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Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson’s Disease Using Bidirectional Deep-Brain-Computer Interfaces



In Press

Modulation of beta bursts in subthalamic sensorimotor circuits predicts improvement in bradykinesia. Kehnemouyi, Y.M.*, Wilkins, K.B.*, Anidi, C.M., Anderson, R.W., Afzal, M.F., Bronte-Stewart, H.M. Brain. (In Press)

Clinicians must adjust deep brain stimulation (DBS) parameters for people with Parkinson’s disease based on time-intensive, empirical, and subjective assessments of motor behavior, which presents a critical unmet need for a biomarker that would enable more precise, personalized adjustments of DBS using real-time biomarker feedback in freely moving individuals. The results of this study solve this unmet need by demonstrating for the first time the interdependence of precise location of neuromodulation of sensorimotor networks, optimal restoration of neural signaling and improvement in movement during high frequency subthalamic nucleus (STN) DBS. These results provide valuable insight into the mechanism of STN DBS in Parkinson’s disease in that STN DBS-related improvements in movement are related to the reduction in the beta oscillopathy within the sensorimotor STN. With the advent of commercially available sensing neurostimulators such as the Medtronic Percept PC™ system, these results demonstrate the feasibility and provide the necessary basis for physicians to track patient-specific beta oscillopathies combined with lead locations as a biomarker to adjust clinical neurostimulator settings. Additionally, the development of next generation sensing neurostimulators such as the Summit RC+S™ now allows for the implementation of control policy algorithms based around movement band burst duration driven closed-loop DBS in freely moving people with Parkinson’s disease.

Publications

A validated measure of rigidity in Parkinson's disease using alternating finger tapping on an engineered keyboard. Trager MH, Wilkins KB, Koop MM, Bronte-Stewart H. Parkinsonism Relat Disord. 2020 Nov 2;81:161-164. doi: 10.1016/j.parkreldis.2020.10.047. Online ahead of print.PMID: 33157435  

Quantitative Digitography Measures Fine Motor Disturbances in Chronically Treated HIV Similar to Parkinson's Disease. Prabhakar V, Martin T, Müller-Oehring EM, Goodcase R, Schulte T, Poston KL, Brontë-Stewart HM. Front Aging Neurosci. 2020 Oct 7;12:539598. doi: 10.3389/fnagi.2020.539598. eCollection 2020. PMID: 33132893  

Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson's Disease. O'Day JJ, Kehnemouyi YM, Petrucci MN, Anderson RW, Herron JA, Bronte-Stewart HM. Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:3612-3616. doi: 10.1109/EMBC44109.2020.9176638. PMID: 33018784

A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson's Disease. Petrucci MN, Anderson RW, O'Day JJ, Kehnemouyi YM, Herron JA, Bronte-Stewart HM. Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:3617-3620. doi: 10.1109/EMBC44109.2020.9176196. PMID: 33018785

Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson's Disease Using Bidirectional Deep-Brain-Computer Interfaces. Bronte-Stewart HM, Petrucci MN, O'Day JJ, Afzal MF, Parker JE, Kehnemouyi YM, Wilkins KB, Orthlieb GC, Hoffman SL. Front Hum Neurosci. 2020 Aug 31;14:353. doi: 10.3389/fnhum.2020.00353. eCollection 2020. PMID: 33061899

Gait variability is linked to the atrophy of the Nucleus Basalis of Meynert and is resistant to STN DBS in Parkinson's disease. Wilkins KB, Parker JE, Bronte-Stewart HM. Neurobiol Dis. 2020 Oct 9:105134. doi: 10.1016/j.nbd.2020.105134. Online ahead of print. PMID: 33045357

The turning and barrier course reveals gait parameters for detecting freezing of gait and measuring the efficacy of deep brain stimulation. O'Day J, Syrkin-Nikolau J, Anidi C, Kidzinski L, Delp S, Bronte-Stewart H. PLoS One. 2020 Apr 29;15(4):e0231984. doi: 10.1371/journal.pone.0231984. eCollection 2020. PMID: 32348346 Free PMC article.

Neural closed-loop deep brain stimulation for freezing of gait. Petrucci MN, Neuville RS, Afzal MF, Velisar Anca, Anidi CM, Anderson RW, Parker JE, O'Day JJ, Wilkins KB, Bronte-Stewart HM. Brain Stimul. 2020 Jul 4;S1935-861X(20)30136-4. doi: 10.1016/j.brs.2020.06.018. Online ahead of print

Safety of Plasma Infusions in Parkinson's Disease. Parker, J.E., Martinez, A., Deutsch, G.K., Prabhakar, V., Lising, M., Kapphahn, K.I., Anidi, C.M., Neuville, R., Coburn, M., Shah, N. and Bronte‐Stewart, H.M. Mov Disord. 2020 doi:10.1002/mds.28198

