Frontal Alpha Asymmetry, a Potential Biomarker for the Effect of Neuromodulation on Brain’s Affective Circuitry—Preliminary Evidence from a Deep Brain Stimulation Study

ABSTRACT:Objective: To systematically evaluate how different deep brain stimulation of the subthalamic nucleus (STN-DBS) amplitude, frequency, and pulse-width electrical parameter settings impact speech intensity, voice quality, and prosody of speech in Parkinson’s disease (PD). Methods: Ten individuals with PD receiving bilateral STN-DBS treatments were seen for three baseline and five treatment visits. The five treatment visits involved an examination of the standard clinical settings as well as manipulation of different combinations of frequency (low, mid, and high), pulse width (low, mid, and high), and voltage (low, mid, and high) of stimulation. Measures of speech intensity, jitter, shimmer, harmonics–noise ratio, semitone standard deviation, and listener ratings of voice quality and prosody were obtained for each STN-DBS manipulation. Results: The combinations of lower frequency, lower pulse width, and higher voltage settings were associated with improved speech outcomes compared to the current standard clinical settings. In addition, decreased total electrical energy delivered to the STN appears to be associated with speech improvements. Conclusions: This study provides preliminary evidence that STN-DBS may be optimized for Parkinson-related problems with voice quality, speech intensity, and prosody of speech.

Download Full-text

Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson’s disease: A potential biomarker for optimal electrode placement

Brain Stimulation ◽

10.1016/j.brs.2020.09.024 ◽

2020 ◽

Vol 13 (6) ◽

pp. 1765-1773

Author(s):

Jennifer C. Andrews ◽

François D. Roy ◽

Fang Ba ◽

Tejas Sankar

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

H Reflex ◽

Electrode Placement ◽

Reflex Pathway ◽

Potential Biomarker ◽

Deep Brain Stimulation Surgery ◽

Deep Brain

Download Full-text

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

Clinical Neurophysiology ◽

10.1016/j.clinph.2020.02.021 ◽

2020 ◽

Vol 131 (6) ◽

pp. 1221-1229

Author(s):

Zachary T. Irwin ◽

Mohammad Z. Awad ◽

Christopher L. Gonzalez ◽

Arie Nakhmani ◽

J.Nicole Bentley ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Side Effects ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Cortical Activity ◽

Potential Biomarker ◽

Deep Brain

Download Full-text

Neural Closed Loop Deep Brain Stimulation for Freezing of Gait

10.1101/19011858 ◽

2019 ◽

Author(s):

Matthew N. Petrucci ◽

Raumin S. Neuville ◽

M. Furqan Afzal ◽

Anca Velisar ◽

Chioma M. Anidi ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Closed Loop ◽

Freezing Of Gait ◽

Control Variable ◽

Field Potential ◽

Preliminary Evidence ◽

Open Loop ◽

Percent Time ◽

Deep Brain

AbstractFreezing of gait (FOG), a devastating symptom of Parkinson’s disease (PD), can be refractory to current treatments such as medication and open-loop deep brain stimulation (olDBS). Recent evidence suggests that closed-loop DBS (clDBS), using beta local field potential power from the subthalamic nucleus (STN) as the control variable, can improve tremor and bradykinesia; however, no study has investigated the use of clDBS for the treatment of FOG. In this study, we provide preliminary evidence that clDBS was superior to olDBS in reducing percent time freezing and in reducing freezing behavior (gait arrhythmicity) in a person with PD and FOG. These findings warrant further investigation into the use of clDBS to treat FOG while also minimizing the total energy delivered to maintain a therapeutic effect.

Download Full-text

Use of Functional MRI to Assess Effects of Deep Brain Stimulation Frequency Changes on Brain Activation in Parkinson Disease

Neurosurgery ◽

10.1093/neuros/nyaa397 ◽

2020 ◽

Author(s):

Marisa DiMarzio ◽

Radhika Madhavan ◽

Ileana Hancu ◽

Eric Fiveland ◽

Julia Prusik ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Magnetic Resonance ◽

