2857DOI Listing
March 2020

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

Front Neurosci 2020 31;14:41. Epub 2020 Jan 31.

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States.

Introduction: Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.

Methods: We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi ( = 3) or STN ( = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).

Results: Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.

Conclusion: Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.
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http://dx.doi.org/10.3389/fnins.2020.00041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006239PMC
January 2020

Short latency cortical evoked potentials elicited by subthalamic nucleus deep brain stimulation: Commentary and results from paired pulse studies.

Clin Neurophysiol 2020 02 2;131(2):465-467. Epub 2019 Dec 2.

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2019.11.015DOI Listing
February 2020

Risk of developing an abdominal aortic aneurysm after ectatic aorta detection from initial screening.

J Vasc Surg 2020 06 7;71(6):1913-1919. Epub 2019 Nov 7.

Department of Surgery, Sacramento VA Medical Center, Mather, Calif; Department of Surgery, University of California, Davis, Sacramento, Calif. Electronic address:

Objective: Current abdominal aortic aneurysm (AAA) surveillance guidelines lack any follow-up recommendations after initial abdominal aortic screening diameter of less than 3.0 cm. Some reports have demonstrated patients with late AAA formation and late ruptures after initial ultrasound screening detection of patients with an aortic diameter of 2.5 to 2.9 cm (ectatic aorta). The purpose of this study was to determine ectatic aorta prevalence, AAA development, rupture risk, and risk factor profile in patients with detected ectatic aortas in a AAA screening program.

Methods: A retrospective chart review of all patients screened for AAA from January 1, 2007, to December 31, 2016, within a regional health care system was conducted. Screening criteria were men 65 to 75 years of age that smoked a minimum of 100 cigarettes in their lifetime. An ectatic aorta was defined as a maximum aortic diameter from 2.5 to 2.9 cm. An AAA was defined as an aortic diameter of 3 cm or greater. Patients screened with ectatic aortas who had subsequent follow-up imaging of the aorta with a minimum of 1-year follow-up were analyzed for associated clinical and cardiovascular risk factors. All data were collected through December 3,/2018. A logistic regression of statistically significant variables from univariate and χ analyses were performed to identify risks associated with the development of AAA from an initially diagnosed ectatic aorta. A Cox proportional hazard model was used to assess survival data. A P value of less than .05 was considered statistically significant.

Results: From a screening pool of 19,649 patients, 3205 (16.3%) with a mean age of 72.1 ± 5.3 years were identified to have an ectatic aorta from January 1, 2007, to December 31, 2016. The average screening ectatic aortic diameter was 2.6 ± 0.1 cm. There were 672 patients (21.0%) with a mean age of 73.0 ± 5.7 years who received subsequent imaging for other clinical indications and 193 of these patients (28.7%) with ectatic aortas developed an AAA from the last follow-up scan (4.2 ± 2.5 years). The average observation length of all patients was 6.4 ± 2.9 years. No ruptures were reported, but 27.8% of deaths were of unknown cause. One patient had aortic growth to 5.5 cm or greater (0.15%). Larger initial screening diameter (P < .01), presence of chronic obstructive pulmonary disease (P < .01), and active smoking (P = .01) were associated with AAA development.

Conclusions: Patients with diagnosed ectatic aortas from screening who are active smokers or have chronic obstructive pulmonary disease are likely to develop an AAA.
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http://dx.doi.org/10.1016/j.jvs.2019.08.252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203000PMC
June 2020

The 10-year outcomes of a regional abdominal aortic aneurysm screening program.

J Vasc Surg 2019 10 25;70(4):1123-1129. Epub 2019 Mar 25.

Department of Surgery, Sacramento VA Medical Center, Mather, Calif; Department of Surgery, University of California, Davis, Sacramento, Calif. Electronic address:

Objective: In 2007, Medicare established ultrasound screening guidelines to identify patients at risk for abdominal aortic aneurysm (AAA). The purpose of this study was to evaluate AAA diagnosis rates and compliance with screening during 10 years (2007-2016) of the Screen for Abdominal Aortic Aneurysms Very Efficiently Act implementation within a regional health care system.