A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson’s Disease. Petrucci, M.N., Anderson, R.W., O’Day, J.J., Kehnemouyi, Y.M., Herron, J.A., Bronte-Stewart, H.M.  42nd Annual International Conferences of the IEEE Engineering in Medicine and Biology SocietyMontreal, Quebec, Canada, July 20-24 2020

Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson’s Disease. O’Day, J.J., Kehnemouyi, Y.M., Petrucci, M.N., Anderson, R.W., Herron, J.A., Bronte-Stewart, H.M. 42nd Annual International Conferences of the IEEE Engineering in Medicine and Biology SocietyMontreal, Quebec, Canada, July 20-24 2020

Pathological Beta Burst Dynamics are Conserved Across Different Movements in Parkinson’s Disease. Neuville, R.S., Anderson, R.W., Petrucci, M.N., Parker, J.E., Wilkins, K.B., Velisar, A., Bronte-Stewart, H.M. (2020)  MedRxiv 

A Novel Method for Calculating Beta Band Burst Durations in Parkinson’s Disease Using a Physiological Baseline.  Anderson, R.W., Neuville, R.S., Kehnemouyi, Y.M., Anidi, C.M., Petrucci, M.N., Parker, J.E., Velisar, A., Bronte-Stewart, H.M., J Neurosci Methods. 2020 Jun 18;343:108811.doi: 10.1016/j.jneumeth.2020.108811.

Neural Closed Loop Deep Brain Stimulation for Freezing of Gait. Petrucci, M.N., Neuville, R.N., Afzal, M.F., Velisar, A., Anidi, C.M., Anderson, R.W., Parker, J.E., O’Day, J.J., Wilkins, K.B., Bronte-Stewart, H.M. (2019) MedRxiv 

The turning and barrier course reveals gait parameters for detecting freezing of gait and measuring the efficacy of deep brain stimulation. O'Day J, Syrkin-Nikolau J, Anidi C, Kidzinski L, Delp S, Bronte-Stewart H. (2020). PLoS One. 29;15(4):e0231984. doi: 10.1371/journal.pone.0231984. eCollection 2020.

Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients.  Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H. Brain Stimul. 2019 Feb 25.

Neuromodulation targets pathological not physiological beta bursts during gait in Parkinson's disease. Anidi C, O'Day J, Anderson RW, Afzal MF, Syrkin-Nikolau J, Velisar A, Bronte-Stewart H. (2018). Neurobiol. Dis. 120, 107-117.

Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson’s disease. Trager, M.H., Koop, M.M., Velisar, A., Blumenfeld, Z., Nikolau, J.S., Quinn, E.J., Martin, T., and Bronte-Stewart, H. (2016). Neurobiol. Dis. 96, 22–30.

Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. Malekmohammadi M, Herron J, Velisar A, Blumenfeld Z, Trager MH, Chizeck HJ, Brontë-Stewart H Mov Disord. 2016 Mar;31(3):426-8. doi: 10.1002/mds.26482. Epub 2016 Jan 27.

Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials. Houston B, Blumenfeld Z, Quinn E, Bronte-Stewart H, Chizeck H. Conf Proc IEEE Eng Med Biol Soc. 2015;2015:3427-31. doi: 10.1109/EMBC.2015.7319129.

High Frequency Deep Brain Stimulation and Neural Rhythms in Parkinson's Disease.
Blumenfeld Z, Brontë-Stewart H.  Neuropsychol Rev. 2015 Dec;25(4):384-97. doi: 10.1007/s11065-015-9308-7. Epub 2015 Nov 25

Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation. Quinn, E. J., Blumenfeld, Z., Velisar, A., Koop, M. M., Shreve, L. A., Trager, M. H., Hill, B. C., Kilbane, C., Henderson, J. M. and Brontë-Stewart, H. (2015),  Mov. Disord. doi: 10.1002/mds.26376

Arrhythmokinesis is evident during unimanual not bimanual finger tapping in Parkinson’s disease
Trager MH, Velisar A, Miller Koop M, Shreve LA, Quinn EJ, Bronte-Stewart H.  Journal of Clinical Movement Disorders 2015, 2:8  doi:10.1186/s40734-015-0019-2

Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease
Blumenfeld Z, Velisar A, Miller Koop M, Hill BC, Shreve LA, Quinn EJ, Kilbane C, Yu H, Henderson JM, Brontë-Stewart H. PLoS One. 2015 Mar 25;10(3):e0121067. doi: 10.1371/journal.pone.0121067. eCollection 2015.

