Neural correlates of metacognition: Disentangling the brain circuits underlying prospective and retrospective second-order judgments through noninvasive brain stimulation.

Metacognition encompasses the capability to monitor and control one's cognitive processes, with metamemory and metadecision configuring among the most studied higher order functions. Although imaging experiments evaluated the role of disparate brain regions, neural substrates of metacognitive judgments remain undetermined. The aim of this systematic review is to summarize and discuss the available evidence concerning the neural bases of metacognition which has been collected by assessing the effects of noninvasive brain stimulation (NIBS) on human subjects' metacognitive capacities. Based on such literature analysis, our goal is, at first, to verify whether prospective and retrospective second-order judgments are localized within separate brain circuits and, subsequently, to provide compelling clues useful for identifying new targets for future NIBS studies. The search was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines among PubMed, PsycINFO, PsycARTICLES, PSYNDEX, MEDLINE, and ERIC databases. Overall, 25 studies met the eligibility criteria, yielding a total of 36 experiments employing transcranial magnetic stimulation and 16 ones making use of transcranial electrical stimulation techniques, including transcranial direct current stimulation and transcranial alternating current stimulation. Importantly, we found that both perspective and retrospective judgments about both memory and perceptual decision-making performances depend on the activation of the anterior and lateral portions of the prefrontal cortex, as well as on the activity of more caudal regions such as the premotor cortex and the precuneus. Combining this evidence with results from previous imaging and lesion studies, we advance ventromedial prefrontal cortex as a promising target for future NIBS studies.

Cold stimulation of the oral cavity redistributes blood towards the brain in healthy volunteers.

BACKGROUND: The aim of this study was to analyze cold stimulation-induced changes in cerebral and cardiac hemodynamics. METHODS: Upon ingestion of an ice cube, the changes in resistance index, mean flow velocity and flow index of the middle cerebral arteries (MCA) were assessed using transcranial Doppler sonography. Extracranial duplex sonography was used to measure the mean flow velocity and resistance index of the right internal carotid artery (ICA). The change in mean arterial pressure, heart rate, root mean square of successive differences (RMSSD) and end-tidal carbon dioxide pressure were analyzed additionally. These changes were compared to sham stimulation. RESULTS: Compared with sham stimulation, cooling of the oral cavity resulted in significant changes in cerebral and cardiac hemodynamics. The cold stimulation decreased the resistance index in the MCA (-4.5% ± 5.4%, p < 0.0001) and right ICA (-6.3% ± 15.6%, p = 0.001). This was accompanied by an increase in mean flow velocity (4.1% ± 8.0%, p < 0.0001) and flow index (10.1% ± 43.6%, p = 0.008) in the MCA. The cardiac effects caused an increase in mean arterial pressure (1.8% ± 11.2%, p = 0.017) and RMSSD (55% ± 112%, p = 0.048), while simultaneously decreasing the heart rate (-4.3% ± 9.6%, p = 0.0001). CONCLUSION: Cooling of the oral cavity resulted in substantial changes in cerebral and cardiac hemodynamics resulting in a blood flow diversion to the brain.

Physical Stimulation Methods Developed for In Vitro Neuronal Differentiation Studies of PC12 Cells: A Comprehensive Review.

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-ß cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells.

Use of imperceptible wrist vibration to modulate sensorimotor cortical activity.

Peripheral sensory stimulation has been used as a method to stimulate the sensorimotor cortex, with applications in neurorehabilitation. To improve delivery modality and usability, a new stimulation method has been developed in which imperceptible random-frequency vibration is applied to the wrist concurrently during hand activity. The objective of this study was to investigate effects of this new sensory stimulation on the sensorimotor cortex. Healthy adults were studied. In a transcranial magnetic stimulation (TMS) study, resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation for the abductor pollicis brevis muscle were compared between vibration on vs. off, while subjects were at rest. In an electroencephalogram (EEG) study, alpha and beta power during rest and event-related desynchronization (ERD) for hand grip were compared between vibration on vs. off. Results showed that vibration decreased EEG power and decreased TMS short-interval intracortical inhibition (i.e., disinhibition) compared with no vibration at rest. Grip-related ERD was also greater during vibration, compared to no vibration. In conclusion, subthreshold random-frequency wrist vibration affected the release of intracortical inhibition and both resting and grip-related sensorimotor cortical activity. Such effects may have implications in rehabilitation.

Chemical and physical influences in bone and cartilage regeneration: a review of literature.

