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*

Deep brain stimulation (DBS) surgery is an important treatment for patients with Parkinson's disease in the middle and late stages. The accuracy of the implantation of electrode at the location of the nuclei directly determines the therapeutic effect of the operation. At present, there is no single imaging method that can obtain images with electrodes, nuclei and their positional relationship. In addition, the subthalamic nucleus is small in size and the boundary is not obvious, so it cannot be directly segmented. In this paper, a complete end-to-end DBS effect evaluation pipeline was constructed using magnetic resonance (MR) data of T1, T2 and SWI weighted by DBS surgery. Firstly, the images of preoperative and postoperative patients are registered and normalized to the same coordinate space. Secondly, the patient map is obtained by non-rigid registration of brain map and preoperative data, as well as the preoperative nuclear cluster prediction position. Then, a three-dimensional (3D) image of the positional relationship between the electrode and the nucleus is obtained by using the electrode path in the postoperative image and the result of the nuclear segmentation. The 3D image is helpful for the evaluation of the postoperative effect of DBS and provides effective information for postoperative program control. After analysis, the algorithm can achieve a good registration between the patient's DBS surgical image and the brain map. The error between the algorithm and the expert evaluation of the physical coordinates of the center of the thalamus is (1.590 ± 1.063) mm. The problem of postoperative evaluation of the placement of DBS surgical electrodes is solved.
Brain Mapping ; methods ; Deep Brain Stimulation ; Electrodes, Implanted ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Multimodal Imaging ; Parkinson Disease ; surgery ; Subthalamic Nucleus

Tinnitus is defined as a perception of sound without any external sound source. Chronic tinnitus is a frequent condition that can affect the quality of life. So far, no causal cure for tinnitus has been documented, and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus' impact on the quality of life. Neuromodulation, a novel therapeutic modality, which aims at alternating nerve activity through a targeted delivery of a stimulus, has emerged as a potential option in tinnitus treatment. This review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options. The main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine. Non-invasive methods such as repetitive transcranial magnetic stimulation, transcranial electrical stimulation, neurofeedback, and transcutaneous vagus nerve stimulation were included, as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation. Some of these neuromodulation techniques revealed promising results; nevertheless, further research is needed, especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce. Various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus. Therefore, in the future, individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.
Deep Brain Stimulation/methods* ; Humans ; Neurofeedback/methods* ; Tinnitus/therapy* ; Transcranial Direct Current Stimulation/methods* ; Transcranial Magnetic Stimulation/methods* ; Vagus Nerve Stimulation/methods*

The electrical conductivity is a passive material property primarily determined by concentrations of charge carriers and their mobility. The macroscopic conductivity of a biological tissue at low frequency may exhibit anisotropy related with its structural directionality. When expressed as a tensor and properly quantified, the conductivity tensor can provide diagnostic information of numerous diseases. Imaging conductivity distributions inside the human body requires probing it by externally injecting conduction currents or inducing eddy currents. At low frequency, the Faraday induction is negligible and it has been necessary in most practical cases to inject currents through surface electrodes. Here we report a novel method to reconstruct conductivity tensor images using an MRI scanner without current injection. This electrodeless method of conductivity tensor imaging (CTI) utilizes B1 mapping to recover a high-frequency isotropic conductivity image which is influenced by contents in both extracellular and intracellular spaces. Multi-b diffusion weighted imaging is then utilized to extract the effects of the extracellular space and incorporate its directional structural property. Implementing the novel CTI method in a clinical MRI scanner, we reconstructed in vivo conductivity tensor images of canine brains. Depending on the details of the implementation, it may produce conductivity contrast images for conductivity weighted imaging (CWI). Clinical applications of CTI and CWI may include imaging of tumor, ischemia, inflammation, cirrhosis, and other diseases. CTI can provide patient-specific models for source imaging, transcranial dc stimulation, deep brain stimulation, and electroporation.
Animal Experimentation* ; Animals* ; Anisotropy ; Brain ; Deep Brain Stimulation ; Diffusion ; Electric Conductivity ; Electrodes ; Electroporation ; Extracellular Space ; Fibrosis ; Human Body ; Inflammation ; Intracellular Space ; Ischemia ; Magnetic Resonance Imaging* ; Methods

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.
Adult ; Aged ; Brain Mapping ; Connectome ; Deep Brain Stimulation ; methods ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neural Pathways ; diagnostic imaging ; physiology ; Oxygen ; blood ; Parkinson Disease ; diagnostic imaging ; pathology ; therapy ; ROC Curve ; United Kingdom

Adult ; Deep Brain Stimulation ; methods ; Female ; Humans ; Tardive Dyskinesia ; therapy

Aged ; Deep Brain Stimulation ; methods ; Dystonia ; surgery ; therapy ; Female ; Globus Pallidus ; surgery ; Humans ; Magnetic Resonance Imaging ; Subthalamic Nucleus ; surgery

Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases (68 with Parkinson's disease, 11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation. Deviation of implanted electrodes from the target nucleus of each patient were measured. Neurological evaluations of each patient before and after the treatment were performed and compared. Complications of the positioning and treatment were recorded.Results The mean deviations of the electrodes implanted on X, Y, and Z axis were 0.5 mm, 0.6 mm, and 0.6 mm, respectively. Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale (UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) for dystonia patients improved significantly compared to the preoperative scores (P<0.001); Complications occurred in 10.1% (8/79) patients, and main side effects were dysarthria and diplopia.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.
Adult ; Aged ; Deep Brain Stimulation ; adverse effects ; methods ; Dystonia ; therapy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease ; therapy ; Retrospective Studies ; Tomography, X-Ray Computed

PURPOSE: As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. MATERIALS AND METHODS: We obtained [15O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. RESULTS: ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. CONCLUSION: Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.
Aged ; Brain/*radionuclide imaging ; Cross-Sectional Studies ; Deep Brain Stimulation/*methods ; Female ; Functional Laterality/*physiology ; Humans ; Male ; Middle Aged ; Parkinson Disease/radionuclide imaging/*therapy ; Positron-Emission Tomography ; Severity of Illness Index ; Subthalamic Nucleus/*physiopathology

BACKGROUNDRecent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.

METHODSForty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.

RESULTSIn the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).

CONCLUSIONSOur results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.

Alzheimer Disease ; physiopathology ; therapy ; Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; methods ; Entorhinal Cortex ; physiology ; Fornix, Brain ; physiology ; Male ; Memory ; physiology ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; physiology