Methods: A retrospective chart review of all patients screened for AAA from 2007 to 2016 within a regional Veterans Affairs health care system was conducted. Screening criteria were men 65 to 75 years of age who smoked a minimum of 100 cigarettes in their lifetime. An AAA was defined as a maximum aortic diameter ≥3 cm. A comparison was made of the AAA diagnosis rate and clinical adherence rate of screening criteria between the first 5 years and total years evaluated. AAA-related mortality was identified by using terminal diagnosis notes or autopsy reports. All data were recorded by August 31, 2017.

Results: A total of 19,649 patients (70.7 ± 4.8 years of age, mean ± standard deviation) were screened from January 1, 2007, to December 31, 2016. There were 9916 new patients screened from 2012 to 2016. A total of 1232 aneurysms (6.3% total patients) were identified during the 10-year period. The overall AAA diagnosis rate has declined from 7.2% in the first 5 years to 6.3% in 10 years (13.5% decrease; P < .01). There were 66 patients found with AAA ≥5.5 cm (5.3% of AAAs), and 54 of these patients received successful elective repair. A total of 2321 patients died (11.8%) and 6 deaths were suspected AAA ruptures (0.03%) within the analysis period. A total of 3680 patients screened (18.7%) did not meet screening criteria: 593 patients were <65 years of age, 3087 patients were >75 years of age, and 59 patients were women. This rate has declined from 28.2% within the first 5 years to 18.7% overall in 10 years (33.7% decrease; P < .01). The compliance of screened patients using screening criteria improved significantly from 61.7% in 2007 to 92.4% in 2016 (P < .01). The overall compliance rate since implementation of the screening program during the past 10 years is 81.3%.

Conclusions: The overall 10-year rate of AAA diagnosis is 6.3%. There are more smaller aneurysms (3.0-4.4 cm) detected and fewer large AAAs ≥5.5 cm in the last 5 years compared with the first 5 years of the screening program. The overall AAA-related mortality rate of all screened patients is 0.03%. There were 54 patients with AAA ≥5.5 cm who underwent successful elective repair resulting from the AAA screening program. The overall compliance of screened patients using screening criteria improved significantly from 61.7% in 2007 to 81.3% since implementation of the screening program during the past 10 years.
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http://dx.doi.org/10.1016/j.jvs.2019.01.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945495PMC
October 2019

Design and testing of a 96-channel neural interface module for the Networked Neuroprosthesis system.

Bioelectron Med 2019 15;5. Epub 2019 Feb 15.

1Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI USA.

Background: The loss of motor functions resulting from spinal cord injury can have devastating implications on the quality of one's life. Functional electrical stimulation has been used to help restore mobility, however, current functional electrical stimulation (FES) systems require residual movements to control stimulation patterns, which may be unintuitive and not useful for individuals with higher level cervical injuries. Brain machine interfaces (BMI) offer a promising approach for controlling such systems; however, they currently still require transcutaneous leads connecting indwelling electrodes to external recording devices. While several wireless BMI systems have been designed, high signal bandwidth requirements limit clinical translation. Case Western Reserve University has developed an implantable, modular FES system, the Networked Neuroprosthesis (NNP), to perform combinations of myoelectric recording and neural stimulation for controlling motor functions. However, currently the existing module capabilities are not sufficient for intracortical recordings.

Methods: Here we designed and tested a 1 × 4 cm, 96-channel neural recording module prototype to fit within the specifications to mate with the NNP. The neural recording module extracts power between 0.3-1 kHz, instead of transmitting the raw, high bandwidth neural data to decrease power requirements.

Results: The module consumed 33.6 mW while sampling 96 channels at approximately 2 kSps. We also investigated the relationship between average spiking band power and neural spike rate, which produced a maximum correlation of R = 0.8656 (Monkey N) and R = 0.8023 (Monkey W).