Nowadays several studies demonstrate the influence of chemical and physical stimulation to bone and cartilage exist. The first studies date back to the 50s and for a long time, they did not have a strong impact on clinical practice. In recent times, however, the findings arising from these studies are increasingly used to address clinical problems such as osteoarthritis or non-unions. The aim of this article is to make a review of the literature of the state of the art about physical and chemical influences on bone and cartilage.

[Reactions in the organ of Corti to electrical stimulation : StED technology for detecting changes]. / Reaktionen im Corti-Organ auf elektrische Stimulation : StED-Technologie zum Nachweis von Veränderungen.

Increasing numbers of cochlear implant patients have residual hearing. Despite surgical and pharmacological efforts to preserve residual hearing, a significant number of these patients suffer a late, unexplained loss of residual hearing. Surgical trauma can be excluded as the cause. To investigate this phenomenon and because cells in their native environment react differently to stimuli (such as electrical current) than isolated cells, whole-organ explants from cochleae may be a better model. For early detection of synaptic changes in the organ of Corti, a high-resolution microscopic technique such as stimulated emission depletion (StED) can be used. The aim of this study was establishment of a qualitative and quantitative technique to determinate changes in the organ of Corti and its synapses after electrical stimulation. Explanted organs of Corti from postnatal rats (P2-4) were cultured on a coverslip for 24 h and subsequently exposed to biphasic pulsed electrical stimulation (amplitude 0.44-2.0 mA, pulse width 400 µs, interpulse delay 120 µs, repetition 1 kHz) for another 24 h. For visualization, the cytoskeleton and the ribbon synapses were stained immunocytochemically. For an early detectable response to electrical stimulation, the number of synapses was quantified. Organs of Corti without electrical stimulation served as a reference. Initial research has shown that electrical stimulation can cause changes in ribbon synapses and that StED can detect these alterations. The herein established model could be of great importance for identification of molecular changes in the organ of Corti in response to electrical or other stimuli.

Pulsed electromagnetic field may accelerate in vitro endochondral ossification.

Recapitulation of embryonic endochondral bone formation is a promising alternative approach to bone tissue engineering. However, the time-consuming process is one of the reasons the approach is unpractical. Here, we aimed at accelerating the in vitro endochondral ossification process of tissue engineering by using a pulsed electromagnetic field (PEMF). The rat bone marrow-derived stem cells were chondrogenic or hypertrophic differentiated in a three-dimensional pellet culture system, and treated with different intensities of PEMF (1, 2, and 5 mT with modulation frequency 750 Hz, carrier frequency 75 Hz and a duty ratio of 0.8, 3 h/day for 4 weeks). The effects of PEMF on hypertrophy and endochondral ossification were assessed by safranin O staining, immunohistochemistry, and quantitative real-time polymerase chain reaction. The results suggest that PEMF at 1, 2, and 5 mT may inhibit the maintenance of the cartilaginous phenotype and increase cartilage-specific extracellular matrix degradation in the late stage of chondrogenic differentiation. In addition, among the three different intensities, only PEMF at 1 mT directed the differentiation of chondrogenic-induced stem cell pellets to the hypertrophic stage and promoted osteogenic differentiation. Our findings provide the feasibility to optimize the process of in vitro endochondral ossification with PEMF stimulation.

High-Intensity Laser Therapy in Pain Management of Knee Osteoarthritis.

Knee osteoarthritis (KO) is an important health condition, affecting one third of people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise, and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms: low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). This paper aimed to stress the advantages of HILT based on a greater wavelength, higher energy delivery, and deeper tissue penetration. Research on 23 published trials revealed that the analgesic effect is rapid, cumulative, and long lasting. Compared to sham, to LLLT, or to other combinations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed a reduction in intra-articular inflammation.

Current advances in engineering meniscal tissues: insights into 3D printing, injectable hydrogels and physical stimulation based strategies.

The knee meniscus is the cushioning fibro-cartilage tissue present in between the femoral condyles and tibial plateau of the knee joint. It is largely avascular in nature and suffers from a wide range of tears and injuries caused by accidents, trauma, active lifestyle of the populace and old age of individuals. Healing of the meniscus is especially difficult due to its avascularity and hence requires invasive arthroscopic approaches such as surgical resection, suturing or implantation. Though various tissue engineering approaches are proposed for the treatment of meniscus tears, three-dimensional (3D) printing/bioprinting, injectable hydrogels and physical stimulation involving modalities are gaining forefront in the past decade. A plethora of new printing approaches such as direct light photopolymerization and volumetric printing, injectable biomaterials loaded with growth factors and physical stimulation such as low-intensity ultrasound approaches are being added to the treatment portfolio along with the contemporary tear mitigation measures. This review discusses on the necessary design considerations, approaches for 3D modeling and design practices for meniscal tear treatments within the scope of tissue engineering and regeneration. Also, the suitable materials, cell sources, growth factors, fixation and lubrication strategies, mechanical stimulation approaches, 3D printing strategies and injectable hydrogels for meniscal tear management have been elaborated. We have also summarized potential technologies and the potential framework that could be the herald of the future of meniscus tissue engineering and repair approaches.

