Name: Procedure for Concurrent At-Home Symptom Reports and Neural Recordings
Uploaded: 2023-07-07T12:40:00
Description: Watch this Scientific Journal Video about Procedure for Concurrent At-Home Symptom Reports and Neural Recordings at JoVE.com

procedure for concurrent at-home symptom reports and neural recordings

주요 우울증 치료를 위한 뇌심부자극술

Major depressive disorder (MDD) is a neuropsychiatric disease characterized by network-level aberrant activity and connectivity1. The disease manifests a variety of symptoms that vary across individuals, fluctuate over time, and may stem from different neural circuits2,3. Approximately 30% of individuals with MDD are refractory to standard-of-care treatments4, highlighting a need for new approaches.
Deep brain stimulation (DBS) is a form of neuromodulation in which electrical current is delivered to targeted areas of the brain with the goal of modulating the activity. DBS for the treatment of MDD has been very successful in some applications5,6, but has also failed to replicate in larger studies7,8. All of the cited studies employed open-loop stimulation9, in which the delivery of putative therapeutic stimulation was continuous with fixed parameters. In contrast, closed-loop stimulation delivers stimulation based on a programmed biomarker or neural activity pattern associated with the symptom state10. There are two main implementations of closed-loop stimulation: responsive stimulation and adaptive stimulation11. Responsive stimulation delivers bursts of stimulation with constant parameters (e.g., frequency, amplitude, pulse width) when the programmed criteria are met. With adaptive stimulation, stimulation parameters dynamically change as a function of the measured biomarker, according to the algorithm, which may have multiple fix points or automated continuous adjustment. Stimulation can be continuous or intermittent with adaptive stimulation. Adaptive stimulation has shown superior efficacy to open-loop stimulation in controlling symptoms of Parkinson&#39;s disease12. Responsive neurostimulation for epilepsy13 is Food and Drug Administration (FDA)-approved, while early investigations of responsive stimulation for MDD14 and adaptive stimulation for Tourette syndrome15 and essential tremor16 also show therapeutic benefit.
To implement closed-loop stimulation, a physiological signal must be selected and tracked to inform when stimulation should be delivered. This feedback is the key difference between open-loop and closed-loop stimulation and is realized by selecting a biomarker. This protocol provides a procedure for determining a personalized biomarker according to the constellation of symptoms experienced by a given individual. Future meta-analyses across patients will reveal if there are common biomarkers across individuals or if the heterogeneous presentation of MDD symptoms and the underlying circuitry necessitates a personalized approach17,18. Using DBS devices capable of both sensing neural activity and delivering electrical stimulation allows for both the discovery of this biomarker and the subsequent implementation of closed-loop neuromodulation. This approach presupposes a close temporal relationship between neural activity and specific symptom states and may not be applicable for all indications or symptoms.
While indications such as Parkinson&#39;s disease and essential tremor have symptoms that can be measured using peripheral sensors (e.g., tremor, rigidity), symptoms of MDD are typically reported by the patient or assessed by a clinician using standardized questions and observation. In the context of amassing sufficient data to calculate a personalized biomarker, clinician assessments are not practical, and thus patient reports of symptoms through rating scales are used. Such scales include visual analog scales of depression (VAS-D), anxiety (VAS-A), and energy (VAS-E)19, and the six-question form of the Hamilton Depression Rating Scale (HAMD-6)20. Concurrent recordings of neural activity and completion of these self-report symptom ratings provide a paired dataset that can be used to look at relationships between spectral features of the neural signal related to or predictive of high-symptom states.
Computational approaches, such as state-space modeling, can be used to uncover relationships between symptom states and neural features. Graph theoretic methods are attractive for characterizing a state-space21 because they enable the discovery of states over different timescales by explicitly modeling the temporal proximity between measurements22. A symptom state-space model identifies periods of time in which there is a common phenotype of the patient&#39;s symptoms and may pinpoint symptom sub-states in which the ratings on specific dimensions of the patient&#39;s depression differ based on the environment or context. A closed-loop approach relies on the detection of symptom states based on underlying brain activity. Machine learning classification is a final step that helps identify a combination of statistical features derived from brain activity signals that best distinguishes two or more symptom states14. This two-stage approach explains the variability in a patient&#39;s symptoms over time and links systematic patterns of symptom variation to brain activity.
The present protocol utilizes the NeuroPace Responsive Neurostimulation System (RNS)13,23. Procedures to determine the optimal stimulation site(s) and parameters are outside the scope of this protocol. However, the stimulation capabilities of a given device are important to consider when designing closed-loop neurostimulation. For the device used in this protocol, stimulation is current-controlled and delivered between the anode(s) and cathode(s). One or more electrode contacts or the Can (implantable neurostimulator [INS]) can be selected as the anode(s) or cathode(s). Stimulation frequency (1-333.3 Hz), amplitude (0-12 mA), pulse width (40-1000 &#181;s per phase), and duration (10-5000 ms, per stim) are all pre-programmed. The prior parameters can be set independently for up to five stimulation therapies; these therapies are delivered sequentially if the detection criteria continue to be met. It is not possible to deliver multiple stimulation waveforms simultaneously (e.g., one cannot deliver two different frequencies of stimulation concurrently). The stimulation waveform is a symmetric biphasic rectangular wave and cannot be changed.

저자 스포트라이트: 우울증 치료에서 폐쇄 루프 심부 뇌 자극의 치료 이점 

주요 우울 장애의 바이오마커 중심의 맞춤형 치료를 위한 폐쇄 루프 신경자극

We are assessing the therapeutic benefit of closed-loop personalized deep brain stimulation for the treatment of major depressive disorder. This protocol outlines how to identify a personalized neural biomarker that is correlated with symptom severity, and then program an implanted neurostimulator to administer stimulation using that biomarker. Prior applications of deep brain stimulation for depression used continuous stimulation, which was always on, regardless of symptom status.This protocol describes using closed-loop stimulation in which we only deliver stimulation during high symptom states. Continued work to identify biomarkers for control of closed-loop stimulation will facilitate an approach where we can target the unique time courses of different symptoms.

Watch this Scientific Journal Video about Procedure for Concurrent At-Home Symptom Reports and Neural Recordings at JoVE.com

Procedure for Concurrent At-Home Symptom Reports and Neural Recordings  

동시 재택 증상 보고 및 신경 기록 절차

환자에게 원격 모니터와 지팡이, 자석 및 설문 조사를 완료하기 위한 장치를 포함한 장비를 설정하도록 지시합니다. 원격 모니터를 켜고 지팡이를 사용하여 장치를 조사합니다. 그런 다음 마지막 심문 이후의 전기 피질 검사 기록을 원격 모니터에 다운로드합니다.이식형 신경자극기 위로 자석을 문지르면 자석 기록이 시작됩니다. 타이머를 시작하고 이전에 생성된 고유한 REDCap URL을 사용하여 증상 설문 조사를 완료합니다. 4분이 경과하거나 환자가 설문 조사를 완료한 후 중 더 긴 시간 동안 환자는 이식형 신경자극기 위로 자석을 다시 스와이프하여 다른 기록을 트리거합니다. 최소 80초 후 지팡이를 사용하여 장치를 다시 조사하고 두 개의 자석 스와이프에서 원격 모니터로 데이터를 전송합니다. 적어도 하루에 한 번, 이더넷을 사용하여 원격 모니터를 인터넷에 연결하고 원격 모니터에서 데이터 전송 및 동기화를 선택하여 수집된 데이터를 클라우드로 보냅니다.

Research

JoVE Journal

Neuroscience

Procedure for Concurrent At-Home Symptom Reports and Neural Recordings

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major ...