Assessment of rTMS treatment effects for methamphetamine use disorder based on EEG microstates.

Microstates have been proposed as topographical maps representing large-scale resting-state networks and have recently been suggested as markers for methamphetamine use disorder (MUD). However, it is unknown whether and how they change after repetitive transcranial magnetic stimulation (rTMS) intervention. This study included a comprehensive subject population to investigate the effect of rTMS on MUD microstates. 34 patients with MUD underwent a 4-week randomized, double-blind rTMS intervention (active=17, sham=17). Two resting-state EEG recordings and VAS evaluations were conducted before and after the intervention period. Additionally, 17 healthy individuals were included as baseline controls. The modified k-means clustering method was used to calculate four microstates (MS-A∼MS-D) of EEG, and the FC network was also analyzed. The differences in microstate indicators between groups and within groups were compared. The durations of MS-A and MS-B microstates in patients with MUD were significantly lower than that in HC but showed significant improvements after rTMS intervention. Changes in microstate indicators were found to be significantly correlated with changes in craving level. Furthermore, selective modulation of the resting-state network by rTMS was observed in the FC network. The findings indicate that changes in microstates in patients with MUD are associated with craving level improvement following rTMS, suggesting they may serve as valuable evaluation markers.

Cortical and subcortical microstructure integrity changes after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and relates to clinical outcomes.

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.

Pharmacological adjuncts and transcranial magnetic stimulation-induced synaptic plasticity: a systematic review.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have been used to improve our fundamental understanding of TMS-induced synaptic plasticity. METHODS: We systematically reviewed the literature pairing pharmacological adjuncts with TMS plasticity-induction protocols in humans. We searched MEDLINE, PsycINFO, and Embase from 2013 to Mar. 10, 2023. Studies published before 2013 were extracted from a previous systematic review. We included studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. RESULTS: Thirty-six studies met our inclusion criteria (28 in healthy and 8 in clinical populations). Most pharmacological agents have targeted the glutamatergic N-methyl-d-aspartate (NMDA; 15 studies) or dopamine receptors (13 studies). The NMDA receptor is necessary for TMS-induced plasticity; however, sufficiency has not been shown across protocols. Dopaminergic modulation of TMS-induced plasticity appears to be dose-dependent. The GABAergic, cholinergic, noradrenergic, and serotonergic neurotransmitter systems have small evidence bases supporting modulation of TMS-induced plasticity, as do voltage-gated calcium and sodium channels. Studies in clinical populations suggest that pharmacological adjuncts to TMS may rescue motor cortex plasticity, with implications for therapeutic applications of TMS and a promising clinical trial in depression. LIMITATIONS: This review is limited by the predominance in the literature of studies with small sample sizes and crossover designs. CONCLUSION: Pharmacologically enhanced TMS largely parallels findings from ex vivo preparations. As this area expands and novel targets are tested, adequately powered samples in healthy and clinical populations will inform the mechanisms of TMS-induced plasticity in health and disease.

Neuromodulation in migraine.

The International Neuromodulation Society defines therapeutic neuromodulation as the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body. Neuromodulation for the treatment of migraine is an evolving field offering further insight into the pathophysiology of migraine as well as advanced therapeutics. Central and peripheral neuronal targets have been explored in the efforts to reduce the frequency and severity of attacks. Invasive and noninvasive techniques have been developed, targeting either the central or peripheral nervous system. Noninvasive central neuromodulation techniques have the benefit of a low side effect profile in addition to higher level of evidence for use thanks to sham-controlled trials; however, these modalities are less clinically available for use. Noninvasive transcutaneous neuromodulation techniques that target the peripheral nervous system have provided devices that are available over the counter or by prescription. Several of these devices are effective for abortive and preventive treatment of migraine. Invasive techniques such as cranial nerve stimulation with implanted stimulator devices or spinal cord stimulation may be used for more aggressive management in patients refractory to other treatments. Overall, neuromodulation techniques can be particularly beneficial for medically complex or refractory patients, those that prefer nonmedication options, and those that have experienced adverse effects from medications.