Interventions Facilitating Recovery of Consciousness Following Traumatic Brain Injury: A Systematic Review.

People who experience disorders of consciousness (DoC) following a severe traumatic brain injury (TBI) have complex rehabilitation needs addressed by occupational therapy. To examine the effectiveness of interventions to improve arousal and awareness of people with DoC following a TBI. For this systematic review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched six databases in collaboration with a research librarian. Twenty-seven studies were included and grouped thematically. Multimodal sensory stimulation, familiar voices telling structured stories, and transcranial direct current stimulation had a moderate level of evidence. Multimodal sensory stimulation had the strongest evidence in support of its use in clinical practice. Occupational therapy practitioners should administer multimodal stimuli frequently as studies reported administering these interventions at least twice daily. Occupational therapy practitioners should incorporate personally relevant, meaningful, salient stimuli into interventions when treating patients with DoC.

Environmental enrichment accelerates the acquisition of schedule-induced drinking in rats.

Environmental enrichment (EE) provides an improvement in the housing conditions of experimental animals, such as laboratory rats, with greater physical and social stimulation through toys and company in the home cages. Its use is known to influence performance of experimental protocols, but these effects have not been well determined in the schedule-induced drinking (SID) procedure. The main goal of this study was to investigate the effects of EE on the acquisition of SID in 24 12-week-old male Wistar rats, divided into two groups, a group with EE housed with toys and companions, and a group without enrichment in individual housing conditions without toys (social isolation and no environmental enrichment, INEE). A total of 25 sessions, under a fixed time 30 s food reinforcement schedule and with access to water in the experimental chambers were carried out. Sessions lasted 30 min. The results showed that the EE group developed faster the excessive drinking pattern of SID, and drank to higher levels, than the INEE group. The greater development of SID in the EE group contradicts the view of schedule-induced behavior as linked to stress reduction and better suits with the conception of induction related to positive reinforcement.

Hybrid Therapeutic Device (CUHK-OA-M2) for Relieving Symptoms Induced by Knee Osteoarthritis.

The symptoms of knee osteoarthritis (KOA) severely affect the life quality of the elderly population. Low-level laser therapy, heat therapy, and massage therapy are widely used as independent treatments for joint disorders. However, there are very limited reports of a combination of these therapies into an integrated device for KOA so far. This study aims to develop a novel hybrid therapeutic device that can meet various requirements for knee therapy. Our hybrid therapeutic device (CUHK-OA-M2) integrated with low-level laser therapy, heat therapy, and local massage therapy can effectively provide patients with KOA with relief from their clinical symptoms. A pilot test of 50 community-dwelling elderly volunteers with KOA was performed. Finally, 43 volunteers completed two treatment periods (30 days each) and two post-treatment periods (30 days each). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were collected and analyzed after each period. The outputs of the low-level laser, heating, and massage therapies significantly decreased the WOMAC scores in terms of pain, stiffness, function and total WOMAC after two treatment periods (p < 0.05). Although the score increased slightly after the post-treatment period, it was still lower than the baseline, indicating the treatment outcome could last for an extended period. Therefore, our CUHK-OA-M2 device, as an integrated multi-functional hybrid therapeutic device, is therapeutically significant for treating osteoarthritis symptoms on the knee joints of elderly subjects.

A systematic investigation of the effects of TGF-ß3 and mechanical stimulation on tenogenic differentiation of mesenchymal stromal cells in a poly(ethylene glycol)/gelatin-based hydrogel.