Conclusion: Our experimental results show that we can record and transmit 96 channels at 2ksps within the power restrictions of the NNP system and successfully communicate over the NNP network. We believe this device can be used as an extension to the NNP to produce a clinically viable, fully implantable, intracortically-controlled FES system and advance the field of bioelectronic medicine.
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http://dx.doi.org/10.1186/s42234-019-0019-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098219PMC
February 2019

Cortical Decoding of Individual Finger Group Motions Using ReFIT Kalman Filter.

Front Neurosci 2018 5;12:751. Epub 2018 Nov 5.

Robotics Graduate Program, University of Michigan, Ann Arbor, MI, United States.

To date, many brain-machine interface (BMI) studies have developed decoding algorithms for neuroprostheses that provide users with precise control of upper arm reaches with some limited grasping capabilities. However, comparatively few have focused on quantifying the performance of precise finger control. Here we expand upon this work by investigating online control of individual finger groups. We have developed a novel training manipulandum for non-human primate (NHP) studies to isolate the movements of two specific finger groups: index and middle-ring-pinkie (MRP) fingers. We use this device in combination with the ReFIT (Recalibrated Feedback Intention-Trained) Kalman filter to decode the position of each finger group during a single degree of freedom task in two rhesus macaques with Utah arrays in motor cortex. The ReFIT Kalman filter uses a two-stage training approach that improves online control of upper arm tasks with substantial reductions in orbiting time, thus making it a logical first choice for precise finger control. Both animals were able to reliably acquire fingertip targets with both index and MRP fingers, which they did in blocks of finger group specific trials. Decoding from motor signals online, the ReFIT Kalman filter reliably outperformed the standard Kalman filter, measured by bit rate, across all tested finger groups and movements by 31.0 and 35.2%. These decoders were robust when the manipulandum was removed during online control. While index finger movements and middle-ring-pinkie finger movements could be differentiated from each other with 81.7% accuracy across both subjects, the linear Kalman filter was not sufficient for decoding both finger groups together due to significant unwanted movement in the stationary finger, potentially due to co-contraction. To our knowledge, this is the first systematic and biomimetic separation of digits for continuous online decoding in a NHP as well as the first demonstration of the ReFIT Kalman filter improving the performance of precise finger decoding. These results suggest that novel nonlinear approaches, apparently not necessary for center out reaches or gross hand motions, may be necessary to achieve independent and precise control of individual fingers.
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http://dx.doi.org/10.3389/fnins.2018.00751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231049PMC
November 2018

Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings.

Nat Commun 2018 06 1;9(1):2155. Epub 2018 Jun 1.

Department of Neurology, Comprehensive Epilepsy Program, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48109, USA.

The rate of interictal high frequency oscillations (HFOs) is a promising biomarker of the seizure onset zone, though little is known about its consistency over hours to days. Here we test whether the highest HFO-rate channels are consistent across different 10-min segments of EEG during sleep. An automated HFO detector and blind source separation are applied to nearly 3000 total hours of data from 121 subjects, including 12 control subjects without epilepsy. Although interictal HFOs are significantly correlated with the seizure onset zone, the precise localization is consistent in only 22% of patients. The remaining patients either have one intermittent source (16%), different sources varying over time (45%), or insufficient HFOs (17%). Multiple HFO networks are found in patients with both one and multiple seizure foci. These results indicate that robust HFO interpretation requires prolonged analysis in context with other clinical data, rather than isolated review of short data segments.
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http://dx.doi.org/10.1038/s41467-018-04549-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984620PMC
June 2018

Closed-Loop Continuous Hand Control via Chronic Recording of Regenerative Peripheral Nerve Interfaces.