[Research advances in neuromodulation techniques for blood glucose regulation and diabetes intervention].

Diabetes and its complications that seriously threaten the health and life of human, has become a public health problem of global concern. Glycemic control remains a major focus in the treatment and management of patients with diabetes. The traditional lifestyle interventions, drug therapies, and surgeries have benefited many patients with diabetes. However, due to problems such as poor patient compliance, drug side effects, and limited surgical indications, there are still patients who fail to effectively control their blood glucose levels. With the development of bioelectronic medicine, neuromodulation techniques have shown great potential in the field of glycemic control and diabetes intervention with its unique advantages. This paper mainly reviewed the research advances and latest achievements of neuromodulation technologies such as peripheral nerve electrical stimulation, ultrasound neuromodulation, and optogenetics in blood glucose regulation and diabetes intervention, analyzed the existing problems and presented prospects for the future development trend to promote clinical research and application of neuromodulation technologies in the treatment of diabetes.

Acupuncture combined with repeated transcranial magnetic stimulation for upper limb motor function after stroke: A systematic review and meta-analysis.

BACKGROUND: Upper limb motor dysfunction after stroke is an important factor affecting patients' motor function and daily life. Acupuncture and repetitive transcranial magnetic stimulation are effective methods for stroke rehabilitation. However, a systematic and comprehensive overview of the combined efficacy of the two is lacking. OBJECTIVE: Through a systematic review and meta-analysis of randomized controlled trials, this study aimed to assess the effectiveness of acupuncture combined with repetitive transcranial magnetic stimulation on upper extremity motor function in post-stroke patients. METHODS: The relevant randomized controlled trials on acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of upper limb motor disorders after stroke were searched in PubMed, Embase, Cochrane Library, Web of Science CNKI, VIP, Wanfang, and CBM databases. After screening clinical trials that met the inclusion criteria, data extraction was conducted independently by two investigators. Meta-analysis was performed using RevMan 5.4 software. RESULTS: After the screening, 18 articles were included, with a total of 1083 subjects. The results of meta-analysis showed that combination therapy could effectively improve the patients' upper limb motor function (MD = 7.77, 95%CI [6.32, 9.22], P < 0.05), ability of daily living (MD = 8.53, 95%CI [6.28, 10.79], P < 0.05), and hemiplegic shoulder pain (MD = - 1.72, 95%CI [- 2.26, - 1.18], P < 0.05). Meanwhile, for neurophysiological indexes, combined treatment could significantly shorten the latency of motor evoked potential and central motor conduction time (MD = - 1.42, 95%CI [- 2.14, - 0.71], P < 0.05); (MD = - 0.47, 95%CI [- 0.66, - 0.29], P < 0.05), and also could increase the amplitude of motor evoked potential (SMD = 0.71, 95%CI [0.28, 1.14], P < 0.05). CONCLUSION: According to the results of the meta-analysis, we can conclude that acupuncture combined with repeated transcranial magnetic stimulation can significantly improve the upper limb motor function and daily living ability of stroke patients.

Study on after-effect of electroacupuncture with different time intervals on corticospinal excitability in primary motor cortex. / ä¸åŒé—´éš”æ—¶é—´ç”µé’ˆå¯¹åˆçº§è¿åŠ¨çš®å±‚çš®è´¨è„Šé«“å ´å¥‹æ€§çš„åŽæ•ˆåº”ç ”ç©¶.

OBJECTIVES: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. METHODS: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). RESULTS: The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). CONCLUSIONS: Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Effectiveness of Repetitive Transcranial Magnetic Stimulation Combined With Transspinal Electrical Stimulation on Corticospinal Excitability for Individuals With Incomplete Spinal Cord Injury: A Pilot Study.