Background: High post-surgical failure rates following tendon injury generate high medical costs and poor patient recovery. Cell-based tendon tissue engineering has the potential to produce fully functional replacement tissue and provide new strategies to restore tendon function and healing. In this endeavour, the application of mesenchymal stromal cells (MSCs) encapsulated in biomaterial scaffolds has shown great promise. However, a consensus on optimal promotion of tenogenic differentiation of MSCs has yet to be reached, although growth factors and mechanical cues are generally acknowledged as important factors. Methods: In this study, we prepared a hydrogel cell culture system consisting of methacrylated poly(d,l-lactic acid-ethylene glycol-d,l-lactic acid) (P(LA-EG-LA)) and gelatin methacrylate (GelMA) to encapsulate human bone marrow-derived MSCs (hBMSCs). We further systematically investigated the influence of static and intermittent cyclic uniaxial strain mechanical stimulation, in combination with transforming growth factor-ß3 (TGF-ß3) supplementation, on tenogenic differentiation of hBMSCs. Results: Increased TGF-ß3 concentration upregulated the tenogenic genes Scleraxis (SCX) and collagen type I (COL1A1) but showed no effects on tenascin-c (TNC) and collagen type III (COL3A1) expression. Mechanical stimulation had no observable effect on gene expression, but intermittent cyclic uniaxial strain stimulation improved matrix deposition. Together, these data provide new insights into how TGF-ß3 and mechanical stimulation regulate MSC tenogenesis, with TGF-ß3 promoting the expression of key tenogenic genes whilst mechanical stimulation aided matrix deposition in the engineered tissue. Furthermore, intermittent cyclic uniaxial strain at 3% elongation and 0.33 â€‹Hz for 1 â€‹h/day showed improved matrix effects compared to static strain. Conclusion: Together, the most promising result for tenogenic differentiation of hBMSCs was identified as treatment with 5 â€‹ng/ml TGF-ß3 under intermittent cyclic uniaxial strain (3% strain; 0.33 â€‹Hz; 1 â€‹h/day). This knowledge is of importance for the development of an improved protocol for tenogenic differentiation of MSCs and thereby for tendon tissue engineering. The translational potential of this article: Tissue-engineered strategies for tendon repair require a consensus on the differentiation of mesenchymal stromal cells to tenocytes, which is currently lacking. This article provides a systematic investigation of two main tenogenic differentiation conditions to further development of a tenogenic differentiation protocol.

Effectiveness of Somatosensory Stimulation for the Lower Limb and Foot to Improve Balance and Gait after Stroke: A Systematic Review.

This systematic review's purpose was to evaluate the effectiveness of lower-limb and foot somatosensory stimulation to improve balance and gait post-stroke. PRISMA reporting guidelines were followed. Included studies: randomized controlled trials (RCTs), published in English with ethical approval statement. Studies of conditions other than stroke, functional electrical stimulation, and interventions eliciting muscle contraction, were excluded. AgeLine, AMED, CINAHL PLUS, EMBASE, EMCARE MEDLINE, PEDro, PsycARTICLES, PsycINFO, SPORTDiscus, Web of Science and Cochrane central register of controlled trials were searched from 1 January 2002 to 31 March 2022. Two authors independently screened results, extracted data and assessed study quality using Cochrane Risk of Bias 2 tool; 16 RCTs (n = 638) were included. Four studies showed a medium or large standardized between-group effect size (Cohen's d) in favor of somatosensory stimulation, in relation to: customized insoles (d = 0.527), taping (d = 0.687), and electrical stimulation (two studies: d = 0.690 and d = 1.984). Although limited by study quality and heterogeneity of interventions and outcomes, with only one study's results statistically significant, several interventions showed potential for benefit, exceeding the minimally important difference for gait speed. Further research with larger trials is required. This unfunded systematic review was registered with PROSPERO (number CRD42022321199).

Physical Stimulation Combined with Biomaterials Promotes Peripheral Nerve Injury Repair.

Peripheral nerve injury (PNI) is a clinical problem with high morbidity that can cause severe damage. Surgical suturing or implants are usually required due to the slow speed and numerous factors affecting repair after PNI. An autologous nerve graft is the gold standard for PNI repair among implants. However, there is a potential problem of the functional loss of the donor site. Therefore, tissue-engineered nerve biomaterials are often used to bridge the gap between nerve defects, but the therapeutic effect is insufficient. In order to enhance the repair effect of nerve biomaterials for PNI, researchers are seeking to combine various stimulation elements, such as the addition of biological factors such as nerve growth factors or physical factors such as internal microstructural modifications of catheters and their combined application with physical stimulation therapy. Physical stimulation therapy is safer, is more convenient, and has more practical features than other additive factors. Its feasibility and convenience, when combined with nerve biomaterials, provide broader application prospects for PNI repair, and has therefore become a research hot spot. This paper will review the combined application of physical stimulation and biomaterials in PNI repair in recent years to provide new therapeutic ideas for the future use of physical stimulation in PNI repair.

Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration.

Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)-loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.

Animal models for epileptic foci localization, seizure detection, and prediction by electrical impedance tomography.