Parkinson Disease ◽

Brain Stimulation ◽

Rating Scale ◽

Standard Of Care ◽

Preliminary Evidence ◽

Current Standard ◽

Frequency Changes ◽

Deep Brain

ABSTRACT BACKGROUND Models have been developed for predicting ideal contact and amplitude for subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Pulse-width is generally varied to modulate the size of the energy field produced. Effects of varying frequency in humans have not been systematically evaluated. OBJECTIVE To examine how altered frequencies affect blood oxygen level-dependent activation in PD. METHODS PD subjects with optimized DBS programming underwent functional magnetic resonance imaging (fMRI). Frequency was altered and fMRI scans/Unified Parkinson Disease Rating Scale motor subunit (UPDRS-III) scores were obtained. Analysis using DBS-OFF data was used to determine which regions were activated during DBS-ON. Peak activity utilizing T-values was obtained and compared. RESULTS At clinically optimized settings (n = 14 subjects), thalamic, globus pallidum externa (GPe), and posterior cerebellum activation were present. Activation levels significantly decreased in the thalamus, anterior cerebellum, and the GPe when frequency was decreased (P < .001). Primary somatosensory cortex activation levels significantly decreased when frequency was increased by 30 Hz, but not 60 Hz. Sex, age, disease/DBS duration, and bilaterality did not significantly affect the data. Retrospective analysis of fMRI activation patterns predicted optimal frequency in 11/14 subjects. CONCLUSION We show the first data with fMRI of STN DBS-ON while synchronizing cycling with magnetic resonance scanning. At clinically optimized settings, an fMRI signature of thalamic, GPe, and posterior cerebellum activation was seen. Reducing frequency significantly decreased thalamic, GPe, and anterior cerebellum activation. Current standard-of-care programming can take up to 6 mo using UPDRS-III testing alone. We provide preliminary evidence that using fMRI signature of frequency may have clinical utility and feasibility.

Download Full-text

Deep Brain Stimulation in Huntington’s Disease—Preliminary Evidence on Pathophysiology, Efficacy and Safety

Brain Sciences ◽

10.3390/brainsci6030038 ◽

2016 ◽

Vol 6 (3) ◽

pp. 38 ◽

Cited By ~ 18

Author(s):

Lars Wojtecki ◽

Stefan Groiss ◽

Christian Hartmann ◽

Saskia Elben ◽

Sonja Omlor ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Brain Stimulation ◽

Preliminary Evidence ◽

Efficacy And Safety ◽

Deep Brain

Download Full-text

Differences in functional connectivity profiles as a predictor of response to anterior thalamic nucleus deep brain stimulation for epilepsy: a hypothesis for the mechanism of action and a potential biomarker for outcomes

Neurosurgical FOCUS ◽

10.3171/2018.5.focus18151 ◽

2018 ◽

Vol 45 (2) ◽

pp. E7 ◽

Cited By ~ 19

Author(s):

Erik H. Middlebrooks ◽

Sanjeet S. Grewal ◽

Matthew Stead ◽

Brian N. Lundstrom ◽

Gregory A. Worrell ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Pilot Study ◽

Functional Connectivity ◽

Mechanism Of Action ◽

Brain Stimulation ◽

Default Mode Network ◽

Refractory Epilepsy ◽

Default Mode ◽

Potential Biomarker ◽

Deep Brain

OBJECTIVEDeep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising therapy for refractory epilepsy. Unfortunately, the variability in outcomes from ANT DBS is not fully understood. In this pilot study, the authors assess potential differences in functional connectivity related to the volume of tissue activated (VTA) in ANT DBS responders and nonresponders as a means for better understanding the mechanism of action and potentially improving DBS targeting.METHODSThis retrospective analysis consisted of 6 patients who underwent ANT DBS for refractory epilepsy. Patients were classified as responders (n = 3) if their seizure frequency decreased by at least 50%. The DBS electrodes were localized postoperatively and VTAs were computationally generated based on DBS programming settings. VTAs were used as seed points for resting-state functional MRI connectivity analysis performed using a control dataset. Differences in cortical connectivity to the VTA were assessed between the responder and nonresponder groups.RESULTSThe ANT DBS responders showed greater positive connectivity with the default mode network compared to nonresponders, including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobule, and precuneus. Interestingly, there was also a consistent anticorrelation with the hippocampus seen in responders that was not present in nonresponders.CONCLUSIONSBased on their pilot study, the authors observed that successful ANT DBS in patients with epilepsy produces increased connectivity in the default mode network, which the authors hypothesize increases the threshold for seizure propagation. Additionally, an inhibitory effect on the hippocampus mediated through increased hippocampal γ-aminobutyric acid (GABA) concentration may contribute to seizure suppression. Future studies are planned to confirm these findings.

Download Full-text