Repetitive Transcranial Magnetic Stimulation (rTMS) and transspinal electrical stimulation (tsES) have been proposed as a novel neurostimulation modality for individuals with incomplete spinal cord injury (iSCI). In this study, we integrated magnetic and electrical stimulators to provide neuromodulation therapy to individuals with incomplete spinal cord injury (iSCI). We designed a clinical trial comprising an 8-week treatment period and a 4-week treatment-free observation period. Cortical excitability, clinical features, inertial measurement unit and surface electromyography were assessed every 4 weeks. Twelve individuals with iSCI were recruited and randomly divided into a combined therapy group, a magnetic stimulation group, an electrical stimulation group, or a sham stimulation group. The magnetic and electric stimulations provided in this study were intermittent theta-burst stimulation (iTBS) and 2.5-mA direct current (DC) stimulation, respectively. Combined therapy, which involves iTBS and transspinal DC stimulation (tsDCS), was more effective than was iTBS alone or tsDCS alone in terms of increasing corticospinal excitability. In conclusion, the effectiveness of 8-week combined therapy in increasing corticospinal excitability faded 4 weeks after the cessation of treatment. According to the results, combination of iTBS rTMS and tsDCS treatment was more effective than was iTBS rTMS alone or tsDCS alone in enhancing corticospinal excitability. Although promising, the results of this study must be validated by studies with longer interventions and larger sample sizes.

Electric Field Navigated 1-Hz rTMS for Poststroke Motor Recovery: The E-FIT Randomized Controlled Trial.

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training-related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil. METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial). The sham coil appearance mimicked the active coil but without the weak electric field in the NICHE trial sham coil. Outcomes measured 1 week, and 1, 3, and 6 months after the end of treatment included the following: upper extremity Fugl-Meyer (primary, 6 months after end of treatment), Action Research Arm Test, National Institutes of Health Stroke Scale, quality of life (EQ-5D), and safety. RESULTS: Of 60 participants randomized, 58 completed treatment and were included for analysis. Bayesian analysis of combined data from the E-FIT and the NICHE trials indicated that active treatment was not superior to sham at the primary end point (posterior mean odds ratio of 1.94 [96% credible interval of 0.61-4.80]). For the E-FIT intent-to-treat population, upper extremity Fugl-Meyer improvement ≥5 pts occurred in 60% (18/30) active group and 50% (14/28) sham group. Participants enrolled 3 to 6 months following stroke had a 67% (31%-91% CI) response rate in the active group at the 6-month end point versus 50% in the sham group (21.5%-78.5% CI). There were significant improvements from baseline to 6 months for both active and sham groups in upper extremity Fugl-Meyer, Action Research Arm Test, and EQ-5D (P<0.05). Improvement in National Institutes of Health Stroke Scale was observed only in the active group (P=0.004). Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P=0.72). CONCLUSIONS: Intensive motor rehabilitation 3 to 12 months after stroke improved clinical impairment, function, and quality of life; however, 1 Hz-repetitive transcranial magnetic stimulation was not an effective treatment adjuvant in the present sample population with mixed lesion location and extent. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03010462.

The severity of acute hypoxaemia determines distinct changes in intracortical and spinal neural circuits.