Surgical resection of lesions and closed-loop suppression are the two main treatment options for patients with refractory epilepsy whose symptoms cannot be managed with medicines. Unfortunately, failures in foci localization and seizure prediction are constraining these treatments. Electrical impedance tomography (EIT), sensitive to impedance changes caused by blood flow or cell swelling, is a potential new way to locate epileptic foci and predict seizures. Animal validation is a necessary research process before EIT can be used in clinical practice, but it is unclear which among the many animal epilepsy models is most suited to this task. The selection of an animal model of epilepsy that is similar to human seizures and can be adapted to EIT is important for the accuracy and reliability of EIT research results. This study provides an overview of the animal models of epilepsy that have been used in research on the use of EIT to locate the foci or predict seizures; discusses the advantages and disadvantages of these models regarding inducement by chemical convulsant and electrical stimulation; and finally proposes optimal animal models of epilepsy to obtain more convincing research results for foci localization and seizure prediction by EIT. The ultimate goal of this study is to facilitate the development of new treatments for patients with refractory epilepsy. This article is categorized under: Neuroscience > Clinical Neuroscience Psychology > Brain Function and Dysfunction.

Using Subthreshold Vibratory Stimulation During Poststroke Rehabilitation Therapy: A Case Series.

Subthreshold vibratory stimulation to the paretic wrist has been shown to prime the sensorimotor cortex and improve 2-week upper extremity (UE) therapy outcomes. The objective of this work was to determine feasibility, safety, and preliminary efficacy of the stimulation over a typical 6-week therapy duration. Four chronic stroke survivors received stimulation during 6-week therapy. Feasibility/safety/efficacy were assessed at baseline, posttherapy, and 1-month follow-up. For feasibility, all participants wore the device throughout therapy and perceived the stimulation comfortable/safe. Regarding safety, no serious/moderate intervention-related adverse events occurred. For efficacy, all participants improved in Wolf Motor Function Test and UE use in daily living based on accelerometry and stroke impact scale. Mean improvements at posttherapy/follow-up were greater than the minimal detectable change/clinically important difference and other trials with similar therapy without stimulation. In conclusion, the stimulation was feasible/safe for 6-week use. Preliminary efficacy encourages a larger trial to further evaluate the stimulation as a therapy adjunct.

Predicting upper extremity motor improvement following therapy using EEG-based connectivity in chronic stroke.

BACKGROUND: Uncertain prognosis presents a challenge for therapists in determining the most efficient course of rehabilitation treatment for individual patients. Cortical Sensorimotor network connectivity may have prognostic utility for upper extremity motor improvement because the integrity of the communication within the sensorimotor network forms the basis for neuroplasticity and recovery. OBJECTIVE: To investigate if pre-intervention sensorimotor connectivity predicts post-stroke upper extremity motor improvement following therapy. METHODS: Secondary analysis of a pilot triple-blind randomized controlled trial. Twelve chronic stroke survivors underwent 2-week task-practice therapy, while receiving vibratory stimulation for the treatment group and no stimulation for the control group. EEG connectivity was obtained pre-intervention. Motor improvement was quantified as change in the Box and Block Test from pre to post-therapy. The association between ipsilesional sensorimotor connectivity and motor improvement was examined using regression, controlling for group. For negative control, contralesional/interhemispheric connectivity and conventional predictors (initial clinical motor score, age, time post-stroke, lesion volume) were examined. RESULTS: Greater ipsilesional sensorimotor alpha connectivity was associated with greater upper extremity motor improvement following therapy for both groups (p < 0.05). Other factors were not significant. CONCLUSION: EEG connectivity may have a prognostic utility for individual patients' upper extremity motor improvement following therapy in chronic stroke.

Effects of multi-mode physical stimulation on APP/PS1 Alzheimer's disease model mice.

Some researchers and clinics have reported that non-drug treatments for Alzheimer disease (AD) such as electrical stimulation, light stimulation, music stimulation, laser stimulation, and transcranial magnetic stimulation may have beneficial treatment effects. Following these findings, in this study, we performed multimodel physical stimulation on APP/PS1 mice using visible light, music with a γ rhythm, and an infrared laser. And the effects of physical stimulation on APP/PS1 mice were evaluated by behavioral analysis, the content of amyloid (Aß40 and Aß42), and NISSL staining of hippocampal tissue slices. The results of subsequent behavioral and tissue analyses showed that the multi-model physical stimulations could relieve APP/PS1 mice's dementia symptoms, such as the behavior ability, the content of Aß40 and Aß42 in the hippocampal tissue suspension, and Nissl staining for hippocampal tissue analyses.