Identification of a personalized intracranial biomarker of depression and response to DBS therapy

Frank, Adam Charles; Larson, Paul; Norbu, Tenzin; Lee, Anthony T; Lee, A Moses

doi:10.1016/j.brs.2021.06.009

Cited by 10 publications

(10 citation statements)

References 11 publications

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“…Previous studies searching for a physiological biomarker have primarily focused on periodic, oscillatory data, eliminating the aperiodic component by normalizing power band signals to a baseline period for trial-level analyses in task-based designs 32 , or by regressing out the negative linear slope with techniques such as IRASA 33 and FOOOF 34 . These studies have identified potential biomarkers for treatment response and mood in various frequency bands (theta 11 , alpha 9,10 , beta 7,9 , high and low gamma 7,9,35 ) across affective regions. However, the wide variety of reported frequency bands may all be driven by a common underlying phenomenon – a change in the power law slope across all frequency bands.…”

Section: Discussionmentioning

confidence: 99%

Aperiodic neural activity is a biomarker for depression severity

Hacker,

Mocchi,

Xiao

et al. 2023

Preprint

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A reliable physiological biomarker for Major Depressive Disorder (MDD) is necessary to improve treatment success rates by shoring up variability in outcome measures. In this study, we establish a passive biomarker that tracks with changes in mood on the order of minutes to hours. We record from intracranial electrodes implanted deep in the brain – a surgical setting providing exquisite temporal and spatial sensitivity to detect this relationship in a difficult-to-measure brain area, the ventromedial prefrontal cortex (VMPFC). The aperiodic slope of the power spectral density captures the balance of activity across all frequency bands and is construed as a putative proxy for excitatory/inhibitory balance in the brain. This study demonstrates how shifts in aperiodic slope correlate with depression severity in a clinical trial of deep brain stimulation for treatment-resistant depression (TRD). The correlation between depression severity scores and aperiodic slope is significant in N=5 subjects, indicating that flatter (less negative) slopes correspond to reduced depression severity, especially in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient response to MDD treatment, facilitating individualized therapies in both intracranial and non-invasive monitoring scenarios.One sentence summaryThe aperiodic component of the power spectral density robustly tracks depression severity on the order of minutes to hours.

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Section: Discussionmentioning

confidence: 99%

Aperiodic neural activity is a biomarker for depression severity

Hacker,

Mocchi,

Xiao

et al. 2023

Preprint

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“…For example, a memory prosthesis described by Kahana [ 57 - 59 ] and closed-loop spinal cord stimulation to treat chronic pain [ 60 ] also rely on state-dependent, field-potential based algorithms and stimulation, where the bi-directional elements are required. Similarly for neuropsychiatry, a neuromodulation depression system might also benefit from a full-duplex approach [ 35 , 36 ]. In summary, the methods and results described here are useful for a broader range of applications than classical DBS for movement disorders, where field potentials might be useful as the input.…”

Section: Discussionmentioning

confidence: 99%

“…At this time, full-duplex communication is expected to be the method preferred for most movement disorders [ 6 , 20 , 24 , 33 , 34 ]. Some recent studies of closed-loop DBS for psychiatric disorders [ 35 , 36 ] and for refractory epilepsy [ 37 , 38 ] have also explored the use of full duplex paradigms. Therefore, the pathophysiology of the disease under study, such as minimum ranges of detectable neural signals and acceptable time latencies between sensing and stimulation responses set the key specifications for the device ( supplementary material , table 1 available online at stacks.iop.org/JNE/19/026025/mmedia ).…”

Section: Introductionmentioning

confidence: 99%

Concurrent stimulation and sensing in bi-directional brain interfaces: a multi-site translational experience

et al. 2022

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Objective: To provide a design analysis and guidance framework for the implementation of concurrent stimulation and sensing during adaptive deep brain stimulation (aDBS) with particular emphasis on artifact mitigations. Approach: We defined a general architecture of feedback-enabled devices, identified key components in the signal chain which might result in unwanted artifacts and proposed methods that might ultimately enable improved aDBS therapies. We gathered data from research subjects chronically-implanted with an investigational aDBS system, Summit RC+S, to characterize and explore artifact mitigations arising from concurrent stimulation and sensing. We then used a prototype investigational implantable device, DyNeuMo, and a bench-setup that accounts for tissue-electrode properties, to confirm our observations and verify mitigations. The strategies to reduce transient stimulation artifacts and improve performance during aDBS were confirmed in a chronic implant using updated configuration settings. Main results: We derived and validated a “checklist” of configuration settings to improve system performance and areas for future device improvement. Key considerations for the configuration include 1) active instead of passive recharge, 2) sense-channel blanking in the amplifier, 3) high-pass filter settings, 4) tissue-electrode impedance mismatch management, 5) time-frequency trade-offs in the classifier, 6) algorithm blanking and transition rate limits. Without proper channel configuration, the aDBS algorithm was susceptible to limit-cycles of oscillating stimulation independent of physiological state. By applying the checklist, we could optimize each block’s performance characteristics within the overall system. With system-level optimization, a ‘fast’ aDBS prototype algorithm was demonstrated to be feasible without reentrant loops, and with noise performance suitable for subcortical brain circuits. Significance: We present a framework to study sources and propose mitigations of artifacts in devices that provide chronic aDBS. This work highlights the trade-offs in performance as novel sensing devices translate to the clinic. Finding the appropriate balance of constraints is imperative for successful translation of aDBS therapies.

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“…DBS in the left ALIC resulted in a broad power increase in the right BNST, including significant increases in low and high gamma power, and an overall improvement of symptoms ( 21 ). Zhang et al reported seven patients underwent Habenula (HB)–DBS surgery and found the LFP asymmetry in the left and right HB.…”

Section: Lfps In Mddmentioning

confidence: 99%

Local field potentials in major depressive and obsessive-compulsive disorder: a frequency-based review

Zhang

Xiong

et al. 2023

Front. Psychiatry

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ObjectivesThe purpose of this paper is to provide a mini-review covering the recent progress in human and animal studies on local field potentials (LFPs) of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD).Materials and methodsPubMed and EMBASE were searched to identify related studies. Inclusion criteria were (1) reported the LFPs on OCD or MDD, (2) published in English, and (3) human or animal studies. Exclusion criteria were (1) review or meta-analysis or other literature types without original data and (2) conference abstract without full text. Descriptive synthesis of data was performed.ResultsEight studies on LFPs of OCD containing 22 patients and 32 rats were included: seven were observational studies with no controls, and one animal study included a randomized and controlled phase. Ten studies on LFPs of MDD containing 71 patients and 52 rats were included: seven were observational studies with no controls, one study with control, and two animal studies included a randomized and controlled phase.ConclusionThe available studies revealed that different frequency bands were associated with specific symptoms. Low frequency activity seemed to be closely related to OCD symptoms, whereas LFPs findings in patients with MDD were more complicated. However, limitations of recent studies restrict the drawing of definite conclusions. Combined with other measures such as Electroencephalogram, Electrocorticography, or Magnetoencephalography and long-term recordings in various physiological states (rest state, sleep state, task state) could help to improve the understanding of potential mechanisms.

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Identification of a personalized intracranial biomarker of depression and response to DBS therapy

Cited by 10 publications

References 11 publications

Aperiodic neural activity is a biomarker for depression severity

Aperiodic neural activity is a biomarker for depression severity

Concurrent stimulation and sensing in bi-directional brain interfaces: a multi-site translational experience

Local field potentials in major depressive and obsessive-compulsive disorder: a frequency-based review

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