The purpose of this study was to examine how two common methods of continuous hypoxaemia impact the activity of intracortical circuits responsible for inhibition and facilitation of motor output, and spinal excitability. Ten participants were exposed to 2 h of hypoxaemia at 0.13 fraction of inspired oxygen ( F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol) and 80% of peripheral capillary oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol) using a simulating altitude device on two visits separated by a week. Using transcranial magnetic and peripheral nerve stimulation, unconditioned motor evoked potential (MEP) area, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and F-wave persistence and area were assessed in the first dorsal interosseous (FDI) muscle before titration, after 1 and 2 h of hypoxic exposure, and at reoxygenation. The clamping protocols resulted in differing reductions in S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ by 2 h ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol: 81.9 ± 1.3%, F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol: 90.6 ± 2.5%). Although unconditioned MEP peak to peak amplitude and area did not differ between the protocols, SICI during F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping was significantly lower at 2 h compared to S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping (P = 0.011) and baseline (P < 0.001), whereas ICF was higher throughout the F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping compared to S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping (P = 0.005). Furthermore, a negative correlation between SICI and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (rrm  = -0.56, P = 0.002) and a positive correlation between ICF and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (rrm  = 0.69, P = 0.001) were determined, where greater reductions in S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ correlated with less inhibition and less facilitation of MEP responses. Although F-wave area progressively increased similarly throughout the protocols (P = 0.037), persistence of responses was reduced at 2 h and reoxygenation (P < 0.01) during the S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol compared to the F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol. After 2 h of hypoxic exposure, there is a reduction in the activity of intracortical circuits responsible for inhibiting motor output, as well as excitability of spinal motoneurones. However, these effects can be influenced by other physiological responses to hypoxia (i.e., hyperventilation and hypocapnia). NEW FINDINGS: What is the central question of this study? How do two common methods of acute hypoxic exposure influence the excitability of intracortical networks and spinal circuits responsible for motor output? What is the main finding and its importance? The excitability of spinal circuits and intracortical networks responsible for inhibition of motor output was reduced during severe acute exposure to hypoxia at 2 h, but this was not seen during less severe exposure. This provides insight into the potential cause of variance seen in motor evoked potential responses to transcranial magnetic stimulation (corticospinal excitability measures) when exposed to hypoxia.

The Efficacy and Safety of Different Noninvasive Therapies in the Treatment of Central Poststroke Pain (CPSP): A Network Meta-Analysis and Systematic Review.

OBJECTIVE: To evaluate the efficacy and safety of noninvasive therapies in the treatment of central poststroke pain (CPSP) by network meta-analysis and to provide an evidence-based basis for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, Wanfang, and VIP were searched for clinical randomized controlled studies on noninvasive therapy for CPSP. The retrieval time limit was from the establishment of each database to July 2022. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included randomized controlled trials (RCTs). Stata 14.0 was used for network meta-analysis, and Review Manager 5.3 software was used for traditional meta-analysis. RESULTS: Twelve RCTs involving 8 treatment schemes and 641 patients were finally included. The results of the network meta-analysis showed the following rankings in visual analysis scale (VAS): super laser injury on stellate ganglia (SLI) > transcranial direct current stimulation (tDCS) > music therapy (MT) > repetitive transcranial magnetic stimulation (rTMS) > continuous theta burst stimulation (cTBS) > transcutaneous acupoint electrical stimulation (TAES) > common therapy (CT). The total clinical efficiency ranked as follows: psychological training of mindfulness (PT) > rTMS > CT. Clinical adverse reactions ranked as follows: rTMS > MT > CT > SLI. CONCLUSIONS: Noninvasive complementary therapy can effectively alleviate the pain of CPSP patients, and the efficacy and safety of SLI are relatively significant. However, due to the limitations of this study, the efficacy ranking cannot fully explain the advantages and disadvantages of clinical efficacy. In the future, more multicentre, large sample, double-blind clinical randomized controlled trials are needed to supplement and demonstrate the results of this study.

Functional disorders - new proposals for definition, psychosomatics, somatization. / Zaburzenia funkcjonalne ­ nowe propozycje definicji, klasyfikacji, psychosomatyka, somatyzacja.

Functional Disorders are common medical problems both in primary and in secondary health care. The mechanisms that cause symptoms such as primary pain, fatigue, dizziness are still unknown. Various classifications, including ICD-10 or DSM-5, describe these conditions differently, and new proposals are being developed e.g. in ICD-11, RDoC. Many controversies are evoked by lack of unequivocal explanatory theory. The early psychoanalytical concept has been modified by other explanations, such as immunological abnormalities, dysfunction of vegetative system and HPA axis, central sensitization, diverted processes of perception or predictive processes within cognitive homeostasis dysregulation. Insufficient scientific evidence makes therapies unsuccessful and justifies further study. Psychotherapy, pharmacology and complementary medicine are supplemented by new experimental methods of treatment connected with progress in neuroscience. The recently developed non-invasive Transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS) and - neurofeedback (EEG-NF), based on EEG registration, are undergoing tests. Applying complex mathematical algorithms to localized bioelectrical signal sources makes it possible to modulate and reshape connections of neuronal networks within specific cortex areas. This article presents the current state of knowledge concerning functional disorders, highlighting the ways in which different definitions of FD have an impact on approaches to treatment.