The effect of medication and the role of postural instability in different components of freezing of gait (FOG).
Natel J, Bronte-Stewart H. Parkinsonism Relat Disord. 2014

Perceptual errors increase with movement duration and may contribute to hypokinesia in Parkinson's disease
Koop MM, Hill BC, Bronte-Stewart HM. Neuroscience. 2013

Resting beta hypersynchrony in secondary dystonia and its suppression during pallidal deep brain stimulation in DYT3+ Lubag dystonia.
Whitmer D, de Solages C, Hill BC, Yu H, Bronte-Stewart H. Neuromodulation. 2013

Improved efficacy of temporally non-regular deep brain stimulation in Parkinson's disease.
Broker DT, Swan BD, Turner DA, Gross RE, Tatter SB, Koop MM, Bronte-Stewart H, Grill WM. Exp Neurol 2013

Deficits in visuospatial processing contribute to quantitative measures of freezing of gait in Parkinson's disease
Nantel J, McDonald JC, Tan S, Bronte-Stewart H. Neuroscience. 2012: 221 151-6

Effect of medication and STN-DBS on postural control in subjects with Parkinson's disease
Nantel J, McDonald JC, Bronte-Stewart H. Parkinsonism Relat Disord. 2012; 18 (3): 285-9

High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson's disease
Whitmer D, de Solages C, Hill B, Yu H, Henderson JM, Bronte-Stewart H. Front Hum Neurosci. 2012: 6 155

New drugs/devices. Deep brain stimulation (DBS)
Bronte-Stewart HM, Neurology Clin Pract. 2012; 12 (2): 67 - 71

Deep Brain Stimulation for Parkinson's Disease. An expert consensus and review of key issues
Bronstein JM, Tagliati M., Alterman RL, the Deep Brain Study group. Archives of Neurology. 2011; 68 (2): 165

Deep brain stimulation in "on"-state Parkinson hyperpyrexia
Klepitskaya O, Cole W, Henderson J, Bronte-Stewart H. Neurology. 2011; 76 (7 Suppl 2): S69-71

Effect of medication and STN-DBS on postural control in subjects with Parkinson's disease
Nantel J, McDonald JC, Bronte-Stewart H. Parkinsonism Relat Disord. 2011

Human subthalamic neuron spiking exhibits subtle responses to sedatives
Maciver MB, Bronte-Stewart HM, Henderson JM, Jaffe RA, Brock-Utne JG. Anesthesiology. 2011; 115 (2): 254-64

Immediate versus delayed switch from levodopa/carbidopa to levodopa/carbidopa/entacapone: effects on motor function and quality of life in patients with Parkinson's disease with end-of-dose wearing off
Lew MF, Somogyi M, McCague K, Welsh M and Lce Qol Study group. Int J Neurosci. 2011; 121 (11): 605 - 13

Inclusion and exclusion criteria for DBS in dystonia
Bronte-Stewart H, Taira T, Valldeoriola F, Merello M, Marks WJ, Albanese A, Bressman S, Moro E. Mov Disord. 2011: 26 Suppl 1 S5-16

Maximal subthalamic beta hypersynchrony of the local field potential in Parkinson's disease is located in the central region of the nucleus
de Solages C, Hill BC, Yu H, Henderson JM, Bronte-Stewart H. J Neurol Neurosurg Psychiatry. 2011; 82 (12): 1387-9

Repetitive stepping in place identifies and measures freezing episodes in subjects with Parkinson's disease
Nantel J, de Solages C, Bronte-Stewart H. Gait Posture. 2011; 34 (3): 329-33

Bilateral symmetry and coherence of subthalamic nuclei beta band activity in Parkinson's disease
de Solages C, Hill BC, Koop MM, Henderson JM, Bronte-Stewart H. Exp Neurol. 2010; 221 (1): 260-6

Clinical motor outcome of bilateral subthalamic nucleus deep-brain stimulation for Parkinson's disease using image-guided frameless stereotaxy
Brontë-Stewart H, Louie S, Batya S, Henderson JM. Neurosurgery. 2010; 67 (4): 1088-93; discussion 1093

Socioeconomic Trends in Deep Brain Stimulation (DBS) Surgery
Lad SP, Kalanithi PS, Patil CG, Itthimathin P, Batya S, Bronte-Stewart H, Boakye M, Henderson JM. Neuromodulation. 2010; 13 (3): 182-6

A comparison of treatment thresholds in two large Parkinson's disease clinical trial cohorts
Marras C, Lang AE, Eberly SW, Oakes D, Fahn S, Schwid SR, Hyson C, Shoulson I; Parkinson Study Group DATATOP and PRECEPT investigators. Movement Disorders. 2009; 24 (16): 2370 - 8

A longitudinal program for biomarker development in Parkinson's disease: a feasibility study
Ravina B, Tanner C, Dieuliis D, Eberly S, Flagg E, Galpern WR, Fahn S, Goetz CG, Grate S, Kurlan R, Lang AE, Marek K, Kieburtz K, Oakes D, Elliott R, Shoulson I; Parkinson Study Group LABS-PD Investigators. Movement Disorders. 2009; 24 (14): 2081 - 90

Excessive postural sway and the risk of falls at different stages of Parkinson's disease
Frenklach A, Louie S, Koop MM, Bronte-Stewart H. Mov Disord. 2009; 24 (3): 377-85