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result(s) for
"Zachs, Daniel P."
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Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep
by
Nolan, Michael A.
,
Wang, Karen
,
Weng, Feng-Ju
in
Animals
,
Bacterial Proteins - genetics
,
Bacterial Proteins - metabolism
2015
Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.
Journal Article
Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis
2019
Targeted noninvasive control of the nervous system and end-organs may enable safer and more effective treatment of multiple diseases compared to invasive devices or systemic medications. One target is the cholinergic anti-inflammatory pathway that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis. Here we report that daily noninvasive ultrasound (US) stimulation targeting the spleen significantly reduces disease severity in a mouse model of inflammatory arthritis. Improvements are observed only with specific parameters, in which US can provide both protective and therapeutic effects. Single cell RNA sequencing of splenocytes and experiments in genetically-immunodeficient mice reveal the importance of both T and B cell populations in the anti-inflammatory pathway. These findings demonstrate the potential for US stimulation of the spleen to treat inflammatory diseases.
Modulation of the cholinergic pathway and spleen function can reduce inflammation with invasive implants. Here, the authors show that non-invasive ultrasound stimulation of the spleen reduces disease severity in a mouse model of inflammatory arthritis, partly via altering B and T cell function.
Journal Article
Ultrasound does not activate but can inhibit in vivo mammalian nerves across a wide range of parameters
2022
Ultrasound (US) has been shown to stimulate brain circuits, however, the ability to excite peripheral nerves with US remains controversial. To the best of our knowledge, there is still no in vivo neural recording study that has applied US stimulation to a nerve isolated from surrounding tissue to confirm direct activation effects. Here, we show that US cannot excite an isolated mammalian sciatic nerve in an in vivo preparation, even at high pressures (relative to levels recommended in the FDA guidance for diagnostic ultrasound) and for a wide range of parameters, including different pulse patterns and center frequencies. US can, however, reliably inhibit nerve activity whereby greater suppression is correlated with increases in nerve temperature. By prohibiting the nerve temperature from increasing during US application, we did not observe suppressive effects. Overall, these findings demonstrate that US can reliably inhibit nerve activity through a thermal mechanism that has potential for various health disorders, though future studies are needed to evaluate the long-term safety of therapeutic ultrasound applications.
Journal Article
Neurophysiological differences between dexmedetomidine sedation and natural sleep across the rodent lifespan: implications for aging and perioperative brain health
by
Nolan, Michael A.
,
Mir, Fayaz A.
,
Toledano, Sarah
in
Anesthesia
,
Anesthesiology
,
Animal cognition
2026
Purpose
Dexmedetomidine is commonly used for its sedative and neuroprotective effects, but its impact on brain activity and sleep architecture is not fully understood. Emerging evidence suggests it may improve postoperative outcomes, particularly in older adults, by promoting sleep-like states with stable hemodynamics, reducing posttraumatic stress, and decreasing delirium. This study aims to better characterize the neurophysiological profile of dexmedetomidine-induced sedation by comparing it to natural sleep in both young and aged mice.
Methods
Twelve 4–5 month old and six 10–18-month-old C57BL/6 J male mice were used. Animals were implanted with electroencephalography/electromyography electrodes. After at least 7 days of recovery, animals received intraperitoneal injections of saline or dexmedetomidine (50–400 µg/kg) and sleep–wake states were recorded for 5–12 h.
Results
Dexmedetomidine significantly increased delta (0.5–4 Hz) power beyond levels observed during natural non-rapid eye movement (NREM) sleep, followed by suppression of both high frequency (> 10 Hz) electroencephalography activity and REM sleep in a dose dependent manner. Body posture was sprawled during dexmedetomidine versus curled as during natural sleep. Notably, at the transition into sedation, dexmedetomidine induced high-voltage spikes resembling high-voltage spindles and spike wave discharges. These spikes were more prominent in the prefrontal cortex compared to the parietal cortex and aged animals exhibited more high voltage spikes than young adult animals.
Conclusion
The combination of elevated delta power, high-voltage spikes, suppression of high-frequency activity, and sprawled body posture during dexmedetomidine-induced sedation indicates a state of unconsciousness that is neurophysiologically distinct from natural NREM sleep in mice. These findings highlight important age-related differential responses to dexmedetomidine and help inform its safe and effective use in vulnerable patient populations.
Journal Article
Rib detection using pitch-catch ultrasound and classification algorithms for a novel ultrasound therapy device
by
Zebarjadi, Maryam
,
Lim, Hubert H.
,
Organ, Anna J.
in
Bioelectronic medicine: engineering advances
,
Biomedical and Life Sciences
,
Biomedical Engineering/Biotechnology
2023
Background
Noninvasive ultrasound (US) has been used therapeutically for decades, with applications in tissue ablation, lithotripsy, and physical therapy. There is increasing evidence that low intensity US stimulation of organs can alter physiological and clinical outcomes for treatment of health disorders including rheumatoid arthritis and diabetes. One major translational challenge is designing portable and reliable US devices that can be used by patients in their homes, with automated features to detect rib location and aid in efficient transmission of energy to organs of interest. This feasibility study aimed to assess efficacy in rib bone detection without conventional imaging, using a single channel US pitch-catch technique integrated into an US therapy device to detect pulsed US reflections from ribs.
Methods
In 20 healthy volunteers, the location of the ribs and spleen were identified using a diagnostic US imaging system. Reflected ultrasound signals were recorded at five positions over the spleen and adjacent ribs using the therapy device. Signals were classified as between ribs (intercostal), partially over a rib, or fully over a rib using four models: threshold-based time domain classification, threshold-based frequency domain classification, logistic regression, and support vector machine (SVM).
Results
SVM performed best overall on the All Participants cohort with accuracy up to 96.25%. All models’ accuracies were improved by separating participants into two cohorts based on Body Mass Index (BMI) and re-fitting each model. After separation into Low BMI and High BMI cohorts, a simple time-thresholding approach achieved accuracies up to 100% and 93.75%, respectively.
Conclusion
These results demonstrate that US reflection signal classification can accurately provide low complexity, real-time automated onboard rib detection and user feedback to advance at-home therapeutic US delivery.
Journal Article