IEEE Trans Neural Syst Rehabil Eng 2018 02;26(2):515-526

Loss of the upper limb imposes a devastating interruption to everyday life. Full restoration of natural arm control requires the ability to simultaneously control multiple degrees of freedom of the prosthetic arm and maintain that control over an extended period of time. Current clinically available myoelectric prostheses do not provide simultaneous control or consistency for transradial amputees. To address this issue, we have implemented a standard Kalman filter for continuous hand control using intramuscular electromyography (EMG) from both regenerative peripheral nerve interfaces (RPNI) and an intact muscle within non-human primates. Seven RPNIs and one intact muscle were implanted with indwelling bipolar intramuscular electrodes in two rhesus macaques. Following recuperations, function-specific EMG signals were recorded and then fed through the Kalman filter during a hand-movement behavioral task to continuously predict the monkey's finger position. We were able to reconstruct continuous finger movement offline with an average correlation of and a root mean squared error (RMSE) of 0.12 between actual and predicted position from two macaques. This finger movement prediction was also performed in real time to enable closed-loop neural control of a virtual hand. Compared with physical hand control, neural control performance was slightly slower but maintained an average target hit success rate of 96.70%. Recalibration longevity measurements maintained consistent average correlation over time but had a significant change in RMSE ( ). Additionally, extracted single units varied in amplitude by a factor of +18.65% and -25.85% compared with its mean. This is the first demonstration of chronic indwelling electrodes being used for continuous position control via the Kalman filter. Combining these analyses with our novel peripheral nerve interface, we believe that this demonstrates an important step in providing patients with more naturalistic control of their prosthetic limbs.
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http://dx.doi.org/10.1109/TNSRE.2017.2772961DOI Listing
February 2018

Advancing the Certified in Public Health Examination: A Job Task Analysis.

Public Health Rep 2017 Jul/Aug;132(4):518-523. Epub 2017 Jun 22.

6 Center for Education Testing and Evaluation, University of Kansas, Kansas City, KS, USA.

Objectives: In 2014, the National Board of Public Health Examiners performed a job task analysis (JTA) to revise the Certified in Public Health (CPH) examination. The objectives of this study were to describe the development, administration, and results of the JTA survey; to present an analysis of the survey results; and to review the implications of this first-ever public health JTA.

Methods: An advisory committee of public health professionals developed a list of 200 public health job tasks categorized into 10 work domains. The list of tasks was incorporated into a web-based survey, and a snowball sample of public health professionals provided 4850 usable responses. Respondents rated job tasks as essential (4), very important (3), important (2), not very important (1), and never performed (0).

Results: The mean task importance ratings ranged from 2.61 to 3.01 (important to very important). The highest mean ratings were for tasks in the ethics domain (mean rating, 3.01). Respondents ranked 10 of the 200 tasks as the most important, with mean task rankings ranging from 2.98 to 3.39. We found subtle differences between male and female respondents and between master of public health and doctor of public health respondents in their rankings.

Conclusion: The JTA established a set of job tasks in 10 public health work domains, and the results provided a foundation for refining the CPH examination. Additional steps are needed to further modify the content outline of the examination. An empirical assessment of public health job tasks, using methods such as principal components analysis, may provide additional insight.
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http://dx.doi.org/10.1177/0033354917710015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507425PMC
July 2017

Robust tactile sensory responses in finger area of primate motor cortex relevant to prosthetic control.

J Neural Eng 2017 08;14(4):046016

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States of America.

Objective: Challenges in improving the performance of dexterous upper-limb brain-machine interfaces (BMIs) have prompted renewed interest in quantifying the amount and type of sensory information naturally encoded in the primary motor cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to tactile stimulation, as well as passive and active movement of the limbs. However, recent work in this area has focused primarily on proprioception. Here we examined instead how tactile somatosensation of the hand and fingers is represented in M1.

Approach: We recorded multi- and single units and thresholded neural activity from macaque M1 while gently brushing individual finger pads at 2 Hz. We also recorded broadband neural activity from electrocorticogram (ECoG) grids placed on human motor cortex, while applying the same tactile stimulus.

