Ultrasound has emerged as a non-invasive neural modulation technique. Its mechanisms of action in the brain involve mechanical, cavitation, and thermal effects, which modulate neural activity by activating mechanosensitive ion channels, enhancing cell permeability, and improving blood circulation. The ultrasound-piezo-electric systems, based on the coupling between ultrasound and piezoelectric materials, can generate wireless electrical stimulation to promote neural repair, significantly improving therapeutic outcomes for neurodegenerative diseases and showing potential as a replacement for traditional invasive deep brain stimulation techniques. The ultrasound-responsive piezoelectric drug delivery system combines mechano-electrical conversion capability of piezoelectric materials with the non-invasive penetration advantage of ultrasound. This system achieves synergistic therapeutic effects for neurodegenerative diseases through on-demand drug release and wireless electrical stimulation in deep brain regions. It can effectively overcome the blood-brain barrier limitation, enabling precisely targeted drug delivery to specific brain regions. Simultaneously, it generates electrical stimulation in deep brain areas to exert synergistic neuroreparative effects. Together, these capabilities provide a more precise, efficient, and safe solution for treating neurodegenerative diseases. This review summarizes the neural regulatory mechanisms, technical advantages, and research progress of the ultrasound-responsive piezoelectric drug delivery systems for neurodegenerative disease therapy, aiming to offer novel insights for the field.
Humans ; Neurodegenerative Diseases/drug therapy* ; Drug Delivery Systems/methods* ; Blood-Brain Barrier ; Ultrasonic Waves ; Brain ; Ultrasonic Therapy ; Deep Brain Stimulation/methods*

The gradient coils of MRI equipment can induce vibrations in implantable medical devices, causing periodic vibrations of implantable medical devices with respect to the surrounding tissue. This not only results in instrument failure but also causes discomfort to the patient. Therefore, studying the vibration characteristics of implantable devices under different scanning sequences and the orientation of the device relative to the magnetic field is crucial for comprehending vibration performance. This study observed the vibration spectra of a full cranial bone-implanted neurostimulator by using laser vibrometry under typical rapid imaging sequences and explored the impact of different magnetic field orientations on vibration. The results demonstrated that the rapid echo sequences induced diverse and rich vibration components, whereas the planar echo sequences caused relatively simple vibrations. Additionally, the strongest vibrations normally occurred in the maximum conductive surface parallel to the phase-coded direction. It revealed the factors influencing the vibrations of skull fixation active implantable devices and provided guidance for enhancing device safety and protecting patient well-being during MR examinations.
Vibration ; Magnetic Resonance Imaging ; Deep Brain Stimulation/instrumentation* ; Magnetic Fields ; Humans

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Transcranial electric stimulation (TES) is a non-invasive, economical, and well-tolerated neuromodulation technique. However, traditional TES is a whole-brain stimulation with a small current, which cannot satisfy the need for effectively focused stimulation of deep brain areas in clinical treatment. With the deepening of the clinical application of TES, researchers have constantly investigated new methods for deeper, more intense, and more focused stimulation, especially multi-electrode stimulation represented by high-precision TES and temporal interference stimulation. This paper reviews the stimulation optimization schemes of TES in recent years and further analyzes the characteristics and limitations of existing stimulation methods, aiming to provide a reference for related clinical applications and guide the following research on TES. In addition, this paper proposes the viewpoint of the development direction of TES, especially the direction of optimizing TES for deep brain stimulation, aiming to provide new ideas for subsequent research and application.
Transcranial Direct Current Stimulation/methods* ; Deep Brain Stimulation ; Brain/physiology* ; Head ; Electric Stimulation/methods*

Closed-loop transcranial ultrasound stimulation technology is based on real-time feedback signals, and has the potential for precise regulation of neural activity. In this paper, firstly the local field potential (LFP) and electromyogram (EMG) signals of mice under different intensities of ultrasound stimulation were recorded, then the mathematical model of ultrasound intensity and mouse LFP peak/EMG mean was established offline based on the data, and the closed-loop control system of LFP peak and EMG mean based on PID neural network control algorithm was simulated and built to realize closed-loop control of LFP peak and EMG mean of mice. In addition, using the generalized minimum variance control algorithm, the closed-loop control of theta oscillation power was realized. There was no significant difference between the LFP peak, EMG mean and theta power under closed-loop ultrasound control and the given value, indicating a significant control effect on the LFP peak, EMG mean and theta power of mice. Transcranial ultrasound stimulation based on closed-loop control algorithms provides a direct tool for precise modulation of electrophysiological signals in mice.
Mice ; Animals ; Deep Brain Stimulation ; Algorithms ; Electromyography

Alzheimer Disease/therapy* ; Brain/physiology* ; Deep Brain Stimulation ; Humans ; Memory/physiology*

BACKGROUND: Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level. METHODS: We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. RESULTS: The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance. CONCLUSION Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.
Animals ; Deep Brain Stimulation ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Macaca ; Seizures

BACKGROUND: Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model. METHODS: Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups. RESULTS: ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001). CONCLUSION ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.
Adenosine Monophosphate ; Anterior Thalamic Nuclei ; Cyclic AMP-Dependent Protein Kinases ; Deep Brain Stimulation ; Epilepsy/therapy* ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Mossy Fibers, Hippocampal ; Signal Transduction

X-linked dystonia-parkinsonism (XDP) is a rare, adult-onset, progressive, hereditary neurological movement disorder primarily affecting Filipino men with maternal families from Panay province of the Philippines. Medical treatment modalities currently being used have offered temporary symptomatic relief. Surgical management in the form of bilateral globus pallidi internae (Gpi) deep brain stimulation (DBS) has shown promising results and is increasingly being performed in advanced centers, as reported in international literature. Presented herein is the local experience of seven (7) retrospectively reviewed cases from February 2018 to February 2019 in a tertiary center in the Philippines with a particular focus on anesthetic management. All patients were male, from Panay, and presented with progressive dystonia and parkinsonism. All patients underwent planned bilateral, simultaneous DBS electrode, and implantable pulse generator (IPG) placement performed by a multidisciplinary team. Anesthetic management consisted of Bispectral Index (BIS) guided conscious sedation with low dose propofol and remifentanil infusions with a complete scalp nerve block (SB) at the start of the procedure then shifted to awake monitored anesthesia care during electrode placement, microelectrode recording (MER) and macro stimulation testing. All were put under general anesthesia with a supraglottic airway device during the placement of the internal pulse generator (IPG) in the infraclavicular area. All seven patients had successful localization, and insertion of the DBS electrode and discharged improved. The anesthetic management of the DBS used in these cases warrants further investigation and may lead to standardization of future practice.
Deep Brain Stimulation

OBJECTIVE: Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum.METHODS: Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed.RESULTS: Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category.CONCLUSION: Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.
Animals ; Basal Ganglia ; Chromatography, Liquid ; Deep Brain Stimulation ; Entopeduncular Nucleus ; Globus Pallidus ; Glutamates ; Glutamic Acid ; Humans ; Microdialysis ; Neurotransmitter Agents ; Oxidopamine ; Parkinson Disease ; Rats ; Substantia Nigra ; Thalamus ; Tyrosine 3-Monooxygenase