Brain stimulation for chronic pain management: a narrative review of analgesic mechanisms and clinical evidence.

Chronic pain constitutes one of the most common chronic complaints that people experience. According to the International Association for the Study of Pain, chronic pain is defined as pain that persists or recurs longer than 3 months. Chronic pain has a significant impact on individuals' well-being and psychosocial health and the economy of healthcare systems as well. Despite the availability of numerous therapeutic modalities, treatment of chronic pain can be challenging. Only about 30% of individuals with non-cancer chronic pain achieve improvement from standard pharmacological treatment. Therefore, numerous therapeutic approaches were proposed as a potential treatment for chronic pain including non-opioid pharmacological agents, nerve blocks, acupuncture, cannabidiol, stem cells, exosomes, and neurostimulation techniques. Although some neurostimulation methods such as spinal cord stimulation were successfully introduced into clinical practice as a therapy for chronic pain, the current evidence for brain stimulation efficacy in the treatment of chronic pain remains unclear. Hence, this narrative literature review aimed to give an up-to-date overview of brain stimulation methods, including deep brain stimulation, motor cortex stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, cranial electrotherapy stimulation, and reduced impedance non-invasive cortical electrostimulation as a potential treatment for chronic pain.

Short-term plasticity of the motor cortex compensates for bradykinesia in Parkinson's disease.

Patients with Parkinson's disease (PD) show impaired short-term potentiation (STP) mechanisms in the primary motor cortex (M1). However, the role played by this neurophysiological abnormality in bradykinesia pathophysiology is unknown. In this study, we used a multimodal neuromodulation approach to test whether defective STP contributes to bradykinesia. We evaluated STP by measuring motor-evoked potential facilitation during 5 Hz-repetitive transcranial magnetic stimulation (rTMS) and assessed repetitive finger tapping movements through kinematic techniques. Also, we used transcranial alternating current stimulation (tACS) to drive M1 oscillations and experimentally modulate bradykinesia. STP was assessed during tACS delivered at beta (ß) and gamma (γ) frequency, and during sham-tACS. Data were compared to those recorded in a group of healthy subjects. In PD, we found that STP was impaired during sham- and γ-tACS, while it was restored during ß-tACS. Importantly, the degree of STP impairment was associated with the severity of movement slowness and amplitude reduction. Moreover, ß-tACS-related improvements in STP were linked to changes in movement slowness and intracortical GABA-A-ergic inhibition during stimulation, as assessed by short-interval intracortical inhibition (SICI). Patients with prominent STP amelioration had greater SICI reduction (cortical disinhibition) and less slowness worsening during ß-tACS. Dopaminergic medications did not modify ß-tACS effects. These data demonstrate that abnormal STP processes are involved in bradykinesia pathophysiology and return to normal levels when ß oscillations increase. STP changes are likely mediated by modifications in GABA-A-ergic intracortical circuits and may represent a compensatory mechanism against ß-induced bradykinesia in PD.

A C-shaped miniaturized coil for transcranial magnetic stimulation in rodents.