Main Results: Units displaying significant differences in firing rates between individual fingers (p  <  0.05) represented up to 76.7% of sorted multiunits across four monkeys. After normalizing by the number of channels with significant motor finger responses, the percentage of electrodes with significant tactile responses was 74.9%  ±  24.7%. No somatotopic organization of finger preference was obvious across cortex, but many units exhibited cosine-like tuning across multiple digits. Sufficient sensory information was present in M1 to correctly decode stimulus position from multiunit activity above chance levels in all monkeys, and also from ECoG gamma power in two human subjects.

Significance: These results provide some explanation for difficulties experienced by motor decoders in clinical trials of cortically controlled prosthetic hands, as well as the general problem of disentangling motor and sensory signals in primate motor cortex during dextrous tasks. Additionally, examination of unit tuning during tactile and proprioceptive inputs indicates cells are often tuned differently in different contexts, reinforcing the need for continued refinement of BMI training and decoding approaches to closed-loop BMI systems for dexterous grasping.
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http://dx.doi.org/10.1088/1741-2552/aa7329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734857PMC
August 2017

Effect of sampling rate and filter settings on High Frequency Oscillation detections.

Clin Neurophysiol 2016 09 15;127(9):3042-3050. Epub 2016 Jul 15.

Department of Neurology, University of Michigan, MI, USA; Department of Biomedical Engineering, University of Michigan, MI, USA. Electronic address:

Objective: High Frequency Oscillations (HFOs) are being studied as a biomarker of epilepsy, yet it is unknown how various acquisition parameters at different centers affect detection and analysis of HFOs. This paper specifically quantifies effects of sampling rate (FS) and anti-aliasing filter (AAF) positions on automated HFO detection.

Methods: HFOs were detected on intracranial EEG recordings (17 patients) with 5kHz FS. HFO detection was repeated on downsampled and/or filtered copies of the EEG data, mimicking sampling rates and low-pass filter settings of various acquisition equipment. For each setting, we compared the HFO detection sensitivity, HFO features, and ability to identify the ictal onset zone.

Results: The relative sensitivity remained above 80% for either FS ⩾2kHz or AAF ⩾500Hz. HFO feature distributions were consistent (AUROC<0.7) down to 1kHz FS or 200Hz AAF. HFO rate successfully identified ictal onset zone over most settings. HFO peak frequency was highly variable under most parameters (Spearman correlation<0.5).

Conclusions: We recommend at least FS ⩾2kHz and AAF ⩾500Hz to detect HFOs. Additionally, HFO peak frequency is not robust at any setting: the same HFO event can be variably classified either as a ripple (<200Hz) or fast ripple (>250Hz) under different acquisition settings.

Significance: These results inform clinical centers on requirements to analyze HFO rates and features.
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http://dx.doi.org/10.1016/j.clinph.2016.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980189PMC
September 2016

Disruption of corticocortical information transfer during ketamine anesthesia in the primate brain.

Neuroimage 2016 07 16;134:459-465. Epub 2016 Apr 16.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, 48109.

The neural mechanisms of anesthetic-induced unconsciousness have yet to be fully elucidated, in part because of the diverse molecular targets of anesthetic agents. We demonstrate, using intracortical recordings in macaque monkeys, that information transfer between structurally connected cortical regions is disrupted during ketamine anesthesia, despite preserved primary sensory representation. Furthermore, transfer entropy, an information-theoretic measure of directed connectivity, decreases significantly between neuronal units in the anesthetized state. This is the first direct demonstration of a general anesthetic disrupting corticocortical information transfer in the primate brain. Given past studies showing that more commonly used GABAergic drugs inhibit surrogate measures of cortical communication, this finding suggests the potential for a common network-level mechanism of anesthetic-induced unconsciousness.
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http://dx.doi.org/10.1016/j.neuroimage.2016.04.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912854PMC
July 2016

Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates.

J Neural Eng 2016 Feb 14;13(1):016010. Epub 2015 Dec 14.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.

Objective: We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model.

Approach: A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis.

Main Results: From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 μV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude.

Significance: This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the recording site-tissue interface rather than elimination of the glial scar.
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http://dx.doi.org/10.1088/1741-2560/13/1/016010DOI Listing
February 2016

Enabling Low-Power, Multi-Modal Neural Interfaces Through a Common, Low-Bandwidth Feature Space.

IEEE Trans Neural Syst Rehabil Eng 2016 05 20;24(5):521-31. Epub 2015 Nov 20.

Brain-Machine Interfaces (BMIs) have shown great potential for generating prosthetic control signals. Translating BMIs into the clinic requires fully implantable, wireless systems; however, current solutions have high power requirements which limit their usability. Lowering this power consumption typically limits the system to a single neural modality, or signal type, and thus to a relatively small clinical market. Here, we address both of these issues by investigating the use of signal power in a single narrow frequency band as a decoding feature for extracting information from electrocorticographic (ECoG), electromyographic (EMG), and intracortical neural data. We have designed and tested the Multi-modal Implantable Neural Interface (MINI), a wireless recording system which extracts and transmits signal power in a single, configurable frequency band. In prerecorded datasets, we used the MINI to explore low frequency signal features and any resulting tradeoff between power savings and decoding performance losses. When processing intracortical data, the MINI achieved a power consumption 89.7% less than a more typical system designed to extract action potential waveforms. When processing ECoG and EMG data, the MINI achieved similar power reductions of 62.7% and 78.8%. At the same time, using the single signal feature extracted by the MINI, we were able to decode all three modalities with less than a 9% drop in accuracy relative to using high-bandwidth, modality-specific signal features. We believe this system architecture can be used to produce a viable, cost-effective, clinical BMI.
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http://dx.doi.org/10.1109/TNSRE.2015.2501752DOI Listing
May 2016

Universal automated high frequency oscillation detector for real-time, long term EEG.

Clin Neurophysiol 2016 Feb 22;127(2):1057-1066. Epub 2015 Jul 22.

Department of Neurology, University of Michigan, USA; Department of Biomedical Engineering, University of Michigan, USA. Electronic address:

Objective: Interictal high frequency oscillations (HFOs) in intracranial EEG are a potential biomarker of epilepsy, but current automated HFO detectors require human review to remove artifacts. Our objective is to automatically redact false HFO detections, facilitating clinical use of interictal HFOs.

Methods: Intracranial EEG data from 23 patients were processed with automated detectors of HFOs and artifacts. HFOs not concurrent with artifacts were labeled quality HFOs (qHFOs). Methods were validated by human review on a subset of 2000 events. The correlation of qHFO rates with the seizure onset zone (SOZ) was assessed via (1) a retrospective asymmetry measure and (2) a novel quasi-prospective algorithm to identify SOZ.

Results: Human review estimated that less than 12% of qHFOs are artifacts, whereas 78.5% of redacted HFOs are artifacts. The qHFO rate was more correlated with SOZ (p=0.020, Wilcoxon signed rank test) and resected volume (p=0.0037) than baseline detections. Using qHFOs, our algorithm was able to determine SOZ in 60% of the ILAE Class I patients, with all algorithmically-determined SOZs fully within the resected volumes.

Conclusions: The algorithm reduced false-positive HFO detections, improving the precision of the HFO-biomarker.

Significance: These methods provide a feasible strategy for HFO detection in real-time, continuous EEG with minimal human monitoring of data quality.
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http://dx.doi.org/10.1016/j.clinph.2015.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723299PMC
February 2016

Comparison of spike sorting and thresholding of voltage waveforms for intracortical brain-machine interface performance.

J Neural Eng 2015 Feb 11;12(1):016009. Epub 2014 Dec 11.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.

Objective: For intracortical brain-machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials ('spikes') requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials.

Approach: We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of Gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position.

Main Results: We found the highest performance for thresholding when placing a threshold between -3 and -4.5 × Vrms. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data were thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded.

Significance: For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated.
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http://dx.doi.org/10.1088/1741-2560/12/1/016009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332592PMC
February 2015