Objective.Transcranial magnetic stimulation (TMS) is a non-invasive technique widely used for neuromodulation. Animal models are essential for investigating the underlying mechanisms of TMS. However, the lack of miniaturized coils hinders the TMS studies in small animals, since most commercial coils are designed for humans and thus incapable of focal stimulation in small animals. Furthermore, it is difficult to perform electrophysiological recordings at the TMS focal point using conventional coils.Approach.We designed, fabricated, and tested a novel miniaturized TMS coil (4-by-7 mm) that consisted of a C-shaped iron powder core and insulated copper wires (30 turns). The resulting magnetic and electric fields were characterized with experimental measurements and finite element modeling. The efficacy of this coil in neuromodulation was validated with electrophysiological recordings of single-unit activities (SUAs), somatosensory evoked potentials (SSEPs), and motor evoked potentials (MEPs) in rats (n= 32) following repetitive TMS (rTMS; 3 min, 10 Hz).Main results.This coil could generate a maximum magnetic field of 460 mT and an electric field of 7.2 V m-1in the rat brain according to our simulations. With subthreshold rTMS focally delivered over the sensorimotor cortex, mean firing rates of primary somatosensory and motor cortical neurons significantly increased (154±5% and 160±9% from the baseline level, respectively); MEP and SSEP amplitude significantly increased (136±9%) and decreased (74±4%), respectively.Significance.This miniaturized C-shaped coil enabled focal TMS and concurrent electrophysiological recording/stimulation at the TMS focal point. It provided a useful tool to investigate the neural responses and underlying mechanisms of TMS in small animal models. Using this paradigm, we for the first time observed distinct modulatory effects on SUAs, SSEPs, and MEPs with the same rTMS protocol in anesthetized rats. These results suggested that multiple neurobiological mechanisms in the sensorimotor pathways were differentially modulated by rTMS.

Macroscopic resting state model predicts theta burst stimulation response: A randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner. Computational modelling combined with probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil. We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony. Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.

Comparison of Different Rehabilitation Techniques of Traditional Chinese and Western Medicine in the Treatment of Motor Dysfunction After Stroke Based on Frequency Method: A Network Meta-analysis.

OBJECTIVE: The aim of the study is to evaluate the effect of different traditional Chinese and western medicine rehabilitation techniques on motor dysfunction after stroke using a network meta-analysis. METHODS: CNKI, Wanfang, PubMed, Embase, and Cochrane databases were searched from inception to September 2022. We independently searched and screened randomized controlled trials of rehabilitation techniques for poststroke motor dysfunction treatment, evaluated the quality, and analyzed the data using Stata 14.0. RESULTS: Seventy-four randomized controlled trials involving nine rehabilitation techniques and 5128 patients were included. The results of network meta-analysis showed the following orders regarding improvement of the total scores of Fugl-Meyer Assessment, Action Research Arm Test, and Berg Balance Scale: biofeedback therapy > mirror therapy > repetitive transcranial magnetic stimulation > acupuncture therapy > transcranial direct current stimulation > Taichi > common therapy, virtual reality > transcranial direct current stimulation > repetitive transcranial magnetic stimulation > mirror therapy > common therapy, and acupuncture therapy > virtual reality > neuromuscular electrical stimulation > mirror therapy > common therapy > transcranial direct current stimulation, respectively. CONCLUSIONS: Biofeedback therapy had the best comprehensive effect, while virtual reality was the best intervention for improving the index of action research arm test and Fugl-Meyer Assessment-lower extremity. Acupuncture therapy improved lower limb balance function.

Treating fibromyalgia with electrical neuromodulation: A systematic review and meta-analysis.

OBJECTIVE: Several types of electrical neuromodulation (such as transcranial direct current stimulation, tDCS; transcutaneous electrical nerve stimulation) have been applied in the treatment of fibromyalgia. These trials had different outcome measurements, such as subjective pain, pain threshold, depression, anxiety, and functioning. We intended to integrate data from different trials into a meta-analysis to clearly present the clinical value of electrical neuromodulation in fibromyalgia. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing the effect of all types of electrical neuromodulation in patients with fibromyalgia was conducted. The main outcome was subjective pain; the secondary outcomes included depression, anxiety, and functioning. RESULTS: Twenty-five studies and 1061 fibromyalgia patients were included in the quantitative analysis. Active electrical neuromodulation and active tDCS both showed significant effects on subjective pain, depression, and functioning. For different anode tDCS electrode positions, only F3-F4 revealed a significant effect on depression. Meta-regression tDCS effects on depression were significantly associated with age. CONCLUSIONS: Electrical neuromodulation is significantly effective in treating pain, depression, and functioning in patients with fibromyalgia. SIGNIFICANCE: The results may help clinicians to arrange effective treatment plans for patients with fibromyalgia, especially in those patients who reveal limited response to pharmacotherapy and psychotherapy.

Glutamatergic neurotransmission is affected by low-frequency repetitive transcranial magnetic stimulation over the supplemental motor cortex of patients with obsessive-compulsive disorder.

OBJECTIVE: In obsessive-compulsive disorder (OCD), glutamatergic neurotransmission dysfunction played key roles in pathophysiology. The current research assessed changes of neurometabolites in the bilateral striatum of OCD patients receiving low-frequency repetitive transcranial magnetic stimulation (rTMS) using 1H proton magnetic resonance spectroscopy (1H-MRS). METHODS: 52 OCD patients were divided into rTMS treatment group (29) and the control group (medication only) (22). The levels of neurometabolites in the bilateral striatum of patients with OCD were measured using MRS before and after treatment. All participants were taking medication prior to the treatment and the process. RESULTS: Following rTMS treatment, Yale-Brown Obsessive-Compulsive Scale (YBOCS) score was significantly decreased in the rTMS group compared with the control group. Glutamate (Glu) and glutamate and glutamine complexes (Glx) in the bilateral striatum of the rTMS treatment response group increased significantly with the improvement of OCD. Glu in the bilateral striatum and Glx in the right striatum were positively correlated with compulsion after the treatment. CONCLUSIONS: The physiopathological mechanism of OCD may be related to the glutamatergic dysfunction, and the low-frequency repetitive transcranial magnetic stimulation applied to the supplementary motor area can improve OCD symptoms by modulating glutamatergic levels in the bilateral striatum of patients with OCD.

Effect of high-frequency repetitive transcranial magnetic stimulation under different intensities upon rehabilitation of chronic pelvic pain syndrome: protocol for a randomized controlled trial.

INTRODUCTION: Nearly one in seven women worldwide suffers from chronic pelvic pain syndrome (CPPS) each year. Often, CPPS necessitates a combination of treatments. Studies have shown the good therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) upon CPPS. We wish to undertake a randomized controlled trial (RCT) to observe the effect of high-frequency rTMS at different intensities upon CPPS. METHODS AND ANALYSES: In this prospective, double-blinded RCT, 63 female CPPS participants will be recruited and randomized (1:1:1) to high-intensity rTMS, low-intensity rTMS, or sham rTMS. The control group will receive a 10-day course of conventional pelvic floor (PF) rehabilitation (neuromuscular stimulation, magnetic therapy, or light therapy of the PF). On the basis of conventional treatment, participants in the high-intensity rTMS group will receive pulses of 10 Hz with a resting motor threshold (RMT) of 110% for a total of 15,000 pulses. Participants in the low-intensity rTMS group will receive pulses of 10 Hz with an RMT of 80% with 15,000 pulses. The sham rTMS group will be subjected to sham stimulation with the same sound as produced by the real magnetic stimulation coil. The primary outcome will be determined using a visual analog scale, the Genitourinary Pain Index, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale. The secondary outcome will be determined by electromyography of the surface of PF muscles at baseline and after treatment completion. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of Bao'an People's Hospital, Shenzhen, Guangdong Province (approval number: BYL20211203). The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences (Protocol version 1.0-20220709). TRIAL REGISTRATION: Chictr.org.cn, ID: ChiCTR2200055615. Registered on 14 January 2022, http://www.chictr.org.cn/showproj.aspx?proj=146720 . Protocol version 1.0-20220709.